ECCO IT HUB (= ECCO DATABASE) –  PRIVACY POLICY ACCORDING TO GDPR

ECCO IT HUB consists of the following organisational entities with their registered seat in 1030 Wien, Ungargasse 6/13, and is based on a joint controllership agreement according to Article 26 General Data Protection Regulation (“GDPR”):

• ECCO – European Crohn’s and Colitis Organisation (“ECCO”), registered in the Austrian Register of Associations (ZVR) under the registration number 468755685, as well as its daughter entity:
• OCEAiN – Organisation, Congress, Emotion, Association, iNnovation GmbH (“OCEAiN”)

(together hereafter referred to as “ECCO IT HUB” or “we”).

1. Purpose

ECCO IT HUB solely processes your personal data for the purpose of:

• centralised and up-to-date data administration of ECCO Membership, Congress and event participations as well as stakeholder status in order to avoid scattering loss of up-to-date contact details among the business units of the joint data controllers

• ECCO Membership administration
• ECCO Congress abstract submission system
• ECCO Congress delegate registration
• ECCO Congress faculty registration
• ECCO Congress industry webshop and sponsor & exhibitor administration
• ECCO Virtual Congress – access administration
• ECCO Congress CME accreditation and administration
• ECCO e-Learning access administration
• ECCO Educational Workshop registration
• ECCO supplier and employee contact administration

• facilitating communication among stakeholders of the IBD Community (= the data subjects in the ECCO Database) and making relevant data visible via the ECCO Website and the ECCO App (including the display of names and affiliations of Congress speaker and ECCO Officer and the disclosure of conflicts of interest, names and affiliation)
• Promotion of ECCO Congress and Association activities
• ECCO Congress programme publication
• ECCO Congress abstract publication
• ECCO Virtual Congress platform
• ECCO Congress onsite speaker centre
• ECCO Disclosure policy of potential conflicts of interest
• ECCO Organs communication & meeting organisation
• ECCO General Assembly voting administration
• ECCO Manuscript development (Guidelines, Topical Reviews, Scientific Workshop Papers, Position Statements)
• ECCO e-Learning content development
• ECCO e-Guide content development
• Publication of ECCO News
• ECCO Website security measures and fraud prevention
• the collection and selection process with respect to open research calls, open manuscript-project calls and open calls for positions in ECCO
• Nomination collection for IBD Intensive Course for Trainees and N-ECCO School held at the annual ECCO Congress
• ECCO Organs elections - application collection
• ECCO Fellowships and Grants - application collection
• ECCO Manuscript- application collection (Guidelines, Topical Reviews, Scientific Workshop Papers, Position Statements)
• ECCO CONFER project case proposal collection
• facilitating the whole process of submission, review and publication of scientific abstracts of the annual ECCO Congress as well as facilitating the scientific review of ECCO Fellowships and Grants application
  • ECCO Congress Abstracts – scientific review
  • ECCO Fellowships and Grants – scientific review
• conducting statistical analyses and reports
• ECCO Congress, Membership and project statistics
• ECCO Website statistics for internal market research purposes
• ECCO App statistics
• ECCO Congress industry badge scanners

2. Legal basis of data collection

ECCO IT Hub only processes your personal data as follows:

• We will ask your consent to process your data in the following areas of our Website/App. You may withdraw your consent at any time. The withdrawal of your consent shall not affect the lawfulness of processing based on consent before its withdrawal:
  • ECCO Website cookies
  • ECCO Portal Account set-up
  • ECCO App installation and usage
  • ECCO e-Learning access for non-member health-care professionals until the age of 35
  • ECCO eNewsletter subscription of ECCO Portal Account Holders (without Membership)
  • Replies to open calls of ECCO (ECCO Organs, Manuscripts, Fellowships and Grants, IBD Intensive Course for Trainees, N-ECCO School, CONFER project)
  • ECCO Educational Workshop registration
  • ECCO Congress Abstract submission
  • ECCO Scientific Reviewer status
  • ECCO Congress Faculty invitations (with a separate publication consent for congress material and, for poster presentations, the consent to be contacted by delegates with regards to their poster)
  • Personal contributions to ECCO Virtual Congress
  • Publication of personal disclosure information of potential conflicts of interest, of e-Learning and e-Guide material, of ECCO manuscripts and ECCO News

 

• in performance of our (pre-)contractual obligation
  • ECCO Congress registration
  • ECCO Congress exhibition and sponsorship
  • ECCO supplier and employee contact administration

 

• on legitimate interest according to of Article 6 of the GDPR:
  • ECCO Membership administration for the fulfilment of our association purpose.

 

• Photo policy:
  • Portrait pictures are submitted by data subjects themselves or taken by the ECCO photographer are based on your explicit consent, which can be withdrawn according to point 7 below.
  • As event organisers, ECCO and OCEAiN reserve the right on their legitimate interest to use ECCO Congress photos and film footage of the official ECCO photographers and film team (as also stated in the ECCO Congress registration terms and conditions) as well as to use photos of other ECCO events in which you might be captured.

Should you have a strong objection about a specific item, you can still address ECCO Office as outlined in point 7 below.

These photos and film footage are intended for reporting about the event on the ECCO Website, in the ECCO eNewsletters, in promotional material (such as Congress break slide) and in printing material (such as the ECCO Anniversary Book series). 

3. Data categories: What kind of data?

Your personal data will not be subject to further processing in a way and manner that are incompatible with the intended purposes listed above.

ECCO Website

ECCO IT Hub processes the IP address of ECCO Website visitors and cookie information chosen by you and as explained in the cookies setting banner:

• The IP address is transmitted with every server request. ECCO IT Hub and its provider of statistical services do not store IP addresses permanently, but use them for session identification purposes and to prevent attacks only. The following information will be stored in the server logs: the IP address of the requesting computer, together with the date, time, which file is requested (name and URL), what amount of data is transferred to you, a message as to whether the request was successful, identification data of the browser used and the operating system used, as well as the website from which access was made (if access is via a link).

 

• The ECCO Website uses Matomo Analytics software, which relies on cookies as well. They are stored on your computer and generate information for the analysis of the ECCO webpages used by you (including your IP address in anonymised form), which is stored on a server located in Austria.

 

• During your visit to the ECCO Website, some information is collected and analysed for web controlling purposes. This information is provided by your browser. The following data are collected:
  • Requests (file name of the requested file) (e.g., beispiel.de/index.html)
  • Browser type/browser version (e.g., Internet Explorer 6.0)
  • Browser language (e.g., English)
  • Operating system used (e.g., Windows XP)
  • Inner resolution of browser window
  • Screen resolution
  • JavaScript activation
  • Java on /off
  • Cookies on / off
  • Colour depth
  • Referrer URL (the previously visited web site)
  • Time of access
  • Clicks
  • Total orders, if any
  • Content of forms, if any (in the case of text fields, e.g. name and password, only the information “completed“ or “not completed“ is transmitted)
  • The ECCO Website relies on several so-called cookies, which are small text files that are placed on your computer and saved by your browser ( - access all cookie details under the cookie banner). Cookies cannot be used to identify specific individuals and do not contain personal data. Most of the cookies used are so-called “session cookies” that are deleted at the end of your browser session. In addition, there are some persistent cookies used to recognize you as a returning visitor to the website.

 

ECCO Portal Account Holders in ECCO IT Hub

ECCO IT Hub processes the following personal data as provided by you in setting up an ECCO Portal Account and choosing to participate in further interactions:

• name,
• email
• addresse(s)
• phone number(s)
• postal addresse(s)
• fax
• gender
• date of birth
• age
• profession
• professional specialization
• expertise & particular areas of interest
• HCP (health care professional) status,
• your ECCO Membership status (which may also be published once per year with names per country in the context of the ECCO Congress),
• applications to open calls, event and project participation(s)
• disclosures of potential conflicts of interest,
• reimbursement data,
• portrait pictures and event photos and film footage
• passport details for congress invitation letters.
• In addition, the scientific review process generates a review result for the submitters of abstracts and applications for fellowships and grants which will be stored in connection with the abstract submitted via the submitter’s account.
• The election process generates a ranking result which is kept confidential within ECCO Office archives.

If you participate in the ECCO App and/or an ECCO virtual event, you can choose to share your personal information as well as your opinion in public debates with the other participants.

• The content of all postings and the contribution to public debates is solely your responsibility as participant who chose to actively share information. Neither ECCO or OCEAiN nor their expert volunteers or staff members can be held liable for this posted content, while ECCO and OCEAiN reserve the right to edit, rectify or delete postings of participants for good faith or legal reason.
  • Self-management of consent-based data of ECCO Portal Account used for single-sign on solution in ECCO App: your first name, last name, and email address (= you can reject that the ECCO Portal data is shared with the ECCO App)
  • Self-management of data storage and data subject rights (= the users can delete themselves): social media, website, address, job title, biography, company, country, topics of interest, portrait picture, written chat contributions
  • No data storage; self-management of data subject rights in live engagement (= you can decide themselves when to turn on/off the camera/mic/screen sharing): camera image, audio transmission, image and screen sharing
  • While text postings on the social wall can be deleted by you on your own (= self-management of data subject rights) and with this deletion also the answer comments, you cannot delete on your own your answer-comments to postings.

You may withdraw your consent regarding consent based data at any time. The withdrawal of your consent shall not affect the lawfulness of processing based on consent before its withdrawal.

4. Data received from third parties (Article 14 of the GDPR)

Please note that in the context of the following group registration, nomination and submission processes, ECCO IT HUB received your personal data via the contact person of the respective group registration:

• Membership Group Registrations
  • Source of the data: tour operator agencies booking group memberships
  • Purpose: invitation to pre-paid ECCO Membership
  • Legal Basis: consent of data subject to tour operator agencies booking group registrations; these tour operators are under a contractual obligation with ECCO to collect your consent for this registration in advance.
  • Data categories processed: last name, email address and country

 

• Congress Group Registrations
  • Source of the data: tour operator agencies booking group registrations
  • Purpose: invitation to pre-paid ECCO Congress Registration
  • Legal Basis: consent of data subject to tour operator agencies booking group registrations; these tour operators are under a contractual obligation with OCEAiN to collect your consent for this registration in advance.
  • Data categories processed: last name, email address and country, badge-pick-up and certificates of attendances of their invited delegates in tour operator profile

 

• Nomination process of the candidates for the IBD Intensive Course for Trainees
  • Source of the data: National Representatives of ECCO Country Members
  • Purpose: invitation to free-of-charge educational course at ECCO Congress
  • Legal Basis: consent of data subject to respective ECCO National Representative submitting nominations for this course; legitimate interest of data subject to be admitted to this selective course.
  • Data categories processed: first name, last name, email address, city, country, years of experience, letter of intent

 

• Nomination process of candidates for the N-ECCO School
  • Source of the data: N-ECCO National Representatives of ECCO Country Members
  • Purpose: invitation to free-of-charge educational course at ECCO Congress
  • Legal Basis: consent of data subject to respective ECCO National Representative submitting nominations for this course; legitimate interest of data subject to be admitted to this selective course.
  • Data categories processed: first name, last name, email address, city, country, phone number

 

• Congress Abstract submission process for an author group
  • Source of the data: Abstract submitter
  • Purpose: participation in the abstract selection for Abstract presentations at the ECCO Congress
  • Legal Basis: consent of data subject to submitting author of the author group; legitimate interest of data subject to participate in this scientific abstract selection.
  • Data categories processed: first name, last name, email address, institute, department, city, country, conflicts of interest

Please note that data subjects of such group registrations are contacted by ECCO Office within the first month with full transparency about this general ECCO Privacy Policy outlined here. 

As a data subject, you can address the contact point and data protection officers indicated above as well as the data protection authority indicated below.

5. Data recipients and sub-processors:

• European recipients and sub-processors:

In order to adequately fulfil the intended purposes listed above, ECCO IT Hub contracts primarily data processors based in the European Union – including but not limited to:

• COVR / Netropolix : https://www.netropolix.be/ for the customer management system of the ECCO Database
• SOL4: https://www.sol4.at/ for ECCO Website Support
• Conference Compass: https://www.conferencecompass.com/ for the ECCO App software
• Rapidmail: rapidmail.de for ECCO eNewsletter distribution,
• Viveum: www.viveum.com  as ePayment system on the ECCO Website
• GTN: https://gtn-solutions.com/ as e-Learning platform support

 

In the group registration processes, group leaders have a restricted duplicate-check option via entering the correct email address and name.

• Non-European recipients and sub-processors:

 

• In case applications are submitted to the scientific review in the context of Fellowships and Grants application reviews and the Congress Abstract reviews, this process includes individual experts from outside of Europe.

 

• In case that Educational Workshops take place outside of Europe, the registration lists for this respective Workshop are shared with the local organiser.

 

• The ECCO Virtual Congress and event platform relies on some US-based IT Services such as the Vimeo video player and the Zoom online conference platform as well as on European IT Services with US-based sub-processors such as chat tools (incl. Slido: https://www.sli.do/ and Conference Compass: https://www.conferencecompass.com/  ) and networking tools. Online educational events will rely on a selection of these services as well.

 

• The ECCO Virtual Congress platform - and the online exhibition in particular - also features links to external company websites and chat tools – which are declared as such. This privacy policy and the terms and conditions of the ECCO Virtual Congress do not apply to these external websites, which need to be consulted separately for cookie and data protection policies. These websites are not within the responsibility of ECCO and OCEAiN, who may therefore not be held liable.

 

In case you explicitly consent to badge scanning in the ECCO Congress exhibition or satellite symposia, we transfer your personal data (Name; Contact details) to the exhibition or sponsor companies of the congress, some of which do have their head-quarters in the USA.  The current list of exhibitors can be found on the annual Congress Website (accessible via https://www.ecco-ibd.eu/congresses-and-events.html )  in the exhibitor section. You may withdraw your consent at any time. The withdrawal of your consent shall not affect the lawfulness of processing based on consent before its withdrawal.

6. Data storage time-frame:

ECCO IT Hub of course also observes the principle of storage limitation for personal data.

• IP address of ECCO Website visitors: The server logs are saved in order to be able to check the system security, to administrate the website technically and to be able to optimize the offer. The server logs are stored for the duration of 3 months. After this period the identity of the user can no longer be determined, even by ISPs.
• Anonymised IP address storage in the Matomo Analytics software of the ECCO Website: 24 months
• ECCO IT Hub will process the following data of Portal Account Holders until withdrawal of consent, but not longer than for 7 years:
  • name,
  • email
  • addresse(s)
  • phone number(s)
  • postal addresse(s)
  • fax
  • gender
  • date of birth
  • age
  • profession
  • professional specialization
  • expertise & particular areas of interest
  • HCP (health care professional) status,
  • your ECCO Membership status (which may also be published once per year with names per country in the context of the ECCO Congress),
  • applications to open calls, event and project participation(s)
  • disclosures of potential conflicts of interest,
  • reimbursement data
  • passport details for congress invitation letters.
  • In addition, the scientific review process generates a review result for the submitters of abstracts and applications for fellowships and grants which will be stored in connection with the abstract submitted via the submitter’s account.
  • The election process generates a ranking result which is kept confidential within ECCO Office archives.

• Beyond that time, ECCO IT Hub will only process your data (including photographs and video material) for association archive purposes, or if we are obliged to process your personal data by law.

Personal (non-scientific) supporting documents (such as letters of intent, CVs, publication lists), submitted in the context of applications to open calls, event and project participation(s)are stored not longer than 3 years.

7. Your rights as data subject:

Should you be affected by our processing of personal data, you have the right at any time to request access to, rectification, or erasure of personal data, or restriction of the processing concerning your personal data or to object to processing as well as the right to data portability.

As data subject, you may withdraw your consent for

• ECCO Website cookies (via deinstallation on user side)
• ECCO Portal Account set-up
• ECCO App installation and usage (via deinstallation on user side)
• ECCO e-Learning access for non-member health-care professionals until the age of 35
• ECCO eNewsletter subscription of ECCO Portal Account Holders (without Membership)
• Replies to open calls of ECCO (ECCO Organs, Manuscripts, Fellowships and Grants, IBD Intensive Course for Trainees, N-ECCO School, CONFER project)
• ECCO Educational Workshop registration
• ECCO Congress Abstract submission
• ECCO Scientific Reviewer status
• ECCO Congress Faculty invitations (with a separate publication consent for congress material)
• Personal contributions to ECCO Virtual Congress
• Publication of personal disclosure information of potential conflicts of interest, of e-Learning and e-Guide material, of ECCO manuscripts and ECCO News
• ECCO Congress – Industry Badge Scanner consent
• Portrait pictures (and event photos and film footage)

from ECCO IT HUB to process your personal data at any time under This email address is being protected from spambots. You need JavaScript enabled to view it. or This email address is being protected from spambots. You need JavaScript enabled to view it. or by postal mail to ECCO Office, Ungargasse 6/13, A-1030 Vienna, Austria.

Please note that the withdrawal of your consent shall not affect the lawfulness of processing based on consent before its withdrawal, and that in certain circumstances ECCO IT Hub is entitled or else required to process certain forms of personal data for a period extending beyond the withdrawal of consent, either due to our contractual relationship with you, or else due to legal requirements.

According to Art. 13 (2) e GDPR, you are not obliged to agree to the processing of your data. However, please also note

• that in case of the withdrawal of consent you will not be able to benefit or use all functions of ECCO IT Hub;
• that in case of disagreement with the processing of necessary data for (pre-) contractual obligations, the business transaction cannot be implemented;
• that in case you disagree with the legitimate interest according to of Article 6 of the GDPR regarding ECCO Membership, you will not be able to become an ECCO Member.

You directly access and modify your information via your personal log-in under the following link: https://cm.ecco-ibd.eu/cmgateway/member/NW/index.html?module=relationmanager&config=normal#manageprofiles.

In case you believe that the processing of your personal data does not comply with the provisions of data protection, you can – other legal remedies in law courts or under administrative law notwithstanding – make a complaint with a supervisory authority, in particular in the Member State of your habitual residence, place of work or place of the alleged infringement. In Austria, the supervisory authority is the Austrian Data Protection Authority (Österreichische Datenschutzbehörde).

According to Art. 13 (2) f GDPR, ECCO IT HUB does not generate automatic decisions including data profiling.

8. Nature of joint data processing by ECCO and OCEAiN:

The essence of the ECCO IT Hub arrangement according to Article 26 GDPR:

(Updated with JCA revised text per March 15, 2020)

DESCRIPTION OF JOINT DATA PROCESSING OPERATIONS:

The ECCO Database constitutes the core for all projects on the side of ECCO Association as well the side of OCEAiN GmbH, who is in charge of organising the annual ECCO Congress, the e-Learning platform and publishing the ECCO News magazine.

As the ECCO Congress constitutes the annual meeting of the ECCO Members and other stakeholders in the field of inflammatory bowel diseases, the ECCO Database has a significant intersection set of data subjects as the same data subjects can be ECCO Members and Congress Delegates. 

The data subjects in the ECCO Database are health care professionals, pharma industry representatives, patient representatives and students in the field of inflammatory bowel diseases with an interest in both ECCO Association activities and ECCO Congress and e-Learning activities. In addition, the ECCO Database captures press contacts, as well as employees and contact persons of tour operator agencies booking group registrations and of supplier companies, which are contracted to implement projects of ECCO and OCEAiN. 

MEANS OF JOINT DATA PROCESSING OPERATIONS: 

With the increasingly enhanced digitalisation of the joint data processing operations over the past years, the ECCO Website with a Login-Area called the ECCO Portal constitutes the main entrance door to all activities of ECCO and OCEAiN.

The ECCO Portal Account is the “front” side entrance door to and, after personal Login-In, the front side display of the respective personal data-set captured in the ECCO Database.

As soon as an ECCO Portal Account holder applies for ECCO Membership or engages in another activity, joint processing takes place in the ECCO Database: the use of synergy effects in data harmonization also aims to facilitate access of  data subjects to activities within the larger framework of ECCO IT Hub (e.g. distribution of our newsletters, promotion of our Congress and educational/scientific activities, access facilitation via the publisher/distributor of our publications). 

Depending on the status of the data subject (e.g.: Membership status, Congress Registration statutes, Scientific Reviewer Status), the data subject can access various online tools (e.g.: online application process per open call, registration process for workshops or ECCO Congress, industry webshop)  and various levels of online content (e.g.: applications received for internal or scientific review, e-Learning material, meeting documents).

Most of the functionalities are directly provided by the ECCO Database suppliers and do not need data transfers to other suppliers.

The ECCO Website and the ECCO Database are hosted on a rented ECCO Server space in Austria.

Additional Platforms and technology needed are solved with a single-sign on technology with the ECCO Database, which are in particular

• the ePayment tool used to process online credit card payments for ECCO Membership and ECCO Congress Registrations.
• the e-Learning platform which is accessible to all ECCO Members and also to health care professionals as ECCO Portal Account holders without active ECCO Membership up to the age of 35. The single-sign on mechanism is based on an age check, which takes place within the ECCO Database before the access interface is enabled to the e-Learning Platform.
• the ECCO App: upon installation of the ECCO App (offering a dedicated section for ECCO Association and another dedicated section for the annual Congress) on the data subject’s mobile device, first name, last name and email address is shared with the App provider company to allow the single-sign-on mechanism. In case of additional consent of the data subject chosen in  the settings of the App, the personal status (of Membership or Congress Delegates) can be shared in order to be visible for a chat-function tool.

 

In addition, two further joint data processing platforms are used to facilitate project management and communication:

• the ECCO Office inhouse server
• the eNewsletter Mailing Platform

PURPOSE OF JOINT DATA PROCESSING OPERATIONS: please refer to point 1 above.

CATEGORIES OF DATA PROCESSED UNDER THIS AGREEMENT: please refer to point 3 above.

DATA STORAGE LIMITATION: please refer to point 6 above.

ALLOCATION OF DATA PROTECTION TASKS/DUTIES (under Art. 26 GDPR)

The data protection tasks done jointly are

• provision of information according to Article 26 paragraph 2 sentence 2 GDPR
• common contact point for the fulfilment of data subjects’ requests,
• information obligation according to Article 13 / 14 GDPR,
• fulfilment of the request of access,
• fulfilment of the request of rectification,
• fulfilment of the request of erasure and restriction of processing,
• notification to recipients (Article 19 GDPR),
• fulfilment of the request of data portability, processing of withdrawals,
• implementation of technical and organisational measures (Article 32 GDPR),
• review and adaption of technical and organisational measures,
• maintenance of a record of processing activities

 

The data protection tasks done separately are:

• selection and assignment of data processors
• processing of notifiable data breaches

 

CONTACT POINT ACCORDING TO ARTICLE 13, 14 and 26 GDPR:

ECCO Office
Ungargasse 6/13, A-1030 Vienna, Austria.
Tel: +43-(0)1-710 2242-0
Fax: +43-(0)1-710 2242-001

E-Mail: This email address is being protected from spambots. You need JavaScript enabled to view it. or This email address is being protected from spambots. You need JavaScript enabled to view it.

 

Data ProTection Officer ACCORDING TO ARTICLE 37 GDPR:

Knyrim Trieb Rechtsanwälte OG

Mariahilfer Straße 89a, A-1060 Wien

T: +43 1 909 30 70, F: +43 1 9093639

E: This email address is being protected from spambots. You need JavaScript enabled to view it., W: www.kt.at

FN 462250f, HG Wien

Current JCC eTOC

Please find here the JCC eTOC service, the table of contents for each new issue that is always being updated. Don’t miss this excellent tool for keeping up-to-date on newly published articles.

Journal of Crohn's and Colitis Current Issue N28 Stress and Inflammatory Bowel Disease – are there any differences during flare and remission?Wed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Patients with Inflammatory Bowel Disease (IBD) often experience that stress has a negative effect on the disease. Studies have also shown a possible connection between stress and active IBD. This study aims to investigate the patients´ level of stress (both subjective and objective) in relapse and in remission. With this information we may determine if the levels of stress are higher in active disease compared to remission.

Methods

Inclusion criteria were having diagnosis with ulcerative colitis or Crohn`s disease, being over 18 years old, and having a flare in IBD. Measurements were made in cortisol in saliva and filling in the questionnaires Short Health Scale (SHS) and Perceived Stress Scale (PSS). All measurements were done at the beginning of the flare and then a second time when the patient was classified as being in remission. Flare and remission were determined by endoscopic examination and fecal calprotectin.

Results

A total of 20 patients completed the study. Median age was 45 years. A number of 17 (85%) had ulcerative colitis, and 12 (60%) were women. The levels of cortisol showed normal values both in active disease and in remission. Neither the results in PSS showed any differences between active and non-active disease. However, the results showed medium high values of stress in both measurements (table 1). SHS showed improvements in all four questions, but mostly in question 1 concerning symptoms.

Conclusion

No significant differences could be found in levels of stress when measuring cortisol and experienced stress in flare and in remission. However, the PSS showed that the participants had medium high levels of stress at both measurements. This could indicate a more constant stress in patients with IBD. A weakness in this study is the difficulty in measuring cortisol at the same time in each patient. Another weakness is the small population. There is still a need to examine the connection between stress and IBD. Concerning this study there is a wish to more closely investigate possible differences within each patient.Read more N44 Implementing Electronic Documentation of a Nurse-Led IBD Advice LineWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Beaumont Hospital is a tertiary referral centre providing care to over 4500 patients with inflammatory bowel disease (IBD). This service offers an IBD nurse telephone advice line per international IBD standards. This was established to allow patients on-demand access to our service, improving the overall quality of care.

Aims/Background

• Time-to-response is recorded for all calls• Calls and emails are audited every month to ensure• Local KPIs are met• Identify potential weakness in service (i.e. access to emergency clinic spots)• Ensure continued improvement and service evolution• Track appropriate use of service by patients

Methods

Data was collected by establishing an Excel spreadsheet due to a lack of infrastructure to support a database. The spreadsheet will document the date of the call, date of the return call, patient name, hospital identification number, consultant name, reason for calling, and intervention time spent with each patient. Based on the initial audit of findings, the Patient Satisfaction Survey was distributed (n=110) and recorded.Patient feedback to identify areas for education and service development

Results

Two thousand six hundred and thirty-three (2,633) calls were received from January 2022 to September 2022. Auditing is performed monthly, identifying areas requiring improvement. Patients are frequently re-educated on how to best engage with our service. Pathways have been established to divert the calls to the appropriate alternative services such as administrators, endoscopy department, infusion services, and GP services, freeing our service for the appropriate calls only—30% of calls related to IBD flares. IBD nurses directly managed 82% of patients with flares. Overall, 75% of calls were managed virtually by an IBD nurse. An online patient satisfaction survey showed that 98% of patients expressed excellent satisfaction with the advice line service.

Conclusion

The precise documentation guided the established lean pathways for prescription renewal and pathways to redirect patients to endoscopy and non-IBD queries. The study results in aids to establishing protocols to limit prescriptions for patients who are non-compliant with blood/visits. It developed written and verbal information for patients on parameters for appropriate service use—education of patients: Modified written and oral patient education. The results of an online patient satisfaction survey showed 98% of patients report satisfaction with “excellent. The precise documentation and measurement of all the calls received facilitates service improvements and locally appropriate patient care. Patient involvement in improvement projects allows improvements to develop with patients at the centre.Read more N43 The East Kent experience of switching from intravenous infliximab to subcutaneous, benefits to the patients, the service and financial implicationsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

This project started due to two main problematics, Medical Day Unit (MDU) capacity and costs savings. Infliximab is used to treat IBD, and is initially administered by infusion, arranged by MDU. Due to increased need of biologics, MDU capacity decreased and patients waited a minimum of 6 weeks for first treatment, which can cause flares and, consequently, need steroids or attendance to A&E. If patients were able to self-administer treatment, they would not need to attend MDU and those appointments could be used for new patients. Treatment costs savings have positive financial implications to the Trust. Another benefit is that patients have more independence and do not have to attend MDU for their infusions.

Methods

To organize this, we had regular meetings with our Homecare Pharmacy team so we could understand the implications to our service, Homecare availability for the increase of prescriptions and homecare company for stock requirements and availability of a nurse visit.Once all processes were clear, we visited MDU frequently for face-to-face discussion with patients at their appointment. During these conversations, we demonstrated what supplies the patient will receive and explained with demonstration pens. We noted that patients feel more reassured if they can be familiar with the injections and raise any concerns. During the days we could not attend MDU, we arranged letters for the patients, and had positive feedback as they contacted our helpline showing interest to switch. Another strategy is to discuss this process before starting treatment, so patients can have everything arranged while having their loading doses.

Results

Before organising this, we had 14 patients on infliximab subcutaneous injections. From April 2023 to 16/11/23 we have switched 58.4% of patients. Potential cost saving to the trust includes no VAT payment on homecare products, no nursing time cost, medical devices and disposable cost and MDU cost. From patient feedback it is shown that patients prefer subcutaneous injections as this reduces the time spent in MDU, cost of travel and better symptom control. This is work in progress and we will have further information on successes at the year end.

Conclusion

Our goal was to switch 40% of infliximab by the third quadrimester and have switched 58.4%. This is an ongoing process, patients are started on infliximab regularly so need to ensure they are aware of this option. This project has been very successful for both patients and the Trust. We only switched back 3 patients due to side effects and flares. We will continue with this initiative so we can promote patient independence, decrease waiting times for loading doses and to improve cost savings to the Trust.Read more N16 Discontinuation of anti-TNF therapy in patients with inflammatory bowel disease in remission: a qualitative study on shared decision making and patients perspectiveWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Anti-tumor necrosis factor (TNF) therapy has been the mainstay for managing patients with moderate to severe inflammatory bowel diseases (IBD). Despite its effectiveness, anti-TNF therapy is associated with several side effects such as infections and infusion reactions, as well as considerable costs. Discontinuation of therapy may be considered in patients in long-term remission. Since prediction of the risk of relapse for an individual patient is difficult, shared decision making (SDM) on this decision is highly essential. The aim of this qualitative study is to explore the considerations of IBD patients in remission concerning the decision on discontinuation of anti-TNF therapy.

Methods

This is an explorative, single center study. Semi-structured interviews were conducted in adult IBD patients in clinical remission, after discontinuation of the anti-TNF therapy as treatment option was discussed by the patient and their treating gastroenterologist. Patients were identified by purposive sampling. Interviews were performed at the outpatient clinic or by telephone. The interviews were recorded, transcribed verbatim and thematically analyzed. Patients were interviewed until saturation was reached.

Results

Twelve patients were interviewed; age 25-79 years, 7 (58%) males, 7 CD and 5 UC. The duration of the anti-TNF treatment varied from 6 to 16 years. Seven patients were on first-line biological therapy, while 5 were on second or third-line biological therapy. With regard to the therapy decision, 5 patients decided to discontinue their anti-TNF treatment and 7 continued. Three main themes were identified in the interviews: patient considerations regarding the decision, patient education and perceived support of the physician. Key factors influencing decisions included the fear of relapse, with personal impact often prioritized over quantifying the risk. The memory of a previous ‘traumatizing period’ discouraged discontinuation. Notably, some patients were unaware of the efficacy of restarting anti-TNF therapy and alternative options in case of treatment failure. The study highlighted patients’ high appreciation for the support provided by gastroenterologists during the shared decision-making process.

Conclusion

Since considerations on discontinuation of anti-TNF therapy are diverse among patients, a thorough exploration of fears and impact of a relapse on the personal life is essential during the shared decision making process. Patient education on the therapeutic options in case of relapse is essential to reach a well-considered decision.Read more N23 Incorporating a patient facing application and home calprotectin based patient initiated follow up and monitoring in IBD Home® digital careWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The need for directed self-are is fundamental to the safe management of relapsing and remitting course in IBD and access to timely assessment and modification of treatment is essential during IBD flares to avoid the need for hospitalisation. Similarly, scheduled care models may cause significant disruption to activities of daily living for patientsIBD Home is a whole system model is comprehensive, integrated, and holistic approach to value-based care to provide `multidisciplinary ring` of supported care around the needs of patients in their own homes. Electronic- and virtual-based platforms have been developed to routinely monitor IBD patients and guide appropriate interventions. We incorporated a patient-facing app called MyIBD Care^® and CalproSmart^™ self-calprotectin test in two cohorts of patients participating in IBD Home in our IBD unit

Methods

Eligible IBD patients were invited to participate in the project. We piloted two cohorts of patients in this phase – cohort 1: patients in long-term remission on no therapies /and or mezalazine . Cohort 2: Patients on self-administered biologics or immunomodulatory agents. Following consent to digital data sharing and training, home FC results and patient reported measures entered by patient in portal of My IBD Care App. The interval of PROMS and frequency of home calprotectin tests were personalised to the cohort. IBD care navigator reviewed the information and those with raised calprotectin was reviewed virtually by IBD nurse in the clinician portal with a bidirectional record of the contact.

Results

1382 patients were eligible and invited to participate the two cohorts (29.5% of the entire Hull IBD cohort). 594 patients (43%) joined cohort (284 in cohort 1 and 310 in cohort 2). 550 patients (total number of PROMS 2309, mean 4.25) completed PROM. PROM engagement is depicted in figure 1. One hundred and forty seven patients had an intermediate or high calprotectin results among whom 94 had symptoms suggestive of flare on PROMs. In patients with elevated home calprotectin test 42 needed in person appointment and 24 others had change in therapy. One hundred and eleven patients in cohort 1 did not require an annual clinic review because of PROM result and low calprotectin levels. At 12 months, 41 patients (6.9%) were withdrawn from the cohorts.

Conclusion

Patient initiated follow up using My IBD care app along with self-monitoring of calprotectin is feasible in IBD patients in long-term remission and may reduce in person appointment. In those who join, the engagement to the PROM completion and continuation in pathway remains high at 12 months .Identification of suitability and studying patient preferences is important to increase uptake rates in digital pathways.Read more N24 Supporting psychosocial and emotional wellbeing and building resilience in family members of people with IBD: a co-design studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

IBD affects the quality of life (QoL) of both the patient and their family members. Our previous systematic review and qualitative research study found that family members of IBD patients express a need for improved information about IBD, networking opportunities, and increased access to support services such as IBD nurses, counsellors, or psychologists. While existing studies recognise the challenges faced by family members, there is a lack of interventions to address their psychosocial and emotional burdens. Therefore, this study aims to co-design and develop an intervention to support family members’ psychosocial and emotional wellbeing and build familial and individual resilience.

Methods

The study employed co-design approach informed by Design Thinking to explore family members’ needs, prioritise problems, and generate ideas for developing the new intervention. The co-design process comprised two sequential online workshops with individuals with IBD (n=4), family members (n=9), and IBD nurses (n=2). Workshop data were recorded in both video and audio formats, and transcribed verbatim. Reflexive thematic analysis was used to analyse the data.

Results

The study identified two priority areas for supporting family members of individuals with IBD: information and psychosocial support. Within these domains, specific solutions were pinpointed: (1) Improving access to information related to IBD and facilitating easier adaptation to living with the condition — achievable through educational materials, online resources, or support groups. (2) Increasing opportunities for networking and peer support, feasible through online forums, support groups, or social events. (3) Enhancing access to professional support services, such as counselling or therapy, to provide coping mechanisms and necessary emotional support. Additionally, a logic model and a prototype for a web-based online resource, aimed at supporting psychosocial and emotional wellbeing, were developed.

Conclusion

This co-design process delineated support priorities for family members of people with IBD, as well as offering suggestions for interventions aimed at fostering family members’ psychosocial and emotional wellbeing while promoting familial and individual resilience. We now plan to test this novel intervention in a feasibility study.Read more N35 Inflammatory Bowel Disease (IBD) nurses' knowledge practice and attitudes related to Microscopic Colitis (MC)Wed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Microscopic Colitis (MC) is affiliated with and increasingly recognized as an Inflammatory Bowel Disease (IBD). Crohn's Disease and Ulcerative Colitis (IBD) were first described over a century ago. Microscopic Colitis was first described in 1976 and the last decade has seen increasing awareness and European guidelines developed. There is no education on microscopic colitis for IBD nurses and it is not known of the practice of MC by IBD nurses in Ireland. Furthermore it is not incorporated in the Nurse European Crohn's and Colitis Organisation (N-ECCO) guidelines. The aim was to assess knowledge, practice and attitudes of IBD nurses in relation to MC.

Methods

A quantitative cross sectional survey research methodology was conducted using a 17 point questionnaire. 29 (n=29) IBD nurses from the IBD national association of Ireland (IBDNAI) responded from a total of 52 (55.7%). The inclusion criteria was 1) registered practicing nurse 2) on IBDNAI register 3) willing to participate. Data was recorded and analysed using SPSS software. Descriptive statistics were implemented. Cronbach's Alpha for instrument reliability was 0.789.

Results

The majority were female (90%) between ages 36-55 years (86%). The greater number (41%) had over 11 years of experience, followed by 38% with 1-5 years experience. The highest work location was Clinical Nurse Specialist 65.5% (n=19) and the majority qualified at Post Grad level (27.6%, n=8) or Masters level (34.5%, n=10).Mean and standard deviation scores for knowledge indicated no significant variation but variation was most significant with treatments for MC. Knowledge and years of experience revealed no significant variation. Less than one year experience (Mean 1.50 SD.707) and greater than 11 years (Mean 1.42 SD.669)Knowledge scores for symptoms are high (65.5%-90%) but investigations and treatments are average (31%, 38% and 48.3%). In relation to practice the majority of IBD nurses 71% do not receive referrals and 78.5% do not review patients diagnosed with MC at the out-patient department. Attitudes from IBD nurses regarding MC as part of the IBD nurse caseload, 42.8% said no and 57.10% said yes. 67% agreed that MC should be incorporated into the N-ECCO guidelines.

Conclusion

Education on Microscopic Colitis for IBD nurses is required nationally in Ireland which will improve the integration into practice. IBD nurses are best placed to care for patients diagnosed with MC. Recognition for MC to be incorporated into the Nurse European Crohn's and Colitis (N-ECCO) guidelines needs to be considered.Read more N38 Male patients with Crohn's Disease and perianal fistulae and their experience of sexuality and dialogue with healthcare professionals about their sexuality - a qualitative interview studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The incidence and prevalence of inflammatory bowel disease (IBD) has increased significantly over the last 30 years. IBD most often debuts in young adulthood and can have an impact on the patient's body image, intimate relationships and sexual function. The aim of this study was to explore how male patients with Crohn's disease and perianal fistulae, experience how their disease affects their sexuality, and how they experience the dialogue with healthcare professionals about sexuality and their related challenges.

Methods

A qualitative study based on a phenomenological hermeneutic approach was applied. Six male participants with Crohn's disease and perianal fistulae were recruited from an outpatient clinic at a regional hospital, Lillebaelt hospital, Vejle and Kolding. Data were collected via semi-structured telephone interviews. The transcribed interviews were analyzed using qualitative content analysis as described by Graneheim and Lundman. The analysis encompassed both a manifest and a latent level.

Results

The analysis led to the development of five themes:1) The disease and sexuality. Flare-ups in the participants Crohn's disease posed an obstacle to intimacy, negatively affecting their sexlife during flare-ups. The participants used problem-focused and emotional coping strategies to overcome these limitations in their relationships, regarding intimacy and sex.2) The phases of life - importance for sexuality. Sexuality was affected at different stages in life, independent of the participants' Crohn's disease. The balance with family, relationships, small children and work life, also had an impact on the participants desire for sex and intimacy with their partner and vice versa.3) The importance of fistulas for sexlife. Acitive fistuala negatively affected the participants' sexuality. Their masculinity was affected by erectile dysfunction, which was a common complication to surgery.4) Sexuality - an omitted topic in healthcare dialogue. Sexuality was often an omitted topic in the healthcare dialogue, even though the topic was important to the participants.5) Is sex taboo? Sexuality was a topic the participants considered to be impacted by taboo, which encompassed both the participants and the health care professionals.

Conclusion

In patients with Crohn's disease and fistulae, sexuality must be seen in a bio-psycho-social perspective. Gender roles and coping strategies are important topics to include in the health care professionals dialogue with these patients.Read more N39 Exploring the impact of an Inflammatory Bowel Disease Biologics Nurse on the management of a biologics serviceWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Biologics nurses play a critical role in the management of patients receiving treatment for Inflammatory Bowel Disease (IBD).Their impact spans various facets of patient care and service management. Prior to December 2021 all patients who required biological therapy were reviewed by any member of the IBD nursing team. This review would entail a comprehensive history taken, screening bloods ordered and explained and a thorough ex[planation of the risks and benefits of the medication including a detailed explanation of the use of the drug. The nurses were also responsible for the preparation of biologic prescriptions and checking of bloods. With a number of nurses undertaking this can lead to duplication of work or patients not receiving medication timely.

Methods

A business was written to secure funding for extra nurses and was unsuccessful. At the time of the Covid pandemic workload escalated to an extent that the current IBD Helpline and nurse led clinics could not continue in their present form. Resulting in a suspension of nurse clinics which led to a backlog of reviewing patients who required biological therapy, thus delaying their treatment. A meeting was convened with the senior management team and staffing numbers were increased resulting in the development of a biologics nurse.

Results

A band 6 biologics nurse was employed who completely transformed the biologics service. One person completing a role independently assumes total responsibility for all of the tasks annexed to the role. This involved patients education and support, monitoring and assessment of patients, coordination and communication with patients and relevant departments. It also included quality improvement, patient advocacy, emotional support to patients and patient empowerment/ One person responsible for this role has now led to a reduction in complaints, more timely treatment, less missed treatment appointments and a single point of contact for patients and departments. Our biologics nurse has not only achieved all of these roles but has been fundamental in the biologic switch to more coast effective biological therapies.

Conclusion

The impact of a dedicated biologics nurse in an IBD service is significant. They enhance the overall quality of care, improve patient outcomes, and contribute to the efficient functioning of the service by ensuring proper management, patient education, and support throughout the treatment journey. The team have had an increased number of praise and favourable comments from patients, families and departments that interact with our service such as the Medical Day Unit. The introduction of this role has been invaluable to our service has increased to such an amount that the team could do with a second nurse in post.Read more N40 Surveying outcomes of service user experience on the effects of the transition process in paediatric IBD (PIBD) patients in a tertiary PIBD centreWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Background: We conducted a prospective survey with our PIBD patients and parents seeking outcomes in accordance with our ICN- Improve Care Now participation goals to ‘Improve and optimize the care of children and teens with IBD in underserved and underrepresented populations by addressing healthcare disparities’.

Methods

Methods: We sent out a survey to our PIBD patients focusing on their overall satisfaction with the service we deliver in relation to their transition and transfer pathway. We prospectively sent this to our patient cohort of 280 PIBD patients.

Results

Results: 69/280 patients and parents (25%) responded, of whom 53/69 (77%) completed the entire survey. Of those responders 45/53 (85%) were mothers speaking on the behalf of their children aged 5-12 years (n=20 patients). 4/53 (7%) patients completed the survey themselves, of whom 3 (75%) were aged between 12-18 years. When asked about if they understood what will happen when your child moves form paediatric to adult care, 24/53 (45.61%) of patients said they had not been spoken to about transition in the last 12 months. Additionally, the survey asked if the IBD team had spoken to the patients about any worries and concerns they had regarding their transition over the last 12 months, 25/53 (48.21%) responded that they had not been spoken to about this.

Conclusion

Conclusion: Our survey has highlighted the importance of promoting the transition process throughout the patient’s IBD journey. Just under 50% of patients reported that they had not been spoken to about this process, which highlights the improvements needed. This process can be developed by identifying patients earlier and establishing clear transition pathways that must be followed in order to improve effective patient experiences with transition.Read more N10 Evaluation of the impact of an IBD nurse in an Inflammatory Bowel Disease CenterWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

In some European countries, IBD nurse is not a recognized status. IBD nurses are general care nurses who wants to improve their knowledges and get involved in the « Care and Support » of IBD patients. An increasing number of IBD centers are using the services of IBD nurse. The aim of this study was to evaluate prospectively the activity and impact of IBD nurse on the management of IBD patients in an IBD center.

Methods

From March 13th to June 13th, 2023, all patients having interacted with IBD nurse in an expert center, were prospectively recorded. The main points were, the number and characteristics of patients, means and reasons of contact, actions implemented, follow-up and, finally, patient satisfaction assessed using a standardized questionnaire (visual analog scale from 0 to 10).

Results

During three months, 132 patients, 69 women and 63 men (47% Ulcerative Colitis, 52% Crohn's disease and 1% indeterminate colitis), with a median age of 40 years (16 to 87), had contacted the IBD nurse. The means of contact were phone call: n =131 (42%), text messages: n = 25 (8%), e-mail: n = 69 (22%), face-to-face consult: n = 86 (27.5%) and teleconsulting: n = 1 (0.5%).The reasons for contact were:Three hundred and twelve contacts had led to 315 actions divided into seven groups:Over this period, IBD nurse was contacted 22 times by 19 patients for a real or perceived emergency. These situations were managed by a multidisciplinary team, and resulted in reinsurance (68%), referral to others medical specialist (18%) or hospitalization (14%).Overall satisfaction with the IBD nurse intervention was 10/10 for 78% of patients and 9/10 for 11%. To the question: “do you think that the intervention of the IBD nurse improves disease management?”: 78.5% agreed at 10/10 and 7% at 9/10. To the question: “do you think contact with the IBD nurse improves access to care: 67.5% agreed at 10/10 and 3.5% at 9/10.The main patients’ advice / reviews to improve care were: to adjust levels of follow-up according to the patient and his/her needs, to strengthen the IBD Nurse coordination team to limited days off, to have explanation sheets and reports of IBD Nurse intervention, to develop more workshops for patients in the Education program.

Conclusion

This pilot study showed the importance of the IBD Nurse activity in an expert center. The patients who benefited from this care were very enthusiastic about it.Reasons for contacts N= % advices/questions/information 121 39% scheduling/organization appointment issue 60 19% care-providing (biological check-up + starting treatment) 77 25% emergency 22 7% request for an appointment/Information with IBD nurse 19 6% request for a patient education session (PE) 13 4% Read more N11 The effect of progressive relaxation techniques on disease activity, anxiety, sleep, and quality of life in individuals with Ulcerative ColitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The aim of the study was to determine the effect of progressive relaxation techniques on disease activity, anxiety, sleep quality, and quality of life in individuals with ulcerative colitis.

Methods

This study was conducted as a randomized controlled three-arm experimental study. A total of 56 patients with ulcerative colitis were randomly divided into a progressive relaxation (n=19), placebo (n=19) and control (n=18) group. The data of the study were collected using the "Individual Identification Form", "Partial Mayo Score", "State-Trait Anxiety Inventory", "Pittsburgh Sleep Quality Index", and "Inflammatory Bowel Disease Quality of Life Questionnaire". Progressive relaxation techniques were applied to individuals in the progressive relaxation group by providing a video and educational brochure and practicing at least once a day for 25-minute sessions for 8 weeks; a special music selection for relaxation was played for individuals in the placebo group for at least one 25-minute session a day for 8 weeks. No application was made to individuals in the control group. Data collection forms were applied to all individuals before and 4th and 8th weeks after the application.

Results

The average age of the participants in the study was 38.75±11.47, and 51.8% of them were female. It was found that there was a decrease in disease activity scores at the 4th and 8th weeks in both the progressive relaxation and placebo groups, with a greater decrease observed in the progressive relaxation group.This difference was not statistically significant.Anxiety levels of the individuals, it was found that there was a statistically significant decrease in both state and trait anxiety score averages at the 4th and 8th weeks in both the progressive relaxation and placebo groups, with a higher percentage of decrease observed in the progressive relaxation group (p<0.05).Sleep quality score averages at the 4th and 8th weeks, it was found that there was no statistically significant change in the control group, while the score averages of both the progressive relaxation and placebo groups significantly decreased, with a higher percentage of decrease observed in the progressive relaxation group (p<0.05).In the progressive relaxation and placebo groups, it was found that the life quality score averages significantly increased at the 4th and 8th weeks, with a higher percentage of increase observed in the progressive relaxation group (p<0.05).

Conclusion

Our study has shown that progressive relaxation techniques can reduce anxiety levels and improve sleep and quality of life in individuals with ulcerative colitis.Read more N12 The Experience of Post-traumatic Growth Process in Newly Diagnosed Chinese Patients with Crohn’s Disease: A Longitudinal Qualitative StudyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The impact of Crohn’s disease (CD) is not purely negative, it may become an opportunity for patients to undergo positive psychological adjustments and achieve personal growth. To date there has been limited in-depth research to understand the patients’ experiences of post-traumatic growth (PTG) process following an CD diagnosis using a qualitative study with a longitudinal perspective.

Methods

A longitudinal qualitative design was adopted. Sixteen newly diagnosed Chinese patients with CD were recruited through purposive sampling. Semi-structured interviews were conducted on three occasions: 3, 6 and 12 months post-diagnosis. Data were collected between November 2021 and December 2022. Data analysis of each time point was based on conventional content analysis. Afterwards, all data were combined for a comprehensive re-analysis to capture change.

Results

Four themes and fifteen sub-themes were formed through analysis (table 1). The process of PTG was shown in Figure 1. Within the first year post-diagnosis, patients with CD experienced considerable physical discomforts and psychological distress. Their personal development was also limited. With increased disease knowledge, and driven by a strong sense of responsibility and external support, the patients’ disease acceptance transformed from "difficult to accept" to "have to accept" to "should accept" then to "be able to accept". Living with CD, they actively engaged in monitoring disease condition, cooperating with treatment, exploring patterns of flare-ups, relieving stress and focusing on problem solving to eliminate negative emotions, and regaining hope and positively planning for future. Over time, the impact of CD on the patients’ lives became smaller, they integrated their disease as a part of themselves, and achieved personal growth. This growth was manifested by "developing closer relationships with others", "increasing personal strength", "changing in life philosophy" and "emerging new possibilities". Overall, as disease duration increased, the disease related sufferings diminished, and CD patients’ disease acceptance improved. In addition, as time goes by, the patients’ ability to self-manage disease enhanced, and their experience of personal growth increased.

Conclusion

The process of PTG in patients with CD within the first year of diagnosis primarily consists of four stages: "enduring hardships", "accepting illness", "living with illness", and "achieving personal growth". This growth was not linear, but rather cyclical. Nurses could provide targeted guidance to patients based on the trajectory identified in this study, helping them unearth inner resources and create conditions for PTG.Read more ECCO Grant Immune-epithelial crosstalk boosting intestinal repair in ulcerative colitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background and Aims

1.3 million people in Europe suffer from inflammatory bowel disease (IBD). Its most prevalent subtype is ulcerative colitis (UC), a chronic colon inflammation of unknown etiology. The breakdown of intestinal epithelial barrier integrity is a key event initiating intestinal inflammation in UC, and remission requires epithelial repair. Repair is modulated by inflammatory signals which exert anti- but also pro-proliferative effects. It is unknown how the epithelium integrates inflammatory signals to finetune repair, limiting current therapeutic strategies in UC to symptomatic suppression of inflammation with potential detrimental effects on repair. With this project, I aim to gain a molecular understanding of immune cell-epithelial crosstalk in UC to inform targeted therapies that suppress detrimental inflammation and boost epithelial repair.

Methods

To this end, I propose a novel, interdisciplinary approach, venturing beyond traditional approaches by employing my host lab’s expertise on epithelial injury and repair in combination with my competence in mucosal immunology and a novel visual proteomics technique to decipher immune cell-epithelium crosstalk driving epithelial repair in UC. Specifically, I will generate a high-resolution proteome map of the repairing colonic mucosa of patients with UC to identify potential immune cell-epithelium crosstalk, validate candidates and assess the reparative potential of the identified crosstalk in human intestinal epithelial cells using organoid cultures.

Anticipated Impact

Current therapeutic strategies in UC, focused on immune suppression, still feature high rates of primary or secondary non-response, fueling disease progression and decreasing patient quality of life. This highlights a key unmet clinical need for alternative therapeutic approaches. I anticipate that the identified immune-mediated drivers of epithelial repair will provide novel molecular targets for future pharmacological interventions aiming to mitigate inflammation-induced epithelial barrier loss and to boost repair capacity. This will improve patient quality of life and reduce treatment costs.Read more ECCO Grant Ablating perianal fistulizing Crohn’s disease through genetically engineered patient specific induced pluripotent stem cells (iPSC)-derived stromal cellsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background and Aims

Despite the wide range of available therapies treatment of perianal fistulizing Crohn’s disease (pCD) remains challenging. Therefore, exploring new effective therapies is of crucial importance. Local injection of allogeneic mesenchymal stromal cells has been reported to be effective, however, application of these cells is hindered by their limited expandability and differences in therapeutic effect due to donor variations. To overcome these problems, induced pluripotent stem cells (iPSC) can be used to create stromal cells as iPSC can be propagated indefinitely in their undifferentiated state. Therefore, the aim of our study is to generate patient specific iPSC-derived stromal cells of patients with pCD. Furthermore, we will engineer programmed death-ligand 1 (PD-L1)-expressing cultures to enhance the immunomodulatory capacity of these stromal cells. Last, preclinical testing of these cells will be performed in experimental colitis models.

Methods

Ten patients with pCD will be included at the outpatient clinic in the Erasmus Medical Center (EMC). Patient specific iPSC will be generated from peripheral blood in the iPSC core facility of the EMC. iPSC cultures will be exposed to a low dose of retinoic acid creating stromal cells. The variety of stromal cells will be sorted using a FACS and a stromal specific sorting panel. In parallel, cultures will be engineered, using CRISPR-Cas technology, to express PD-L1. Mixed lymphocyte reactions will be performed to assess the ability of both transduced and non-transduced cultures to provoke the proliferation of non-MHC matched T-lymphocytes. Next, cultures will be generated to express murine PD-L1 to assess their immunomodulatory capacity in established experimental colitis models to provide essential knowledge for a future clinical trial.

Anticipated Impact

With this study, we are taking the first steps towards improved remission rates of perianal fistulas in the future. On the long-term, this will result in reduction of health care costs.Read more D-ECCO Grant Personalizing the dietetic strategy in children with IBD: exploring an antioxidant approachWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background and Aims

Diet is a key element in the pathogenesis and treatment of Inflammatory Bowel Disease (IBD). Also, oxidative stress (OS) is involved in IBD onset and evolution. Our group is conducting a multicenter trial (the OxIBDiet study, NCT0451301) to explore the OS imbalance in both children and adults with IBD, compared to matched controls, the genetic variants of genes implicated in OS and the effects of an Antioxidant diet (AoD) on these patients. Preliminary results have shown a great imbalance in the total antioxidant capacity in IBD compared to healthy matched controls, particularly in IBD children, and a clear improvement of the antioxidant capacity and oxidant parameters after 3 months of AoD. Aims of this study are: 1. To identify IBD subjects’ responders to a specific dietetic treatment (on the basis of clinical, biochemical and genetic characteristics); 2. To evaluate the effect of antioxidant compounds on stem cell derived 3D models of the intestinal epithelium by organ-on-a-chip technology; 3. To characterize the effect of AoD and Mediterranean diet in terms of inflammatory pattern.

Methods

A machine-learning algorithm that integrates clinical parameters, anthropometrics, blood parameters and genetic data measured in OxIBDiet cohort will be generated and validated in a new cohort of 30 IBD children (15 CD and 15 UC). Human intestinal organoids will be generated from 10 patients, in which an endoscopy is planned for disease reassessment, and levels of interleukins and TNF-alfa will be measured, after stimulation with antioxidant compounds. Thirdly, cytokine analysis in serum from OxIBDiet cohort who performed dietetic sub-study will be evaluated.

Anticipated Impact

Results of this study will provide useful indications on factors that influence redox imbalance in IBD and will permit to identify patients who may benefit from a personalized dietetic approach, especially an AoD.Read more D-ECCO Grant Dietary patterns during early life and risk of inflammatory bowel diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background and Aims

Diet plays a key role in modulating the intestinal microbiota, thereby impacting the regulation of intestinal inflammation. The Western diet has been linked to non-communicable diseases such as obesity, cardiovascular disease, diabetes, and metabolic syndrome, and its role in inflammatory disorders is subject to increasing attention. It is of interest to understand, how maternal nutrition directly impacts fetal development and, together with the child’s own nutrition, influences the later susceptibility to immune mediated diseases. This ambitious project will assess how maternal exposures and dietary patterns during pregnancy combined with early life exposures at birth influence the risk of inflammatory bowel disease (IBD) in offspring.

Methods

We will use the Danish National Birth Cohort (about 100,000 women and 91,383 children were included in the cohort) in which 72,821 completed the food frequency questionnaire (FFQ) in early pregnancy and nationwide health data to 1) characterize the dietary patterns of mothers in mid-pregnancy, and 2) use this information to assess the association of maternal dietary pattern with risk of IBD in offspring. Furthermore, we will examine 3) the impact of diets rich in ultra-processed foods, and 4) mothers' fish consumption in mid-pregnancy and the association with risk of IBD in offspring.

Anticipated Impact

The applicant has assembled a unique team of collaborators, which, together with access to exclusive Danish resources, will guarantee the success of the project, with the primary objective is to understand how diet influences the development and worsening of IBD, improve quality of life, and to pave the way for improved dietary guidance for a growing global group of young people with chronic diseases.Read more N-ECCO Grant Spiritual needs of patients with inflammatory bowel disease and their caregivers: a European cross-sectional nursing studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Aims

Spirituality is the search for meaning or purpose in life (Delgado, 2005), not strictly from a religious perspective. Spiritual well-being is positively connected with physical and psychic well-being, and achieving the first is likely to help to maintain the latter (Bożek et al., 2020). Individuals with chronic disorders or experiencing a life-changing condition (e.g. Inflammatory Bowel Disease - IBD), may have gone through a spiritual quest of some sort that can produce spiritual anguish or 'spiritual distress', interpreting the disease as a punishment, feeling as a victim of 'superior injustice', losing faith in prayer (Klimasiński et al., 2022), but data on the spiritual needs (SpNs) of IBD patients are lacking.The main objective of this project is to describe the SpNs of IBD patients to provide information to IBD nurses on how to address these needs.

Methods

A multilingual cross-sectional electronic survey will be carried on assessing the SpNs of patients using the Spiritual Needs Questionnaire (SpNQ). The tool is made up of items assessing the importance attributed by patients to SpNs using a 4-point Likert scale (Büssing et al., 2010), and is available in ten European languages, but it could be translated and validated in other European languages inside the project in case of anticipated participation by a country that need the questionnaire available in the local language if a collaboration with IBD clinicians and patients in that country will be possible.

Anticipated Impact

The findings of such a study can provide better consideration of SpNs in the treatment of IBD patients, emphasizing the importance of addressing SpNs for IBD nurses in managing IBD patients, adopting the tools to screen patients for these needs; furthermore, the results of this project can provide additional evidence of the importance of nursing in IBD patients’ care.Read more N-ECCO Grant Supporting psychosocial and emotional well-being and resilience in family members of people with IBD: an intervention co-design and feasibility studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background and Aims

This ongoing PhD project seeks to develop a person-centred, evidence-based, theoretically informed prototype intervention to support psychosocial and emotional well-being and resilience in people with IBD’s family members (FMs). PhD project focuses on the intervention development and feasibility testing. The development phase has already been undertaken using a co-design approach informed by Design Thinking. A systematic review and qualitative research have been conducted and published, and co-design workshops have been held with people with IBD (n=4), FMs (n=9), and IBD nurses (n=2), revealing a preference for online-based intervention. Therefore, the aim of this study is to translate the paper-based intervention prototype into electronic format. The online prototype will be a) tested for acceptability and b) effect signal. The feasibility of the study design will be evaluated.

Methods

A sequential mixed methods approach, based on the UK Medical Research Council (MRC) Evaluation Framework. The intervention feasibility study will test the acceptability of content and delivery of the intervention and ascertain active feedback. The feasibility of the study design will be evaluated the recruitment, data collection, retention, and analysis strategies. A two-arm feasibility RCT with nested qualitative evaluation will be used to evaluate the newly developed intervention among 60 FMs. Participants will be recruited via Crohn’s & Colitis UK and Bowel Research UK charities. The 60 participants will be randomly allocated into intervention and control groups using 2:1 randomisation. The qualitative component will use purposive sampling from the intervention arm to elicit feedback on the content and format with up to 20 participants.

Anticipated Impact

Results from this intervention development and feasibility study will help revise the intervention, incorporate changes to the study protocol (if necessary), and develop a large-scale RCT for efficacy trailing of a complex intervention to benefit service users.Read more IIS Registry Grant Risk of relapse and retreatment success after vedolizumab discontinuation in IBD patients in long-standing remissionWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background and Aims

Treatment withdrawal and “cycling” of anti-TNFs has been extensively investigated in the recent years. To date, none or scarce data are available for biological agents other than anti-TNFs, such as vedolizumab (VDZ), which is the first non-anti-TNF agent approved for the treatment of inflammatory bowel disease (IBD). Our aim will be to investigate the risk of relapse and retreatment success in IBD patients that discontinue vedolizumab due to sustained steroid-free remission.

Methods

This will be a prospective observational study in which two groups of patients in sustained remission will be formed, i.e., patients stopping vedolizumab and patients continuing the treatment. Differences regarding rates of disease flares, IBD-related hospitalisations and surgeries will be analysed. The rate of retreatment success in patients presenting a flare after discontinuation will also be recorded. In addition, potential predictive factors of disease relapse will be investigated to provide future guidance on the patient profile that might benefit the most from intermittent VDZ treatment. The study will last 3 years in total, with the first year dedicated to patient inclusions.

Anticipated Impact

Only few data are currently available regarding intermittent treatment with vedolizumab. Therefore, this study may provide insights on when to interrupt this biologic with high probability of maintaining remission, while also showing high-risk features that would suggest against stopping the treatment. The use of treatment cycles may represent an impactful cost reduction for our healthcare systems as well as a decrease of potential side effects that are an inevitable consequence of years of immunosuppression.Read more IIS Registry Grant Modelling Inflammatory Bowel Diseases trajectories combining dynamic, multifactorial, Artificial Intelligence-based approachesWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background and Aims

The aim of this project is to model Inflammatory Bowel Diseases (IBD) progression using an innovative approach that considers the manifestation of the disease from a dynamic and multifactorial point of view, with a focus on model explainability.

Methods

With the aim of modelling the course of IBD in the study population of the UR-CARE registry, an innovative approach will be applied consisting of the combined use of two different data-driven Artificial Intelligence techniques, namely dynamic Bayesian networks and Process Mining. Specifically, these two approaches will be jointly used to model IBD progression trajectories, providing a broader overview of the disease through the description of its patterns of progression (including clinical events, treatments and/or outcomes) and the interactions between clinical variables. The potential of the proposed methodology to address the predictive needs of chronic IBD progression, such as the forecasting of the next relapse, the effect of a therapy, or the impact of a risk factor, will also be explored.

Anticipated Impact

On the one side, IBD patients experience constant uncertainty regarding disease progression, while clinicians, on the other hand, need tools that can support them in understanding the multidimensionality of disease progression. In this scenario, AI can be the key to successfully satisfy these needs, effectively investigating the disease processes, allowing to describe pathological evolution over time, handling and capturing patients’ inter-variability, and providing tools to forecast disease evolution. By adopting an ad-hoc developed analytic approach, this project can help in better understanding IBD mechanisms and best care strategies, defining the relationships among the patient characteristics and the sequence of experienced clinical events, evaluating the impact of key elements on disease’s prognosis. These results would be useful not only to better manage the disease from a clinical and care point of view, but also in economic terms.Read more N33 Experience of inflammatory bowel disease patients in relation to the practice of anal intercourseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Sexual health should be part of the management of people with chronic diseases. Receptive anal intercourse is a relatively common practice, and in Inflammatory Bowel Disease (IBD) it can be clearly compromised by the perianal and rectal involvement that many patients present. Understanding the experience of people with IBD in relation to anal intercourse will provide information to help them live their sexuality in a full and healthy way.

Methods

Observational, descriptive, cross-sectional study. Creation of ad-hoc online questionnaire through the REDCap platform. The study population was people between 18 and 75 years with IBD who have or have had sexual intercourse. The survey was distributed through social networks, advanced practice nurses and patient associations (ACCU). The study was approved by the Ethical Committee for Clinical Research of Hospital Universitari Germans Trias i Pujol, (reference PI-22-255, approval date November 11, 2022)

Results

1111 surveys answered, 766 (68.8%) completed. Mean agewas 41.86 years (SD10.32), 560 (73.3%) were women, and 50% had a university education. Sixty per cent (460) have Crohn's disease and 765 people (75.4%) are on immunosuppressive treatment. 22.4% (171) report perianal disease. 34.8% (266) practice anal sex, of these more than 60% do not use a condom during anal sex. 7.6% clean their bowels, 32.4% dilate their anus beforehand, and 60.5% use lubricants. Injuries, tearing and bleeding are reported after anal sex, with 78.5% of women reporting pain. More than 30% think that anal sex increases the urge to go to the toilet and 22% think that it worsens their IBD.

Conclusion

As nurses results obtained in this study direct us towards two main themes. We have to be aware of focusing on health education for the prevention of sexually transmitted diseases and the prevention of possible complications produced by anal sex.Read more N34 Transition of Inflammatory Bowel Disease patients from pediatric to adult Care: A single-center ten-years experienceWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Transition of adolescents with inflammatory bowel disease (IBD) to adult care is a challenge for patients, families, and healthcare providers. Considering that ~ 25% of IBD patients are diagnosed before the age of 16 years, and that these patients are at higher risk for poorer clinical disease outcomes. interest in the transition of care has been increasing considerably in the last decade.To assess the main clinical and epidemiological features of peadiatric IBD patients in a single pediatric center in Sardinia, Italy, at diagnosis and at the time of transition to the adult center

Methods

From January 2014 to June 2023 we performed a multicenter, observational, cross-sectional study that included pediatric patients with IBD enrolled in the only pediatric IBD reference center in Sardinia. Data were obtained from the patients’ medical records and from a questionnaire administered at the inclusion visit.

Results

Sixty-five IBD patients were enrolled (UC 40, CD 25, M 32, F 33). Median age at diagnosis was 13 years (IQR 2-18). After a median disease duration of 8 years (IQR: 1-25), no UC patients experienced proximal estension of proctitis or left-sided colitis, and no CD patients experienced new localizations of disease.Fifteen patients developed extraintestinal manifestations. No significant difference was found in median diagnostic delay (DD) between UC [4 months (IQR: 1-84)] and CD patients [4,5 months (IQR: 1-48)].At the transition visit, overall, twenty-nine patients (44,6%) were exposed to one biologic agent (vs 3% at baseline; p<0.02); 0 patients (0%) were exposed to two biologic agents. 4,6% of patients (3/ 65) underwent surgery

Conclusion

Our results provide important insights into the clinical and epidemiological features of pediatric IBD population, and while waiting for a nation Italian registry, present eligible data on the IBD population in SardiniaRead more N04 Impact of phase angle on nutritional assessment and disease activity in patients with Ulcerative ColitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

An increase in the prevalence of Ulcerative Colitis (UC) has been reported, especially in Latin America, malnutrition occurs in up to 70% of patients with active disease. The complete assessment of nutritional status is the best method to make an adequate diagnosis since it considers 4 parameters, anthropometry, biochemistry, clinical, and dietary, however, it is very extensive and there are other methods such as bioelectrical impedance (BIA), which is a non-invasive way to estimate the percentage and amount of fat, muscle, water and phase angle (PhA). Moreover, PhA has been proposed as a marker of cell integrity which may be a substitute for complete nutritional assessment. Therefore, the study aimed to evaluate the effectiveness of PhA in the nutritional diagnosis of patients with UC.

Methods

A cross-sectional study was carried out in patients with UC and healthy controls. Body composition was measured in both groups to obtain the PhA. U Mann-Whitney test was used to compare the data. Patients were classified according to their PhA, considering a normal value of >6.1° and a low value of >6.1°.

Results

The study included 60 UC and 120 controls, 65% were women, and 35% men, the PhA was lower in UC compared to the controls, in addition to the fact that patients with active disease had a lower PhA compared to patients with remission (5.6±0.9 vs 6.06±0.8, p<0.05). In our study, patients with a low PhA had a lower amount of weight (Active: 60.5±13.6 vs 70.3±.8, p=0.018, Remission: 57.1±11.4 vs 69.4±8.7, p=0.006), dry lean mass (Active: 13.8±3.6 vs 18.2±.6, p=0.009; Remission: 13.1±2 vs 19.7±5.3, p<0.001), total body water (Active: 27.4±6.2 vs 32.9±4.6, p=0.028; Remission: 25.3±3.8 vs 34.4±9.2, p=0.003), and intracellular water (Active: 51.9±3.2 vs 55.1±3.3, p=0.042; Remission: 49.3±10.7 vs 55.8±3.6, p=0.025 ) regardless of disease activity. In this population, we can observe that the inflammation markers (ESR, CRP) were increased in accordance with the activity of the disease associated with PhA, which is consistent with what has been reported in the literature.

Conclusion

The PhA is modified in patients with UC compared to healthy patients, even more so when they have active disease. Women with active UC are those at risk of malnutrition and cardiovascular risk measured by PhA and CCI. PhA is effective in diagnosing malnutrition in patients with UC regardless of conventional parameters for evaluating nutritional status (Figure 1).Read more N02 Inflammatory bowel disease patients with impaired quality of life on biologic therapy benefit from the support of an IBD nurse specialist: Results of a randomized controlled trial in Germany (IBDBIO-ASSIST study) - The IBD nurses perspectiveWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

IBD nurses play an important role in the Multidisciplinary Team of managing patients with IBD. IBD_BIO-ASSIST was a randomised controlled trial assessing the efficacy of care provided by an IBD nurse specialist in improving health-related quality of life (QoL) in IBD patients on biologic therapy in an outpatient setting in Germany.

Methods

In total, 1086 IBD patients on biologic therapy were randomly assigned to either a control group (CG) receiving usual IBD care or an intervention group (IG) receiving additional care from an IBD nurse. Two IBD nurses per site received an extra study specific IBD training before including patients. The primary outcome was disease-specific QoL (sIBDQ) assessed at months (M) 6, 12, and 18. In addition, IBD nurses provided a final assessment of various aspects of their work in the context of the study at M6 (T0) and M15 (T1), and patients were asked about their satisfaction level with the IBD nurses.

Results

The analysis of patients with impaired QoL at baseline (EQ-VAS < 75 [median]), showed an improvement in sIBDQ over 6 M that became significant at M12 and remained significant through M18 (baseline: IG 4.24; CG 4.31; M18: IG 5.02; CG 4.76; P= .017) (Table 1). Regarding the 5 aspects of fun, usefulness, successful discussions in consultations with patients, successful support of patients, and appreciation by patients, the nurses expressed positive assessments (“completely” and “rather”) at both measurement points, with values of more than 90% (Fig. 1). About 20% to 30% of the nurses reported being rather dissatisfied with two aspects of their jobs: time and space resources for discussions and recognition by physicians. 94% of patients in the IG felt that the additional care provided by the IBD nurses was highly beneficial.

Conclusion

IBD patients with impaired QoL derived a significant benefit from the additional care provided by an IBD nurse specialist, leading to meaningful improvements in sIBDQ over the long term. The survey results from the IBD nurses and patients in the IG revealed a very positive perception of the new form of care. It is noteworthy that an improvement in care provision was reported both by the nurses and the participating patients. Some physicians also experienced benefits from the intervention as they were relieved of certain time-consuming tasks by the IBD nurses. It should be noted that more than 20% of the IBD nurses did not feel sufficiently appreciated by physicians, and about 30% criticised the lack of time and space resources. When introducing the IBD nurse-led care concept into usual practice, these aspects should be considered.Read more P1211 A faecal microbial signature, in combination with faecal calprotectin, to optimise endoscopic activity monitoring in Crohn’s DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Monitoring Crohn's Disease (CD) endoscopic activity (EA) is crucial to identify disease progression and tailor treatment. Faecal calprotectin (FC) provides a non-invasive and cost-effective alternative to colonoscopy; however, it exhibits only a moderate correlation with EA in CD, highlighting the need for a non-invasive approach that either replaces or complements FC.This study aimed to identify a faecal microbial signature that could offer more precise monitoring of EA in CD.

Methods

A cohort of 55 CD patients was recruited from four Spanish hospitals. All participants provided a faecal sample before undergoing colonoscopy for the analysis of FC levels and microbial markers abundances, including Eubacteria (EUB), Escherichia coli (ECO), Faecalibacterium prausnitzii (FPRA) and its phylogroups I and II (PHG-I, and PHG-II), Ruminococcus spp. (RUM), Akkermansia muciniphila (AKK), Methanobrevibacter smithii (MSM), Clostridium clusters I and XIV (CLO, and XIV), Enterococcus sp. (ENT), Roseburia sp. (ROS), and Gammaproteobacteria (GAM). The Simplified Endoscopic Score for Crohn’s Disease (SES-CD) was employed to assess EA, being remission and activity defined as SES-CD≤2 and SES-CD>2, respectively.

Results

FC levels showed a significant correlation with SES-CD (r_s=0.778, p<0.001) and a cut-off of 250 μg/g discerned EA with 86.49% sensitivity (SS), 75.65% specificity (SP), 77.06% positive predictive value (PPV) and 84.53% negative predictive value (NPV). Significant differences were identified when comparing the relative abundances of ECO (p<0.005), GAM (p<0.005), and RUM (p=0.026) between activity and remission. The relative abundance of ECO (r_s=-0.495, p<0.001), GAM (r_s=-0.492, p<0.001), and RUM (r_s=0.274, p=0.042) also showed a significant correlation with SES-CD. None of the microbial markers alone exceeded FC performance.The combination of FC levels with the abundances of the microbial markers ECO, RUM, GAM, PHG-II, and XIV in a unique signature outperformed FC alone in discerning EA, with 97.57% SS, 93.59% SP, 91.65% PPV, and 97.57% NPV. The false positive (FP) and negative (FN) rates were reduced by 60.00% and 75.00%, respectively, compared to FC alone. Notably, all the FN presented mild endoscopic activity, indicating accurate monitoring of patients with moderate or severe EA.

Conclusion

A new faecal microbial signature combined with FC has been defined to monitor EA in CD with higher performance than FC alone. This tool may improve clinical decision support systems in CD management, refining endoscopic allocation, and providing a more patient-friendly and cost-effective approach. Further studies are needed to validate these results.Read more P1212 Effects of Enterococcus faecalis-derived Gelatinase E on HCT116 colorectal cancer cellsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The leading cause of death in colorectal cancer (CRC) patients is metastasis to crucial organs, such as the lung, brain and liver. The tumour microenvironment (TME) influences metastasis heavily. One important component in the TME of CRC is the microbiota. Microbiota can affect several pathways related to the origin of metastasis and reorganization of the extracellular matrix. One of the possible contributors to early CRC metastasis is Enterococcus faecalis. E. faecalis produces Gelatinase E (GelE), a quorum-sensing protein with collagenolytic properties. The primary goal of our study was to determine the effect of GelE on CRC behaviour, and especially on migration and invasion in HCT-116 human CRC cells. Moreover, we aimed to uncover the underlying pathways by which GelE influences CRC cells.

Methods

Extracellular GelE was purified from E. faecalis strain V583 from the culture medium. HCT-116 cells were cultured and exposed to different concentrations of GelE. We performed a viability assay using CCK-8 to assess potential toxicity of GelE. To test effects of GelE on collagen structure, we measured stiffness of collagen-I. A transwell assay was used to assess the influence of GelE on invasive capacity of cells through a collagen-I matrix. GelE exposed cells were assessed for shape and motility markers using immunofluorescent staining for β-catenin (cell shape) and loss of E-cadherin (cell motility marker). For mechanistic insight of GelE exposure on HCT116, we performed proteomics analysis on the cells.

Results

GelE treatment did not affect relative cell viability of HCT116 cells up to a concentration of 100 μg/ml. Exposure to GelE caused a concentration-dependent increase in HCT-116 cell invasion through collagen-I. The immunostainings showed a downregulation of E-cadherin, indicating an induction of cell motility. Immunostaining for β-catenin showed a statistically significant effect on cell shape, becoming more elongated, an additional indication of cell motility. Proteomics showed possible mechanistic pathways that explain the increased motility including activation of the SMAD pathway, RhoGTPAse activation and activation the urokinase-plasminogen system. Reactome database analysis on the proteomics data also revealed an increase in cell-cycle related pathways.

Conclusion

Our results indicate that E. faecalis-derived GelE drives HCT-116 invasion with an elongated motility. Therefore, drugs inhibiting the activity of GelE could decrease the risk of metastasis in patients with a high E. faecalis V583 abundance in the TME.Read more P1213 The effects of Escherichia coli Nissle 1917 on the gut microbiota composition in ulcerative colitis patientsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Escherichia coli Nissle (EcN) 1917 is a Gram-negative bacterium currently used as probiotic in the management of infectious gastroenteritis and ulcerative colitis (UC).We evaluated the effect of administration of EcN on the composition of the gut microbiota and on intestinal permeability in patients affected by UC.

Methods

Five patients with stable UC were treated with EcN one pill daily for ten days followed by two pills per day for further twenty days. Fecal samples were collected before the treatment (T0), after ten days (T1) and after one month of treatment (T2). Alpha diversity, microbiota composition and taxonomy were analyzed.

Results

Alpha diversity increased through treatment: Good’s coverage index revealed an increase in the number of operational taxonomic units (OTUs) at T2. At phylum taxonomic level, Firmicutes relative abundance decreased at T1 compared to T0. At family level, Clostridiacae relative abundance at T1 was higher than T0 and T2. The T test on gut microbiota variations at species level reveals the variability at the two timepoints (T0 and T2), with significant increase for Actinomyces, Anaerostipes, Bacteroides, Bulleidia, Corynebacterium, Dialister, Enterobacteriaceae, Erysipelotrichaceae, Finegoldia, Granulicatella, Lactobacillaceae, Peptoniphilus, Phascolarctobacterium, Roseburia, Serratia, Veillonellaceae, Veillonella dispar.Furthermore, the administration of EcN improved intestinal permeability, assessed on a CaCO2 monolayer.

Conclusion

Treatment with EcN leads to an improvement in the qualitative composition of the gut microbiota in patients affected by UC, in terms of both diversity and taxonomy. These effects are stronger at the end of treatment.Read more N21 Shared Decision Making: A Qualitative Exploration of Clinical Nurse Specialists in GastroenterologyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Clinical Nurse Specialists (CNS) participation in the Shared Decision Making (SDM) process and understanding basic concepts and principles related to the decision-making process are critical. (Storms et al. 2015). The core concept role of CNS includes a clinical focus on direct and indirect care of the patients in the specialist area, health educator and trainer, patient advocate, audit and research and consultation (NCNM, 2008). They have many opportunities to participate in the SDM process with patients arising from clinic visits, telephone helpline services and multidisciplinary team meetings. Nurses are progressively deemed influential in shared decision-making; however, studies on the SDM role of the CNS are limited; our study investigates the experiences of CNS in SDM, in the speciality of gastroenterology (GI) in both medical and surgical.

Methods

This study adopted a qualitative descriptive style. The survey was distributed to medical and surgical GI CNS at a tertiary referral hospital. This study aimed to look at three aspects of CNS's SDM experience: the CNS's knowledge about SDM, generating discussion and coordination, and respect for sociocultural factors. Semi-depth interviews were conducted for data collection. There were 11CNS participants from surgical and medical GI specialities, including IBD, hepatology, endoscopy, upper GI, and colorectal nursing. All interviews were recorded and transcribed verbatim and coded.

Results

Six themes emerged from the data collected: perceptions, attitudes, positive change, influential factors, reflection and obstacles. SDM is an unknown concept for the majority of the CNS.CNS self-identified as integral to the speciality and the patient's primary contact.

Conclusion

CNS has little understanding of the SDM concept. SDM is perceived as MDT (Multi-Disciplinary Team) making decisions without patient involvement. Formal education and increased awareness of the SDM process are essential for CNS active participation in individual patients. The procured knowledge of SDM enhances the CNS's confidence in active participation in MDT team meetings and the SDM process. It consequently improves patient experience, knowledge and participation in the SDM process.Read more N22 Compliance with Anti-TNF Alpha Treatment and Quality of Life of Inflammatory Bowel Patients: A Descriptive and Correlational StudyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Today, anti-TNF agents are often preferred in the treatment of inflammatory bowel diseases. During this long-term treatment, patients' compliance with the treatment is very important. This study aims to determine the relationship between compliance with anti-TNF alpha treatment and quality of life in inflammatory bowel patients.

Methods

This study is currently being carried out at Gazi Hospital Gastroenterology Department, Inflammatory Bowel Diseases Outpatient Clinic. The study will be carried out between November and February 2024. Data are collected using the "Patient Information Form", "Inflammatory Bowel Diseases Quality of Life Scale", "Anti-TNF Alpha Treatment Compliance Scale". Whether the variables were suitable for normal distribution was determined by the Kolmogorov-Smirnov test. Since parametric test assumptions were not met, Mann-Whitney U test, Kruskal Wallis test and Sperman correlation analysis were used in the analysis of scale scores. Statistical significance value was accepted as p<0.05.

Results

In this section, the pilot results of the study are presented and its implementation is ongoing (Number of patients reached: 117). The mean age of the patients participating in the study was determined to be 38.99±13.73 (minimum=18, maximum=68). It was determined that 53.7% of the patients were male, 57.3% were married and 42.7 of them had no children. The diagnosis of 65% of patients is Crohn's disease. The rate of patients being diagnosed with inflammatory bowel disease for 3-5 years was found to be 29.9%. The total score of the Inflammatory Bowel Diseases Quality of Life Scale was found to be 160.04±32.24 (minimum=88.00, maximum=224.00). The total score of the Anti-TNF Alpha Treatment Compliance Scale was found to be 2.36±0.72 (minimum=1.00, maximum=4.58). It was determined that there was a strong negative relationship between the total scores of the scales (p= <0.001).

Conclusion

It can be said that the treatment compliance of the patients is at a moderate level and their quality of life is at a good level. The relationship between patients' treatment compliance and their quality of life is also negative.Read more P1173 Higher total antioxidant capacity of diet is associated with reduced surgery risk in individuals with Inflammatory Bowel Disease in a prospective cohort studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Oxidative stress exacerbates inflammatory Bowel Disease (IBD), and dietary antioxidants are proposed as a promising manner to counteract this imbalance. However, the role of individual antioxidants in the complex milieu of the human body may exhibit synergistic or interactive effects. The research has yet to comprehensively examine the impact of dietary total antioxidant capacity (TAC) on IBD prognosis. To fill this knowledge gap, this study aimed to investigate the assocaitions between dietary TAC and risk of related surgery among individuals with IBD in a prospectively recruited cohort.

Methods

We included 2439 individuals with IBD at baseline from UK Biobank. All participants have completed a web-based validated 24-h dietary recall up to five rounds in 2009-2012, reporting their consumption of more than 200 foods and beverages. We calculated the TAC of the diet using the oxygen radical absorbance capacity method and were grouped by quintiles. The outcomes of interest were IBD-related surgery (bowel resection, perianal-related surgery, Strictureplasty, and ileoanal pouch formation), ascertained via linkage to national inpatient data. Cox proportional hazard models were applied to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs).

Results

During a mean follow-up of 10.4 years, we identified 261 incident surgical cases related to IBD. The mean age of the participants was 56.9 years, and 51% were females. When comparing extreme quintiles of dietary TAC, individuals with higher dietary TAC were associated with a lower risk of related surgery (HR 0.57, 95% CI 0.38-0.86, P=0.007). The inverse associations between dietary TAC and related surgery were consistent among individuals with ulcerative colitis (HR comparing extreme quintiles 0.59, 95% CI 0.36-0.96, P=0.036). For individuals with Crohn’s disease, the associations were not significant when comparing extreme quintiles of dietary TAC (HR 0.51, 95% CI 0.25-1.03, P=0.060), while we observed a significant 9% risk reduction (HR 0.81, 95% CI 0.65-1.00, P=0.048) of related surgery by per 1-SD increment in dietary TAC among individuals with Crohn’s disease.(Table 1)

Conclusion

In this large large-scale population-based cohort study, we observed that higher dietary TAC was associated with reduced risk of related surgery in individuals with IBD. Our findings provide insights that could inform dietary recommendations and potentially improve IBD management strategies.Read more P1169 Multimorbidity and Disease Trajectories in Patients with INFLAMMATORY BOWEL DISEASES: Insights from Observational and Genetic AnalysesWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The multi-morbidity pattern of inflammatory bowel disease (IBD) remains under-explored. We integrated both observational and genetic data to elucidate multisystem comorbidities and health consequences of IBD.

Methods

Phenome-wide association study (PheWAS) based on the international classification of disease (ICD)-diagnosed IBD was conducted to explore its associations with 1,053 unique clinical outcomes in the UK Biobank. Disease trajectory analyses were implemented to illustrate sequential patterns of IBD-related comorbidities. The associations of genetic liability to IBD proxied by a polygenic score with identified clinical outcomes were examined to strengthen causality (N=385,917). To investigate potential shared genetic bases and causality, we performed a cross-trait linkage disequilibrium score regression (LDSC) and two-sample Mendelian randomization (TSMR) analysis using the FinnGen biobank (N=377,277). The impact of IBD subtypes and the age at diagnosis were also evaluated in sensitivity analyses.

Results

A total of 5,782 cases with IBD (3,940 cases with UC and 1,800 cases with CD) were diagnosed at baseline in the UK Biobank. Observational PheWAS revealed elevated risks of all-cause mortality with HRs of 1.34 (95%CI=1.24-1.45, P<0.001), 1.61 (95%CI=1.41-1.83, P<0.001) and 1.22 (95%CI=1.10-1.34, P<0.001) for patients with IBD, CD or UC respectively. Increased mortality risk was noted across pediatric, early-onset, and later-onset IBD patients. Sequential patterns of IBD-related comorbidities were primarily found in cardiometabolic, respiratory, digestive and autoimmune diseases. The polygenic PheWAS, LDSC and TSMR analyses supported both strong genetic correlations and causal associations of IBD with immune-mediated (notably psoriatic arthropathies, psoriasis, dermatitis, asthma) as well as non-autoimmune diseases ( pneumonia, anemias, and renal failure).

Conclusion

Our observational and genetic analyses suggest multisystem comorbidities and consequences of IBD, highlighting the need for multidisciplinary clinical management and investigation of shared biologically or genetically regulated mechanisms in the pathogenesis of IBD.Read more P1206 Mechanistic implications of the Mediterranean diet in patients with newly diagnosed Crohn’s disease- multi-omic analysis of a prospective cohortWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The Mediterranean diet (MED) is hypothesized to play a protective role in Crohn’s disease (CD) etiology, yet the underlying mechanisms remain unclear. Here we explored the association between adherence to MED, CD course, clinical and inflammatory markers, and microbial and metabolite composition in patients with newly diagnosed CD.

Methods

Patients with newly diagnosed CD were recruited and prospectively assessed. Food frequency questionnaires (FFQ) were collected each visit and assessed for adherence to MED, using a predefined IBDMED score, alongside validated MED adherence screeners. The Crohn’s disease activity index (CDAI) was used to evaluate clinical activity and serum and fecal samples collected for fecal calprotectin, C-reactive protein (CRP), and microbial composition using 16S rRNA sequencing. Baseline serum and fecal metabolomics were analyzed using a targeted quantitative metabolomics approach. Patients were classified as having a complicated course if during follow-up, they were steroid dependent, switched ≥2 biologics, hospitalized or underwent CD-related surgery.

Results

We recruited and prospectively observed 271 consecutive patients with newly diagnosed CD (52% males, average age- 31±12 years, inflammatory phenotype, B1- 75%) and collected 636 FFQs (range 1-5 FFQ per patient). Adherence to MED was associated with a non-complicated course and was inversely correlated with CDAI, fecal calprotectin, CRP and microbial dysbiosis index (all p<0.05). Increasing adherence to MED over time was associated with decreasing CDAI and fecal calprotectin in patients with complicated and non-complicated courses (p<0.05). Diet microbial interactions revealed two microbial clusters, showing that adherence to MED and intake of its recommended foods positively correlated with commensals and short-chain fatty acid producers including Faecalibacterium. Conversely, adherence to MED inversely correlated with a cluster of members of the Proteobacteria and included Ruminococcus gnavus. Diet metabolomics interactions revealed two clusters showing that adherence to MED positively correlated with multiple serum and fecal organic compounds, vitamin derivatives, plant metabolites, amino acids and tryptophan metabolites and inversely associated with fecal triglycerides, ceramides and cholic acid, the major primary bile acid (FDR<0.1).

Conclusion

Adherence to MED is associated with lower levels of primary bile acids and microbial dysbiosis and with a beneficial microbial and metabolite composition in patients with newly diagnosed CD. This may drive the inverse association of MED with clinical activity, inflammatory markers and complicated course. Microbial and metabolite-targeted dietary approaches like MED, should play a role in CD management.Read more P1207 Microbiome composition determines sustained remission after the Crohn’s Disease Exclusion Diet (CDED) with or without Partial Enteral Nutrition in adults with mild-moderate Crohn’s disease; Results from the CDED-AD Pilot Randomized Controlled TrialWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The Crohn's Disease (CD) Exclusion Diet (CDED) is an established dietary therapy for children with active mild-to-moderate CD. A recent randomized controlled trial showed efficacy in mild-to-moderate CD in adults. We have previously demonstrated the impact of CDED on the microbiome of children. The aim of this work was to assess if we can determine sustained clinical remission (SCR) from the baseline microbiome composition and examine the effect of CDED on microbiome composition in adult CD.

Methods

This was an open-label, prospective, randomized, controlled pilot trial involving patients with mild-to-moderate CD and evidence of active inflammation. Patients were randomly assigned to receive CDED with partial Enteral Nutrition (PEN) or CDED alone, both for 24 weeks. The V4V5 region of the 16S rRNA gene was amplified and sequenced, and reads were processed using QIIME2 and the SILVA database. Relationships between the microbiome, SCR, and Fecal Calprotectin (FC) were analyzed using logistic regression, Poisson Principal Component Analysis, paired T-Tests and subsampling ranking forward selection.

Results

Clinical remission (CR) at weeks 6, 12 and 24 was achieved in 62.5%, 52.5%, and 50% of patients, respectively. Week 0, 6, 12 and 24 stool samples were available for 35,32,30 and 26 patients, respectively. In patients with SCR, defined as remission at both weeks 12 and 24, the baseline microbiome revealed lower alpha diversity compared to those without SCR (p=0.018), and differing Microbiome principal components (PC) scores (p < 0.01). PC1 and PC3, characterized mainly by Alistipes, Faecalibacterium and UCG-002 predicted SCR (P<0.01). PC2 predicted elevated FC>250 µg/g at week 12 (p=0.004). Baseline abundance of Haemophilus was associated with decreased SCR probability (p<0.01). At week 6 in the entire cohort, there was a significant decrease in Actinobacteriota (p=0.035) and a significant increase in Bacteroidota (p=0.003). Additionally, there was a significant increase in several genera, including beneficial Alistipes and Oscillibacter (p<0.02) in those who achieved CR after 6, 12, or 24 weeks. Higher Firmicutes at week 6 were associated with FC<250 at week 12 (p=0.031). An uncultured genus from the Oscillospiraceae family was significantly associated with a decrease in the probability of SCR (p<0.01) and was significantly increased at week 6 in patients who did not attain CR (p<0.05).

Conclusion

The baseline microbiome composition was associated with SCR and FC<250 at week 12 in adult patients treated with CDED (with or without PEN) over 24 weeks. This suggests that the microbiome could be useful tool to identify patients who would benefit from long-term dietary intervention.Read more P1208 MH002, an optimized live biotherapeutic product, for the treatment of inflammatory bowel diseases, has mode-of-actions linked to restoration of intestinal dysbiosis, mucosal integrity, and immune homeostasisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

MH002 is a live biotherapeutic product consisting of 6 well-characterized commensal strains, that is in clinical development for the treatment of Ulcerative Colitis (UC) and acute Pouchitis. Both are multifactorial disorders which occur through a combination of dysregulated host inflammatory mechanisms and interactions with gut microbiota.

Methods

Faecal slurries of 6 UC patients with active disease were prepared to inoculate a standardized in vitro gut model (SHIME®) which mimics the colon microbiome of patients. A total of 24 simulators were run for 8d, with a single dose administration of MH002 (human equivalent dose [HED] ~1) or vehicle on Day0. Butyrate production in the simulators was quantified daily and host response effects were assessed in in vitro cell-based assays using samples from Day1. Caco-2 cells were co-cultured with human peripheral blood mononuclear cells and treated for 48h with Day1 samples, followed by transepithelial electrical resistance (TEER) and cytokine measurements. Wound healing was assessed by imaging of monolayers of T84 cells, scratched and treated with Day1 samples.Furthermore, the effects of MH002 (daily, 24d, HED ~30) on disease activity index (DAI; body weight [BW], stool consistency, occult blood), local inflammation, and mucosal damage were evaluated in acute dextran sulfate sodium (DSS) induced colitis, when administered to C57BL/6 mice (15/group) as from 14d prior to DSS intake, and compared to 5-aminosalicylate (5-ASA; daily, 24d, 150mg/kg) and vehicle. Animals were euthanized in the acute (Day7; 10/group) and recovery phase (Day11; 5/group).

Results

In vitro administration of MH002 to patient-derived colonic microbiomes restored within 1d butyrate production and increased efficiency to improve epithelial barrier integrity, modulate T-cell-mediated immune responses, and promote mucosal wound healing in in vitro cell cultures (Table 1).DSS intake induced a significant decrease in relative BW and an increase in DAI. A significant recovery (BW, DAI, stool consistency) was observed at Day11 for MH002 and 5-ASA. Moreover, at Day11, macroscopic inflammation (colon weight/length ratio) and histologic scores were lower with MH002 and 5-ASA as compared to vehicle (Figure 1).

Conclusion

By restoring intestinal dysbiosis and epithelial integrity, and attenuating local inflammation, MH002 treatment should lead to lower disease activity and, ultimately, to clinical remission without immune suppression. Indeed, study MH002-UC-201 in mild-to-moderate UC was completed with favourable treatment effects (endoscopic improvement, faecal calprotectin normalization, improved stool consistency) and no safety concerns (Abstract Vermeire et al.; EudraCT 2020-004355-33).Read more P1209 Baseline gut microbiota composition and function reflect response to 5-ASA treatment in Ulcerative ColitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Mesalazine (5-ASA) is a key initial treatment of ulcerative colitis (UC); recent studies have highlighted the role of the gut microbiota in 5-ASA metabolism. There is no established means of predicting treatment outcome. We sought to investigate changes in the gut microbiota and metabolome with 5-ASA treatment, and whether such changes may reflect clinical outcomes.

Methods

Longitudinal faeces, serum and urine samples were collected from patients with newly diagnosed UC before and after 5-ASA treatment. We documented longitudinal microbiota and metabolome changes with 5-ASA treatment and compared baseline gut microbiota and metabolome in responders (simple clinical colitis activity index (SCCAI) of <4 and faecal calprotectin (FC) of <100 µg/g) and non-responders to 5-ASA. Stool bacterial profiling was performed via 16S rRNA gene sequencing of the V1/V2 hypervariable regions. Host and microbial metabolites in stool, serum and urine were detected and semi-quantitated using liquid chromatography mass spectroscopy (LC-MS) and nuclear magnetic resonance spectroscopy (¹H-NMR). Kruskal-Wallis tests and paired analyses using a Wilcoxon rank test were used and p values were adjusted using Benjamini-Hochberg false discovery rate (FDR) correction.

Results

37 patients newly diagnosed with UC were recruited. Samples were collected at baseline and a median of 83 days (IQR 22.5 days) later; there were 27 responders and 10 non-responders. Comparing pre- and post- 5-ASA treatment samples demonstrated a reduction in gut microbial α diversity (P=0.01) (Fig 1). Faecal methionine increased with 5-ASA (P=0.04) in all patients, and isovalerate reduced with 5-ASA (P<0.01). Similar reductions after 5-ASA were noted in serum glycoprotein B (GlycB) (P=0.02).At baseline, responders tended to have increased α diversity compared to non-responders, but not statistically significantly (P=0.09). Similarly, there were β diversity differences, although these did not reach significance (P=0.06). At baseline non-responders had a higher relative stool abundance of Bacteroidetes and Firmicutes (P<0.01) compared to responders. Agathobacter, Coprococcus and Blautia genera were enriched in non-responders (P=0.05). At baseline, urinary hippurate was higher in patients going on to respond to 5-ASA compared to non-responders (P=0.04); faecal lysine (P<0.01) and putrescine (P=0.01) levels were also higher in non-responders at baseline. 5-ASA responders had reductions in faecal 2-methylbutyrate and isobutyrate (P=0.02) longitudinally.

Conclusion

We have shown that baseline relative abundance of certain taxa (such as Blautia), urinary Hippurate and faecal lysine reflect response to 5-ASA. Alterations in the gut microbiome and metabolome are associated with 5-ASA treatment.Read more N17 Exploration of medication non-adherence in Inflammatory Bowel Disease patients: A systematic reviewWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Inflammatory bowel disease (IBD) has recognised medications to maintain remission and prevent relapse. Yet between 53–75% of people with IBD do not take medications as prescribed. Identifying and improving medication adherence in IBD is a primary treatment goal to keep symptoms quiescent.This systematic review aims to identify why people are adherent and non-adherent to IBD medications.

Methods

Studies exploring medication adherence for IBD conducted between 2012-2022, were identified in six electronic databases.The quality of quantitative and qualitative studies was assessed using a scoring system or the Critical Appraisal Skills Programme, respectively.

Results

39,603 participants were included across 79 studies investigating IBD medication adherence, mainly from single outpatient clinic populations, using cross-sectional surveys.Most data were quantitative, rated medium quality. Few studies were based around a theory to explain adherence.Non-adherence was most typically measured using a version of the Morisky Medication Adherence Scale or the study’s own self-report questionnaire, with non-adherence ranging from 4.3%-88.9%.In multivariable analysis of quantitative data, younger age and female gender were usually associated with non-adherence. The presence of smoking, psychological issues (depression, treatment concerns, anxiety) or lower social status were also significant non-adherence risk factors. Most typically investigated were clinical variables, many being significantly related with non-adherence, including medication type (specifically 5-ASA), route (oral, rectal, subcutaneous, intravenous), high and low disease activity and poor disease/medication knowledge. Significant results were often contradictory between studies, as was the relationship direction with non-adherence.Forgetting medication was the main reason for non-adherence in qualitative interviews, with side effects, costs, medication concerns and busy lifestyle also variables.Cohort-specific factors were reported for non-adherence in pregnant women, adolescents and patients during COVID.ConclusionAdherence to treatment is essential in IBD. Yet a large and confusing literature exists regarding factors underpinning non-adherence.Clinicians should be aware of those non-modifiable factors, to help identify relevant patients and support their treatment programme.Potentially modifiable factors including medication regimes, route and patient knowledge, could be targeted to improve adherence in IBD.Theoretically informed interventions need to be developed. A successful evidence-based intervention supporting medication adherence could help improve quality of life for patients living with IBD, whilst providing patient-centred care and minimising health costs.Read more N18 The experience of the IBD patients with a permanent or temporary stoma: update of the literatureWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Surgery is indicated in selected patients with inflammatory bowel disease (IBD).Annually, 2000 (0.66%) of these individuals in the UK and an estimated 24,000 (1.5%) in the USA undergo surgery resulting in a permanent or temporary stoma. The audience of patients undergoing a stoma surgery is very broad and consists of not only elderly people, but also young adults, fertile or pregnant women.Fear of having a stoma is a major concern for people with IBD. And this aspect goes beyond the simple therapeutic aspect but it encroaches upon the psychological, occupational, relational, educational, financial and domestic area.This study aims to analyze the Quality of Life (QoL) outcomes of IBD patients with temporary or permanent stoma

Methods

To identify, evaluate and synthesis the lived experiences of IBD patients having a stoma, a meta-synthesis has been performed following the Sandelowski and Barroso guidelines (2007).Studies included: primary studies in English language, conducted using qualitative methodology that explore the subjective experience of IBD patients having a temporary or permanent stoma; studies that debated the experiences lived during the period of having a stoma; studies published from January 2013 to October 2023. The instrument Critical Appraisal Skills Program (CASP) has been used for the qualitative evaluation of the included studies (Image 1)

Results

Sixteen studies have been analyzed and the most of them involved more than one medical or research institution. The included studies described different areas of the perceived experience of 3046 IBD patients with a stoma. A total of 30 labels have been classified into 12 sub-themes, grouped in a total of five themes. (a) Surgery is a trigger for possible psychological disorders such as PTSD and (b) the positive perception of the stoma as an effective therapy in the management of IBD symptoms are the most frequent labels in the studies (Table 1)

Conclusion

The results of this study contributed to provide evidence about the experience of stoma-bearing IBD patients.Healthcare providers should offer improved interdisciplinary counselling earlier in the course of IBD so as to inform and enpower the patient and allow for shared decision-making. Patient information, education and support groups are crucial when managing IBD patients and optimizing patient-reported outcomes.This counts especially for young subjects that would be less prone to accept a stoma.Taken together, these findings provide further proof of the complex interplay between various psychological aspects.Our findings are consistent with previous research, which suggest, in terms of direction for psychological operations,that an increased focus in the educational and management of the disease is crucialRead more P1202 Genome wide association study result for inflammatory bowel disease: A single institute experience in TaiwanWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Inflammatory bowel disease (IBD) have two major subtype disease, including Crohn’s disease(CD) and Ulcerative colitis(UC). These two diseases of IBD in which abnormal reactions of the immune system induced inflammation and ulcers in any part of gastrointestinal tract from oral cavity to rectum, especially in colon and small intestine. Now, IBD still not have an identifiable cause and many articles that discussion about risk loci of IBD was published in recent years. Hence, we try to identify the risky locus related with IBD.

Methods

From January 1992 to December 2023, we retrospectively reviewed the medical records of patients diagnosed as inflammatory bowel disease at our hospital. We also use Phecode Map with ICD9 codes for finding out more pateints. Then, we used the our hospital’s genetic data warehouse to assay these patient’s genome for identifying the specific loci associated with inflammatory bowel disease.

Results

A total of 286 patients with inflammatory bowel disease from January 1992 to December 2023 was in medical record. The number of Crohn's disease and ulcerative colitis were 102 and 184 respectively. However, only 85 patient with CD and 145 patient with UC were in our hospital’s genetic data warehouse. In addition, we seek cooperation with our hospital’s artificial Intelligence Center for using Phecode Map with ICD9 codes for finding out more patients. Finally, 660 case was in genetic data warehouse.The our result of Genome-wide association study (GWAS) for inflammatory bowel disease that identified 15 potential SNPs, such as RTN4, EML6, CLHC1, MYO10, EFEMP1, ADCY2, TPD52 etc.. Two of 15 potential SNPs, NPAS3, DSCAM has been found to be a risky SNPs of IBD in past study and our result of GWAS for IBD. Another 13 SNPs was potential association with IBD in our result, but not well-known risky gene in past research. Only one genetic locus: CRY2 had statistically significant difference and vaule of -log10(p) is more than 6. But, no similar thesis was reported after we review other published papers about loci associated with inflammatory bowel disease. The relationship between CRY2 and inflammatory bowel disease is still pending investigation.

Conclusion

Although, around 200 genomic loci was considered to be associated with inflammatory bowel disease. But, the precise mechanism by which these loci contribute to IBD were still being investigated. However, more genetic loci associated with IBD was identified can lead us to approach the understanding of the underlying biology of the disease.Read more P1203 Fecal transplantation for Ulcerative Colitis from diet conditioned donors followed by dietary intervention results in favorable gut microbial profile and decreased gut inflammation compared to fecal transplantation aloneWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Several fecal microbial transplantation (FMT) approaches for ulcerative colitis (UC) have been investigated with conflicting results. We have recently published the clinical outcomes from the CRAFT UC Trial using FMT with the UC Exclusion Diet (UCED), a novel diet for active UC, compared with FMT alone. Here we aimed to compare the two FMT strategies in terms of microbial profile and functional outcomes.

Methods

Subjects recruited to the CRAFT UC study with available pre- and post-intervention fecal samples were included. Seven donors received diet conditioning for 14 days in line with the UCED principles. Group 1 received single donor standard FMT by colonoscopy on Day 1 and rectal enemas on Days 2 and 14 without dietary conditioning of the donor (N=11). Group 2 received FMT as above but with dietary pre-conditioning of the donor and UCED for the patients (N=10). Pre- and post-intervention fecal samples were assessed by DNA shotgun metagenomic sequencing to obtain microbial compositional and functional data. Data was analyzed using a multivariable linear regression mixed effects model and spearman correlation. Benjamini-Hochberg correction was used for multiple testing with p-values<0.05 and q-values<0.2 considered significant.

Results

Following diet conditioning, donors had significant depletion in microbial metabolic pathways involved in the biosynthesis of sulfur-containing amino acids. Only patients in Group 2 receiving FMT from diet conditioned donors followed by the UCED showed significant shifts towards the donors’ microbial composition (ADONIS: R2=0.15, p=0.008). Eubacterium sp AF228LB was significantly increased post-intervention in Group 2 (β-coefficient 2.66, 95% CI 2.1 to 3.3) and was also inversely correlated with fecal calprotectin levels (rho=-0.52, p=0.035). Moreover, microbial metabolic pathways involved in gut inflammation and barrier function including ribonucleotides biosynthesis (β-coefficient 0.29, 95% CI 0.07 to 0.51) and branched chain amino acids (β-coefficient 0.44, 95% CI 0.16 to 0.72) were enriched post intervention only in Group 2 and were significantly correlated with decrease in fecal calprotectin (rho=-0.78, p=0.01 and rho=-0.58, p=0.09, respectively).

Conclusion

FMT from diet conditioned donors followed by the UCED diet led to microbial alterations associated with favorable microbial compositional and functional profile related to sulfur metabolic pathways, which translated to decreased gut inflammation. Our findings support further exploration of additive benefit of dietary intervention for both donors and patients undergoing FMT as a potential treatment of active UC.Read more P1190 Inflammatory Bowel Disease Treatment Economics: Assessing the Financial Ramifications and Striving for Healthcare EquityWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Inflammatory Bowel Disease (IBD) has emerged as a public health challenge. In addition to the health effects on patients, IBD also carries a significant economic impact. The diagnosis, treatment, and follow-up of IBD entail considerable costs for both patients and the healthcare system. Therefore, understanding the economic impact of this disease is crucial for making informed decisions about its management and resource allocation. The aim of this study was to determine the short-term (one month) and long-term (twelve months) economic impact of medical care and surgical treatment in patients diagnosed with IBD at a tertiary-level hospital in Mexico.

Methods

A retrospective study was conducted, which included 118 patients diagnosed with IBD and treated at the IBD Clinic of the "Dr. Eduardo Liceaga" General Hospital in Mexico over the past 12 months. The economic impact of both medical treatment (conventional and biological) and surgical treatment in managing IBD was evaluated. For the calculation of medical treatment costs, the unit costs of medications were based on maximum retail prices at a conventional pharmacy. Surgical treatment costs were based on the hospital's provided costs. Individual costs for each patient were recorded and tabulated, and the total cost for each treatment regimen was calculated at one and twelve months. Descriptive statistical methods were used to analyze the data to obtain measures of central tendency and dispersion.

Results

The average monthly cost of medical treatment for a patient with IBD is estimated to be $11,612.45 Mexican pesos (MXN), resulting in a total cost of $139,349.40 MXN over 12 months. Considering all our patients, the total cost of medical care reaches $16,443,229.20 MXN in 12 months. Regarding surgical treatment, there is an average cost of $626,847.45 MXN per surgical event in patients with IBD. The total cost of surgical treatment for our IBD patients, encompassing a total of 24 patients, amounts to $15,043,379 MXN. Therefore, medical treatment appears to be more cost-effective compared to surgical treatment (the total cost of medical treatment for the 121 patients over one year is $16,443,229.20 MXN, while the total cost of surgical treatment for the 24 patients is $15,043,379 MXN). In our institution, 95% of the IBD Clinic patients receive free medical care. This represents significant cost savings for patients.

Conclusion

This study provides evidence regarding the economic impact of medical and surgical treatment in patients with IBD. The results support the consideration of medical treatment as the more cost-effective option while emphasizing the significance of free medical care in improving equitable access and alleviating the financial burden on patients and their families.Read more P1191 Genetic determinants for smoking behaviour improve our understanding of sporadic versus familial Inflammatory Bowel DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Inflammatory bowel disease (IBD) is influenced by genetic and environmental factors. The latter are often difficult to quantify and may vary over time, unlike genetics. Here, instead of looking at actual smoking behaviour, we explored the impact of genetic determinants of smoking behaviour on IBD risk in sporadic and familial IBD.

Methods

We calculated polygenic scores (PRS) for smoking initiation, smoking cessation, age of smoking initiation, and cigarettes per day in 2784 sporadic cases (1700 CD, 1084 UC), 682 non-IBD controls, and 60 multiplex IBD families with ≥3 affected first-degree relatives (FDR) (142 CD, 31 UC and 100 unaffected FDR). PRS were calculated for different p-value thresholds (5e-8, 1e-5, 0.01, 0.05, 0.1, 0.5 and 1), and based on effect estimates of Saunders et al (Nature 2022, table 1). Groups were compared using logistic regression. P<1.43e-3 was the significance threshold for Bonferroni correction.

Results

Sporadic IBD cases had a higher PRS for smoking initiation than controls (p=4.49e-3), which was driven by the CD cases (p=7.17e-4, fig 1A). CD cases also showed a trend for a higher PRS for cigarettes per day (p=0.026). In familial cases compared to unaffected FDR, we observed some differences in PRS for smoking, but none survived multiple testing (fig 1B). Comparing familial and sporadic cases, we found that the PRS for age at smoking initiation was higher in familial than in sporadic UC (p=9.09e-4, fig 1C). Familial CD showed a trend towards a lower PRS for age at smoking initiation (p=0.023) and smoking cessation (p=0.013) than sporadic CD. Familial CD cases are thus more at risk than sporadic CD cases as they genetically tend to start smoking younger, while the opposite is seen for UC. Also, unaffected FDR of UC families showed a lower PRS for age at smoking initiation (p=5.47e-5, fig 1D) than controls, giving them additional protection. The PRS for smoking cessation (p=3.88e-5) and cigarettes per day (p=4.47e-3) was greater in unaffected FDR of mixed families than in controls, while familial mixed cases had a lower cigarettes per day PRS than sporadic cases (p=1.59e-4).

Conclusion

We found that genetic determinants of smoking behaviour are associated with disease risk in familial and sporadic IBD. While CD risk overall is associated with a greater genetic propensity for smoking initiation, the higher risk in families is linked to genetic age at start of smoking. Meanwhile, unaffected FDR of these families are protected through a higher genetic propensity to stop smoking in mixed families, or to start smoking sooner in UC families, compared to population controls. This study improves our understanding of familial vs sporadic IBD, and could help stratify individuals at risk of IBD.Read more P1192 Deciphering the colonic immune landscape of UC from cellular senescence by integrated bioinformatics analysis and machine learningWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Nowadays, there has been extensive interest in cellular senescence in gastrointestinal diseases. However, the pathological mechanism of cellular senescence in UC and its involvement in colonic immune characteristics remain enigmatic. Therefore, we aimed to investigate the contribution of cellular senescence-related signatures to the colonic immune landscape in UC based on bioinformatics combined machine learning strategy.

Methods

Three gene sets of UC were selected from the Gene Expression Omnibus database, including two training sets and one testing set. We identified cellular senescence-associated differentially expressed genes (DEGs) in UC and performed functional enrichment analysis. Afterwards, signature genes were determined by machine learning algorithms including least absolute shrinkage and selection operator (LASSO) regression, support vector machine recursive feature elimination (SVM-RFE), and artificial neural network (ANN). Furthermore, distinct immune microenvironment abnormalities in UC were comprehensively explored, and the correlation between the signature genes and the colonic immune landscape of UC was also evaluated. Based on the signature genes, we clustered UC samples into distinct subtypes by consensus clustering analysis. Finally, we performed validation of the signature genes in dextran sulfate sodium salt (DSS)-induced colitis.

Results

41 cellular senescence-associated DEGs in UC were identified by intersecting DEGs with the cellular senescence-associated genes from the CellAge database, which were associated with cellular senescence and immune pathways. Following that, seven signature genes were determined by the machine learning method of LASSO regression, SVM-RFE, and ANN, comprising CXCL1, MMP9, CYR61, BAG3, PEX19, RPS6KA6, and ETS2, which were also validated in the testing set. Furthermore, we obtained the most correlated pairs of UC signature genes-immunocytes and found these signature genes were highly corelated with neutrophils and activated CD4⁺ memory T cells. Additionally, the expression profiling of human leukocyte antigen genes and immune checkpoints were also analyzed. Subsequently, two molecular subtypes related to senescence that exhibit significantly different immune characteristics were identified. Finally, the mRNA levels of the signature genes were confirmed in DSS-induced colitis, which were congruent with results gained from the datasets.

Conclusion

In summary, the result has emphasized the essential function of cellular senescence-associated genes in controlling the immune microenvironment for UC. The exploration of the etiopathogenesis of UC through cellular senescence is anticipated to lead to novel advancements in disease diagnosis and potential treatments.Read more P1193 NOD2 and Beyond: Unmasking Tobacco-Induced Epigenetic Changes in Crohn's DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Smoking has been shown to have a very negative impact on Crohn's disease (CD). Indeed, this harmful habit induces the early onset of the disease and doubles the risk of postoperative recurrence. This research project involves a thorough analysis of omics data, with a primary focus on DNA methylation, one of the most prevalent epigenetic modifications. Our hypothesis is that tobacco-induced alterations in gene methylation pattern of subcutaneous adipose tissue (SAT), particularly within key pathways, contribute to a more adverse disease profile in smokers.

Methods

A comprehensive epigenome-wide analysis was conducted using the Illumina EPIC/450k array to investigate subcutaneous adipose tissue in patients with CD, encompassing both smokers and non-smokers. Utilizing tools such as dmpfinder and Bumphunter (minfi), differentially methylated positions (DMPs) and regions (DMRs) were identified. Additionally, gene expression analysis for key genes was performed to establish correlations between methylation and subsequent gene expression, not only in SAT but also in other fat depots such as visceral adipose tissue (VAT) or peripheral blood mononuclear cells (PBMCs).

Results

A distinctive DNA methylation pattern in the SAT of smokers compared to non-smoker CD patients was identified (Fig. 1A). Over 27,270 DMPs associated with significant biological processes related to DNA damage, inflammation, or immunity were uncovered (Fig. 1B-C). Additionally, more than 13,000 DMRs located in the promoter region were identified (Fig. 1C). The relationship between methylation levels in the promoter regions and subsequent gene expression on SAT was validated for selected genes. Specifically, NOD2 exhibited higher DNA methylation in the promoter region among smokers compared to non-smokers CD patients (p value=0.04), resulting in reduced NOD2 gene expression on SAT (p value=0.04) (Fig.1D). Consistent results were observed in other tissues such as VAT and PBMCs (Fig. 1E). Finally, we observe the implication of NOD2 in pathways related to immune response, inflammation or apoptosis and a trend indicating that lower NOD2 expression is associated with higher levels of C-reactive protein (CRP)(Fig. 1F).

Conclusion

Our study reveals that smoking produces DNA methylation changes on SAT of CD patients and affects the expression of several key genes involved in the pathogeny of CD. Particularly, our results unveil a new link between tobacco-smoking and lower NOD2 expression and associate this to an elevated levels of PCR, paving the way for a fresh perspective in exploring disease prognosis.Read more P1222 Gut microbiome differences regarding lifestyle and the history of COVID-19 infection in ulcerative colitis patientsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The microbiome contributes to the pathogenesis of ulcerative colitis (UC) but the contribution of different lifestyle and environmental factors to the compositional variability of the gut microbiota is unclear. Also, it is known that microbiota plays an important role in infectious diseases like coronavirus disease 2019 (COVID-19).

Methods

In 6-month time (June 2021 to December 2021) 49 UC outpatients from Riga East Clinical University Hospital were included in a Cross-sectional study. All patients were divided into groups according to COVID-19 status (COVID-19posvs COVID-19neg) within 6 months. The effect of the lifestyle (smoking cigarettes, alcohol intake, sports activities, and high psychological stress level) and COVID-19 to the gut microbiota in patients with UC was investigated. For taxonomical classifying of the gut microbiome metagenome data, MetaPhlAn v.2.6.0 tool was used. In further analysis gut microbiome (mostly bacteria phyla) and related data was analysed with SPSS 20.0.

Results

Out of 49 patients, 31(63%) were male and 18(37%) were female, the mean age was Md=38 [IQR:34-51]. Fourteen patients (28.6%) have been COVID-19 pos and 35(71.4%) COVID-19 neg. There were no statistically significant differences between COVID-19 pos and COVID-19 neg patients and their microbiota, nor between COVID-19 pos symptomatic 12(24.5%) and asymptomatic 37(75.5%) patients and their gut microbiome. Out of 49, 24(49%) were doing sports, of those 18(51.4%) were COVD-19neg vs. 6 (42.9%) COVID-19pos, p=0.82. Evaluating differences in the gut microbiome regarding physical activities there was no statistical significance. Of 49 patients, 30(61.2%) have smoked before, while 19(38.8%) haven’t smoked. Medium smoking time was 8 years Md=8 [IQR:4.50-20.0]. Analysing gut microbiome in smokers/non-smokers, and the length of smoking, there were found no statistically significant differences. Thirty-five (71.4%) were using alcohol, and 14(28.6%) were not. Those who were using alcohol had statistically significantly more Firmicutes in their gut microbiome Md= 64.8[IQR:53.7-70.4] than no users Md=48[IQR:37.5-66.3], p=0.041. Regarding high stress levels, those who had less stress 18(36.7%), had more Actinobacteria in their gut microbiome Md=11.7[IQR:6.92-14.8] vs stressful patients 31(63.3%) Md=6.03[IQR:2.23-13.8], p=0.03.

Conclusion

There were no changes in gut microbiome in COVID-19 positive and COVID-19 negative patients, nor in smokers and no smokers. Alcohol users had more bacteria Firmicutes in their gut microbiome. There were no differences in gut microbiome in UC patients doing or lacking sports. UC patients with less stress had more Actinobacteria in their gut microbiome.Read more P1223 Lactobacillus rhamnosus GG/p40 encapsuled cationic host defense peptide play protective roles on immune-related colitis by inducing differentiation and immune suppression of regulatory T cellsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The immune-related colitis (IRC) is the most prominent in immune-related adverse events (irAE). The association between gut microbiota and IRC development has been revealed. Our study aimed to explore the protective effect and mechanism of the probiotic Lactobacillus rhamnosus GG (LGG) and its secretory protein p40 on IRC. The self-assembled cationic host defense peptide (CHDP) hydrogel was applied to protect oral p40 protein from digestive damage and target enriched the site of colitis.

Methods

The IRC model mice were intervened with LGG by gavage (i.g.), p40 by enema (en.), or p40 encapsuled by CHDP (i.g.). The T cell phenotype of colonic lamina propria mononuclear cells (LPMC) was measured by flow cytometry. The indocyanine green (ICG) encapsuled by CHDP was gavage in IRC model mice, the distribution of CHDP was monitored by fluorescence signals imaging via IVIS, to assess the adhesive effect of CHDP in mice colitis. In vitro, the proportion of regulatory T cells (Treg) differentiated was measured by LGG supernatant co-cultured with CD4⁺ naïve T cells, and the division index of CD4⁺T cells was measured by LGG supernatant co-cultured with CD4⁺T cells and Treg (CD4⁺T cells: Treg=1:1) by carboxyfluorescein succinimidyl ester (CFSE) staining test.

Results

Compared with DSS+anti-PD-1+anti-CTLA-4 IRC model group, LGG (i.g.) group had lower weight loss, DAI score, histopathological score, relative IL-6 and TNF-α mRNA level, IL-6 and TNF-α concentration and higher colon length (P<0.05) (Fig.1A-L). P40 (en.) group had lower weight loss, DAI score, histopathological score and higher colon length (P<0.05) (Fig.1M-T). CHDP+p40 (i.g.) group had lower weight loss, DAI score, histopathological score, relative IL-6 and TNF-α mRNA level, IL-6 concentration and higher colon length (P<0.05) (Fig.1M-W). The percentages of CD25⁺FoxP3⁺Treg/CD4⁺T cells of colonic LPMC in LGG, p40 (en.), and CHDP+p40 (i.g.) group were significantly higher than IRC model group (P<0.05) (Fig.1X-Z, α). The average 28hr-residual rate of fluorescence imaging radiance in IRC-CHDP+ICG group was higher than both NC-CHDP+ICG and IRC-ICG group (Fig.2β-δ), and the average radiance of colon in IRC-CHDP+ICG group was also the highest (P<0.05) (Fig.2ε-ζ). In vitro, LGG 10⁷ CFU/mL, 10⁸ CFU/mL and 5 × 10⁸ CFU/mL (P<0.05) could significantly promote Treg differentiation with concentration dependent manner (Fig.2η-ι), and the suppression of Treg on CD4⁺T cells with lower division index compared with control group (Fig.2κ).

Conclusion

LGG/p40 played protective role by promoting the differentiation and immune suppression of Treg cells in IRC. CHDP hydrogel could protect p40 protein from the digestive damage, and target enriched the inflamed lesion to improve the efficacy.Read more P1224 Predicting response to nutritional therapy in newly diagnosed children with Crohn’s Disease (CD) using multi-omics approachWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Background. One third of children with Crohn's disease (CD) will fail treatment with exclusive enteral nutrition (EEN) but predictors of response have been hitherto lacking. In this prospective cohort study, we aimed to use multiomic data to predict EEN response in treatment-naïve children with CD.

Methods

Methods. Children commenced on EEN at CD onset were followed through 8 weeks. Stool was collected for microbiome and metabolomics, and serum for metabolomics. Disease indices and clinical data were recorded. Targeted quantitative metabolomics approach was applied to analyze fecal and serum samples using a combination of direct injection mass spectrometry with a reverse-phase LC-MS/MS custom assay. DNA extracted from stool was sequenced and 16S rRNA gene was amplified. Feature selection was first utilized, using Recursive Feature Elimination with Cross-Validation (RFECV). For each omic analysis and the multiomic integration, selected components were fitted into a machine learning random forest (RF) model.

Results

Results. Included were 51 children (aged 14.8±2.7 yrs) treated with EEN, of whom 34 (66%) were responders; 36 (70%) had serum metabolomics, 20 (39%) fecal metabolomics and 31 (61%) microbiome data while 17 (33%) had all components. Clinical data and standard labs did not predict response (Table). The individual omic models ranked several key metabolites and microbes (Figure) and were able to predict EEN response with an accuracy ranging at 0.806-0.850 (Table). Serum 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid (CMPF), fecal phenylethylamine and fecal alpha-aminobutyric acid were higher in non-responders while serum malic acid and fecal 3-methyladipic acid were higher in responders (Fig. A-B). Moreover, levels of Veillonela and Bifidobacterium species alongside Blautia genus were higher in responders while Lachnospiraceae and Fusicatenibacter genus were higher in non-responders (Fig. C). The final multiomic model which included also clinical data, retained components from serum and fecal metabolomics but none from the microbiome; it predicted EEN response with high accuracy of 0.882 (Table). Higher level of serum 2-hydroxyglutraic acid, 2-hydroxy-2-methylbutyric acid and fecal 3-methyladipic acid were detected in responders. In non-responders there were higher level of serum alpha-aminobutyric acid, valeric acid, isovaleric acid, alpha-aminobutyric acid and kynrenine and alongside with increased fecal kynrenine/tryptophan ratio, both part of the tryptophan metabolism and kynrenine pathway (Fig. D).

Conclusion

Conclusion. In this multi-omic analysis, we generated a,metabolomics-based multiomic model to predict response to EEN, unravelling related biological insights.Read more P1225 The interplay of donor-derived gut microbiota correlates with the efficacy of combination therapy of fecal microbiota transplantation with antibiotics for ulcerative colitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Our previous reports suggest fecal microbiota transplantation (FMT) following bowel cleansing with amoxicillin, fosfomycin, and metronidazole (Antibiotic FMT: A-FMT) improved its efficacy and the recovery of the Bacteroidota species composition, which is associated with ulcerative colitis (UC) severity. Building upon these previous findings, we considered that manipulating the intestinal microbiome to improve the intestinal immune system seems to be a feasible therapeutic regimen for patients with UC. In this study, we explored the gut microbiota signatures through elucidating donor-derived microbe that colonized the recipients and examined the contributions of these microbe to the efficacy of A-FMT.

Methods

In this study, 97 patients with active UC were enrolled between March 2014 and October 2019, of whom 49 patients were individually assigned a different donor on a one patient-to-one donor basis. FMT was performed via colonoscopy after a two-weeks oral administration of three antibacterial agents. The Lichtiger’s clinical activity index (CAI) at 4 weeks after A-FMT treatment was defined as "response" if the CAI was ≤9 points and improved by ≥3 points. Each case contributed three fecal samples (pre A-FMT, post A-FMT, and Donor). 16S rRNA gene sequence analysis was performed on 147 collected fecal samples, and 6,501 Amplicon Sequence Variants (ASV) were identified and characterized.

Results

In responders, the relative abundance of 6 taxonomies including Alistipes were significantly abundant in both post A-FMT treatment samples and their donors’ samples, while 6 other taxonomies were significantly low. In non-responder, significantly low proportion of donor-derived and significantly high proportions of patients-origin and/or new ASV were observed compared with responders. The similarity of gut microbiota composition between donor and post A-FMT treatment was predominantly higher in responders compared to non-responders (Figure 1).

Conclusion

This study revealed that the engraftment of specific donor-derived microbes is a major factor in A-FMT outcomes, which may be the foundation for precision FMT. Rational identification of patient and donor characteristics can further advance the development of A-FMT therapy for UC.Read more N37 Fatigue in Japanese patients with Inflammatory Bowel Disease: a comparative study based on a systematic reviewWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Fatigue is a common symptom in patients with inflammatory bowel disease (IBD), often persisting even when the disease is in a state of remission. In addition, it is associated with a diminished quality of life (QOL). However, in Japan, only few studies have focused on fatigue in patients with IBD. The Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-F) scale has shown reliability and validity in assessing fatigue in patients with IBD, and studies using this scale have been conducted worldwide. In this study, we aimed to examine the current state of fatigue among Japanese patients with IBD using the FACIT-F scale and compare these findings with data from the global studies through a systematic review.

Methods

Data from 488 patients with IBD treated at a specialized IBD clinic were analysed. Patient characteristics, such as sex, age, and disease duration, along with FACIT-F scores, height, and weight were included as survey items in the questionnaire administered to patients. Data on the disease names and activities, as determined by the Crohn's disease activity index and partial Mayo score, were obtained from medical records. For international comparison, information on age, sex, country, disease duration, body mass index, and disease activity was extracted from each article and listed alongside FACIT-F scores. We conducted a search on PubMed using the search terms ‘inflammatory bowel disease’ OR ‘Crohn's disease’ OR ‘ulcerative colitis’ AND ‘fatigue’ AND ‘FACIT-F’ OR ‘FACIT’ OR ‘FACIT-fatigue’. After applying our predetermined inclusion criteria, we selected eight studies that met our requirements.

Results

The articles of the systematic review included population sizes ranging from 100 to 1185 patients. Patients’ age varied between the late 30s and early 50s, and the proportion of male patients ranged from 39% to 66%. The duration of disease was approximately 10 years. The proportion of disease names and activities was diverse. The overall mean FACIT-F scores ranged from 38.9 ± 11.0 to 41.6 ± 8.6, while the medians [interquartile ranges] ranged from 30 [22-39] to 41 [35-47]. For each article that presented the FACIT-F scores as means ± standard deviations, the t-tests revealed no statistically significant differences. Overall, the FACIT-F scores were higher (indicating higher QOL) in the remission phase than in the active phase. Additionally, these scores were higher in male patients than in female patients and in patients with ulcerative colitis than in those with Crohn’s disease. These findings were consistent across all countries included in this study.

Conclusion

The FACIT-F scores of Japanese patients with IBD demonstrated a similar trend to those of other countries.Read more N20 Sexual health in IBD can be brought up with help from toolsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Sexual topics can be tabooed; both for patients with IBD and for the health care professionals (HCPs). Patients with IBD have more sexual problems than the background population. A considerable number of patients with IBD have other autoimmune diseases (Ads), which may exacerbate sexual problems. Based on patient reported data, we aimed to develop communication tools and models for talks about patients' sexual health. Furthermore, we aimed to generate informative patient leaflets for different ADs including one specific for patients with IBD.

Methods

A cross-sectional e-survey on sexual health among patients with IBD, dermatological- and/or rheumatologically diseases (both solely and in combination). Patients were invited consecutively as they tuned up in the out-patient clinics at our university hospital. Participation were anonymous and access were possible by using a QR-code.The questions were ad hoc designed and focused on 1) disease-related sexual problems, 2) partner-related sexual problems, and 3) the need (and current practise) for talks with HCPs about sexual health. In addition, the participants could add qualitative descriptions. Quantitative data were analysed using descriptive statistics. NVivo™ were used to code the qualitative data. Based on the survey results we developed and implemented communication tools in daily practise.

Results

170 patients scanned the QR-code. 142 responded (61% females, 44% had IBD, 49% had a dermatologically disease, 40% had a rheumatologically disease, 33% had ≥ 2 AD). 51% of participants with only 1 AD reported disease-related sexual problems vs 71% for participants with ≥ 2 ADs. In IBD, the main reasons for impaired sexual health were: pain, fatigue, fistulas, incontinence and mental reasons. 86% responded that they didn't talk to HCPs about sexual issues (38% wish the HCPs to bring up the topic, 34% felt the topic to be a taboo, and 25% found it difficult to address problems).Based on the findings, specialist nurses with knowledge of all 3 ADs developed communication tools. The tools were tested and evaluated by both patients and reviewed by Clinic for Sexual Health and include: i) communication aid for nurses; ii) action card for nurses; iii) leaflets to patients with IBD.

Conclusion

Disease-related sexual problems are common for patients with IBD and ADs. Even more prevalent for patients with more than one AD. Sexual health is seldom a topic between patients and HCPs. Based on patient reported data, simple tools are developed and implemented.Figure 1: Typical levels of topics for the HCPs talks with patients about sexual health. HCPs will most often be able to help patients by focusing on the 2 lower levels.Read more P1154 Mediterranean dietary approaches to stop hypertension intervention for neurodegenerative delay (MIND) diet can reduce Inflammatory Bowel Disease risk: a prospective cohort studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The global increasing prevalence of Inflammatory Bowel Diseases (IBD) places a substantial burden on families and society at large. The lack of a definitive cure for this chronic condition underscores the critical need for effective preventive measures. Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet, emphasizing natural plant-based foods while limiting animal products and high-saturated fats, emerges as a promising dietary approach. This study aims to bridge the gap in understanding the impact of the MIND diet on IBD risk.

Methods

We utilized data from 187,549 participants in the UK Biobank who provided dietary information and were free of IBD at baseline. Dietary information including the consumption of over 200 common foods and 30 beverages was collected for five rounds by a validated web-based 24-hour dietary recall questionnaire. A MIND diet score was evaluated based on the intake of ten beneficial and five unhealthy food groups and was further grouped by tertiles. The outcome of interest was Crohn’s disease (CD) and ulcerative colitis (UC), ascertained via inpatient data and primary care data. Cox proportional hazard models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs).

Results

After a mean follow-up of 10.7 years, we documented 335 and 655 incident CD and UC. The average age of the participants was 56.2 years, of which 55.0% were females. We found that greater adherence to the MIND diet, represented by higher diet score, was associated with a lower risk of CD (HR comparing extreme tertiles 0.66, 95% CI 0.50-0.89, P=0.006; P-trend=0.005) and UC (HR 0.80, 95% CI 0.65-0.98, P=0.030; P-trend=0.029) (Table 1). In the secondary analysis, we investigated the impact of fifteen individual food components in the MIND diet and found that consumption of olive oil was inversely associated with CD, and consumption of wine was inversely associated with UC.

Conclusion

We found higher adherence to the MIND diet was associated with lower risk of CD and UC. Our findings call for further research on the potential of the MIND diet to prevent IBD.Read more P1156 Characteristics and outcomes of over a million Inflammatory Bowel Disease patients in seven countries: a multinational cohort studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Population-based studies are crucial for gaining insights into epidemiology, risk factors, and outcomes of IBD. However, studies that characterize patient cohorts typically analyze a single resource, apply diverse eligibility criteria, and extract different sets of attributes. This study aims to address this gap by employing a unified data and analysis framework developed by the Observational Health Data Sciences and Informatics (OHDSI) community to longitudinally describe and compare IBD patient cohorts across multiple geographic regions.

Methods

Using routinely collected healthcare data harmonized to the OMOP Common Data Model, we longitudinally characterized IBD patient cohorts across diverse geographic regions. Data sources included insurance claims and electronic health records from primary and tertiary settings. IBD cohorts were defined based on diagnoses and medications, and stratified into various groups (e.g. by sex and age at diagnosis).

Results

We characterized disease trajectory of 462,502 Crohn’s disease (CD) and 589,118 ulcerative colitis (UC) subjects, in 16 databases (DBs) from seven countries worldwide (table 1). There was a noticeable trend toward a decrease in the average age at CD diagnosis in Europe and North America (e.g., 47.5 in 2005-2010 period to 44.3 in 2020-2022 at a US DB) contrasting with more stable patterns in Southeast Asia (e.g., 33.7 to 33.9 respectively in Japan). A similar, though weaker, decrease in diagnosis age has been observed in UC subjects.Prevalence rates of pre-diagnosis symptoms (abdominal pain, diarrhea, and rectal bleeding) were relatively stable over time, with minor differences between DBs. The proportion of females with anxiety was consistently higher across all datasets compared to males. Similarly, depression prevalence ranged between 11% to 46% in females and 0% to 33% in males.Examining surgical outcomes for CD patients, our study uncovered nuanced trends. While there hasn't been a significant decrease in colonic resection rates within one year following diagnosis between the early 2000s and 2020 in US populations, some DBs demonstrated increased resection rates over time (from 11% in 2005 to 14% in 2020 and from 5% to 11% in two different US DBs). A similar trend was observed when examining the colonic resection rate 3 years post diagnosis. Small bowel resection rates were stable along time among most DBs one- and three-years following diagnosis.

Conclusion

This study, leveraging OHDSI network data and tools, provides a comprehensive characterization of IBD patient cohorts from various areas. It furnishes valuable insights into disease trends, demographic variations, outcome, and pre-diagnosis symptoms in CD and UC contributing to a deeper understanding of IBD epidemiologyRead more P1182 What has changed in Inflammatory Bowel Disease during last three decades?Wed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

With its increasing incidence, IBD varies epidemiologically both over the years and geographically. The increase in treatment alternatives over the years has led to differences in the management of patients. Revealing the impact of years on IBD from past to present and realizing the paths we have gone through will make us more conscious of future paths. Therefore, we aimed to reveal the epidemiological findings in our IBD patients over three decades.

Methods

IBD patients followed up at our university hospital, a tertiary center, were included in our study. The demographic, epidemiological and medical data of the patients were recorded retrospectively from the patient files. Descriptive statistics for continuous variables in the study; expressed as mean, standard deviation (SD), number (n) and percentage (%). "Independent T-test" and "One-Way Analysis of Variance (ANOVA)" were calculated to compare continuous measurements according to categorical groups. In the calculations, the statistical significance level was taken as p<0.05 and SPSS (IBM SPSS for Windows, ver.26) statistical package program was used for analyses.

Results

A total of 346 IBD patients, 198 of whom (57.2%) had Crohn's disease and were followed up from the gastroenterology outpatient clinic, were included in the study. The mean age of the patients was 49.07±13.82 years and the mean BMI was 23.02±4.58 kg/m2. 182 (52.6%) of the patients were male. The disease duration was 34.46±12.74 years. The patients were divided into three-decade groups according to their diagnosis dates as years: a total of 84 patients was diagnosed in 1985-2003, 192 patients in 2004-2013, and 70 patients in 2014-2023. The patients were compared within these date groups in terms of age at diagnosis, gender, first biological agent preference, and the time when the first biological agent was started (Fig.1). From the first decade to the third decade, the proportion of patients diagnosed with Crohn's disease was 50%, 57.3%, 65.7%, respectively, and the proportion of patients diagnosed with UC was 50%, 42.7% and 34.3%, respectively (p<0.05). The rates of requiring hospitalization at initial diagnosis were 48%, 42.2%, and 40%, respectively, from the first decade to the third decade (p<0.05). The need for bowel surgery at diagnosis (for Crohn's disease patients) was 33.3%, 26.36% and 13.04% within 3 decades, respectively (p<0.05).

Conclusion

While the rate of patients diagnosed with Crohn's disease has increased compared to 30 years ago, the rate of patients diagnosed with UC was decreased. While the need for hospitalization at diagnosis and the need for surgery in CD have decreased in the last decade compared, biological agents have been started earlier in IBD patients in the last decade.Read more P1183 Perception of the role of diet on symptom exacerbation in patients with Inflammatory Bowel DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

A substantial proportion of patients with inflammatory bowel disease (IBD) believe that diet plays an important role in disease activity. As a result, IBD patients often change their dietary regimen in order to improve their symptoms and to prevent recurrences, however most of them choose self-imposed dietary restrictions that may lead to malnutrition and to a significant reduction in quality of life. The aim of our study was to evaluate dietary habits and the perception of the relationship between diet and symptoms in IBD patients.

Methods

A semi-structured questionnaire assessing demographics, clinical features, perception of the role of diet on symptom exacerbations and dietary habits including adoption of food restrictions was developed by our gastroenterologists and dietitians and was administered to patients with IBD.

Results

85 patients with IBD (56 with Ulcerative Colitis and 29 with Crohn’s Disease, mean age 55.0 ± 15.9 years, 43 males) were enrolled in the study. Most IBD patients did not perceive diet as a possible cause of disease (68/85 patients, 80.0%) or relapses (70/85 patients, 82.3%), but the majority of them (55/85 patients, 64.7%) believed that certain foods and drinks could worsen disease symptoms. Alcohol, carbonate drinks, milk, spicy and fat foods were often considered as a possible cause of symptom deterioration. Although 50/85 patients (58.8%) stated that they changed their diet after the diagnosis, only 19/85 patients (22.3%) declared to adopt a "restrictive" diet by reducing or avoiding some foods. However, 64/85 patients (75.3%) showed low/intermediate adherence to Mediterranean Diet (MD) (calculated with the MediLite Score), and no patient had high adherence to MD. Finally, the majority of IBD patients declared that they would like to receive more information on diet in relation to their disease.

Conclusion

In our study, the majority of IBD patients perceived that certain foods and drinks could worsen disease symptoms and accordingly changed their diet after the diagnosis. The adoption of restrictive diets is probably more frequent than declared by IBD patients, as suggested by the high prevalence of low/intermediate adherence to MD. Education of healthcare providers is important to improve knowledge and quality of nutrition in IBD patients.Read more P1184 Two simple tools for assessing depression and anxiety in patients with Inflammatory Bowel DiseasesWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), can trigger the onset of depressive and anxiety symptoms. The evaluation of mental well-being in patients with a chronic medical condition is considered a good clinical practice and it is strongly recommended by the World Health Organization. Nevertheless, mental health is not routinely investigated in this context for several reasons, including lack of training by healthcare professionals, stigma associated to mental health and gender-relatedstereotypes. The objectives of our study were to assess the presence of depressive and anxiety symptoms inpatients affected by IBD using two simple validated questionnaires and to identify potential related factors, particularly gender differences.

Methods

We conducted a single center observational study evaluating anxiety and depressive symptoms in patients with IBD treated with biological therapy at the IBD Unit of Ospedale Policlinico of Milan during October 2022. We assessed depressive and anxiety symptoms using respectively the Patient Health Questionnaire-9 (PHQ-9) and the Generalized Anxiety Disorder-7 (GAD-7) that are easy self-administered rating scales. Univariate analyses and regression models were applied for the purpose of the study.

Results

Among a total of 174 consecutive patients, 158 completed the questionnaires. The prevalence of moderate tosevere depression (PHQ-9 score > 9) in the total sample was 18.4%, and it was higher in CD than in UC (21% vs 9.7%). The prevalence of clinically significant anxiety symptoms (GAD-7 score > 9) was 24% (25.7% in CD and 19.3% in UC). Focusing on gender differences, similar prevalence of significant anxiety anddepression was observed between males (M) and females (F); respectively 18.6% M vs 17.6% F for depression (PHQ-9 > 9) and 22.2% M vs 25.4% F for anxiety (GAD-7 > 9). Of note, a relevant association was observed between younger age and higher GAD-7 (β =-0.639; p=0.021) and PHQ-9 (β =-0.604, p=0.055) scores.

Conclusion

Both males and females (especially younger) IBD patients in biological therapy are largely affected bysignificant depressive and anxiety symptoms. The administration of simple questionnaires like PHQ-9 andGAD-7 in routine clinical practice can facilitate early identification of patients requiring mental health support, this is crucial as psychiatric conditions can complicate the course of the disease and adherence to treatments.Read more P1185 IBD Has No Age: Preliminary results of an international survey among older patients with Inflammatory Bowel Disease (IBD)Wed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Future research and health policy can benefit from a better understanding of the characteristics of a globally growing, but often underrepresented, older population with Inflammatory Bowel Disease (IBD). The aim is to evaluate the characteristics of this population, including frailty, comorbidity, and reported therapy goals through a survey.

Methods

An international, anonymous online survey was conducted among older patients (aged ≥ 60 years) with Crohn’s disease (CD), ulcerative colitis (UC) and IBD-unclassified (IBD-U). The survey was developed by the European Federation of Crohn’s and Ulcerative Colitis Associations (EFCCA), translated in 21 languages and distributed in 46 countries through national IBD associations affiliated with the EFCCA. The survey contained questions about demographic- and IBD characteristics, IBD-therapy and symptoms. Clinical disease activity was assessed by the Harvey-Bradshaw Index (HBI) (≥ 4) for CD, and 6-point Mayo score (≥ 1.5) for UC and IBD-U. Self-reported versions of the Geriatric-8 (G8) questionnaire and Charlson Comorbidity Index were included to assess frailty (G8 ≤ 14) and comorbidity, respectively. Respondents were asked to choose three out of the following 12 therapy goals they considered most important: to experience less abdominal pain, decrease inflammation, prevent/postpone IBD surgery, not feel fatigued, stop using corticosteroids, decrease diarrhea/incontinence, maintain or get to their preferred weight, be comfortable with their body image, or to preserve/restore their mobility, social life, good mood or sexual activity. Descriptive analyses were performed using R, version 4.3.

Results

Out of 2191 respondents, 1785 (81.4%) completed the survey for the variables of interest and were retained for analyses. Respondents were mainly from the Netherlands (47.2%), Norway (9.1%) and Italy (8.4%). Mean age was 67.3 years (Standard Deviation (SD) 5.9), 61% was female, and 58.1% was retired. The most common type of IBD was CD (50.9%). Clinical disease activity was found in 33% of respondents. Therapy with aminosalicylates was most common among patients with UC (58%), biological therapy among patients with CD (44%). Frailty was reported by 39% of respondents and 64% of respondents reported to have one or more comorbidities. Three therapy goals that were most frequently reported were: to not feel fatigued (56.1%), to be of good mood (42.2%) and decrease in diarrhea/incontinence (31.1%).

Conclusion

Preliminary results from the "IBD Has No Age" survey suggest that it will contribute a wealth of knowledge to the IBD landscape, providing insight in a range of IBD characteristics, frailty, comorbidity and therapy goals in an older population with IBD.Read more P1210 Gut microbiota profiling and disease course in patients with ulcerative colitis in clinical remissionWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The inflammatory bowel diseases, encompassing ulcerative colitis (UC) and Crohn’s disease (CD) are characterized by a relapsing-remitting disease course. Despite achieving remission, approximately one-third of the patients relapse annually and yet the microbiota associated with relapse remains elusive. We hypothesized that distinctions in gut microbial composition among patients in clinical remission could potentially influence the disease course. We aimed to discern a distinctive microbial signature in patients with UC in clinical remission, which could serve as a predictive marker for the sustained clinical remission.

Methods

This was a prospective observational cohort study conducted as a collaborative work between Dayanand Medical College and Hospital (DMCH), Ludhiana, and Institute of Microbial Technology (IMTECH), Chandigarh. Adult (≥18 years age) patients with an established diagnosis of mild UC (defined as no previous requirement of immune-modulators or biologics to induce or maintain remission) and in clinical remission, were included between January 2019 and December 2020 and followed for one year. The clinical remission was defined as partial Mayo score <2 for at least 6 months, with endoscopic Mayo score 0 and fecal calprotectin <100 µg/g within 4 weeks of enrolment. Utilizing using 16S rRNA metabarcoding based metagenome analysis, the bacterial composition of the collected stool samples were determined.

Results

During the study period, 34 patients (mean age 41.41±13.89 years, 20 [58.82%] males) meeting the eligibility criteria were included for analysis and followed up for one year. (Figure 1) The majority of the patients (21, 61.76%) had left sided colitis. On follow-up, 14 patients (41.17%) experienced a disease relapse (median time to relapse 6 [3-8.25] months). The phyla Firmicutes, Actinobacteria, Bacteroidetes and Proteobacteria were abundant in both the groups [sustained remission (n=20) and disease relapse (n=14)], but specific phyla were enriched in each cohort, Actinobacteria in remission and Proteobacteria in relapse groups. The genera Escherichia, Klebsiella, Enterobacter, Enterococcus, Streptococcus were enriched in relapse group. Interestingly the genus Clostridium was enriched in relapsed cohort whereas genera like Bifidobacterium, Prevotella, Bacteroides, Alistipes, Faecalibacterium were abundant in the remission cohorts.

Conclusion

There are inter-individual differences in the gut microbiota profile of patients with UC in clinical remission. These microbial differences can serve as determinants of the disease course.Read more P1162 Upadacitinib in Crohn’s Disease Patients: for what type of patients in real world setting ?Wed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The oral selective JAK kinase inhibitor, Upadacitinib (UPA; Rinvoq®) has been shown to induce and maintain clinical response and remission in Crohn’s disease (CD), but also in rheumatic and skin diseases. We report here on the largest Swiss experience in "off label" use of this drug.

Methods

A chart review of the Crohn’s and Colitis Center Beaulieu Lausanne and Gastroenterology Center Bulle of CD patients was conducted.

Results

Eighty-nine IBD patients were exposed to UPA treatment. After exclusion of 22 patients (UC and unknown consent status) we analyzed patients’ characteristics of 67 CD patients (72% women) treated between April 2019 and Nov. 2023. All patients had previously failed or were intolerant to, at least, one anti-TNF agent, 75% had been exposed to 4 or more biologics/ small molecules and two-third had received all classes of biologics. Disease location and behavior were mostly ileo-colonic and inflammatory (L3B1) or ileal only and stricturing (L1B2). Half of the patients had co-existing extraintestinal manifestations (mostly spondylarthritis and arthralgias). Advanced combination therapy was used in 27% of cases with anti-TNF agents (n=10), vedolizumab (n=6) and ustekinumab (n=2). UPA was prescribed after a median disease duration of 14 years (range 1-68) for a mean treatment duration of 14 months (mo) (+/- 9.1 SD; range 1-37). Forty-four CD patients (66%) were still on UPA at the time of study completion. A partial or complete response was observed in 51/67 patients (76%) with a mean decrease of CRP of 10.4 mg/l (+/- 17.6 SD) and calprotectin of 610 mcg/g (+/- 1165 SD). Adverse events were mostly viral infections, acnea, hypercholesterolemia, fatigue and headaches.

Conclusion

Upadacitinib is a good treatment option in difficult to treat CD patients with aggressive disease behavior, alone or in combination in case of concomitant rheumatic and gastrointestinal indications.Read more P1163 Incidence and risk of hip replacement rate in patients with inflammatory bowel disease in TaiwanWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The incidence and prevalence of inflammatory bowel disease (IBD) are low but increasing in Taiwan. Management of comorbidities such as osteoporosis is becoming increasingly important in treating patients with IBD. Hip fracture is the most serious consequence of low bone mineral quality and is associated with excess risk of mortality. The present study aimed to investigate the total/partial hip replacement in IBD patients in Taiwan.

Methods

In a matched nationwide cohort study, we evaluated the risk of total/partial hip replacement in IBD patients. We conducted univariable and multivariable Cox models to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). The Kaplan-Meier curves were plotted to describe the cumulative incidence of hip replacement among the two cohorts.

Results

a total of 51,301 patients with IBD and 153,903 patients without IBD were included in this study. In Table 1, distribution of gender, age, comorbidities, and medications were similar between two cohorts (SMD<0.1), except stroke, renal insufficiency, steroid, 5-ASA and anti-osteoporotic agents. The mean (standard deviation) age was 51.00 (17.76) and 49.89 (16.85) years and the sex ratio between female and male was approximately 50% and 50% in two cohorts, respectively. As shown in Table 2, patients with IBD had a significantly higher risk of hip replacement than the control group (adjusted HR=1.11, 95% CI=1.03-1.19). For the sake of a visual picture of cumulative incidence of hip replacement, consider the graphic representation in Figure 1 (Kaplan-Meier plot). Compared to female individuals, male individuals had significantly lower risks of hip replacement (adjusted HR=0.73, 95%CI=0.68-0.78). Older patients had more risk of hip replacement. Individuals aged 40-59, aged 60-79, aged >79 had significantly higher risks of hip replacement (adjusted HR >1, p-value<0.05) compared to individuals aged 20-39. Table 3 showed that IBD patients who are females, aged 40-59, or steroid users tended to have a higher risk of hip replacement compared to individuals without IBD (adjusted HR > 1, p-value < 0.05). We further stratified different dose of steroid use in IBD and non-IBD cohorts in Table 4. IBD patients receiving different steroid doses did not show influence on the risk of hip replacement. We demonstrated no difference in the hospital days, mortalities and morbidities among patients with hip replacement in non-IBD and IBD cohorts in Table 5. Higher rate of GI bleeding in IBD group had a significant difference than non-IBD group.;

Conclusion

Our present results indicate that patients with IBD had an overall higher total/partial hip replacement in Taiwan.Read more P1119 Increased risk of chronic respiratory disease among individuals with Inflammatory Bowel Disease in a prospective cohort studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Cross-sectional evidence suggests a higher burden of chronic respiratory diseases in people with inflammatory bowel disease (IBD), but there is a lack of prospective evidence to clarify the direction of their associations. This study aimed to investigate the association of IBD with the risk of two major chronic respiratory diseases, chronic obstructive pulmonary disease (COPD) and asthma.

Methods

We included 430,414 participants from UK Biobank and followed them from recruitment (2006-2010) to 2021. COPD and asthma cases were obtained from inpatient data and death register. Using Cox proportional hazards models, we estimated the multivariable-adjusted hazard ratios (HR) with 95% confidence intervals (CIs) of developing COPD and asthma in participants with IBD compared with IBD-free groups. We also investigated the association among Crohn's disease (CD) and ulcerative colitis (UC) with the risk of COPD and asthma.

Results

Over a median follow-up of 143 months, there were 11,196 incident COPD and 9831 asthma cases. The adjusted HRs of developing COPD (HR=1.54, 95% CI: 1.33-1.79) and asthma (HR=1.52, 95% CI: 1.29-1.79) were higher for those with IBD when compared with IBD-free participants. Participants with CD and UC were also found to have a higher risk of COPD (CD: HR=1.71; 95% CI: 1.36-2.15; UC: HR=1.45; 95% CI: 1.20-1.75) and asthma (CD: HR=1.73; 95%CI: 1.33-2.25; UC: HR=1.41; 95%CI: 1.15-1.73) when compared with those free of IBD (Table 1).

Conclusion

This study suggested that individuals with IBD have a higher risk of developing COPD and asthma, highlighting the importance of preventing chronic respiratory diseases among IBD patients.Read more P1140 Complementary and alterantive medicicne in patients with Inflammatory Bowel Disease in PolandWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

There is an increasing interest in complementary and alternative medicine (CAM) in patients with chronic diseases, including inflammatory bowel disease (IBD). We decided to investigate this problem because there is still not much data on this interesting and underestimated topic.

Methods

This single-center, cross-sectional study was conducted between October 2021 and June 2022 among patients of the Department of Gastroenterology of the National Institute of Medicine of the Ministry of Internal Affairs and Administration, both hospitalized and outpatients. Patients with IBD were asked to complete an anonymous survey that included questions about the use of CAM, their type and reason for use. The questionnaire also included data on the course of the disease, treatment and socio-demographic information.The results of qualitative variables were expressed as frequencies and percentages. We used the chi-square and Mann-Whitney U tests.

Results

435 patients were included in the study: 203 women (46.9%) and 230 men (53.1%). In this group, there were 250 (58.5%) with Crohn's disease (CD) and 177 (41.5%) with ulcerative colitis (UC). The average duration of the disease is 10.9 years. A little more than a half of patients received immunosuppressive and biological treatment. Among respondents, 66.9% (291) had ever used CAM. CAM was statistically more frequently used by people treated with immunosuppressive 60.26% (p=0.002) and biological drugs 72.51% (p=0.004), as well as people with higher education 71.75% (p=0.006) and secondary education 58.97 % (p=0.009), living in large cities 73.63% (p=0.006) and earning the highest income 85.51% (p<0.001). Age, gender, disease duration, use of other drugs (5-ASA, steroids) and disease diagnosis (UC vs. CD) did not influence the use of CAM. As many as 74.1% of CAM users use various types of dietary supplements. 61.5% of respondents follow special diets, 56.9% take probiotics, and 53.4% take herbs. Patients most often gain knowledge about CAM from other patients, family members (76.3%) and from the Internet (76.3%). The treatment is carried out independently, without medical supervision, and only 62.1% of patients inform the gastroenterologist about the use of CAM.

Conclusion

Our research shows that CAM is very often used by IBD patients in Poland, especially among patients with severe disease treated with immunosuppressive and biological therapy. This is particularly important for patient safety, taking into account the possible risk of interactions with conventional drugs and the usually lack of medical supervision.Read more P1141 Global perspectives on managing Inflammatory Bowel Disease (IBD) during pregnancy and lactation: current state and the necessity for enhancementsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Reproduction is an essential part of life. Our aim was to obtain a global perspective on IBD management by gastroenterologists (GIs) during preconception, pregnancy, lactation and neonatal period.

Methods

An anonymous survey (75 questions) was developed to investigate different aspects of clinical practice concerning the management of pregnancy and breastfeeding in patients with IBD. A national representative from each European country, USA, Latin America, Australia and New Zealand was selected to distribute the survey among their GI colleagues who treat patients with IBD (irrespectively of their experience).

Results

A total of 856 GIs from 36 countries participated in the survey. Among the participants, 63% had over a decade of experience as GIs, and 61% identified themselves as IBD specialist (IBDologists). The most relevant survey results and sub-analyses based on expertise are presented in tables 1 and 2. In the management of pregnant patients in remission, treatment discontinuation occurred either consistently or occasionally as follows: 20% thiopurines, 37% vedolizumab, 31% ustekinumab, and 96% small molecules. Notably, 13% did not always discontinue small molecules in patients contemplating pregnancy. Safety was the main reason for discontinuing IBD therapy during pregnancy. Contrary to the recommendations in clinical practice guidelines, many GIs avoid starting oral or rectal budesonide, anti-TNF, vedolizumab or ustekinumab during a disease flare. Further, a third of GIs would start thiopurines for a flare during pregnancy. Moreover, 13% will never perform a colonoscopy in a pregnant patient to guide decision making. Half of GIs implemented a dedicated outpatient follow-up program for pregnant patients in remission, with 87% enrolling all pregnant patients in this program. Concerning breastfeeding, 14% believed that all drugs can be used while breastfeeding. Regarding offspring’s vaccination, about 20% recommend against the administration of non-live vaccines and only 50% recommended avoiding live vaccines during the first 12 months for children exposed to anti-TNF in-utero. Among those GIs who recommended delaying vaccines in such cases, only 41% recommended testing the infant for detectable anti-TNF levels if live vaccines were required. Among the surveyed GIs, only a minority had a referral obstetrician, and only 35% referred patients with active or complicated IBD, while 45% had a referral paediatrician with expertise in IBD.

Conclusion

The management of IBD during pregnancy, lactation, and neonatal period is notably suboptimal, even among GIs specifically dedicated to IBD. It is crucial to address this current need and implement urgent educational measures in this area.Read more N26 Disease outcomes and patient’s perspectives after switching biologics from intravenous to subcutaneous administration. A real-world experience in a tertiary IBD-unitWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Since 2022, subcutaneous (SC) formulations of infliximab (IFX) and vedolizumab (VDZ) became available. This study aims to assess patients’ perspectives on potential switch to SC administration.

Methods

A prospective observational, nurse-led study was performed at the Ghent University Hospital. Patients treated with IV IFX or VDZ, deemed suitable by the treating physician based on the DIAMOND multi-stakeholder position statement of the Belgian IBD Research and Development group (BIRD), were offered switch to SC administration between 01/01/2022-30/06/2023. Participants were asked to fill out questionnaires regarding personal perspective on a potential switch to SC administration. Data was collected using REDCap®. Descriptive and univariate analyses were performed with Excel ®. The study was approved by the Ethical committee of UZ Ghent (ONZ-2022-0296).

Results

In total 404 patients receiving IV IFX or VDZ were identified within the inclusion period. Of those, 196 received 8-weekly treatment. After screening by the treating physician, 157 patients met the inclusion criteria of whom 84 agreed to participate (Figure 1).Questionnaires were filled out completely by 70 of the included patients. Fourty patients were treated with VDZ (57.1%) and 42.9% with IFX. Fourty-three patients (61.40%) had Crohn’s disease, 26 (37.1 %) had ulcerative colitis and 1 (1.4 %) indeterminate colitis. Fifteen patients (21.4%) had previous experience with SC self-injections. Thirty-four participants (48.6%) chose to switch to SC administration of their current treatment, 36 refused (51.4%).In general, patients were aware of the possibility to switch to SC administration before entering the study as 71% knew this formulation was available. Main information channels were: treating physician (56%) and/or IBD nurse (58%).Univariate analyses comparing switchers versus non-switchers are shown in Table 1. Patients who refused switch were more concerned about potential adverse events (agree: 61.1% vs 23.5%), loss of response (agree: 41.4% vs 11.4%) or incompliance (agree: 47.2% vs 14.7%) with SC formulations. Furthermore, the associated physician visit at the IV-administration unit was deemed more important to non-switchers (agree: 88.9% vs 55.9%).Patients who switched were less concerned about potential differences in healthcare costs (disagree: 70.6 vs 36.1%) and felt that regular visits to the IV-administration unit had big impact on QoL (agree: 64.7% vs 11.2%).

Conclusion

Patient’s perspectives differed significantly between those who chose to switch to SC IFX/VDZ and those who remained under the IV formulation. This should be considered when discussing treatment options with the patients and confirms the importance of patient engagement in managing IBD.Read more P1121 The risk of inflammatory bowel disease following serious infectious mononucleosis: A Danish nested case-control studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Epstein-Barr virus (EBV) infects ~95% of adults globally and limited early life transmission opportunities can delay EBV exposure till adolescence/early adulthood, increasing the risk of severe EBV infection, which most commonly manifests as infectious mononucleosis (IM). This study sought to investigate a potential aetiological association between IM and inflammatory bowel disease (IBD).

Methods

In this longitudinal nested case-control study, Danish nationwide registries were used to identify 37,156 IBD patients and 222,936 sex- and age-matched healthy controls, between 2005-2021. Logistic regression was used to calculate the odds ratio (OR) for IM hospitalisation prior to IBD diagnosis stratified by sex, age at IM diagnosis, age at IBD diagnosis, and IBD subtype (Crohn’s disease [CD] or ulcerative colitis [UC]). Additionally, exposure-controlled time-to-event analyses were used to explore the association between IM hospitalization and poor IBD prognosis. This association was measured using the occurrence of IBD-related hospitalization, surgery, complication and/or anti-TNF therapy commencement up to 10 years post-IBD diagnosis.

Results

Previous IM hospitalisation was significantly associated with the development of both CD (OR: 1.44, 95% CI: 1.20-1.73) and UC (OR: 1.27, 95% CI: 1.09-1.47). Sex was not found to be a significant effect modifier of this association for either CD (p=0.4) or UC (p=0.9). Those hospitalised with IM at a younger age had a higher odd of developing CD than those hospitalised in early adulthood (0-14-years OR: 2.60 [95% CI: 1.41-4.59]; >20-years OR: 2.04 [95% CI: 1.23-3.25]). A similar pattern was observed for UC development (0-14-years OR: 2.62 [95% CI: 1.44-4.55]; >20-years OR: 1.50 [95% CI: 0.97-2.25]). Poor disease prognosis following hospitalisation with IM within 10 years post-IBD diagnosis was only seen in CD (CD IRR: 1.52 [95% CI: 1.20-1.92]; UC IRR: 0.87 [95% CI: 0.65-1.16]).

Conclusion

This study demonstrated an association between IBD development and prior hospitalisation with IM, indicating the possibility of EBV infection as a significant contributor to IBD development. Strengthening understanding of IBD development can contribute to the prevention of IBD and improve management.Read more P1168 Anthropometric trajectories prior to the development of inflammatory bowel disease in Danish school-aged children and adolescents from 1997 to 2017Wed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Compromised nutritional status during the disease course can be a major clinical challenge in children diagnosed with inflammatory bowel disease (IBD). However, a key question is knowing how long these changes precede the disease; to this end, the impact of childhood-onset IBD on mean Z-scores for length/height (HAZ), weight (WAZ) and body mass index (BAZ) before and after IBD diagnosis will be evaluated.

Methods

The study used a nationwide children's database that collects health information from health visitors and school nurses and linked these data to anthropometric measurements at birth, diagnosis and family history obtained from national registries. Individuals with birth weight and length/height measurements and at least two weight and length/height measurements (at least one at school age) within +/- 4 SD at ages 1-16.5 years were included. Within this population, individuals with IBD diagnosed by two hospital contact at age 5-17 years were identified. Age- and sex-specific Z-scores were computed using generalized additive models for location scale and shape models on the study population and applied to the IBD population. Linear mixed models were used to estimate mean Z-scores in years before and after IBD diagnosis.

Results

In the period 1997-2017, data from 1,305,852 schoolchildren were recorded, and the final sample, after applying the inclusion and exclusion criteria, was 707,918 individuals with a median of 3 pairs of height and weight (IIQ: 2, 5) measurements collected. There were 1,424 cases of IBD [Crohn disease (CD), n= 784; ulcerative colitis (UC), n= 640] with a mean age at diagnosis of 14.16 years old. Preliminary data (results presented in the figure) show that the decline of WAZ, HAZ and BAZ markers in schoolchildren was observed years before IBD diagnosis, remaining for a later period, with a different pattern among individuals diagnosed with CD or UC. Individuals with a later diagnosis of CD, compared to UC, became progressively less healthy, showing a clear decline in anthropometric markers approximately 3 years earlier (UC individuals approximately 1 year earlier) and with a slower recovery after diagnosis.

Conclusion

Preliminary findings show that impaired linear growth and lower weight and body mass index can be observed at least 3 years before diagnosis in schoolchildren with CD and that they are more prominent in this population compared to UC cases. These results emphasize the importance of frequent nutritional screening and monitoring, with the aim of identifying the need for early intervention and providing a healthy transition to adulthood.Read more N19 Nurses' difficulties in supporting the sexual well-being of patients with inflammatory bowel diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Sexual well-being is a state of sexual happiness and satisfaction that combines mental stability and physical health as well as builds on mutual caring and intimacy with the partner. Patients with inflammatory bowel disease (IBD) undergo distress as they experience dating, marriage, and childbirth while living with the disease. Previous studies have indicated the importance of support related to sexual well-being but have suggested that it is a difficult topic for discussion. Hence, this study sought to clarify nurses' specific difficulties and barriers in supporting the sexual well-being of patients with IBD.

Methods

Nurses who had considerable experience caring for with patients with IBD were recruited using a snowballing method or opportunistic sampling. Semi-structured interviews were conducted via a video meeting system. Some examples of the interview questions include ‘Please tell us about your experience talking with patients about romantic relationships and sexual concerns and ‘Could you tell us about your difficulties in supporting patients with IBD in relation to their sexual concerns?’ We performed a reflexive thematic analysis.

Results

We interviewed 20 participants (Male: 4, Female: 16) in 13 facilities, 2 of which were focus group interviews. The mean length of experience in IBD nursing was 13 years. Three themes were identified as reflecting the difficulties nurses faced in discussing sexual issues with their patients: ‘The nurses' experience and their relationships with patients’, including gender and age barriers and difficulties in building rapport; ‘Assessment of sexual well-being’, including difficulties in broaching the issue and identifying people who needed support; and ‘Education for patients and nurses in supporting sexual well-being’, including lack of materials for patients and lack of opportunities for nurses to learn. Most participants rarely experienced discussions about sexual topics and did not initiate conversations about sexual well-being on their own.

Conclusion

Due to the sensitive topic of sexual issues, the difficulties described by nurses were influenced by the level of rapport with patients, the lack of training on how to handle the topic, and the lack of resources. Our results suggest the need for further research into approaches to reduce nurses' difficulties, while considering the identified barriers and needs related to the sexual well-being of patients with IBD.Read more ECCO Grant Dissecting the role of S1PR1 modulator in the mucosal regeneration of Ulcerative ColitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background and Aims

Ozanimod, a potent sphingosine 1-phosphate (S1P) 1/5 receptor agonist, first approved for the treatment of adults with moderately to severely active UC in the USA and in the EU, has showed promising results in terms of both tolerability and efficacy reducing inflammatory processes and inducing disease remission. The selectivity of Ozanimod for S1PR1 is 27 times that for S1PR5. Therefore, is plausible that the beneficial effects of Ozanimod are mediated by S1PR1, which is constitutively expressed not only by immune cells, but also by epithelial, endothelial, and stromal cells. However, its function on non-immune cells has been neglected. Based on preliminary data demonstrating a faster recovery of mucosal damage in mice with a conditional deletion of S1PR1 in the epithelia and endothelia compartments, our hypothesis is that the inactivation of S1PR1 not only inhibits immune cell trafficking, but also promotes tissue repair. Based on this background, the main objectives will be to exploit the Ozanimod effects during the process of mucosa healing, and to investigate the molecular pathways activated by Ozanimod on epithelial and endothelial cells.

Methods

Pre-clinical validation of Ozanimod, in vivo model of UC in association with conditional knockout mice for S1PR1 on epithelial and endothelial cells, stimulation of primary endothelial cells from UC patients and human induced pluripotent stem cell-derived intestinal organoids (iHOs) will be used to address our aims. Transcriptomics, functional assay, immune characterization, WB validation will be performed.

Anticipated Impact

In short and medium term, we will improve the knowledge on the role of S1PR1 in the processes of mucosal healing and identify the molecular pathways involved in the response to the mucosal damage mediated by the ozanimod in non-immune cells. The results of this study may improve the treatment options for UC patients.Read more ECCO Grant Dissecting the intestinal mucosa-associated HUMoral immune response in ileal Crohn’s Disease: the HUM-CD studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background and Aims

The pathophysiology of Crohn's disease (CD) is complex and not fully understood. While CD can affect the entire gastrointestinal tract, it primarily affects the terminal ileum. The underlying mechanistic reasons for this preferential location are unknown. Patients with isolated ileal CD have higher levels of circulating IgG antibodies targeting flagellins. These antibodies are associated with the ileal location of CD as well as with a complicated phenotype (intestinal stenosis and fistulae). Cellular determinants of this humoral response in ileal CD are yet to be unraveled. Techniques to study B cells at the single-cell levels have tremendously evolved these recent years and our laboratory has developed expertise in most of these techniques. The objectives of our study are to comprehensively characterize the humoral B cell response in patients with ileal CD.

Methods

To fulfill our aim, we will use different approaches:1. Extensive characterization of the B cell cellular and molecular landscape of the intestinal ileum in CD as compared to homeostasis states at the single-cell level2. Dissection of the intestinal B cell antigen-specific response in CD and assess differences between inflamed and non-inflamed, and ileal and colonic mucosa and the cross-reactivity of the flagellin-specific response3. Identification of the antigenic reactivity and clonal dynamics of memory B cells extracted from the terminal ileum of patients with CD.We will work from human samples, collected from ileal, colonic biopsies, and blood of patients with CD and healthy controls using

Anticipated Impact

Using advanced B-cell-focused single-cell techniques, we will unravel the humoral response at the ileal level and its association with clinical outcomes. By doing so, we aim to identify the main antigenic drivers and putative therapeutic targets of ileal CD.Read more ECCO Grant Risk of cardiovascular disease in patients with inflammatory bowel disease (IBD)Wed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background and Aims

Although evidence has suggested an increased risk of venous thromboembolism and arteriosclerotic events in patients with inflammatory bowel disease (IBD), there are still substantial knowledge gaps about the long-term risk of cardiovascular disease (CVD) in patients with IBD and how CVD risks vary by disease histological and clinical activity. The aims of this project are: 1) to investigate the long-term risk (both absolute and relative) of CVD in patients with IBD, and 2) to assess CVD risks for patients in different phases of histological and clinical periods of IBD.

Methods

We will apply epidemiological and statistical methods to tackle the proposed research questions through using data from a comprehensive linkage of a nationwide histopathology cohort, one quality register for IBD, and several nationwide registers in Sweden. Individual informed consent will be waived as the study is register-based.

Anticipated Impact

The project will address several important knowledge gaps and benefit the IBD community in multifaceted ways. Findings from Aim 1 will help us identify patients with IBD at a high risk of developing CVD and enhance the awareness of screening, management, and treatment of cardiovascular risk factors in patients with IBD among healthcare professionals as well as patients and their families. Findings from Aim 2 will contribute towards an improved comprehension of CVD risk in different periods of histological and clinical activity, which can offer novel insights into guiding current therapeutic strategies aiming to mitigate the risk of adverse cardiovascular events in IBD patients. Overall, knowledge from our project can provide valuable evidence for the development of clinical guidelines for CVD management in patients with IBD. Currently, such guidelines remain underdeveloped.Read more P1103 Incidence of Crohn's disease in patients with perianal fistula surgeryWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Perianal fistula (PAF) is one of the most common complications of Crohn's disease (CD) and is more frequent in Asian countries. However, there is a lack of data about the prevalence of CD in patients with PAF. We aimed to investigate CD incidence and risk factors in patients who underwent anal fistula surgery.

Methods

National health insurance service databases from 2013-2017 were used to identify patients with PAF surgery. The case definition comprises operation codes or diagnosis-related groups of anal fistula. The incidence of CD was investigated among the patients who underwent PAF surgery. We analyzed the risk factors associated with Crohn's disease in patients who received anal surgery. The time interval from surgery to CD diagnosis and the cumulative incidence of PAF after diagnosis of CD were investigated.

Results

172,397 PAF surgeries were performed during the study period (male 146,643, female 25,754). The incidence of PAF surgery in the general population was 6.77 (95% CI 6.73-6.8) per 10,000 person-years. (11.48 (11.42-11.54) for males, 2.03 (2.00-2.05) for females). The rate of CD was higher in a person who had undergone multiple PAF surgeries, females, and teenagers. More than 50% of teenagers who received three or more PAF surgeries were diagnosed with CD. The median time from PAF to a diagnosis of CD was 14.4 months (4-40.4 months). The prevalence of PAF at CD diagnosis was 48.2% (male 52.8%, female 36.8%), and the cumulative incidence rate at the 5-year follow-up was 61.4% (male 67.6%, female 43.6%).

Conclusion

This study reveals the relationship between CD and PAF surgery in Korea. The incidence of CD in patients with PAF is relatively high, and children, women, and patients with multiple surgeries are more likely to be accompanied by Crohn's disease. These features could be used to monitor the patient to allow timely diagnosis of CD.Read more P1126 Navigating the Future: Minimally Invasive Surgery Trends in Ulcerative ColitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Minimally invasive surgery (MIS) has been associated with lower rates of postoperative complications in ulcerative colitis (UC), both in the elective and emergency setting, compared to the traditional open approach. Despite these findings, some clinical guidelines state that minimally invasive surgery is not superior to open surgery in UC and emphasize an individual approach based on the surgeon’s judgment. This study analyzed the trends in open and minimally invasive approaches in total colectomies for UC.

Methods

A retrospective analysis was conducted on the ACS-NSQIP database encompassing all patients undergoing total colectomy for UC from 2012 to 2021. The primary endpoint involved analyzing open, laparoscopic, hand-assisted, and robotic surgery trends. A time series analysis was performed to forecast the future direction of these surgical techniques. Quarter (Q) and admission year were reported for time trend analysis. Dynamic relationships between various time series representing different surgical techniques were modeled using Vector Autoregressive (VAR) models. These models were employed to predict future trends in operative approaches until Q2 of 2025, along with 95% confidence intervals.

Results

A total of 7099 patients (44.5% female) were included, with a mean age of 45.1 (±17.8) years and mean BMI of 25.5 (±7.7) kg/m². Smoking was reported in only 8.7% of patients, with 49.1% classified as ASA 3 and 41.4% as ASA 2. Most patients (71.5%) were on steroids or immunosuppressants at the time of intervention.At the beginning of the study period, nearly half of the interventions were performed with an open approach (45.2%), followed by laparoscopy (35.7%) and hand-assisted laparoscopy (19%). Trends indicated a decline in open surgery to 17.7% by Q2 of 2021, with an increase in laparoscopic (45%), hand-assisted (25%), and a consistent growth of robotic surgery to 12.3%. Forecasting shown in Figure 1 suggested a continuous decrease in open surgery until Q2 of 2025 (8.7%, 95% CI 0-32.5%), with laparoscopic (51.2%, 95% CI 26.4-75.9%), hand-assisted (29.1%, 95% CI 11.9-46.3%), and robotic (11.0%, 95% CI 7.5-14.6%) approaches on the rise.

Conclusion

Minimally invasive surgical techniques have steadily grown over the past decade in the treatment of ulcerative colitis. Predictions indicate continued growth, displacing traditional open approach, which may persist as a rescue procedure.Read more P1127 Diagnostic delay and economic burden in IBD: a multicenter italian experience in patients treated with biologicsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Inflammatory bowel diseases (IBDs), Crohn's disease (CD) and ulcerative colitis (UC), are chronic and immune-mediated diseases with a relapsing-remitting trend. The overall incidence of these diseases is increasing. However, it is estimated that more than one third of patients experienced symptoms for more than one year before diagnosis. Delay in IBD diagnosis has several clinical, therapeutic and economic implications. Early diagnosis and proper treatment are the cornerstones for improving the standard of care for these patients.This study aims to evaluate the diagnostic delay (DD) in patients with IBD and to analyze the clinical burden of the delay in IBD diagnosis in patients treated with biological drugs.

Methods

An observational and retrospective study was performed in IBD patients, regularly followed in four IBD Units. Data regarding delay in IBD diagnosis were assessed through a questionnaire evaluating the disease course. Moreover, data about biologics dispensation were obtained from the medical records in the period 2020-2022

Results

344 IBD patients were enrolled (UC 228, CD 116, M 198, F 146). Median age at diagnosis was 42 years (IQR 9-82); Median DD was 12 months (IQR: 6-24). No significant difference was found in median DD between UC [12 months (IQR: 4.5-12.0)] and CD patients [12 months (IQR: 12-48)]. However, the proportion of patients with a DD >24 months was significantly (p=0.007) higher in CD (41/110 = 37,3%) than in UC patients (20/220=9%).After a median disease duration of 10 years (IQR: 4-17), overall, 164 patients (49.7%) were exposed to one biologic agent, 105 patients (31.8%) were exposed to two biologic agents, 61 (18.5%) to three or more biologic agents. 18,5% of patients (61/330) underwent surgery.The statistical analysis showed that DD >24 months was not statistically significant associated with history of ≥ 2 biological drugs (p=0.51). Conversely, there was association with surgical treatment (p=0.004).

Conclusion

The diagnostic delay in IBD represents a challenge with clinical and, therapeutic impact. It’s crucial to cooperate with general practitioner and gastroenterologists not dedicated to IBD in order to reduce the diagnostic delay and guarantee an effective, appropriate and early treatment that will improve the patients’ quality of life and meanwhile reduce the health care system costs.Read more P1144 Forecasting the Future Prevalence of Inflammatory Bowel Disease in Korea through 2048: An Epidemiologic Study Employing Autoregressive Integrated Moving Average ModelsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The global escalation of Inflammatory Bowel Disease (IBD) has precipitated an increased burden of disease and economic impact, particularly accentuated within the Asian context. The primary objective of this study is to predict the future prevalence trajectory of IBD in Korea and elucidate the pattern of its evolution.

Methods

Data from the Korean National Health Insurance Service (2004–2018) were analyzed using a validated diagnostic algorithm to identify IBD patients. An autoregressive integrated moving average (ARIMA) model, employing 2004–2017 data, predicted future trends based on past values and error correction. The model's accuracy was validated against the actual 2018 patient count. We projected IBD patient numbers and prevalence from 2018 to 2048, using a generalized linear model (GLM) to determine influencing factors.

Results

A consistent annual increase in the number of IBD cases across all age groups was observed from 2004 to 2018, with prevalence peaking in the 20–39 age group. The validation of our prediction model demonstrated an acceptable range of error for IBD prevalence, with a 2.45% error rate and a mean absolute difference of 2.61. The 2018–2048 projections confirm a steady rise in Crohn’s disease (CD), ulcerative colitis (UC), and IBD prevalence across both genders (Figure 1). IBD prevalence is projected to increase from 104.19 per 100,000 in 2018 to 149.59 per 100,000 by 2028, and further to 239.73 per 100,000 by 2048 (95% confidence interval [CI]: 223.73–255.73), marking a 130% increase. By 2048, the prevalence rates for UC and CD were estimated to be 159.40 per 100,000 (95% CI: 137.38–181.42) and 91.11 per 100,000 (95% CI: 0.81–181.41), respectively. The Average Annual Percent Change (AAPC) of IBD is predicted at 4.51%, varying from a 2.77% decrease in those over 60 to a 14.20% increase in the 20–39 age group. Gender-stratified forecasts show a higher AAPC in males (6.17%) compared to females (2.75%) over the next 30 years. The highest AAPC, valued at 19.48, was noted in the male group aged 20–39 years. GLM analysis indicates significant age, gender, and temporal effects on IBD prevalence, with marked gender disparities in specific age groups for both CD and UC. In UC, males aged 20–39 experienced a significantly higher increase in prevalence than females. For CD, males also showed a higher prevalence increase than females in the 20–39 and 40–59 age groups (all interaction p-values < 0.05; Table 1).

Conclusion

This study forecasts a significant increase in Korean IBD prevalence by 2048, especially among males and the 20–39 age group, highlighting the need to focus on these high-risk demographics in future disease management.Read more P1145 Assessing disease control in inflammatory bowel disease (IBD) – a real world cross-sectional study in the UKWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

There is a paucity of data on disease control in patients with inflammatory bowel disease (IBD) in clinical practice. The Proportion Of suboptimal Disease Control And Strategy of Treatment in IBD (PODCAST-IBD) multicentre, non-interventional study aimed to quantify real-world rates of disease control using the STRIDE-II recommendations, explore contributors to, and the economic burden of, suboptimal disease control.

Methods

Cross sectional assessment of patients with IBD attending routine clinic appointments was carried out in four UK centres between Oct 2022 and Jan 2023. Clinician-reported outcomes, patient-reported outcomes and retrospective data from medical chart review were used to assess IBD control against red flags aligned to the STRIDE-II recommendations (Table). Health care resource utilisation (HCRU) was calculated using NHS reference costs.

Results

Data was available from 198 patients (Crohn's disease [CD]: 103, ulcerative colitis [UC]: 95) and most were currently receiving long-term IBD-specific treatment (CD: 85%, UC: 78%). IBD was suboptimally controlled in 52.4% (54/103) of patients with CD and 45.3% (49/95) with UC. Impaired quality of life (QOL), defined as Short inflammatory bowel disease questionnaire (SIBDQ) score <50, was the most frequent contributor to suboptimal disease control for both UC and CD. Other frequent contributors were systemic steroid overuse, extraintestinal manifestations (EIM), failure to achieve clinical improvement and perianal disease (Figure). Suboptimal disease control has a detrimental impact on fatigue and disability, demonstrated by lower (indicating more fatigue) mean total FACIT-F score in suboptimally controlled disease (CD: 81.5 vs 125, UC: 87.4 vs 122.8) and IBD Disk, a 10-item self-questionnaire used to assess IBD-related disability. HCRU more than doubled in patients with suboptimal vs optimal control (CD: £4,746 vs £1,924; UC: £2,428 vs £1,121), driven by more hospital admissions and emergency room visits in patients with suboptimal disease control. Patients with suboptimal disease control had higher rates of work productivity loss than those with optimal control (CD: 41.7% vs 11.9%, UC: 38.0% vs 22.6%).

Conclusion

This UK cross-sectional study found that IBD was suboptimally controlled in around one-half of patients based on STRIDE-II recommendations. Of those with suboptimally controlled disease one-third had impaired QOL making it the most common contributor. Suboptimal control of IBD had a considerable economic impact; HCRU more than doubled and productivity fell. Physicians could consider regular QOL assessments to prompt timely disease monitoring to enable identification of early active disease and ensure appropriate treatment.Read more P1174 The disease course of elderly patients with Inflammatory Bowel Disease two years prior to their deathWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The number of elderly patients with inflammatory bowel disease (IBD) is increasing. Hence, more patients will be dying with their IBD. Limited research has examined the disease course of IBD in the aging body, particularly in the period preceding their death. The purpose of this study was to investigate the disease course of elderly IBD patients leading up to the end of their lives.

Methods

This was a nationwide population-based study using the national Danish registries. We used a validated algorithm to identify patients that were diagnosed with Crohn’s disease (CD), ulcerative colitis (UC) and IBD unclassified (IBDU) in a period between 1976-2018 from the Danish National Patient Registry. This information was linked with other national Danish registers which provided data on dates of death, cancer, hospitalisations, and corticosteroid usage. We included 6,183 IBD patients aged 65 and above at death, with no cancer or palliative treatment at the time of death. We analysed IBD-related hospitalisations, corticosteroid usage, and disease relapses (defined as a combined endpoint of corticosteroid prescription and/or hospitalisation, or both), in the two-year period before death.

Results

We analysed CD, UC and IBDU patients separately, and observed a noticeable spike in hospitalisations, prescription rates of corticosteroids and disease relapses in the last two months before the IBD patients’ death. Out of 6,183 IBD patients, 954 (15.43%) were hospitalised in the last two years before their death (see Table 1 for key characteristics). In the last two months, hospitalisation rates were 139 (28.66%) for CD patients, 155 (23.96%) for UC patients and 83 (34.87%) for IBDU patients. Corticosteroids were prescribed to 1,054 (17.05%) out of 6,183 IBD patients, and in the last two months 90 (20.45%) CD patients, 149 (20.13%) UC patients, and 67 (19.36%) IBDU patients received a corticosteroid treatment. Overall, 1,652 (26.72%) IBD patients experienced a disease relapse two years preceding their death, and during the last two months, 553 (22.45%) CD patients, 194 (24.01%) UC patients and 228 (20.25%) IBDU patients experienced relapses.

Conclusion

During the two-year period prior to death, we observed that hospitalisation, prescription, and relapse rates were highest during the final two months of life. For better understanding of the disease course of elderly IBD patients, further research should investigate the cause of death and differences between early- and late disease-onset patients as well as establish a cohort for comparison.Read more P1175 Abdominal Pain is Associated with Poor Quality of Life in Quiescent Inflammatory Bowel Disease: A Cross-sectional Study of the SPARC Inflammatory Bowel Disease CohortWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Abdominal pain (AP) is common in patients with active inflammatory bowel disease (IBD) and has been associated with poor quality of life (QOL). Despite greater therapeutic options, symptoms persist in a subset of patients. Data is lacking regarding AP in patients with objectively documented quiescent disease. Among endoscopic quiescent disease: (1) estimate prevalence of AP, (2) assess predictors of worse AP, (3) describe its impact on validated QOL measures.

Methods

This cross-sectional study used prospectively collected data from SPARC (Study of a Prospective Adult Research Cohort) IBD, a multicenter longitudinal study of well-phenotyped adult IBD patients initiated by the Crohn’s & Colitis Foundation in 2016. Quiescent IBD was defined as Mayo endoscopy score <2 for ulcerative colitis (UC) and SES-CD score <3 for Crohn’s disease (CD). Patient reported outcomes (PROs) within 30 days of endoscopy were analyzed. Patients with ostomy or IPAA were excluded. Self-reported AP was categorized as none, mild, or moderate/severe. Univariate statistics used Pearson’s Chi-square and Kruskal-Wallis tests.

Results

A total of 973 patients with quiescent IBD (606 CD; 367 UC) were included in the study (Table 1). AP was more commonly reported in quiescent CD (31.2% mild, 15.5% moderate/severe) as compared to quiescent UC (23.4% mild, 10.1% moderate/severe) (p<0.001). In the entire quiescent cohort, those with mild or moderate/severe AP were more likely to be female sex (63.1% mild; 67.4% moderate/severe; p<0.001), higher BMI (28.4 mild; 30.0 moderate/severe; p=0.008) and have more recent tobacco use (p=0.004). Ileocolonic involvement was more commonly seen in moderate/severe AP. Mild and moderate/severe AP was associated with subjective fecal urgency, stool frequency, and bloody stool (all p<0.001). Disease behavior in CD was not associated with abdominal pain.General well-being was poorer for those with more severe AP (p<0.001), though this did not appear to result in more frequent recent ED visits or hospitalizations. Figure 1 depicts the PROMIS responses. Overall, worse AP was associated with universal worse scores on all PROMIS measures and subscales (all p<0.001). Data suggested that more severe AP had the greatest impacts on the "Fatigue" subscale.

Conclusion

In this study of patients in SPARC IBD with endoscopic quiescent IBD the overall prevalence of AP was 41.7% overall and more commonly reported in CD as compared to UC. AP was associated with a greater prevalence of other symptoms, worse general well-being, and poorer quality of life across all measures. Further research is needed to elucidate the pathophysiology for presence of AP in quiescent IBD and develop personalized management approaches.Read more P1176 The Influence of positive family history on the phenotype and clinical course of inflammatory bowel disease: A Systematic review and meta-AnalysisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The phenotypes and clinical course of familial and sporadic inflammatory bowel disease (IBD) are not yet well-established. We sought to perform a systematic review and meta-analysis to assess the pooled influences of positive family history on disease characteristics and clinical outcomes in IBD.

Methods

We searched MEDLINE, EMBASE, and the COCHRANE library to identify full text articles analyzing disease phenotypes and clinical courses in IBD based on the presence or absence of a family history of IBD. A meta-analysis was performed using a random-effects model to pool estimates and report odds ratios [ORs].

Results

A total of 14 studies were identified as eligible for the meta-analysis. A positive family history (of any degree) of IBD was associated with a lower prevalence of extensive colitis in ulcerative colitis (OR 0.83, 95% confidence interval [CI] 0.72-0.94) but was not associated with most phenotype features including male gender (OR 0.89, 95% CI 0.74-1.07), small intestine involvement (OR 1.11, 95% CI 0.81-1.52), and stricturing or penetrating disease behavior (OR 0.99, 95% CI 0.76-1.29) in Crohn's disease, extraintestinal manifestations (OR 1.26, 95% CI 0.89-1.78), or perianal fistula (OR 1.02, 95% CI 0.84-1.23). Additionally, various clinical outcomes of IBD including IBD-related hospitalization (OR 1.52, 95% CI 0.93-2.47), corticosteroid use (OR 0.91, 95% CI 0.58-1.44), immunomodulator use (OR 1.07, 95% CI 0.98-1.17), biologics use (OR 1.13, 95% CI 0.91-1.42), and intestinal resection surgery (OR 1.01, 95% CI 0.83-1.23) were not associated with family history. In the subgroup analysis of studies analyzing first-degree family history alone, family history was also not associated with small intestine involvement, stricturing or penetrating behavior, perianal fistula, corticosteroid use, immunomodulator use, biologics use, or intestinal resection surgery.

Conclusion

Familial cases with IBD exhibited a lower prevalence of extensive colitis compared to sporadic cases, but the overall disease phenotype and clinical course were similar in both types of IBD.Read more P1177 Perceptions of patients with Inflammatory Bowel Disease and first degree relatives on prediction and prevention of diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Significant advances have been made in understanding the preclinical stages of IBD, and in identifying risk factors and biomarkers to predict IBD onset. With the use of predictive testing to identify patients at risk of developing the disease, it would be possible to intervene and try to mitigate that risk. However, the feasibility of such strategy, would depend on whether individuals at risk of developing IBD would be willing to undergo predictive testing and preventive interventions.

Methods

A Redcap® electronic survey, available in five languages, was disseminated by clinicians and patient’s associations to patients with IBD, first-degree relatives (FDRs) of those with IBD, parents with IBD and healthy children at risk (based on family history), and healthy couples with multiple children including one with IBD. Participants were asked to express their concerns regarding their own or offspring’s risk of developing IBD and acceptable predictive testing and preventive interventions.

Results

817 individuals (75% women, mean age of 41±12 years) living in 28 different countries participated. The majority were parents with IBD of healthy at-risk children (59%). Among individuals with IBD, 50% had Crohn's disease, 55% were on biologic treatment, 25% had undergone surgery, and 62% reported a significant impact on their quality of life. Overall 85% expressed willingness for predictive testing, favoring minimally-invasive methods. Half of participants would agree to cross-sectional imaging and 38% would accept a colonoscopy. The main benefits recognized with predictive testing were the possibility of starting preventive interventions to minimize the risk of developing IBD (74%) and obtaining an earlier diagnosis (63%). Anxiety from a positive result was a concern (57%). A total of 98% would accept preventive interventions. The most accepted were quitting smoking (64%), physical exercise (81%), dietary modification/supplementation (86%/71%) and probiotics (79%); with the optimal duration of the intervention to last up to one year (33%). Participants deemed a risk of minor adverse events up to 10% acceptable, with 33% tolerating a higher risk if disease risk was reduced by 75%. Half agreed that costs should be supported entirely or shared (39%) with the government.

Conclusion

In this international survey of patients with IBD or parents of children at-risk of developing IBD, minimally-invasive predictive testing would be well accepted as well as non-pharmacological and highly effective preventive interventions.Read more P1214 The crosstalk between oral and intestinal microbiota in inflammatory bowel disease patientsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Background: Previous studies reported that oral microbes can migrate to the gut, but the relationship between oral and intestinal microbiota in inflammatory bowel disease (IBD) is still unclear.

Methods

Here, we investigated the oral and gut microbiota of patients with Crohn’s disease (CD) and ulcerative colitis (UC), as well as their healthy relatives. We combined second- and third-generation sequencing based on the 16S rRNA gene to analyze the oral and fecal microbiota.

Results

A total of 97 IBD patients (59 CD and 38 UC) and 94 healthy relatives were included in the study. Our finding showed that CD and UC patients had higher levels of pathogenic bacteria in both their oral and fecal microbiota. In IBD patients, the gut microbiome was more influenced by the oral microbiome compared to healthy relatives, particularly in CD. We also observed an interesting interaction between Veillonella and Escherichia-Shigella in CD, and the presence of Veillonella in the gut was associated with disease activity. We developed diagnostic models that combined oral and fecal genera, which effectively distinguished CD (AUC=0.8478) and UC (AUC=0.7826) from healthy relatives, as well as predicted active inflammation in CD (AUC=0.9226) and UC (AUC=0.9158). Additionally, our third-generation sequencing results revealed an increase in Parvimonas micra in the oral cavity of IBD patients, and this was positively correlated with its presence in the feces.

Conclusion

These findings suggest that both oral and gut microbiota may play a crucial role in the development of IBD and could be potential targets for intervention.Read more P1215 Blastocystis is very rare in faeces of children with Crohn’s disease: quantity, subtyping and association with the faecal bacteriomeWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Blastocystis is a single-cell gut protist, presumably an indicator of gut health. We aimed to assess its occurrence and subtypes in a longitudinal set of faecal samples from recently diagnosed paediatric patients with Crohn's disease (CD) and compare it to similar longitudinal collections from children having other chronic immunopathological diseases without gut pathology (type 1 diabetes, T1D, and juvenile idiopathic arthritis, JIA), as well as to control subjects.

Methods

At a single tertiary centre, 626 samples were collected from 156 subjects: 40 with CD (mean age 12.5 years), 57 with T1D, 10 with JIA and 49 healthy. Specific real-time PCR detected and quantified Blastocytis, whereas massively parallel amplicon sequencing showed its subtype. The relationship between Blastocystis and the bacterial community was assessed by 16S rDNA amplicon profiling.

Results

Blastocystis was detected in 4.0% (9/223) stool samples in CD, six of them being of a very high quantity and originating from a single patient in long-term remission with a less common CD phenotype (L2, colonic, according to Paris classification). Subject-wise positivity of Blastocystis in CD (3/40, 7.5%) was significantly lower than in either T1D (21/57, 37%), JIA (2/10, 20%), or in healthy children (14/49, 29%). There was no notable difference in the subtype repertoires among diagnoses. The faecal bacteriome had higher alpha diversity in Blastocystis-positive samples. The Blastocystis-positive bacteriomes had slightly yet significantly (p<0.001) different overall community composition across all diagnoses (Figure 1), which was also reflected by the suggestive differential abundance of several taxa (e.g. Ruminococcaceae and Prevotellaceae increased, Bacteroidaceae and Rikenellaceae decreased).

Conclusion

We performed a large molecular survey on Blastocystis in longitudinal samples of three different paediatric diagnoses and healthy subjects. We document an unusual long-term carriage of very high loads of Blastocystis in a patient with colonic CD phenotype in clinical remission. Otherwise, however, Blastocystis is very rare among paediatric patients with CD, in contrast to two other chronic immunopathologic childhood diagnoses (T1D, JIA). Further longitudinal observation will show whether Blastocystis might return in patients with well-controlled CD upon ameliorating their bacteriome composition.

Institutional Grants/Research Supports

Supported by Ministry of Education, Youth and Sports of the Czech Republic, programme INTER-EXCELLENCE II, project LUC23165.Read more P1216 Oral Health status in Inflammatory Bowel Disease patientsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Inflammatory bowel diseases (IBD) affect de gastrointestinal tract primarily as it occurs in oral Crohn´s disease (CD) or as an extraintestinal manifestation (EIM) as aphthous stomatitis either in CD or ulcerative colitis (UC). Moreover, data suggest that IBD patients have a higher prevalence of caries and periodontal disease. The aim of our study was the characterization of oral heath in a cohort of IBD patients compared with a control group without IBD and determine the need of oral health intervention in IBD population.

Methods

This was a collaborative transversal cohort study between an IBD medical appointment in a tertiary hospital and a faculty of dental medicine. Patients from IBD appointment were invited to participate and gave their informed consent. The only exclusion criteria were the incapacity to open the mouth or give a written informed consent. Data was collected regarding demographics, disease characterization, activity, previous IBD related surgeries and current and previous IBD treatments. The control group were heathy controls matched by age and sex. Oral health assessment was achieved by an intraoral clinical examination with the aid of artificial light, oral mirror and WHO periodontal probe. Periodontal diagnosis was achieved through an online periodontal chart (https://www.periodontalchart-online.com), and classified according to periodontal health, periodontitis (stage and grade) and gingivitis. Oral examination provided the Decayed, Missing due to caries, and Filled Teeth Score (DMFT Score) and need for dental treatment and/or prosthetic rehabilitation.

Results

Oral health status of IBD patients confirm the high incidence of PD, with a prevalence of 55.3% and 69.4% for CD and UC patients, respectively. It is important to refer most of the patients diagnosed with PD suffer from the most severe stage of the disease (III and IV), which is not observed for the control group. Poor oral health status is also evident due to the need for dental treatment, since 88.1% of IBD patients need dental treatment and 38.1% need prosthetic rehabilitation (table 1).

Conclusion

IBD affects mainly the digestive system, however there is growing evidence that it also has implications for oral health, namely in periodontitis development, as shown in this study. Thus, good oral hygiene practices, including regular dental check-ups and personalized protocol of periodontal therapy are essential for these patients. Moreover, the collaboration between gastroenterologists and dental professionals is crucial to providing comprehensive care for patients with IBD, addressing both their gastrointestinal and oral health needs.Read more P1217 The gut microbiota as a determinant in the development of post-surgical recurrence in Crohn`s diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Crohn's disease (CD), is a chronic condition with a growing incidence in recent decades. Despite the development of new biologic therapies it is estimated that up to 70% of CD patients will require surgical intervention during their lifetime. However, surgery is not considered curative even in cases where a resection of all macroscopic involvement is performed, and the management of post-surgical recurrence remains a therapeutic challenge.Bacterial dysbiosis has been postulated as a precipitating factor in CD and may play a significant role in the development of post-surgical recurrence (PSR) of this condition.We prospectively studied the characteristics of bacterial diversity in patients with CD following ileocecal resection to identify the predictive value of intestinal microbiota in the onset of PSR.

Methods

We collected fecal and healthy and affected intestinal mucosal samples from 12 patients with CD who underwent surgery during the course of their disease. PSR was defined using a Rutgeerts index ≥i2b. The microbiota was assessed using 16S rRNA sequencing, and a correlation analysis was conducted between the intestinal microbiota and clinical variables of the patients.The study was conducted in accordance with the Helsinki Declaration, and all patients were recruited from among those undergoing scheduled colonoscopy for clinical indications at the Gastroenterology Unit of the University Clinical Hospital San Cecilio in Granada, Spain.

Results

In patients with CD and severe recurrence, mucosa-associated microbiota was characterized by a significant reduction in alpha and beta diversity compared to subjects in clinical remission.An enrichment of bacteria belonging to the phyla Bacillota and Pseudomonadota was observed, along with a reduction in Bacteroidota in subjects with PSR.We observed a negative correlation between the presence of E. coli and Shigella in patients in clinical remission and those actively undergoing treatment with biological therapy.

Conclusion

The recolonization of microbiota after ileocecal resection differs between patients with and without recurrence, with Fusobacteria and butyrate-producing bacteria being the most prominent contributors to driving PSR. The reduction in the abundance of short-chain fatty acid-producing bacteria and stimulators of anti-inflammatory cytokines like IL-10 could create a proinflammatory environment conducive to the development of PSR.These findings may provide valuable insights into the disease prognosis, allowing for the identification of patients at higher risk of recurrence and laying the groundwork for more targeted therapeutic approaches after surgeryRead more N09 Transition Success Score as a valid quantitative measure to evaluate the effect of transitional care in IBD patientsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Transition programs are designed to prepare adolescent patients with inflammatory bowel disease (IBD) for their new role in adult care. The outcome of these programs is often assessed in a qualitative way (patient satisfaction, quality of life, disease burden). However, there is no quantitative measure to evaluate the effect of a transition program. The aim of this study was to develop and validate a Transition Success Score (TSS) by the identified key components of successful transition.

Methods

The TSS was developed through an international Delphi consensus study, with the expert panel of pediatric and adult healthcare providers and patients. The top 10 key outcome items associated with success of transition were collated into one questionnaire. In every round, the minimum response rate required was 80%, and a consensus of more than 80% was necessary for each item. After four rounds of discussion, a consensus was reached on the initial version of the TSS. This score included seven items for adult healthcare providers to evaluate the patient's disease management behavior, including shared decision making, therapy adherence, and appointment attendance. Additionally, two items concern patient and parent experience concerning the transition period. The TSS was subsequently employed and validated in a prospective multicenter cohort of young adult IBD patients, who made the transfer 9-15 months ago, in the Netherlands.

Results

In seven hospitals, 160 IBD patients (median age 19.05, male 48.8%, Crohn's disease 56%, median age at diagnose 13.97) completed the TSS, at 9-15 months after transfer to adult care. Hypothesis testing for construct validation revealed significant association of characteristics related to transition care such as knowledge (RTT), independence (TRAQ), and quality of life (IBDQ) (p=<0.005). In addition, Rasch analysis for structural validation showed that the TSS was discriminating at lower levels of transition success (Figure 1). Internal consistency, as measured by Cronbach alpha, was acceptable at 0.64. TSS was significantly lower in patients with high disease burden, exacerbation within the first year after transfer and parental dependency. Also, TSS was lower in certain patient profile types, characterized as either "laid back, nonchalant" or "worried and uncertain".

Conclusion

The Transition Success Score (TSS) can serve as a quantitative measure to help identify IBD patients who did not have successful transition to adult care. TSS can be utilized for identifying factors that impact successful transition and for measuring the effect of various transition programs in IBD.Read more ECCO Grant Analysis of the tolerogenic role of the liver in controlling intestinal inflammationWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background and Aims

There is a close anatomical connection between the liver and the intestine. This connection is further highlighted by the association between Primary Sclerosing Cholangitis (PSC) and Inflammatory Bowel Disease (IBD). Interestingly, PSC-associated IBD (PSC/IBD) presents with milder colitis symptoms compared to Crohn's disease and Ulcerative Colitis. We hypothesize that PSC has a protective impact on IBD, which is mediated by Foxp3+ regulatory T cells. This hypothesis is supported by our preliminary data. However, the mechanism by which PSC induces tolerance in the intestine remains unknown and answering this question is the aim of this proposal.

Methods

In Objective 1, we will test the hypothesis that changes in the intestinal microbiota mediate the protective effects of PSC on IBD. We will compare the intestinal microbiota in patients with PSC/IBD and IBD. This analysis will be complemented by functional experiments. Specifically, we aim to engraft germ-free wild type (WT) mice with fecal microbiota from PSC/IBD and IBD patients, as well as from Mdr2-deficient and WT mice. In these mouse models, we will analyze the effect of the microbiota on effector and regulatory T cells and on colitis susceptibility. In Objective 2, we will test whether changes in the composition of bile acids mediate the protective effects of PSC on IBD. To test this, we will deliver specific bile acids identified by us into Il10-deficient mice and analyze their impact on colitis severity and the intestinal T cell repertoire. Moreover, we will decipher how those bile acids impact the intestinal microbiota. Using in vitro assays, we will further test the direct effect of specific bile acids on T cell differentiation.

Anticipated Impact

Finally, our long-term aim is to understand how the liver induces immunological tolerance in the intestine. This knowledge could pave the way for new targeted therapies for inflammatory diseases.Read more ECCO Grant Investigating the role of gut eukaryotic virome in contributing to colorectal cancer carcinogenesisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background and Aims

Eukaryotic-targeting viruses have recently attracted considerable interest in gastrointestinal diseases such as ulcerative colitis (UC) and colorectal cancer (CRC)1–3, the fourth leading cause of cancer death in the world4. UC and CRC share several factors influencing their etiogenesis, including intestinal dysbiosis2,5–7. Our group has recently published a work pinpointing a gut virome-associated Orthohepadnaviridae protein, namely Hepatitis B protein X (HBx) to correlate with UC pathogenesis and promote intestinal inflammation in mice by disrupting the epithelial barrier and shaping the gut mucosal immune environment, independently of the microbiota3. Moreover, we showed that HBx is able to induce DNA damagerelated processes and active biological processes related to the Wnt pathway3 known to be involved in colorectal carcinogenesis8. Our preliminary results raised the hypothesis that a specific virome-derived protein may fill the gap existing between intestinal inflammation and CRC onset by stimulating pro-inflammatory and/or pro-carcinogenic effects. To verify this hypothesis, we here propose to address the following Aims:Aim 1. To evaluate the carcinogenic effects and phenotypes induced by HBx in vivo.Aim 2. To unveil the molecular and cellular dynamics of HBx-induced effects in vitro.

Methods

Aim 1. Two mouse models of carcinogenesis will be used. The first will be the orthotopic model of CRC performed by injecting HBx-overexpressing Caco-2 cells in the rectal mucosa. The second will be performed by continuously challenging mice with the HBx protein directly into the rectal mucosa over 10 weeks. Tumor growth will be monitored over time and tumor samples will be characterized for histology and multidimensional flow cytometry analysis. Distal organs will also be analyzed to evaluate the extent of the metastasization.Aim 2. 3D models of intestinal mucosa microenvironment will be set up with HBxoverexpressing epithelial cells cocultured with intestinal immune and stromal cells. Then cells will be analyzed by single-cell transcriptomics and RNA pseudotime.

Anticipated Impact

Our study proposes an unconventional understanding of CRC carcinogenesis, investigating whether and how a eukaryotic virome-associated protein promotes CRC and exploring gut virome-dependent cellular and molecular mechanisms during CRC carcinogenesis.Read more ECCO Grant Serotonin gets into your genes: the role of histone serotonylation in inflammatory response and visceral hypersensitivity in Crohn’s DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background and Aims

More than 70% of CD patients experience visceral hypersensitivity (VH) despite reaching remission. VH treatment is difficult because the mechanism of its complication is unknown. Serotonin is mainly produced in the gut and regulates several physiological processes, such as intestinal immunity and pain. Disturbances in serotonin levels are associated with CD severity and VH. Intriguingly, we have recently observed that serotonin can covalently bind to glutamine at position 5 on histone H3 tail, leading to histone serotonylation (H3Q5ser) in peripheral blood mononuclear cells (PBMCs). Another study has demonstrated that H3Q5ser can also occur in cultured neuronal cells. Our objective is to investigate the role of this newly discovered epigenetic signature (H3Q5ser) in immune cells and enteric neurons in CD and its potential impact on the transcriptional programs of the inflammatory response and VH.

Methods

To accomplish this goal, we will first determine the concentrations of serotonin in the mucosa and serum of active CD patients compared to healthy controls and establish how these levels relate to the enhancement of H3Q5ser in immune cells and enteric neurons. To study the functional role of H3Q5ser in cell activation, we will use site-directed or oligonucleotide- mediated mutagenesis to induce a point mutation in cultured enteric neuron cell lines and PBMCs to remove the binding site for serotonin on histone. Both wild-type and mutant cells will be incubated with or without serotonin and subjected to chromatin immunoprecipitation sequencing and RNA sequencing profiling to investigate the effect of H3Q5ser on the transcriptional programs associated with inflammation and VH.

Anticipated Impact

This project will provide a comprehensive understanding of the impact of the changes in serotonin concentrations on H3Q5ser-related gene expression in CD- associated VH and the inflammatory response. Our anticipated impact is subsequent studies that monitor H3Q5ser in VH in CD patients during treatment.Read more ECCO Grant Untangling the gut phagosome dynamics of the relapse/remission cycle in ulcerative colitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background and Aims

The course of ulcerative colitis (UC) is usually characterized by intertwining periods of remission and relapse. Most microbiome UC studies focus on the gut bacteriome. However, recent studies on animal models suggest that phage-mediated bacterial cell lysis may play a role in sustaining gut inflammation, proving the phageome (collection of bacteriophages) should not be ignored in this disease. Therefore, this project aims to: 1) characterize the gut phageome of patients with UC who suffer from frequent relapses, 2) compare temporal dynamics of gut the phageome between patients and healthy controls, 3) To model interactions between bacteriome, mycobiome, phageome on one hand, and lifestyle factors (diet, stress levels, medication) on the other 4) To infer host status (relapse versus remission of the disease) based on phageome composition, and using interactions inferred in Objective 3.

Methods

The cohort comprises 24 patients with UC (14 of whom suffered from relapse) and 10 healthy controls, with stool samples collected monthly for a year. Phageome profiling will be achieved via shotgun sequencing of phage genomes from the same stool samples. This dataset will be interrogated together with bacterial (16S rRNA) and fungal (ITS) amplicon data, which have just been generated. Available metadata include disease symptoms, diet, stress levels, work productivity, medication, and faecal calprotectin. Dynamic time-wrapping algorithms will be used to align time series of microbial members with similar temporal dynamics. Dynamic Bayesian Network modelling will infer interactions between microbiome members and predict future relapse.

Anticipated Impact

The phageome is the often neglected (“dark matter”) part of the microbiome, but has defining interactions with bacteria. We will expand knowledge on inter-species dynamics during relapse and remission cycles of UC. This will potentially lead to new microbiome-related relapse predictors, which may contribute to new prognostic tools in UC, and potentially inform therapeutic avenues.Read more ECCO Grant Investigating regenerative pathways in salivary glands to mitigate oral manifestations of inflammatory bowel diseasesWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background and Aims

Inflammatory bowel diseases (IBD) impact 4-16% of patients with extraintestinal manifestations in the upper gastrointestinal (GI) tract, including stomach and esophageal ulcers, dry mouth, taste alterations, halitosis, ulcers, and periodontitis. The underlying mechanisms remain unclear. This study hypothesizes that intestinal inflammation disrupts upper GI tract homeostasis by impairing salivary gland functions and aims to:Aim 1: Elucidate cellular and molecular mechanisms of intestinal inflammation on upper GI tract mucosa and salivary glands.Aim 2: Evaluate therapeutic potential of liver X receptor (LXR) activation in restoring salivary gland function in colitis-induced oral pathology.

Methods

I will use a novel mounting method for spatial proteogenomic analysis of upper GI tract mucosa to identify colitis-induced perturbations. Salivary glands will be studied separately, employing bulk and single-cell transcriptomic profiling to identify mechanisms driving colitis-induced atrophy, dysfunction, and candidate regenerative pathways. Additionally, salivary gland organoids will be used to study regeneration mechanisms in vitro, such as LXR activation, and the therapeutic potential of successful candidate pathways will be tested in vivo using pre-clinical models of colitis and salivary gland damage/repair (irradiation).

Anticipated Impact

This research will provide insights into mechanisms by which intestinal inflammation disrupts upper GI tract homeostasis through salivary gland impairment and assess the role of candidate pathways in salivary gland regeneration. In the short to medium term, findings may contribute to developing novel therapeutic strategies for managing colitis-induced oral pathology, benefiting the IBD community by improving patients' quality of life.Read more P1107 Clinical characteristics and prognosis of very young adult-onset Crohn's disease: Results from the Prospective CONNECT StudyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Although the A2 group according to the Montreal classification accounts for the largest proportion among patients with Crohn’s disease (CD),¹ there has been a lack of studies comparing the clinical characteristics and prognosis according to the age at diagnosis within the A2 group.

Methods

We utilised data from the prospective CONNECT study—a nationwide, multicentre cohort study of CD patients in Korea.² Of 1,175 participants, a total of 945 patients (80.4%) were categorised as Montreal classification of age A2 (≥17 and <40 years at diagnosis). They were further divided into two groups based on the age at diagnosis: very young adult-onset group (≥17 and <20 years, n=275) and young adult-onset group (≥20 and <40 years, n=670).

Results

Isolated ileal diseases were more common in the young adult-onset group (21.5% vs. 30.7%), whilst the frequency of stricturing (B2) or penetrating (B3) behaviours was tended to be lower in the very young adult-onset group than in the young adult-onset group (16.7% vs. 29.7%) (Table 1). Twenty-five patients (9.1%) in the very young adult-onset group underwent intestinal resection compared to 91 patients (13.6%) in the young adult-onset group (p=0.072). The very young adult-onset group had a longer intestinal resection-free survival than the young adult-onset group (p=0.04) (Figure 1a). More patients in the very young adult-onset group received systemic corticosteroids compared with those in the young adult-onset group (62.2% vs. 48.8%, p<0.001) and the corticosteroid-free survival was shorter in the very young adult-onset group compared with the young adult-onset group (p<0.01) (Figure 1b). Complicated behaviors (B2, adjusted hazard ratio [aHR] 4.03, 95% confidence interval [CI] 2.42–6.70, p<0.001; B3, aHR 6.39, 95% CI 4.21–9.72, p<0.001) was independently associated with the risk of intestinal resection.

Conclusion

The very young adult-onset group exhibited distinct disease behaviour at diagnosis and different clinical outcomes compared with the young adult-onset group. Within the A2 group (≥17 and <40 years at diagnosis), the risk of intestinal resection appears to be driven by the intestinal complications.References1. Silverberg MS, et al. Toward an integrated clinical, molecular and serological classification of inflammatory bowel disease: report of a Working Party of the 2005 Montreal World Congress of Gastroenterology. Can J Gastroenterol 2005;19 Suppl A:5A–36A.2. Hong SW, et al. Clinical features and long-term prognosis of Crohn's disease in Korea: Results from the Prospective CONNECT Study. Gut Liver 2022;16(6):907–920.Financial support: This work was supported by the Research Program funded by the Korea Disease Control and Prevention Agency (2022ER050400).Read more P1122 Comorbidities Associated with Pediatric Onset Inflammatory Bowel Diseases: A Population-Based StudyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Inflammatory bowel disease (IBD) can be associated with various disorders, including dermatological, rheumatological, or psychiatric conditions. However, little is known about the incidence of these co-morbidities in paediatric-onset IBD at the population-based level.

Methods

All patients diagnosed with Crohn's disease (CD) or ulcerative colitis (UC) before the age of 17 between 1988 and 2011, and included in the EPIMAD population-based registry, were followed retrospectively until 2013. In this population, we collected information on comorbidities present at diagnosis, as well as events related to the development of a new chronic condition, hospitalization, or an infectious event of interest (as pneumopathy, meningitis, or pyelonephritis) reported in the medical records during the follow-up period.

Results

A total of 1,344 patients were included, comprising 1,007 (74.9%) with CD and 337 (25.1%) with UC. The median age at diagnosis was 14.3 years (IQR [11.7; 16.0]). During a median follow-up of 8.3 years ([4.3-13.9]), 361 (26.9%) patients exhibited at least one comorbidity. At diagnosis, 9.4% (95% CI [7.8% - 11.0%]) of patients had at least one comorbidity. The cumulative incidence of comorbidity was 13% (95% CI [11% - 14%]) at 1 year after diagnosis and 20% (95% CI [17% - 22%]) at 5 years. No association was found between the risk of comorbidity and the clinical characteristics at IBD diagnosis. However, the cumulative incidence of comorbidity was higher in the diagnosis period 2001-2011 than in the period 1988-1993 (HR=1.7 [1.2-2.2]; p<0.001). The most frequent comorbidities were infectious (5.6%), dermatological (5.5%), and pulmonary (5.3%) (Figure 1). The most common infectious events included bacteraemia, digestive tract infection with Clostridioides difficile, and viral infection with Herpesviridae or parvovirus B19, with a cumulative incidence during follow-up of 1.2%, 1.0%, and 0.9%, respectively. During follow-up, viral infections with HBV, HCV, or HIV were observed in 0.2% of patients, and pneumopathy was diagnosed in 0.7% of patients. Eczema and asthma were the predominant dermatological and pulmonary comorbidities, affecting 2.6% and 5.1% of patients, respectively.

Conclusion

In this paediatric-onset IBD population-based cohort, the most common comorbidities were infectious, dermatological, and pulmonary. Bacteraemia emerged as the most prevalent severe infectious event during follow-up, affecting 1.2% of patients.Read more P1123 Social isolation, loneliness, and incident inflammatory bowel disease: results from a large prospective cohorts and Mendelian randomizationWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Background Social isolation and loneliness pose significant public health challenges globally. The objective of this study is to investigate the association between social isolation, loneliness, and the risk of inflammatory bowel disease (IBD), ulcerative colitis (UC) and Crohn's disease (CD).

Methods

Methods 275,157 UK adults from the UK Biobank (UKB) was analyzed. The exposures of interest were social isolation and loneliness. Social isolation was measured by the frequency of meeting family/friends, leisure and social activity, and communal/solitary living. Loneliness was evaluated by the subjective feeling of loneliness and the willingness to confide in others. The primary endpoint was incident IBD, including UC and CD. The twosample Mendelian randomization (MR) analysis was based on the genome-wide association studies of UKB and the a nonoverlapping European ancestry GWAS study.

Results

Results The UKB cohort study documented 1,565 IBD (1063 UC and 492 CD) cases during a mean follow-up of 13.49 years. Social isolation and loneliness showed significant associations with an elevated risk of IBD in UKB (social isolation [moderate vs least]: aHR 1.13, 95% CI 1.02-1.26; social isolation [most vs least]: aHR 1.31, 95% CI 1.01-1.70; loneliness [yes vs no]: aHR 1.29, 95% CI 1.04-1.60). These associations were evident among moderate genetic susceptibility to IBD. Social isolation and loneliness jointly increase the risk of IBD onset, with an aHR of 1.60 (95% CI 1.21-2.12). Two-sample MR analyses determined that engaging in fewer leisure/social activities (OR 3.42, 95% CI 1.55-7.58; 3.32, 95% CI 1.29-8.55; 3.09, 95% CI 1.35-7.07) were associated with increased IBD, UC and CD risk, whereas more activities-sports club or gym (OR 0.37, 95% CI 0.15-0.88) was associated with reduced IBD risk.

Conclusion

Conclusion Social isolation and loneliness are each associated with an elevated risk of IBD especially for individuals with a moderate genetic risk for IBD, with MR analyses suggesting potential causal links. The findings highlight the importance of promoting initiatives to address social isolation and loneliness as part of IBD prevention strategies.Read more P1142 Antibiotic use in the twelve months prior to ileal pouch-anal anastomosis increases the risk for pouchitis: A population-based Danish cohort studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Pouchitis is the most common complication after ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC), however clinical and environmental risk factors for pouchitis remain poorly understood. We explored the relationship between specific clinical factors and the incidence of pouchitis.

Methods

We established a population-based cohort of all adult persons in Denmark undergoing proctocolectomy with IPAA for UC between January 1, 1996 and May 31, 2020. We used Cox Proportional Hazard modeling and logistic regression to assess the impact of antibiotic and non-steroidal anti-inflammatory drug (NSAID) exposure and appendectomy on the primary outcome of diagnosis of acute pouchitis in the first 2 years after IPAA surgery. A 2-year time window was utilized given the clinical relevance of early pouchitis and to mirror prior studies in both administrative claims and the Danish health registers.

Results

Among 1,616 eligible patients, 738 (46%) developed pouchitis in the first 2 years after IPAA. Among all patients undergoing IPAA surgery for UC, 51% were prescribed antibiotics in the 12 months prior to the index date and 17% were prescribed NSAIDs in the 12 months prior to the index date. In Kaplan-Meier analyses, those persons who were prescribed antibiotics in the 12 months prior to the final stage of IPAA surgery were significantly more likely to develop pouchitis in the 2 years after the index date when compared to patients who were not prescribed antibiotics (p<0.001, Figure 1B). Additionally, male patients demonstrated a decreased risk for pouchitis in the first 2 years after the index date when compared to female patients (p=0.014, Figure 1A). Antibiotic exposure in the 12 months prior to IPAA was associated with an increased risk of pouchitis (adjusted Hazard Ratio [aHR] 1.40, 95% CI 1.21-1.62) after adjusting for year of surgery and sex (Table 1). In a secondary analysis, compared to persons without any antibiotic prescriptions in the 12 months prior to IPAA, the risk of pouchitis was increased in those with 1 or 2 courses of antibiotics in that period (aHR 1.29, 95% CI 1.10-1.51) and 3 or more courses (aHR 1.79, 95% CI 1.43-2.23, Figure 1C). NSAID exposure in the 12 months prior to IPAA and appendectomy were not associated with risk of acute pouchitis (p=0.201 and p=0.865 respectively).

Conclusion

In this population-based cohort study, we demonstrated that antibiotic exposure in the 12 months prior to IPAA is associated with an increased risk of acute pouchitis. Future prospective studies may isolate specific microbial changes in at-risk patients to drive earlier interventions.Read more P1143 Per- and poly-fluoroalkyl substances (PFAS) exposure is associated with later occurrence of inflammatory bowel diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Environmental chemical exposures are increasingly acknowledged as risk factors for inflammatory bowel disease (IBD). Per- and poly-fluoroalkyl substances (PFAS), a large class of persistent fluorinated organic chemicals, widely used in the modern environment, may be implicated in IBD etiology, but data are conflicting.

Methods

We investigated the association of PFAS mixture concentrations in pre-diagnostic serum with adult-onset IBD in a pilot study within the pre-clinical Proteomic Evaluation and Discovery in an IBD Cohort of Tri-service Subjects (PREDICTS) study. This is a nested case-control study of military personnel with Crohn’s disease (CD), ulcerative colitis (UC), and age-, sex-, and race-matched healthy controls with serum samples obtained at four-time points 1-10 years prior to IBD diagnosis. Using untargeted liquid-chromatography high-resolution mass spectrometry analytical approach, we conducted an untargeted metabolomic analysis and semiquantitative measurement of fluorinated compounds, including legacy PFAS and emerging PFAS chemicals. We used weighted quantile sum regression models adjusted for confounders to study the association of PFAS as a mixture with the odds of CD and UC at each time point.

Results

Our study sample included individuals with CD, UC, and matched healthy controls (n=25, each group, 4 samples per individual). Baseline characteristics were similar across cases and controls. We identified nine well known PFAS compounds and 27 other known fluorinated compounds. The chemical mixture of fluorinated compounds, including the known PFAS, in the serum samples within one year of diagnosis was associated with higher odds of CD and UC [odds ratio (OR) 2.13, 95% CI 1.33, 3.41, and 1.76, 95% CI 1.15, 2.68, respectively] per one unit increase in decile. These associations remained consistent for the PFAS mixture measured in serum at all four time points up to 10 years prior to diagnosis for both CD and UC (Figure). Major contributors to the overall mixture indices included legacy PFAS, as well as emerging PFAS chemicals.

Conclusion

We observed a substantial increase in the odds of CD and UC among individuals with higher serum PFAS mixture levels up to 10 years prior to diagnosis. Studies to understand underlying mechanisms are ongoing.Read more P1164 Early monitoring of ustekinumab concentration after induction is related to clinical remission in ulcerative colitis & Crohn`s disease - STOCUSTE studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Ustekinumab (UST), an anti-interleukin-12/23 antibody, is used to treat moderate to severe inflammatory bowel disease (IBD). The STOCUSTE study includes IBD patients treated with UST at four teaching hospitals in Stockholm to provide long-term follow-up data. We investigated in a real-world setting the utility of therapeutic drug monitoring (TDM) to optimize treatment and correlated the serum concentrationof UST to clinical outcomes.

Methods

This retrospective study includes patients diagnosed with Crohn’s disease (CD) and ulcerative colitis (UC) treated with UST and followed until withdrawal of treatment for any reason, or until end of study,July 31, 2021. Concentration data and dosing interval were collected at each follow-up (3, 6, 9, 12, 24,36, 48, 60 months) in relation to presence of remission defined as Physician Global Assessment (PGA)= 0.

Results

In total, 418 patients were included, 322 (48% females) with CD and 96 (46% females) with UC. In 229 patients the UST concentration was analyzed at least once and never in the remaining 188 patients. In general, the UST serum concentrations were above 1 μg/ml. At 3 months follow-up, patients in remission had a significant higher concentration of UST compared to non-remitting patients. (Table 1) in the total cohort, as well as when analyzed separately in UC ad CD. There was no significant difference in UST concentrations at 6 months or later between patients in remission versus non-remission for either IBD diagnosis. Further, TDM was related to higher rates of remission at 3 months of follow-up.

Conclusion

In this study, early measurement of serum UST (≤3 months) correlated to the clinical response. Serum concentrations at later time points were similar in patients in remission and in patients with active disease. These results from a real-world setting might partly be explained by that serum concentrations were not taken in a systematic manner.Read more P1165 Epidemiology and distinct features of inflammatory bowel disease in South Asia: a systematic reviewWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Inflammatory bowel disease (IBD) is rising at an alarming rate in South Asia (SA, Afghanistan, Bangladesh, Bhutan, India, Maldives, Nepal, Pakistan, and Sri Lanka). However, studies detailing the epidemiology and clinical features of IBD in this region are limited. The purpose of this review is to comprehensively synthesise data on IBD in South Asia.

Methods

We developed and performed a systematic search in four biomedical electronic databases (Ovid Medline, Embase (Ovid), Global Health, Web of Science) and in relevant scientific meeting abstracts to identify all observational and interventional studies on the epidemiology, natural history, phenotype, therapeutics, and psychosocial features of IBD in SA from inception to November 15, 2021. The titles and abstracts of all the publications were screened and reviewed by two independent reviewers (SS, AJ). A descriptive review of the relevant data extracted from the selected publications was analysed.

Results

Of 11,673 eligible studies, 4416 were duplicates, 800 were reviewed in full text, and 413 were eligible for inclusion in one or more categories.The following are the main findings of the systematic review: IBD incidence is higher in SA compared to other Asian countries. Similarly, IBD incidence and period prevalence are higher among SA immigrants compared to other immigrants. Ulcerative colitis (UC) is more prevalent than Crohn’s disease (CD) in SA across all age groups. Family history of IBD is important risk factor for IBD in SA. The mean delay in IBD diagnosis in SA is 2 years, and it is associated with increased risk of strictures and surgery. Male sex, small intestinal disease, perianal involvement, and penetrating and stricturing disease behaviour are predictors of surgery in CD. Disease duration and extent of colitis are risk factors for colorectal cancer. Colonic distribution and inflammatory behaviour is common in CD, whereas left sided colitis is common in UC. Steroids and azathioprine are mainstays of treatment, biologic use is less than 2%. Depression, anxiety, and post-traumatic stress are common among SA patients with IBD.

Conclusion

This comprehensive review highlights the current epidemiological trends and features of IBD in SA. Contrary to previous viewpoints, IBD in SA is similar in severity, complications, and burden as that in developed countries, and warrants urgent clinical interventions and allocation of resources.Read more P1198 Pediatric inflammatory bowel diseases in patients with genetic syndromes: a case-control multicentre SIGENP studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Genetic syndromes are associated with a strong susceptibility to autoimmune disorders with an increased risk of developing inflammatory bowel diseases (IBD). However, data regarding the impact of genetics in the development of IBD are limited (Gatti S. et al, Frontiers in Pediatrics 2021). Furthermore, patients with genetic syndromes are affected by multiple comorbidities which increase diagnostic and therapeutic complexity as well as the risk of developing adverse reactions to drugs.

Methods

In this retrospective, multicenter case-control study, we recruited IBD children with a genetic syndrome (cases: group 1) and 2 matched IBD patients for each case (controls: group 2) comparable for gender, age at diagnosis, type of IBD and follow-up period. IBD subjects were diagnosed at 11 Italian pediatric IBD units between 2010 and 2022. Monogenic VEO-IBD were excluded. Genetic data were collected. Clinical and disease characteristics, presence of comorbidities, use of drugs and side effects, surgical outcomes and mortality were compared at diagnosis and at the last follow-up between the 2 groups.

Results

A total of 23 IBD children with a genetic condition/syndrome (Table 1) and 46 matched controls were identified.In all cases, except 5 the diagnosis of IBD followed the genetic diagnosis. Thirty patients had Crohn’s disease (CD) and 39 had Ulcerative Colitis (UC). The 2 groups were comparable in terms of gender, age at diagnosis (8,9±4.6 vs 9.4±4.4 years), duration of follow up (5.6±3.4 vs 4.1±2.9 years) and severity of disease at diagnosis evaluated by w-PCDAI (34,7±23,5 vs 43,1±20,4) and PUCAI (45,3±16 vs 46,2±15,5) scores. Diagnostic delay was longer in patients with genetic conditions compared to controls, without reaching statistical significance (11,1 vs 4,6 months; p= 0,06). Prevalence of comorbidities was significantly higher in group 1 compared to controls both at diagnosis (43,4 vs 11,5%; p <0,005) and at last follow-up (39,1 vs 11,6%; p <0,02). Use of immunosuppressors, steroids and biologic drugs was similar at diagnosis and at last follow-up in the 2 groups. More IBD patients in group 1 developed side effects related to immunosuppressors (26 vs 4%; p < 0,02), while no difference was observed in biologics-related side effects. The need of surgery was comparable in the 2 groups (13 vs 13,9 %), whereas mortality was slightly higher in patients with IBD and genetic syndrome (13 vs 7%).

Conclusion

In pediatric IBD patients the presence of genetic syndromes does not significantly modify the course of the disease itself, but increases complexity due to the multiple comorbidities and immunosoppressive drug toxicity.Read more P1199 An Inflammatory Bowel Diseases Integrated Resources Portal (IBDIRP)Wed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease (CD), is a chronic and debilitating gastrointestinal disorder that affects millions of people worldwide. Research on IBD has generated massive amounts of data, including literature, metagenomics, metabolism, bioresources, and databases. We aim to create an IBD Integrated Resources Portal (IBDIRP) that provides the most comprehensive resources for IBD.

Methods

An integrated platform was developed that provides information on different aspects of IBD research resources, such as single nucleotide polymorphism, genes, transcriptomics, microbiota, metabolism, single cells, and other resources. Valuable and comprehensive IBD-related data were collected from PubMed, Google, GMrepo, gutMega, gutMDisorder, Single-cell Portal, and other sources. Then, the data were systematically sorted, and these resources were manually curated.

Results

We systematically sorted and cataloged more than 312 unique risk single nucleotide polymorphism associated with IBD in the single nucleotide polymorphism section. We presented over 890 IBD-related genes based on the database collection in the gene section. We also obtained 153 manually curated IBD transcriptomics data, including 12,388 samples, on the GEO database. The sorted IBD-related microbiota data from three primary microbiome databases (GMrepo, gutMega, and gutMDisorder) were available for download. We selected 23,149 IBD-related taxonomic records from these databases. Additionally, we collected 24 IBD metabolism studies with 2,896 participants in the metabolism section. We introduced two interactive single-cell data plug-in units that provided data visualization based on cells and genes. Finally, we listed 18 significant IBD web resources, such as the official ECCO and IOIBD websites, IBD scoring tools, IBD genetic and multi-omics resources, IBD biobanks, and other useful research resources.

Conclusion

The IBDIRP website is the first integrated resource for global IBD researchers. This portal will help researchers by providing comprehensive knowledge and enabling them to reinforce the multi-dimensional impression of IBD. The IBDIRP website is accessible via www.ibdirp.com.Read more P1200 Study of correlation between polymorphisms of vitamin D metabolism genes and perianal disease in Crohn's diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Vitamin D (VD) is a fat-soluble vitamin essential for calcium homeostasis and that acts at the extraskeletal level. UVB skin exposure allows the synthesis of provitamin D. This undergoes a first hydroxylation in the leaver by the CYP2R1 enzyme and a second hydroxylation in the kidney by the CYP27B1 enzyme: active VD is obtained. VD is transported into the circulation by VDBP and exerts its activity in the target cells binding its VDR receptor. Finally, VD is inactivated by the renal enzyme CYP24A1.Perianal disease (pCD) is a severe phenotypic manifestation of CD that may present as perianal fistula, abscess, recto-vaginal fistula, or stenosis. Among the mechanisms involved in its pathogenesis we recognise local inflammation and intestinal microbiota alteration. Vitamin D (VD) seems to act on these elements.As there are currently no studies on this subject in the literature, the aim of this study is to evaluate the presence of an association between SNPs of genes coding for enzymes, transporters and receptors involved in the VD pathway and the occurrence of pCD in CD patients.

Methods

The study was carried out on the biological samples of 206 patients with CD, including 34 with pCD, who were followed up at the inflammatory bowel disease clinic in Turin, Italy. Through the use of Real-Time PCR, the genotype distribution of the following genes were assessed: VDR, CYP27B1, CYP24A1, and GC. For the association study, chi-square test was performed with calculation of p value and, when significant, logistic regression and calculation of OR with 95% CI was performed.

Results

Studying the association between SNPs and the presence of pCD, the following results were obtained: BsmI p=0.0470 and Apal p=0.0251. For BsmI heterozygous genotype there was an OR=2.5 (95% CI 1.2-5.3) of developing perianal disease and p value=0.02, while for ApaI heterozygous there was OR=2.91 (95% CI 1.3-6.6) of presenting pCD, with p value=0.01.

Conclusion

In the literature, there are several studies examining the association between the heterozygous Aa genotypes of ApaI and Bb genotypes of BsmI and increased inflammatory markers. In addition, some studies suggest that these two genotypes represent a risk factor for some diseases, including multiple myeloma, systemic lupus erythematosus, and mild cognitive disorder. This study demonstrates for the first time an impact of polymorphisms of genes associated with the VD pathway in predicting the onset of pCD. Specifically, the presence of the heterozygous genotype of BsmI and ApaI significantly increases the risk. Future studies need to be performed in different and larger cohorts of patients in order to confirm these data.Read more P1201 Association between Inflammatory Bowel Disease and Henoch-Schönlein purpura: A Bidirectional Two-Sample Mendelian Randomization StudyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Henoch-Schönlein purpura (HSP) is a systemic small-vessel vasculitis, and its association with inflammatory bowel disease (IBD) has been the focus of considerable research. Despite numerous studies, it remains uncertain whether and in which direction causal relationships exist between HSP and IBD. To reveal the causal association between HSP and IBD, we conducted a bidirectional two-sample Mendelian randomization analysis using publicly available genome-wide association study (GWAS) summary statistics.

Methods

We obtained summarized data for IBD, Crohn's disease (CD), ulcerative colitis (UC), and HSP from various GWAS. To estimate causality, we used inverse-variance weighted approaches. Additionally, we conducted several sensitivity analyses. In our causality estimates, we present odds ratios (ORs) and 95% confidence intervals (CIs).

Results

We found that CD (OR: 1.12, 95% CI: 1.00 to 1. 25, P < 0.05), but not UC (OR: 1.04, 95% CI: 0. 909 to 1.19, P > 0.05), had significant positive causal effects on HSP risk. However, the overall result of the MR study demonstrated that there was no causal link between genetic predisposition to IBD and an increased risk of HSP (OR: 1.10, 95% CI: 0.989 to 1.23, P > 0.05). Regarding the reverse directions, no significant causal associations were discovered.

Conclusion

It appears that CD and HSP are causally related, which could influence clinical decisions regarding the management of CD in patients diagnosed with HSP. However, neither overall IBD nor UC has a causal effect on HSP.Read more P1230 Integrated analysis of microbiome and metabolome reveals disease-specific profiles in inflammatory bowel disease and intestinal Behcet’s diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Gut microbial and metabolic characteristics in intestinal Behcet’s disease (BD), a condition sharing many clinical similarites with ulcerative colitis (UC) and Crohn’s disease (CD), are largely unexplored. This study aimed to investigate the gut microbial and metabolic characteristics, as well as potential biomarkers in intestinal BD, comparing them with UC and CD, along with healthy controls.

Methods

Patients with UC, CD, and intestinal BD, along with healthy volunteers undergoing diagnostic endoscopies, were enrolled. Colon tissue and stool samples were analyzed using 16S ribosomal RNA sequencing, assessing microbial diversity, taxonomic composition, and functional profiling by phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt). Plasma metabolomic analysis was performed using gas chromatography and ultra-performance liquid chromatography-time-of-flight mass spectrometry, and quantitative enrichment analysis (QEA) was performed.

Results

In total, 100 patients (35 UC, 30 CD, and 35 BD) and 41 healthy volunteers were enrolled. While CD exhibited reduced microbial diversity in colon tissue, BD showed no significant decrease. The taxonomic profile of intestinal BD resembled healthy controls more than UC or CD but exhibited specific distinct features. Common changes across all conditions included a decrease in five beneficial bacteria producing short-chain fatty acids (Fusicatenibacter saccharivorans, Coprococcus comes, Blautia obeum, Dorea formicigenerans, and Roseburai ceciola). Additional changes in intestinal BD included a decreased abundance of Subdoligranulum variable and Blautia wexlerae, which were shared features with either UC or CD. Intestinal BD-specific alterations involved decreased abundance of certain bacteria, including Bacteroides fragilis. Metabolomic profiles of intestinal BD by QEA showed similarity to CD and distinction from UC and controls, with pronounced functional changes in energy metabolism and genetic information processing, correlating with microbial functional analysis by PICRUSt.

Conclusion

This integrative analysis unveiled both common and distinctive profiles in intestinal BD when compared to UC, CD, and controls. The study identified potential biomarkers, contributing to a deeper comprehension of the unique features in these diseases, which could serve as key elements for elucidating their pathogenesis.Read more P1231 7-ketositosterol in high-temperature heating oils aggravates colitis by gut microbiota dysbiosis induced-PDLIM3 activationWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Diet and gut microbiota alteration are considered as the most important environmental factors triggering inflammatory bowel disease. Phytosterols are rich in edible oils, and can be oxidized to oxyphytosterols during high-temperature cooking. Previous studies have indicated that oxyphytosterols exposure exerted potential adverse effects in cell and animal models. It remains unknown whether oxyphytosterols could promote colonic inflammation. 7-ketositosterol has the highest proportion in oxyphytosterols.

Methods

The fried and baked foods intake was collected and compared in IBD patients and healthy individuals. 7-ketositosterol was synthesized from β-sitosterol and impacts of 7-ketositosterol on intestinal inflammation was evaluated in colitis mice models. 16S rRNA and transcriptome sequencing were carried out. Furthermore, fecal microbiota transplantation was carried out to evaluate the effect of gut microbiota. Protein interaction of Staphylococcus lentus and PDLIM3 was explored by co-immunoprecipitation.

Results

The fried and baked foods intake in IBD patients was much more than that of healthy individuals, with higher exposure to oxyphytosterols. 7-ketositosterol (KS) aggravated mice colitis. KS increased the abundance of Actinobacteria (p=0.023). Meanwhile, the abundance of potential pathogens such as Staphylococcus (p=0.004) and Corynebacterium_1 (p=0.003) were increased in KS group, while the abundance of short chain fatty acids producing bacteria were decreased. Transcriptome data showed KS increased the expression of PDLIM3 (p=0.004). PDLIM3 expression was demonstrated to increase in intestinal epithelial cells, and the expression tendency of p-p38 and p-p65 was consistent with PDLIM3. In addition, KS did not exacerbate DSS induced colitis after antibiotic cocktails treatment, and PDLIM3 expression decreased in parallel. The gut microbiota from KS also aggravated DSS induced colitis in antibiotic treated mice. Proteins from Staphylococcus lentus could interact with PDZ domain and promote PDLIM3 expression.

Conclusion

7-ketositosterol in high temperature heating oils such as fried foods could aggravate colitis by modulation of gut microbiota. Gut microbiota interacted with PDZ domain, promoted PDLIM3 expression and then activated p38MAPK/NF-κB signaling pathway.Read more P1232 Alterations in microbial composition in patients with newly diagnosed Crohn's disease over a course of one year: data from a prospective longitudinal real-world studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Gut microbial composition in Crohn's disease (CD) is variable, changing with specific interventions. We aimed to explore the dynamics in microbial alterations in a cohort of patients with newly diagnosed Crohn's disease (ndCD) over one year.

Methods

This was a prospective longitudinal real-world study of patients with ndCD¹ naïve to therapy who were treated at the physician's discretion. Clinical outcomes at one year were corticosteroid-free clinical remission (CSFR) and biochemical remission ([BR], CRP<1mg/dL and FC<150ug/g). We sequenced paired stool samples from diagnosis and after one year using 16S rRNA gene (V4) and analyzed changes in diversity and dysbiosis indices. A linear mixed-effect model was constructed to identify factors associated with microbial alterations and to identify specific genera that drove the alterations while controlling for confounders.

Results

Seventy-five patients completed one-year follow-up (49.3% female, median age 27 years [IQR 22-38.5], therapeutic interventions: 45 patients on biological therapies [43 anti-TNF], 26 antibiotics, 10 corticosteroids, 5 underwent surgery, and 59 various nutritional interventions). Rates of CSFR, BR, and conjoined CSFR-BR at one-year post-diagnosis were 64%, 56%, and 45.3%, respectively. We observed an overall significant increase in microbial Shannon diversity (H index), p<0.001, and decreased microbial dysbiosis index (MDI), p=0.007, from baseline to one year. On subgroup analysis, these alterations were significant among patients who achieved the clinical outcomes (all p<0.05) and even more prominent among patients who were on biological therapies (both indices p<0.001). Notably, in the biological therapy subgroup, the microbial composition at diagnosis was less diverse and more dysbiotic than in the non-biological subgroup. In the latter, microbial composition at diagnosis was less disrupted and remained relatively stable over time. Linear mixed model analysis corroborated a positive association between biological therapy and the positive dynamics in microbial indices (H-index, p=0.020 and MDI, p=0.040). Fifteen specific genera drove the microbial alterations over time (Table 1), while alterations in the relative abundance of some genera correlated with changes in clinical biomarkers and clinical indices (Figure 1).

Conclusion

The microbial composition of this real-world cohort of patients with ndCD improved over the course of one year, which was significant for patients who achieved clinical outcomes and was more prominent for patients requiring biological therapy. In this subgroup, the microbial signature was less diverse and more dysbiotic when diagnosed; this likely led the significant improvement over time.1 Yanai H,et al. Crohns Colitis 360 2023;5:otad064Read more P1233 Serum insulin is associated with c-reactive protein and gut microbial diversity in inflammatory bowel diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Obesity, impaired glucose tolerance and unfavorable lipid profile are established risk factors for cardiovascular disease. Patients with inflammatory bowel disease (IBD) may be at increased risk of cardiovascular disease, and new therapies such as JAK inhibitors may further add to this risk. C-reactive protein (CRP) is a marker of systemic inflammation that may increase with active IBD and is correlated with metabolic risk in non-IBD cohorts. Diet, in particular consumption of ultra-processed foods, has been linked to gut dysbiosis and the onset, course, and response to treatment of both IBD and metabolic disease. The aim of this study was to identify metabolic risk in a cohort of individuals with IBD through an analysis of diet, metabolic parameters and stool microbial diversity.

Methods

This two-week prospective case-control study enrolled non-diabetic individuals with IBD in clinical remission and healthy individuals (HC). Baseline body mass index (BMI), waist circumference (WC) and waist to hip ratio, detailed diet diary, serum metabolic and inflammatory parameters, stool bacterial microbiota and faecal calprotectin (FC) were examined.

Results

Eighty-one participants; 57 with IBD (26 ulcerative colitis (UC), 31 Crohn’s disease (CD)) and 24 HC participants were recruited. In the IBD group, there was a positive correlation between serum insulin, triglycerides, BMI and WC with CRP and a negative correlation between HDL and CRP (Table 1). There were no associations between measured metabolic risk factors and FC. Stool microbial alpha diversity of the IBD group was lower than that of the HC cohort, with lower species richness (IBD 21.4 v HC 26.8, p<0.01) and Shannon’s diversity index (SDI) (IBD 3.1 v HC 3.4, p=0.03) (Figure 1). In the IBD group, there was a negative association between serum insulin and CRP with stool species evenness (SE) and SDI (insulin: SE r=-0.41, adj-p=0.02, SDI r=-0.39, adj-p=0.02; CRP: SE r=-0.4, p=0.02, SDI r=-0.4, p=0.02) and a negative association between intake of processed meat and stool alpha diversity metrics (SE r=-0.39, adj-p=0.046 and SDI r=-0.42, adj-p=0.02 respectively). There were no significant associations between serum metabolic profile and dietary intake with stool alpha diversity in the HC group.

Conclusion

Unhealthy diet, higher body weight and suboptimal glucose control were positively associated with CRP in participants with IBD. Gut microbiota with reduced diversity may be a common link between adverse metabolic outcomes and IBD. Serum insulin should be explored as a common biomarker of metabolic and gut microbial health.Read more N25 "I Felt So Alone” Exploration of experience of being newly diagnosed with inflammatory bowel disease: a phenomenological studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Individuals recently diagnosed with Inflammatory bowel Disease (IBD) often have unmet informational and psychological needs, leading to distress and anxiety. This lack of support negatively affects their quality of life, mental health, social functioning, and physical outcomes. Additionally, the absence of counselling and peer support isolates many people and places an emotional burden on them. Delayed diagnosis or misdiagnoses due to symptoms being dismissed by health professionals exacerbate the problem. Acknowledging these unmet needs and adverse outcomes, this study aims to shed light on patients' experiences to inform improvements in clinical practice, support services, and workplace policies, particularly during the immediate diagnosis phase.

Aim

The aim of this study is to explore the experience of people newly diagnosed with IBD and their need for support.

Methods

The study employed interpretive phenomenology semi-structured interviews following a topic guide and analysed the data using Braun & Clark's (2023) thematic analysis method and Nvivo software. Crohn's and Colitis UK (CCUK) charity acted as the gatekeeper for access to participants. Participants were purposively selected on specific criteria: IBD diagnosis ≤1 year, aged 16 or older, English language proficiency and diversity of demographic and clinical variables.

Results

Of 49 volunteers who responded to the research advertisement, 15 were selected based on eligibility criteria. Participant characteristics are shown in Table 1. Four themes emerged (Fig 1), with 12 subthemes. Participants expressed extreme dissatisfaction, either due to misdiagnosis or diagnostic delays, indicating the need for timely streamlined diagnosis. Additionally, IBD diagnosis itself triggered distress and anxiety. Participants reported the need for continuous psychological counselling and peer support. Due to symptoms like blood loss and diarrhoea, IBD profoundly affects physical health, emotional wellbeing, social interactions, and work-life balance, hence challenging patients' sense of normalcy. However, patients demonstrated resilience via lifestyle adjustments, social support networks, and coping strategies.

Conclusion

This qualitative study sheds light on the profound impact of an IBD diagnosis. It reveals emotional struggles and the need for streamlined diagnosis and psychological support. Lifestyle disruptions affect physical and mental health, but participants adapt through support and coping. These insights have practical implications for improving care, mental health services, workplace adjustments, social support, and coping resources for the newly diagnosed IBD population. Future research should expand to larger, diverse patient samples.Table 1:Read more N36 Inflammatory Bowel Disease Dysplasia Surveillance Pathway (IBD DSP)Wed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

UK-wide concerns have arisen regarding patients with Inflammatory Bowel Disease (IBD) on surveillance lists being missed or dropped off waiting lists due to the COVID-19 pandemic's impact on waiting times and lists.An IBD surveillance link nurse role was developed involving clinical sessions with a gastroenterology consultant. The IBD Dysplasia Surveillance pathway (DSP) was created to improve education and counselling for high-risk patients, alleviate concerns, and facilitate shared decision-making in IBD care.

Methods

All patients with dysplasia with a background of IBD are referred to the IBD MDT. After discussion the patients are referred to the DSP clinic. The clinic maintains a dysplasia database capturing all high-risk patients with dysplasia, demographic data, co-morbidities, grade of dysplasia and scheduled endoscopy are collated. Outcome measures of did not attend (DNA) and missed cancers were analysed.

Results

Since April 2022, 170 patients have been referred to the DSP, with 52 reviewed in the surveillance Clinic and 16 referred to joint surgical clinics, with 15 invisible, 34 visible, three high-grade dysplasia and 25 low-grade dysplasia cases. Four patients underwent surgery, and two patients declined surgery. Sixteen patients underwent yearly colonoscopies. Two patients DNA for their colonoscopy. There were no missed cancers.

Conclusion

The IBD Dysplasia Surveillance Pathway is a systematic approach for IBD surveillance. It improves communication between IBD and endoscopy teams. The clinic's hybrid approach improves accessibility and engagement with surveillance, reducing cancellations/DNA of surveillance colonoscopies in the IBD patient population, and facilitating the BSG guidelines for cancer surveillance.Read more P1110 Collagenous colitis, clinical features, risk factors and treatment outcome: A large case series from the largest teaching Hospital in London, UKWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Microscopic colitis is a cause of chronic watery, non-bloody diarrhoea diagnosed mainly on histology after taking biopsy from macroscopically normal colonoscopy. Thereby mainly two subtypes can be identified: Lymphocytic and collagenous colitis. So far, no biomarkers for the diagnosis of microscopic colitis have been identified. Here, we looked at, risk factors and treatment outcome of collagenous colitis in large series of cases.

Methods

In this study, we analysed all cases of collagenous colitis diagnosed from 2018-2022 in the Northeast London from 5 different teaching hospitals. 104 cases were identified and their electronic health record from hospital and from the primary care physicians (GP) were manually reviewed.

Results

In this cohort, 24% male, 76% female with ratio of (1:3), with mean age of 65 years. Forty percent were active or ex-smoker. PPI uses were associated with in 81% cases. While NSAIDS and statin were associated in 56% and 49% cases respectively. We also found that SSRI use were noted about 31% cases.Painless watery diarrhoea was the main cause for referral in 90% of cases, while complaint of abdominal pain noted in only 39% cases. Thirty-five (35%) cases noted to have history of weight loss. Forty-eight (48%) patients received treatment with Budesonide, 46% treated with loperamide, 5% with Immunomodulator or Biologics and 1% Bismuth Subsalicylates respectively. Other autoimmune disease were associated in 6% cases and 2% cases were associated with Coeliac disease. in Nineteen (19%) of cases symptoms improved immediately after stopping above associated drugs without any specific therapy.Twenty-five (25%) percent relapses 6 months after stopping of therapy. Patients present with abdominal pain, and arthralgia were significantly (p<0.001) higher risk of relapsing compared to patients with other symptoms.

Conclusion

In this large series of collagenous colitis, we found that in addition to associated drug use is not only risk, patient presents with abdominal pain and arthralgia have higher risk of relapse, after stopping of therapy of collagenous colitis . Further studies are needed to identify biomarker of this frustrating disease which has significant impact on patients of quality of life.Read more P1111 Prevalence and risk factors for active tuberculosis in Tunisian IBD patientsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

IBD patients are at risk of active tuberculosis,given the use of immunosuppressive treatments.Our country is an endemic region for tuberculosis,which may increase this risk.The aim of our study was to estimate the prevalence of active tuberculosis in IBD patients with prior screening and to investigate associated risk factors.

Methods

This was a retrospective and descriptive study,including all IBD patients admitted in the department,who had a screening for latent tuberculosis,over a 10-year period[2012-2022].Patients with less than 12 months' follow-up were excluded.

Results

We included 100 patients, 52 men and 48 women.Crohn's disease(CD)was present in 86% of cases,and ulcerative colitis in 14%.CD was predominantly ileocolic (47%).The phenotype of luminal CD was inflammatory, stenosing and fistulizing in 36.6%,28% and 35.4% of cases respectively.Anoperineal involvement was present in 41.9% of CD patients.At the time of screening, patients were on salicylates, steroids and thiopurines in 13%,27% and 22% of cases respectively.Body mass index median was 22.7kg/m².Two-thirds of patients(65%)were in a flare-up at the time of screening,with 50.8% in moderate severity, and 3.1% in severe acute colitis.Ninety patients had a negative TST.The quantiFERON test was positive in 9 patients and indeterminate in one,in four of them, the TST was also positive. There were no abnormalities on chest X-rays in all patients.Fifteen patients received chemoprophylaxis, mainly because of suspected latent tuberculosis, but also because of severe undernutrition despite a negative workup in 3 patients.Chemoprophylaxis was isoniazid monotherapy for 9 months,except for 3 patients who received isoniazid and rifampicin dual therapy for 3 months.The prevalence of active tuberculosis in our patients was 11%.The median time from onset of tuberculosis to screening was 12 months.Almost all patients were on anti-TNFα monotherapy(n=4) or combotherapy(n=6).One patient was on azathioprine only. Chest CT scans showed signs suggestive of tuberculosis in only 2 patients.Among patients who developed active tuberculosis, 2 had previously received chemoprophylaxis for a positive TST. In a univariate study,we analyzed all variables for risk factors associated with the occurrence of tuberculosis in our patients.Apart from the use of anti-TNF drugs(p=0.03),no statistically significant associations were found:severity of relapse during screening(p=0.3),undernutrition as evidenced by a low BMI(p=0.92),albuminemia(p=0.77),C reactive protein(p=0.8).

Conclusion

The median delay to onset of active tuberculosis suggests post-screening transmission.This is further evidence of the need to shorten the time required for systematic updating of the tuberculosis work-up in endemic countries.Read more P1124 Nutritional assessment and validation of GLIM Criteria in Inflammatory Bowel Disease patientsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

There is currently no validated method of assessing nutritional status in non-hospitalised patients with inflammatory bowel disease (IBD). The Global Leadership Initiative on Malnutrition (GLIM) has developed criteria for malnutrition including phenotypic criteria (low BMI, and reduced fat-free mass index (FFM)) and etiologic criteria: reduced food intake or malabsorption and chronic inflammation. In the GLIM algorithm, malnutrition is diagnosed by a combination of at least one phenotypic and at least one etiologic criterion. Gender differences in nutritional indices may be relevant, especially variables assessing weight loss, nutritional intake and digestive symptoms, where different eating habits and symptom expression are known between the sexes. The aim of the study is to validate the GLIM criteria in patients with IBD, including the gender perspective, and to assess the influence of psychosocial factors.

Methods

Multicentre, prospective, observational, analytical study in non-hospitalised IBD patients. A total of 368 patients with a 1:1 male to female ratio will be included. At the baseline visit GLIM criteria will be assessed along with other nutritional parameters, clinical and demographic characteristics of IBD. Validation of the GLIM criteria will be done with the 6 and 9 month incidence of complications associated with malnutrition (hospitalisations, emergency department visits, medical consultations, IBD complications, surgery and quality of life impairment), with specific analysis by gender and type of IBD.

Results

To date, a total of 204 IBD patients have been included (104 women; 104 with Crohn's disease [CD], 97 with ulcerative colitis [UC] and 3 with non-specific colitis); with a median age of 52 (SD 14.3) years. The prevalence of malnutrition according to GLIM criteria was 18.1% and 44.1% of patients were at risk of malnutrition, 20.1% by phenotypic criteria and 24% by etiological criteria. In the subgroup analysis, 20.2% of CD patients and 16.5% of UC patients were malnourished according to GLIM criteria. Risk of malnutrition was found in 45.1% and 39.2% in CD and UC, respectively.

Conclusion

The prevalence of undernutrition according to GLIM criteria is higher in CD than in UC.Read more P1125 Incidence and Neoplastic Risk Associated with Colonic Stricture in Pediatric-Onset Crohn's Disease: A Population-based StudyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The identification of colonic stricture in patients with Crohn's disease (CD) often leads to surgery due to concerns about associated neoplasia. Nevertheless, information regarding the neoplastic risk associated to colonic stricture is still limited. The objective of this study was to assess both the incidence of colonic stricture in pediatric-onset CD and the associated neoplastic risk at the population-based level.

Methods

All patients diagnosed with CD before age 17 between 1988 and 2011, and included in a population-based registry, were followed until 2013. Colonic stricture was defined as a narrowing of the digestive lumen observed on endoscopic or radiological examination. Excluded were stricture in the ileocaecal valve, anal canal, or low rectum. Univariate risk factors for colonic stricture were explored using Cox proportional hazards models with time-dependent variables, and a multivariable Cox model analysis was performed.

Results

A total of 1,007 patients diagnosed with CD between 1988 and 2011 were included. Median age at diagnosis was 14.5 years [IQR: 12.0-16.1]. Throughout the follow-up period (median follow-up, 8.8 years [4.6-14.2]), patients were predominantly exposed to 5-aminosalicylates (88.1%), immunosuppressants (70.6%), and biologics (47.9%). Colonic stricture was diagnosed in 52 patients, including 11 at CD diagnosis. The cumulative incidence of colonic stricture in CD was 2.9% [1.8%-4.0%] at 5 years. The overall incidence rate of colonic stricture in CD was 5.4 cases/1000 person-years, 95% CI [4.1-7.1]. In multivariable analysis, an increased risk of colonic stricture was observed during periods of active disease (HR = 2.62, [1.40-4.89], p<0.01). Conversely, the absence of colonic involvement at diagnosis (HR = 0.18, [0.04, 0.80], p<0.05) or treatment with aminosalicylates (HR = 0.39, [0.19-0.79], p<0.05) was associated with a lower risk of colonic stricture. After a median follow-up of 6.4 [2.4-12.7] years, colonic stricture surgical resection was performed in 29 patients (55.8%). Colon adenocarcinoma was detected in one patient (1.9%) within 6 months after the diagnosis of colonic stricture.

Conclusion

In this population-based study of pediatric-onset Crohn's disease, 52 patients (5%) experienced colonic stricture, with a 2.9% incidence rate observed after 5 years of follow-up. Additionally, one patient (2%) presented with an associated adenocarcinoma.Read more P1149 Risk of Clostridioides difficile infection in patients with inflammatory bowel diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Patients with inflammatory bowel disease (IBD) are at increased risk of Clostridioides difficile infection (CDI). CDI in IBD patients has been associated with poor clinical outcomes including higher morbidity and mortality. Immunosuppressant therapy has been proposed as a risk factor for CDI. However, the particular relationship between biologic therapy and CDI is controversial. We aimed to assess whether biologic therapy increased the risk of developing CDI in three cohorts of patients with immune-mediated inflammatory diseases (IBD and rheumatic diseases).

Methods

We conducted a retrospective study including three cohorts: IBD patients receiving biologic therapies (IBD-Bio), IBD patients treated with non-biologic therapies (IBD-Bio-naïve), and patients with rheumatic diseases receiving biologics (RHEUMA-Bio). Different biologic agents were considered for IBD-Bio cohort: infliximab, adalimumab, golimumab, certolizumab, ustekinumab, and vedolizumab. For RHEUMA-Bio, the biologics included were infliximab, adalimumab, golimumab, certolizumab, ustekinumab, secukinumab, etanercept, abatacept, tocilizumab, rituximab, guselkumab and ixekizumab. We estimated the incidence rate (IR) of CDI episodes between 2015 and 2021 among the three cohorts. Risk factors of CDI were assessed using logistic regression model. Furthermore, we performed subgroup analysis to identify risk factors of CDI in the IBD cohorts (IBD-Bio and IBD-Bio-naïve) and within the IBD-Bio cohort. We used R software for data analysis.

Results

Overall, we included 1868 patients, 603 in IBD-Bio, 440 in IBD-Bio-naïve, and 825 in the RHEUMA-Bio cohort. The number of CDI episodes was 3, 42, and 25 for the RHEUMA-Bio, IBD-Bio, and IBD-Bio-naïve cohorts, respectively. The IR for CDI was 1.27 100 person-years (95% confidence interval [95% CI], 0.91-1.71) for IBD-Bio, followed by 0.95 100 person-years (95% CI 0.61-1.40) for IBD-Bio-naïve and declined to 0.07 100 person-years (95% CI 0.01-0.20) for RHEUMA-Bio cohort. We identified having IBD (odds ratio [OR]:18.98, CI 95% 5.82- 61.92, p<0.001) as the major risk factor for developing CDI after adjusting for age, sex, need for biologics, and comorbidities in the three cohorts. Among IBD patients, there were no differences in CDI between biologic and naive cohorts. Within the IBD-Bio cohort, the number of biologics received (OR: 1.56, CI 95% 1.22- 2.01, P<0.001) and short disease duration (1.08, CI 95% 1.04- 1.13, P<0.001) were associated with a higher risk of CDI.

Conclusion

The major risk factor associated with CDI development was the diagnosis of IBD. Biologic therapy was not associated with a higher risk of CDI. In IBD patients on biologic therapy, the number of biologics received increased the risk of CDI.Read more P1150 The sulfur microbial diet and prognosis of individuals with Inflammatory Bowel Disease in a prospective cohort studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Intestinal sulfur-metabolizing microbes and its products like hydrogen sulfide can impact gut health and involves course of multiple gastro intestinal diseases. Recent studies demonstrated a specific diet pattern, sulfur microbial diet, can significantly influence these microbes. The sulfur microbial diet was delineated as a specific dietary pattern linked with the augmentation of sulfur-metabolizing microorganisms in humans, wherein an enhanced prevalence of these bacteria potentially escalates microbial hydrogen sulfide synthesis. This offered an opportunity to improve and modify disease course of chronic gastrointestinal diseases like inflammatory bowel disease (IBD) via the diet pattern that needed evidence. We aimed to prospectively examine the associations between sulfur microbial diet and the prognosis of individuals with IBD.

Methods

We included 1528 participants with IBD (477 Crohn’s disease [CD] and 1051 ulcerative colitis [UC]) from the UK Biobank. Sulfur microbial diet was a dietary index defined a priori based on increased abundance of 43 bacterial species involved with sulfur metabolism. We assessed adherence to this dietary pattern using validated 24-hour dietary recalls that were collected in 2009-2012 for five rounds. Two outcomes, bowel resection surgery and colorectal cancer (CRC), were obtained based on the national health databases. Cox proportional hazard models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs).

Results

After a mean (SD) follow-up of 9.9 (2.3) years, we documented 117 bowel resection surgeries events and 28 incident CRC. Compared to participants in the lowest tertile of sulfur microbial diet scores, those in the highest scores were associated with 76% higher risk of bowel resection surgeries (HR 1.76, 95% CI 1.12-2.77, P=0.014; P-trend=0.037) and 268% higher risk of CRC (HR 3,68, 95% CI 1.19-11.35, P=0.023; P-trend=0.019) in IBD (Table 1).

Conclusion

A higher sulfur microbial diet score was associated with an elevated risk of bowel resection surgery and CRC in individuals with IBD. More research is needed to explore whether this association differs across disease subtypes and locations.Read more P1166 Thiopurines and Risk of Cancer in Patients with Inflammatory Bowel Disease -A Danish Nationwide Cohort study 1996-2018Wed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Thiopurines are frequently used in patients with inflammatory bowel disease (IBD). The aim of this study was to assess the cancer risk of thiopurine monotherapy and thiopurine in combination with biologics compared to unexposed IBD patients.

Methods

Incident Danish IBD patients from 1996 to 2018 were identified in the national registers. Time at risk started at the date of IBD diagnosis and exposure status was time-dependent. Exposure was defined as registration of thiopurine and/or biologics. A lag period of 6 months was introduced at the first thiopurine registration as it was unlikely to have caused an effect on any immediate cancer case. If no new registration of thiopurines occurred 6 months from the last registration, the patient was assigned to the discontinued group. Non-melanoma skin cancer was analysed separately to avoid masking severe cancer forms and excluded from the overall cancer analyses. Cox regressions were performed to assess the risk of first cancer and risk estimates were presented as hazard ratios (HR) with 95% confidence intervals (CI). Only the incidence bar plot included non-IBD controls, matched on age, sex and municipality. Controls were unexposed to thiopurines.

Results

In total, 43,404 IBD patients were followed for a median of 8.2 years (IQR:3.7-14.2) from diagnosis. During follow-up, 7,736 Crohn’s disease (CD) (50.6%) and 6,632 ulcerative colitis (UC) patients (23.6%) were exposed to thiopurines. Cancer occurred in 1,292 (8.4%) CD and 1,840 (6.5%) UC patients. Both monotherapy and combination therapy were associated with developing any cancer (HR: 1.61 (95%CI:1.42-1.84) and (HR: 3.15 (95%CI:2.10-4.73), respectively) compared to unexposed IBD patients. In the elderly (>65 years), this was particularly apparent (Figure 1). The association between cancer and thiopurines was observed in non-melanoma skin-, melanoma-, urinary tract-, female genital organ-, lymphoid tissue-, colorectal- and digestive organ cancers. In patients who discontinued thiopurines, the HR returned to the level of unexposed HR: 1.01 (95%CI:0.91-1.13). The association with different cancer forms were higher in patients with >4 years and 1-4 years of thiopurine exposure, HR 1.58 (95%CI:1.37-1.82) and HR 1.24 (95%CI:1.07-1.44), compared to unexposed.

Conclusion

Thiopurines were associated with an increased risk of cancer in both mono- and combination therapy, especially in the elderly. This was noticeable in patients with 1-4 and >4 years of exposure, with 24% and 58% increased risk compared to unexposed. Reassuringly, discontinuation of thiopurines returned the risk to baseline and the absolute number of cancers was low. This warrants closer monitoring of all IBD patients, especially the elderly in combination therapy.Read more P1167 Inflammatory Bowel Disease: a phenome-wide pre- and post-diagnostic association studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), is known to be associated with various extra-intestinal manifestations, impacting organ systems beyond the gastrointestinal tract. Identifying comorbidities in IBD and the timing of their development can provide valuable insight into the mechanisms underlying IBD development.

Methods

We conducted the first population- and disease-wide phenomic association study in IBD, using >6 million ICD-10 coded healthcare contacts from 10 years before and up to 17 years after IBD diagnosis to investigate associations with 1583 diseases. To explore co-morbidities with potential aetiological significance with IBD, we additionally assessed the strength of association with all diseases in the pre-diagnostic compared with the post-diagnostic period. To correct for multiple testing, we adjust our significance threshold (p<0.05) with the Bonferroni correction, resulting in an adjusted p-value of 7.90×10, which we refer to as disease-wide statistical significance.

Results

We identified 312 disease-wide statistically significant associations with 125 of these diseases appearing up to 10 years before diagnosis. The risk of immune-mediated diseases and extra-intestinal manifestations are among those diseases increased up to 10 years prior to IBD diagnosis (psoriasis: CD-RR: 2.57, 95% CI: 2.00-3.29; UC-RR: 1.54, 95% CI: 1.25-1.87; enteropathic arthropathies: CD-RR: 3.57, 95% CI: 2.65-4.78; UC-RR: 1.8, 95% CI: 1.38-2.32). This was also the case for gastroenterological and liver disorders (gall stones: CD-RR: 1.82, 95% CI: 1.62-2.04; UC-RR: 1.26, 95% CI: 1.15-1.37; acute pancreatitis: CD-RR: 1.83, 95% CI: 1.30- 2.53; UC-RR: 2.27, 95% CI: 1.84-2.79). The risk of cardiometabolic diseases and neuropsychological disorders had increased disease-wide statistical significance both pre- and post-diagnostically, whereas potential sequelae of treatment, such as osteoporosis (CD-HR: 2.56, 95% CI: 2.30-2.86; UC-HR: 1.92, 95% CI: 1.79-2.07) or herpes simplex infections (CD-HR: 4.04, 95% CI: 2.76-5.91; UC-HR: 1.69, 95% CI: 1.2-2.38) were primarily seen post-diagnostically. Of potential aetiological importance to CD, diagnosis with infectious mononucleosis (RR: 1.87, 95% CI: 1.37-2.52) was significantly associated with the pre- compared to the post-diagnostic period.

Conclusion

Our results demonstrate IBD as an essentially multisystemic disease, particularly manifesting as gastrointestinal, metabolic, immune, and neuropsychological disorders, present up to 10 years prior to IBD diagnosis. Infectious diseases of aetiological interest identified warrant further investigation.Read more P1204 Oral Streptococcus mutans isolates aggravated colitis in miceWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The incidence of inflammatory bowel disease (IBD) is increasing year by year and the mechanism is unclear. A great number of studies have shown that the gut microbiota composition of IBD patients has changed and the diversity of gut microbiota decreases. The abundance of firmicutes decreases, and the abundance of Proteobacteria increases, which eventually leads to the immune disorders and intestinal inflammation. The mouth is the "gateway" of the digestive tract, which has various microbiota. The entry of extraneous microbiota from the mouth into the intestines play an important role in influencing the composition of the gut microbiota. The continuous disorder of the oral microenvironment (such as periodontitis and dental caries) are also closely related to intestinal inflammation.

Methods

A series of in vivo and in vitro experiments were conducted to investigate the effect and mechanism of S. mutans on colitis mice.

Results

S.mutans strain UA159 which is closely related to dental caries significantly aggravated colitis in DSS induced mice, as shown by body weight loss, shorter colon length, and increased inflammatory histological scores (Fig1A). UA159 up-regulated intestinal pro-inflammatory cytokines and inhibited the expression of barrier molecules in DSS mice (Fig1B). The proportion of adaptive immune cells (Th1, Th17) was up-regulated in intestinal lamina propria of UA159-administered mice (Fig1C-D).The fecal microbiota composition of UA159 mice was different from control group. The pro-inflammatory effects of UA159 on DSS mice disappeared when antibiotics were used to eliminate the intestinal microbiota. It is suggested that S.mutans may play a proinflammatory role by influencing the intestinal microbiota of mice (Fig1E).We followed 55 IBD patients for more than 1 year and found that IBD patients with poor control had a higher proportion of S.mutans in saliva (Fig1F). S.mutans strains were isolated from IBD saliva samples and were found to cluster in different branches in the phylogenetic tree (Fig1G). S.mutans isolates have different pro-inflammatory effects on colitis mice and intestinal epithelial cells (Fig1H-I). Subsequent experiments are under way to further explore the mechanism leading to the differences of the pro-inflammatory effects.

Conclusion

Our study were the first to find that oral S.mutans has aggravated intestinal inflammation. S.mutans UA159 aggravated colitis in mice through damaging intestinal mucosal barrier function, enhancing immune response and disrupting intestinal microbiota (Fig1J). The difference in pro-inflammatory effect of S.mutans derived from different IBD patients saliva may be related to the individual clinical outcome.Read more P1205 Features of the gut microbiota that associate with clinical outcomes of fecal microbiota transplantation in Ulcerative Colitis: a systematic review and meta-analysisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Evidence continues to accumulate highlighting the potential of fecal microbiota transplantation (FMT) to induce remission in patients with ulcerative colitis (UC). However, rational donor and recipient selection strategies and predictive biomarkers are needed to increase its efficacy. This systematic review provides a comprehensive evaluation of the current literature on microbial factors of FMT donors and UC recipients that relate to clinical outcomes.

Methods

The MEDLINE, Embase and Cochrane databases were systematically searched through April 2023 for relevant studies. The quality of studies and risk of bias was analyzed with Joanna Briggs tools and a compound critical appraisal-score. Additionally, species-level data from two randomized controlled trials (TURN and FOCUS) were re-analyzed from a compositional perspective.

Results

Out of 2983 citations identified, 47 met the inclusion criteria, of which 20 fulfilled quality appraisal. Higher clinical response rates were associated with higher bacterial alpha-diversity of stools of UC recipients at baseline and following FMT, and with higher FMT donor alpha-diversity. Engraftment of the donors’ microbiota was often reported but could not be clearly linked to clinical response, possibly because not every donor has an ideal microbiome. Taxa most frequently reported to be related to response included members of the Lachnospiraceae family (e.g., Eubacterium rectale, Blautia obeum) and Oscillospiraceae family (e.g., Faecalibacterium prausnitzii, Ruminococcus bromii) whereas members of the Proteobacteria and Fusobacteria phyla and Ruminococcus gnavus were reported to correlate to non-response. Low virome richness and low Caudovirales bacteriophages at baseline as well as a decrease of Candida levels following FMT, were associated with clinical response. Compositional analyses showed that a clinical response is associated with a shift away from a low diversity, Bacteroides2-enterotype-like composition towards one of high diversity either dominated by various butyrate producers, the Christensenellaceae-Methanobrevibacter trophic network or a high diversity composition with abundant but not excessive levels of Prevotella copri.

Conclusion

In this systematic review we found distinctive features of microbial profiles of both donors and UC recipients to relate to clinical response to FMT. The predictive value of microbial markers should be further explored in future clinical studies to move towards a personalized FMT approach and delineate ‘super-donor’ profiles.Read more N01 “Just Live with it”- Exploring patients’ experience of using IBD-F scale in clinical practice – A mixed methods study using focus groups and cross-sectional questionnairesWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Inflammatory bowel disease (IBD) related fatigue is one of the most common, yet debilitating symptoms reported by patients with IBD. The causes for the issue are not fully understood, and patients and clinicians alike struggle to communicate about this topic in consultations. In 2014, the IBD-F scale was created to assist this communication, and this study aimed to explore its role in the experiences of patients assessing and managing their IBD fatigue with Health Care Professionals (HCP’s).

Methods

A mixed methods study was conducted consisting of an online survey and 3 online patient focus groups. The survey was advertised through patient charities and explored individual fatigue assessment and management. 24 patients from across the UK were recruited to participate in the online focus groups, providing 243 minutes of discussion. This data was recorded, transcribed, and anonymised before being coded by two independent researchers.

Results

The online survey received 426 responses. 272 (64%) respondents reported fatigue levels between 7-10 on a scale of 0-10. When the medical assessment of their fatigue was explored, only 41(10%) respondents reported a medical assessment of the fatigue, 27 (6%) reported being offered support or advice, and 5 (1%) reported that the fatigue had been reassessed. 162 (38%) respondents said they would use the IBD-F on a regular basis and wanted this information to be shared with their medical teams, and 136 (32%) requested the results be attached to their clinical record.The topics arising from the patient focus groups support the notion that fatigue is both overwhelming, and underserved. The main findings are collated into three main themes or “desires”, constructed to represent the patient’s call to HCP's; 1) The desire to “Give up”, 2) The desire to be heard, 3) The desire to change their situation. All groups reported a desire to improve clinical and public education around IBD fatigue and introduce communication tools like the IBD-F into clinical consultations and medical notes.

Conclusion

This mixed methods exploration highlights a significant, perceived gap in clinical provision for patients experiencing IBD related fatigue. IBD patients are reporting a sense of alienation and abandonment from HCP’s, but also a resounding desire to utilise their voices to educate their medical teams and a willingness to take advantage of additional resources to help improve education, communication and treatment of this symptom. Further research is needed to explore this phenomenon from the HCP’s perspective, and to explore the practical implications of the suggested changes to IBD fatigue education, assessment, and management within these clinical settings.Figure 1:Read more P1093 Early life exposure to agriculture and biodiversity influences Crohn’s disease risk in a population-based cohort studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Specific pollutants and environmental exposures are implicated in modulating inflammatory bowel disease (IBD) risk. Crohn’s disease (CD) clustering has been reported in agricultural areas. However, the role of environmental exposures, particularly in early life, towards IBD risk, has not been systematically evaluated.

Methods

We conducted a nationwide population-based cohort study during the study period extending from January 1, 1995, to September 1, 2020, using cross-linked Danish registers, maps, and inventories to ascertain the impact of agricultural land use, biodiversity, green space, urban space, blue space, and natural vegetation density index during pregnancy and the first two years of life on IBD, CD, and ulcerative colitis (UC) risk, using adjusted Cox proportional hazards regression analyses. We adjusted for the following covariates: sex, maternal age at delivery, calendar year of birth, municipal-level socioeconomic status, and first-degree relative with IBD.

Results

Of 1,438,487 individuals included in the study who were followed from age 2 years until a median (IQR) age of 14 (8-20) years, 3,768 individuals were diagnosed with IBD. Exposure to the highest and third quartiles of agriculture land use during early life, relative to the lowest quartile, were associated with increased IBD risk (aHR 1.16, 95% CI 1.02, 1.31 and 1.19, 95% CI 1.07, 1.32, respectively). Conversely, exposure to the highest and third quartiles of biodiversity in early life, compared to the lowest quartile, were associated with a lower IBD risk (aHR 0.90, 95% CI 0.82, 1.00 and 0.90, 95% CI 0.82, 0.99, respectively). These associations were driven by differences in CD risk (Figure), but there was no association with UC risk. Other environmental exposures were not associated with IBD risk.

Conclusion

In a nationwide cohort with long-term follow up data, early life exposure to agriculture land use was associated with an increase in CD risk, while higher biodiversity was protective.Read more P1105 Short-term exposure to environmental air pollution and inflammatory bowel disease flares: a time-stratified case cross-over studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Some epidemiological studies suggest that long-term exposure to environmental air pollutants, such as particulate matter (PM), could have a role in inflammatory bowel disease (IBD) incidence and pathogenesis. However, less is known about the potential effect of short-term air pollution exposure. The aim of this study is to investigate whether short-term exposure to environmental air pollution is associated with the occurrence of IBD flares.

Methods

Anonymized hospital discharge records (HDR) with ICD-9-CM codes 555 (Crohn’s disease) and 556 (ulcerative colitis) for years 2002-2009 from all hospitals of the Lombardy region were collected. All HDR of adult patients (18-75 years) resident in Milan were included, except for recurrent hospitalizations within 6 months. Each record was assigned daily PM ≤10 µm (PM10) concentrations at municipality level by averaging PM10 levels of the day of admission with the levels of the day before (lag01) and of each preceding day up to six days before (lag06). To evaluate the association between PM10 and IBD-related hospitalizations, a time-stratified case-crossover study design was applied. Conditional logistic regression models, calculating Odds Ratios (OR) and 95% Confidence Intervals (95%CI) per increments of 10 µg/m3 of PM10, were performed.

Results

Overall, 2,176 hospital admissions (males=1,137, Crohn’s disease=1,264, ulcerative colitis=912) were included. In the entire population no clear association between PM10 and IBD-related hospitalization was identified, notwithstanding a small risk increase for males (OR: 1.03; 95%CI: 0.99-1.08 at lag04). When further stratifying for ICD code, an increased risk of hospitalization for "left-sided ulcerative colitis" (ICD code: 556.5) was found in males only, for exposures in all days preceding hospitalization up to lag04 (1.28; 1.05-1.28; 59 cases, 207 controls) (Figure 1). In females, the association was weaker, although positive (1.14; 0.91-1.42; 49 cases, 164 controls). No relevant findings emerged when looking at other ICD codes.

Conclusion

We observed an increased risk of IBD-related hospitalization in male patients with left-sided ulcerative colitis per increasing levels of air pollution in the days preceding hospital admission. Although preliminary, our findings suggest the possible role of sex as an effect modifier of the influence that air pollution might exert on IBD flares. Further studies are needed to better comprehend the complex framework characterizing the interplay between environmental and individual factors contributing to IBD.Figure 1.Association between IBD-related hospitalization and PM10 levelsRead more P1106 Is indoor radon associated with new diagnosis of inflammatory bowel disease patients?Wed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Inflammatory Bowel Diseases (IBD) are a group of pathologies of unknown etiology associated with some environmental factors, only partially identified. The role of indoor radon, a radioactive gas, has not been formally studied and it might play a role on the onset of the disease. The aim of this study is to analyze the role of individual residential radon exposure on the incidence of IBD in a radon-prone area also characterized as a high incidence IBD region.

Methods

A case-control study was developed in the health area of Santiago de Compostela (Galicia, Spain) between June 2020 and September 2023, including incident cases with IBD. Controls were selected trough a frequency matching based on sex and age and without IBD. All participants had to be living at least 5 years in the same dwelling, those with a change of address in the last 5 years prior to diagnosis were excluded. Endoscopic index, imaging techniques and analytic parameters were collected. Radon levels measured over three months in the participants’ home were compared between cases and controls, and between the different types of IBD. Each individual was provided with a residential radon meter (a RSKS trace detector), given and read by the Galician Radon Laboratory, a certified radon laboratory. Procedure is summarized in Figure 1. Radon concentrations were categorized into three groups, 0-99 Bq/m³, 100-299 Bq/m³ and >299 Bq/m³. Results are expressed as Odds Ratios with their 95%CI obtained through logistic regression.

Results

178 incident cases and 178 controls (102 ulcerative colitis, 70 Crohn’s disease and 6 unclassified colitis) were included, with a median age of 51 years old (IQR 40 – 59.5). 51.7% were females. Median radon levels of IBD patients´ homes were 144.5 (IQR 83 – 260) and median radon levels of controls´ homes were 189.5 (IQR 112 – 292.5) (figure 1). Adjusting by age and sex, high radon levels showed a negative association for the development of IBD (taking levels of 0-99 Bq/m³ as reference, OR 100-299 Bq/m³ is 0.5 (95%CI 0.3-0.8), and OR >299 Bq/m³ is 0.5 (95%CI 0.3-0.9). Results are shown in table 1. Analyzing women and men separately, there are no statistically significant differences (p>0.05 in each group). Taking into account the different types of IBD, radon levels show the same negative association but without statistical association.

Conclusion

High radon levels might be a protective factor for developing IBD overall and its most common types, Crohn’s disease and ulcerative colitis. Further studies in other areas with lower radon concentrations will be necessary to corroborate whether it influences the incidence of IBD.Read more P1132 Fecal incontinence in Inflammatory Bowel Disease (IBD): associated factors and impact on the quality of life of patients in an IBD clinic in SwitzerlandWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Literature on prevalence of fecal incontinence (FI) in inflammatory bowel disease (IBD) and associated factors has not been thoroughly studied. IBD is a chronic disease with high morbidity and significant impact on quality of life. Awareness of prevalence and associated factors of FI would make gastroenterologists more conscious of its burden, leading to targeted clinical assessment and treatment.

Methods

We conducted a cross-sectional study, looking at risk factors for FI and its impact on quality of life. The study population consisted of IBD patients aged from 16 to 80 years old in an IBD clinic in Switzerland. Patients with a stoma, a J-Pouch and an unspecified IBD were excluded. The survey had 53 questions, with demographics and main clinical variables. The quality of life of patients was assessed using the World Health Organization quality of life scale. Disease severity was measured based on the short Crohn’s disease activity index (SCDAI) for Crohn’s disease (CD) and using the simple clinical colitis activity index (SCCAI) for Ulcerative colitis (UC). Logistic regression was used to calculate crude and adjusted odds ratio (OR), applying 95% confidence intervals (CI).

Results

450 questionnaires were randomly distributed. 392 patients met the inclusion criteria. 116 patients (29.5%) reported FI. Factors associated with FI included: age > 50 years old [OR 2.74 (CI: 1.57-3.89)]; one or more vaginal delivery [OR 2.49 (CI: 1.32-4.71)];disease duration > 15 years [OR 2.04 (CI: 1.31-3.16)], abdominal pain [OR 2.56 (CI: 1.60-4.09)], diarrhea [OR 3.70 (CI: 2.26-6.04)], blood in stool [OR 3.33 (1.88-5.89)], more than 3 bowel movements/day [OR 4.50 (CI: 2.79-7.26)],night bowel movements [OR 3.98 (CI: 2.36-6.71)] and an SCCAI ≥ 3 [OR 6.06 (CI: 2.62-14.02)]. There was also a positive association between the presence of one or more extraintestinal manifestation (EIM) [OR 1.64 (CI: 1.03-2.61)] and FI. General well-being [OR 2.61 (CI: 1.65-4.14)] was inversely associated with FI. Similarly, depression and anxiety were associated with FI, respectively; [OR 2.43 (CI: 1.27-4.68) and OR 1.88 (CI: 1.07-3.30)]. Noticeably, 35.3% of patients with FI could not hold their stools for more than 5 minutes, and 14.7% were unable to hold their stools for more than a minute.

Conclusion

FI was highly prevalent (29.5%) in our survey. Age, vaginal delivery, disease duration >15 years, abdominal pain, diarrhea, blood in stool, >3 bowel movements /day, night bowel movement, SCCAI ≥ 3, ≥ 1 EIM were associated with FI. The quality of life was significantly impacted, and anxiety and depression were associated with FI. These implications highlight the need for interventions aimed at enhancing physical and mental health outcomes among individuals with IBD.Read more P1133 Relative survival and cause-specific mortality of a Chilean Inflammatory Bowel Disease cohortWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

In the past two decades, multiple studies have shown an improvement in outcomes of inflammatory bowel disease (IBD) patients including a decreasing mortality associated with new treatments, surveillance, and healthcare support. There are no large studies in Latin-American countries addressing survival and death causes in IBD patients. We aimed to assess relative survival (RS) and causes of death in Chilean IBD patients.

Methods

IBD patients treated in a tertiary reference centre (Pontificia Universidad Católica of Chile, Santiago, Chile) since January 1990 were included in a local database. Death certificates were analysed to obtain the date and specific cause of death. The recorded time started on the date of definitive diagnosis and lasted until death or censoring on December 31^st, 2020. The survival of IBD patients was compared with the life expectancy of the Chilean general population based on official life tables collected in the Human Mortality Database (www.mortality.org). The RS was computed using the Ederer II method implemented in the RELSURV package of the R software. A RS greater than 1.0 indicates that the analysed cohort has a higher survival than the expected survival of the reference population for the same age, sex and date at which age was coded. Inclusion of 1.0 within 95% CI indicates no difference between observed and expected survival. Data were also expressed graphically as the observed cumulative survival curves over time and the 95% confidence interval (CI) and compared to the reference population.

Results

We included 1,289 IBD patients with a media age at diagnosis of 35.9±14 years, 40.9% males and a follow-up of 22,525 patients-year. Ulcerative Colitis, Crohn’s disease and IBD unclassified patients comprised 50.2%, 43.1% and 6.7% of the cohort, respectively. A total of 106 patients (8.9%) died during the study period. Compared with the general population, the survival of IBD patients was higher (RS = 1.04; 95% CI: 1.02-1.07) at 20 years of follow-up (Table and Figure). This higher RS in IBD patients was observed in males and females, as well as CD patients and IBD patients older than 40-year-old (Table). The main causes of death in IBD patients were cancer (34%), infections (27.7%) and cardiovascular diseases (21.3%).

Conclusion

Compared to the general population, a higher long-term survival was observed in this large cohort of Chilean IBD patients. These findings may be due to a closer surveillance of this group of patients. Causes of death mirrored those in previously reported cohorts; therefore, a special care should be pay on their prevention in Latin-American countries as well.Read more P1146 Familial Coaggregation of Inflammatory Bowel Disease with Cardiovascular Disease: a Nationwide Multigenerational Cohort StudyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Genetics contribute to the development of both inflammatory bowel disease (IBD) and cardiovascular disease (CVD). Although an increased risk of CVD has been documented in IBD patients, little is known about the risk of CVD in family members of patients with IBD.

Methods

In this Swedish nationwide multigenerational cohort, we identified patients with biopsy-confirmed IBD (≥18 years) who had at least one family member living in Sweden at their date of diagnosis from 1969 through 2017. Each patient was matched with up to five IBD-free reference individuals from the general population. We then identified 205,642 first-degree relatives (FDRs: father, mother, full-siblings, offspring) and 44,790 spouses of IBD patients as well as 1,015,010 FDRs and 222,969 spouses of their reference individuals. These family members were followed from the later date of turning 18 years or their linked IBD patients/reference individuals being diagnosed/matched (i.e., index date), until the interested CVD outcome, heart transplant, emigration, death, or 31/12/2020, whichever came first. The primary outcome was any incident CVD and CVD mortality. Secondary outcomes included incident ischemic heart disease, heart failure, cerebrovascular disease, deep vein thromboembolism, pulmonary embolism, and atrial fibrillation/flutter. Flexible parametric survival models estimated the adjusted hazard ratio (aHR) with 95% confidence interval (CI).

Results

FDRs of IBD patients were at higher risks of incident CVD (aHR=1.04, 95%CI: 1.03 to 1.05) and CVD mortality (aHR=1.03 [1.00 to 1.06]) than FDRs of reference individuals (Figure 1). The increased risks were significant for almost all secondary outcomes, with point estimates hovering around a two to eight percent increased risk. Similar patterns were observed by IBD subtypes, sex, age and calendar period at index date, and family relationship of FDRs. In contrast, spouses demonstrated no increased risks of incident CVD or CVD mortality.

Conclusion

Relative risks of incident CVD and CVD mortality were only slightly increased in FDRs of patients with IBD, but not at all in spouses, suggesting no need for extra vigilance for CVD among family members of IBD patients.Read more P1147 Symptoms of irritable bowel syndrome are common in patients in remission from Inflammatory Bowel Disease: Results from an observational population-based cohort study in NorwayWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The present study aimed to estimate the prevalence of irritable bowel syndrome [IBS] symptoms and associated variables in a prospective cohort of patients with inflammatory bowel disease [IBD] in remission one year after diagnosis.

Methods

Adult patients [≥18 years old] with ulcerative colitis [UC] and Crohn’s disease [CD] were recruited from the Inflammatory Bowel Disease in South-Eastern Norway [IBSEN] III study, a population-based inception cohort. The prevalence of IBS-like symptoms was assessed using the Rome IV criteria for patients in remission one year after their IBD diagnosis was made. Three different definitions of remission were applied to evaluate IBS prevalence. Remission was defined as either endoscopic [Mayo endoscopic score 0 for UC, no visible ileal or colonic inflammation for CD] or biochemical [calprotectin ≤150 µg/g or ≤250 µg/g]. Results were compared to IBS prevalence in the general Norwegian population, as represented by data from the Trøndelag Health Study [HUNT4 study] ¹. Demographic, psychosocial and disease-related factors associated with IBS-like symptoms were evaluated with uni- and multivariate logistic regression. Substantial fatigue was defined as a score of ≥4 on the Fatigue Questionnaire [FQ].

Results

Of 1320 patients with UC or CD who met for one-year follow-up, 635 patients completed the Rome IV questionnaire [response rate 48.1%; 52.1% female; mean age 44 years]. For 151 patients in endoscopic remission, 16.6% [95% CI: 11.0-23.5] reported IBS-like symptoms compared to 19.7% [95% CI: 14.9-25.2] of 244 patients with calprotectin ≤ 150 µg/g, and 21.8% [95% CI: 17.2-27.1] of 284 patients with calprotectin ≤ 250 µg/g. All three definitions of remission resulted in significantly higher prevalence of IBS-like symptoms compared to the Norwegian population [HUNT4 study; 9.5%; 95% CI: 9.2-9.8; p<0.005]. In multivariate analysis, IBS-like symptoms were independently associated with substantial fatigue [odds ratio (OR) 3.05, 95% CI: 1.48-6.27, p=0.002] and female sex [OR 2.67, 95% CI: 1.34-5.32, p =0.005].

Conclusion

Patients in IBD-remission one year after diagnosis reported a prevalence of IBS-like symptoms between 17% and 22%, depending on the definition of remission. This prevalence was significantly higher than that reported in the general Norwegian population. IBS-like symptoms were independently associated with substantial fatigue and female sex.Reference1. Johansen SG, Ness-Jensen E. The changes in prevalence and risk of irritable bowel syndrome over time in a population-based cohort, the HUNT study, Norway. Scand J Gastroenterol 2022:1-7.Read more P1170 Long-term outcomes of newly diagnosed Inflammatory Bowel Disease (IBD) patients: results from the nationwide EpidemIBD study of GETECCUWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Aims: 1) To describe the main epidemiological and clinical characteristics of patients at IBD diagnosis and the long-term outcomes; 2) to analyse the use of drugs for IBD, and the need of hospitalisations and surgeries; 3) to compare IBD management based on the type of disease and the resources of the hospitals.

Methods

Prospective, population-based nationwide registry. Adult patients diagnosed with IBD, Crohn’s Disease (CD), Ulcerative Colitis (UC) or IBD unclassified, during 2017 in the 17 Spanish regions were included. Patients who consented were followed-up for 5 years (yr) after diagnosis. Treatment was grouped into 5 categories: mesalamine (oral or topical), steroids (intravenous, oral, or topical), immunomodulators (thiopurines, methotrexate or cyclosporine), biologics (anti-TNF, vedolizumab, ustekinumab) or JAK inhibitors (JAKi), and surgery. Hospitals were classified into high resources and low resources ones. Cumulative incidence of exposure to each of the studied treatments was estimated by Kaplan-Meier curves; curves were compared with log-rank test.

Results

3,301 incident cases of IBD diagnosed during 2017 in 108 hospitals, covering over 22 million inhabitants in Spain (about 50% of the population), were enrolled into the follow-up study. Main characteristics of the cohort are summarised in table 1. Median diagnosis delayed was 3.5 months (5.6 in CD and 2.7 in UC, p<0.001). During the 5-yr follow-up, 25% of UC patients progressed to more extensive involvement, while 8% of CD patients with inflammatory behaviour progressed to either stricturing or fistulising behaviour. Most of the patients who received mesalamine, corticosteroids, or immunomodulators initiated treatment within the first 2 years after diagnosis (figure 1). However, the cumulative incidence of biologics/JAKi usage steadily increased over time, reaching 49% by the 5-yr timepoint in CD. In terms of surgeries, a progressive increase in cumulative incidence was observed in CD; the incidence of colectomy remained stable in UC from the 2^nd year post-diagnosis. A higher cumulative incidence of biologics/JAKi usage, hospitalisations, and surgeries was observed in CD at high resources hospitals; no differences were observed in the use of other therapeutic resources or the management of UC.

Conclusion

In the EpidemIBD large-scale epidemiological study, we have observed that the delay in diagnosing IBD is shorter than previously described. Approximately 50% of patients with CD and 20% of patients with UC ended up receiving biologics/JAKi in the first 5 yrs following diagnosis. The percentage of patients undergoing surgery was lower than previously reported; in the case of UC, the majority of colectomies occurred within the first 2 yrs after diagnosis.Read more P1171 The impact of biological and small molecule therapy on time to colonic resection and cancer rates in patients with Ulcerative ColitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The expanding medical armamentarium in ulcerative colitis (UC) has contributed to increased control of inflammation. However, simultaneously, postponed colonic resection with an accumulative inflammatory burden might lead to an increased risk of CRC. Recent studies have reported conflicting results regarding the incidence of colorectal cancer (CRC) in UC patients.

Aim

To analyse the impact of advanced medical therapies (defined as biologicals and small molecules) on time to colonic resection and risk of CRC in UC patients.

Methods

Consecutive patients ≥18 years with established UC who underwent colonic resection between January 2003 and October 2022 at the Academic Medical Centre Amsterdam or the University Hospital Leuven were included. Primary outcomes were time to colonic resection and CRC rate in colonic specimens, compared between four time periods: P1 (2003-2007), P2 (2008-2012), P3 (2013-2017) and P4 (2018-2022). Secondary outcomes were the effect of advanced medical therapy on time to resection, cancer stage and risk of CRC. CRC was staged according to the AJCC TNM classification (advanced cancer defined as T3/T4, N1/2 or M1).

Results

A total of 716 patients were included. The usage of advanced medical therapies prior to surgery increased from 38.2% in P1 to 90.2% in P4 (p<0.001). However, this did not result in an increased time to colonic resection (P1: 7 years (2-12) vs P2: 6 years (2-14) vs P3: 7 years (3-14) vs P4: 7 years (2-14), p=0.94). CRC was diagnosed in 72 (10.1%) patients, and this incidence did also not change over time. Time to resection was significantly longer (median 18 years, IQR 10-24) in CRC patients compared to the overall cohort. The majority of CRC patients (64.8%) were diagnosed with advanced cancer, which did not decrease over time. Patients using advanced medical therapies had significantly shorter follow-up compared to therapy-naïve patients (6 years vs. 10 years, p<0.001), which resulted in a decreased risk of CRC (OR 0.17, p=<0.001). However, the finding of an incidental carcinoma rate (i.e. not preoperatively diagnosed) in this group was 18% whereas this was only 4% in patients without advanced medical therapy (p=0.08). Moreover, the incidence of advanced CRC was numerically higher in UC patients who received ≥2 therapies (83.3% vs 61.0%, p=0.14).

Conclusion

This study demonstrated that in the last two decades, the increased usage of advanced medical therapies did not result in an increased time to resection, nor in a decreased CRC rate in UC patients undergoing colonic resection. A higher incidence of incidental and advanced cancers was seen in patients with ≥2 therapies. Therefore, care should be taken with improved tailored surveillance in this group.Read more P1172 Epidemiology and initial presentation of newly diagnosed inflammatory bowel diseases in a Danish population-based inception cohort – results from the IBD Prognosis StudyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

It is unclear whether the incidence of inflammatory bowel diseases (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), continues to increase. In this study, we aimed to investigate the occurrence and initial disease presentation of IBD in a population-based setting. In addition, we aimed to identify predictors of an early severe disease presentation.

Methods

The study was conducted as part of IBD Prognosis Study, an ongoing Danish prospective population-based inception cohort study that includes incident patients with IBD according to the Copenhagen Diagnostic Criteria since May 2021, covering the catchment areas of approximately 20% of the Danish population (1.1 million). In this analysis, cutoff for data analysis was in May 2023. Crude incidence rates and European Standard Population (ESP)-adjusted rates were calculated. A multivariable logistical regression model was constructed to identify predictors of a severe disease presentation, defined as the composite need for systemic steroids, immunomodulators, biologics, or IBD-related surgery within three months of disease.

Results

In total, 554 patients (UC: 344, CD: 210) fulfilled the inclusion criteria, resulting in the following crude incidence rates per 100,000 person-years: IBD 23.4 (95% CI 21.5-25.4), UC 14.0 (12.6-15.6), and CD 8.6 (7.4-9.8). ESP-adjusted rates were: IBD 20.4 (18.2-22.9), UC 11.8 (10.2-13.0), and CD 7.9 (6.5-9.9) (Figure 1).Among patients with UC, 81 (26.3%) and 95 (30.8%) had left-sided or extensive colitis at disease onset, respectively, while 61 (30.3%) and 62 (30.8%) patients with CD had ileal or ileocolonic disease. Stricturing or penetrating CD behaviour was observed in 24 (11.9%) and 11 (5.5%) patients, respectively. A high proportion of patients needed hospitalization (CD: 68 (33.8%), UC: 60 (19.5%), p=0.001) and IBD-related surgery (CD: 21 (10.4%), UC: 10 (3.2%), p=0.004) at the time of diagnosis.In multivariable analysis, a severe disease presentation of UC at the time of diagnosis was associated with left-sided or extensive disease distribution, thrombocytosis, and increased levels of C-reactive protein (CRP) (Table 1). In patients with CD, stricturing, or perianal disease, as well as anemia, levels of albumin, CRP, and calprotectin were predictive of this endpoint (Table 1).

Conclusion

The incidence of UC and CD in Denmark appears stable compared to historical data from the previous decades.1 The study identified clinical predictors of a severe disease presentation from the time of diagnosis, emphasizing the critical need for early risk stratification and intervention strategies.Reference:1 Dorn-Rasmussen M et al., J Crohns Colitis. doi: 10.1093/ecco-jcc/jjac138.Read more P1234 The gut microbiome as a reporter of health, and its associations with different exposuresWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The prevalence of metabolic and immune-mediated diseases has increased in the last century, with many of these diseases showing alterations in the gut microbial composition. We previously reported (PMID:35197084) that a large group of bacteria shows constant differential abundance (increase and decrease) across multiple diseases and can therefore provide a general indication of the host's health. We aimed to utilize a “health index” based on these bacteria to compare how different exposures are associated with this index as potential contributors to general health.

Methods

The gut microbial composition was derived using fecal 16S sequencing (V4), and the per-participant microbial health index was calculated. Exposures, diseases, and laboratory results were recorded at sample collection.

Results

372 participants (62% males, median age 57y, Table 1) were included (the study is ongoing). Median BMI was 25 (IQR 23-28), with 9% smokers. Participants are relatively fit: only 22% reported performing physical activity less than once weekly, and the median average steps (for the 55% that reported their daily average) is 6000 steps/day (IQR 4500-8000). Subjects performing more frequent physical activity (>3 times/week) had a higher gut microbial health index (p=0.009) in comparison to less than once weekly. Subjects having no documented disease (22%) had higher indexes, and the number of diseases negatively correlated with the health index (rho=-0.19, p=0.004). A higher microbial health index (Figure 1) was found in subjects drinking >=4 coffee cups/day vs. less or no coffee (p=0.002). Interestingly, a higher percentage of eosinophils was positively correlated with a higher index (p=0.002). Lower health index was recorded in subjects who reported dietary supplements intake (p=0.01), those with above-normal levels of uric acid (p=0.02), with primary hypertension or fatty liver (p=0.02), and those taking beta-blockers (p=0.009) or glucose-lowering medications (p=0.003). The microbial health index positively correlated with Faith alpha diversity (rho=0.47). Still, in some cases, each factor was linked with different features suggesting that these microbial-based factors (diversity and health index) captured a complementary epiphenomenon of the microbiome. For example, only higher alpha diversity (but not health index) was linked with the daily bowel movement frequency (p=0.0008).

Conclusion

Using the gut microbial health index, we developed a methodology to assess correlations between different lifestyles, diets, and health. This approach may highlight personal modifiable factors that can be translated into risk prevention strategies for improving general health reported by microbial composition.Read more P1236 Oral microbiota dysbiosis in Inflammatory Bowel Disease patientsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Recent data pointed that IBD is strictly related to gut microbiota although less is known about the connection between oral microbiota and IBD. It is also known that dysbiosis can lead to oral pathologies. Moreover, microbiome changes under therapeutic agents’ administration for IBD treatment have been described, including the identification of some bacteria as potential predictive markers for treatment effectiveness. The aim of our study was the quantification of salivary Firmicutes and Bacteroidetes in a cohort of IBD patients compared with a control group without IBD.

Methods

This was a collaborative transversal cohort study between an IBD consultation in a tertiary hospital and a faculty of dental medicine. Patients from IBD consultation were invited to participate and gave their informed consent. The exclusion criteria were the incapacity of mouth opening or give a written informed consent. Demographic and clinical data was collected. Oral health status was accessed to determine the periodontal diagnosis. Unstimulated saliva samples were collected before the oral examination for the quantification by quantitative real-time PCR. Statistical analysis was performed with SPSS 29.0 using Kruskal–Wallis H and Mann-Whitney U tests, and p values ≤ 0.05 were considered statistically significant.

Results

IBD patients presented an increased abundance of Firmicutes, both for UC (3.4 x10^-5) and CD (4.9x10^-5) as well as an increased abundance of Bacteroidetes for both UC (1.6 x10^-5) and CD (1.4x10^-5), when compared to the control group (figure 1).No significant differences were found between different treatments groups or no treatment (table 1) in abundance of Firmicutes and Bacteroidetes, respectively, of UC (p = 0.292 and p = 0.912) and CD (p=0.413 and p=0.254) patients. Additionally, no significant differences were found for Firmicutes and Bacteroidetes abundances, respectively, regarding: CD versus UC (p=0.600 and p=0.971), active disease and remission (based on a composite criterion for inactive disease considering HBI <5 for CD or a PMS ≤ 2 for UC, and FCP cut-off value of 150 mg/Kg), (p= 0.071 and p=0.242), smoking status (p=0.558 and p=0.488) and presence or absence of oral health (p=0.260 and p=0.556).

Conclusion

The oral microbiota characterization of IBD patients showed an elevated abundance of Firmicutes and Bacteroidetes when compared with healthy controls. These findings are valuable indicators of dysbiosis, emphasizing the intricate interplay between gut and oral microbiome in the context of inflammatory conditions. Future research is needed to clarify the oral-gut microbiome axis in IBD.Read more P1237 Development of an algorithm to identify the best donor-recipient match for FMT in IBD patients based on immune system/microbiota interactionsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

IBD are characterized by uncontrolled immune responses, in genetically predisposed individuals, to the dysbiotic microbiota. Its modulation has thus emerged as a potential therapeutic strategy . Fecal microbiota transplantation (FMT) showed encouraging results for the treatment of mild-to-moderate ulcerative colitis (UC) patients. However, currently the success rate of FMT in UC patients is around 30%, and there are no criteria to predict it.We hypothesized that the immune system-microbiota interaction can dictate which graft will be accepted or rejected. Thus, we generated an algorithm to identify the best donor-recipient match for FMT treatment in IBD patients based on the functional interaction of recipient's immune system with possible donors' microbiota .

Methods

Mucosal and circulating immune cells isolated from 16 active UC patients, potentially eligible for FMT, were exposed to the microbiota of a panel of 8 potential healthy FM donors collected in the FM biobank of the Policlinico Hospital, Milan. The functional profile of recipients' immune cells before and after the in vitro exposure to the possible donors’ microbiota was assessed by cytokine production, gene expression profiling and activatory or inhibitory surface molecules modulation on T cells. Sequencing of the microbiota of each individual FM donor was performed by 16S. These functional data were used to develop an algorithm to identify the best donor-recipient match based on the capability of individual donors’ microbial ecologies to simultaneously reduce the inflammatory functional profile and increase the tolerogenic functional profile of the recipient's immune cells

Results

We demonstrated that mucosal immune cells from UC recipients exhibited a variety of responses upon exposure to the microbiota from distinct healthy donors, which clusters in two different enterotypes. Each UC recipient exhibited specific preferences for one or more FM donor in the reduction of the inflammatory profile of immune cells and concomitantly enhancement of anti-inflammatory cytokines. On te basis of these data we generated an algorithm capable of predicting the most successful functional interaction between donors and recipients.

Conclusion

Our study suggest that specific functional characteristics of both the donor microbiota and the recipient's immune system should be considered when selecting an optimal donor-recipient match for FMT. This study contributes to the development of a screening tool for donor selection in FMT, enabling personalized and effective therapeutic interventions for UC patientsRead more P1238 Exploring the Role of Klebsiella variicola and Klebsiella pneumoniae in Pediatric Ulcerative Colitis PathogenesisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Recent studies indicated that Klebsiella (K) pneumoniae (isolated from the stool of IBD patients) and K. variicola (isolated from the mesenteric tissue of Crohn disease patients) have the potential to induce inflammation in epithelial and preadipocyte cells, exacerbating colitis in murine models. We isolated these strains from pediatric ulcerative colitis (UC) patients' appendix (relevant to UC pathogenesis given the protective effects of appendectomy) and other non-inflamed colon sections. We hypothesized that these isolates are invasive and induce inflammation in UC. These strains have not been previously studied in UC.

Methods

K. variicola and K. pneumoniae were isolated from two pediatric UC patients' appendices and other non-inflamed colon sections and identified using 16S DNA Sanger sequencing. Virulence of the two strains was determined by infecting Caco2 cell lines and performing adhesion and invasion assays, quantifying biofilm formation, and assessing barrier functions using transepithelial electrical resistance (TEER) measurement. Importantly, we monitored the production of pro-inflammatory (e.g., IL-8, TNF-α) and anti-inflammatory (IL-10) cytokines using reverse transcriptase quantitative polymerase chain reaction (RT-qPCR).

Results

K. variicola and K. pneumoniae exhibited high levels of biofilm formation compared to adherent-invasive Escherichia coli (AIEC), which are commonly isolated from IBD patients. Furthermore, the Klebsiella strains adhered to epithelial cells within 2-3 hours post infection. TEER experiments showed compromised barrier integrity after 6 hours and overnight infection. Except for K. pneumoniae isolated from the ascending colon, the tested strains exhibited a significant increase in IL-8 expression. Similarly, K. variicola from the peri-appendicular region demonstrated elevated TNF-α gene expression.

Conclusion

K. variicola and K. pneumoniae isolated from UC patients have the potential to form biofilms, disrupt barrier integrity, and trigger inflammatory responses. These findings unravel a potential role for pathogenic Klebsiella strains in driving UC pathogenesis. Importantly, these data shed light on the role of appendix-associated bacteria in the development of UC. Future work includes using comparative genomics to map the virulence determinants of these bacteria.Read more N41 Individual with Crohn's Disease Nursing Care According to Neuman Systems ModelWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Individualized care is important in managing chronic diseases such as Crohn's. Nursing models provide integrated nursing care specific to the individual. Neuman Systems Model is a holistic approach and multi-dimensional model that aims to provide a unifying focus for understanding people and their environment, making an organized approach to different nursing problems, and includes all physiological, psychological, sociocultural, spiritual and developmental variables that affect the individual. In this case, nursing care given by an IBD (inflammatory bowel diseases) nurse according to the Neuman Systems Model will be discussed.

Methods

Data were collected by the researcher using the 6-item questionnaire of the Neuman Systems Model by face-to-face interview at the inflammatory bowel diseases outpatient clinic, with written consent from a 20-year-old female patient. Differences in perception of the nurse and the patient were identified. The patient's withdrawal from sports and education due to Crohn's disease is defined as personal stressor, the weakening of social relationships is defined as interpersonal stressor, and the Covid-19 pandemic is defined as impersonal stressor. With the data collected, nursing care was planned for the nursing diagnoses of social isolation, impaired body perception and fatigue. As a result of the applied nursing interventions, it was observed that there was an improvement in the patient's social life, body perception and fatigue level.

Results

This case shows the effect of using the Neuman system model in nursing care given to a Crohn's patient on patient outcomes.

Conclusion

It is recommended to use theories in nursing care.Read more N42 New tool for IBD nurses to support IBD patientsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

There are about 58000 Inflammatory Bowel Disease (IBD) patients in Finland. The number has doubled in ten years. Over 5500 IBD patients live in the Pirkanmaa region. Patients are treated in three different hospitals and there are eight trained IBD nurses in adult services. Patients can contact a call back-system at any hour of the day. With growing number of patient contacts there is a need for additional contact channels and ways of support for patients care.

Methods

TaysPolku is an app developed by Buddy HealthCare where IBD patients can see their appointments, upcoming procedures, information packages, medication instructions, videos and questionnaires related to their treatment all in one place. TaysPolku provides automatic reminders and enables them to contact their own care unit directly via message. IBD nurses has been part of creating material for TaysPolku. IBD nurse explains the app and creates TaysPolku for the patient after providing the necessary information. The app is downloaded from app stores, verified by strong authentication. The app works with any face ID or pin number chosen by the patient.

Results

TaysPolku was introduced in June 2021 and the first users were patients receiving intravenous biologicals. IBD nurses informed about the new service during the infusion visits and provided written material. In the next phase, TaysPolku was set up for biological self-injecting patients. Currently, TaysPolku have been created 299 patients at Tampere University Hospital Tays. The utilization rate of the created TaysPolku is high. Messages on TaysPolku has been send/received 3896 times. The messages feature enables the care unit to reach everyone using TaysPolku simultaneously. It is used in all three hospitals and every IBD nurses take care of it. Satisfaction with TaysPolku has been good for both patients and IBD nurses. Patient questionnaire highlighted the benefits, and the answers highlighted the ease of use of the service."A well-functioning system ""Reminds me very much of the lab, questions and treatment days. Easy to useand connect. There could also be a connection to other departments when care is taken in other departments as well"

Conclusion

Different forms of service are needed with the growing number of patients, and a digital app that supports the patient's self-care has been proven to work. Further development is underway to offer a similar service to all IBD patients in the region.Read more N31 HLA-DQA1*05 detection in saliva, an effective alternative in the monitoring and control of patients with Inflammatory Bowel DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The development of Inflammatory Bowel Disease (IBD) appears to be related to genetic susceptibility and an excessive immune response of the intestinal mucosa.Tumour necrosis factor (anti-TNF) therapies are the most widely used biologic drugs to treat immune-mediated diseases, but repeated administration may induce the formation of anti-drug antibodies. The ability to identify patients at increased risk of developing anti-TNFα antibodies would facilitate the selection of therapy and the use of preventive strategies.It has been shown that approximately 40% of the European population carries the HLA-DQA1*05 allele, and that its presence could have an important impact on treatment as it has been associated with:- Increased risk of immunogenicity of anti-TNFα therapy, regardless of concomitant treatment or anti-TNFα drug selected.- Decreased efficacy due to the formation of neutralising antibodies, leading to possible primary or secondary failures.- Occurrence of adverse events such as infusion reactions or hypersensitivity reactions.- Alterations in pharmacokinetics, so that drug clearance is accelerated regardless of whether the antibodies are neutralising.In our hospital we have the possibility to request the determination of the HLA-DQA1*05 allele through a detection kit in saliva.The main aim is to present a useful and effective tool for the detection of the HLA-DQA1*05 allele.

Methods

The methodology requires the inclusion of 30 newly diagnosed patients, patients naïve to biological treatment or patients on treatment with a first biological drug for no more than 24 months, by both the doctor and the nurse.The nurse will explain the previous preparation to the patient and will collect the sample using the saliva detection kit. Once the results have been received, the physician is notified.

Results

The detection of the HLA-DQA1*05 allele in our patients is 36.84%, a percentage similar to that detected in the European population through the detection of the HLA-DQA1*05 allele in blood.

Conclusion

- Having the ability to identify individuals at high risk of anti-TNF antibody formation and apply targeted combination therapy to these individuals is very valuable in clinical practice.- Saliva determination of the HLA-DQA1*05 allele is an efficient and cheaper alternative in hospitals where HLA-DQA1*05 detection in blood is not available in the laboratory.- The extraction and performance of the technique is simple, fast, obtaining the results within 5 days of submission, and convenient for both the patient and the healthcare professional.Read more N32 Implementation of chromoendoscopy in colorectal cancer screening in patients with Inflammatory Bowel DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Patients with inflammatory bowel disease (IBD) have a higher risk of colorectal cancer (CRC), so we must implement the best available endoscopic technique to detect it early, decreasing the risk of CRC and death.There is low adherence to CRC screening by chromoendoscopy with dye in patients with IBD, despite the fact that national and international clinical practice guidelines consider this technique of choice based on the available evidence.

Description Of The Initiative

The standardization of a screening procedure, based on the evidence of endoscopy, allows any member of the team, doctor or nurse, to detect the need for the indication, improving screening in terms of follow-up interval and technique.Likewise, the inflammatory nurse will have to know the technique to be able to inform the patient and improve their adherence, preparation and resolve doubts.The main aim is early detection of dysplasia and CRC.The side aims are:▪ To improve the implementation of chromoendoscopy as a technique for CRC screening.▪ Improve patient adherence to colonoscopy.

Methods

The development of an endoscopic follow-up procedure according to risk factors in patients with ulcerative colitis and colonic Crohn's disease, in which chromoendoscopy is the technique of choice. The technique in our center is with 0.4% carmine indigo diffusion with catheter-diffuser, but it is possible to adapt other alternatives according to availability.The procedure establishes the follow-up interval at 1, 3 or 5 years depending on the low, medium or high risk, respectively, depending on the activity, extent and duration of the disease, presence of stenosis and pseudopolyps, primary sclerosing cholangitis and/or family history of CRC.

Results

In our center, 100% of screenings are performed by chromoendoscopy with dye, by a single expert endoscopist, scheduled with a longer examination time than a conventional colonoscopy and with optimization of bowel preparation.

Conclusion

CRC screening of patients with IBD should preferably be performed with chromoendoscopy with dye, establishing follow-up intervals depending on known risk factors, both clinical, endoscopic and histological, and this indication should be standardized in a procedure that is known to all members of the team.Read more P1081 Pharmacokinetics and immunogenicity of the ustekinumab biosimilar candidate ABP 654 in patients with moderate-to-severe plaque psoriasisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

ABP 654 is being developed as a biosimilar candidate to ustekinumab reference product (RP), a biologic agent used in the treatment of certain chronic, immune-mediated, inflammatory diseases. Previously, we reported no clinically meaningful differences in efficacy or safety between ABP 654 and ustekinumab RP in a 52-week randomised, double-blinded, active-controlled study in patients with moderate-to-severe plaque psoriasis. Here, we describe the pharmacokinetics (PK) and anti-drug antibody (ADA) results from the same study.

Methods

A total of 563 patients were randomised in a 1:1 ratio to receive ABP 654 or ustekinumab RP at a subcutaneous dose of 45 mg (baseline body weight [BW] ≤ 100 kg) or 90 mg (baseline BW > 100 kg) (Fig. 1). Serum samples for PK and ADA evaluations were collected at various timepoints. Concentrations of ABP 654 and ustekinumab RP were measured using an electrochemiluminescent (ECL) assay based on the Meso Scale Discovery platform. All ADA samples were tested in a validated binding, acid-dissociation ECL assay. Samples testing positive for binding antibodies were evaluated for neutralising ADA in a validated ECL-based affinity capture elution assay.

Results

From baseline to Week 52, the geometric least-squares (LS) means of trough serum concentrations were similar between the ABP 654 and ustekinumab RP groups. In addition, the geometric LS means of serum concentrations were similar post Week 28 for patients (ABP 654, n=25 and ustekinumab RP, n=34) who received dose intensification. Of patients with a post-baseline ADA result through Week 28, 52 (18.6%) patients in the ABP 654 group and 104 (37.1%) patients in the ustekinumab RP group tested positive for binding ADAs. Of these, 24 (8.6%) patients in the ABP 654 group and 50 (17.9%) patients in the ustekinumab RP group tested positive for neutralising ADAs. For dose intensification patients with a post-baseline result post Week 28, no patients in the ABP 654 group tested positive for binding or neutralising ADAs, and 2 (5.9%) patients in the ustekinumab RP group tested positive for binding and neutralising ADAs.

Conclusion

Throughout the study, serum trough concentrations remained comparable between ABP 654 and ustekinumab RP. While the percentages of binding and neutralising ADAs were numerically lower for the ABP 654 group compared with the ustekinumab RP group through Week 28 (and in patients who received dose intensification), the available clinical efficacy, safety, and PK data suggest that these differences were not clinically impactful. Overall, the results support a conclusion of no clinically meaningful differences between ABP 654 and ustekinumab RP.Read more P1091 Cross-domain dynamics of the fungal-bacterial microbiome in patients with ulcerative colitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Background: Candida in the gut has been recently linked to inflammatory activity in UC. However, the relationship between Candida abundance and the bacterial microbiome remains poorly understood, and how these relationships evolve over disease course in UC is unknown.

Methods

Methods: We utilized data from the Study of a Prospective Adult Research Cohort with IBD (SPARC-IBD) from IBD Plexus to examine the taxonomic composition of the fungal mycobiome and bacterial microbiome cross-sectionally and longitudinally in time. Differential abundance was assessed using a log-transformed linear model on microbial relative abundances, with a false discovery rate of <0.25. Spearman’s correlations and co-abundance networks were utilized to examine relationships between fungi, bacteria, and disease activity. Changes in fungi and bacteria within-subjects was assessed over 2 timepoints, with respect to clinical inflammatory status, and abundances were compared using Wilcoxon signed rank tests.

Results

Results: Among 212 patients with UC, 166 patients were in clinical remission (78.3%) while 46 demonstrated clinical activity (21.7%). During clinical activity, there were increases in Candida (q-val<0.05), bacterial family Desulfovibrionaceae (q-val<0.05), and genus Bilophilia (q-val<0.05) [Fig 1A]. During remission, there were reductions in Candida, with increases in family Lachnospiraceae (q-val<0.05), including genus Anaerostipes (q-val=0.09), Blautia (q-val=0.09) and Roseburia (q-val=0.21) [Fig 1B]. Active disease positively correlated with Candida and Desulfovibrionaceae, and negatively correlated with family Lachnospiraceae. During remission, a positive network was present between family Lachnospiraceae, Bifidobacteriaceae, and Eggerthellaceae, which was disrupted during activity, while an antagonistic relationship was evident between Candida and Saccharomyces during remission.Among 25 patients with persistent remission over time (median time interval ~ 4 months), there were no changes in fungal abundances over timepoints. Among patients evolving from activity to remission (n=7), Saccharomyces significantly increased (p-val<0.05), with no significant change in Candida, although there was a trend towards reduction (mean relative abundance at t₁=0.28 vs t₂=0.11). Concurrently among bacteria, both Bifidobacterium and Anaerostipes significantly increased (p-val<0.05).

Conclusions

Candida and bacteria from families Lachnospiraceae may have opposing associations with inflammatory status in ulcerative colitis, suggesting they may demonstrate competitive ecological niches. Whether reduction of Candida species may expand protective bacteria should be tested adjunctive to immunosuppressive or microbial modulation therapies.Read more P1108 Factors Associated with Delayed Diagnosis of Inflammatory Bowel Disease and Risk of Complications: Analysis of the Brazilian National RegistryWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The Brazilian Organization for Crohn's Disease and Colitis (GEDIIB) has established a national registry of inflammatory bowel disease (IBD). Timely diagnosis and treatment of the disease are crucial to mitigate the risk of complications in this patient population. Therefore, this study aimed to assess the variables associated with delayed diagnosis and the frequency of complications in IBD patients in Brazil.

Methods

A cohort study was conducted from August 2020 to August 2023. Data were obtained from medical records and patient consultations using the REDCap platform, with approvals from the ethics boards of participating institutions. Patients were categorized based on the time from symptom onset to diagnosis: < 1 year, 1 to 1 year 11 months, and ≥ 2 years. Socioeconomic and clinical data, such as disease extension, use of biological therapy, and complications like the need for surgery or hospitalization, were evaluated.

Results

The study included 2,436 patients, with 1,147 diagnosed with ulcerative colitis (UC) and 1,289 with Crohn's disease (CD). Of these, 62% were managed in public centers, and 38% in the private system. The age at diagnosis was 38 ± 15.5 years for UC and 33.7 ± 14.9 years for CD, with females predominating (64.5% for UC and 53.4% for CD). Among UC patients, disease extension included pancolitis (43.5%), left colitis (28.8%), and proctitis (27.7%). The time between symptom onset and diagnosis was longer in CD patients (p<0.001), as follows: < 1 year (UC 58.4% and CD 50.9%), 1 to 1 year 11 months (UC 22.3% and CD 21.1%), and ≥ 2 years (UC 19.3% and CD 28%). The shortest interval in UC patients was observed in private services (p<0.001), Southern and Northeastern regions of Brazil (p<0.001), and in patients without extraintestinal manifestations (EIM) (p=0.003). No differences were noted regarding disease extent, need for surgery, hospitalization, presence of cancer, or use of biological therapy. In CD patients, the shortest interval was observed in private services (p<0.001), the Southern region of Brazil (p<0.001), and was associated with a lower rate of hospitalization due to complications or disease activity (p=0.032). Among those who underwent surgery (35.6%), patients operated on in a public university hospital experienced a greater delay in diagnosis (p=0.014). No differences were observed regarding the presence of perianal disease, need for surgery, cancer, or use of biological therapy.

Conclusion

The window of opportunity is imperative to reduce complications, especially in CD. Further epidemiological studies are needed to shape national public health policies, emphasizing early diagnosis and appropriate treatment of IBD.Read more P1109 Differences of Clinical Phenotype Between Familial and Sporadic Crohn's Disease in East ChinaWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Family history is one of the strongest risk factors for Crohn's disease (CD) while few studies have focused on whether family history influences the clinical features, disease course, and severity of CD. There is still controversy about the difference between sporadic and familial CD. This study aimed to compare the phenotypic features of familial CD with sporadic CD in Chinese populations.

Methods

We included 2,043 patients diagnosed with CD. Familial CD was defined as CD patients having one or more first-, second-, third-, fourth-degree or above relatives with CD. Sporadic CD patients hospitalized during the same period were matched 1:3 by age and gender. Differences in clinical characteristics, phenotype distributions, extra-intestinal manifestations, and complications at diagnosis, as well as treatment regimens and surgeries, were compared between familial and sporadic CD.

Results

A total of 55 familial CD and 165 sporadic CD were identified. The familial CD was associated with a higher rate of past appendectomy history (20.00% vs 6.67%, P=0.009), more intestinal perforation at onset (12.73% vs 3.03%, P=0.012), more anal lesion (85.45% vs 68.48%, P=0.023) and gastrointestinal perforation (14.55% vs 5.45%, P=0.040) at diagnosis, higher rate of past intestinal surgery history (50.91% vs 29.70%, P=0.007), more number of intestinal surgeries (1.50[IQR 1.00-2.00] vs 1.00[IQR 1.00-1.00], P=0.037), longer duration of follow-up (54.00 months[IQR 21.50-125.00] vs 41.00 months[IQR 14.00-79.00], P=0.017), lower rate of taking biologicals for current maintenance (61.82% vs 76.97%, P=0.043), lower tendency to upgrade to biologicals during follow-up (69.09% vs 85.37%, P=0.013), higher possibility to experience gastrointestinal obstruction (23.64% vs 11.52%, P=0.047) and abdominal abscess during follow-up (9.09% vs 2.42%, P=0.045).

Conclusion

Familial CD is associated with a more aggressive clinical phenotype compared with sporadic CD.Read more P1128 Reducing diagnostic delay of Extra-Intestinal Manifestations in patients with Inflammatory Bowel Disease: a comparative study between a multidisciplinary immune-mediated diseases outpatient clinic and conventional referral specialistsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Extraintestinal manifestations (EIMs) can occur in up to 47% of patients diagnosed with inflammatory bowel disease (IBD); hence the early detection of EIMs in IBD patients is crucial to prevent structural damage. However, there is a substantial variation in the reported time to diagnosis of EIMs due to a lack of a standardised approach. We, therefore, evaluated the length of time to diagnose EIMs through an integrated immune-mediated diseases (IMIDs) outpatient clinic (IMID-C) compared to a standard outpatient clinic (SO-C). Secondary endpoint included the impact of diagnostic time on the time to therapy, thereby aiming for an early control of disease

Methods

We conducted a single-centre cohort observational study including IBD patients ≥18 yo presenting red flags for EIMs who underwent outpatient visits through a multidisciplinary IMIDs clinic between 2018-2022 and we compared this group to a historical cohort, with similar clinical features, who underwent conventional visits by individual referral specialists from 2017 to 2022. Diagnostic delay was defined as the period from the occurrence of red flags to diagnosis of EIMs. Survival curves were plotted for assessing the differences in terms of diagnostic delay and time to treatment between IMID-C and SO-C within 18 months.

Results

We enrolled 238 IBD patients; 127 were referred to the IMIDs Clinic Group (IMID-G) and 111 to the Standard Outpatient Clinic group (SO-C). Demographic details are summarised in Table 1. The average time to EIMs diagnosis was 2,48±1,8 months for IMID-C and 5,36±2,3 months for SO-C (p=0.005). In both groups, most patients (38,6% in IMID-C and 44 in SO-C) referred red flags for peripheral arthritis (PA). In IMID-C, chronic back pain was reported by 23,6% of patients, similarly in SO-C 27,9% had chronic back pain. Overall, the majority of patients received a diagnosis of PA (IMID-C=37,5%; SO-C=33,7%) and spondyloarthropathy (IMID-C=32,1%; SO-C=33,7%). Significantly, more patients in the IMID-C group (34, 26,8%) received treatment with immunomodulators in addition to their ongoing therapy compared to the SO-C group (17, 17,3%; p=0.04). Details of therapeutic strategies are summarized in Table 2. Survival curves revealed a significant reduction of diagnostic delay and time to therapy in IMID-C compared to SOC-C group (log-rank test, p<0.001)

Conclusion

Attending a dedicated IMIDs clinic can enhance the diagnostic process for EIMs in IBD patients, thereby reducing diagnostic delays. Disease-modification trials are eagerly awaited to assess the long-term impact on disease progression, quality of life and disabilityRead more P1129 Fistulising Crohn's Disease in a large Australasian cohort - Crohn's Colitis Cure (CCC) Data Insights ProgramWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Fistulising Crohn’s disease (fCD) affects up to 40% of people with Crohn’s disease (CD) over their lifetime, leading to perianal pain, faecal incontinence and sepsis. Despite its high prevalence, the burden of disease, treatment and “natural history” in the current biologic therapy era are poorly described. This study explored demographics, disease and treatment factors in a real-world cohort

Methods

The clinical quality registry (CQR) is created from deidentified data flowing into a registry during documentation in routine care. The CQR was interrogated in December 2022. People with CD with a care encounter in the last 14 months at one of 20 treating centres were included (n=3039). People with a current fistula were defined as those with an actively draining fistula on most recent clinical assessment, radiologic or endoscopic investigation. Previous fCD was defined as the prior presence of a fistula with most recent documentation showing resolution

Results

There were 3039 people with CD with a mean age of 43.1 years (SD +/- 16.23). 49% of the total CD cohort were female with a mean disease duration of 13.7 years (SD +/- 10.1). 532 (17.5%) people with CD had fCD documented in the CQR, with 220 current and 312 previous fCD. People with current or previous fCD were younger than those with no prior fistulising disease (40.5 & 39.6 vs 44.1, p=0.005 & p<0.001). Male gender was more commonly seen in those with current (58% p=0.022) or previous fCD (58% p=0.007) compared to those with no prior fCD (50% n=1270)People with current and previous fCD had higher rates of current biologic use compared to those with no prior fCD recorded (75.5% & 68.3% vs 48.9%, p<0.001 & p<0.001, respectively). Of those on biologic therapy, people with current or previous fistula were more likely to be on anti-TNF therapy (Adalimumab or Infliximab) compared to those with no history of fCD (85.5% & 82.2% vs 68.1%; p<0.001 & p<0.001 respectively). People with active or previous fCD were less likely to have ever been on steroid therapy compared to those without a history of fistulising disease (23.6%, 24.4% & 32.3%, p<0.001 & p<0.001)People with current or previous fCD had higher rates of CD-related hospital admissions compared to those without a history of fCD (5% & 6% vs 1.9%, p<0.001 and p<0.001 respectively). People with previous fistulising disease had higher rates of surgery within the last 12 months compared to people with no prior fCD (21.2% vs 13.3%, p<0.001)

Conclusion

People with current and previous fCD continue to experience higher hospitalisation rates for disease related complications and more frequently require surgical procedures. This highlights the importance of proactive management of fCD to reduce morbidity and avoidable healthcare utilisationRead more P1151 Incidence and risk factors of thromboembolic events in Pediatric-Onset Inflammatory Bowel Disease: a population-based studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Patients with inflammatory bowel disease (IBD) are known to be more susceptible to thromboembolic events. However, limited data on the incidence and risk factors for both venous (VTE) and arterial thromboembolic events (ATE) have been documented at the population level, especially in pediatric-onset IBD.

Methods

All patients diagnosed with Crohn’s disease (CD) or ulcerative colitis (UC) before the age of 17 years from 1988 to 2011 in a prospective population-based registry were retrospectively followed until 2013. Every VTE and ATE occurring during the follow-up period were included. Cox proportional hazard models with hazard ratio (HR) were performed using time dependent variable except for patient’s characteristics at diagnosis.

Results

A total of 1,344 patients diagnosed with IBD between 1988 and 2011, including 1,007 (75%) patients with CD and 337 (25%) with UC, with a median age at diagnosis of 14.3, IQR [11.7-16.0] years were included. After a median follow-up of 8.3, IQR [4.3–13.9] years, 15 (1.1%) VTE and 2 (0.15%) ATE occurred at a median age of 20.4, IQR [16.6-24.5] years (younger age: 14.8 years). The global incidence rate for both VTE and ATE was 1.32 per 1000 person-years, 95%CI [0.77 - 2.11]. In CD patients, the incidence of VTE was 1.41 per 1000 person-years, 95%CI [0.77 - 2.37], whereas it stood at 0.33 per 1000 person-years, 95%CI [0.01 - 1.85] in UC patients. The risk of VTE and ATE did not change over the study period. Periods of active disease (HR 8.4 [2.3-30.5], p=0.0002), the 3-months postoperative period (HR 16.4 [5.2-52.3], p=0.0002) and hospitalization (HR 21.7 [7.5-62.9], p<0.0001) were found to be associated with an increased risk of VTE.

Conclusion

The risk of both arterial and venous thromboembolism was low in this pediatric-onset IBD population-based cohort. VTE were strongly associated with active disease, surgery and hospitalization among IBD patients.Read more P1152 Health-related quality of life among Irish Inflammatory Bowel Disease patients: a cross-sectional survey using the EQ-5D-5LWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Inflammatory Bowel Disease (IBD), which includes Crohn’s disease (CD) and ulcerative colitis (UC) is a chronic, lifelong illness that has multiple impacts on patients’ physical and mental health. Approximately 40,000 individuals in Ireland have IBD and the burden on quality of life is expected to be substantial. Health-related quality of life (HRQoL) utilises quality weights (utilities), measured on a ‘0’ to ‘1’ scale where ‘0’ is defined as a health state equivalent to being dead and ‘1’ is full health, and is often used as a measure of population health status to inform public health and health care policy. Previous evidence has shown that a reduced HRQoL in patients with IBD is associated with higher disease activity, increased medication use, increased sick leave, decreased work participation, smoking, rheumatic symptoms, female gender, and having CD. Despite this evidence, there is a paucity of data on the impact of IBD on the HRQoL of IBD patients in Ireland.

Methods

A cross-sectional, online study was developed aimed at IBD Patients in Ireland and patients were recruited through study invites advertised on The Crohn's and Colitis Ireland social media channels and among patient representatives of INITIative IBD. Information on quality of life was collected using the EuroQol EQ-5D-5L questionnaire. Descriptive statistics describe sociodemographic and clinical characteristics. Categorical variables are summarized as frequencies and percentages. Utility scores are presented as the mean and standard deviation (SD). To evaluate factors correlating with HRQoL in IBD patients, a univariate regression model was applied. Significant variables (p<0.05) were further included in a multivariable ordinal least squares regression model.

Results

A total of 161 IBD patients were recruited. The average EQ-5D-5L utility score was 0.76. Average utility scores were similar for UC (0.76) and CD (0.75) patients, with IBDU patients scoring slightly higher (0.80). Average utility scores were highest for those aged 50-59 years (0.93), with an average utility score for those aged 30-39 of 0.71. Average utility scores were higher in males (0.78). Utility scores ranged from .133 to 1. When compared with those in remission, patients with severe disease severity had significantly lower utility scores (β=-.261; p=0.000).

Conclusion

Findings suggest that HRQoL in IBD patients in Ireland varies according to disease severity. These findings may indicate that follow-up care should include generic HRQoL measurements along with disease-specific as an objective tool for monitoring IBD disease course. This research offers important information for policy-makers for developing better strategies for IBD patients, as well as clinicians, academics and IBD patients.Read more P1178 Detection of occult liver disease in patients with Inflammatory Bowel DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Investigation of liver disease is recommended in the ECCO Guidelines for Extraintestinal Manifestations in Inflammatory Bowel Disease (IBD). The aim of this study was to analyse the prevalence of liver disease in IBD patients, to examine the frequency of different aetiologies, and to investigate a possible correlation between the severity of liver disease and IBD.

Methods

Cross-sectional descriptive study including all patients with inflammatory bowel disease (IBD) of nine hospitals in Spain. The study of liver disease was carried out in two phases: patients with FIB-4 greater than 1.3 (greater than 2 in those aged 65 years or more), as well as those with APRI greater than 0.5 and/or elevated transaminases were selected as those at risk of liver disease. In the second phase, these patients underwent a medical history, comprehensive blood tests, abdominal ultrasound with SWE elastography and Fibroscan® (including transitional elastography (TE) and Controlled Attenuation Parameter (CAP)).

Results

In total, 5302 patients were enrolled and 1640 (31%) were identified as at risk for liver disease. The University Hospital of Burgos has completed the second phase of the study in patients diagnosed with IBD between 2010 and 2021 (n=151). Of these patients, 72.2% were male and the median age was 61 years. Ulcerative colitis (57%) was the most common type of IBD and 62% of the patients were overweight or obese, while 12% of the patients had high-risk alcohol consumption. Metabolic hepatic steatosis was the most frequent cause of liver disease (35%).Moderate/severe steatosis was detected in 44.3% of patients by CAP and 24% by ultrasound. The prevalence of advanced fibrosis was 10.6% and 12% when assessed by ET and SWE, respectively. Notably, 12.6% displayed ultrasound signs of chronic liver disease.A positive correlation was found between the ET and the SWE for liver fibrosis, with a correlation coefficient of ĸ = 0.663.On univariate analysis, an increased risk of significant fibrosis (p=0.011) and moderate/severe steatosis (p=0.00) was found only in those who were overweight or obese. However, no association with severity of liver disease was found for perianal disease, use of immunosuppressants or history of previous surgery.

Conclusion

The incidence of unrecognised liver disease in IBD patients is substantial, with metabolic hepatic steatosis being the most common cause. The severity of liver disease in these patients cannot be ignored, with one in ten patients having advanced fibrosis. In the univariate study, only obesity was found to correlate with the severity of steatosis and fibrosis, while IBD severity showed no significant association with liver disease severity.Read more P1179 Long-term impact of COVID-19 on the disease course of IBD: a meta-analysisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Viral infections have been implicated in the exacerbation of immune-mediated inflammatory diseases like inflammatory bowel disease (IBD). The COVID-19 pandemic, therefore, sparked interest in whether infection with the virus has an adverse effect on the course of IBD. Since the existing evidence is conflicting and limited by a small sample size, we performed the very first meta-analysis to study the long-term impact of SARS-CoV-2 infection on the disease course of IBD.

Methods

We performed a systematic literature search in MEDLINE and EMBASE for studies that explored the risk of adverse IBD outcomes following a SARS-CoV-2 infection. We used the random effects model meta-analysis to calculate the pooled hazard ratio for the risk of IBD flares following the acute phase of COVID-19. Subgroup meta-analysis was carried out for the risk of the outcomes by IBD subtype. Meta-regression was carried out for sex and duration of follow-up. The ROBINS-E tool for observational studies was used to assess the quality of the studies.

Results

A total of 5 studies were included in the meta-analysis. The studies were based on cohorts from Denmark, Italy, the US, and a cohort from a consortium of the EU comprising a total of 34977 SARS-CoV-2 positive IBD patients and 53270 IBD patients without the infection as controls. Two of the studies had a high risk of bias according to the quality assessment tool. The meta-analysis did not show an increased risk of IBD-related outcomes in IBD patients who contracted a SARS-CoV-2 infection compared to those who did not (HR: 1.0514, CI: 0.7547- 1.4646, p= 0.7671). There was substantial heterogeneity between the included studies (91%, p<0.01). There was no significant difference between CD and UC patients in terms of disease flare (CD- HR: 0.9134, CI: 0.8163-1.0220; UC- HR: 0.8257, CI: 0.7549-0.9032). Neither sex nor the duration of follow-up was a predictor of the overall effect size.

Conclusion

In this group of patients, SARS-CoV-2 infection does not increase the risk of adverse outcomes related to IBD. High-quality studies with longer follow-up duration are required to understand the long-term impact of SARS-CoV-2 infection on IBD prognosis.Read more P1180 Smoking behaviour and changes after diagnosis in patients with Crohn's disease in a tertiary referral hospital: A retrospective explorative studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Smoking is the best-known environmental risk factor for poor outcome of Crohn’s disease (CD). Since smoking cessation improves the prognosis of CD, patients are encouraged to quit smoking. This study aimed to assess the smoking behaviour among CD patients and explore changes after diagnosis of CD.

Methods

This is a retrospective single tertiary center cohort study of 1267 patients with CD with a median follow-up of 16.8 years (IQR - 18.3) whose characteristics are recorded via a validated data software (IBDIS, Inflammatory Bowel Disease Information System). Smoking behaviour was categorized into never smokers, current smokers, and ex-smokers (those who quit smoking at any point). The primary objective was smoking cessation during follow-up. The probability of smoking was calculated for those CD patients who smoked at the time of diagnosis of CD by means of Kaplan-Meier estimates. Statistical analyses were conducted using R software, employing log-rank tests for estimating differences with a significance level of alpha = 0.05.

Results

In total 1,128 CD patients with a complete data set were analysed (Table 1). 161 (14.2%) patients started and stopped smoking prior to diagnosis of CD. At the time of diagnosis, 541 patients (47.9%) were smokers, and 239 (44.2%) of them quit smoking during follow up. The median time from CD diagnosis to cessation for the 239 patients who were smokers at the time of diagnosis and subsequently quit was 8.6 years (IQR - 10.6 years). 80 patients (7%) started smoking after diagnosis, with 50 of these patients quitting thereafter. The probability of smoking in those CD patients who smoked at the time of diagnosis decreased over time to 0.96 (95% CI 0.95-0.98) at 1yr, 0.85 (95% CI 0.83-0.89) at 5 yrs, 0.71 (95% CI 0.67-0.76) at 10 yrs, and 0.52 (95% CI 0.47-0.57) at 20 yrs after diagnosis for the entire cohort with no significant difference between genders (p=0.76) (Figure 1a). Patients who were diagnosed 2010 and later (n=182) were more likely to stop smoking than patients diagnosed before 2010 (n=359) (p<0.001) (Figure 1b). However, the probability to smoke 10 years after the diagnosis was still high in both groups (0.62 (95% CI 0.52-0.74) and 0.75 (95% CI 0.71-0.79), respectively).

Conclusion

A substantial proportion of CD patients smoked at the time of diagnosis. 20 years after diagnosis around half of the patients still continued to smoke. Improved smoking cessation programs are needed to reduce the impact of smoking on the course of the disease.Read more P1181 Prevalence and trend of anemia in a large cohort of children with inflammatory bowel diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Anemia is a common extraintestinal manifestation in inflammatory bowel disease (IBD) with an impact on patients’ quality of life. Our aim was to determine the prevalence of anemia and its characteristics at the diagnosis in children with inflammatory bowel disease (IBD) and to investigate its trend during follow-up.

Methods

We conducted an observational, multicenter cohort study including data of IBD children with anemia at the diagnosis enrolled in the Italian Society of Pediatric Gastroenterology, Hepatology and Nutrition (SIGENP) IBD registry. Demographic, clinical, laboratory and endoscopic data were collected at the diagnosis and anemia trend was evaluated at 1-year follow-up. Anemia was diagnosed based on the WHO criteria and classified as mild, moderate, and severe accordingly.

Results

Five hundred eighty-nine [295 CD (50%) and 294 UC/IBDU (50%)] out of 1634 with IBD presented with anemia, resulting in a prevalence of 36%. Anemia rate was higher in CD than in UC (39% vs 33%, p = 0.009). Most patients presented at the diagnosis with moderate anemia (55%). The most common forms of anemia were iron deficiency anemia (IDA) and combined inflammatory and IDA anemia (InflIDA), both present in 42% of children. Only 15% of children had anemia of inflammation. Children with CD had higher rates of mild anemia than UC (38% vs 33%, p<0.0001), while severe anemia was more common in UC (13% vs 6%, p= 0.001) as well as IDA (53% vs 31%, p<0.0001). Younger age and lower albumin levels significantly correlated with the severity of the anemia in CD. In UC, females were more likely to experience severe anemia (69% vs 47%, p=0.02) and an extensive disease was more prevalent in children with moderate and severe anemia then in those with mild anemia (p=0.01 and p=0.03, respectively). At 1 year, 99 children (17%) were still anemic. At multivariable logistic regression analysis, baseline wPCDAI and SES-CD significantly correlated with the persistence of anemia at 1 year in CD. No variables correlated with the persistence of anemia in UC.

Conclusion

More than one-third of pediatric patients present with anemia at the diagnosis of IBD, most commonly moderate. A severe anemia is most common in UC compared to CD. Iron deficiency anemia (alone or in its form of InflIDA) is the most common cause of anemia in children with IBD. One out of five is still anemic after 1 year from the diagnosis.Read more P1218 Non-invasive point-of-care stool sample for detection of Cytomegalovirus infection in patients with Active or Refractory Ulcerative Colitis using multiplex polymerase chain reaction (mPCR): a pilot feasibility studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Cytomegalovirus (CMV) infection is associated with more flare-ups and deteriorates the prognosis of active inflammatory bowel disease (IBD). Patients with refractory IBD should be tested for CMV colitis, especially if they are not responding to immunosuppressive therapy. The prevalence of CMV co-infection ranges from 10% to 30% in steroid-refractory acute colitis. Concurrent CMV-colitis is associated with an increased risk of worse therapeutic outcomes, resistance to corticosteroids, and need for salvage therapy. One of the two gold standards of diagnosis of CMV colitis in IBD patients with active disease requires the analysis of tissue biopsies using PCR. The aim of our pilot study was to evaluate the diagnostic accuracy of non-invasive point-of-care faecal samples using mPCR for detecting CMV in patients with ulcerative colitis compared to standard practice biopsies PCR.

Methods

We performed a prospective, observational, feasibility study including 62 consecutive patients with active ulcerative colitis (UC) requiring intravenous steroids or steroid-refractory UC in the Department of Gastroenterology of University Hospital „Tsaritsa Yoanna – ISUL", from April 2022 to October 2023. In all UC patients, colonic tissue biopsies were performed and analyzed by qualitative CMV PCR. Faecal sample mPCR CMV was performed on the positive patient cohort to compare the feasibility of (ME) Panel IVD using FilmArray mPCR (Biofire, bioMerieux, France). All the tested patients had undergone immunosuppressive therapy and initial stool specimen cultures were obtained to exclude infection with C. difficile and other pathogen flora.

Results

Out of 62 active UC patients with colonic tissue samples qualitative CMV PCR, n=5 (8%) were positive. Of these n=5 UC patients, n=4 (80%) were positive from the Fecal sample mPCR CMV, resulting in a compatibility of 80% for diagnosing CMV in these patients by the two DNA extraction methods. Calculated Sensitivity and diagnostic accuracy was 80% (95% CI) for the mPCR CMV. The patient cohort predominantly comprised males (75%) with a median age of 45 years (range: 30–72 years). Three patients (75%) out of this cohort group were treated with peroral antiviral agent Valganciclovir, one (25%) of them went into clinical and endoscopic remission after the treatment and two patients (50%) received colectomy. The median time performing the Faecal sample mPCR CMV was approx. 1 hour.

Conclusion

This novel faecal mPCR point-of-care test is a promising, fast and easy non-invasive tool for detection CMV in active or refractory UC patients, comparable with the colonic tissue CMV-DNA PCR.Read more P1219 Changes in gut microbiota of patients with inflammatory bowel disease receiving biologic therapyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Inflammatory bowel disease (IBD), comprising the predominant forms Crohn’s disease (CD) and ulcerative colitis (UC), is associated with compositional and metabolic changes in the intestinal dysbiosis. The aim of this study is to evaluate the composition in the microbiota of IBD patients who received biologic therapy

Methods

This is a prospective study recruited 14 patients with IBD received biologic therapy and 13 IBD controls who received conventional treatment . The taxonomic composition of the gut microbiota was determined by 16S ribosomal RNA gene sequencing of stool samples. The stool samples at baseline, weeks 6 and 48 after biologic therapy initiation were assessed. We also evaluated the level of inflammation and treatment response of biologics by BD activity score (CD patient by Crohn’s disease activity index [CDAI] and in UC patient by Mayo score).

Results

In CD group, we recruited 7 CD patients receiving biologic therapy (Anti-tumor Necrosis Factor for 4 and anti-integrin for 3) and 6 controls.In UC group, we recruited 7 UC patient receiving biological therapy (Anti-tumor Necrosis Factor for 2 and anti-integrin for 5) and 7 controls.Community α-diversity was lower in patients at baseline of biologics group compare to controls significantly but increase abundance and richness after achieving remission in trend at week 6 and week 48, respectively. In Top 10 taxon bacterial distribution, the Firmicutes were increase its abundances gradually ( relative abundance in biologics W0,W6,W48 and controls were 46.3%, 51.7%,62.0%, and 66.4%, respectively). Conversely, the Bacteroidetes were decrease its abundances ( relative abundance in biologics W0,W6,W48 and controls were18.3%, 18.8%, 10.2% and 6.4%, respectively). Increased F/B ratio significantly after biologics therapy also found in our study. (F/B ratio were 9.4, 12.5,64.0,and 84.3,respectively).Patients in control group had higher abundance of Firmicutes of the phylum.By contrast, Enterobacteriaceae and Bacteroidaceae were significantly more abundant in patients of biologics group at W0 .

Conclusion

Treatment with biologic therapy induced improvement of community diversity and increased F/B ratio in IBD patients which seemed correlate the level of clinical inflammation. The dysbiosis-representative bacteria, such as Enterobacteriaceae, could induce colonic inflammation,were more abundant in patients who had higher activity of IBD. Further larger prospective studies are needed to determine whether the biologic therapy could induce long-term changes of intestinal microbiome.Read more P1220 Dysbiosis of the gut microbiota and decreased fecal levels of short-chain fatty acid in patients with Ulcerative Colitis: a hospital-based case-control studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Ulcerative Colitis (UC) is a typical intractable disease whose number of patients is increasing worldwide, and studies have suggested that the gut microbiota and its metabolites are closely involved in its pathogenesis and severity. However, to date, no study has comprehensively compared the microbiomes or metabolomes of UC patients and healthy controls after considering important confounding factors such as age, gender, race, and other lifestyle factors. Therefore, we conducted this clinical study to compare the compositions and diversity of the gut microbiota and the fecal metabolites between age-, sex-, and race-matched patients with Ulcerative Colitis (UC) and those without.

Methods

In total, 90 outpatients with UC (UC group) and 90 without a history of gastrointestinal diseases and their family members (without UC group) were recruited.

Results

The UC group had a significantly lower abundance of the genus Bifidobacterium, Faecalibacterium, and Lactobacillus than the without UC group. Furthermore, the UC group had a significantly lower alpha-diversity of the gut microbiota than the without UC group. The UC group had a significantly lower level of fecal SCFAs than the without UC group. These results remained significant after adjusting for sex, age, and smoking status. Furthermore, the expression of a group of genes encoded by the gut bacteria that are involved in the biosynthesis of tetrapyrrole was significantly lower in the UC group than in the without UC group.

Conclusion

Gut microbiota dysbiosis and low SCFA levels, as well as reduced tetrapyrrole biosynthetic capacity by the gut bacteria, may contribute to the development of UC. Moreover, regardless of the severity, duration, and type of UC, the gut microbiota and its metabolites were in a stable state of dysbiosis in patients with UC.Read more P1221 Analysis Of Oral And Intestinal Microbiome Of Korean Patients With Crohn's DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

We aimed to conduct a study comparing the fecal and oral microbiomes of Korean Crohn's disease patients with those of healthy individuals. Since most of microbial study of inflammatory bowel disease patients are conducted overseas, this study would reveal if the microbiome of Korean patients and patients of other countries are the same or not. Also, since the process of fecal sample collection is inconvenient, saliva sample analysis was performed to find a relevance of disease activity.

Methods

This single center study recruited patients with CD between September 2022 and January 2023. At first visitation, stool collecting tube and saliva collecting tube were given to CD patient. Collected stools samples and saliva samples were sent to the environmental bioengineering laboratory in Korea University and assessed by 16S rRNA sequencing.

Results

26 CD patients and 6 healthy individuals were enrolled to this study. In the comparison of helathy individual’s fecal microbiome, the flora of fecal sample of CD patients were slightly different. The diversity of microbiome was decreased in CD patients compared to healthy individuals. There were 17 species existed only in CD patient’s feces. The most frequently detected one was Ruminococcus gnavus, and the the highest abundance was Unclassified Fusobacterium. In the phylum level of bacteria, Bacteroidota, Firmicutes, and Proteobacteria were predominant. Saliva samples showed no significant difference between CD patient and control.

Conclusion

Fecal sampling can be usefully used as a diagnostic test technique that can reflect CD patients’ microbiota. Similar to patient in overseas, dysbiosis of fecal microbiome and abundant species were detected.Read more N05 Are we meeting the sexual wellbeing concerns of patients with IBD and a stoma? A survey on current practice in addressing sexual wellbeingWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

People with inflammatory bowel disease have a high incidence of stoma formation, either temporary or permanent. Although a stoma can be a life saver, for some it can negatively impact body image and psycho-emotional wellbeing. Sexual function can also be affected by a poor body image. Therefore, intimacy and sexuality should be addressed in clinical settings during stoma care. We aimed to explore the experiences of sexual wellbeing concerns of people living with IBD and a stoma, and how these were addressed by healthcare professionals.

Methods

This was Stage 1 of an international mixed method study. Data were collected via an anonymous online survey advertised on social media platforms and charity webpages.

Results

These are the quantitative results. 134 participants with IBD responded: 11 had colostomy and 123 had ileostomy. Time from stoma formation to survey response was between 2 weeks to 32 years. Peristomal hernia was reported by 27.6% (n=37) participants. Only 30.5 % (n=41) reported that sexual wellbeing was discussed around the time of their stoma formation, mainly with their surgeon or stoma nurse. Some 33.5% (n=45) reported having had no intimacy and sexuality concerns at all at the time of stoma formation. The patient perspective on barriers for asking healthcare professionals (HCPs) questions about sexual wellbeing despite having concerns, were reported as being ashamed to ask, afraid of being judged by their HCPS, and not knowing what to ask as being overwhelmed with technical information related to stoma care. Around 66% (n=89) reported having concerns related to their intimacy and sexuality following stoma formation, with the top three reported concerns being appearance/body image, fear of rejection from partner, and bag leakages. All participants reported wanting sexual wellbeing discussed routinely at any point of care, and the majority wanted partners involved in these discussions.

Conclusion

Patients expect to be informed about intimacy and sexuality aspects as an integral part of stoma care. Current practice does not meet the patient’s care needs, with potential for having a negative impact on their overall quality of life, since a significant number of ostomates report sexual wellbeing concerns after the stoma formation.Sexual wellbeing conversations should be an integral part of perioperative and stoma care to prevent persistent concerns within this patient group. Not providing adequate information during stoma care about sexual wellbeing can negatively impact their quality of life. The results will form the basis of an interview guide for the second (interview) stage of the study, to understand better the reasons behind these findings.Read more P1048 Mirikizumab administration experience from Ulcerative Colitis patients: Survey data from the LUCENT clinical programWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Mirikizumab (MIRI) is an anti-IL-p19 antibody approved for moderately-to-severely active ulcerative colitis (UC). The recommended dose regimen has 2 parts: MIRI administration begins with intravenous (IV) infusion every 4 weeks (Q4W; 3 total) and is followed by maintenance dosing of subcutaneous (SC) injections (2 injections per dose) Q4W. Self-injection of SC MIRI is allowed after patient training. This study investigated patient satisfaction with and acceptability of MIRI IV infusions and SC injections during the LUCENT program.

Methods

This was a cross-sectional, 30-min, web-based survey. Patients were eligible if they were enrolled in LUCENT-3, a phase 3, open-label, long-term extension study of MIRI. Patients entered LUCENT-3 from the AMAC phase 2 study, or the LUCENT-1 and LUCENT-2 phase 3 studies. The survey covered patient satisfaction with and acceptability of IV infusions during the AMAC, LUCENT-1, or LUCENT-2 (extended or reinduction) studies and SC injections during the AMAC, LUCENT-2, or LUCENT-3 studies (Figure 1). Survey questions had responses based on 5-point Likert scales (Table 1). The survey was completed during LUCENT-3; MIRI SC injection experience at the time of survey varied from >2 yrs to ≥3 yrs. Subgroup analyses (primary: age and sex) were made using Fisher's exact tests.

Results

The survey was completed by 93 patients from 11 countries (mean age, 42.9 yrs; 54.8% male; 69.9% White). Most patients were satisfied or very satisfied with IV infusions (82.8%) and SC injections (91.4%). More than 89% of patients retrospectively reported that their satisfaction with either administration method remained the same or improved over time. Most patients indicated receiving 2 SC injections (96.8%) and receiving SC injections Q4W (97.8%) were somewhat or completely acceptable. Patients (95.1%) agreed that the self-injection device was easy to use. 97.8% were satisfied or very satisfied with the administration of MIRI overall, 96.8% agreed or strongly agreed that they would recommend MIRI to someone with UC, and 90.3% agreed or strongly agreed that improvements in their UC outweighed any dissatisfaction with the administration method. Acceptability of MIRI administration differed by age (p=0.0369). More patients aged ≥40 yrs than <40 yrs found the MIRI administration completely acceptable (98.2% vs. 89.2%). Overall satisfaction with the IV infusions differed by sex (p=0.0159). More females than males were satisfied or very satisfied with the IV infusions (92.9% vs.74.5%).

Conclusion

Most UC patients were satisfied with and acceptable of receiving MIRI by IV infusions and SC injections and found the dosing of 2 SC injections Q4W acceptable.Read more N06 Self-care in patients affected by inflammatory bowel disease: SELF-IBD observational study in a single centerWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Self-care is an active process to maintain and promote health in chronic disease situations, and is effective in the results of many chronic diseases. So far, few studies have been conducted on the self-care of IBD. The study of self-care in IBD is also motivate, by the increase in prevalence in the coming years and the impact on health resources it could have. In addition, the study of self-care in relation to socio-sanitary features and habits within the population affected by IBD may be the beginning to identify areas for educational interventions by health care personnel. The primary objective of this study is to describe the levels of self-care maintenance, monitoring and management in patients with IBD.

Methods

Cross-sectional observational study to evaluate self-care in IBD patient. The questionnaire used was the Self-Care of Chronic Disease Index (SCCII). The SCCII investigates three aspects of self-care, maintenance, monitoring and management and the self-efficacy. The sociodemographic characteristics and some patient habits such as smoking habit, fatigue, exercise, sleep, nutrition and supplement use, were investigated. Ethics Committee approved

Results

We enrolled 85 patients with an average age of 44.8±16.8, of which 51.8% (female) and 50.6% (CD), 48.4% (UC). The level of self-care (SCCII) areas investigated ranged from score levels of 71.30 (Self-maintenance), 79.52 (self-monitoring), 68.94 (self-management) and 75.70 (self-efficacy). In the area of self-care maintenance the aspects that seem least considered by patients (never or rarely) are stress management (44.1%) and exercise (40%). Only 57.6% of patients often or always get enough sleep and only 22.3% of patients follow a healthy diet. The presence of fatigue seems to affect 68% of patients in the self-monitoring phase. In the area of self-management, only 41.2% of patients (often or always) try to rest during the day and only 52% of the sample succeeds continuously with the appearance of symptoms. In self-efficacy, it seems that 85.8% of the patients interviewed persist in following the treatment even when it is difficult. It seems that men have more significant levels of self-maintenance score 74. vs 68.8 (p>0.01) than women. Table 1 shows the average self-care scores in relation to the habits investigated.

Conclusion

From the results of our study it seems that patients with IBD have adequate levels of self-care (score ≥70), although sleep/rest, diet and exercise seem not to be highly considered by patients. Future studies may investigate which specific sociodemographic and clinical characteristics can be identified as predictors of maintaining self-care, self-care management and self-confidence, to improve areas of nurse educational intervention.Read more P1049 Effectiveness and safety of subcutaneous infliximab in Crohn’s disease patients with immunogenic failure of intravenous infliximabWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Immunogenicity is a major reason for secondary loss of response to infliximab (IFX). Recent work suggested potentially lower immunogenicity of subcutaneous compared to intravenous infliximab. However, it is unknown whether re-exposure of patients with immunogenic failure of IFX to its subcutaneous formulation is safe and effective. Here, we analysed the safety and effectiveness of subcutaneous IFX (CT-P13) in patients with Crohn’s disease (CD) and history of secondary loss of response of intravenous IFX due to anti-drug antibodies (ADA).

Methods

In a retrospective analysis conducted at medical centers in Germany (Dresden) and the Czech Republic (Prague), patients with clinical (Harvey-Bradshaw Index ≥ 5) and/or biochemical (faecal calprotectin >250 µg/g) active CD and previous treatment failure in the context of IFX immunogenicity underwent re-exposure to subcutaneous IFX. Treatment was initiated with either 4 subcutaneous injections 120 mg CT-P13 weekly followed by biweekly injections, or directly with 120 mg CT-P13 subcutaneous biweekly. Harvey-Bradshaw Index, faecal calprotectin, IFX serum concentration and ADA were assessed until month 12.

Results

Twenty CD patients were included (table 1). The majority of patients (90 %) had previous treatment with ≥ 3 biologics. 75% and 50 % of patients continued IFX treatment until month 6 and 12, respectively. No immediate hypersensitivity reactions were observed. Two patients (10%) discontinued IFX due to delayed hypersensitivity. Lack of treatment effectiveness led to infliximab withdrawal in 7 cases (35%) and one patient (5%) was lost to follow up after month 6. IFX serum concentrations increased from baseline (median 0 µl/ml ± 0 interquartile range/IQR) until month 12 (median 22.8 µl/ml, 10.0 IQR), while ADA levels decreased (50.6 AU/ml, 48.3 IQR and 0.0 AU/ml, 0 IQR at baseline and month 12, respectively). Clinical remission at month 12 was observed in 27% and biochemical remission in 38% of patients with active Crohn's disease at baseline. 67 % of patients with clinical inactive Crohn's disease at baseline remained in clinical remission until month 12.

Conclusion

Subcutaneous infliximab after previous failure and immunogenicity of intravenous infliximab was well tolerated and effective in a cohort of patients with refractory Crohn’s disease.Read more N07 JAKne: JAK inhibitor associated acne, a real-life single-center experienceWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Three Janus kinase (JAK) inhibitors, tofacitinib (TFC), filgotinib (FIL) and upadacitinib (UPA), have been approved for treatment of Crohn’s disease (CD) and/or ulcerative colitis (UC). During the IBD registrational trials, acne was reported as adverse event (AE) in 5-7% of UPA treated patients, but not in the FIL and TFC programs. Hence, we assessed the prevalence of JAK inhibitor associated acne in a real-life cohort.

Methods

All patients initiating JAK inhibitors for active moderate-to-severe CD or UC at our center were included. Patients were prospectively monitored at prespecified timepoints, and specifically assessed for AEs including acne. Affected patients completed a visual analogue scale (VAS) to assess the impact of acne on their quality of life. All pictures of skin lesions were assessed by a dermatologist specialized in inflammatory skin diseases.

Results

In total, 46 patients initiated TFC, 40 FIL and 79 UPA. None of the TFC or FIL treated patients reported new onset of acne. Instead, 17 (21.5%) patients (9 CD, 8 UC; median [IQR] age 28.2 [25.2-45.0]; 47.1% female) spontaneously reported acne during UPA therapy. Most (89.5%) reported new onset of acne, while 2 (10.5%) mentioned a deterioration of existing acne during UPA induction. Previous acne during adolescence was reported by 46.2%. Lesions were present in the face (82.3%), back (23.5%), chest (23.5%) and scalp (11.8%). The acne phenotype included inflammatory papules in all patients, but also pustules (66.7%), nodules (33.3%), cysts (11.1%) and comedones (11.1%) were observed. A median VAS score of 5.5 [5.0-7.0] highlighted the impact on the patient’s quality of life, though no patient interrupted UPA due to acne. Six (35.2%) patients were referred to a dermatologist for acne. Most patients (82.4%) received topical skin therapy during UPA induction based on a standard operation procedure approved by the dermatologist and communicated via the IBD nurses. Three patients (17.6%) received antibiotics during UPA induction because of acne. During UPA maintenance, 5 patients (29.4%) reported resolution of skin problems with only 1 requiring continued skin therapy. Ten patients (58.7%) continued topical skin therapy during maintenance, with 4 of them requiring continued antibiotic treatment for at least 3 months. A single patient was deescalated from UPA 30mg to 15mg QD because of severe acne, with little improvement.

Conclusion

In this real-world experience, JAK inhibitor associated acne was uniquely linked to UPA, occurring in one fifth of patients. This is more prevalent than observed in the registrational trials. Awareness and patient education are therefore important, as well as early referral to the dermatologist for appropriate treatment.Read more P1044 Mirikizumab Pharmacokinetics and Exposure-Response in a Phase 2 Study in Patients With Moderately to Severely Active Crohn’s DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Mirikizumab (miri) is a humanized anti–interleukin-23-p19 monoclonal antibody approved for the treatment of ulcerative colitis (UC) and under development for Crohn’s disease (CD). This analysis characterises miri pharmacokinetics (PK) and the relationship between miri exposure and efficacy response using data from a phase 2 trial in adults with moderately to severely active CD.

Methods

AMAG was a randomised, double-blind, placebo-controlled trial conducted in 14 countries. Patients received placebo, miri 200 mg, 600 mg, or 1000 mg as induction regimens administered intravenously (IV) every 4 weeks (Q4W) through Week 12, followed by 36 weeks of maintenance treatment with continuous treatment of miri 200 mg, 600 mg, or 1000 mg IV or miri 300 mg administered subcutaneously (SC) Q4W. PK parameters were analysed by non-linear mixed-effects modelling. Covariate effects on miri exposure were evaluated using simulation-based estimations. Exposure-response (ER) for patients achieving endoscopic response by Simple Endoscopic Score for Crohn’s Disease (SES-CD) at Weeks 12 and 52 were assessed using logistic regression models.

Results

186 patients were included. The estimated systemic clearance (CL), central volume of distribution (V), and SC bioavailability (F) were 0.022 L/hr, 3.31 L, and 33.4%, respectively. Lower baseline values for SES-CD (indicative of a less severe CD) were associated with reduced CL. Lower body weight and higher albumin levels were also associated with reduced CL. Higher body weight was associated with higher V and lower baseline body mass index correlated with higher SC F. Impacts on PK parameters were small relative to random variability and not considered clinically relevant. The model-based ER analyses for endoscopic response probability at Week 12 detected a significant treatment effect relative to placebo (p<0.001) and a significant ER (p=0.001) in a dose range of 200-1000 mg. The ER analyses indicated near maximal efficacy for IV dose between 600 mg and 1000 mg during the Induction Period. There was no significant relationship between miri exposure and the probability of achieving endoscopic response by SES-CD at Week 52, indicating exposures produced by the maintenance doses provided similar efficacy.

Conclusion

Miri PK characteristics in adults with active CD were consistent with miri UC studies. Overall, none of the covariates identified as being significantly correlated with miri PK parameters were considered clinically relevant. No patient factors evaluated in this analysis justify dose adjustment. These findings support the miri induction dose 900 mg IV Q4W and maintenance dose 300 mg SC Q4W selected for phase 3 CD study.Read more N08 Awareness of Inflammatory Bowel Disease-associated Colorectal Cancer risk and its management in patients with Inflammatory Bowel Disease: a systematic reviewWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Inflammatory bowel disease (IBD) increases the risk of colorectal cancer (CRC). Although literature exists on patients’ general IBD knowledge, little is known about IBD patients’ awareness of CRC risk. This systematic review aimed to explore the literature on IBD patients’ knowledge, attitudes, and awareness of CRC risk and its management.

Methods

Medline, EMBASE, and PubMed databases were searched from inception to November 2023. All study designs and publication types were included. Non-English articles and those assessing general IBD knowledge were excluded. Cochrane’s ‘checklist of items to consider in data extraction’ was adapted for data extraction and the appraisal tool for cross-sectional studies (AXIS) was used to appraise the quality of included studies. All data relevant to the review question were extracted from the included studies and were thematically analysed for main themes.

Results

Twenty-three studies (17 full papers and 6 conference abstracts), including 4674 participants (2481 Ulcerative Colitis, 53.5% females) were included (PRISMA diagram Figure 1). The quality of included studies ranged from moderate to low. Overall, 18 studies reported CRC risk knowledge, 3 studies reported patients’ knowledge of CRC symptoms and risk factors, 7 reported attitudes towards cancer screening and 8 reported patient knowledge or attitude towards colectomy for dysplasia. The review found that IBD patients were moderately aware of the CRC risk, poorly aware of the symptoms and risk factors for CRC, and moderately feared this complication of IBD. Most overestimated their own risk of CRC and wanted more discussion with health professionals. Although the role of colonoscopy in cancer screening and diagnosis was well known, patients expressed mixed attitudes towards it due to the unpleasantness of bowel preparation, discomfort, or fear of colonoscopy complications. Low awareness of screening initiation time and varied willingness to undergo colectomy for dysplasia, irrespective of the extent of risk, was reported. Surgery was reported to be a last resort.

Conclusion

Limited literature exists on IBD patients’ awareness of CRC risk and its management to confidently infer the level of awareness and extent of educational needs of IBD patients. More research is needed to establish patients’ understanding of CRC risk and to optimise management.Read more P1045 Comparative Efficacy of Fecal Microbiota Transplantation for Clostridioides Difficile Infection in Patients with and without Inflammatory Bowel Disease: A Retrospective Cohort StudyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Clostridioides difficile infection (CDI) significantly exacerbates and worsens the prognosis of inflammatory bowel disease (IBD). While fecal microbiota transplantation (FMT) is recognized as a safe and efficacious therapy for patients battling recurrent or refractory CDI, but comparative studies focusing on the success rates in IBD and non-IBD patients remain scarce. Our study aims to shed light on this gap in knowledge.

Methods

In this retrospective cohort study conducted at Chang Gung Memorial Hospital between April 2019 and February 2023, patients undergoing FMT via colonoscopy for recurrent or refractory CDI were enrolled. Participants were categorized into IBD and non-IBD groups based on their underlying conditions. We compared baseline characteristics and clinical outcomes at one-month and one-year follow-up intervals. CDI diagnosis was confirmed through positive CD toxin A/B genes and associated clinical symptoms. Donor specimens were sourced from Chang Gung Microbiota Therapy Center's fecal bank.

Results

Our study included 88 patients who received FMT, comprising 30 in the IBD group and 58 in the non-IBD group. The indications were recurrent CDI in 31 patients, refractory CDI in 54, and both conditions in 3 patients. Among the IBD subgroup, 20 patients had ulcerative colitis, and 10 had Crohn's disease. In the baseline comparison, the IBD group was significantly younger (mean±SD, 45.23±16.45 years vs. 61.90±24.40 years, P = 0.001) and had fewer comorbidities such as hypertension (10.0% vs. 55.2%, P < 0.001), diabetes mellitus (6.7% vs. 31.0%, P = 0.014), and cancer (3.3% vs. 31.0%, P = 0.012) than the non-IBD group. Additionally, the IBD group had less prior Fidaxomin use (6.9% vs. 26.3%, P = 0.021) and fewer HMG-CoA reductase inhibitor users (0.0% vs. 15.5%, P = 0.025). Post-FMT, IBD severity indices showed significant improvement at one month. The mean partial Mayo score in the IBD group decreased by 2.9 points, the endoscopic Mayo subscore decreased by 0.7 points, and the Crohn’s Disease Activity Index decreased by 79.98 points. At this time, the IBD group showed a similar percentage of negative CDI toxin A/B tests (83.3% vs. 63.8%, P = 0.174) but had lower clinical remission rates (79.5% vs. 96.5%, P = 0.006) compared to the non-IBD group. However, at the one-year follow-up, the eradication rate (94.4% vs. 73.9%, P = 0.112) and clinical remission rate (84.2% vs. 90.3%, P = 0.661) were comparable between both groups. No safety issues or adverse effects were reported in any of the patients.

Conclusion

FMT demonstrates safety and efficacy in treating recurrent or refractory CDI in both IBD and non-IBD patients, also aiding in mitigating IBD-associated inflammation.Read more N45 Nurse intervention in patients with Inflammatory bowel disease: impact in their quality of lifeWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Physical inactivity is considered as a modifiable risk factor in chronic diseases¹ and IBD. Regular physical activity could help patients with IBD by reducing some IBD complications, such as improving immune response, increasing muscle mass and strength, and improving bone density.The aim of this study is to determine the impact of a Nurse intervention, on Physical Activity, in quality of life of IBD patients.

Methods

Quasi-experimental study before and after. 20 patients, both sex, with IBD from Hospital Universitario del Henares, 18-65 years old, in clinical remission or mild activity; IBD ≥ 6 months. Exclusion: physical impairment for daily activities (cardiac, orthopedic or cognitive impairment); pregnancy; surgery < 3 months.Nurse intervention on physical exercise: 4 group sessions of 60 minutes, 10 months follow-up. Training on strength and endurance exercises by a physiotherapist adapted to each patient’s special needs.Data were collected in Inflammatory Bowel Disease Questionnaire 32 (IBDQ-32), Rapid Assessment of Physical Activity (RAPA), Hospital Anxiety and Depression Scale (HADS). Variables: quality of life, physical activity, IBD activity, socio-demographic, health status and lifestyle. A descriptive analysis was carried out with qualitative and quantitative variables. Four dimensions of quality of life index and impact of exercise on quality of life were calculated, before and after intervention with Students-T.

Results

Quasi-experimental study before and after. 20 patients, both sex, with IBD from Hospital Universitario del Henares, 18-65 years old, in clinical remission or mild activity; IBD ≥ 6 months. Exclusion: physical impairment for daily activities (cardiac, orthopedic or cognitive impairment); pregnancy; surgery < 3 months.Nurse intervention on physical exercise: 4 group sessions of 60 minutes, 10 months follow-up. Training on strength and endurance exercises by a physiotherapist adapted to each patient’s special needs.Data were collected in Inflammatory Bowel Disease Questionnaire 32 (IBDQ-32), Rapid Assessment of Physical Activity (RAPA), Hospital Anxiety and Depression Scale (HADS). Variables: quality of life, physical activity, IBD activity, socio-demographic, health status and lifestyle. A descriptive analysis was carried out with qualitative and quantitative variables. Four dimensions of quality of life index and impact of exercise on quality of life were calculated, before and after intervention with Students-T.

Conclusion

There are non-significative differences in quality of life before and after intervention. Patients increased their physical activity after intervention. Regular physical activity is a useful tool for improving quality of life in patients with IBD.Read more P1028 Clinical decision support tool for vedolizumab can predict treatment persistence in Crohn's disease but not in ulcerative colitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Vedolizumab (VDZ) has displayed up to 82.9% treatment persistence as a first-line biologic for ulcerative colitis (UC) and ranked third in the second line. It ranked fourth in treatment persistence as the first or second-line biological therapy in Crohn's disease (CD). Factors most commonly associated with treatment outcomes have been indicators of more aggressive disease, like refractoriness to corticosteroids and tumour necrosis factor (TNF) alpha inhibitors, elevated baseline patient-related outcomes (PROs), comorbidities in CD and faecal calprotectin. Pre-treatment prediction of response and long-term persistence could help optimise treatment in an individual patient.

Methods

We performed a retrospective single-centre cohort study based on the UR-CARE registry. Data for 129 patients treated with VDZ from July 2016 until April 2023 were analysed. A validated clinical decision support tool (CDST) for CD and UC was used to stratify patients according to the probability of response to VDZ. We used Kaplan-Meier survival curves to analyse treatment persistence at week 52, depending on the CDST group for CD and UC. The association between the CDST group and the optimisation of VDZ therapy was evaluated using the chi² test.

Results

The study included 57 CD patients, median age 34 years, 38.6% male, and 72 UC patients, median age 32.1 years, 59.7% male. Patients with CD had longer disease duration (4.1 years) than UC patients (2.6 years). 33.3% of CD patients had ileo-colonic disease, 24.6% had upper GI involvement, 33.3% had fistulising disease, and 56.1% had prior surgery. 63.9% of patients with UC had pancolitis, and 34.7% had concomitant corticosteroids at baseline. Before VDZ, more than half of patients were exposed to TNF alpha inhibitors in both CD and UC (57.9% and 52.8%, respectively). We found significantly higher treatment persistence in CD patients stratified into groups with intermediate (group 1) and high (group 2) probability of response, according to CDST compared to the group with low (group 0) probability of response. The VDZ therapy was discontinued in 76.9%, 28.6% and 6.3% of patients within CDST groups 0, 1, and 2, respectively. The association was statistically significant (p < 0.001). In UC, however, we could not confirm any significant difference in treatment persistence between CDST groups. The VDZ therapy was discontinued in 50.0%, 34.9%, and 21.9% in groups 0, 1, and 2, respectively. While the trend between discontinuation of the VDZ and CDST groups can be observed, the association was not statistically significant (p = 0.165).

Conclusion

In our study, treatment persistence for VDZ could be predicted using CDST for CD, but not for UC.Read more N46 Stress after an Ulcerative Colitis diagnosis: examining the role of psychological factors in Ulcerative Colitis using Interpretative Phenomenological AnalysisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

People with ulcerative colitis (UC) report higher levels of stress, anxiety, and depression than the general population. 89% of people with IBD in the UK surveyed in 2019 said they found coping hard. However, most relevant research relies on generic stress questionnaires which ignore confounders typical in UC, such as fatigue. This study aims to provide rich, detailed accounts of how individuals encounter stress after a UC diagnosis.

Methods

An hour-long, semi-structured interview was conducted in January 2022 with a 76-year-old man, reporting high levels of perceived stress and diagnosed with UC three months previously. He was asked about stressors, coping and support during UC diagnosis and beyond. Interpretative Phenomenological Analysis (IPA) examines the detailed, unique interpretation of a significant experience to an individual. IPA methodology follows four stages: exploratory notes; formulating Experiential Statements (ESs) summarising the meaning of the experience to the interviewee; connecting similar ESs and developing Personal Experiential Themes (PETs), the three to five most important elements of the participant’s experience.

Results

Four PETs were formulated:My UC needs a positive, practical mental approach, not an emotional oneMixed experience with healthcare services affected my anxiety and disease managementMy UC symptoms and overall health affected my emotional well-being and copingI believe there is an absence of evidence on UC’s causes, cure, or helpful lifestyle changesThe interviewee didn’t "dwell on these things" although he felt "it’s another thing and I’m going to have to deal with this long term". He "could email the nurse there if I had any problems and I did at one stage and got an instant reply" but at other times he felt "abandoned here because nobody is taking me seriously. I keep phoning these people up, they keep passing me to other people". He had developed "strategies to cope with being diagnosed" but was surprised "nobody seems to know why [UC onset] happens. There isn’t a cure for it. They don’t seem to know what causes these flare-ups etc. etc. and all we know is that it’s going to carry on."

Conclusion

Our interviewee described his symptoms and existing health and healthcare services as stressors, his family and clinicians’ support, his practical, unemotional approach to coping and the need to keep positive. IPA comprehensively captured the interviewee’s interpreted experiences after an UC diagnosis, charting nuanced relationships between stressors, support, and coping. Our study will analyse a further nine individuals’ experiences of stress in the year after an UC diagnosis to inform development of an intervention enhancing resilience to stress.Read more P1029 Prevalance and risk factors of thromboembolism in Inflammatory Bowel DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Inflammatory bowel disease (IBD), as a chronic inflammatory condition, can affect atherosclerotic process, arterial events, and increase the formation of venous thromboembolism. The aim of this study was to determine the frequency of thromboembolism and the risk factors associated with acute thromboembolism in our IBD cohort.

Methods

A total of 3133 patients with 1414 Crohn's Disease (CD), 1667 Ulcerative Colitis (UC) and 52 Indeterminate Colitis who were admitted between 1999 and 2021 were retrospectively analyzed. Patients with acute arterial events and venous thromboembolism (n=39) during the follow-up period were compared with a control group (n=78) of the same gender and same diagnosis. Patients with Behçet's syndrome (n=126),systemic vasculitis (n=16) and hereditary thrombophilia (n=5) were excluded.

Results

Among 3133 IBD patients, number of patients with arterial events or venous thromboembolism at any time was 124, and the frequency was 3,95%. A total of 132 thromboembolic events, 86 arterial (65,2%) and 46 venous (34,8%) were recorded.Coronary artery disease was significantly higher in the UC group (2,3% vs. 1,2%; p=0.028). During follow-up, 40 acute thromboembolic events, 25 arterial and 15 venous, were seen in 39 patients (frequency 1,24%). There was no significant difference between the CD and UC groups in terms of acute thromboembolism (p=0.871). The presence of exacerbation, the presence of hospitalization, the number of priot hospitalizations and clinical activity at the last visit were associated with both arterial and venous thromboembolism; smoking history, age at diagnosis, body-mass index, non-mucosal CD (Montreal B2-B3) and higher basal CRP were associated with arterial thromboembolism only; higher CRP at the last visit, annual exacerbation frequency, presence of an additional inflammatory disease, presence of complications (surgery, abcess), longer total steroid traetment duration and also recent steroid therapy were associated only with venous thromboembolism. In regression analysis, recent steroid therapy and additional inflammatory disease were considered as independent risk factors for venous thromboembolism whereas age at diagnosis of IBD was considered as an independent risk factor for arterial events.

Conclusion

In addition to risk factors such as age, smoking and obesity, parameters indicating disease activity, inflammatory comorbidities and recent steroid therapy appear to be associated with acute thromboembolism in IBD patients.Read more N47 Spiritual needs of patients with IBD: preliminary results of a pilot studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Inflammatory bowel disease (IBD) includes Crohn's Disease (CD) and Ulcerative Colitis (UC), and both lead to manifestations that affect the patient's quality of life (QoL). The issue of chronicitỳ makes the disease difficult to manage and requires a radical change in patients’ habits, leading to a decrease in QoL after diagnosis. The literature emphasises how spiritualitỳ positively influences the psychophysical well-being of chronic patients and consequently their QoL.This study aims to describe the spiritual needs of patients with IBD to promote holistic care and improve their QoL and aims to explore their eventual association with sociodemographic and clinical variables.

Methods

A cross-sectional study was carried out in the outpatient gastroenterology clinics of a university hospital, administering the validated Spiritual Needs Questionnaire (SpNQ) during outpatient follow-up visits to patients over 18 years of age after informed consent to participate in the study. The SpNQ consist of 27 items divided into four domains: Religious needs, Needs for Inner Peace, Existential needs, and Giving/Generativity Needs. Some clinical and sociodemographic data were also collected.

Results

A total of 103 completed the questionnaire: 53% had CD, 35% UC and 12% had undetermined IBD. 44% were males the median age was 45 years, and half of the sample was more than 10 years from IBD diagnosis. More than 40% were in biologics, 47% had a high educational level, 28% were smokers, and 4% had a stoma. 65% were Christian, 26% had no religion, and the frequency of their participation in religious gatherings varies from never (15%), to rarely (59%) and often (26%).They cultivate their spirituality mainly by conducting their existence in accordance with values that are fundamental to them (47.7%), staying in contact with nature (30.5%), praying (15.8%), engaging in introspection and self-knowledge (14.7%), volunteering (12.6%), and practising extreme sports (10.5%).The analyses showed statistically significant differences between sexes regarding the domains "Needs for Inner Peace" and "Religious Needs" (p<0.001) more relevant to women than men, and significant differences between ages regarding the domains "Existential Needs", more relevant to middle age (p=0.037), and "Giving/Generativity Needs", more relevant to middle age and to elderly (p=0.015).

Conclusion

Spiritual needs may play a major role in the care of patients with IBD, and nursing should consider this dimension to improve the holistic care of the patients. Research should be expanded through studies involving a larger sample size and evaluating the IBD outcome by acting on spiritual needs.Read more P1038 Does combination immunomodulator therapy impact real-world biologic effectiveness in Inflammatory Bowel Diseases?A propensity score analysis in patients treated with anti-TNF and non-anti-TNF biologics in the UK IBD BioResourceWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Randomised controlled trials have demonstrated that the combination of infliximab and azathioprine is superior to either drug as monotherapy both in patients with Crohn’s Disease (CD) and ulcerative colitis (UC). Data on the combination of other biological agents -including other anti-TNFs, vedolizumab and ustekinumab- and immunomodulators (IMMs) is lacking or shows conflicting results. Given the risks of combination therapy, physicians are often hesitant on whether to combine IMMs with biologic therapies.

Methods

We measured the effectivenessof biologic therapies [infliximab (IFX), adalimumab (ADA), golimumab (GLM), vedolizumab (VDZ) and ustekinumab (UST)] in patients with UC and CD with and without IMM use enrolled in the UK Inflammatory Bowel Disease (IBD) BioResource over long durations of followup.Demographic, disease, treatment and outcome data were retrieved. Inverse probability of treatment weighting (IPTW) was used to balance groups of those receiving vs those not receiving IMM using a propensity score-weighting approach accounting for baseline patient or disease related clinical characteristics. Effectiveness of treatment was based on persistence free of treatment discontinuation or treatment failure. Failure was defined as occurring if any of the following occurred: (a) clinician-recorded treatment failure (b) start of treatment with a different advanced therapy (c) occurrence of resectional or defunctioning bowel surgery. We compared Kaplan Meier curves for treatment failure-free survival after IPTW and used a log rank test for differences between the groups.

Results

In UC, we included 2479 patients receiving IFX (1173 on IMM), 1117 ADA (401 on IMM), 188 GLM (77 on IMM) and 1256 VDZ (392 on IMM). In CD, we included 5956 patients receiving IFX (3062 on IMM), 4524 ADA (1898 on IMM), 1067 VDZ (340 on IMM) and 627 UST (198 on IMM).As expected, combination IMM therapy was associated with increased drug effectiveness for IFX in both UC and CD. Combination IMM therapy was also associated with increased effectiveness of ADA in CD. For all other drugs, there was no significant benefit for combination IMM. Hazard ratios(HRs) for the effect of IMM of each drug effectiveness in UC and CD are summarised (Figure 1).

Conclusion

We confirm prior results indicated that IFX effectiveness is improved by concomitant use of an IMM in both UC and CD.In contrast to RCT data but in accordance to other robust real-world studies, we find evidence that for ADA in CD concomitant IMM can increase drug effectiveness. We find no evidence of benefit for concomitant IMM for other biologics in UC or CD.Read more N48 Exploring & evaluating the benefits of initiating an IBD Transition clinicWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Establishing an Inflammatory Bowel Disease (IBD) Transition Clinic can bring about several significant benefits. This includes providing continuity of care, specialised care, education in new treatment, emotional support, collaboration and coordination of care, empowering patients and assisting in adherence to medication and follow up appointments. In the author's history within the Trust there has never been an established IBD Transition clinic. This has led to young adults delayed in transitioning to adult services without any formal handover.

Methods

The IBD Consultant Nurse felt that the young adults were given a second class service and that they were not receiving the care and advice that they needed in the difficult time of being a young adult with a long term condition. They enlisted the help of a paediatric gastroenterologist and worked with the paediatric operations team and a cohort of patients were booked into a three monthly clinic held on a Saturday as this was felt the best day for engaging both patients and family. The paediatric gastroenterologist and IBD Consultant Nurse undertook the clinic jointly.

Results

A number of clinics were undertaken and the IBD Consultant Nurse asked for all patients to be assigned to an adult gastroenterologist after the first appointment. At the joint clinic all medication was discussed and a personalised plan of care was adopted for all patients to allow a smooth transition into adult services. The feedback from patients and family members was extremely favourable and all patients felt that they had been given all of the required information, a personalised care plan and were prepared to be transitioned to adult care. All patients were given a post clinic questionnaire on their satisfaction of the Transition clinic. The clinic was recently stopped as a adult gastroenterologist felt that this should not have been undertaken by a nurse and that they can only be undertaken by doctors. The current waiting time to be reviewed by a gastroenterologist is currently around 65weeks which could lead to a delay in treatment.

Conclusion

Ideally establishing a nurse-led transition clinic requires collaboration among healthcare providers, administrative support, and resources dedicated to its development. Additionally, an emphasis on patient and family involvement in the planning and execution stages can lead to a more patient-centric and successful transition program. This clinic was extremely successful but has had to stop as the gastroenterologists feel that only gastroenterologists can undertake transition clinics and should not be nurse led. Unfortunately this will lead to transition patients having an extended delay into adult services.Read more P1002 De novo and drug-induced skin manifestations in Inflammatory Bowel Disease patients: The impact of anti-tumour necrosis factor therapyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Skin disorders in inflammatory bowel disease (IBD) consist of extra-intestinal manifestations (EIM) or drug-induced lesions. This study explores de novo skin lesions and the emergence of immune-mediated skin disorders induced by anti-tumour necrosis factor (anti-TNF) agents.

Methods

Patients with EIMs, de novo skin lesions, and drug-induced skin eruptions were identified from an IBD patient database on advanced therapies. Data on time intervals from the initiation of IBD treatment to the development of skin disorders, causative agents, and subsequent management were collected.

Results

In a cohort of 1,773 patients (993 with ulcerative colitis, 746 with Crohn’s disease, and 31 with IBD unclassified), 30% (549) exhibited skin manifestations, with 28% (491 cases) showing de novo skin conditions. Identified skin manifestations included psoriasis/psoriasiform rash (18.3%), eczema (16.3%), seborrheic dermatosis (13.8%), acne (9.8%), actinic keratosis (5.3%), rosacea (4.7%), erythema nodosum (EN, 3.5%), cutaneous Crohn's disease (CCD, 2.6%), folliculitis (1.8%), pyoderma gangrenosum (PG, 1.5%), and others. Of the skin lesions, 31.8% (175) occurred before the IBD diagnosis, with a median duration of 8 years, while 51.9% (286) developed post-diagnosis unrelated to therapies.Biologic therapies improved extraintestinal skin lesions in 19 patients (3.4%). Notably, all 3 EN cases and 4 out of 5 PG cases achieved full resolution with biological treatments, leading to improved IBD activity. Similarly, 9 out of 10 Crohn’s disease patients with CCD showed improved skin conditions following biological treatmentsFifty-eight patients (3.3%) experienced drug-induced skin lesions, with a median age at IBD diagnosis of 35 years (ranging from 17 to 67). The majority (91.3%) of cases were attributed to anti-TNF agents, and psoriasiform lesions were the most prevalent (60.3%). The median duration from treatment initiation to the onset of drug-induced skin lesions was 23 months (ranging from 0 to 115 months). Among the affected individuals, 19 using originator anti-TNF agents developed skin lesions, with 13 having psoriatic lesions. In comparison, 34 patients on biosimilar anti-TNF agents developed skin lesions, and 23 of them had psoriatic lesions. The progression of skin lesions led to anti-TNF discontinuation in 33 patients, of whom 25 transitioned to Vedolizumab or Ustekinumab. Resolution occurred in 22 patients.

Conclusion

Anti-TNF-induced skin lesions, notably psoriasiform lesions, appear to be more prevalent in the biosimilar era among IBD patients, often leading to discontinuation. Nevertheless, resolution is possible through strategic switches to alternative biologic agents.Read more ECCO Pioneer Award Functional assessment of the microbiome in persistent IBD-related psychological symptomsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background and Aims

It is well established that patients with inflammatory bowel disease (IBD) experience psychological comorbidities, and that these symptoms persist upon remission of the IBD in more than 50% of patients. The mechanisms underlying this clinical association are unknown, which hampers to objectify the problem and limits the possibilities to intelligently consider targeted treatments. We recently observed behavioral anomalies and neuroinflammation in a mouse model of extinguished chronic colitis, enabling the fundamental study of psychological symptoms in IBD. Fueled by technical evolutions to characterize translationally active bacteria at the single-cell level, their importance in colitis, and a proof-of-concept stool transplantation experiment, the purpose of this project is to determine if specific bacterial functions drive persistent neuroinflammation upon IBD remission.

Methods

First, a state-of-the-art flow-cytometry based method will be used to temporally map translationally active bacteria during the course of extinguished chronic colitis. Second, the same functional microbial analysis will be achieved in human fecal samples of IBD patients in remission before and after treatment for fatigue, and results will be compared with persistent bacterial changes found in mouse flora. Finally, causality of associated bacteria to induce neuroinflammation will be tested by transplantation studies of bacterial communities isolated from the previous tasks.

Anticipated Impact

This research may impact the field in the short-term by creating solid scientific awareness that psychological comorbidities are intrinsically linked with IBD remission, and by more specifically attributing a role for specific bacterial functions in these symptoms. In addition, the technique applied may open novel insights for the IBD microbiome community. In the medium-term, this project aims to shed light on the actual bacterial mechanisms that lead to neuroinflammation and behavioral anomalies, which in the long-term could help identify biomarkers for diagnostic purposes or microbiome-related targets to design rational therapeutics for patients with IBD suffering from psychological comorbidities.Read more P1046 Home calprotectin testing: An east London experienceWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Monitoring of inflammatory bowel disease (IBD) using home faecal calprotectin (FCP) testing kits was adopted widely during the Sars-Cov-2 pandemic. CalproSmart is a kit which allows patients to measure FCP at home and upload the results to a smart phone application allowing remote monitoring. Recent NHS long term recovery plan has highlighted the importance of ensuring equity of access with service development¹. Following the British Society of Gastroenterology guidance during the pandemic we introduced the system to our hospital in Newham, one of the most ethnically diverse regions of the UK². The aim of this pilot study was to evaluate the uptake of the kits, patient acceptability and how they impacted on IBD care.

Methods

62 patients with stable IBD were invited to take part in the study over a 12 month period. They were sent four FCP tests and instructions on how to enrol onto the CalproSmart portal. The participants who enrolled on the portal were then sent a post-study questionnaire.

Results

28 of the 62 patients invited (45%) enrolled onto the CalproSmart portal. 14 of these 28 patients (50%) completed the post-study questionnaire.The patients invited to take part were from a variety of ethnic backgrounds, the average age was 36 and there were a mix of Ulcerative Colitis (60%) and Crohn’s (40%) diagnoses. When comparing those invited and those who used the home kit, uptake varied according to gender and ethnicity. 57% of women invited used the home kit compared to 34% of males. Additionally, despite 69% of the borough’s population being non-white, 50% of those using the home tests were white (see table 1).The post –study questionnaire showed that both the sample kit and the application were found easy to use by 12 (86%) and 13 (93%) of the patients, respectively. 11 patients (79%) reported they found the results of the FCP home kit helpful and 6 patients (50%) felt the FCP home kit improved the treatment of their disease (see figure 1).10 patients (71%) reported they preferred a home test to dropping stool samples at the hospital. The reasons for this were the convenience of not having to visit the hospital (90%) and the speed in which they got the results (80%).

Conclusion

This study demonstrates that home FCP tests are an easy-to-use tool and patients prefer them to attending the hospital. The home kit was well received in a diverse area of London with a mix of ethnic groups and socio-economic backgrounds.However, the ethnicity of patients using the home tests did not reflect the diversity of the invited participants or the borough. This suggests there needs to be additional exploration into their barriers to access and consider any extra support needed to improve uptake of patient initiated monitoring.Read more ECCO Global Grant Genetic risk factors for IBD in its emergent phase in sub-Saharan AfricaWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background and Aims

Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), is an idiopathic, chronic, and frequently disabling inflammatory disorder of the intestines characterized by a dysregulated mucosal immune response. The pathophysiology of the disease remains incompletely understood. Genetic factors affecting disease are under investigation, however, genetic studies in non-European populations are scarce and it is an urgent scientific, social, and ethical requirement that research in under-studied populations is prioritized. The objective of this study is to understand the genetics of IBD in sub-Saharan African ancestry populations and to identify genetic factors that affect pathogenesis of IBD in this region.

Methodology

A case-control study will be conducted from January 2024 to December 2025. Consecutive eligible subjects with IBD and controls will be invited to take part in the study. Data will be collected through chart review, structured interviews, and collection of saliva samples for genotyping using the H3Africa chip in the first instance. Genome-wide imputation and replication analysis will be done. Single-marker association analyses will be performed using the Cochran Armitage trend and logistic regression test after correction for population structure. We will look at known European ancestry and African American (AA) IBD-associated variants as well as variants that are unique to our populations (we will be able to look at local admixture in the AA population to see if these variants are replicated).

Anticipated Impact

This study will contribute significantly to knowledge of genetic risk factors for IBD in sub-Saharan Africa. It may also help to identify potential complications of treatments such as thiopurines which have been commonly used in European populations but where experience of use in sub-Saharan Africa is lacking.Read more P1047 Observational study of tofacitinib in Ulcerative Colitis in Sweden (ODEN) – Interim analysis of health-related quality of life and fatigueWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Ulcerative colitis (UC) has a major impact on daily life. The Janus Kinas (JAK) inhibitor tofacitinib is effective in achieving remission in UC, but prospective real-world evidence concerning the effect on health-related quality of life (HRQoL) and fatigue are still scarce. Fatigue is a component of UC that is notoriously difficult to treat and not unambiguously related to inflammatory activity. ODEN is an ongoing Swedish multicentre prospective observational study of tofacitinib in UC. In this interim analysis, we assessed the effectiveness on HRQoL and fatigue during the first 16 weeks.

Methods

Patients with UC and active inflammation were enrolled 2020-2023 when starting tofacitinib as per clinical indication. To measure various aspects of impairment of daily life, the validated questionnaires Short Health Scale (SHS), EQ-5D-5L [Swedish value set], and IBD-fatigue scale (IBD-F) were used. These data and information concerning clinical, biochemical, and endoscopic outcomes were collected in an e-CRF linked to the Swedish National Quality Registry for Inflammatory Bowel Disease (SWIBREG). For HRQoL outcomes, per protocol analysis was applied. Paired t-test and Wilcoxon’s signed-rank test were used for mean and median differences, respectively.

Results

In total, 103 patients were included. Baseline data are shown in Table 1a. For patients still on tofacitinib treatment, all four dimensions of the SHS (symptoms, social function, disease related worry, and general well-being) improved significantly, Table 1b. A median decrease of one point from baseline was seen at week 8 in each of the parameters, which was maintained through week 16 with a tendency towards further improvement. EQ-5D-5L showed an impairment mainly in the aspects of pain/discomfort and ability to participate in common daily activities. Improvement in these dimensions was seen from baseline to week 16. The overall EQ-5D-5L index improved significantly from baseline (0.80) to week 8 (0.86) and week 16 (0.89), as did the EQ VAS 0-100 reflecting overall health (58, 71, and 74, respectively). A significant improvement in IBD-F part 1 and 2 was seen at week 8 and 16, Figure 1.

Conclusion

This study demonstrates that tofacitinib treatment covariates with positive changes in a variety of measures of patients’ quality of life, including improvements in self-assessed overall wellbeing. Finally, fatigue significantly improved during tofacitinib treatment. Thus, tofacitinib treatment shows association with meaningful improvements in multiple aspects of quality of life during the first 16 weeks of treatment.Read more ECCO Fellowship Effect of diet on disease development and faecal microbiota transplantation efficacy in humanized SAMP/Yit and DSS mice modelsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background and Aims

The gut microbiome and diet have been shown to be associated with IBD pathogenesis, and to be implicated as triggers in disease development. Increasing evidence shows that dysbiosis and Western diets may drive and sustain intestinal inflammation. Therefore, faecal microbiota transplantation (FMT) has been hypothesized to restore a balanced microbiome, leading to reduced inflammation and improved intestinal function.The mechanisms by which FMT exerts its therapeutic effects in IBD are not fully understood. Yet, FMT has shown promising effects in controlling disease in randomized controlled studies in UC. In contrast, data on FMT in CD are scarce and worsening of disease has even been described (Vermeire et al., 2016). Unfortunately, up to day, this different effect of FMT in UC versus CD remains unexplained.Therefore, the aim of this project is to evaluate the effect of FMT in a preclinical model of CD, and compare it to a UC-model and study the effect of ultra-processed Western diets.

Methods

The mice models which will be used include the acute DSS-induced colitis model for UC and the spontaneous terminal ileitis (SAMP/Yit) model for CD. Upon humanization of the mice with UC or CD patient’s stool, mice will be randomized to dietary interventions being a Western diet, a regular diet, or a Mediterranean diet. Subsequently, the mice will be randomized to receive either autologous (patient) FMT or one out of four healthy donor FMTs possessing different enterotypes.

Anticipated Impact

By evaluating, clinical endpoints, as well as microbiota and transcriptomic endpoints, this project will provide insights in the differences between FMT success in UC and CD, as well as in the importance of donor selection (enterotype matching) and additional effect of dietary interventions on inflammation. Herewith predicting that this project will aid to bring microbiota-targeted treatment strategies to the IBD clinic.Read more P986 Effectiveness of the adjuvanted recombinant zoster vaccine (RZV) in preventing herpes zoster (HZ) among patients ≥50 years of age with Inflammatory Bowel Disease in the United States: A retrospective real-world database analysis from 2018 to 2021Wed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Patients with inflammatory bowel disease (IBD) are at higher risk of developing HZ compared to general population.¹ The US Food and Drug Administration (FDA) approved RZV for adults ≥50 years of age (YOA) in Oct 2017 and for adults ≥18 YOA who are or will be at increased risk of HZ due to immunodeficiency or immunosuppression, as patients with IBD, in Jul 2021. This study addresses an information gap for RZV vaccine effectiveness (VE) in preventing HZ among IBD patients ≥50 YOA.

Methods

We conducted a retrospective matched cohort study using the Optum Clinformatics Data Mart healthcare administrative claims database from Jan 2018 to Dec 2021. Patients ≥50 YOA with IBD who received 2 RZV doses with dose interval ≥28 days (RZV [2-dose] cohort) were 1:3 matched to their unvaccinated counterparts (non-RZV cohort) by age, medication category, and other confounders (propensity score). The index date for RZV cohort was the date of the second dose and for non-RZV cohort was the same index date as their vaccinated match. Follow-up started from index date +30 days until earliest date of HZ occurrence, end of enrolment, death, receipt of HZ vaccine, or study end. The first HZ episode during follow-up was identified using an algorithm that included ICD-10 diagnosis code, inpatient or outpatient claims and/or HZ antiviral medication used within 7 days pre/post-HZ diagnosis. Incidence rates (IRs) of HZ were calculated overall, stratified by condition (ulcerative colitis [UC], Crohn’s disease [CD]) and age. Cox hazards models were used to estimate overall and stratified hazard ratios (HRs). VE (%) was calculated as (1−HR) × 100. A similar approach was used to evaluate VE for patients who received 1 RZV dose.

Results

We identified 6501 RZV vaccinated and 19962 matched unvaccinated IBD patients who were included in the 2-dose analysis (Table). The IR of HZ was 2.92/1000 person-years (PY) in the RZV cohort and 10.96/1000 PY in the non-RZV cohort, resulting in a VE of 73.4% (95% confidence intervals [CIs]: 60.8-82.0) for IBD patients (Figure). VE against HZ was 63.5% (95%CIs: 43.0-76.6) and 85.7% (95%CIs: 69.5-93.3) in UC and CD 2-dose cohorts. IRs and VE stratified by condition and age are presented in Figure. Adjusted VE for IBD patients who received 1 RZV dose was 63.4% (95%CIs: 24.9-82.2).

Conclusion

Our analysis provides real-world evidence that RZV vaccination is effective in preventing HZ in IBD patients ≥50 YOA and reduce the burden in this population with increased risk of HZ. These findings are consistent with the available literature on RZV effectiveness in patients with IBD, suggesting that this population could greatly benefit from RZV vaccination.1. Yun H et al, Arthritis Rheumatol 2016;68:2328-37

Funding

GSKRead more ECCO Fellowship Generation of an IBD single-cell multiome ATLAS for deeper understanding of IBD sub-phenotypesWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background and Aims

Inflammatory Bowel Disease (IBD) is one of the most prevalent gastrointestinal diseases worldwide (1, 2, 3). Disabling symptoms affect the quality of life of IBD patients, and incurred disability and healthcare costs result in a high socio-economic burden (1, 4, 5). Despite new biologicals and small-molecule drugs, patients deal with high rates of non-response, requiring therapy switching without evidence-based guidance on optimal therapy choices for each specific disease condition.

Methods

In an effort to better understand the disease pathomechanisms underlying IBD, an essential role has been played by single-cell RNA sequencing (scRNAseq). Two scRNAseq studies, one in Crohn’s disease (CD) (Martin e.a., Cell 2019), and one in ulcerative colitis (UC) (Smillie e.a., Cell 2019), characterized the molecular and functional heterogeneity of phenotypically similar IBD cases, and gave us the first clues on the mechanism underlying non-response to anti-TNFa. However, the statistical power of these studies is limited due to their small cohort sizes (6, 7, 8). To acquire further insights into IBD, and to definitively establish the mechanism underlying anti-TNFa non-response without having to generate costly new single-cell experiments, we propose harmonizing smaller IBD scRNAseq studies and performing large-scale meta-analyses. Specifically, our goal is to start with meta-analyzing four IBD scRNAseq datasets (two CD, each ~100 ind, and two UC, each ~30 ind) and to perform a powerful meta-analysis. To easily add more datasets we will create a pipeline for integrating scRNAseq data.

Anticipated Impact

The large meta-analysis will allow us to get more insight into the mechanisms underlying disease subphenotypes, and to get insight into the effect of commonly used IBD therapies (anti-TNFa, thiopurines) on the gut mucosal composition and inflammatory pathways. The datasets and related results will be made publicly available through a single-cell IBD ATLAS web interface, fulfilling the need for an easily queryable large IBD scRNAseq dataset.Read more P987 Impact of Crohn’s Disease Location on Biologic Therapy Persistence and the Risk of Intestinal Surgery: Insights from the ENEIDA Registry (the DISCOLOC Study)Wed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Crohn's disease (CD) presents differences in genetics, inflammatory components, and microbiota depending on its location. Therapy efficacy may be linked to disease location, but existing research has yielded conflicting results. This study aims to investigate the impact of CD location on first-line biologic therapy requirement and persistence and the risk of intestinal resections.

Methods

CD patients included in the prospectively maintained ENEIDA registry between January 2005 and May 2023 were considered for the study. Demographics, disease phenotype and location, complications, the utilization of biologic therapies, and intestinal surgeries were analyzed. Cox proportional hazards and Kaplan-Meier methods were used for the analysis of biologic requirement and persistence and risk of surgery.

Results

A cohort of 17,508 patients was included, with a median follow-up period of 6 years (IQR 2-10 years). The most common disease locations were ileal (43.3%) and ileocolonic (39%), with lower frequency for colonic (16.4%) and upper-gastrointestinal disease (1.2%). A first biologic was used in 54.5% of patients (n=9,543), with a higher 5-year requirement in ileocolonic disease compared to ileal and colonic disease (60.1% vs 53% vs 49.9%, p<0.001). Ileal disease presented the lowest 5-year persistence rate compared to ileocolonic and colonic location (39% vs 41.6% vs 45.1%, p=0.004). Ileal location (aHR 1.084, 95%CI 1.006-1.167), female sex (adjusted Hazard Ratio [aHR] 1.173, 95%CI 1.096-1.254), extraintestinal manifestations (aHR 1.163, 95%CI 1.080-1.251), a history of abdominal surgery (aHR 1.539, 95%CI 1.426-1.661) were independent predictors of drug discontinuation. The cumulative need for intestinal resections was 25.8% (n=4,512), with ileal disease showing the highest hazard for 5-year surgery compared to ileo-colonic and colonic location (19.5% vs 17.8 vs 8.3%, p<0.001). Ileal disease (aHR 1.194, 95%CI 1.101-1.295), stricturing (aHR 2.575, 95%CI 2.378-2.787) and penetrating phenotypes (aHR 2.485, 95%CI 2.261-2.734), a history of biologic therapy (aHR 1.386, 95%CI 1.262-1.522) and smoking (aHR 1.089, 95%CI 1.004-1.180) were independent predictors of intestinal resections. Survival analysis for biologic requirement, persistence, and the risk of intestinal resections is illustrated in Figure 1.

Conclusion

Ileal disease is associated with a higher requirement for biologic therapy, showing the poorest persistence. It also demonstrates the highest probability of intestinal resections among CD locations. These findings provide valuable insights into tailoring treatment strategies based on CD location.Read more P1075 Outcomes in patients stopping biologic during the first trimester of pregnancy : a retrospective monocentric studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Both the American Gastroenterological Association (AGA) and the European Crohn's and Colitis Organisation (ECCO) recommend to continue biologic during the whole pregnancy and until the third trimester, respectively. However, these positions are associated with a baby's exposure to the drug and from our clinical practice are not necessarily in line with patients' wishes and fears. In patients in full clinical and biologic remission, stopping biologic before it is actively transported through the placenta (around the week 20) would be a possible approach to get around these drawbacks. We aimed to assess the outcome of disease activity and pregnancies in patients stopping biologic before the week 20.

Methods

We performed a retrospective monocentric study. All patients who gave birth between 2010 and 2023 were included. The following parameters were collected: clinical and demographic characteristics, biomarkers (CRP and faecal calprotectin before pregnancy and during the 3 trimesters), IBD treatment at time of pregnancy, whether it was stopped during pregnancy, when and in what circumstance (patient versus medical agreement). We also looked at the disease course, whether a relapse occurred (defined as the need to take corticosteroids, a biologic, or surgical resection), and the pregnancy outcome.

Results

A total of 185 pregnancies were reported in 143 patients (73.4% Crohn disease and 26.6% ulcerative colitis). Patient's characteristics are shown in Table 1. Among these women, 106 (74.1%), 32 (22.4%) and 5 (3.5%) reported one, two or 3 or more pregnancies, respectively. Figure 1 summarises the treatments during these reported pregnancies, disease activity outcomes and pregnancy outcomes. The biologic was stopped before conception for 9 pregnancies and 90 pregnancies started under biologics (anti-TNF, vedolizumab or ustekinumab). Of these, biologic was continued until delivery in 10 (11.1%) patients, whereas it was stopped before the week 20 for the others (88.9%). Among patients who stopped biologics before conception, before the week 20, and those who continued biologics through delivery: 3/9 (33.3%), 13/80 (16.3%; including 10/66 or 15.2% among those stopping on medical agreement) and 4/10 (40%) relapsed, respectively. Among the 10 relapses in patients who stopped in first trimester on medical agreement, 6 had normal biomarkers before cessation (unknown for the others).

Conclusion

Biologic discontinuation before week 20 on medical agreement was associated with relapse in 15.2% of cases. Fate of disease activity and pregnancies in patients stopping biologic before week 20 should be studied prospectively in a dedicated study.Read more P988 Preliminary report on short-term post-operative outcomes of robotic versus laparoscopic approach for restorative procto-colectomy with ileal-pouch-anal anastomosis in ulcerative colitis: a comparative studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Restorative proctocolectomy with ileal pouch–anal anastomosis (IPAA) performed in two or three stages has become the standard surgical treatment in patients with ulcerative colitis (UC) in which the medical management fails. It is a technically complex operation associated with significant morbidity that can be performed with a laparoscopic or robotic approach. Robotic colorectal surgery is gaining popularity because it overcomes many of the mechanical and optical disadvantages of laparoscopy, although limited data are available regarding its safety, efficacy, and costs. This study compares the postoperative short-terms surgical outcomes of the two surgical approaches.

Methods

Robotic and laparoscopic restorative proctocolectomy procedures with IPAA consecutively performed between June 2015 and May 2023 were retrospectively collected. Inclusion criteria was UC not responders to medical therapy. Exclusion criteria was conversion to open surgery. Primary analyzed outcome were complications rate in the first month (30 days) according to Clavien Dindo Score and length of hospital stay (days). Statistical analysis was performed with a dedicated software (SPSS).

Results

A total of 54 patients with UC refractory to medical therapy were included, with 31 laparoscopic procedure and 23 robotic procedures.Demographic data were comparable between two groups in terms of age (48.7 vs 45.7 years; p= 0.62), BMI (22,0 vs 23,7 Kg/m2; p= 1.311) and ASA score (p=0,72).Short-term complications defined as Clavien Dindo scores 2-3, (compared with score 1) were 13% in the robotic group and 31% in the laparoscopic group (RR= 0.27, 95% conf. interv. 0.11-1.06). In particular, no high-grade Clavien-Dindo complications occurred in the robotic group while 3 events (grade 3) occurred in the laparoscopic group. No surgical reintervention was needed in both groups.Length of hospital stay was a mean of 7.3 days in lap-group and 6.3 days in rob-group with no statistical significativity (p=0,09).

Conclusion

This preliminary study concludes that robot-assisted surgery allows a reduction of short-term complications compared to laparoscopic approach. Moreover, robotic surgery allows a reduction of length of hospital stay although not statistically significant. Limits of the study were the retrospective design and the low numerosity of the sample, although comparable with the experiences already published.Read more P868 Patients with inflammatory bowel disease who are intolerant to thiopurine treatmentWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Approximately 15-40% of patients with inflammatory bowel disease (IBD) treated with thiopurines experience side-effects that leads to drug withdrawal. The aim of this retrospective observational study was to compare patients who stop thiopurine treatment due to side effects with patients who tolerate thiopurine treatment in the use of other IBD treatments, the risk of surgery and in the chance of reaching remission (a median faecal calprotectin level < 200 mg/g).

Methods

We included all patients in our clinic who were born after 1956 and diagnosed with Ulcerative colitis (UC) and with Crohn´s disease (CD) after the year of 2006 (n=698). In the patients who at least once started thiopurine treatment, prescription of IBD drugs, surgery and f-calprotectin values were noted for the first five years after start of thiopurine treatment. Patients who stopped treatment due to intolerance (side effects) was compared to patients who were tolerant to thiopurine treatment (no side-effects reported).

Results

The proportion of patients with IBD who initiated thiopurine treatment at our clinic was 44% (32% UC and 64% CD). For patients who started thiopurine treatment 31% (n=94) had to stop treatment within five years due to side effects. Patients who stopped thiopurine treatment due to intolerance were significantly older (median age 32 vs 25 years, p=0.002), were significantly more often on steroids (89% vs 76%, p=0.009) and used to a lesser extent TNF inhibitors at the start of thiopurine treatment (3% vs 9%, p=0.062). There were no statistically significant differences in the proportion of patients that at least once yearly used steroids, TNF-inhibitors or surgery in the first five years after initiated thiopurine treatment between the group of patients who stopped due to intolerance and the group of patients who were tolerant to thiopurine treatment. Budesonide treatment and non TNF-inhibitor biologic therapy was significantly more common used in the patients that stopped thiopurine treatment due to side-effects. The proportion of patients with a median faecal calprotectin >200 mg/g was significantly higher in the patients with UC who stopped thiopurine treatment due to side effects (Figure).

Conclusion

Patients who stopped thiopurines due to side-effects did not in general differ in the use of other treatment for IBD the first five year after initiated thiopurine treatment, except for the use of budesonides and non-TNF inhibitor biologics which was more commonly used in patients who stopped thiopurines due to side-effects. Patients with UC who stopped treatment due to side-effects had higher faecal calprotectin levels at follow-up than patients who tolerated thiopurines.Read more P1018 Population pharmacokinetic and exposure-response analyses for efficacy and safety of risankizumab in subjects with moderately to severely active Ulcerative ColitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Risankizumab (RZB) has been evaluated in subjects with moderately to severely active ulcerative colitis (UC) in the INSPIRE and COMMAND trials. Population pharmacokinetic (PPK) and exposure-response (ER) analyses were conducted at the end of Phase 2b and following Phase 3 to characterize RZB PK and its relationship with clinical efficacy and safety to support Phase 3 induction dose selection, and the final dose recommendations for induction and maintenance treatment.

Methods

PPK analyses in UC used a previously developed PPK model for Crohn’s disease with additional evaluation of covariates relevant to UC. ER relationships between RZB exposures and efficacy endpoints at the end of induction (Week 12), re-induction (Week 24; exploratory only) and maintenance (Week 52) periods were established using exploratory graphical analyses and logistic regression modeling. ER analyses for safety were performed for key variables through Weeks 12, 24 and 52 using graphical analyses.

Results

A two-compartment model with first-order absorption for SC administration and first-order elimination adequately described RZB PK. Among the various covariates assessed, body weight, baseline (BL) serum albumin, BL high-sensitivity C-reactive protein, BL fecal calprotectin, sex, advanced therapy IR status, BL pancolitis and corticosteroid use were statistically correlated with RZB clearance but their impact on exposure was not clinically relevant for efficacy.ER analyses for efficacy using Phase 2b induction data showed that while incremental improvement in efficacy was predicted with doses increasing from 1200 to 1800 mg, the magnitude of difference in efficacy was modest especially for endoscopy-driven endpoints. Phase 3 ER analyses for efficacy showed statistically significant trends of exposure-dependent increase in efficacy following induction treatment with 1200 mg IV at Week 0, 4 and 8, with greater response rates observed with higher exposures across all evaluated endpoints at Week 12, in line with the results from Phase 2b. ER analyses for maintenance demonstrated an exposure-dependent increase in efficacy for Week 52 endpoints, with modest improvement in efficacy when increasing the dose from 180 mg to 360 mg, and largely overlapping confidence intervals. ER analyses for safety indicated no apparent exposure-dependent safety events over the induction or maintenance treatment.

Conclusion

The PPK and ER analyses of RZB in subjects with UC characterized the disposition of RZB and its relationship to efficacy and safety, as well as the lack of impact by intrinsic and extrinsic factors on PK and efficacy. Results supported the final dosing regimen recommendations for the treatment of moderately to severely active UC.Read more P1090 Exposure to an inflammatory prenatal environment and the risk of Inflammatory Bowel Disease in the offspring: a population-based cohort studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The strongest independent risk factor for developing Inflammatory Bowel Disease (IBD) is a family history with IBD. The early life, including the intra-uterine period, is critical for immune system maturation and therefore, exposures during early life can influence IBD risk. We conducted this study to understand if the risk of IBD in the offspring of women with IBD is due to an inflammatory prenatal environment in addition to genetic predisposition.

Methods

Using cross-linked nationwide Danish health registers, we identified all individuals born in Denmark from 1997 to 2022 as well as their legal parents. Of these, we identified all individuals diagnosed with IBD and the date of diagnosis. The follow up period was from the date of birth until date of IBD diagnosis, death, emigration, or August 1, 2022, whichever occurred first. We performed Cox proportional hazards analyses adjusted for calendar period to assess the risk of IBD in individuals born of mothers diagnosed with IBD before childbirth, those diagnosed with IBD after childbirth, and those with no IBD diagnosis. Since paternal IBD status would be unlikely to influence the prenatal environment, we performed corresponding analyses of paternal IBD status as a negative control analysis.

Results

We identified 1,290,358 children born in Denmark between 1997 and 2022. Of these, 10,041 (0.8 %) had a mother with IBD before childbirth and 9,985 (0.8 %) had a mother with IBD onset after childbirth. Individuals were followed for a total of 18,370,420 person-years, with a median (IQR) follow up time of 14.4 (8.6, 19.9) years. A total of 3,537 individuals were diagnosed with IBD before the end of follow up. The hazard ratio of IBD in individuals born of mothers diagnosed with IBD before childbirth was 6.29 (95% CI 5.23, 7.56) compared to those whose mother did not have IBD. The corresponding hazard ratio for those diagnosed with IBD after childbirth was 3.88 (95% CI 3.27, 4.60) (p<0.001). In our negative control analysis assessing risk based on paternal IBD status, risk was increased in the same direction. Hazard ratios of IBD were 5.26 (95% CI 4.22,6.56) and 3.73 (95% CI 3.10, 4.50) (p<0.001), respectively (Figure 1).

Conclusion

In this population-based cohort study, the risk of IBD is highest among individuals with either parent diagnosed with IBD before childbirth. These findings suggest that the timing of parental IBD diagnosis, in addition to family history of IBD, influences IBD risk. Since these associations are consistent across maternal and paternal IBD status, genetic predisposition may play a weightier role than a prenatal inflammatory environment in the IBD risk of offspring to IBD patients.Read more P869 Deep ulcers in acute Ulcerative Colitis at index endoscopy predict corticosteroid resistanceWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Ulcerative Colitis (UC) is a chronic inflammatory disease affecting the colon. Its acute form can be life-threatening, necessitating hospital admission and intravenous (IV) corticosteroid treatment. This study aimed to predict IV corticosteroid response in acute UC patients based on endoscopic findings at admission.

Methods

Individuals admitted to the hospital for acute UC for intravenous corticosteroid treatment were selected. Those with gastrointestinal infections and those without endoscopy at admission were excluded.

Results

A retrospective analysis was conducted on a cohort of 62 patients, of which 25.8% did not respond to IV steroids. No significant associations were found between demographic, clinical, and laboratory parameters and corticosteroid response at admission. Rectosigmoidoscopy was performed for all patients upon hospitalization, and the Mayo Endoscopic Score (MES) and Ulcerative Colitis Endoscopic Index of Severity (UCEIS) were obtained. The results revealed significant differences in median UCEIS scores between non-responders and responders (7, IQR 3 vs. 5, IQR 1, p=0.011). Notably, a UCEIS score of ≥5 demonstrated a sensitivity of 100% in identifying patients who did not respond to corticosteroids, although with a lower specificity of 22.7%. Furthermore, the MES exhibited a statistically significant association with treatment response (p=0.002), with a MES≤2 having a negative predictive value of 92.9% for IV steroid resistance. Importantly, the presence and type (small vs. large) of ulcers at the initial endoscopy were found to be the most effective predictive factor for corticosteroid response (AUC=0.745; 95%CI=0.594-0.896; p=0.005), as 57.1% of patients with deep ulcers were non-responders.

Conclusion

The importance of evaluating ulcer severity during endoscopic assessment in patients with acute ulcerative colitis is underscored by our findings. Notably, the presence of deep mucosal ulcerations should prompt consideration for intensifying therapy.Read more P1104 Shifting Surgical Landscape in Crohn's Colitis: Laparoscopic Supremacy and Robotic UpsurgeWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Crohn's disease (CD) is a chronic inflammatory bowel disorder that can cause transmural inflammation throughout the digestive tract. When CD affects the colon, it is known as Crohn's colitis (CC), a serious condition often requiring surgical resection. Surgical trends in CC have changed significantly over the past decade, shifting towards minimally invasive surgery, with laparoscopic and robotic procedures becoming increasingly common. This study examines how surgical trends in CC have changed in recent years and predicts how they may change.

Methods

We conducted a retrospective analysis using the ACS-NSQIP database, focusing on patients who underwent colonic resections for CC between 2012 and 2021, including 20,109 patients. Our main goal was to examine trends in open, laparoscopic, hand-assisted, and robotic surgery. We utilized time series analysis, specifically quarter and year of admission data, and employed Vector Autoregressive (VAR) models to explore the dynamic relationships among these surgical techniques. To analyze the time trends, we reported the quarter (Q) and year of admission. These models enabled us to forecast future trends, accompanied by 95% confidence intervals, extending our predictions up until Q2 of 2025.

Results

As shown in Figure 1, open surgery has been the most common approach to CC since Q1 2012, accounting for 52.3% of all procedures. Laparoscopic surgery was the next most common approach, at 33.3%, followed by hand-assisted laparoscopy at 14.4%. Laparoscopy rapidly expressed market supremacy, by steadily becoming the most widespread approach by Q2 of 2017, representing 42.2% of CC surgery and peaking in Q2 2020 at 43.5%. This growth in laparoscopy came at the expense of open surgery, which experienced a significant decline, reaching its lowest point of 28.5% in Q2 2021. Hand-assisted procedures gradually increased in popularity over the years but remained less popular than open and laparoscopic methods, peaking at 24.0% in Q4 2019. Robotic procedures experienced slow but steady growth, from 1.9% in Q1 2013 to 10% in Q2 2021.Future trends suggest that laparoscopy will continue to grow steadily, reaching 45% (95% CI 28.2-61.7%) by the end of our prediction period. Robotic surgery is poised to significantly shift CC surgery trends, with resections expected to reach 12.6% (95% CI 9.3-15.8%) by Q2 2025, while a subsequent decline in open procedures to 20.8% (95% CI 0-43%).

Conclusion

Laparoscopic surgery has emerged as the favored surgical approach in CC and is expected to maintain its supremacy into the near future. Open colonic resections are anticipated to decline, making way for the increasing prevalence of robotic surgery.Read more P1019 "Totality-of-the-evidence" of proposed ustekinumab biosimilar SB17"Wed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

SB17 is a proposed biosimilar to Stelara [ustekinumab reference product (UST-RP)], which is a fully human IgG1/kappa monoclonal antibody to interleukin (IL)-12/23. In accordance with regulatory guidelines, "totality-of-the-evidence" proofs similarity between a proposed biosimilar and its reference product and includes analytical, non-clinical and clinical data.^{1, 2} SB17 is under review by regulatory agencies to be approved as ustekinumab biosimilar. The proposed justification for extrapolation of indications for SB17 was justified based on "totality-of-the-evidence" (i) MoA of ustekinumab binding to p40 subunit of IL-12/23, which has been associated with immune-mediated diseases, including approved indications of UST-RP (ii) overall data from the comparability comparison to UST-RP using analytical methods showing similar molecular structure and in vitro function (iii) PK studies showing similar exposure, and PD studies in healthy subject and (iv) efficacy and safety (including immunogenicity) based on studies in patients with moderate-to-severe psoriasis (PsO). The phase III study was conducted in ustekinumab-naïve patients with PsO as the most sensitive design to assess potential differences in efficacy and the risk of immunogenicity. The objective of this report is to describe the biosimilarity of SB17 to UST-RP with regard to potential extrapolation from PsO to other indications.

Methods

Analytical comparability of SB17 to UST-RP was assessed in ELISA binding assays. PK equivalence, efficacy, safety, tolerability, and immunogenicity similarity were assessed in clinical trials of healthy subjects and PsO patients.

Results

In the analytical assessment, SB17 was highly similar to the EU- and US-UST-RP in overall critical and non-critical quality attributes. Evaluation of IL-12 and IL-23 neutralization and binding activities, MoA-related biological activities, showed similarity between SB17, EU-, and US-UST-RP. ³In a phase I study, SB17 and EU- and US-UST-RP had similar PK and comparable safety, tolerability, and immunogenicity (Table 1).⁴In a phase III study of 503 patients with moderate to severe PsO, SB17 had equivalent efficacy and comparable safety and immunogenicity to UST-RP up to Week 28 (Table 1).⁵

Conclusion

With similar target binding and PK and confirmed similarity in efficacy and safety for PsO patients, SB17 is proposed to be highly similar to UST-RP in physicochemical, non-clinical, and clinical similarity studies. "Totality-of-the-evidence" data for SB17 supports its extrapolation to UST-RP indications.Read more P866 Management of fistulizing Crohn's Disease in a moroccan population: about 125 casesWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Crohn's disease is an inflammatory enterocolitis, which may be complicated by enteroenteric, enterovesical, rectovaginal, enterocutaneous and anoperineal fistulas. This is a retrospective study of fistulizing Crohn's disease cases followed in our gastroenterology department.

Methods

We report a retrospective and descriptive study, covering all cases of fistulizing Crohn's disease, collected in the hepato-gastroenterology department at our university hospital center during a 9-year study period, from 2015 to 2023. All patients with digestive and/or anal crohn's fistula were included. Comparison of categorical variables was performed with Fisher's exact test using SPSS 10.0 software. The significance level was p < 0.05.

Results

125 patients had a fistulizing form of Crohn's disease. The location of fistulas was represented by anoperineal fistulas (32.6%), followed by enteroenteral (22.9%) and enterocutaneous (23%) fistulas, then enterovesical (9%) and rectovaginal (3.8%) fistulas. Surgical treatment was immediately indicated in all cases of enterocutaneous and enterovesical fistulas, and 66.7% of rectovaginal fistulas. Proctological drainage was performed in 57.1% of cases of anoperineal fistulas. 33 cases of anoperineal fistulas and one case of recto-vaginal fistulas were treated with infliximab. Clinical remission was also significantly associated with medical treatment with biologics versus immunosuppressants (P=0.0018). Surgical treatment remains indicated in the majority of cases of fistulizing Crohn's disease.

Conclusion

Fistulizing Crohn's disease poses a problem for medical and surgical management. Surgical treatment remains indicated in the majority of Crohn's fistula cases. This study also showed that endoscopic recurrence and clinical remission were significantly associated with the type of postoperative medical treatment.Read more P1120 New-onset Inflammatory Bowel Disease is uncommon in patients with psoriasis, psoriatic arthritis and spondylarthritis treated with secukinumab: a retrospective cohort study in a tertiary centreWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Secukinumab (SEC) is an IL-17A inhibitor prescribed in patients with immune mediated inflammatory diseases like psoriasis (PsO), psoriatic arthritis (PsA) and spondylarthritis (SpA). Conflicting data are available on the onset of inflammatory bowel disease (IBD) among patients after the start of SEC. We aimed to provide data evaluating pre-existing and newly diagnosed IBD in patients being treated with SEC.

Methods

All patients receiving SEC at a single tertiary centre in The Netherlands between 2012-2022 were identified through the pharmacy registry. Data from electronic medical records were retrospectively collected: baseline (i.e. at initiation of SEC) characteristics, medical history (including pre-existing IBD), use of (disease modifying) concurrent medication, clinical symptoms, biochemistry (C-reactive protein, faecal calprotectin), endoscopy with pathology and cross-sectional imaging (CT, MRI, intestinal ultrasound). Patients were excluded if they received ≤3 doses of SEC.

Results

A total of 351 patients were included with one or more of the following indications for SEC treatment: PsO in 166/351 (47%), PsA in 130/351 (37%), axial SpA in 130/351 (37%), peripheral SpA in 31/351 (9%) and juvenile idiopathic arthritis in 1/351 (0.3%). Frequently used co-medication were NSAIDs (44%), topical corticosteroids (37%) and methotrexate (16%). Median follow-up time was 48 months (IQR 22,74). In total, ten patients with IBD were identified: 5/351 (1.4%) patients had pre-existing IBD (2/5 Crohn’s disease, 3/5 ulcerative colitis) and 5/351 (1.4%) patients developed IBD after SEC initiation (3/5 Crohn’s disease, 1/5 ulcerative colitis, 1/5 IBD-unclassified) (Table 1). All new-onset IBD cases were confirmed with endoscopy and pathology. Predominant clinical symptoms were diarrhoea, abdominal pain and haematochezia. In patients with new-onset IBD median time from initiation of SEC to development of clinical symptoms was 1.3 months (range 0-12) and median time to diagnosis was 7.5 months (range 3-16). Out of patients with pre-existing IBD in remission 2/5 developed clinical symptoms after start of SEC with a median time to development of 9 months (range 6-12); 3/5 patients sustained remission. After starting SEC 25% of patients reported gastrointestinal symptoms, however diagnostic work-up took place in only 52% of these patients revealing no signs of IBD.

Conclusion

In our cohort new-onset IBD after SEC initiation was uncommon (<2%) with a short median time to onset. IBD seemed equally distributed among indications. Caution and monitoring of gastrointestinal symptoms during SEC treatment is warranted in patients with pre-existing IBD, considering the possibility of an exacerbation.Read more P1020 Developing and Validating a Clinical Prediction Model Using Biomarkers to Assess Clinical Response and Severity of Crohn's Disease 12 Weeks After Initiation of Biological TherapyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Despite the evolution of therapeutic strategies for Crohn’s disease (CD), many patients exhibit resistance to numerous biological agents, necessitating a transition to other advanced therapies. Therefore, the early and accurate prediction of the response to biological agents in treating CD is crucial. We sought to evaluate potentially useful biomarkers in predicting clinical response to biological agents in the management of CD.

Methods

This retrospective cohort study included data from adult CD patients who were naïve to biological treatments and maintained regular follow-up at a tertiary referral hospital between January, 2017 to June, 2022. Two prediction models were built to predict the Crohn's Disease Activity Index (CDAI) response at 12 weeks in its ordinal scale. The two clinical models included age, gender, and previous CD surgery. In model-1, we included 8-weeks neutrophile-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) in their log scale as biomarkers of interest. Model-2 had 8-weeks neutrophile, platelet, monocyte, and lymphocyte counts in their natural scale. We built the prediction models using proportional odds model. Performance metrics were C-statistic for discrimination, brier score, visual calibration curve with bootstrap internal validation were used.

Results

A total of 104 patients were included, with a male predominance of 57.7% of the sample. The median age of the participants was 26 years (IQR: 21.00 – 36.00), and the median CDAI score was 237 (IQR: 125.25 – 256.0). Additionally, 43.3% of our population had undergone previous IBD surgery . The majority of the cohort initiated their treatment infliximab (59.6%), followed by adalimumab (35.6%). Model-1 has C-statistic of 0.678 compared to 0.682 for model-2. Brier scores for models 1 and 2 were 0.187 and 0.180, respectively. However, visual calibration curves showed better calibration of model-1 after bootstrapping internal validation corrected for over optimism. Odds ratio (OR) estimates of having higher odds of severe CDAI score at 12 weeks for model 1 were being female (OR: 2.20, 95% CI 1.04 –4.66; p = 0.04), higher NLR at week 8 (OR: 1.94, 95% CI 1.03– 3.65; p = 0.04), higher PLR at week 8 (OR 1.38, 95% CI 1.05– 1.8; p = 0.02), and higher CDAI score prior to the initiation of biological therapy (OR: 2.15, 95% CI 1.12– 4.13; p = 0.02).

Conclusion

The clinical prediction model that includes potentially useful biomarkers such as NLR and PLR at 8-weeks were well calibrated to predict a CDAI score at week 12 for the treatment response. Clinicians may find useful to implement prediction models in their clinical practice to evaluate the response of their patients.Read more P867 Abdominally targeted yoga-based physical exercises as a therapeutic intervention for Inflammatory Bowel DiseasesWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Physical activity (PA) has positive effects on general well-being and stress. The effect of abdominally targeted PA on IBD disease measures and patient’s quality of life (QoL) is currently unknown.We aimed to examine the effect of routine, abdominally targeted, physical exercise sets, designed exclusively for IBD patients, on patients’ QoL and clinical response.

Methods

This randomized (1:1), controlled, double-blinded study assessed the effect of a set of 10-minute videos of specific abdominally targeted physical exercises inspired by Yoga, postulated to increase blood flow to the abdomen, on patients' disease activity and QoL, compared to a control general exercise videos. All patients signed an informed consent form. Patients performed either abdominally targeted (intervention) or control exercises, sequenced and performed by a trained and experienced yoga instructor, through an online application, at least 5 times/week.Disease activity (HBI/ SCCAI), inflammatory indices (CRP, fecal calprotectin), and QoL measures (PROMIS questionnaire), were compared before and after 30-days of the intervention. For collective analysis of patients, a combined clinical score scale was used (Table 1). Change in calprotectin was calculated as the initial minus the end value.

Results

Twenty-six mild-moderate patients with IBD (age 39.3±10 years) were randomized to perform either intervention (8 CD, 7 UC), or control (7 CD, 4 UC) sets of exercise. Upon completion, most IBD patients training with either the interventional or control videos, exhibited significant improvements in their clinical scores. Among the patients in the interventional arm, the clinical score decreased from 1.1±0.4 to 0.4±0.6 (p<0.001), and in the control group from 1.4±0.5 to 0.9±0.7 (p<0.01). Interestingly, calprotectin significantly decreased only in the interventional group, in comparison to the control (Delta calprotectin: 40.8±122 vs. -431±652μg/g, respectively, p≤0.01). No improvements were observed in CRP. QoL measures improved in the intervention group in pain (13.6±14%, p<0.005), anxiety (14.3±24%, p<0.05), fatigue (18.8±19%, p<0.05) and in social activities (7.1±9%, p<0.05). In contrast, in the controls, only anxiety score improved (8.3±9%, p<0.05). No differences were observed in scores of sleep disturbances, depression, and physical function in either group.

Conclusion

Routine PA can significantly improve IBD clinical scores and symptoms. Abdominally targeted exercises are associated with an additional improvement in clinical scores, fecal calprotectin and in self-perceived level of interference in pain and routine daily functions. These results suggest a positive effect of physical exercise in IBD and prompt further study.Read more P820 Targeting MM-SES-CD < 22.5 for endoscopic improvement is feasible in a clinical trial of Crohn’s disease: A post-hoc analysis of SEAVUEWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

It has been demonstrated that a Modified Multiplier of the SES-CD (MM-SES-CD) < 22.5 is the optimal endoscopic threshold that is associated with a low risk of disease progression using data from the CALM long-term extension study. To determine whether or not this threshold would be a pragmatic target within the setting of a clinical trial, we performed a feasibility analysis using data from the phase 3 SEAVUE clinical trial.

Methods

We considered data from 373 patients from the SEAVUE clinical trial who had available endoscopic data at baseline and were treated with ustekinumab (n=187) or adalimumab (n=186). As participants were only required to have a single ulcer at the time of enrollment in SEAVUE, we further restricted the population to those with MM-SES-CD > 22.5. The primary outcome was MM-SES-CD < 22.5 at week 52. Secondary outcomes were common targets for endoscopic healing in clinical trials, including SES-CD reduction of ≥ 50%, SES-CD < 4, and SES-CD < 3. Clinical remission, defined as CDAI < 150, was also assessed at week 52. Sensitivity analyses were planned to restrict the population to those with moderate to severely active disease activity, defined as MM-SES-CD ≥ 31.

Results

Of the 373 participants, 55.2% (206/373) participants achieved a MM-SES-CD < 22.5. A total of 206 participants had a MM-SES-CD > 22.5 at baseline, of which 91 (44.2%) attained a MM-SES-CD < 22.5 at week 52. A greater proportion of participants achieved this outcome compared to SES-CD reduction of ≥ 50% (85/206, 41.3%), SES-CD < 4 (52/206, 25.2%), and SES-CD < 3 (36/206, 17.5%) at week 52 (Table 1). A total of 144 participants had moderate to severely active endoscopic disease at baseline (MM-SES-CD ≥ 31), of which 55 (38.2%) achieved a MM-SES-CD < 22.5 at week 52. This was similar to the number of patients who achieved SES-CD reduction of ≥ 50% (61/144, 42.4%), and greater than the number of patients who achieved SES-CD < 4 (34/144, 23.6%) or SES-CD < 3 (21/144, 14.6%) at week 52. Of the 144 participants with a MM-SES-CD ≥ 31 at baseline, a total of 71 received adalimumab and 73 received ustekinumab. Compared to adalimumab, a numerically greater proportion of those treated with ustekinumab achieved MM-SES-CD < 22.5 [33/71 (45.2%) vs. 22/71 (31%), p=0.079] and clinical remission [48/73 (65.8%) vs. 36/71 (50.7%), p=0.067] at week 52.

Conclusion

Based on this feasibility analysis, a MM-SES-CD < 22.5 is a feasible target to attain in clinical trials of Crohn’s disease. Further, use of the MM-SES-CD for measurement of endoscopic burden could lead to different conclusions being obtained from clinical trials of CD that are clinically and prognostically more relevant.Read more P1021 Comparison of subcutaneous and intravenous infliximab in patients with inflammatory bowel disease showed no differences in immunogenicity or treatment persistence at one yearWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The effectiveness of infliximab (IFX) in inflammatory bowel disease (IBD) can be impaired by the formation of anti-drug antibodies (ADA). Subcutaneous (SC) IFX has a different pharmacokinetic profile compared to intravenous (IV) administration. These differences may affect the risk of immunogenicity and we sought to explore this in a retrospective study.

Methods

We performed a retrospective study in Leeds, United Kingdom. Adult patients starting IFX for the first time between January 2019 and June 2022 were identified. All received standard induction with three IV doses followed by either: 1) maintenance SC IFX 2-weekly (standard practice from 2021), or 2) maintenance IV IFX (standard practice until 2021). We compared ADA levels, IFX trough levels and treatment persistence between groups after 12-months of treatment. ADA levels above 10 AU/ml were considered positive and ADA levels above 50 AU/ml as clinically relevant.

Results

After excluding 41 patients (16 stopped IFX after IV induction, 24 moved to SC after >4 IV doses, and 1 lost to follow-up), 101 patients receiving maintenance SC IFX were compared to 108 patients continuing with maintenance IV IFX. At 12-months, prevalence of ADA positivity was similar in both groups (48.1% SC vs 50.6%; p=0.775). Clinically relevant ADA levels (>50 AU/ml) were also similar (21.1% SC vs 26.5% IV; p=0.481). Additionally, there were no statistically significant differences in terms of detectable IFX trough levels and treatment persistence after 12-months of treatment between the two groups. Patients receiving combination therapy with IFX and immunomodulators showed a significant reduction in ADA formation irrespective of the route of IFX administration. 34.8% of patients receiving combination therapy had detectable ADA compared to 65.2% receiving IFX monotherapy (OR 0.28 (95% CI 0.13-0.58; p=0.001)). Treatment persistence was also significantly higher in those receiving combination therapy compared with monotherapy at 12-months (73.3% vs. 51.9%; p=0.004). The proportion of patients with detectable drug levels at 12-months was also higher with combination therapy (91.3% vs. 72.7%; p=0.005).

Conclusion

There were no significant differences in ADA levels, IFX levels, and treatment persistence between the SC and IV routes of IFX administration after 12 months of treatment. Concurrent use of immunomodulators was associated with reduced immunogenicity and better treatment persistence regardless of the route of maintenance IFX. Clinicians should advise patients on the benefits of immunomodulator combination therapy when initiating IFX regardless of route of administration.Read more P1073 Opioid use Before and After First Diagnosis of Crohn’s Disease: A Swedish Nationwide Cohort Study 2008-2020Wed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The ongoing opioid misuse epidemic, initially sparked by over-prescription, presents challenges in managing severe pain in Crohn’s disease (CD). Despite associated negative effects, such as narcotic bowel syndrome and susceptibility to chronic use, opioids are frequently prescribed for CD patients. However, data on the evolution of opioid use before and after the initial CD diagnosis in a European context are limited.

Methods

This nationwide cohort study utilized the Swedish Patient Register to identify adults with a first CD diagnosis between 1 January 2008 and 31 December 2017, residing in Sweden at least two years before and three years after the diagnosis. For each CD patient, we included up to 10 reference individuals from the general population matched on birth year, sex, calendar year, and place of residence. Data on dispensed opioid prescriptions were retrieved from the National Prescribed Drug Register. Opioid use history was categorized into non-users (no dispensations), intermittent users (≥1 dispensation in 1–3 periods), and chronic users (≥1 dispensation in all periods) based on the four preceding six-month periods before the first CD diagnosis. Opioid use per six-month period was estimated from two years before to five years following CD diagnosis (corresponding index date for matched reference individuals) and coarsened exact matching was employed to account for confounding (birth year, sex, education, and history of psychiatric disorders and cancer).

Results

We included 12,539 incident CD patients and 116,073 matched reference individuals. During the two years before the first CD diagnosis, CD patients (and 3.9% vs 10.4% and 1.4%, respectively) were more often intermittent (22.3% vs 10.4%) or chronic (3.9% vs 1.4%) opioid users than matched reference individuals. Prior to diagnosis, opioid use per six-month period was twice as common among CD patients than in reference individuals. Following a peak in the first year after the diagnosis, the prevalence of dispensed opioids per six-month period stabilized at a three-fold level among CD patients (13.6%; 95% CI: 13.0, 14.3) compared with the reference individuals (5.5%; 95% CI: 5.4, 5.7) (Figure 1). The 6-month prevalence of opioid use five years after CD diagnosis was 7.6% (95% CI: 7.0, 8.2), 22.9% (95% CI: 21.1, 24.6), and 79.5.4% (95% CI: 73.2, 85.7) for CD patients classified as non-users, intermittent, or chronic users two years before diagnosis, respectively.

Conclusion

CD patients exhibited elevated opioid use two years before their initial diagnosis, which persisted at a three-fold level compared to matched reference individuals for five years post-diagnosis. This pattern persisted despite publicly-funded healthcare and modern CD therapy accessibility.Read more P843 Effectiveness and tolerability of methotrexate combined with biologics in patients with Crohn’s disease: A multicenter observational studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Methotrexate (MTX) combination therapy with biological agents has gained increasing interest. Here, we assessed the efficacy and tolerability of the MTX combination therapy in patients with Crohn’s disease (CD).

Methods

We performed a multicenter observational study with 185 patients with CD with MTX and biologics combination therapy; the patients were recruited from three IBD Clinics in Korea. We evaluated the outcomes of the MTX combination therapy and examined the predictive factors of clinical and endoscopic remission.

Results

MTX was administered orally to 62.7% of patients; the mean dose was 15.5 mg per week, and the mean treatment duration was 36 months. Of the 169 patients treated with MTX combination therapy for over 6 months, the steroid-free clinical remission rates were 34.3%, 26.0%, 29.8%, and 32.7% at 4, 12, 18, and 24 months, respectively. Previous thiopurine use was a significant negatively associated independent factor (p < 0.001), and a higher dose of MTX (≥15 mg/week) was a positively associated independent factor of steroid-free clinical remission (p = 0.035). Ninety-six patients underwent follow-up endoscopy after 28 months, and 36 (37.5%) achieved endoscopic remission. Longer disease duration (p = 0.006), ileocolonic type of Montreal location (p = 0.036), and baseline C-reactive protein (CRP) level of more than 5 mg/L (p = 0.035) were significant negatively associated independent factors and a higher dose of MTX (≥15 mg/week) was a positively associated independent factor of endoscopic remission (p = 0.037).

Conclusion

MTX combination therapy with biologics was effective and tolerable in patients with CD.Read more P1058 Safety and effectiveness of subcutaneous infliximab formulation in difficult-to-treat Crohn’s Disease patients with previous exposure to intravenous infliximab: A case-seriesWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Despite the increased therapeutic armamentarium for Crohn’s Disease (CD), a relevant proportion of patients fail to respond to multiple therapies and ultimately require surgery. Intravenous (IV) infliximab (IFX) reinduction after a drug holiday is associated with reduced drug efficacy and both acute and delayed infusion reactions, due to immunological mechanisms and development of antidrug antibodies, and is currently contraindicated. Recently, a subcutaneous (SC) formulation of IFX has been developed, demonstrating equal efficacy and safety with a better immunogenicity profile (i.e. biobetter). This study evaluated the safety and effectiveness of retreatment with SC IFX in CD patients previously exposed to IV IFX.

Methods

Data were retrospectively collected through the Electronic Medical Record. Patients included were IV IFX-experienced and subsequently treated with SC formulation after a period of drug holiday ≥ 1 year. Collected data included demographics, disease characteristics and activity, current and previous treatment, adverse events, and reasons for previous anti-TNFα discontinuation.

Results

12 patients with CD were included. Mean age at diagnosis and disease duration were 16.2 (±6.7 SD) and 15.6 years (±7.4 SD) respectively. All patients had failed at least three biologics, and 7 patients underwent previous surgery. The main reason for IV IFX discontinuation was secondary failure (4 patients, 33%). Median time from IV suspension to SC treatment start was 106.5 months (IQR=98.5) with median treatment duration of 24 (IQR=37.5) and 7.5 (IQR=4.5) months for IV and SC IFX respectively. SC IFX was introduced as an add-on dual biologic therapy in 5 patients (3 treated with Ustekinumab, 2 with Vedolizumab).Overall, one adverse event with SC IFX was reported: a grade 2 serum sickness reaction, which led to treatment discontinuation. No immediate allergic reactions were reported. 10 patients had at least 6 months of follow-up. Median HBI reduction at 6 months from SC IFX begin was significant (p<0.05), varying from 7.5 (IQR=3.5) to 3.5 (IQR=4).C-Reactive Protein levels normalized in 3 (38%) patients, reduced in 2 (25%), and remained stable in 3 (38%). Faecal calprotectin normalized in 2 (29%) patients, reduced in 1 (14%), remained stable in 2 (29%), and increased in 2 (29%). At 6 months steroid free remission rate (HBI≤4) was 66%.

Conclusion

This is the first report showing that SC IFX reinduction in CD patients previously exposed to IV IFX is safe, even after a long drug holiday. It might be regarded as a rescue option in difficult-to-treat patients, either alone or combined with other immunosuppressants.Read more P1089 Disease characteristics at time of diagnosis of adult onset inflammatory bowel disease and the risk of venous thromboembolism in the modern era – A Swedish nationwide cohort study 2007-2021Wed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Studies from mainly before the wide use of targeted therapies and guidelines for thromboprophylaxis indicate that patients with inflammatory bowel disease (IBD) are at a doubled risk of venous thromboembolism (VTE). We studied the risk of VTE in a modern-day cohort of patients with IBD, overall and in subgroups of disease characteristics.

Methods

Using Swedish healthcare registers, we identified a nationwide population-based cohort of 55,252 patients with incident IBD between 2007 and 2021 with a median follow-up time of 6.5 years. Patients were matched by age, sex, calendar year and county of residence with up to ten reference individuals from the general population (N=536,067). The primary outcome was VTE, including pulmonary embolism and deep vein thrombosis. Incidence rates per 1,000 person-years and hazard ratios (HR) were calculated for IBD in general and according to disease subtype, sex, age and disease characteristics at diagnosis. HRs stratified by matching variables (model 1) and additionally adjusted for comorbidities and socioeconomic factors (model 2) were estimated by using Cox regression.

Results

The incidence rate of VTE among patients with IBD was 5.03 per 1,000 person-years compared with 2.34 per 1,000 person-years among reference individuals (Table 1). This corresponded to a doubled incidence of VTE (HR=2.18, 95% confidence interval (CI)=2.07-2.29, model 1). Adjusting further for covariates in model 2 had only minor effects on the HR. The HR was consistent across IBD subtypes and sex. The relative risk was higher for those with younger age (18-39 years) at IBD diagnosis (HR 2.52, 95% CI: 2.22-2.83) with a risk difference of 1.25 per 1,000 person-years. The IR, 10.64 per 1,000 person-years, and risk difference, 5.42 per 1,000 person-years, was the highest for those with elderly onset (≥60 years) IBD. There was a stronger association for those with extensive ulcerative colitis (E3), primary sclerosing cholangitis, extraintestinal manifestations and perianal disease. HRs for VTE were persistently elevated across follow-up time, but was higher during the first year of follow-up (Figure 1).

Conclusion

The risk of VTE was doubled in these modern-day data and remained elevated across follow-up time. Disease characteristics associated with higher inflammatory burden at diagnosis and older age are markers of increased risk. This underscores the importance of continuous vigilance and individual assessment of risk factors for VTE in patients with IBD.Read more P1059 Use of preoperative transjugular intrahepatic portosystemic shunt (TIPS) in patients with Inflammatory Bowel Disease and cirrhosisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Colorectal surgery in patients with inflammatory bowel disease (IBD) and cirrhosis is associated with high morbidity related to portal hypertension. Thought to reduce surgical risk, transjugular intrahepatic portosystemic shunt (TIPS) may be used to decrease portal pressures. In this study, we aimed to characterize surgical outcomes of patients with IBD and cirrhosis who underwent preoperative TIPS at a large tertiary care center.

Methods

We retrospectively identified patients with IBD and cirrhosis who had undergone TIPS between 2010-2023 for portal decompression prior to colorectal surgery. All other indications for TIPS led to patient exclusion. Demographic and medical data was collected, including surgical indication and portal pressure measurement. Data on surgical outcomes were compiled through chart review.

Results

We identified 10 patients (60% male) with IBD and history of decompensated cirrhosis who underwent preoperative TIPS for portal decompression (Table 1). Surgical indications were colonic dysplasia (50%), refractory IBD (50%), and stenosis or stricture (30%). All patients were deemed nonsurgical candidates due to significant surgical risk from portal hypertension. Following multidisciplinary coordination, patients underwent TIPS for portal decompression at a median of 47 days (IQR 34-80) prior to colorectal surgery. TIPS was associated with significant reduction in portal pressure (22.5 vs 18.5mmHg, p<0.01) and portosystemic gradient (12.5 vs 5.5mmHg, p<0.01) in all patients. Of 10 patients, 30% had TIPS-related complications (transient fluid overload and encephalopathy). In terms of surgical complications, 40% of patients required intraoperative blood transfusion (range: 1-4 units). Postoperatively, 30% of patients had surgical site bleeding and 10% had wound dehiscence, although none required reoperation. Systemic complications occurred in 30% of patients, with systemic signs of infection being the most common. Transaminitis (50%) and coagulopathy (40%) were also common. Median hospital stay was 7 days (IQR 5.5-9.3), with 40% of patients being readmitted within 30 days. Most common cause of readmission was systemic infection (75%), abdominal abscess (50%), or electrolyte abnormality (50%), with one patient requiring reoperation for wound dehiscence. Ninety-day and 1-year survival was 100% and 90% respectively.

Conclusion

In our series of patients with IBD and cirrhosis requiring surgery but deemed nonsurgical candidates, preoperative TIPS lead to portal decompression and facilitated successful surgical intervention despite heightened risk. Nevertheless, significant operative and postoperative complications were noted. Future studies are needed to determine optimal surgical timing following TIPS placement.Read more P844 Frequency and effectiveness of dose de-escalation of biologic therapy in Inflammatory Bowel Disease: The RAINBOW-IBD study of ENEIDAWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Biologic dose escalation is associated with increased costs and potential safety concerns; therefore, de-escalation could be considered in patients in remission after dose escalation. However, data on de-escalation outcomes is scarce. Primary aim: To describe the frequency and the evolution after de-escalation of infliximab (IFX), adalimumab (ADA), golimumab (GOL), vedolizumab (VED), and ustekinumab (UST). Secondary: To investigate the durability of dose de-escalation, the factors associated with relapse after de-escalation, and the effectiveness of a re-escalation.

Methods

Adult patients from ENEIDA registry who previously had their biologic dose escalated, were included. De-escalations (either decreasing the dose or lengthening the interval of administration) were specifically analysed. Survival curves assessing the impact of several variables on clinical relapse were compared using the log-rank test. Predictive factors associated with the risk of relapse after dose de-escalation were assessed by Cox-regression.

Results

A total of 669 de-escalations from 5,096 previous dose escalations were performed (13%). The incidence rate of dose de-escalation per patient-year of follow-up was: 6% (95% confidence interval [CI]=5.8-6.2%), 9% (7.4-10.7%), 5% (1-9%), 6% (5.4-6.6%), and 3% (2.9-3.1%) in patients receiving IFX, ADA, GOL, VED and UST, respectively (Figure 1).The favourable evolution after dose de-escalation (maintaining remission or response) was: 106/132 (80%) and 131/132 (99%) for IFX; 157/209 (75%) and 208/209 (99%) for ADA; 5/5 (100%) and 5/5 (100%) GOL; 14/16 (88%) and 16/16 (100%) for VED; and 9/12 (75%) and 11/12 (92%) for UST. The probability of maintaining the dose de-escalated at 12 months was: 86%, 86%, 88%, 82%, and 90% for IFX, ADA, GOL, VED and UST, respectively (Figure 2).Predictive factors of relapse after de-escalation were as follows: 1) IFX: previous biologic exposure (Hazard ratio [HR]=2.7, 95%CI=1.1-6.9), and 2) ADA: age at dose de-escalation (HR=1.08, 95%CI=1.02-1.15). Variables associated with the risk of relapse with other biologics could not be identified. Response and remission were recaptured after re-escalation, respectively, in: 11/12 (92%) and 7/12 (58%) for IFX; 22/22 (100%) and 13/22 (59%) for ADA; 1/1 (100%) and 0/1 (0%) for GOL; 2/2 (100%) and 2/2 (100%) for VED; and 1/1 (100%) and 1/1 (100%) for UST.

Conclusion

In the largest cohort of patients with dose escalation of biologic treatment in real-life, approximately 10% of the patients have a dose de-escalation in the long-term. If carried out, the durability of the de-escalation seems to be high over time. In those who relapse after dose de-escalation, re-escalation of therapy is effective in more than half of the patients.Read more P1074 Impact of body mass index (BMI) on clinical outcomes and drug levels in patients with Crohn’s disease receiving maintenance treatment with subcutaneous infliximab: A post hoc analysis of the LIBERTY-CD studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Obesity and high levels of visceral adipose tissue are associated with lower response rates to intravenous (IV) infliximab (IFX).¹ Subcutaneous (SC) IFX is a novel formulation that demonstrated superiority to placebo as maintenance therapy in patients (pts) with moderate-to-severe active Crohn’s disease (CD) in the Phase 3 LIBERTY-CD study. Assessing efficacy of SC IFX by BMI is important as, unlike the IV formulation, pts receive a fixed dose. This post hoc analysis aimed to assess the association between BMI and the efficacy of SC IFX therapy.

Methods

Data from LIBERTY-CD (NCT03945019) were analysed; 231 pts from the SC IFX arm were divided into four subsets by their BMI: underweight (BMI <18.5 kg/m², n=27); normal (18.5–24.9 kg/m², n=133); overweight (25–29.9 kg/m², n=53); obese (≥30 kg/m², n=18). Co-primary endpoints at Week (W) 54 (clinical remission [CD Activity Index (CDAI) score <150]; endoscopic response [≥50% decrease in Simple Endoscopic Score for CD (SES-CD) from baseline (BL)]) and W54 change from BL in CDAI score were assessed by BMI subset. Correlations between BMI and CDAI score, SES-CD or median trough level of infliximab (TLI), and the impact of BMI on W54 TLI, were evaluated. Analyses were conducted in a descriptive manner.

Results

At W54, there were no statistically significant differences in co-primary endpoints or change from BL in CDAI score across BMI subsets, despite descending trends in rates of achieving co-primary endpoints, change in CDAI score and TLI with increasing BMI (Table). From the underweight to obese subsets, clinical remission rates were 63.0%, 66.2%, 58.5% and 44.4% (p=0.125), endoscopic response rates were 55.6%, 36.1%, 41.5% and 27.8% (p=0.207) and median changes from BL in CDAI score were −227.3, −212.9, −196.2 and −204.5 (p=0.358). No significant correlations were observed between BMI and CDAI score (Pearson r=0.0972/p=0.141; Spearman rank r=0.0619/p=0.349) or BMI and SES-CD (Pearson r=0.0446/p=0.507; Spearman rank r=0.0375/p=0.577), while there was a weak, but significant, negative correlation between BMI and TLI (Pearson r=−0.2808/p<0.001; Spearman rank r=−0.2829/p<0.001) (Figure). Additionally, there was a significant difference in median W54 TLI across BMI subsets from underweight to obese (17.0, 13.6, 9.3 and 6.6 µg/mL; p=0.007) (Table).

Conclusion

While there was a significant difference in TLI across BMI subsets, there was no statistically significant impact of BMI on W54 clinical or endoscopic outcomes. These results could be explained by the relatively high TLI achieved with the SC formulation. Further larger and longer-term studies including pts with morbid obesity and utilising body composition assessment are warranted.¹Yarur A et al. Gastroenterology 2023;165:963–75.Read more P1060 Diverting Ostomy for Crohn’s Pancolitis in Pediatric PatientsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Childhood-onset Crohn’s disease (CD) is characterized by extensive anatomic involvement, with high rates of panenteric CD. Given the fact that total colectomy for these patients result in permanent loss of colonic absorption of nutrients, ostomy can be a good surgical option for children with Crohn’s pancolitis requiring surgical intervention. The purpose of this study was to retrospectively review the outcome of diverting ostomy for Crohn’s pancolitis in children.

Methods

Children with Crohn’s disease involving total colon with or without small intestine who underwent surgery were included. Preoperative patient features including extent of disease using Paris classification, nutritional status and medications were recorded. Outcomes analyzed included postoperative medication changes, nutrition and growth changes, postoperative complications and need for further operative interventions.

Results

We identified 13 patients with a median age of 11 years (range 5 months-15 years), all of whom had pancolitis at the time of surgery. All 13 patients underwent stoma formation, initially. Three patients received colectomy after median 24 months. Takedown rate was 38% (n=5) and the time from stoma formation to takedown was median 13 months (range 10-34 months). Weight and height z-score have been improved after ostomy.

Conclusion

Children with CD pancolitis could benefit from diverting ostomy which offers an opportunity to spare the large intestine partially or completely which could improve nutrition and growth. Outcome comparison between diverting ostomy and colectomy should be discussed with larger study populations.Read more P845 Vedolizumab induces endoscopic healing uniformly irrespective of disease location: post-hoc analysis of the LOVE-CD trialWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Vedolizumab (VDZ) is a gut-selective anti–α4β7-integrin monoclonal antibody approved for the treatment of Crohn's disease (CD). We performed a post-hoc analysis of the LOVE-CD trial to evaluate the effect of disease location on endoscopic healing.

Methods

LOVE-CD is a prospective multicentre study of VDZ therapy in adult patients with moderate-severe CD (Crohn's Disease Activity Index (CDAI) >220 and presence of ulcers at endoscopy). Patients received VDZ 300 mg infusions at weeks 0-2-6 followed by 8 weekly infusions up to week 52. An additional infusion at week 10 was given to patients without clinical response (CDAI decrease <70 points). Corticosteroids had to be withdrawn by week 26. Ileocolonoscopies were performed at weeks 0, 26, and 52, recorded, and centrally scored by 2 independent readers using the Simple Endoscopic Score for Crohn's Disease (SES-CD). The primary endpoint for this analysis was the proportion of patients, stratified by disease location (according to Montreal classification), with ulcer-free endoscopy (absence of any ulceration; SES-CD ulcer score 0) at week 52. Key secondary endpoints at week 52 were the proportion of patients, stratified by disease location, with endoscopic remission (SES-CD <4 for L2/L3 CD or <2 for L1 CD, and no subscores >1), with combined steroid-free clinical and endoscopic remission (CDAI<150 and endoscopic remission), the segmental healing rates, and ulcer healing rates stratified by disease duration.

Results

186 patients were included in this intention to treat (ITT) analysis: 42 (22.6%) with L1, 52 (28.0%) with L2, and 92 (49.5%) with L3 disease. Baseline characteristics are shown in table 1. At week 52, the primary endpoint (absence of all ulcerations) was attained in 15/42 patients with L1 (35.7%), 20/52 with L2 (38.5%) and 25/92 with L3 CD (27.2%) (ITT, NRI (p=0.327)). Endoscopic remission was observed in 12/42 patients with L1 (28.6%), 20/52 with L2 (38.5%), and 29/92 with L3 disease (31.5%) (ITT, NRI (p=0.558)). The combined endpoint of clinical-endoscopic remission was reached in 9/42 L1 (21.4%), 16/52 L2 (30.8%), and 23/92 L3 patients (25.0%) (ITT, NRI (p=0.571)). Resolution of ileal ulcers was achieved in 15/40 L1 patients (37.5%) and 37/90 L3 patients (41.1%) (ITT, NRI (p=0.698)), resolution of colonic ulcers in 21/52 L2 (40.4%) and 45/90 L3 patients (50.0%) (ITT, NRI (p=0.268). Patients with early CD (disease duration <2 years) had higher ulcer healing rates than patients with late CD (47.5% versus 24.8%) (ITT, NRI (p=0.002)).

Conclusion

This post-hoc analysis of LOVE-CD shows that disease location does not affect endoscopic healing rates with VDZ in CD. However, early CD is associated with significantly higher endoscopic remission rates compared to late CD.Read more P1061 TEV-48574, an anti-TL1A antibody in development for use in IBD, is safe and well tolerated following 16 weeks of subcutaneous treatment in adults with severe uncontrolled T2-low/non T2 asthmaWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

TEV-48574 is a human antibody that targets tumor necrosis factor (TNF)-like ligand 1A, also known as TNF superfamily member 15 (TNFSF15). It is in clinical development as a potential treatment for ulcerative colitis (UC) and Crohn’s disease (CD). TL1A signalling is believed to amplify immune-mediated inflammation in asthma and inflammatory bowel disease (IBD); thus, targeting TL1A may mitigate over-activation of immune responses. A proof-of-concept phase 2A study evaluated safety, tolerability and efficacy of TEV-48574 as treatment for adults with severe uncontrolled asthma (Clinicaltrials.gov NCT04545385). Although the study terminated (after meeting pre-specified criteria for futility at a preplanned interim analysis) the drug demonstrated favourable safety, tolerability and immunogenicity data, supporting the potential use of anti-TL1A treatment in patients with UC and CD.

Methods

TEV-48574 was administered as a loading dose followed by 7 maintenance doses given subcutaneously (sc) every 2 weeks for 16 weeks in adult patients (n = 65) with severe T2-low asthma with no/low inflammation at baseline. The primary efficacy endpoint was reduction in patients who experience loss of asthma control (LoAC). Patients were monitored for LoAC at bi-weekly visits and daily by use of a handheld spirometer/e-diary. Safety was assessed throughout the study.

Results

Of 65 randomized patients, 64 received at least one dose of study drug and were included in the safety analysis (33 active drug; 31 placebo). There were no severe AEs, treatment related SAEs, deaths, or withdrawals due to adverse events, and no medical device-related issues. There were no clinically meaningful changes in lab parameters, vital signs or ECGs. Furthermore, there was no evidence of immune suppression, opportunistic infections, or malignancies. Mild treatment-related adverse reactions occurred in both treatment groups (erythema and pruritus in two placebo patients; erythema in one TEV-48574 treated patient). Mild injection site reactions occurred more frequently (not statistically different) in the TEV-48574 group. Treatment-emergent anti-drug antibodies were reported in patients taking TEV-48574 (3 patients; 9.09%), with no anaphylactic or severe systemic reactions.

Conclusion

Overall, TEV-48574 administered every 2 weeks over 16 weeks demonstrated a favourable safety and tolerability profile with no emerging safety signals or evidence of immunosuppression. This is consistent with TL1A being an amplifier of inflammation. Treatment with TEV-48574 may dampen excessive inflammation without inducing a state of immunodeficiency in patients with conditions such as UC or CD, supporting further development in these indications.Read more P846 Impact of 5-ASA discontinuation in children with ulcerative colitis under biological therapyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Mesalamine (5-ASA) is recommended as a first-line medication for inducing and maintaining remission in mild to moderate ulcerative colitis (UC), but indications regarding its use in children with moderate to severe disease treated with biologics are lacking. We aimed to evaluate whether discontinuing 5-ASA might impact the outcomes of children with UC treated with anti-TNFα.

Methods

Retrospective, single-center, case-control study of children with UC receiving anti-TNFα therapy between January 2018 and January 2023 and with a minimum follow of 6 months. Children who discontinued 5-ASA within six months from the biological therapy initiation were compared to those who continued mesalamine as maintenance therapy. Every 6 months, during a 2-year follow-up, major outcomes defined as disease flares, IBD-related hospitalization, surgery, need for step-up treatment were recorded.

Results

Ninety-eight children were included in the final analysis, 51 (52%) maintained 5-ASA and 47 (48%) discontinued 5-ASA. The 2 groups were comparable for all the baseline clinical and demographic characteristics. At 6 months, the cumulative incidence of major outcomes, acute severe colitis and need for step up treatment was significantly higher in children who discontinued 5-ASA (p < 0.05). Throughout the follow-up period, children who discontinued 5-ASA were at significant higher risk of hospitalization (Log Rank p=0.02), need for step up treatment (Log Rank p=0.02) and acute severe colitis (Log Rank p=0.003).

Conclusion

Our data suggest that 5-ASA discontinuation might have a negative impact on the clinical course of children with UC treated with anti-TNFα in terms of major outcomes. However, conclusive evidence regarding this matter requires prospective randomized trials.Read more P1088 Real-world data on the treatment with Upadacitinib in a biological-experienced Crohn's disease cohortWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Upadacitinib was approved for the treatment of Crohn's disease in June 2023. However, real-world data, especially in biological-experienced patients, is scarce. We aimed to determine the treatment efficacy and persistence of Upadacitinib in treatment-experienced Crohn's disease (CD) patients

Methods

All patients treated for Crohn's disease in the IBD outpatient clinic of the University Hospital Frankfurt from 06/23-11/23 were retrospectively analyzed. Data on clinical (Harvey-Bradshaw index (HBI)) and biochemical disease activity (fecal calprotectin FC), as well as patient history, were collected. Patients were followed up for at least 12 weeks.

Results

Twenty patients with CD were included. All patients had already received at least one biological agent before starting upadacitinib. Six patients reported extraintestinal manifestations, most commonly arthralgia. Five patients had stenosis of the terminal/neoterminal ileum, and one patient underwent surgery during Upadacitinib induction. Five patients had preexisting fistulae; four reported fistulae activity at treatment initiation. The median Harvey-Bradshaw Index was 11. We report an HBI reduction after induction (8.5). The median FC level at induction was 719 ug/g. After the induction, the median FC was 216 ug/g. Nineteen of the twenty patients completed the induction period of 12 weeks at the time of this interim analysis. All patients continued with 30mg of Upadacitinib post-induction. The most common adverse event was acne. No significant changes in the patients' lipid status were observed.

Conclusion

We report preliminary real-world data on the treatment with upadacitinib. In our interim analysis, Upadacitinib is an effective and safe treatment in biological-experienced CD patients.Read more P982 Patients in trials of moderate-to-severe CD who are exposed to placebo are more likely to suffer harm than those receiving active treatment: The lack of clinical equipoise in traditional study designsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Crohn’s disease (CD) is a relapsing-remitting inflammatory disease of the gastrointestinal tract characterized by a progressive nature and a variety of complications. There are many challenges to the recruitment of eligible individuals into clinical trials for IBD, including the availability of multiple standard-of-care treatment options and patient refusal to participate in randomized placebo (PBO)-controlled trials due to fear of receiving PBO. Patient harm across clinical trials for moderate-to-severe CD has not been adequately examined. We sought to quantify the potential harms to patients recruited to PBO.

Methods

We reviewed phase 3 clinical trials of therapies including anti-TNF-alpha (infliximab, adalimumab, certolizumab pegol), anti-integrin (vedolizumab, natalizumab, etrolizumab), anti-interleukin (IL) 12/23 (ustekinumab), anti-IL23 (ustekinumab, risankizumab), and Janus kinase inhibitor (upadacitinib). We analyzed the proportions (# of pts. with events/cohort size) of adverse events (AEs), serious adverse events (SAEs), disease exacerbation AEs (DEAEs), and disease exacerbation SAEs (DESAEs). We calculated Number Needed to Harm (NNH), 1 / (Incidence rate in cohort) for PBO (NNHPBO) and experimental therapy (NNHRx) in each trial. Maintenance phase NNHs were categorized as treat-through (TT) or re-randomized (RR).

Results

We identified increased probability of AEs in the PBO arm of 5/12 induction (NNHPBO= 1.2-3.6; NNHRx=1.2-5.2), 3/6 TT maintenance, and 6/9 RR maintenance (NNHTTPBO= 1.2-3.4; NNHTTRx= 1.1-4.5; NNHRRPBO= 1.0-2.0; NNHRRRx= 1.1-1.4). There was an increased probability of SAEs for patients exposed to PBO in 4/11 induction (NNHPBO= 6.6-24.7; NNHRx= 4.8-26.6), 5/6 TT, and 8/9 RR (NNHTTPBO= 3.4-15.1; NNHTTRx=3.6-19.0; NNHRRPBO= 6.0-13.1; NNHRRRx= 8.1-11.9). Patients were at increased probability of DEAEs in the PBO arm of 5/8 induction (NNHPBO= 6.3-12.3; NNHRx= 10.0-62.0), 5/5 TT, and 6/9 RR (NNHTTPBO= 3.1-8.5; NNHTTRx= 4.4-24.0; NNHRRPBO= 2.5-7.0; NNHRRRx= 7.1-9.4). There was an increased probability of DESAEs for patients exposed to PBO in 5/6 induction (NNHPBO = 10.4-42.4; NNHRx= 43.2-206.0), 3/4 TT, and 3/4 RR (NNHTTPBO= 11.4-42.4; NNHTTRx= 8.2-216.0; NNHRRPBO= 15.5-26.8; NNHRRRx= NA).

Conclusion

In PBO-controlled clinical trials of therapies for moderate-to-severe CD there are increased AEs and SAEs for patients exposed to PBO, notably in DEAEs and DESAEs. Induction treatment responders re-randomized in maintenance to PBO experienced greater harms (i.e. lower NNH) than TT PBO patients. These findings raise concerns about clinical equipoise and support ongoing efforts to design trials with active comparator arms and adaptive or platform methodologies.Read more P1094 Rectal cancer in patients with inflammatory bowel disease - a nationwide cohort studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Patients with inflammatory bowel disease (IBD) have an increased risk of colorectal cancer. The aim of this study was to investigate surgical outcome and survival in patients with rectal cancer (RC) with and without IBD.

Methods

The study was performed as a national population-based cohort study based on the Colorectal Cancer Data Base (CRCBaSe). All patients ≥18 years of age with a diagnosis of stage I-III RC treated with curative intent during the period 1997-2021 were included, with preliminary data for 1997-2016 available. Overall and disease-free survival after surgery was compared between patients with and without a previous diagnosis of IBD. Adjusted flexible parametric survival models were used to estimate proportional and time-dependent hazard ratios (HRs) with 95% confidence intervals (CIs). Updated data until 2021 with addition of cause-specific survival and perioperative data will be made clear by the time of the ECCO congress.

Results

In all, 16,263 patients with RC were included in the study, 1997-2016, among whom 235 had IBD. Patients with IBD were significantly younger, had a higher CCI, and lower tumours at diagnosis of RC, compared with patients without IBD. Among IBD patients, 45 (19.2%) were previously operated with colectomy, and 14 of these were reconstructed with ileorectal anastomosis. Among IBD patients, pT4 tumours were more prevalent (8.9%) than in patients without IBD (5.1%). Clear resection margins were less common in patients with IBD (90.6%) versus patients without IBD (95.1%). From preliminary adjusted analyses allowing the relative mortality rate to vary over follow-up time, RC patients with IBD experienced worse progression-free survival during the second year after surgery, after which their progression-free survival was superior in comparison with IBD-free patients.

Conclusion

The prognosis in RC patients with and without IBD varied over time. RC patients with IBD had an inferior progression-free survival initially, followed by an improved prognosis for the majority of the follow-up time. Despite a higher rate of pT4 tumours, R1-resections and lower tumors among IBD patients, unadjusted overall survival did not differ significantly compared to non-IBD CRC patients.Read more P847 Effectiveness of tofacitinib in ulcerative proctitis compared to left sided colitis and pancolitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Ulcerative proctitis (UP), though associated with high symptom burden and poor quality of life, is excluded from most of the randomized controlled trials in UC. We aimed to analyse the effectiveness of tofacitinib in UP, and compare it to that in left sided colitis (LSC) and pancolitis (PC).

Methods

This was a prospective observational cohort study. Patients with either steroid-dependent or refractory ulcerative colitis, who received tofacitinib, were divided into three groups based on the disease extent [UP, LSC and PC]. The primary outcome was comparison of proportion of patients in clinical remission in the three groups, at weeks 8, 16 and 48. Safety outcomes were reported using incidence rate per patient year of exposure.

Results

Clinical remission was achieved in 47%(15/32), 24%(23/94), and 43%(23/54) of patients at week 8, 56%(18/32), 37%(35/94), and 55%(30/54) of patients at week 16, and 59%(19/32), 38%(36/94), and 24%(13/54) of patients at week 48 in groups UP, LSC and PC, respectively. (Figure 1) Corticosteroid-free clinical remission rates were significantly higher in patients in groups UP at week 48. Five (15%) patients with UP were primary non-responders to tofacitinib at week 16, while three (9%) patients had secondary non-response at week 48. The median fecal calprotectin values at week 8 were 119.5 (53.75-611.25), 134 (63-456) and 208 (48.25-876) in patients with UP, LSC and PC, respectively. Similarly at week 48, the median fecal calprotectin values were the lowest in patients with UP (57[36-99]) as compared to patients with LSC (113[41-572]) and PC (150[89-1562]). The endoscopic remission rates at week 48 were similar in all the three groups (31%, 21% and 18% in groups UP, LSC and PC, respectively (UP vs LSC, p=0.25; UP vs PC, p=0.18; LSC vs PC, p=0.68). The probability of sustained clinical response was highest in patients with UP (cumulative probability of maintaining response 0.88) followed by groups LSC (cumulative probability of maintaining response 0.74) and PC (cumulative probability of maintaining response 0.60). The between group difference, was significant (Log Rank, p=0.03). (Figure 2) Patients with UP had the lowest incidence of adverse effects.

Conclusion

The effectiveness of tofacitinib in inducing and maintaining remission is greater in patients with UP compared to LSC and PC.Read more P848 Risankizumab Effectiveness in Ustekinumab-naïve and Ustekinumab-experienced Patients with Crohn’s Disease- Real-world Data from a Large Tertiary CenterWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Risankizumab and ustekinumab are both IL23 inhibitors approved for treating moderate to severe Crohn’s disease (CD). They are distinguished by the fact that ustekinumab targets p40, the shared subunit of both IL23 and IL12, while risankizumab targets the p19 subunit and thus selectively inhibits IL23. The effectiveness of risankizumab in ustekinumab-experienced patients is of particular interest due to similar mechanisms of action. We present a large long-term real-world experience with risankizumab in ustekinumab-naïve and ustekinumab-experienced patients with CD.

Methods

We prospectively followed patients with CD treated with risankizumab in our center and documented their disease activity score at weeks 2, 4, 8, 12, 26, and 52 after treatment initiation. Patients treated for active luminal disease, defined as HBI≥5, fecal calprotectin≥250, or evidence of active disease per ileocolonoscopy or imaging were included. Patients who stopped treatment due to ineffectiveness or intolerance were counted as non-responders for the purpose of remission-rate calculation at each time point.

Results

102 patients with CD with active luminal disease were treated with risankizumab and had at least 12 weeks of follow-up. Of them 46 (45%) were ustekinumab-naïve, and 56 (55%) were ustekinumab-experienced. The ustekinumab-experienced patients had longer disease duration and higher rates of prior bowel resection and exposure to multiple advanced therapies (Table 1). The baseline median HBI was higher in the ustekinumab-experienced group. Both groups had a continuous downward trend throughout the follow-up period (Figure 1A). At week 12, 74% (34/46) of the ustekinumab-naïve and 55% (31/56) of the ustekinumab-experienced patients achieved steroid-free clinical remission (SFCR) (P=0.06). At week 26, SFCR rates were 76% (25/33) and 60% (21/35) in ustekinumab naïve and experienced patients respectively (P=0.2). In a subgroup of patients with a follow-up of one year, 71% (5/7) and 40% (6/15) were in SFCR at week 52 (P=0.36) (Figure 1B). Of the patients who achieved SFCR at week 12, 85% in both groups maintained SFCR at week 26 (23/27 and 17/20 in ustekinumab-naïve and ustekinumab-experienced cohorts, respectively).

Conclusion

In this large real-world experience with long-term follow-up, we found that patients with CD treated with risankizumab were statistically similarly likely to achieve and sustain SFCR regardless of prior ustekinumab experience. Non-statistical differences noted may reflect the longer disease duration and prior treatment exposure of the ustekinumab-experienced group. These findings support the consideration of risankizumab as a treatment option for patients with CD regardless of their prior exposure to ustekinumab.Read more P983 Treatment of patients with moderate-to-severe Crohn’s disease with subcutaneous infliximab leads to an endoscopic response across all segments of the colon and terminal ileum: A post hoc analysis of the LIBERTY-CD studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Mucosal healing (MH) has been associated with positive long-term clinical and surgical outcomes in patients (pts) with Crohn’s disease (CD).¹ Patterns of MH vary by therapeutic agent, with limited efficacy in the terminal ileum.^2–4 This post hoc analysis aimed to investigate the pattern of endoscopic MH across intestinal segments in pts who received subcutaneous (SC) infliximab (IFX) maintenance treatment in the Phase 3 LIBERTY-CD study.

Methods

LIBERTY-CD demonstrated superior efficacy of SC CT-P13 120 mg every 2 weeks (Q2W) vs placebo (PBO) after IV IFX induction for clinical remission and endoscopic response at Week (W) 54.⁵ This post hoc analysis evaluated centrally read and batch analysed Simple Endoscopic Score for Crohn's Disease (SES-CD) values obtained at screening, W22 and W54 for 5 ileocolonic segments (rectum; left, transverse and right colon; and terminal ileum). Pts with missing data or who underwent dose escalation to SC IFX 240 mg Q2W upon loss of response from W22 were imputed as non-responders. Endoscopic complete MH (CMH; defined as SES-CD=0) or partial MH (PMH; defined as ≥50% decrease in the SES-CD from screening) were evaluated for segments that had endoscopic abnormalities at screening (segmental SES-CD ≥1 at screening). Results were analysed descriptively.

Results

Among all randomised pts (N=343; SC CT-P13: n=231, PBO: n=112), the most frequently affected segment at screening was the left colon (187/343; 54.5%), followed by the right colon (185/343; 53.9%), rectum (163/343; 47.5%), terminal ileum (156/343; 45.5%) and transverse colon (134/343; 39.1%). In an analysis of all affected segments, endoscopic CMH rates were higher with SC CT-P13 vs PBO (Figure 1A). Endoscopic CMH rates in the terminal ileum at W54 were 46.7% and 19.6% in the SC CT-P13 and PBO arm, respectively (p=0.0014). PMH rates were also significantly higher in the SC CT-P13 arm across all segments at W22 and W54 (Figure 1B), with rates in the terminal ileum of 64.8% and 33.3% in the SC CT-P13 and PBO arm, respectively (p=0.0003).

Conclusion

SC IFX 120 mg Q2W led to high and consistent endoscopic MH rates across all segments, including the terminal ileum. Early observation of endoscopic MH (at W22) underscores the potency of SC IFX treatment. Further studies are warranted to investigate the association between segmental MH and long-term outcomes.¹Otte ML et al. World J Gastroenterol 2023;29:1157–72.²Danese S et al. Gastroenterology 2019;157:1007–18.³Reinisch W et al. J Crohns Colitis 2017;11:425–34.⁴Wu Y et al. Therap Adv Gastroenterol 2020;13:1756284820976923.⁵Hanauer SB et al. Gastroenterology 2023;164(S6):S220–1.Read more P1102 Adherence to a Mediterranean dietary pattern in patients with Crohn's disease in remission is associated with lower fecal calprotectin levelsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The Mediterranean Diet (MD) was recently found to be beneficial for Crohn’s Disease CD patients in various stages of the disease. The MD emphasizes the intake of foods that are fiber-rich and high in polyphenols, along with avoidance of ultra-processed foods (UPF) and a low intake of red meat. Previous data show that these dietary patterns could promote gut health and mucosal healing. However, little is known about the overall adherence to the MD and its association with biochemical activity in CD patients in remission. Therefore, we aimed to assess overall adherence to the MD and to investigate the association between adherence to the MD and fecal calprotectin (FC) levels in patients with CD in clinical remission and fecal biochemical inactivity.

Methods

A cross-sectional analysis of a prospectively maintained database of patients with CD in clinical remission [Harvey-Bradshaw Index (HBI)<5] and fecal biochemical inactivity (FC <250µg/g). FC levels of ≤150µg/g was further categorized as significant biochemical inactivity.Patients were assessed for their medical status, clinical and biochemical disease activity, and nutritional intake by using a Food Frequency Questionnaire (FFQ). The Israeli Mediterranean dietary screener (I-MEDAS) was used to assess adherence to the MD. A positive score for each food component was assigned when a specific cut-off criterion was met. For overall adherence to the MD, the median score of the study sample was used as a cut-off for the classification of “adherence” or “non-adherence”.

Results

A total of 88 patients were included in this analysis. A high proportion of patients qualified for a positive score for low consumption of butter and margarine (96.6%), salty snacks (94.3%), and savory pastries (83.0%), while a low proportion of patients qualified for a positive score for high intake of whole grains (8.0%), fish (20.9%), fruit (9.1%), and legumes (28.4%) (Figure 1). Twenty-nine patients (32.9%) were adherent to the MD. This group of patients had higher rates of significant biochemical inactivity (i.e., FC≤150µg/g), compared to non-adherent patients (96.6% vs. 79.7% respectively, p=0.036) and lower occurrence of soft/liquid stool (p=0.044). Furthermore, low intake of savory pastries and red/processed meat was associated with significant biochemical inactivity [p=0.026 and p=0.020, respectively.

Conclusion

Overall adherence to the MD among patients with CD in clinical remission and biochemical inactivity is relatively low, with a low intake of beneficial food groups on one hand, and a low intake of UPF on the other hand. Adherence to the MD was associated with lower FC levels. Future studies should examine the long-term effects of the MD on the maintenance of clinical and biochemical remission.Read more P842 Assessment of body composition parameters in patients with inflammatory bowel disease treated with biological therapyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

There is growing evidence of the role of biological therapy (BT) in improving body composition parameters (BCP) in inflammatory bowel disease (IBD) patients. Since myopenia and high adiposity affect prognosis and could lead to treatment failure, there is the need for expanding the assessment of BCP in clinical practice beyond traditional measures like body mass index (BMI).

Methods

A cross-sectional study included 151 IBD patients treated with BT (80 males, 83 Crohn`s disease, 68 ulcerative colitis, mean age 37). Bioelectrical Impedance Analysis (InBody170) was done to estimate: body weight, BMI, skeletal muscle mass (SMM), body fat mass (BFM), percent body fat (PBF), fat free mass (FFM). Dividing SMM, FFM and BFM by height squared, we calculated the skeletal muscle mass index (SMI), fat-free mass index (FFMI) and fat mass index (FMI).

Results

In relation to BMI, 84 (55.6%) patients had healthy weight, 41 (27.2%) were overweight, 13 (8.6%) were obese and 13 (8.6%) were classified as underweight. Clinical remission was present in 139 (92.6%) patients. The average values of the measured BCP are as follows: body weight 71.7kg (41.4-123.7); body height 174.6±10.9cm; BMI 23.7kg/m² (15.1-36.9); PBF 24.6% (5-48); SMI 9.7kg/m² (6.3-13.5); FFMI 17.5kg/m² (12.0-23.5); FMI 5.7kg/m² (1.0-17.3). Muscle mass parameters were significantly higher in the group of patients treated with BT longer than 3 months (SMI p=0.01, FFMI p=0.02), while in the group of patients treated longer than 1 year we observed, apart from muscle mass parameters, a significant increase in adiposity parameters (FMI p=0.02, PBF p=0.06). [WU1] Patients who previously had the need for change of BT type had significantly higher values of FMI (p=0.04). Patients with extraintestinal manifestations (EIMs), compared to the group without EIMs, had statistically significantly lower values of body weight (p=0.02), SMI (p=0.01), and FFMI (p= 0.01). There was no statistically significant difference in BCP by IBD subtype, presence of clinical remission, BT type and protocol, previous operations, corticosteroids, mesalazines and azathioprine use.

Conclusion

The duration of treatment with BT can significantly affect muscle mass and adiposity parameters, leading to improved muscle mass parameters after 3 months of therapy, while an increase in adiposity markers is observed after 12 months of BT. Our findings suggest a potential association between EIMs and muscle mass alterations, as well as a relationship between the need for a change in BT type and higher adiposity parameters.Read more P984 VEST: The UK vedolizumab real life experience study in Inflammatory Bowel DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The characteristics and outcomes of patients treated with vedolizumab in routine healthcare settings have not been widely evaluated in the UK.

Methods

Prospective, multicentre observational study of 364 patients started on vedolizumab in UK practice from January 2017 until February 2019 using the UK IBD Registry clinical web-based tool. For the present analysis, the primary outcome was drug survival (persistence) at 1-year, defined as attendance for infusion ≥48 weeks after the first dose. Secondary outcomes were: Clinical remission (CR, based on partial Mayo score [≤1] or Harvey Bradshaw index [≤4]), physician global assessment (PGA), IBD-Control Questionnaire (IBD-Control-8, IBD-Control-VAS and individual item scores), laboratory parameters and adverse events.

Results

Age (mean): 44 yrs; Males: 48%; IBD duration (mean): 6 yrs; Prev. resection: 18%; Steroids at baseline: 39%; Outcomes are summarized in Table 1. 37% of CD patients were assessed as being in clinical remission at baseline. Overall, 210 (58%) continued treatment beyond 48 weeks. At 1 year, 67.1% and 52.3% of CD and UC patients were in clinical remission with a clear improvement in QoL as assessed by IBD-Control -8. There were significant improvements across each IBD-Control-8 domain, including fatigue, with few patients considering switching treatment at that point (Figure 1).

Conclusion

Vedolizumab was effective in clinical practice with 58% of patients remaining on treatment at one-year. Baseline status differed significantly from those recruited into RCTs. Patient reported outcomes demonstrated significant and meaningful improvements across physical, psychological, social and treatment domains.Read more N27 Group meetings for adolescents with IBD: results of a survey on patients’ interestsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The increase in both the incidence and prevalence of IBD, especially in people under 21 years of age^1,2,3 outlines new issues to be considered in caring for these patients, like the psychosocial effects on both adolescents and their families, school absences, and developmental delay². The need for better support to improve their HRQoL⁴, the embarrassment related to the disease, the anxiety about a sudden appearance of gut symptoms, frequent hospital admissions, and diet restrictions, can lead to social isolation^5,6. Group meetings designed to make adolescents and young adults with IBD meet each other and with healthcare professionals (HCP) who are experts in IBD can create a safe environment in which to discuss fears, everyday problems and possible solutions, and any doubt about their condition. This could also provide support, suggestions, and opportunities to peer-compare, further promoting social relationships. This study investigated their willingness to participate in this experience and what they consider important to discuss.

Methods

A focus group involving HCP from a paediatric gastroenterology clinic and interviews with a sample of patients provided the basis on which a clear and easy-to-understand survey was developed concerning interest in the project, willingness to participate, topics to be discussed, and needs of peer relationship. The survey was then performed collecting anonymous data to avoid any kind of potential bias.

Results

Twenty-two patients aged 14 to 19 years completed the survey, showing their poor occasions of discussion about the disease and its related issues with other patients (54.5% of them do not know people with IBD) even if they can talk with their family, HCP and peers outside the hospital or outpatient clinic settings (tab 1). The willingness to participate in a group meeting is higher in the oldest subjects, and they show the highest interest in a peer relationship with patients of the same age and expert HCP. The topics considered more significant are 'nutrition' and 'mood' (described by almost two-thirds of patients) followed by ‘symptoms’ and ‘social life’ (fig 1). The best meeting schedule from the patient's point of view is every 6-8 weeks, with both in-person and virtual participation.

Conclusion

This study provides useful information on the feasibility and willingness of young patients with IBD to participate in such interventions. After the experimental application of group meetings, it will be mandatory to let patients provide feedback on this activity and to assess their effects on patients’ psychosocial well-being.References (DOI)1 10.1016/j.crohns.2013.01.0102 10.1053/j.gastro.2021.12.2823 10.1016/j.gtc.2023.05.0014 10.1093/ibd/izy0415 10.1007/s10880-021-09778-06 10.1111/hsc.13755Read more P829 Clostridioides difficile infection in patients using vedolizumab and antiTNF: incidence and consequences (CDIFVEDO study of GETECCU)Wed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Clostridioides difficile infection (CDI) is a frequent cause of flares in inflammatory bowel disease (IBD) and it is related to higher risk of colectomy and mortality. The incidence of CDI in IBD is higher than in the general population and it has increased in recent years. Biologic therapy could be risk factor for CDI, but the evidence is scarce.The aim of the study was to compare CDI incidence between IBD patients treated with anti-tumor necrosis factor (antiTNF) agents and VDZ. Secondary endpoints were outcomes related to CDI (hospital admission, intensive care monitoring, colectomy) and IBD (steroids requirement, switch of biologic therapy, surgery).

Methods

Retrospective observational multicenter study conducted in 23 Spanish hospitals, promoted by GETECCU, including patients with ulcerative colitis or Crohn’s disease with colonic involvement who had CDI after complete induction of antiTNF (group 1) or VDZ (group 2) between 2018 and 2021. Hospitals also provided the total number of patients who initiated antiTNF or VDZ during that period.The chi-square test was used to compare categorical variables, and the Mann–Whitney U-test to compare quantitative variables.

Results

A total of 3860 IBD patients with antiTNF treatment and 780 with VDZ were reviewed. 63 patients with CDI were identified: 45 in group 1 and 18 in group 2. Incidence of CDI was statistically higher in group 2 than in group 1 (2.3% vs 1.2% respectively; p=0.01). Baseline characteristics of patients with CDI in both groups are shown in Table 1. Risk factors for CDI (chronic kidney failure, hospitalization, previous antibiotic usage, previous CDI) were distributed similarly between groups, except proton pump inhibitor treatment (35.6% in group 1 vs 76.5% in group 2; p=0.01).No significant differences in the evolution of CDI were found between groups. Hospital admission rate was 53.3% in group 1 and 27.8% in group 2 (p=0.09). None required intensive care or colectomy caused by CDI. Recurrent CDI (within 8 weeks) occurred in 8.9% in group 1 and 11.1% in group 2 (p=0.79).Outcomes of IBD were similar between groups, regarding steroid treatment (51.1% in group 1 vs 50% in group 2; p=0.94) and switch of biologic therapy (37.8% in group 1 vs 50% in group 2; p=0.37). During follow-up, there was 1 case (group 1) of perforation in the 1st month and 5 patients (4 in group 1; 1 in group 2) required surgery for medically refractory disease between the 3rd and 6th month. One patient (group 1) died (non-IBD or CDI-related cause).

Conclusion

Incidence of CDI was higher during VDZ therapy compared with antiTNF. The evolution of CDI and IBD tends to be similar between groups. More data are needed to consider VDZ as a risk factor of CDI.Read more P1026 Clinical decision support tool for vedolizumab could not predict outcome in ulcerative colitis patients – a retrospective real-life single-centre cohort studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Early intervention with biologics can slow the progression of ulcerative colitis (UC), thus improving long-term outcomes. As treatment options in UC expand, the positioning of advanced therapies is becoming more important. The ability to identify patients with UC who are more likely to respond well to a specific drug before initiation of treatment could help physicians navigate within the proposed treatment algorithm. Dulai et al. derived and validated a clinical decision support tool (CDST) for the prediction of response to vedolizumab (VDZ) in UC.

Methods

We performed a retrospective single-centre cohort study based on UR-CARE registry data. Data for 72 UC patients treated with VDZ from July 2016 until April 2023 were analysed. CDST for UC was calculated using four variables: absence of exposure to a tumour necrosis factor (TNF) alpha inhibitor, disease duration of ≥ 2 years, moderate baseline endoscopic activity and baseline albumin concentration. Patients were then stratified into three probability groups: group 0 with low (≤ 26 points), group 1 with intermediate (27 to ≤ 32 points) and group 2 with high (> 32 points) probability of response. To test the association between CDST, clinical remission (CR) (defined as PRO2 £ 1 with rectal bleeding score 0), corticosteroid-free remission (CSFR) and endoscopic activity (defined as no change in endoscopic activity, endoscopic improvement (EI) (change of endoscopic Mayo of ≥1), or endoscopic remission (ER) (endoscopic Mayo ≤ 1)) chi² test was used. The difference in faecal calprotectin (FC), depending on whether VDZ was continued or not, was tested by the Mann-Whitney U test.

Results

In our cohort, 59.7% of patients were male, the median age was 32.1 years, the median duration of disease until VDZ was 2.6 years, and 63.9% had pancolitis. 34.7% of patients had concomitant corticosteroid treatment at baseline, and 52.8% had been exposed to a TNF-alpha inhibitor. We found no statistically significant association between the CDST group and CR or CSFR at weeks 14 and 52 nor endoscopic activity at follow-up endoscopy. All patients in group 2 responded with lowering of FC 3-6 months after initiating VDZ and continued treatment. Also, patients in CDST group 1 who experienced lowering of FC continued VDZ therapy. In contrast, all patients in CDST group 0 and patients in group 1, who had persistently elevated FC, eventually failed VDZ regardless of optimisation. The difference in FC between those who discontinued VDZ and those who did not was statistically significant (p=0.004).

Conclusion

Our results did not confirm the predictive value of existing CDST for VDZ in UC patients. Novel prediction tools in UC are needed.Read more P830 The potential role of artificial intelligence in selecting the modality of biological therapy in patients with inflammatory bowel diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Selecting an appropriate treatment strategy for inflammatory bowel disease (IBD) is an important task that can significantly alter the clinical course of the disease. Advanced artificial intelligence language models, such as ChatGPT, represent a potential future option that can assist practitioners. ChatGPT can help search the internet for medical facts by summarizing information from medical sources and providing concise explanations, simplifying the process of accessing and understanding medical information.

Methods

A ChatGPT-guided analysis of 89 IBD patients treated at the Clinical Department of Gastroenterology and Hepatology at University Medical Center "Zvezdara", Belgrade was conducted, considering further treatment with some biological drugs. A treatment modality proposal was obtained through communication with the interactive software ChatGPT (OpenAI, CA USA) and providing complete clinical and laboratory data. The alignment of decisions was analyzed, along with an assessment of treatment success in the group with matching and differing choices.

Results

In 72 patients (81%), there was concordance in the choice of therapy between ChatGPT and the medical consultation, while in 17 patients, ideas about the treatment approach differed. The most common difference in the choice of therapeutic modality related to the software's selection of ustekinumab compared to our choice of vedolizumab in patients with Crohn's disease who were not biologically naive, affecting seven patients with these characteristics. In 4 patients with severe ulcerative colitis, ChatGPT recommended using cyclosporine in combination with vedolizumab, contrary to the medical consultation's decision to use Anti-TNFα therapy. The group of patients in whom the artificial intelligence advice differed from the medical consultation was in a clinically more severe stage of the disease (CRP 10.4 vs. 9.1, p=0.0293), with worse endoscopic findings (proportion of severe endoscopic disease SES CD≥33/Mayo score>2, 53% vs. 24%, p=0.019). Taking into account the baseline differences in these patient groups, multiple analyses of covariance did not reveal a significant difference in the ultimate treatment outcome - proportions of endoscopic (p=0.773) and clinical remission (p=0.296) between patient groups.

Conclusion

The integration of advanced artificial intelligence language models may represent a future tactic with the potential to assist practitioners in making decisions about the treatment modality for IBD patients, but clinical experience should be considered.Read more P1072 Upadacitinib appears effective in inducing clinical, biochemical, endoscopic and histologic improvements in previously treatment refractory Ulcerative ColitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Upadacitinib is a novel, oral agent which acts by inhibition of JAK signaling. It has proven efficacy in large-scale, randomised trials for the treatment of UC. We report our real-world experience of upadacitinib as induction therapy in a single centre study of UC patients, including patients who were refractory or intolerant of other advanced therapies.

Methods

We performed a retrospective analysis of outcomes in patients who were commenced on upadacitinib for UC at a tertiary IBD centre between October 2022 to October 2023. The parameters used to assess disease activity were the Simple Clinical Colitis Activity Index (SCCAI), faecal calprotectin (FCP), Ulcerative Colitis Endoscopic Index of Severity (UCEIS) and Nancy Histological Index (NHI). Clinical response was defined as a reduction of SCCAI of ≥3 points, clinical remission as SCCAI of ≤2, biochemical remission as FC<150ug/g. Endoscopic remission was defined as UCEIS 0-1 and histological remission as NHI 0-1. Medical records were reviewed for patient-reported adverse events.Wilcoxon matched-pairs signed rank test was used to compare pre- and post-treatment continuous variables.

Results

42 patients were started on 45mg once daily upadacitinib over this period. 20 were female, the mean age was 39. 31 had left sided disease, 8 had pancolitis. 39 (93%) patients had prior experience of advanced therapy and 22 (52%) had ≥2 prior therapies.At baseline, mean SCCAI was 7 (1-15), and mean FCP 1328 (42-6810) μg/g. Baseline endoscopy demonstrated a mean UCEIS of 5 (3-7) and baseline histology a mean NHI of 3 (1-4).At the 6-week follow up, paired data on clinical and biochemical responses were available in 23 and 27 patients respectively, showing an improvement to a mean SCCAI of 3 (p=0.0004) and mean FCP of 491 μg/g (p=0.002). 16 (70%) achieved clinical response, 14 (61%) were in clinical remission. 15 (56%) had a reduction in FCP to <150 μg/g.Endoscopic reevaluation took place after a minimum of 12 weeks on treatment. Paired endoscopic outcomes in 20 patients demonstrated an improvement of UCEIS to a mean of 1 (p<0.0001), with 16 (80%) patients in endoscopic remission. Week 12 histology showed improvement to a mean NHI of 2 (p<0.0001, n=19), with 9 (47%) patients achieving histological remission.6 (14%) patients were non-responders. 3 required a colectomy, 2 necessitated a switch in medical therapy, 1 remained on extended induction.3 patients (7%) reported facial acne as an adverse event, no others were reported.

Conclusion

Upadacitinib appears effective at inducing significant clinical, biochemical, endoscopic and histological improvements within 12 weeks, amongst a real-world cohort of patients with moderate-to-severe UC that has proved refractory to other advanced therapies.Read more P1027 Optimizing IBD Medication and Therapy: An Interdisciplinary University Outpatient ApproachWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

A large proportion of patients with chronic inflammatory bowel disease (IBD) take a wide range of different medications, which harbor a potential risk of pharmaceutical (pharm.) interactions. Furthermore, these patients frequently seek professional advice regarding additional medications or alternative treatment options. In this study, an interdisciplinary medical-pharmaceutical team conducted a standardized survey and a pharmaceutical medication check in an IBD outpatient department. The aim was to evaluate and enhance individual therapy adherence and medication safety.

Methods

Prior to the appointment, patients were requested to provide their current medication list and to complete a standardized questionnaire regarding their general compliance and any unmet questions or concerns about their IBD therapy. A clinical pharmacist analyzed the questionnaire and carried out a thorough assessment of the list of medications for possible interactions and the potential for improvement. One day before the patient`s appointment, the pharmacist presented his findings to the treating physician, and possible interactions were discussed. After the appointment, patients were asked to complete a second questionnaire regarding their experience and possible changes in therapy, as well as their previous concerns or responses.

Results

The data from Questionnaire 1 showed two main results: (I) Overall adherence to therapy was found to be sufficiently high, as most patients reported taking their medication regularly and being aware of the main principles of their therapy. (II) Many patients expressed concerns about possible long-term side effects of their therapy and indicated that they needed additional information about their medication (Figure 1A).Concerning the provided medication plan, 77% of all participants took more than 5 drugs and in 94% of the cases, no previous medication check had been performed. The involved clinical pharmacists suggested 1.3 interventions per patient and in 50% of all cases, at least one medication was discontinued or newly started (Table 1). In the follow-up survey, most patients stated that the interdisciplinary medical counseling had improved both their knowledge and their sense of security of their IBD treatment (Figure 1B).

Conclusion

The interdisciplinary review and monitoring of the current therapy and the individual medication of IBD patients increased patient-specific compliance and medication safety and should therefore be intensified in the future.Read more P831 Acute infusion reactions due to different biologic agents in a large cohort of patients with Inflammatory Bowel DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The therapeutic armamentarium for inflammatory bowel disease (IBD) includes several biological agents: infliximab (IFX), adalimumab (ADA), vedolizumab (VED) and ustekinumab (UST). Persistence in therapy with these drugs is not satisfactory, not only due to the loss of clinical response over time but also due to adverse events. Acute infusion reactions (AIRs) occur during or within 24 hours of the infusion. The intensity of AIRs ranges from mild (flushing, dizziness, headache, itching, rash) to severe (anaphylactic). The primary aim of this study was to compare the prevalence rates of AIRs due to the different biological agents in a large cohort of patients with IBD and to assess risk factors for AIRs.

Methods

All reports of AIRs occurring from January 2021 to October 2023 in IBD patients treated with different biological agents (IFX, ADA, VED and UST) in a tertiary IBD center were retrospectively reviewed. The electronic records of the identified patients were checked for the type of IBD, whether Crohn's disease (CD) or ulcerative colitis (UC), type of biological agent, route of administration (intravenous or subcutaneous), concomitant immunosuppressive therapies, atopic status. Furthermore, the type of treatment for the AIRs and the subsequent therapy undertaken for IBD were also recorded.

Results

22 AIRs were recorded out of 1911 patients (1.1%). Of these, 16/550 in patients on IFX biosimilars (2.9 %), 4/590 (0.7%) in patients on ADA biosimilars, 2/318 (0.6%) in patients on VED and 0/453 (0%) in patients on UST (Table 1). The difference in the prevalence of AIR rates observed with the different biological agents was statistically significant (p<0.01). 7 of 16 post-IFX AIRs were moderate-severe, with two episodes of anaphylaxis occurring in patients with CD. The two patients treated with VED experienced only mild symptoms, and no anti-reactive treatment has been used; two mild and two moderate AIRs, respectively, have been reported among patients on ADA. 12 of 22 AIRs occurred during the induction period (from the first to the third administration). 7 of 22 patients had previous allergic reactions.

Conclusion

Our real-world data on a large population of IBD patients treated with biologic agents confirm that AIRs are rare and occur mainly in patients treated with IFX biosimilars. Most patients who experienced AIRs were atopic. Almost all patients after AIRs changed biological agents within or out of the same biological class. Further studies are necessary to confirm our results and better characterise the profile of patients at greater risk of AIRs.Read more P1087 A retrospective study on the GLIM criteria for assessing malnutrition in patients with Crohn's Disease and its correlation with clinical outcomesWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

It is a common occurrence for patients with Crohn's disease (CD) to suffer from malnutrition. A novel approach to assessing malnutrition has been devised by the Global Leadership Initiative on Malnutrition (GLIM). Therefore, the objective of this study was to investigate the prevalence of malnutrition in CD patients using GLIM criteria and evaluate the clinical utility of GLIM in this population.

Methods

A retrospective cohort study was conducted with 386 patients with Crohn's disease. Data were extracted from the medical records, including demographic and clinical characteristics. All patients were evaluated using the nutritional screening and diagnosis criteria of the NRS 2002 and the GLM criteria. The prevalence of malnutrition was reported and the relationship between malnutrition and clinical outcome was analyzed.

Results

The prevalence of malnutrition among CD patients was 73.6% and 35.1% in mild malnutrition, 35.4% in moderate malnutrition, and 35.4% in severe malnutrition. The majority (143, 50.4%) of malnourished patients were categorized as B2 or B3 phenotype, with a significant difference (P= 0.001). The malnourished group had significantly higher CDAI scores than the non-malnourished group (122.9±70.5 vs. 77.3±61.3, P<0.001). In the primary cohort, patients at risk of malnutrition with inflammatory load exhibited a significantly worse clinical outcome compared to those without inflammatory load (OR 4.07, 1.56-10.7; P=0.004).

Conclusion

Malnutrition caused by Crohn's disease is a significant issue for numerous patients. Malnutrition identified using the GLIM criteria was found to be associated with CDAI, age, and behavior, providing prognostic value for clinical outcomes.Read more P832 Postoperative fever and CRP levels as predictive markers of postoperative recurrence of Crohn’s disease after ileocolic resectionWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Studies have shown that postoperative C-reactive protein (CRP) levels in patients with Crohn’s disease (CD) undergoing ileocolic resections (ICR) are higher than in control patients operated for cancer. This study aims to verify the association between postoperative fever and CRP levels with CD recurrence.

Methods

We performed a single-centre retrospective study of all CD patients undergoing an ICR between 2009 and 2019. CRP levels and fever (body temperature >38.5 °C) were measured preoperatively and during the first 7 postoperative days (POD). A colonoscopy was performed within 12 months after surgery. Endoscopic postoperative recurrence (POR) was defined as a modified Rutgeerts score ≥i2b. Surgical recurrence as the need for reoperation due to CD recurrence at the level of the ileocolic anastomosis. A multivariate regression model for longitudinal measures was used to obtain estimates of postoperative CRP levels. Association between fever and estimates of CRP levels with endoscopic and surgical POR was evaluated through a multivariate analysis including sex, age, Montreal classification, use of advanced therapies prior to surgery, associated surgical procedures, smoking habit, and continuation/initiation of medical therapy after surgery.

Results

We identified 372 patients, of which 299 (80.4%) had complicated CD (Montreal B2+B3) and 166 (44.7%) already received advanced therapies before surgery. 92 (24.7%) were active smokers at the time of surgery. In 26 patients (7.0%), one or more strictureplasties were performed simultaneously to the ICR. Prophylactic medical treatment was restarted/initiated immediately after surgery in only 9.7% of the patients. Estimates of CRP level at POD -1, +1, +3, and +5 were 9.23 mg/L (CI 7.85;10.86), 63.05 mg/L (CI 58.63;67.80), 82.55 mg/L (CI 75.09;90.76), and 56.79 mg/L (CI 49.76;64.81), respectively. Overall, 154/367 patients (42.0%) with available body temperature measures, experienced fever postoperatively. Endoscopic POR occurred in 144/332 patients (43.37%) with an available colonoscopy within 12 months postoperatively (Table 1). Surgical POR was 7.0% (CI 4.9%-11.1%) and 11.8% (CI 5.7%-8.8%) at 3 and 5 years follow-up, respectively (Figure 1). No association between postoperative fever and CRP levels estimates with either endoscopic (p=0.49; p=0.06) or surgical POR (p=0.52; p=0.07] was observed.

Conclusion

Despite previous evidence suggesting that CD patients develop an enhanced postoperative inflammatory response, CRP levels and fever after ICR do not seem predictive of early endoscopic (<12 months) or long-term surgical POR. Therefore, they should not be considered to stratify patients for postoperative medical prophylactic therapy.Read more P989 Switching from intravenous to subcutaneous vedolizumab in patients with inflammatory bowel disease in clinical remission: a multicenter study from GETECCUWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Despite the established use of intravenous (IV) vedolizumab for treating inflammatory bowel disease (IBD), there's growing interest in exploring the advantages of the novel subcutaneous (SC) administration route. However, comprehensive real-world evidence regarding the extended safety and effectiveness of this approach remains scarce. The aim of the study was to evaluate the effectiveness and safety of vedolizumab SC among IBD patients in clinical remission.

Methods

Multicenter, observational, retrospective study. IBD patients on IV vedolizumab treatment across 24 Spanish hospitals who were in clinical remission were given the option to switch to SC injections or continue with IV treatment. Data encompassing clinical disease activity (assessed through partial Mayo score, and Harvey-Bradshaw Index), biochemical markers (C-reactive protein and fecal calprotectin), adverse events and treatment persistence were retrospectively gathered from prospectively maintained clinical records at baseline, and at weeks 12, 24, and 48. Non-parametric tests were used for comparisons and Kaplan-Meier for survival.

Results

We identified 166 patients, with 19 excluded due to not being in clinical remission and 8 excluded due to absence of follow-up data, resulting in a final inclusion of 139 patients for analysis. Of these, 36 (25.9%) remained on IV vedolizumab, while 103 (74.1%) switched to SC vedolizumab. Both groups exhibited comparable demographic characteristics including age, gender, disease type, disease duration and extension, previous therapy, presence of extra intestinal manifestations and comorbidities (Table 1). However, there were differences in Crohn’s disease behavior among groups (p=0.013).There were not significant differences in clinical, biochemical and fecal calprotectin remission at week 12, 24 and 48 neither in the overall cohort nor assessing Crohn’s disease or ulcerative colitis separately (Figure 1).At the end of follow-up, median duration 47 weeks (29-49), persistence on the same formulation was 85%,1 (2.8%) patient on IV and 4 (3.9%) on SC withdrew the drug (p=0.810), 5 (4.8%) switched back to IV from SC.Adverse events were reported in 1 (2.8%) IV vs 11 (10.7%) SC vedolizumab (p=0.292), most of them being mild skin reactions to SC injection 3 (2.9%).

Conclusion

In our study we found that transitioning from IV to SC vedolizumab in patients with IBD in remission showed comparable effectiveness in maintaining disease remission. Switching to SC formulation appears safe with no new safety signals identified and most adverse events being mild.Read more P1095 Impact of inflammatory bowel disease on the risk of acute coronary syndrome: A Swedish Nationwide cohort study 2003-2021Wed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

There are conflicting data on the risk of acute coronary syndrome (ACS) in patients with inflammatory bowel disease (IBD) and only a few previous reports include patients diagnosed in the last decade. The aim of this study was to assess the risk of ACS in a modern population of IBD patients vs general population comparators.

Methods

In this cohort study, we used nationwide registers to identify patients diagnosed with IBD in Sweden 2003-2021. Every patient was matched by birth year, sex, calendar year of diagnosis, and area of residence with up to ten general population comparators. The primary outcome was incident ACS (i.e. ST-segment elevation myocardial infarction [MI], non–ST-segment elevation MI, unspecific MI and unstable angina). Cox proportional hazard models were used to estimate hazard ratios (HRs).

Results

Overall, 76,517 patients with IBD (Crohn's disease (CD), N=22,732; ulcerative colitis (UC), N=42,194 and IBD-unclassified, N=11,591) and 757,141 comparators were identified (Table 1). During a median follow-up of 8 years, 2546 patients with IBD (37.5/10,000 person-years) were diagnosed with ACS as compared with 19,598 (28.0/10,000 person-years) in the general population comparators. This corresponded to an HR of 1.30 (95% confidence interval [CI]: 1.24-1.35) after adjustings for potential confounders, and approximately 1 extra case of ACS in 100 IBD patients followed for 10 years. HRs for ACS were higher during the first year of follow-up but remained increased even after 5 years of follow-up (Figure 1). The highest HRs for ACS were observed in patients with elderly onset IBD (≥60 years; HR: 1.35; 95% CI: 1.28-1.43) and in patients with CD and UC with extra-intestinal manifestations (HR in CD: 1.58; 95% CI: 1.20-2.09; HR in UC: 1.98; 95% CI: 1.63-2.40). When restricting analyes to patients with elderly onset IBD, the absolute risk increase corresponded to 1 additional case of ACS for every 30 IBD-patient followed for 10 years. In contrast, no increased HRs were observed in patients diagnosed with IBD before the age of 40. But of note, just a few of the patients diagnosed with IBD before 40 years of age were followed-up beyond 50 years of age. HRs for ACS were stable during the whole study period 2003-2021 with no signs of leveling off during recent years.

Conclusion

In this contemporary cohort of patients with IBD, exposed to modern IBD-care, an increased risk for ACS was observed as compared with individuals of the general population. The highest HRs were observed in patients with elderly onset IBD and in patients with CD and UC with extra-intestinal manifestations.Read more P990 A Multi-center, Single-arm, Prospective, Observational, Real-world Study in China to Evaluate Effectiveness of Vedolizumab in the Treatment of Inflammatory Bowel Diseases: First Interim Analysis of Patient-reported OutcomesWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Crohn’s disease (CD) and ulcerative colitis (UC) are types of inflammatory bowel disease (IBD), causing abdominal pain, diarrhea, rectal bleeding and weight loss which is concerning due to increased prevalence and morbidity. As IBD affects quality of life (QoL), improving it is a major treatment goal. Current therapy in IBD includes corticosteroids, immunomodulators, biologics, small molecule drugs, etc. Vedolizumab (VDZ), a gut-specific antibody against α4β7 integrin, is approved in China in moderate to severe UC/CD treatment. This multi-center, single arm, prospective, observational, real-world study (NCT04872491) evaluated safety and effectiveness of VDZ in Chinese UC/CD patients. This first interim analysis presented changes in symptomatic relief and QoL. Safety results are shown separately.

Methods

Enrolled UC/CD patients (>18 years) were treated with 300 mg VDZ by intravenous infusion at week 0, 2, 6, and every 8 weeks till 54 weeks. At data cut-off (October 21, 2022), 307 patients were assessed for symptomatic relief and QoL by patient reported outcomes (PRO) scores, partial Mayo score rectal bleeding sub-score [RBS], stool frequency sub-score [SFS]) in UC; abdominal pain sub-score [APS], loose stool frequency sub-score [LSFS]) in CD at days 3, 7 and 14 and IBD questionnaire (IBDQ), EuroQol-5-Dimension-5-Level index (EQ-5D-5L) and EQ-visual analog scale (VAS) scores in UC and CD from baseline to week 14. Descriptive statistics summarized the effectiveness.

Results

Of 265 patients (UC: 211, CD: 54) analysed for effectiveness, 62.9% were males with mean(±SD) age 43.1±15.0 years and median IBD duration of 883 days. At baseline, mean(±SD) for partial Mayo and HBI scores were 5.185±1.936 and 5.362±3.674 for UC and CD patients respectively.Compared to baseline, UC patients showed significant difference in RBS and SFS scores from days 3 and 7 respectively reflecting rapid onset effect of VDZ (Figure 1). Patients with RBS=0 and SFS≤1 scores improved from 34.78% at baseline to 62.79% at day 14 after treatment. IBDQ, EQ-5D-5L and EQ-VAS mean±SD score changes of 38.853±39.569, 0.046±0.125 and 10.258±14.756 signified improved QoL (Table 1).At baseline, mean±SD APS and LSFS scores in CD patients were 0.692±0.832 and 1.462±1.570 (n=39), which decreased to 0.425±0.594 and 1.325±1.207 (n=40) at day 14 with a mean change of -0.211±0.528 and -0.105±0.981 (Figure 1). VDZ effectively maintained remission in patients with APS≤1 and LSFS≤3 which increased from 35.90% at baseline to 50.00% at day 14. Improved QoL was observed with changes in IBDQ (13.194±31.592) (Table 1).

Conclusion

VDZ effectively improved and maintained symptomatic relief and QoL in Chinese UC/CD patients in real-world settings.Read more P833 Burden of steroid use in patients with moderate ulcerative colitis in Europe and the United StatesWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Steroids are an effective short-term therapy option for induction of remission of ulcerative colitis (UC). However, long-term and frequent steroid use is common in clinical practice despite the risks of complications and adverse events.¹ We aimed to describe disease burden in moderate UC patients (pts) based on their steroid use history.

Methods

Data were drawn from the Adelphi UC Disease Specific Programme™, a cross-sectional survey of gastroenterologists (GIs) and their pts in France, Germany, Italy, Spain, the UK and US from Jan 2020–Mar 2021. GIs reported patient demographics, clinical characteristics, treatments and healthcare resource utilization (HCRU). Pts reported quality of life (QoL) via the EQ-5D, short inflammatory bowel disease questionnaire (SIBDQ), and work productivity and activity impairment (WPAI) questionnaire. Pts had received 5-ASA or immunomodulator with no biologic or Janus kinase inhibitor in the 90 days following treatment initiation, had a history of physician-assessed moderate disease severity or a Mayo endoscopic subscore of 2, and no history of colectomy. Pts were categorized as: no steroids (NS; never received steroids), short term/intermittent (ST/I; currently receiving intermittent steroids or received steroids within the last two years for <90 days), or long term/escalated (LT/E; received steroids for ≥90 days within the last two years or had undergone steroid dose escalation within their current course). Analyses were descriptive.

Results

Overall, 217NS, 88 ST/I and 172 LT/E pts were analysed (Table 1). Median (interquartile range) total steroid use duration was 4.1 (1.6–22.3) months for ST/I and 14.9 (5.8–36.7) months for LT/E. NS (24.4%), ST/I (25.0%) and LT/E (26.2%) pts experienced abdominal pain; 0.5%, 4.6% and 5.2% had severe/extremely severe pain, respectively. Non-bloody diarrhoea was reported by 16.6%, 14.8%, 20.9% of pts, respectively. In the last 12 months, mean (standard deviation; SD) number of health care visits for NS, ST/I and LT/E was 6.1 (6.2), 7.3 (4.8), 8.0 (7.1); mean (SD) number of tests was 20.8 (17.2), 23.3 (15.7), 25.2 (18.2), respectively. NS, ST/I and LT/E patients reported mean EQ-5D scores (0.85, 0.81, 0.79), SIBDQ total scores (54.6, 49.7, 48.3) and overall work impairment (19.4, 23.1, 27.7). Key comorbidities experienced by ST/I and LT/E were hypertension, depression and diabetes (Figure 1).

Conclusion

Patients with long-term or escalated steroid use had high symptom burden, frequent comorbidities, high HCRU, and poor QoL. This highlights the need for alternative treatment approaches for moderate UC patients to avoid long-term steroid use.1. Cross R.K. Inflamm Bowel Dis. 2017;23(10):1689–1701Read more P991 Serum anti-TNF levels correlate with tissue levels in perianal fistulising Crohn’s DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Perianal fistulising Crohn’s Disease (PFCD) affects up to 25% of patients and remains difficult to treat despite medical and surgical advancements.¹ Perianal fistulas have unique immunopathogenic features associated with an aggressive phenotype of CD with studies showing the need for higher drug levels for fistula healing in pCD.^2-4 Unfortunately, no medical therapy has been shown to be more than 40% effective in maintaining sustained remission suggesting a therapeutic ceiling in PFCD management.⁵ This calls for a better understanding of the role tissue drug penetrance plays in PFCD patients on biologic therapy. Previously, Adegbola et al.⁴ failed to identify tissue levels in PFCD patients using a Liquid chromatography-mass spectrometry (LC-MS) assay. Enzyme-linked immunosorbent assay (ELISA) is well validated and used in standard clinical practice for anti-TNF drug level measurement in blood samples. We aimed to determine tissue biologic drug penetrance in PFCD by quantifying rectal and fistula biologic levels in patients on established anti-TNF therapy using ELISA.

Methods

Paired blood, rectal and fistula tract biopsies were collected from 15 patients undergoing examination under anaesthesia for active pCD on established anti-TNF therapy (greater than 14 weeks since induction). Sample handling involved centrifugation within 12 hours of collection into serum and storage at −80°C for blood, snap-freezing with liquid nitrogen and storage at −80°C for tissue. Extraction was with an ELISA buffer based on tissue weight and the supernatants were extracted for anti-TNF measurement. Patient demographics including symptom burden were collected on the day of surgery.

Results

Patient demographics are shown on Table 1. Analysis (Figure 1) showing a trend towards correlation of high symptom burden (PDAI score) with low serum, rectum, and fistula anti-TNF levels (highlighted in yellow) across both Infliximab and Adalimumab patients. Furthermore, serum anti-TNF levels correlated positively with tissue levels in rectum and fistula samples (highlighted in green).

Conclusion

This is a first-of-a-kind experiment to detect anti-TNF levels in PFCD patients on established biologic therapy. We were able firstly to show that patients with highly symptomatic disease tend to have lower drug penetrance in rectum and fistula tract tissue, and secondly that serum anti-TNF levels correlate positively with tissue levels. This study further reaffirms the importance of aiming for high anti-TNF levels in serum to ensure adequate tissue penetrance. Limitations include the small number of patients recruited, and it is unclear how well a single biopsy represents the anti-TNF drug distribution across the entire rectum and fistula tract.Read more P834 Choosing wisely: Ustekinumab in Elderly Crohn’s Patients – A Comparative StudyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The burden of Inflammatory Bowel Disease (IBD) in elderly patients derives from background comorbidities and the elevated risk associated with immunosuppressive treatments. In the present study, we aimed to assess the efficacy and safety of ustekinumab (UST) in elderly patients with Crohn's disease (CD).

Methods

This study was designed as a retrospective-cohort study including patients ≥ 60 years old (elderly) and patients < 60 years (non-elderly) who commenced UST for CD at a large, tertiary medical center. Outcomes were assessed by clinical response evaluation through parameters such as physician global assessment (PGA) and the Harvey-Bradshaw index (HBI), alongside assessment of clinical biomarkers, hospitalization rates, treatment persistence, and the necessity for surgical interventions. A secondary analysis was conducted of elderly patients treated with UST compared to elderly patients treated with vedolizumab (VDZ).

Results

In total, the primary analysis included 99 patients treated with UST (34 elderly patients and 65 non-elderly patients). Duration of follow-up was a median of 12 months (IQR 0). Elderly patients had predominantly an isolated ileal disease (68%) compared to an ileo-colonic disease (36%) in non-elderly patients (p = 0.017). The median age of onset was 68 years (IQR 64-75), and 34 years (IQR 28-42), respectively. Furthermore, elderly individuals were more likely to receive corticosteroids as their initial treatment (44% vs. 14%, <0.001). No differences were demonstrated in disease duration, EIM, phenotype, or previous biological therapy. Following six months of therapy, elderly patients were more likely to achieve complete clinical remission (31% vs. 12%, p = 0.035) as assessed by PGA. The elderly group experienced higher hospitalization rates during the 6-month (21% vs 4.6%, p = 0.029) and the 12-month follow-up period (15% vs. 3.1%, p = 0.045), while surgery rates were comparable between non-elderly and elderly groups (table 1). Concerning elderly UST vs elderly VDZ patients (n=69), no significant differences were observed in clinical response and remission rates between the groups after 6 and 12 months of follow up. In addition, no significant differences were shown in regard to safety (hospitalizations, surgery or therapy cessation rates).

Conclusion

UST is an effective treatment option in elderly CD patients. However, this population had higher hospitalization rates compared to non-elderly patients, greatly owing to age and comorbidities.Read more P1112 Clinical features between familial versus sporadic inflammatory bowel disease: a retrospective single centre studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Inflammatory bowel disease (IBD) is a group of chronic inflammatory conditions of the gastrointestinal tract. The two main types of IBD are Crohn's disease (CD) and ulcerative colitis (UC). Both conditions have a complex and multifactorial etiology, involving a combination of genetic, environmental, and immunological factors. If there is a family history of IBD, particularly in first-degree relatives (parents, siblings), there may be a higher risk for other family members to develop the disease. A retrospective cohort study was conducted between 2010 and 2022, to assess clinical features between familial versus sporadic inflammatory bowel disease

Methods

This observational monocentric retrospective study, includes 903 patients: 794 with IBD, with and without familiarity, referring to the Gastroenterology Service of the "Azienda Sanitaria Universitaria del Friuli Centrale". 10,6% of the patients have familiarity (54,2% with a first degree and 44,8% with a second degree relative). Table 1 provides data on patients and disease characteristics.

Results

The mean age of patients with familiarity for IBD was significantly lower compared to subjects without familiarity. Unexpectedly in our cohort familiarity in CD vs UC subjects were similar (respectively 10.7% vs 11.8%). A slight increase of women in the group with familiarity was detected although not statistically significant. EIMs occurred predominantly in the cohort with familiarity but the difference was not statistical significant. IBD subjects with familiarity need less surgery if compared with those with non familiarity (respectively 14,6% vs 18,2%), but the difference was no significant. Biological drugs have been used earlier and more frequently in patients with familiarity compared with those with not familiarity (29,3% vs 38,5%) although also in this case non significant. No differences on IBD phenotype have been noted between familial IBD vs sporadic IBD. Main data described in Table 2.

Conclusion

In this retrospective cohort study, family history of IBD was present in similar percentage between CD and UC. The only significant data in our cohort was the early age of onset of IBD in patients with familiarity. However IBD familiarity was associated with a trend of decreased risk of surgical procedures, increased use of biological medications and a trend for developing EIMs. While some data, for example the earlier and larger use of biologics could explain the less need of surgery in IBD patients, larger cohorts are essential to define the similarities and differences more robustly between familial and sporadic IBD.Read more P992 Nutraceutical treatment based on a multi-compound formulation composed of Hericium erinaceus, berberine, quercetin, niacin, and biotin could improve the oral 5-ASA effectiveness in mild-to-moderate ulcerative colitis: Results from a two-arm multicentric retrospective observational studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The use of nutraceuticals as adjunctive therapy for ulcerative colitis (UC) is increasingly emerging. HBQ-Complex^® (a compound consisting of Hericium erinaceus, berberine, and quercetin), when added to biotin and niacin (a compound called Enteroflegin^®), has already shown promising results in ex vivo models of UC as well as in other gastrointestinal disorders such as symptomatic uncomplicated diverticular disease. This multicentric observational retrospective study aimed to weigh the effectiveness and safety of Enteroflegin^® in mild-to-moderate UC as adjunctive therapy to oral 5-aminosalicylic acid (5-ASA).

Methods

Mild-to-moderate UC patients [i.e., with a partial Mayo score (PMS) between 2 and 7] on exclusive therapy with oral 5-ASA (i.e., without taking steroids, biologics, small molecules or other prebiotics/symbiotics/antibiotics) were divided into two groups and evaluated at baseline (T0), after three months (T1) and after six months (T2). One group of patients (G1) took 5-ASA plus two Enteroflegin^® tablets for six months, while the other control group underwent only 5-ASA treatment (G2). PMS, faecal calprotectin and 5-ASA dose were collected at each time. Clinical response at T1 and T2 (i.e., reduction in PMS ≥ 2 from baseline) and clinical remission at T1 and T2 (i.e., PMS < 2) were the main outcomes of the study, including compound safety.

Results

One hundred thirty patients [median age 39.5 (30 - 55), BMI 24.4 (22.8 - 26.4) Kg/m², median years since UC diagnosis 10 (3.2 - 18.4)] were retrospectively included. In the sample, 51.5% were male, 47.7% had left colitis, 55.4% had proctitis, and 5.4% had pancolitis. 96.2% were on mesalazine therapy. 40.8% of patients had a PMS consistent with moderate activity. The clinical response rate at T2 (69.4% vs 47.5%, p=0.01) and clinical remission at T1 (17.9% vs 4.2%, p=0.029) and T2 (38.9% vs 19.1%, p=0.03) were higher in G1 than in G2 group (Figure A, p < 0.05). The trend in calprotectin reduction was also more favourable for G1 throughout the study (Figure B, p < 0.05). A dosage of 5-ASA > 3.6 g (OR 4.269, 95% CI 1.322 - 13.79; p=0.015) per day, as well as the use of Enteroflegin® (OR 3.303, 95% CI 1.232 - 8.857; p=0.018), resulted as clinical remission at T2 (i.e., six months) predictors. No adverse events were reported.

Conclusion

The nutraceutical compound Enteroflegin^®, when added to standard therapy with oral 5-ASA treatment in patients with mild-to-moderate UC, increased its real-life effectiveness without safety concerns.Read more P835 Acceptability, feasibility, and adherence of an emulsifier-free diet in healthy volunteersWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Emulsifiers are associated with intestinal inflammation and therefore excluded in new dietary strategies in inflammatory bowel diseases (IBD). We aimed to investigate the feasibility, acceptability, and adherence of an emulsifier-free diet (EFD) in healthy volunteers as part of the FOod Additives on the Mucosal barrier (FOAM) study.

Methods

We recruited 60 healthy volunteers to a 7-week interventional trial. After 1 baseline week of their habitual diet, participants followed an EFD for 6 weeks. Participants were instructed on how to follow an EFD yet were not advised on ultra-processed food (UPF) reduction. Every 2 weeks after starting the EFD (week 2, 4, and 6), subjects were asked about their experience on a 12-item questionnaire, including 5-point Likert scales, open-ended and multiple answer-type questions. Food logs were kept in the smartphone application 'Fatsecret', including photographs to capture brand names. Manual calculation of all days with plausible energy intakes (800-4200 kcals per day for men and 600-3500 kcals for women) for at least 79.5% of the time was performed to exclude incomplete reporting. Emulsifier intake was measured as number of servings of emulsifier-containing foods. Adherence rate was calculated as a percentage of mistake-free days.

Results

Of the 60 healthy volunteers, 2 were excluded due to NSAID use. Median (IQR) age was 25.5 years (23.0-33.0), median BMI was 22.7 kg/m² (21.2-25.6) and 19.0% were male. Median percentage of plausible food logs was 100% (98.0-100%), and 1 subject was excluded due to inadequate dietary reporting.During the EFD, emulsifier intake significantly decreased (baseline vs week 1; p=2.3x10^-9, vs week 6; p=5.3x10^-9, Figure 1A), as well as UPF consumption according to the NOVA classification (baseline vs week 1; p=5.6x10^-7, vs week 6; p=1.6x10^-7, Friedman test with post-hoc paired Wilcoxon, Figure 1B). The adherence rate to the EFD was very high (median 88.1%, IQR 76.2-95.2%). Median number of mistakes during the EFD was 6 (2-14), for a median number of 3 selected food items (1-5). Most mistakes were made in the categories of dairy-like products, meat products, and bakery goods. The top 3 reported challenges included restricted food choices, checking food labels, and longer shopping times (Table 1). At week 6, For 70.7% the EFD was tasty to very tasty and for 72.4% it was acceptable to very acceptable. Hot meals and snacks were the most challenging meal types.

Conclusion

In this 7-week interventional trial in 60 healthy volunteers, adhering to an EFD was feasible and acceptable. While following the EFD, an inadvertent and stable decrease in UPF intake was noted. These finding represent important considerations when designing future dietary trials in IBD.Read more P1113 Depressive symptoms in ulcerative colitis and Crohn's disease – differences in improvement at 1 year follow-upWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Mental health (MH) has been reported to be poorer among patients with inflammatory bowel disease (IBD) than general population. However, it is not known whether MH is more driven by inflammation itself or related to gastrointestinal (GI) symptoms. Also, the dynamics of MH following IBD diagnosis is not well understood.

Methods

In the Swedish Inception Cohort of IBD (SIC-IBD), patients with Crohn’s disease (CD), ulcerative colitis (UC) and unclassified IBD (IBD-U) as well as symptomatic controls (SC) and healthy controls (HC) filled in Patient Health Questionnaire-9 (PHQ-9), a validated screening tool for depression. Patients completed PHQ-9 at diagnosis and at one year follow-up while the controls completed it once. Disease outcome was defined at one year based on requirement of advanced treatments/ surgery.

Results

In total, 286 individuals (16 HC, 89 SC, 62 CD, 104 UC, 15 IBD-U) completed the questionnaire at baseline. HC had significantly lower PHQ-9 score, (fewer depressive symptoms), at baseline compared to all the other groups (p<0.01). The baseline PHQ-9 score was not significantly different between SC and CD, UC and IBD-U patients (p=0.06).At one year follow-up, 38 CD and 53 UC patients completed the PHQ-9. Between baseline and follow-up, UC patients had a significant drop in their PHQ-9 score (p<0.0000001), whereas CD patients did not have any significant change in their PHQ-9 score (p=0.06). Furthermore, UC patients had significantly lower PHQ-9 score compared with CD patients at follow-up (p=0.04, Figure 1).Baseline PHQ-9 score was not correlated with calprotectin at baseline neither in UC nor CD patients (p=0.7 and 0.5 respectively). Also, there was no positive correlation between PHQ-9 score change and calprotectin change in either UC or CD patients, and neither baseline nor follow-up PHQ-9 scores were significantly different in patients with poor or good outcome (p>0.05). When analysed separately by sex, there was still no correlation between baseline PHQ-9 score and outcome in neither CD nor UC patients (p>0.05)

Conclusion

IBD patients have at the time of diagnosis more depressive symptoms than HC, but not different from SC. Depressive symptoms are more related to GI symptoms than IBD specific inflammation or disease outcome. UC patients show more of an improvement in their depressive symptoms one year after diagnosis than CD patients.Read more P958 Comparison of Paediatric Patients and Young Adults with Moderately to Severely Active Crohn’s Disease Treated with Ustekinumab in the REALITI Real-World Evidence Effectiveness StudyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Few approved treatment options exist for paediatric patients (pts) with Crohn’s disease (CD). Paediatric inflammatory bowel disease (IBD) medication approvals are delayed nearly 7 years after adult approvals,¹ resulting in off-label use and potential for incorrect dosing. The REALITI Study evaluated the effectiveness and safety of ustekinumab (UST) in routine clinical care in paediatric pts (age 2-<18) and young adults (age 18-25) with moderately to severely active CD (Short Paediatric CD activity [sPCDAI] score ≥30) using data from the ImproveCareNow (ICN) Registry.

Methods

Effectiveness data from pts with CD treated with UST were extracted from the ICN Registry between 10 January 2010 and 29 February 2020. A supplemental, retrospective chart review was conducted to collect data not in the ICN Registry. The primary endpoint was clinical remission (sPCDAI≤10) at Week (Wk) 52. All data were summarized descriptively, and the proportion of pts achieving clinical remission and associated 2-sided 95% confidence interval were calculated across multiple populations. Rates of discontinuations, IBD-related hospitalizations, surgeries, and serious infections were also calculated.

Results

A total of 479 CD pts in ICN were treated with UST, including 348 paediatric pts and 131 young adults. We report an analysis of 114 paediatric pts who weighed >40 kg and had a sPCDAI ≥30. All pts were treatment refractory; 99.1% had not responded to prior biologic therapies, with less than 1% biologic naïve. Results were compared to 51 ICN young adults with moderately to severely active CD, a population for which UST is approved. Clinical remission at Wk 52 was achieved in 22.8% (26/114; 95% CI: 16.1%, 31.3%) of paediatric pts vs 21.6% (11/51; 95% CI:12.5%, 34.6%) of young adults (Figure 1A). Discontinuation rates through Wk 52 were similar between paediatric pts (25.4%) and young adults (25.5%; Figure 1B).Overall, 36.0% of paediatric pts and 21.6% of young adults had IBD-related hospitalizations. IBD-related surgery was reported in 14.0% of paediatric pts and 11.8% of young adults. Serious infections occurred in 9.6% of paediatric pts and 3.9% of young adults. Opportunistic infections occurred in 1.8% of paediatric pts and 0% of young adults. No events of tuberculosis, malignancy, or anaphylaxis requiring UST discontinuation occurred in either group. No deaths were reported.

Conclusion

This study of real-world data from the ICN Registry found similar remissions rates in paediatric pts and young adults with CD treated with UST, suggesting comparable effectiveness of UST in both age groups. No new safety signals were identified. (Crowley E, et al. J Crohns Colitis. 2022 Feb 23;16(2):331-335.)Read more P836 Prospective evaluation of the switch from adalimumab originator to different biosimilars in IBD patients : acceptability and persistance at 1 yearWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The use of biological therapies represents a major source of direct healthcare costs for inflammatory bowel disease (IBD) in industrialised countries. Several adalimumab (ADA) biosimilars are available for Crohn's disease (CD) and ulcerative colitis (UC) patients. The aims of our study were to assess the acceptance of switching from Humira® to different ADA biosimilars in IBD patients, the biosimilar persistence at 1 year, and the acceptability of the switch.

Methods

From July 2020 to September 2021, we proposed for consecutive and ambulatory IBD patients on maintenance Humira® to switch to one of the five ADA biosimilars available at the time of the study (Amgevita®, Idacio®, Imraldi®, Hulio®, Hyrimoz®) at Lille University Hospital (France). Patients accepting the switch chose a ADA biosimilar with an IBD nurse and were followed prospectively for 1 year. Biosimilar persistence was assessed at 6 and 12 months using the Kaplan-Meier method. Factors associated with switch acceptance and biosimilar persistence were identified by logistic regression tests (Chi-2). Data on efficacy, safety and rate of return to ADA originator were assessed at 6 and 12 months. At 12 months, acceptability of the switch was assessed by a questionnaire.

Results

97 patients (84 CD patients; 13 UC patients) were included in the study. 89/97 patients (91.8%, including 76 CD patients) accepted the switch from ADA originator to a biosimilar. Poor opinion of generic drugs was the only factor associated with refusal to switch. At 12 months, 61 patients (71%) were still on ADA biosimilar and 54 patients (60%) were still treated with the biosimilar initially introduced. During the follow-up, the proportion of patients treated with Hulio® remained stable (around 30%), while the proportion of patients treated with Amgevita®, Idacio®, Imraldi® and Hyrimoz® decreased (from 33.7% to 22.5%, from 20.2% to 5.6%, from 8% to 4.5% and from 10.1% to 5.6%, respectively) (Figure 1). One quarter of patients switched back to ADA originator at 12 months. Thirty-seven patients discontinued the treatment. Among them, 22 patients (59.5%) discontinued due to injection site reactions. Clinical remission rates were stable between the baseline and the 6 and 12 months evaluation (94.4%, 88.8% and 89.2% respectively). The switch from ADA originator to a biosimilar was considered acceptable for 31/38 patients (81.6%) evaluated at 12 months.

Conclusion

A large proportion of IBD patients (91.8%) accepted the switch from ADA originator to a biosimilar and 60% continued ADA biosimilar at 1 year. The high acceptability of the switch encourages the use of ADA biosimilars in clinical practice.Read more P1130 Predictors of Remission within One Year of Advanced Therapy in Paediatric Patients with Ulcerative Colitis – analysis from Czech national registry of biologic treatment (CREdIT)Wed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Data on the outcomes of advanced therapy in paediatric patients with ulcerative colitis (UC) and their predictors are scarce. We aim to assess the association between remission at one year of treatment and pre-specified predictors, including types of advanced therapy.

Methods

Using the Czech national prospective registry of biologic and innovative therapy of IBD (CREdIT), we identified 207 courses of treatment among paediatric UC patients. Disease remission was defined as Paediatric Ulcerative Colitis Index below 10 points. In this preliminary analysis, we employed mixed-effects regression models to attempt to identify an association between pre-specified predictors (duration of disease, first-line treatment, baseline age, baseline PUCAI, extension, ever severe, indication, baseline immunomodulator, drug) and remission at one year of the treatment. A patient, biologic center, and a time period were added as random effects into the models.

Results

Among 132 observations (60 female, 46%) in 108 patients, 85 were with infliximab (64%), 22 with adalimumab (17%), 20 with vedolizumab (15%), 4 with ustekinumab (3%) and 1 with tofacitinib. Most of the observations were from the first line of the biologic treatment (first: 95, 72%, second: 27, 21%, third: 7, 5.3%) and with concomitant immunosuppressive therapy at the beginning of the treatment course (97, 74%). Irrespective of treatment line, remission at 1 year was achieved in 53% (45/85) of infliximab, 36% (8/22) of adalimumab, 60% of vedolizumab and 50% of ustekinumab (2/4) treatment courses. However, we did not find a difference between the individual preparations in either the unadjusted mixed model or multiple mixed regression model. Of the pre-specified predictors, only longer duration of disease to the start of the therapy course was weakly associated with a lower remission rate in the treatment year when adjusted for treatment line (OR 1.16, 95%CI 1.00-1.34). In a sub-analysis of first-line advanced therapy only, 53% (44/83) of infliximab courses and 55% (6/11) of adalimumab courses achieved clinical remission at 1 year. Using a regression mixed model, we did not find any difference between treatment outcomes with these agents.

Conclusion

Based on data from real paediatric clinical practice, only half of patients with UC achieve clinical remission within a year of initiation of advanced therapy. This shows how important is to expand the drug armamentarium also in the paediatric population. Our study shows that time to initiation of advanced therapy may be an important factor even in patients with UC.

Support

The Grant Agency of Charles University in Prague (227023) and the Ministry of Health, Czech Republic, for the conceptual development of the research organisations (00064203).Read more P807 HLA type impact on immunization and efficacy of ustekinumab in IBD patients: a multicenter studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

About 30% of patients treated with ustekinumab will present primary or secondary failure. Outcomes and frequency of ustekinumab immunization are still controversial. Some HLA types (especially DQA1*05) appear to be predictive factors of anti TNFα immunization. This study aimed to assess the impact of HLA type on the risk of immunization and on the efficacy of ustekinumab.

Methods

IBD patients treatede with ustekinumab in Saint-Etienne and Lyon hospitals were included between 2017 and 2023. Ustekinulab through level was measured by ELISA and HLA type (DQA1, DQB1, DRB1) determined by PCR. Anti-drug antibodies (ADA) detection was done using both a "drug sensitive" assay (ELISA) and an innovative "drug tolerant" method based on anti human lambda chain. Data about clinical, biological (CRP, fecal calprotectin) and endoscopic responses were retrospectively collected.

Results

Among the 115 patients included (43% males, mean age of 40 years old), 98 had Crohn disease. Nighty-eight percent of the patients were previously treated with at least one anti-TNFα and 33% of them were immunized. In this study, 43 patients were immunized against ustekinumab with the "drug tolerant" assay and only 2 with the "drug sensitive" method. Immunization tended to reduce (not significatively) clinical, biological and endoscopic responses. Ustekinumab through level was significately higher for patients with good clinical (p = 0.009) and biological (p = 0.036). HLA DQA1*05 or DRB1*03 carriage was associated with higher risk of immunization (OR = 5.13, p = 0.048 / OR = 5.36, p = 0.006) and with a trend to decrease clinico-biological response. Other HLA types, notable DQA1*01 tended to be associated with a lower immunization (OR = 0.7, p=0.3) and a better response (OR = 2.55, p = 0.018). A small group involved (26 patients), combination therapy at induction had no significant benefit in terms of immunization prevention or therapeutic response. Sub-groups analysis seemed to confirm some HLA types involvement, by breaking free of imbalances due to haplotype transmission.

Conclusion

Our study suggests the usefulness of ustekinumab monitoring and a more common immunization than previously described. HLA type seem to influence immunization and ustekinumab response. Some specific HLA types and patients profiles tend to be associated with a higher risk of immunization not only to anti-TNFα but also to ustekinumab.Read more P993 IMPACT-III and IMPACT-III-P questionnaires: the transcultural adaptation and validation in Spanish families. A SEGHNP (Spanish Society of Pediatric Gastroenterology, Hepatology and Nutrition) multicenter studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

IMPACT-III and IMPACT-III-P are Health-Related Quality of Life (HRQoL) questionnaires for pediatric Inflammatory Bowel Disease (p-IBD) patients and their parents/caregivers. They consist of 35 items answered with a 1-5 points Likert scale that evaluate six domains. Higher scores indicate better HRQoL. IMPACT-III has been translated into over 70 languages and validated in several countries. However, the existing IMPACT-III Spanish translation showed room for improvement and none of the tools had been validated in our population. We aimed to perform a transcultural adaptation and validation of the Spanish versions.

Methods

With permission from the questionnaires’ authors, we performed the translation and back-translation by professional translators, followed by evaluation by an expert committee and a small group of p-IBD families (n=12). Members of the SEGHNP (Spanish Society of Pediatric Gastroenterology, Hepatology and Nutrition) were invited to recruit p-IBD patients aged 10-18 and their families (February’21-November’22) to complete the questionnaires. Demographical and clinical data of the p-IBD participants were analyzed. Validation was performed with the Cronbach's alpha coefficient (considering 0.8-0.9 a good internal consistency) and a confirmatory factorial analysis with Varimax rotation (desirable values >0.5). The Kaiser Meyer Olkin (KMO) measure (>0.5 good correlation) and the Bartlett’s sphericity test (p<0.05) were calculated to confirm the adequacy of the factor analysis. The utility (method and completion time) was considered. The correlation coefficient between IMPACT-III and IMPACT-III-P was analyzed. Data were collected and analyzed with REDCap and Stata 16.

Results

We included 370 patients and 356 parents/guardians from 37 hospitals. Descriptive statistics of the participants are shown in table 1. The KMO measure (0.8998 and 0.9228, respectively) and the Bartlett's sphericity test (p-value <0.001 for both) confirmed the factor analysis’ adequacy. The factorial model with four factors, complying with Kaiser’s criterion, explained 89.19% and 88.87% of the variance in the model. Cronbach's alpha (0.9123 and 0.9383) indicated excellent internal consistency. The use of a Likert scoring system and the completion median time of 10 minutes for both tools was considered optimal. The correlation coefficient was 0.92, which was considered excellent.

Conclusion

The SEGHNP versions of the IMPACT-III and IMPACT-III-P are valid and reliable to use with Spanish p-IBD families. Our findings suggest a 4-factor scores in both questionnaires, although the optimal factor structure should be further examined. In our sample, parents/caregivers were good proxies for rating their p-IBD children overall HRQoL.Read more P808 Use of intestinal ultrasound influences the proportion of suboptimally controlled patients: IBD Podcast Study resultsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The IBD-PODCAST study estimates the proportion of patients with Crohn’s disease (CD) and ulcerative colitis (UC) with suboptimal disease control (DC) in a real-world setting. Intestinal ultrasound (IUS) is recommended in international guidelines as a non-invasive tool to assess disease activity and to guide therapeutic decisions in IBD. It is easy to use, inexpensive, can be repeatedly used without limitations and provides an opportunity for immediate patient interaction. The aim of this descriptive analysis was to assess the impact of IUS on the proportion of suboptimal DC in this cohort.

Methods

IBD PODCAST was a non-interventional, cross-sectional, multi-center study conducted across 103 sites in 10 countries. Criteria for suboptimal DC were based on STRIDE-II. Retrospective data on the frequency of imaging (i.e. endoscopies, MRI/MRE/CT and IUS) in the 12 months prior to assessment were collected. We compared clinical decision making, subjective evaluation of DC by patients and physicians and objective criteria of suboptimal DC at the time of assessment (i.e. index) in patients with (i.e. CD+IUS¹², UC+IUS¹²) and without IUS (CD^-IUS, UC^-IUS) in the past 12 months.

Results

2185 patients (CD: n=1108, UC n=1077) with a mean age (SD) of 44.0 (14.8) years and mean disease duration (SD) of 12.4 (9.2) years were included (52.2% male). Imaging was performed in 43.1% (n=477) of CD and 44.6% (n=480) of UC patients within 12 months prior to index. Endoscopy accounted for 77.6% and 88.8%, MRI/MRE/CT for 21.0% and 6.7%, and IUS for 19% (n=89/477) and 16% (n=77/480) of patients with CD and UC, respectively.The proportion of patients with signs of active inflammation at index was higher in patients where IUS was used (CD+IUS¹²: 34% vs CD^-IUS: 9.5%; UC+IUS¹²: 22.6% vs UC^-IUS: 15.3%; Table 1).For UC only, numerically more patients with parameters indicating clinically active disease at index were further monitored or had their treatment adjusted, when IUS was used within the past 12 months. (UC+IUS¹²: 58.6% vs UC^-IUS: 50.7%).Despite the high number of patients with suboptimal DC based on objective criteria, the use of IUS minorly improved the alignment of subjective evaluation of suboptimal DC between the patient and physician, and only in UC (UC+IUS¹²: 37.5% vs UC^-IUS: 32.7%; Fig 1).

Conclusion

Only a minority of patients underwent IUS in this cohort. Yet, this non-invasive tool may be useful if used more frequently. Consistent with others, IUS could aid in holistic disease monitoring for the detection of suboptimal treatment response, clinical decision making and the opportunity for alignment with patients on treatment targets.Read more P1131 Epidemiological Characteristics of Inflammatory Bowel Diseases in The Last Decade: Multi-Center Türkiye DataWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

This study aims to assess the past decade's epidemiology of inflammatory bowel disease (IBD) patients in Türkiye and identify year-to-year variations.

Methods

A total of 3463 patients diagnosed between 2010 and 2022 were included. The patients' demographic and phenotypic characteristics, smoking habits, and family histories were assessed. Differences between geographic regions and age groups were analyzed.

Results

Among patients, 1523 (44%) had Crohn's disease (CD), 1768 (51.1%) had ulcerative colitis (UC), and 23 (0.7%) had indeterminate colitis (Table). Male proportions were higher in both CD and UC patients, with the most common age range for diagnosis being 21-30 years (Figure). Over time, newly diagnosed cases and rates per population increased according to Turkish Statistical Institute data (Figure). Patients were divided into two groups based on diagnosis years (2010-2016 and 2016-2022), CD initially dominated, but UC prevalence grew in the last 6 years (p<=0.001). Recently diagnosed CD patients showed higher inflammatory involvement (78.0% vs. 63.4%; p<=0.001), and the inflammatory phenotype rose post-2016 (75.2% vs. 60.4%; p<=0.001). CD patients had more smokers (24.2% vs. 10.9%; p<=0.001) and family history of IBD (6.8% vs. 4.5%; p=0.004) than UC patients. Patients over 60 years old had a higher male gender ratio (64.4% vs. 55.9%; p<=0.001) and UC frequency (62.2% vs. 52%; p<=0.001) compared to those under 60 years old. The inflammatory phenotype in CD patients was lower in those under 60 years old compared to those over 60 years old (70.4% vs. 85.4%; p<=0.001). The frequency of pancolitis in UC patients was lower in those over 60 years old (31.3% vs. 41.4%; p<=0.001).

Conclusion

In Türkiye, IBD is more prevalent in males and is frequently diagnosed between ages 20 to 30. In CD, inflammatory and ileocolonic involvement is most common, while in UC, pancolitis is observed. The earlier diagnosis peak and increased pancolitis in UC patients might relate to tertiary centers' inclusion with transition clinics and focus on severe cases. Recently, newly diagnosed UC cases have notably surpassed CD cases.Read more P994 Single center assessment of intravenous ustekinumab maintenance in Crohn’s diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Ustekinumab (UST) is usually employed in Crohn’s disease (CD) after anti-tumor necrosis factor (TNF) therapy failure or if anti-TNF therapy is contraindicated. Higher UST trough levels have been associated with better clinical/endoscopic outcomes, so dose escalation (reducing dosing intervals or reinduction) is widely used. Intravenous (iv) maintenance has been proposed, but it has been barely assessed.

Methods

Single center, retrospective case series. All patients with CD starting treatment with UST and receiving at least one dose were eligible. Subjects started on UST in other centers or those prescribed for any indication different than IBD were excluded.Dose escalation to iv maintenance was performed in case of lack or loss of response or persisting significant inflammation in laboratory tests, imaging or endoscopy. Following dose escalation, Harvey Bradshaw Index (HBI), fecal calprotectin and C reactive protein (CRP) were checked at each visit. UST trough levels were also assessed.Primary outcomes were clinical remission (HBI<5) and biochemical remission (fecal calprotectin <250 mg/kg). Adverse events, and treatment persistence were also assessed.

Results

A total of 131 patients treated between May 2017 and August 2023 were included. Sixty (45.8%) patients were escalated to iv UST maintenance after a median of 14.1 (IQR: 8-50.4) weeks of UST treatment. Baseline characteristics are shown in table 1.Patients were started on iv UST maintenance due to persistent inflammatory activity in imaging/endoscopic procedures in 21 (35%), clinical response without remission in 17 (28.3%), low trough concentrations in 16 (26.7%) and primary non-response in 6 (10%). Thirty-three (55%) were receiving sc UST every 4 weeks and 23 (38.3%) started iv maintenance directly after UST induction. At initiation of iv maintenance, patients presented a median HBI index of 4 (IQR: 2-7), a fecal calprotectin of 514 (IQR: 213-1078) mg/kg and UST trough levels of 4.8 (IQR: 3-7.3) μg/mL.Following iv maintenance, UST trough levels increased to 10.9 (IQR: 8-17.4). Clinical remission rates increased from baseline (48.3%) at weeks 8 (79.6%, p=0.001), 24 (72%, p=0.01) and 48 (74.4%, p=0.01). However, the 10-13% increase observed in the biochemical remission rates was not statistically significant (figure 1). Treatment persistence 2 years after starting UST iv maintenance was 72.2% (95% CI: 54.7-83.8%). Only 2 infectious adverse events were observed in the whole cohort (2/131, 1.6%), both in patients receiving sc maintenance.

Conclusion

UST iv maintenance in bio-experienced patients is safe and increases clinical remission rates, although it did not achieve a relevant improvement in biochemical remission rates.Read more P841 Exploring Factors Influencing Rutgeerts Score Changes After Ileocecal Resection in Crohn's Disease PatientsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Ileocecal resection (ICR) is the most common surgery in Crohn's disease patients with a high risk of postoperative endoscopic and clinical recurrence. The Rutgeerts score is an endoscopic tool used to predict postoperative clinical recurrence and guide therapeutic management. The aim of this study is to identify factors influencing the evolution of this score.

Methods

We included all Crohn's disease patients undergoing ICR and who had undergone at least two postoperative colonoscopies during the period [2019-2023]. at the Hepato-Gastroenterology Department of MOHAMMED VI university hospital of Oujda,Morocco.

Results

Forty-six Crohn's disease patients underwent ICR, including 19 females and 27males (sex ratio M/F: 1.4). The mean age of patients was 36 years [26-73], with an average duration of 4 years between diagnosis and ICR. The mean time between surgery and the first follow-up colonoscopy was 10 months, with an average of 18 months between two follow-up colonoscopies. Endoscopic results revealed stability in the Rutgeerts score for 22 patients without the appearance of clinical recurrence signs. Among these patients, 40% were on immunosuppressants (methotrexate n=5, thiopurines n=4), and 60% were on combination therapy. Worsening of the Rutgeerts score was noted in 13 patients, including 30% with perianal manifestations (PAM), 23% with stomas or those who underwent a second surgical intervention during the interval between two colonoscopies, 37% with therapeutic non-adherence, and 10% who stopped treatment. Improvement in the Rutgeerts score was observed in 11 patients, half of whom underwent therapeutic switching or optimization.Identified factors included the use of immunosuppressants or combination therapy, PAM, therapeutic non-adherence, the occurrence of surgery, stomas, therapeutic switching, or optimization.

Conclusion

In conclusion, our study highlights the complexities in post-ileocecal resection management for Crohn's disease. While stability in Rutgeerts scores was observed in some patients, factors such as perianal manifestations, stomas, and therapeutic non-adherence were associated with score worsening. These findings underscore the need for personalized approaches to optimize postoperative care and inform therapeutic decisions in Crohn's disease patients undergoing ileocecal resection.Read more P1155 Impact of COVID19 pandemic and vaccination among IBD patients: a multinational cross sectional surveyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The aim of current study is to evaluate impact of COVID19 pandemic and vaccination against it on the course and symptoms of IBD.

Methods

During a six months’ period, all of the IBD cases who attend in outpatient clinics of nine referral centers in 6 countries include and request to fill a questionnaire about their demographic characters and pattern of IBD, any history of involvement with COVID19 and their vaccination history.

Results

overall 812 cases from 16 countries included (52.4% male) with average age of 36.8 y (range 7 – 76). 68.5% of participants diagnosed as UC and 29.5% as CD. 80% of participants have vaccinated against COVID19 (average 2.3 times, range 1 – 5). Among those who vaccinated (group A) 31.6% experienced side effects and complication without any mortality. The most common complications of vaccination include fever (24%), fatigue (20.1%) and anorexia 8.6%. The most common reasons for vaccination refusal (group B) were fear of vaccine complication (55.5%), no believe in vaccine protection (29.6%) and fear of immunocompromised condition (17.9%). In group A overall 61% of participants involved with COVID 19 (36.2% after vaccination) in comparison with 48.1% in group B (P = 0.0052). Most of the involvements in both groups were not sever and just a minority of patients admitted to hospital (10% in group A and 6.4% in group B). Following COVID involvement, 45.1% of cases suffered with GI symptoms (mostly diarrhea (72.5%) and abdominal pain (64.5%)). In group A, 37.3% of involvements have happened before vaccination.

Conclusion

Vaccination against COVID19 is safe and effective among IBD patients and following vaccination, most of complications are minor and negligible. In case of COVID involvement, it would not be serious and there is no need to hold the medications. Among IBD patients, the most common reason for vaccination refusal is fear of vaccine side effect.Read more P995 Development and validation of a deep learning model based on histological characteristics to predict primary non-response of infliximab in Crohn's diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Predicting primary non-response to infliximab (IFX) is important to select the optimal therapy and utilize personalized management in patients of Crohn’s disease (CD). This study aimed to develop and validate a deep learning (DL) model based on histological characteristics for predicting primary non-response to IFX in CD.

Methods

A training cohort and a validation cohort were recruited from the First Affiliated Hospital of Sun Yat-sen University. Clinical features, serological biomarkers, imaging features and histological characteristics of colonoscopy biopsy at baseline of IFX therapy were obtained as candidate predictors. Primary non-response was assessed at week 14. We developed a model using a multi-instance learning framework. This model combines patch-level features from whole slide images (WSI) with multi-modal information, together with pre-treatment image features and clinical features, to predict the response to infliximab (IFX) therapy. Finally, the model was validated for area under the curve (AUC) in a reference validation cohort.

Results

A total of 131 patients were included in the derivation cohort. The DL model based on pathologic features only had an under-the-curve receiver operating characteristic (AUROC) value of 0.87 in the 10-fold cross-validation cohort. The mean AUROC for the model combining pathologic and radiographic features was 0.88. The DL model achieved the highest AUROC value of 0.91 when combining pathological, radiomics and clinical features (Figure 1). When the pathological film was visualized by attention thermography, it was found that the ulcerated tissue was focused on, especially in areas dominated by neutrophils, lymphocyte aggregation and abnormal crypt structure.

Conclusion

The study developed several accurate DL models for predicting primary non-response to IFX by WSI. The DL model combining pathological, radiomics and clinical features achieving best performance. This model may help clinicians select appropriate therapeutic strategy and avoid unnecessary exposure to IFX in CD patients.Read more P785 Obesity in the response to biological treatments in Inflammatory Bowel Disease patientsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Obesity rates in patients with IBD reach up to 40%. Several authors suggest that obese patients have worse response rates to treatments. The aim of the study is to determine whether body mass index (BMI) influences the response to biological therapies in IBD. Secondly, other risk factors will be analyzed, and response rates to different biological treatments will be compared.

Methods

A retrospective cohort study of patients with IBD on biologic drugs under treatment between February 2013 and September 2022 is presented. Patients were recruited from IBD consultation of a tertiary center (Hospital Rey Juan Carlos, Madrid). Inclusion criteria included being under biologic treatment due to IBD and being näive to these therapies. The follow-up of these patients were carried out from February 2013 to September 2022.The main objective of the study is to determine if BMI influences the response to biological treatment in patients with IBD. As secondary objectives we will try to find the existence of other risk factors for loss of response and between different treatments.Treatment failure was defined as: need of dose increase, switch or swap to another biological treatment, clinical deterioration (measured by clinical indexes), use of systemic corticosteroid therapy, hospitalization, endoscopic inflammatory activity or surgical complications.The percentage loss of response was estimated using Kaplan-Meier curves, and factors influencing long-term response were studied using Cox regression.

Results

A total of 135 patients were included in the study, (mean age of 46.3 years), 59.3% male, 25.9% smokers, with a mean BMI of 26.1 kg/m2 (18.5% with BMI>30 kg/m2). In the study, 60% received infliximab and 45.9% received combined immunosuppressive therapy. Treatment failure was 59.1% in the non-obese and 80% in the obese (p=0.051). There were no differences in long-term response rates according to biologic treatments or disease subtypes. The only predictor factor for long-term response was combined treatment with immunosuppressants (p=0.037).

Conclusion

Obesity is not associated with a higher treatment failure rate in patients with IBD undergoing biological therapy. Combined treatment with immunosuppressants acts as a long-term response factor.Read more P996 Clinical Efficacy and Predictive Factors for the Effectiveness of Granulocyte and Monocyte Adsorption Apheresis Therapy for Ulcerative Colitis：A Retrospective Observational Single Center StudyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Granulocyte and Monocyte Adsorption Apheresis (GMA) is one of the valuable non-immunosuppressive therapies in the treatment of ulcerative colitis (UC). However, due to the limited number of facilities where GMA can be performed, there are few reports on the combined effects of GMA and prednisolone (PSL), the frequency of GMA implementation or predictive factors for the effectiveness. In this study, we examined the combined effect of GMA and PSL as a remission induction therapy, the frequency of GMA and predictive factors.

Methods

A retrospective observational study was conducted at Kushiro Rosai Hospital. We analyzed clinical data from UC patients who underwent GMA from February 2015 to May 2023.

Results

The study included 54 patients (30 males and 24 females), with a median age of 48 years and a median disease duration of 2 years. The median Lichtiger-CAI (L-CAI) was 8. There were 43 patients of pancolitis. There were 51 biologics-naïve patients and 3 biologics-experienced patients. Concomitant medications included 5-ASA agents in 21 patients, immunomodulators in 7 patients, and PSL in 31 patients. The median CRP was 1.19 mg/dl and the median albumin was 3.5 g/dl. Adverse events were observed in 3 patients (fatigue, dizziness, palpitations). The median number of GMA sessions was 10, with 33 patients undergoing twice weekly and 9 patients three times weekly. The clinical remission rate was 80% (43/54), and the clinical response rate was 89% (48/54), with a significant improvement in the median L-CAI from 8 to 3 before and after GMA (P<0.001). In the comparison between the PSL concomitant group and the non-PSL group, the clinical remission rate was 83.9% (26/31) in PSL group and 73.9% (17/23) in non-PSLgroup (P=0.369). The clinical response rate was significantly higher in the PSL group (87% (27/31)) than in non-PSL group (52.2% (12/23)) (P=0.004). There was no significant difference in the clinical remission/response rate between the group that underwent GMA twice a week (76.9% (30/39)/84.6% (33/39)) and three times a week (77.8% (7/9)/77.8% (7/9)). In univariate analysis, biologics-naïve was extracted as a contributing factor to clinical remission. The cumulative remission rate at 52 weeks was 72% overall. There was no significant difference in the cumulative remission rate between the PSL group (76.8%) and the non-PSL group (67.6%) (P=0.524). There was also no significant difference between the twice-weekly group (75%) and the three-times-weekly group (57.1%) (P=0.236).

Conclusion

GMA for UC was found to be useful and safely performed as a remission induction therapy. Concomitant use of PSL increased the clinical response rate. The frequency of GMA showed that three times per week was as effective as two times per week.Read more P786 Evaluation of the efficacy and safety of the use of subcutaneous infliximab in the treatment of inflammatory bowel disease in naïve patientsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The use of intravenous (IV) infliximab in inflammatory bowel disease (IBD) is an established treatment with a demonstrated safety and efficacy profile. Subcutaneous (SC) infliximab is currently available, showing comparable results in disease maintenance, but lacking studies in naïve patients. This study aims to determine whether initial treatment with SC infliximab is as effective and safe in real clinical practice.

Methods

This is a single-center observational study that included patients with clinically active IBD who directly initiated SC infliximab after IV induction (IV 5 mg/kg 0-2 weeks and SC 120 mg/2 weeks at week 6). The primary objective of the study was to evaluate the response to SC treatment at 3 and 9 months in patients naïve for infliximab. Secondary objectives included the need for intensification, rescue treatments (corticosteroids, change of biologic or surgery), the occurrence of adverse effects and pharmacokinetic aspects (blood levels, development of antibodies to infliximab or ATIs). Clinical activity was assessed using the Harvey-Bradshaw Index (HBI) for Crohn's disease (CD) and Partial Mayo Score (PMS) for ulcerative colitis (UC). In addition, biochemical parameters (hemoglobin, albumin, C-reactive protein, and fecal calprotectin) were monitored.

Results

A total of 19 patients were included, 14 with CD and 5 with UC (Table 1). Among them, 16/19 had not received previous biological treatment and 3/19 had received another anti-TNF other than infliximab. They were followed at 3 (18/19) and 9 months (18/19) (Figure 1). Significant improvement (p<0.05) was observed in the parameters of clinical activity (6/18 persisting with mild-moderate activity at 9 months) and biochemical activity (fecal calprotectin). Infliximab levels were adequate at 3 (median 12; range 3.2-39) and 9 months (median 15.9; range 0.3-51). In total, 31.6% of patients (6/19) discontinued treatment: 1/19 due to mild acute urticaria at baseline, 2/19 due to the development of ATIs (one also developed lung abscesses requiring hospitalization) and 3/19 due to loss of secondary response requiring a change of biologic. Of the latter, one also needed treatment with oral corticosteroids. In none of the patients was the treatment intensified or surgery required.

Conclusion

Treatment with SC infliximab in naïve patients seems to be an effective and safe alternative with results comparable to IV infliximab in real clinical practice. In our 9-month study, clinical scores and fecal calprotectin improved significantly, with low immunogenicity rates. Only 31.6% of patients discontinued treatment due to adverse effects or loss of response.Table 1. Baseline characteristics of patientsFigure 1.Evolution of clinical indices and biochemical parametersRead more P1078 The influence of different 5-aminosalicylic acid preparations on mercaptopurine metabolismWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

5-aminosalicylic acid (5-ASA), the cornerstone treatment for ulcerative colitis (UC), can impact thiopurine S-methyltransferase (TPMT) activity and thiopurine metabolism. We performed a post-hoc analysis of OPTIC, a randomised prospective controlled trial comparing mercaptopurine (MP) to placebo while continuing 5-ASA treatment in UC, to provide insight into the influence of different 5-ASA preparations on 6-thioguaninenucleotides (6-TGN) and 6-methylmercaptopurine (6-MMP) levels.

Methods

UC patients with active disease, despite ≥2 g/day 5-ASA treatment, received remission induction therapy with corticosteroids and conjunctively started weight-based MP therapy (1-1.5 mg/kg of bodyweight). For this analysis, the initial TDM measurement, using the Dervieux method, at week 6 was selected to exclude subsequent time points where dose adjustments were made. Different 5-ASA preparations were used, including time-dependent release (Pentasa® 4 g/day), Multi-Matrix (MMX) (Mezavant® 2.4, 3.6 or 4.8 g/day) and pH-dependent release (Salofalk® 3 or 4 g/day). Associations between 6-TGN and 6-MMP levels and 5-ASA preparations were analysed.

Results

In total, 29 patients started MP treatment, 27 patients reached the initial TDM measurement (41% female, median age 46 years [IQR 26-58], median disease duration 6 years [IQR 1-14]). Median 5-ASA dose was 4 g/day (IQR 3-4), the majority was treated with MMX 5-ASA (13/27), followed by time-dependent release 5-ASA (9/27) and pH-dependent release 5-ASA (5/27). Distribution of MP dose, body weight and age were similar across the different 5-ASA groups. At week 6, patients using an MMX 5-ASA formulation were more likely to have toxic 6-MMP concentrations (>5700 pmol/8×10⁸ RBC), but not 6-TGN levels, compared to time-dependent release formulation users (91% vs 38%, P=0.041) as well as an unfavourable 6-MMP/6-TGN ratio (P=0.024). This effect was not dose-dependent. Median 6-MMP levels at week 6 varied statistically significantly between the different 5-ASA preparations: i.e. MMX 5-ASA showed the highest and time-dependent release 5-ASA the lowest 6-MMP level (19000 [IQR 10519-31000] vs 3950 pmol/8×10⁸ RBC [IQR 2200-31000], resp., P=0.026, Figure 1). MP treatment persistence up to week 52 differed numerically between different 5-ASA preparations (MMX: 46%, time-dependent release: 78%, pH-dependent release: 60%), while no differences in hepatotoxicity or leukopenia were seen between 5-ASA formulations.

Conclusion

In UC patients receiving MP treatment, concomitant use of MMX 5-ASA was associated with higher toxic 6-MMP concentrations accompanied with an unfavourable 6-MMP/6-TGN ratio compared to time-dependent release 5-ASA leading to higher MP discontinuation rates.Read more P1030 Inflammatory Bowel Disease helpline contact trends in a real-world Australasian cohort: Crohn’s Colitis Cure (CCC) data insight’s programWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

For optimal outcomes, Inflammatory Bowel Disease (IBD) necessitates lifelong engagement in care. Specialized-IBD-nurse-led helplines improve access to care and reduce associated costs^1,2. Despite this evidence, IBD nurses and helplines receive variable funding and little is known about their use across care sites. We therefore analysed IBD-helpline usage in a large, multi-site real-world Australasian cohort.

Methods

Crohn’s Colitis Care (CCCare), is a cloud-based IBD-specific electronic medical record used in Australia and New Zealand. It includes a "Helpline" tab to support helpline encounter documentation during the point of contact. All entered data feed into an associated, de-identified clinical quality registry (CQR). Helpline-associated data fields, including contact reason and type, were extracted from CCCare’s CQR in November 2023. Data from 6 large adult care sites across Australia and New Zealand were analysed.

Results

In 2022, a total of 6,717 helpline encounters were documented. There was a roughly equal split in contact type; phone accounting for 50.9% (n=3,416) and email for 49.1% (n=3301). The most common reasons for contact were related to medications (n=2,577; 38.4%), investigations (n=1,719; 25.6%) and clinical (n=1,060; 15.8%).More encounters were seen in 2023 (to date of data extract), with 7,540 helpline entries to date (Figure 1). In 2023, the most common form of patient contact was email (70.3%), with phone contact accounting for only (29.8%). The most common reasons for contact were again related to medications (n=2,577; 31.1%), investigations (n=1,162; 22.0%) and clinical (n=1,439; 19.1%). In both years, helpline activity was lowest in January and February, perhaps corresponding to the Holiday season (southern hemisphere summer).

Conclusion

A number of helpline entries were recorded across these 2 years, with activity lowest each summer. The data show a shift in the predominant mode of contact from phone to email in 2023, reflecting evolving communication preferences and making scheduling of helpline support easier.1 - Nicolaides S, Vasudevan A, Van Langenberg D. Inflammatory Bowel Disease Helpline Reduces Subsequent Inpatient Admission Rates. J Crohns Colitis. 2020 Feb 10;14(2):281. doi: 10.1093/ecco-jcc/jjz141. PMID: 31374121.2 - Karimi N, Sechi AJ, Harb M, Sawyer E, Williams AJ, Ng W, Connor SJ. The effect of a nurse-led advice line and virtual clinic on inflammatory bowel disease service delivery: an Australian study. Eur J Gastroenterol Hepatol. 2021 Dec 1;33(1S Suppl 1):e771-e776. doi: 10.1097/MEG.0000000000002249. PMID: 34402467.Read more P787 Use of upadacitinib to treat IBD in post-liver transplantWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Approximately 2% of patients with inflammatory bowel disease (IBD) have concurrent primary sclerosing cholangitis (PSC). Liver transplantation (LT) is sometimes required due to progressive PSC. However, the management of active IBD post-LT is challenged due to concomitant anti-rejection immunotherapies. Janus kinase inhibition has been previously described to have anti-rejection properties in patients who have had renal transplants. Here, we describe our experience with upadacitinib (UPA), a selective Janus kinase-1 inhibitor, for post-LT active IBD combined with anti-rejection immunosuppression therapy.

Methods

This is a retrospective, single-center observational study in a tertiary IBD center. We identified patients with LT treated with UPA for their IBD. Patient related outcomes including transplanted liver status and clinical efficacy and safety of UPA for IBD activity were reviewed.

Results

We identified four patients (3 with Crohn’s disease, 1 with ulcerative colitis) treated with UPA after LT due to PSC, with the UPA indication for the treatment of IBD (n=3) and organ rejection (n=1). Median follow-up was 3 months (interquartile range (IQR) 1.5-7.1), median age at starting UPA was 41.5 years (IQR 40-44), and median interval from the transplant was 3.2 years (IQR 2.3-5.6). Two patients with Crohn’s disease clinically responded to UPA, one weaned off prednisone 30mg/day and remained in clinical remission after reducing UPA from 30 mg/day to 15 mg/day. Two patients developed elevated AST/ALT of up to 107/57 U/L and 83/228 U/L; one required discontinuation of UPA at one month with subsequent AST/ALT normalization; the other remained on UPA with 1.5 month follow-up so far. One UC patient was treated with UPA combined with vedolizumab in an attempt to discontinue prednisone for their immunosuppression for organ rejection, however, they were unable to wean off prednisone due to recurrent ALT and Alk Phos elevations. One patient acquired a mild case of COVID-19 which resolved without change in therapy. No life-threatening adverse events were observed.

Conclusion

We describe 4 patients with IBD who had LT for PSC and who were treated with UPA with successful management of active IBD in 2 cases but lack of efficacy in one case and liver enzyme elevations limiting UPA use in a second. These findings support further exploration of this novel mechanism for treatment of IBD in the post-LT setting.Read more P1086 Re-administration of infliximab in patients with extremely refractory perianal Crohn’s diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

This study aims to evaluate the efficacy of infliximab re-administration to a cohort of patients with extremely refractory perianal Crohn's Disease (CD).

Methods

Retrospective analysis of prospectively collected data in CD patients with perianal disease, who despite being treated with infliximab, had to change treatment either because of primary non-response, secondary loss of response, or due to the occurrence of an allergic reaction. They then became resistant to the other therapies tested, resulting in Infliximab being given again. We then evaluated the clinical response to fistula management (Perianal Disease Activity Index PDAI ≤ 4), as well as the occurrence of adverse reactions in these patients.

Results

We included 14 patients (8 women), with a mean age (SD) of 38.2 (9.5) years. According to the Montreal classification our patients had L1 (n=2), L2 (n=2) and L3 (n=10) disease. After the initial Infliximab failure (even after dose escalation), patients received vedolizumab, ustekinumab and adalimumab without response or with secondary loss of response. Therefore, it was decided to re-administer infliximab with concomitant administration of azathioprine. After 1 year of follow up clinical response (PDAI ≤ 4) was seen in 4 patients (28.5%). Re-administration of infliximab was discontinued in 2 patients due to severe allergic reaction; however, the remaining patients did not experience side effects.

Conclusion

Re-administration of Infliximab may be able to help a small percentage of treatment resistant patients with perianal CD.Read more P1031 Intestinal ultrasound for monitoring therapeutic response in patients with ulcerative colitis treated with upadacytynibWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Intestinal ultrasound (IUS) is a noninvasive method to assess disease activity in inflammatory bowel disease (IBD) although there are still limited data of usefulness of IUS in ulcerative colitis (UC) compared to Crohn’s disease (CD). The aim of the study was to evaluate usefulness of intestinal ultrasound in comparison to endoscopy in assessment of the efficacy of upadacytynib (UPA) in induction of remission in patients with UC.

Methods

This was a prospective, two-centers study in which we enrolled 27 patients with a flare of UC (total Mayo score>7) treated with UPA (8 weeks of induction period). IUS, calprotectin level and laboratory tests were conducted in week 0, 4 and 8. Milano ultrasound criteria (MUC) were used to assess the IUS disease activity.

Results

Among 27 patients 34% achieved clinical remission and 40,6% endoscopic remission already in week 4. After 8 weeks of treatment with UPA clinical remission in 53,1% and endoscopic remission in 56,2% of UC patients were achieved. In IUS the most affected parts of the colon were rectum and sigmoid colon. 100% of the patients had an increased bowel wall thickness (BWT)>3mm in the sigmoid colon and rectum at baseline. In the first 4 weeks of the study, the percentage of patients with an increased BWT in the sigmoid colon and rectum decreased significantly and remained low at week 8. 78% of patients with normalized BWT had endoscopic remission vs 22% without endoscopic remission (p<0.001). There was 74% correlation between MUC and total Mayo score (p=0,013).

Conclusion

Upadacitinib has demonstrated a positive efficacy during induction of remission in UC patients, shown as improvement in IUS parameters as well as in endoscopy improvement. Our data showed a strong correlation between normalization of BWT and endoscopic remission in patients with UC treated with upadacytynib. IUS seems to be a useful and non-invasive method for monitoring disease course and for assessing treatment response in UC patients.Read more P817 Incidence and risk factors of infection in patients with inflammatory bowel disease: longitudinal prospective INFEII registry of GETECCUWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The true effect of having IBD in the development of infections has not been studied in depth since cohort studies are scarce and the results of studies are sometimes contradictory. Especially, this complication has not been addressed prospectively in an incident cohort of patients with IBD.

Aims

To assess, regarding infections in IBD: 1) incidence and type, 2) risk factors, 3) effect of type and the duration of IBD treatment, 4) impact in mortality 5) effect of IBD activity.

Methods

The INFEII registry (ClinicalTrials.gov: NCT02904590) is a prospective study promoted by GETECCU to determine the incidence and risk factors of infection in an inception cohort of patients with IBD and follow-up of at least 5 years. This longitudinal prospective study within the ENEIDA registry was conducted including incident cases with IBD. Patients were recruited between 2016 and 2020 with a planned follow-up of 5 years. All infections were detailed analysed. An infection was considered relevant when: 1) required hospital admission, 2) led to death or endangered the patient’s life, 3) was treated with specific antibiotics,4) occurred recurrently, and/or 5) required change/withdrawal of immunosuppressive treatment.

Results

The INFEII registry recruited 1456 patients from 28 centres throughout Spain. The median follow-up was 71 months (IQR 60-79 months). The description of the cohort is presented in Table 1. Of the 1456 patients included, 580 (40%) presented at least one relevant infection. In total, 1321 infections were collected. One-hundred and seven infections (8%) required hospitalisation and four patients died (0.3%) over infection. Ninety-nine patients were lost to follow-up (22 died and 34 changed hospitals). The most prevalent infections were: ear-nose-throat in 238 cases, urinary tract infections in 237, respiratory in 234, COVID-19 in 133, skin infections in 127, dental in 64 and colitis/enteritis in 64 (Figure 1). From the whole cohort and at some point, in time, 756 (52%) patients received 5ASA, 481 (33%) steroids (369 (25%) oral, 112 (7.7%) intravenous), 568 (39%) azathioprine, 72 (4.9%) methotrexate, 21 (1.4%) tofacitinib, 533 (37%) antiTNF, 141 (9.9%) ustekinumab and 77 (5.3%) vedolizumab. The effect of treatment and IBD activity in each infection is being analysed.

Conclusion

Infections are frequent complications in patients with IBD, presented in 40% of them. Being a woman, having a history of past serious infections or occupational risk may be associated with infection occurrence. It has to be determined if IBD activity and treatment suppose a greater risk for infections. This is a paradigmatic study that implies the first use of the ENEIDA registry in prospective research.Read more N03 Flexibility & Accessibility, e-Literacy, Resourcing and The Human Factor: Early Lessons from EIBD, a UK Qualitative Interview StudyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Since the COVID-19 pandemic, the use of health tools (video/phone consultations, patient portals, and digital applications) has increased in the clinical management of patients with Inflammatory Bowel Disease (PIBD). We aimed to evidence the acceptability of eHealth tools by investigating the shared experience of PIBD and healthcare professionals (HCPs) in using eHealth to carry out follow-up appointments and support self-management.

Methods

An exploratory qualitative method was used. Participants were recruited via professional networks, social media platforms, Crohn's and Colitis UK website and newsletters. Semi-structured interviews were conducted remotely in April/May 2023 using MS Teams or Zoom. Transcripts were analysed using a thematic analysis.

Results

Fifteen HCPs (13 female) participated: IBD specialist nurses (n=9); gastroenterologists (n=2), pharmacists (n=2) and Dieticians (n=2). The 16 PIBD (10 female) participants were living with Crohn’s Disease (n=9), Ulcerative Colitis (n=6), and Inflammatory Bowel Disease Unclassified (n=1); age was reported in ranges 18 -24 (n=3), 24-34 (n=1), 35-54 (n=8), and 55-65 (n=2) and 75-85 (n=1). Time since IBD diagnosis ranged from < 6 months - 43 years (mean time 18.7 years). Some participants had pre-diagnosis symptoms for at least one year (81%) to over five years (25%). Four themes emerged:• Flexibility and Accessibility: PIBD appreciated the ease of virtual appointments and access to test results and information but wanted flexibility and a personal approach to their care; eHealth connected them to their IBD team more easily.• Resource: HCPs wanted better digital training since remote assessment skills differ from in-person assessment skills. They also identified the need for admin support when planning to implement eHealth tools. HCPs and PIBD wondered whether eHealth was primarily a cost-savings exercise, whilst the need for resource efficiencies across the health service was recognised.• e-Literacy: HCPs were concerned that some older PIBD might be excluded from accessing eHealth due to e-literacy and capability issues, perceiving that eHealth is for the younger generation.• The Human Factor: PIBD and HCPs wanted to have already met in person anyone they engaged with later virtually. For PIBD, in-person consultations meant they felt seen or understood, and they described the importance of hands-on abdominal examinations in reassuring them about their health status.

Conclusion

There is an acceptability of eHealth to support the care of PIBD, but HCPs and PIBD still value the Human factor. Concerns over Resourcing, Flexibility and Accessibility and e-Literacy may need addressing to avoid these becoming barriers to the benefits of virtual healthcare in supporting PIBD.Read more P1032 Ileoanal Pouch Salvage Rates with Endoluminal Vacuum Therapy for Early vs. Late Anastomotic LeaksWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Anastomotic leakage is a dreaded complication after ileal pouch-anal anastomosis (IPAA) that occurs in 5-10% of cases. Endoluminal vacuum (EndoVac) therapy has emerged as a minimally invasive option that promotes healing by applying negative pressure to the associated abscess cavity through the anastomotic defect but is typically applied only to early IPAA leaks. We hypothesized that EndoVac for early compared with late leaks would be associated with a higher pouch survival rate.

Methods

We retrospectively reviewed the medical records of consecutive patients who developed a pouch anastomotic leak after IPAA and were treated with EndoVac therapy at our institution between 2005-2023. Patients were stratified into early (30 days) and late (>30 days) leaks. Anastomotic healing was defined as complete closure of the leak site, as evidenced by resolution of symptoms, normal endoscopic and radiographic evaluation, and no further drainage from the presacral space or abdominal wall. Pouch failure was defined as a permanent ileostomy or pouch excision. Figures represent frequency (proportion) or median (range). The probability of pouch survival over time was estimated using the Kaplan-Meier method.

Results

A total of 13 pouch patients underwent EndoVac therapy for leaks by six surgeons (median age, 34 years; 62% male; median body mass index 25.8 kg/m². Diagnoses: ulcerative colitis (n=11), and familial adenomatous polyposis (n=2). The median time to leak diagnosis was 32 (12- 340) days; of these 6 (46%) were early and 7 (54%) were late. All (100%) patients were diverted at the time of EndoVac therapy, 10 (77%) patients were still diverted, and 3 (23%) were rediverted. Patients underwent a median of 5 EndoVac changes (2-22) over a median duration of 34.5 (21-125) days. After EndoVac therapy, complete/near-complete defect healing occurred in 9 (69%), 1 whom required suturing of a small residual defect. Of those with incomplete healing (n=4), 3 (23%) underwent pouch excision and 1 (7.7%) a redo pouch. Comparing early and late leaks, defect healing (66.7% vs 71.4%, p=0.72) and pouch survival (83.3% vs 71.4%, p=0.65) were similar. The overall pouch salvage rate was 77% (10/13).

Conclusion

EndoVac therapy is effective for postoperative pouch leaks and achieves a high rate of pouch salvage in both early and late leaks.Figure 1. CONSORT-style flowchart of IPAA leaks treated with EndoVac therapy.Read more P818 Imaging-based preoperative body composition is associated with the risk of postoperative complications and postoperative endoscopic recurrence in patients with Crohn’s diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Alterations in body composition are common in Crohn’s disease (CD) patients and influence disease outcomes. However, the impact of preoperative body composition on postoperative outcomes is not completely understood. Therefore, this study aimed to investigate the association of preoperative body composition with postoperative complications and endoscopic recurrence in CD patients undergoing ileocolic (re-)resection (ICR).

Methods

CD patients (≥16 years) scheduled for an ICR with a computed tomography (CT) scan available (<12 months prior to ICR) were identified from an ongoing prospective, multicenter cohort study. Skeletal muscle mass (SM), visceral (VAT) and subcutaneous adipose tissue (SAT), and their radiation attenuation (RA) were assessed on a single CT image at L3 using a validated deep-learning automatic segmentation tool (Mosamatic). Low RA is associated with increased tissue triglyceride content (e.g. myosteatosis in case of SM). Cut-offs, based on sex-specific tertiles, were set at the lower and upper tertile for low and high values. The primary outcome was the development of overall postoperative complications within 90 days. Secondary outcomes were postoperative endoscopic recurrence (Rutgeerts’ score ≥ i2b) at 6 months, infectious complications, and moderate to severe complications (Clavien-Dindo ≥ II). Multivariable logistic regression was performed to assess the association of body composition variables with postoperative outcomes, including adjustment for confounders.

Results

121 patients were included (median age 37.1 years (IQR 27.1–53.2), 59.5% female). Median disease duration at surgery was 3.6 years (IQR 0.4–12.7), and 57.0% had prior exposure to ≥ 1 biological. Overall postoperative complications were reported in 51.2%, endoscopic recurrence in 33.3%, infectious complications in 26.4%, and moderate to severe complications in 41.3%. High SM-RA (aOR 0.67; 95%CI 0.16–0.85) and low VAT (aOR 0.38; 95%CI 0.17–0.87) were associated with decreased overall postoperative complications. Low VAT-RA was associated with decreased endoscopic recurrence (aOR 0.21; 95%CI 0.07–0.67), and high SAT with increased infectious complications (aOR 3.05; 95%CI 1.28–7.28).

Conclusion

Low visceral adipose tissue and high radiation attenuation of skeletal muscle (i.e. no myosteatosis) were protective of overall postoperative complications in CD patients undergoing ICR. Low radiation attenuation of visceral adipose tissue (i.e. high triglyceride content) was protective of endoscopic recurrence. High subcutaneous adipose tissue increased the risk of postoperative infectious complications. Further research in larger populations is warranted to validate these findings to improve preoperative stratification and strategies for CD.Read more P1033 Road to exit strategy in patients with inflammatory bowel disease: ready or not?Wed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Whereas there is an emerging consensus on the optimal approach to initiation of a range of therapies in inflammatory bowel disease (IBD), there remains greater uncertainty about the risks, benefits, and timing of stopping treatment when patients are in stable remission on therapy. When planning an exit strategy for drug withdrawal, the risk of disease relapse must be balanced against the risk of drug-related adverse events and healthcare costs. Our study evaluated the risks of disease relapse associated with withdrawal of the biologic therapy in both ulcerative colitis (UC) and Crohn’s disease (CD).

Methods

In this is a retrospective observational study, the exit strategy was proposed to 60 patients regularly followed in two IBD referral centre from 2015 to 2023. The exit startegy was performed as: (i) discontinuation without de-escalation, (ii) progressive de-escalation and (iii) azathioprine as monotherapy. Data on medical history were collected from electronic health records. Chi-square test was used to compare categorical variables. Logistic regression was used to assess the relationship between disease-related characteristics and the onset of disease relapse after the withdrawal.

Results

60 IBD patients were enrolled, 46 patients withdrawal their biologic therapy and 14 patients were in a de-escalation stategy. These 46 patients (15 UC and 31 CD) performed discontinuation without de-escalation (65%), progressive de-escalation (26%) and azathioprine as monotherapy (9%). They withdraw anti-TNF (82%) or other biologics (18%). Most of patients (71%) were on first line of biologic therapy. The median follow-up period after drug withdrawal was 29 months. A disease relapse occurred in 14 patiens with a median period of 12 months. A good recapture of previous therapy was observed in 57% of patients. Logistic regression analysis revealed a trend of significance between biologic therapy duration (p 0.05) and absence of flare-up after exit strategy. No correlation was noticed with duration of endoscopic or clinical remission before starting the drug withdrawal.

Conclusion

There are no specific factors related to a successful exit strategy. Biologic drug discontinuation is something best considered on a case-by-case basis and determined by patient preferences and disease features. We need more specific study in order to identify patients who can stop therapy without undue risk of poor outcomes.Read more P1079 Mindfulness-based cognitive therapy to reduce psychological distress in patients with Inflammatory Bowel Disease: first results of a multicentre randomised controlled trial (MindIBD)Wed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Many patients with Inflammatory Bowel Diseases (IBD) suffer from psychological distress and fatigue. Moreover they report a reduced quality of life. The availability of psychosocial treatment options is limited. As mindfulness-based cognitive therapy (MBCT) has been shown to reduce psychological distress and fatigue, and improve quality of life in other populations, MBCT might also be effective in patients with IBD.

Methods

The MindIBD study was a prospective, multicentre, randomised controlled trial, conducted in one academic and three general hospitals in the Netherlands. Patients of 16 years and older with a confirmed IBD diagnosis were eligible if the IBD was in remission (based on faecal calprotectin <250 mg/kg and no changes in IBD medication for at least three months) and they experienced at least mild psychological distress (based on Hospital Anxiety and Depression Scale (HADS) total score ≥ 11). Participants were allocated in the intervention group (MBCT plus treatment as usual) or control group (treatment as usual alone). Assessments were conducted at baseline, post-intervention (3 months) and at 6, 9 and 12 months after baseline. Primary outcome was the effect on psychological distress post-intervention. Secondary outcomes included fatigue, perceived disease control, disease activity, disease-specific quality of life and positive mental health. This trial was registered at ClinicalTrials.gov: NCT04646785.

Results

A total of 142 IBD patients were randomly assigned to the intervention group (n=70) or the control group (n=72). The study population had a median age of 50 years (IQR 39-59 years), consisted of 91 women (64%) and 68 participants (48%) were diagnosed with Crohn’s disease. Post-intervention, participants in the intervention group showed a mean decrease on the HADS total of 4.7 ± 6.3 points compared to a mean decrease of 1.2 ± 5.2 points in the control group. This difference in improvement of psychological distress was statistically significant (p<0.001), and this benefit was maintained during follow-up (p=0.005). MBCT did also result in a significant improvement on fatigue (p=0.022) and positive mental health (p=0.022) post-intervention. These improvements remained in favour of the intervention group during follow-up, although not significantly different. No differences were found on perceived disease control, disease activity and disease-specific quality of life.

Conclusion

MBCT reduces psychological distress and improves fatigue and positive mental health. Therefore MBCT can be considered as a valuable addition to the limited psychosocial interventions for patients with IBD to improve psychological distress, fatigue and positive mental health.Read more P1070 Utilization of HLA-DQA1*05 haplotype testing in routine clinical practice to stratify advanced therapies: A prospective pilot studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

A potential association between HLA-DQA1*05 allele and development of anti-drug antibodies in Anti-TNF treated Crohn’s Disease patients is reported in the PANTS study. The utility of stratifying treatment based on the HLA-DQA1*05 status has not been evaluated in a biomarker stratified clinical trial and there are no prospective studies evaluating the impact of using HLADQA1*05 in routine clinical practice to decide on monotherapy versus combo therapy while initiating on anti-TNFs. We aimed to determine the impact of carriage of HLADQA1*05 allele to guide the need for concomitant immunomodulators in IBD patients planned for Infliximab therapy.

Methods

In our prospective study, 97 adult IBD patients were included. All patients were screened for HLADQ2 haplotype as part of their routine pre-biologic screen. Stratification was done according to the presence of HLA-DQA1*05 haplotype. HLADQA1*05 positive patients were assigned combo therapy with Infliximab combined with either methotrexate or azathioprine. HLADQA1*05 negative patients were given infliximab monotherapy unless another indication for concomitant immunomodulation was present. Patients were followed for a minimum of one year after drug initiation. Primary outcome was drug persistence, expressed as time to discontinuation of infliximab, segregated by the treatment decision based on HLA-DQA1*05 status. Secondary outcomes were proportion of patients developing anti-drug antibodies and time to antibody development. Statistical analysis was done using Kaplan-Meier curves and log-rank test.

Results

Baseline characteristics are detailed in Table 1. HLA-DQA1*05 was positive in 41/97(42%) of patients and combo therapy was offered to 33/41(80%) of those patients. Immunomodulators were avoided in 39/97(40.2%) patients representing the subset of patients with negative HLADQA*105 to whom no immunomodulator was offered. There was no statistically significant difference in drug persistence rates between the groups treated based on HLA-DQA*105 status. 54/97(55.6%) of the patients developed anti-infliximab antibodies during their follow-up (25/41(60.9 %) in HLA positive and 29/56 (51.7%) in HLA negative). Neutralizing drug antibodies with absent drug levels were detected in 15/97(15.5%) of patients (8/41(19.5%) in HLA positive, 7/56(12.5%) in HLA negative). The median time to antibody development was 33.5 weeks (IQR 22-46.7).

Conclusion

This is the first prospective study suggesting HLA-DQA1*05 haplotype testing can be used in routine clinical practice to stratify therapy based on the need for immunomodulators in infliximab treated IBD patients. HLA-DQA1*05 negative patients may be started on monotherapy with potential for improving safety and reducing costs of immunomodulator monitoring.Read more P819 Postoperative prophylaxis prevents surgical and severe endoscopic recurrence after primary ileocecal resection in CD patientsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Prophylactic medication following ileocecal resection (ICR) is recommended in patients with Crohn’s disease (CD), particularly in patients at increased risk of recurrence. This study aimed to evaluate the effect of prophylactic medication on long-term prognosis.

Methods

A retrospective cohort study was performed in patients with CD who underwent a primary ICR. Patients were divided into two groups: prophylaxis (i.e. initiation of prophylactic medication<12 weeks following ICR) versus no prophylaxis. The primary and secondary outcomes were surgical recurrence and severe endoscopic recurrence (modified Rutgeerts score ≥ i3). To compare the outcomes between both groups, inverse propensity score-weighted comparison was used to adjust for confounding and selection bias. The survival and association between prophylaxis and both outcomes were assessed with Kaplan-Meier analyses and Cox proportional hazard models.

Results

811 patients underwent an ICR [median follow-up 5.8 years (IQR 2.5 – 10.7)](Table 1). Prophylaxis was initiated in 297/811 [37%] patients. In 364/514 [71%] patients without prophylaxis, medication was started after median follow-up 15 months [IQR 7.2 – 46.5]. Cumulative rates of surgical and endoscopic recurrence at 1, 2, 5 and 10 years were significantly lower in patients with prophylaxis versus no prophylaxis [1%, 3%, 9% and 19%, vs. 3%, 4%, 11% and 23%, p < 0.05] and [4%, 8%, 15% and 27% vs. 10%, 16%, 25% and 40%, p < 0.01]. Propensity-scored weighted analysis showed that patients treated with prophylaxis were less likely to experience surgical recurrence [aOR 0.52; 95% CI 0.33 – 0.82] and severe endoscopic recurrence[aOR 0.53; 95% CI 0.35 – 0.81]. In multivariable analysis, prophylaxis was identified as protective factor for surgical [aHR 0.67, 95% CI 0.45 – 0.99] and severe endoscopic recurrence [aHR 0.54, 95% CI 0.37 – 0.78] (Table 2).

Conclusion

Surgical and severe endoscopic recurrence up to 10 years following primary ICR are significantly reduced in patients with CD who received prophylaxis as compared to no prophylaxis. Prophylaxis was associated with the prevention of surgical and severe endoscopic recurrence.Read more P1085 Machine learning to predict the efficacy of ustekinumab for ulcerative colitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Ustekinumab (UST), an anti-IL12/23p40 monoclonal antibody, is now widely used for ulcerative colitis (UC). Meanwhile, there are no established models to predict the efficacy of UST for UC. We previously demonstrated that the machine-leaning approach was useful for finding predictors and developing a prediction tool in vedolizumab (VDZ) treatment for UC (Miyoshi et al. Sci. Rep. 2021). In this study, we aimed to develop a new prediction model for UST in patients with UC.

Methods

UC patients who started UST as a remission induction therapy in Kyorin University Hospital were enrolled as the training cohort (Cohort 1), and at Toho University Sakura Medical Center were enrolled as the test cohort (Cohort 2). Clinical information of 44 items including age, sex, past/concomitant therapy for UC, clinical and endoscopic activity for UC, blood sample, and so on, in week 0, and clinical activity for UC in week 22 were collected. The outcome was defined as steroid-free clinical remission (SFCR) in week 22. Clinical remission was defined as the Lichtiger index (LI) of four or lower. Patients who terminated UST or needed surgery before week 22 were regarded as not achieving SFCR. Random Forest was used for the clinical data in Cohort 1 to identify the promising predictors to achieve SFCR in week 22. Prediction models were developed with these predictors and their prediction ability was validated in Cohort 2.

Results

25 patients (SFCR/non-SFCR=13/12 patients) and 46 patients (SFCR/non-SFCR=27/19 patients) were enrolled as Cohort 1 and Cohort 2, respectively, in this study. First, we examined if a VDZ prediction model that we previously reported could work for predicting the UST efficacy. In Cohort 1, the model showed a positive predictive value (PPV) of 56.3% and a negative predictive value (NPV) of 62.5%. This supports the notion that a prediction model for UST should be different from that for VDZ. From the 44 clinical information, 10 clinical features with the highest contribution to SFCR with UST were detected in Cohort 1. These clinical features included serum albumin, monocyte fraction, height, MCV, total protein, LI, white blood cell count, MCHC, partial Mayo score, and CRP (Figure 1). With these 10 clinical features, the seven prediction models for UST were developed using different algorithms. These models were applied to Cohort 2 to validate the prediction ability. The model that showed the best prediction ability was a support-vector machine polynomial model with PPV 68.8% and NPV 71.4%, respectively.

Conclusion

We developed a new prediction model for the middle-term efficacy of UST in patients with UC. Further studies are needed to develop a prediction model for each molecular-targeted drug.Read more P959 Dose escalated vedolizumab in Inflammatory Bowel Disease - Crohn's Colitis Cure (CCC) Data Insights ProgramWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Vedolizumab is a gut specific integrin antagonist with established efficacy in inflammatory bowel disease (IBD). Many people with IBD fail to achieve adequate or sustained response to standard dosing, thus requiring dose escalation (DE). We aimed to explore the need for escalated dosing and subsequent outcomes in a large real-world cohort.

Methods

We utilised data from the CCC registry entered during routine clinical care at 14 centres across Australia and New Zealand. Data were extracted in October 2023 and included patients on intravenous (IV) and subcutaneous (SC) therapy. DE was defined as maintenance dosing > 108mg SC fortnightly, > 300mg IV Q8weekly and/or additional induction doses. We examined data prior to and at 12 months post DE.

Results

919 people with IBD received Vedolizumab, with 28% (n=261) receiving DE therapy. Median age for the DE cohort was 40 years (IQR 29-56) with median age at diagnosis 26 (IQR 19-39). Median age, age at diagnosis, disease duration and BMI did not vary significantly between the DE and standard dosing cohorts. Most of the DE cohort had Crohn’s (60%) followed by ulcerative colitis (38%) and IBD-unclassified (2%). Half the DE cohort was female (49.8%) with median time to dose escalation being 6 months. 57% (n=111) continued on DE Vedolizumab after 12 months.Median drug level (where measured) increased from 10.3mg/L pre-DE to 19.8mg/L post. Rates of faecal calprotectin (FCP) remission, (FCP <250ug/g) increased at 12 months post DE as did rates of PRO2 and endoscopic remission (p=0.007, 0.034 & 0.016 respectively). Improved remission rates coincided with decreased systemic steroid requirements, which fell by >50% at 12 months post DE (p=0.001). Hospital admissions and radiological investigations were unchanged over the study period, however the need for endoscopic assessment decreased 12 months post DE. Patients receiving DE therapy had increased encounters healthcare providers, with more clinical assessment and Healthline calls at 12 months post DE (p=0.001 & 0.001 respectively).

Conclusion

In an Australasian cohort of people with IBD, over a quarter of individuals receiving Vedolizumab therapy required DE. DE Vedolizumab correlated with improved endoscopic, PRO2 and FCP remission rates at 12 months with reduced steroid use. As biosimilars reduce the cost of DE therapy, further research beyond 12 months examining remission rates, healthcare utilisation and cost analysis in more detail is needed.Read more P1097 The effect of lockdowns during the COVID-19 pandemic on the epidemiology of inflammatory bowel diseases: a comparison of two nationwide cohortsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Mechanistic evidence suggest a link between COVID-19 infections and the development of immune mediated diseases. Additionally, the lockdowns during the pandemic limited the accessibility to medical care, possibly leading to reduced number of diagnosed patients with inflammatory bowel disease (IBD). We aimed to explore these contending trends on the epidemiology of IBD during the COVID-19 pandemic in two countries with different lockdown policies.

Methods

We utilized nationwide IBD cohorts in Israel and Sweden to explore the incidence of IBD during the pandemic (2020-2021) compared to three years prior (2017- 2019). We examined temporal trends through the presence of inflection points by Joinpoint regression analysis and reported average monthly percentage changes (AMPC).

Results

A total of 155,837 patients with IBD were included (Israel, 58,640; Sweden, 97,197). The incidence of IBD was stable during the three years prior to the beginning of the COVID-19 pandemic in February 2020 (AMPC: Israel 0.0% [95%CI -0.5% to 0.4%]; Sweden 0.2% [95%CI -0.3% to 0.7]). Thereafter, the incidence rate in Israel remained stable until November 2020 (AMPC 2.3% [95% CI -13.4% to 29.9%]) and then decreased sharply (AMPC -6.4% [95%CI-20.8% to 17.0%]) until February 2021 and -20.1% [95%CI -38.9% to -4.7%]) from February 2021), while in Sweden, which had a less stringent lockdown policy, the incidence rate decreased slightly until July 2020 (AMPC -3.3% [95%CI -21.6% to 20.3%]), but increased thereafter (AMPC 13.6% [95%CI -12.6% to 27.0%]; Figure).In Israel, the reduced incidence rate during the pandemic (February 2020 to July 2021) was notable mainly in the adult-onset disease, while in Sweden, although the overall incidence rate increased steadily across all age groups, the largest change was apparent among the elderly.

Conclusion

In this study of two nationwide cohorts we found that the initial decrease in incidence of IBD was most apparent in Israel with a more stringent lookdown policy and among elderly in Sweden, the only population there with significant social restrictions during the pandemic. Taken together, it is likely that the reduced incidence stemmed from the limited access to the healthcare system. Future studies are needed to determine the long-term effect of the pandemic on IBD incidence.Read more P769 Impact of discontinuation of anti-TNF therapy: A long term follow-up data of risks and predictors relapse in a large Indian cohortWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Discontinuation of anti-TNF therapy in IBD is an important consideration in TB endemic low resource settings of the developing world. There are no established guidelines on withdrawal of biologics. A proper exit strategy on when and how biologics can be stopped is therefore warranted. We aimed to identify risk factors and rates of relapse post withdrawal in a large real-life cohort of patients from India.

Methods

Prospectively collected data of consecutive patients treated with anti-TNFs from the IBD registry of a large tertiary care centre was analyzed. Demographics,baseline disease characteristics,reasons for discontinuation, response to anti-TNF,and relapse rate after withdrawal were analysed. Time to event analysis was done to evaluate relapse rates over time. Cox proportional hazard analysis and non-parametric tests were performed to identify risk factors of relapse.

Results

Of 8300 patients, only 725(8.7%),(Median age-36y,IQR:26-47,61.2% male,61.2%CD, 32%UC, IBD-U 1.8%) received anti-TNFs. 445 (61.3%) discontinued with median follow up of 54 m(IQR:31-81). Reasons for discontinuation were primary non-response(64,14.3%);secondary loss of response (44,9.8%);financial constraints(27,6.1%);TB reactivation (18,4%), side effects(17,3.2%); infusion reactions(20,4.4%);non-compliance(4,0.9%), and COVID lockdown (6,1.3%).Overall, 232/445 (52%) were in clinical and endoscopic remission while stopping anti-TNFs with median follow up of 41 months(IQR:24.5-67). Relapse rates at 1,2,3,4, and 5 years after discontinuation were 16%,5.6%,5.2%,2.6% and 1.3% respectively. Overall,161/232(69%) patients remained in remission(Fig1A).Patients who stopped after clinical and endoscopic remission had higher likelihood of maintaining remission after discontinuation of biologics (Log-rank test,p=0.001). On multivariate analysis, fistulizing disease(p=0.03), prior history of bowel surgery (p=0.019), immunomodulator usage (p=0.001) and shorter duration of therapy (p=0.017) were associated with significantly higher rate of relapse(Table1). Cumulative time to relapse was significantly longer in those with or without endoscopic remission (median 17.3 vs 7 months;p=0.04)(Fig1B). On the other hand, shorter disease duration (p=0.001) and absence of extra-intestinal manifestations (p=0.009) were associated with lower risks of relapse.

Conclusion

60% of patients discontinued anti-TNF therapy in this real world cohort. However, long-term cumulative relapse rates were low(30%), particularly in non-fistulizing disease, with no history of bowel surgery or extra intestinal manifestations and in endoscopic remission. A definite exit strategy appears feasible and would be a practical and affordable management approach.Read more P960 Comparison of clinical outcomes by induction therapy response status in patients with Inflammatory Bowel Disease (IBD) treated with subcutaneous (SC) versus intravenous (IV) infliximab (IFX): Post hoc analysis of a pivotal, randomised controlled trialWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Clinical associations between initial response and long-term outcome are well established for IV IFX in IBD.^1,2 In 2020, SC IFX was approved in Europe for treating moderate-to-severe Crohn’s disease (CD) or ulcerative colitis (UC), based on a pivotal randomised trial (NCT02883452) comparing SC and IV IFX.³ This post hoc analysis investigated clinical outcomes in patients (pts) treated with SC or IV IFX, by response to IV IFX induction.

Methods

In the pivotal trial, adults with active CD or UC received IV IFX induction (5 mg/kg; Week [W] 0 and W2), before randomisation to SC (n=66) or IV (n=65) arms. W6 clinical response (≥70-point decrease in Crohn’s Disease Activity Index [CDAI] score [CD]; ≥2-point decrease in partial Mayo score with ≥1-point decrease in rectal bleeding subscore or an absolute rectal bleeding subscore of 0 or 1 [UC]) was a stratification factor. The SC arm received SC IFX (120/240 mg for pts weighing <80/≥80 kg) every 2 weeks from W6–54; the IV arm received IV IFX 5 mg/kg every 8 weeks (W6–22), then switched to SC IFX (W30–54). Rates of clinical remission (CDAI score <150 [CD]; partial Mayo score ≤1 [UC]) and trough IFX concentrations (C_trough) were assessed at W6, W30 and W54. Analyses were descriptive.

Results

There were 101 induction responders (IRs) to IV IFX, who were randomised to the SC arm (n=49, 74.2%; SC-IR subset) or the IV arm (n=52, 80.0%; IV-IR subset). Correspondingly, there were 17 (25.8%) and 13 (20.0%) induction non-responders (INRs; SC-INR and IV-INR subsets, respectively). In both study arms, IRs had higher clinical remission rates than INRs at both W30 and W54 (Figure A). Comparing by formulation, the SC-INR subset had nearly twice the W30 clinical remission rate of the IV-INR subset (58.8% vs. 30.8%; p=0.159 [Fisher exact test]). In addition, IV-INR subset clinical remission rates numerically increased after pts switched to SC IFX (W30: 30.8% vs. W54: 46.2%; p=0.476 [McNemar test]). These observations were generally consistent with C_trough findings (Figure B); median C_trough in the IV-INR subset increased from 1.5 to 18.3 µg/mL (p=0.005 [Wilcoxon signe-drank test]) after switching to SC IFX.

Conclusion

Findings suggested associations between initial response to IFX induction therapy and positive long-term outcomes for both SC and IV IFX, and supported potential benefits with SC IFX maintenance therapy for INRs, compared with the option of IV IFX maintenance. Given the post hoc nature of the analysis and the small analysis population (thus statistical inconclusiveness), investigation in larger studies is warranted.¹Murthy SK et al. Inflamm Bowel Dis 2015;21:2090–6.²Wong ECL et al. J Crohns Colitis 2021;15:1114–9.³Schreiber S et al. Gastroenterology 2021;160:2340–53.Read more P1136 Relationship between occupation and Inflammatory Bowel Disease’s activity in newly diagnosed patientsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

It is well known that occupational activity can affect health. The association between type of work and Inflammatory Bowel Diseases (IBD) has been studied previously, but the studies on the topic are scarce and they do not have studied the relationship with clinical activity of the disease. The aim of this study is to elucidate if the type of work is a risk factor for the disease activity and severity in recently diagnosed IBD patients.

Methods

An observational prospective study including incident cases of patients with IBD diagnosed between June 2020 and September 2022 in the area of Santiago de Compostela was developed. Type of work, divided into white collar and blue-collar, sedentariness at work divided into high activity, moderate activity and sedentary activity according to the classification of occupational activity categories using accelerometry, and place of work divided into indoor and outdoor, time at work and contact with animals at work was recorded. All cases were followed-up through one year to assess the evolution of the disease. Endoscopic index at one year from the diagnosis, analytic parameters, hospitalizations related with the disease during the period, treatments administered, and number and severity of flares (measured by Partial Mayo Score and Harvey- Bradshaw) were collected. To analyze the results, a logistic regression was used.

Results

136 patients were included and followed their activity for a year. 68 (50%) were females. 78 (57.4%) had ulcerative colitis, 52 (38.2%) Crohn’s disease and 6 (4.4%) unclassified colitis. 30 patients (22.1%) had at least one flare during this time (23 had 1 flare, 5 two and 2 three), and 4 patients were primary non responders. 7 patients (5.2%) were hospitalized. Neither the type of job (white or blue collar), time at work (working hours per week), physical activity at work (sedentary work, moderate activity or high activity), working outdoor vs. indoor nor contact with animals at work were associated with hospitalization (all p>0.05). When contact with chemicals, solvents and dusts were analyzed, no statistically significant difference was found (p>0.05). Regarding the appearance of flares, high activity at work and working outside were protective factors of the appearance of a flare, with OR 0.1 (0.0 – 0.7) and 0.2 (0.1 – 0.8) respectively (Table 1).After stratifying results according to type of IBD, there were no statistically significant differences.

Conclusion

High activity jobs and working outside are protective factors for a flare appearance in patients with recent diagnosis of IBD. Type of job it is not related with risk of hospitalization.Read more P770 Proactive Infliximab monitoring improves the rates of transmural remission in Crohn’s disease – a propensity score matched analysisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Few patients can reach transmural remission in Crohn’s disease (CD) with currently available therapies. Proactive optimization of Infliximab (IFX) based on trough levels may potentially improve these results.

Methods

Retrospective cohort study including consecutive CD patients starting treatment with IFX. Rates of transmural remission were compared between patients with and without therapeutic drug monitoring (target level: 5-7 µg/mL). A propensity score matched analysis was performed to adjust for potential confounders (figure).

Results

195 CD patients were included, 57.9% receiving proactive therapeutic drug monitoring. The rates of transmural remission were higher in patients under proactive therapeutic drug monitoring (37.2% vs 18.3%, P=0.004) with similar results in the propensity score matched analysis (34.2% vs 17.1%, P=0.025). In multivariate analysis, proactive therapeutic drug monitoring was independently associated with transmural remission: OR 2.95 95%CI(1.44-6.06), P=0.003.

Conclusion

Proactive optimization of IFX based on trough levels increases the rates of transmural remission in CD.Read more P961 Achieving treatment targets in Ulcerative Colitis and reasons for failing to do so: Real world experience in a multi-ethnic asian populationWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

In ulcerative colitis (UC), endoscopic remission (ER) is recommended as a long-term treatment target as it predicts favourable outcomes. We performed this study to identify the proportion of patients who achieved treatment targets as set out in the Selecting Therapeutic Targets in Inflammatory Bowel disease (STRIDE II) consensus. Secondly, we aim to identify the reasons for failing to meet treatment targets.

Methods

This is a retrospective analysis of all UC patients who were seen at Changi General Hospital, Singapore from 1 January 2000 to 31 December 2022. Patients were identified from an existing IBD registry. All patients with confirmed diagnosis of UC were included in the analysis. Those with follow up period less than 1 year or no repeat endoscopy were excluded. We collected baseline demographics, disease characteristics, medications, clinical activity scoring, biomarkers, endoscopic findings and histologic reports.We defined biomarker normalization, ER and histological remission as outlined in the STRIDE II consensus. Next, we compared factors associated with ER. We also assessed possible reasons for failure to achieve ER. SPSS version 26 was used for data analysis.

Results

After excluding 23 patients, a total of 139 patients were analysed with a mean follow-up time of 13.5 years. Figure 1 demonstrates the baseline demographics, disease characteristics, treatment modalities, remission targets and reasons for failure of ER. 96.4% of patients achieved clinical remission with a median time of 8 weeks (IQR: 4). Faecal calprotectin (FC) was not routinely measured at baseline but its use increase significantly after the STRIDE consensus. 53.4% of patients achieved biomarker normalization. ER was achieved in 58.3%. Of the 81 patients who achieved endoscopic remission, 49.4% also achieved histological remission. For patients who had repeat endoscopy within 1 year of diagnosis (35.3%, 49/139), 8.16% had achieved ER with a median time of 34 weeks (IQR: 4).Lower baseline C-reactive protein (CRP), follow-up FC, partial mayo score (PMS) at follow-up and biomarker normalization were associated with ER (Table 1). Interestingly more extensive disease was also associated with ER.The main reason for failing to achieve ER was non-compliance to treatment in 58% of the patients. A smaller proportion of patients refused treatment escalation due to absence of symptoms, cost concerns or repeating endoscopy after treatment escalation.

Conclusion

More than half of all patients with UC achieve long term target of ER in our population and baseline and follow-up biomarkers and PMS are associated with ER. Patients’ compliance is the key reason for failing to achieve ER. Thus, patient education should be reinforced to improve treatment outcomes.Read more P771 Comparing obstructive symptoms and dietary restrictions with Crohn's disease stricture severityWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Stricturing Crohn’s Disease (CD) is characterized by bowel narrowing often leading to obstruction. Obstructive symptoms (OS) have been evaluated in patients with CD strictures using OS scores (STRIDENT). Clinical observations suggest that OS are generally associated with end-stage strictures requiring dietary restrictions and surgery. Evaluating the prevalence of symptoms in strictures is important as regulatory agencies require symptom response to therapies in trials. Intestinal ultrasound (IUS) accurately assesses CD strictures. IUS criteria for ileal strictures includes: 1) bowel wall thickness (BWT) > 3mm, 2) luminal narrowing, and 3) pre-stenotic dilation (PSD) > 2.5 cm. It remains unclear whether stricture severity is correlated with OS (nausea, vomiting, bloating, abdominal pain). We aim to assess if OS and dietary restrictions occur more often in those with more severe strictures (pre-stenotic dilation size).

Methods

In this pilot study, prospective ileal CD patients with inflammatory (non-stricture) phenotype versus definitive or probable strictures were surveyed. OS for the past 2 months were queried in patients with definitive (BWT >3mm, luminal narrowing < 1cm, PSD ≥ 2.5cm), and probable strictures (definitive with PSD < 2.5cm) as identified on IUS. OS queried included nausea, vomiting, bloating, abdominal pain, and dietary restrictions. Chi-squared tests for categorical symptoms and one-way ANOVA (Kruskal Wallis) was used to compare symptom prevalence within the non-stricture or stricture category.

Results

39 patients were recruited with a median diagnosis age of 23.5 years (range 24-69) with 12 non-stricture phenotype (30.8%), 13 definitive (33.3%), and 14 probable stricture (35.9%). Patients with definitive strictures (35.3%) have significantly more nausea than those without strictures (11.8%) (p = 0.01), and no difference with probable strictures. Nausea with probable strictures (41.2%) was not significantly different from non-stricture patients (11.7%) (p = 0.07). In those with definitive versus non strictures, bloating (53.6 % vs 61.5 %, p = 0.69), post prandial pain (57.6 % vs 25.0 %, p = 0.14), and vomiting (10.0% vs. 20.0%, p = 0.47) were not significantly different. No difference was found in obstructive pain (F=2.27, p=0.12) among all groups. Dietary restrictions occurred in 40% (5/12) without strictures, 43.8% (7/12) with probable strictures, and 69.2% (9/13) with definitive strictures.

Conclusion

Nausea was the sole indicator distinguishing definitive from probable strictures. Pain, vomiting, and bloating did not differentiate those with severe from probable strictures, possibly due to dietary restrictions. More recruitment will refine these findings and enable comparison with specific IUS parameters.Read more P1137 Long-term trend of cumulative incidence of venous thromboembolism in Korean patients with inflammatory bowel disease: A nationwide population-based cohort studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Venous thromboembolism (VTE) is a serious extraintestinal manifestation of inflammatory bowel disease (IBD). However, limited research has been conducted on the cumulative incidence of VTE in patients with IBD. Therefore, this study aimed to observe the trend of cumulative incidence of VTE after IBD diagnosis.

Methods

From 2005 to 2016, a population-based cohort study was conducted using health administration claims data from South Korea. IBD and VTE were defined by ICD-10 codes. Incidence density and cumulative incidence rate were analysed. The risk of variables including age, sex, and IBD subtype was comparatively analysed.

Results

A total of 35,508 newly diagnosed patients with IBD between 2005 and 2015 were followed up until 2016. Among them, 634 (1.8%) experienced VTE (619 adults and 15 children). The incidence densities of VTE per 10,000 person-year were 28.90 (range, 27.75–32.54) for overall IBD, 30.07 (range, 27.75–32.54) for adult IBD, and 11.08 (range, 6.20–18.27) for PIBD, respectively. The cumulative incidences of VTE at 0, 1-, 3-, 5-, and 10 years post-diagnosis were 0.01%, 0.30%, 0.80%, 1.30%, and 3.0%, respectively (Figure 1-A). Adulthood, female sex, and ulcerative colitis were associated with an increased risk of VTE (Figure 1-B, C, D).

Conclusion

The study showed a steady and gradual increase in the cumulative incidence of VTE in patients with IBD over a follow-up period of up to 11 years, with a slightly more rapid increase after 8 or 9 years. This trend was even more pronounced in children. This suggests that vigilant monitoring of VTE is necessary in the management of patients with IBD.Read more P805 The persistence of subcutaneous infliximab is equivalent to intravenous form in patients with inflammatory bowel diseasesWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Switching from intravenous (IV) infliximab to subcutaneous (SC) is a new tool in treating patients with inflammatory bowel disease (IBD). This study aimed to evaluate the persistence and tolerance of SC IFX compared to IV IFX and to study outcomes of patients switched back to IV in a real-life patient cohort.

Methods

We conducted a retrospective monocentric study involving consecutive patients with IBD treated with maintenance IV IFX. The switch to SC was offered to patients in clinical remission receiving an IFX IV dose ≤ 10mg/kg every ≥ 6 weeks, and with a favorable patient profile (good adherence to IFX IV treatment, no decompensated psychiatric condition). Two groups were compared: a "switched" group receiving SC and a control group remaining on IV IFX due to an unfavorable patient profile or refusal of the switch.

Results

Among 360 consecutive patients treated by IV IFX, 282 were switched to SC and 78 remained on IV (44 due to refusal and 34 with an unfavorable profile). Both groups were similar in age, sex, and disease type and location; IV IFX dosage and frequency were higher in the IV group.With a median follow-up of 59 (46-67) weeks, SC IFX was discontinued in 28/282 (10%) patients (10 due to relapse, 10 by patient decision, and 8 due to intolerance), whereas it was stopped in 1/78 (1%) IV IFX patient for intolerance (p=0.01). Among the 28 who discontinued SC IFX, 27 reverted to IV, with 4 (1% of the switch group) permanently stopping IFX. Overall, persistence rates for IFX, irrespective of administration route, were comparable between the two groups at 52 weeks: 99% (96-100%) for IV versus 99% (98-100%) for SC (p=0.60). Adverse events were more frequent in the switched group than the control group (10% versus 3%, p=0.03). Primarily, this involved psoriasiform lesions in 9 patients; 4 patients reported an injection site reaction. The proportion of side effects leading to IFX discontinuation or hospitalization was identical in both groups (1 patient, 2%).

Conclusion

In a real-life cohort, switching from IV to SC IFX does not alter treatment persistence. In cases of poor tolerance to SC IFX, IV IFX re-initiation is effective. Switching to SC IFX is a therapeutic option for patients in remission on IV IFX.Read more P962 Clinical and endoscopic remission at 3 months after Acute Severe Ulcerative Colitis is predictive of maintenance therapy outcomes at 12 months - Results from PREDICT UCWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The optimal maintenance regimen after rescue therapy for Acute Severe Ulcerative Colitis (ASUC) is unknown. We aimed to evaluate prospectively the impact of different maintenance regimens after successful infliximab (IFX) rescue, along with factors associated with Month 12 remission.

Methods

Clinical responders at 3 months from PREDICT UC, a randomised trial (NCT02770040) comparing standard and intensified IFX rescue strategies, were evaluated in this prospective cohort study up to Month 12. Maintenance therapies were as follows: (1) Thiopurine monotherapy (azathioprine or mercaptopurine) for thiopurine naïve patients or prior suboptimal thiopurine therapy (TP); (2) Combination thiopurine and IFX therapy 5mg/kg 8-weekly for thiopurine-experienced patients (IFX+TP combo); (3) IFX monotherapy 5mg/kg 8-weekly for thiopurine-intolerant patients (IFX mono). All patients received oral 5-aminosalicylates. Clinical and endoscopic assessments were performed at baseline (Month 3) and Month 12. Clinical remission was defined as a partial Mayo score of 0-1 and endoscopic remission as Mayo Endoscopic Score (MES) of 0-1.

Results

Of 138 patients randomised, 79 entered the maintenance phase. Of these, 56 (71%) received TP, 16 (20%) received IFX+TP combo and 7 (9%) received IFX mono. Baseline characteristics were similar across the 3 maintenance groups. At 12 months, 42 patients (53%) were in clinical remission, 44 patients (56%) were in endoscopic remission, and one patient underwent colectomy. The 3 maintenance groups had similar rates of clinical remission (TP 55%, IFX+TP combo 56%, IFX mono 29%; P=0.39) and endoscopic remission (TP 55%, IFX+TP combo 56%, IFX mono 57%; P=0.99) at 12 months.

Clinical Remission

On univariable and multivariable analysis, no factors were associated with clinical remission at 12 months, including baseline CRP, albumin, partial Mayo score, MES, UCEIS or maintenance strategy.

Endoscopic Remission

Factors associated with endoscopic remission at 12 months included baseline partial Mayo score of 0 (OR 3.36, 95% CI 1.24-9.10, P=0.017), MES of 0-1 (OR 3.48, 95% CI 1.08-11.27, P=0.037) and UCEIS of 0-1 (OR 3.30, 95% CI 1.24-8.76, P=0.016). However, a partial Mayo score cut-off of 0-1 did not reach significance (OR 3.46, P=0.09). No factors associated with endoscopic remission were identified on multivariable analysis.

Conclusion

In steroid-refractory ASUC patients who received IFX rescue, clinical and endoscopic remission at Month 3 were associated with endoscopic remission at Month 12, particularly among patients with greater depth of remission. Month 3 assessment helps identify patients at higher risk of disease progression for whom more intensive treatment may be required.Read more P1157 Burden of herpes zoster in patients with inflammatory bowel disease treated with immunosuppressive agentsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Patients with inflammatory bowel disease (IBD) are at increased risk of infections such as herpes zoster (HZ) due to immunosuppressive (IS) therapy. We conducted a targeted literature review to identify the burden of HZ in patients with IBD treated with IS agents.

Methods

We conducted a PubMed search to collate publications reporting on HZ in patients with IBD receiving IS treatment (from 01/01/2013 to 01/11/2023; excluding preclinical studies, narrative reviews and case reports). Findings were supplemented with a second PubMed search specific to paediatric patients with IBD (aged ≤18 years). Additional publications were included based on authors’ expertise as well as relevant abstracts presented at ECCO and DDW in 2022 and 2023.

Results

Overall, 178 publications were identified and 77 were included, along with ten recent congress abstracts. The most common IS treatments were Janus kinase inhibitors (JAKi), including tofacitinib and upadacitinib, followed by tumour necrosis factor inhibitors (TNFi). Additional treatments included anti-interleukin (IL)-23 agents (risankizumab, ustekinumab, mirikizumab) and sphingosine-1-phosphate (S1P) receptor modulators (etrasimod, ozanimod). HZ incidence rates are typically higher in patients with IBD compared with non-IBD populations (7.02–18.34 vs 3.22–11.29 per 1000 patient years, respectively). In paediatric patients, incidence rates are as high as 8.49/1000 patient years, with a standardised incidence ratio of 3.38 compared with the general population. Two studies reported a significant association between IBD and risk of hospitalisation for HZ in children and adolescents. Patients with IBD aged <50 years may have higher incidence of HZ compared with those aged >60 years without IBD. Risk factors for HZ in IBD patients include older age, lower weight, geographic region, prior TNFi failure and use, dose, and combination of IS medications. Increased incidence of HZ is associated with IS medication, particularly JAKis. Limited data exists on novel anti IL-23 agents and S1P receptor modulators, with some studies reporting a similar risk of HZ in treated patients compared with placebo, and others reporting an increased risk. HZ-related discontinuation is rare. Vaccination can reduce the risk of HZ in treated IBD populations, and studies have identified areas to improve vaccination adherence.

Conclusion

Patients with IBD of all ages, but specifically those aged <50 years, are at higher risk of HZ compared with non-IBD cohorts, and IS medications contribute to this risk. Vaccination against HZ prior to initiating IS treatment could benefit patients with IBD.Read more P806 Development of a clinical model to predict secondary non-response of anti-TNFα treatment on Crohn's diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Secondary non-response to anti-tumor necrosis factor-α (including Infliximab and Adalimumab) in patients with Crohn’s disease (CD) is common. Prediction of secondary non-response is essential for treatment decision for individual patients.

Methods

The clinical model was constructed in a training cohort. Clinical features, serological parameters, genetic biomarkers etc. were obtained as predictors after anti- TNFα therapy. Univariate analysis was performed to eliminate irrelevant predictors with secondary non-response. A logistic regression model was developed using genetic biomarkers and predictors with P < 0.1 in the univariate analysis. Finally, the model was validated with reference to its calibration and clinical decision curve.

Results

In a univariate analysis, infliximab antibodies,white blood cell(WBC), albumin(Alb), previous use of immunosuppressant, switching to other drugs, immunological preparation were found associated with secondary non-response to IFX. Logistic regression analysis with stepwise backward selection P < 0.01 and a clinical model was developed based on the above predictors.

Conclusion

The study presents a model to predict secondary non-response to anti-TNFα in CD. This model can be used to help clinicians adjust the therapeutic strategy for CD patients.Read more P1010 Guselkumab improves abdominal pain and bowel urgency symptoms in patients with moderately to severely active ulcerative colitis: Results from the phase 3 QUASAR induction studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Abdominal pain and bowel urgency are prevalent, burdensome symptoms experienced by patients (pts) with ulcerative colitis (UC) that impact daily life, including social activities. In this study, we use data from the Phase 3 QUASAR Induction Study to assess efficacy of guselkumab (GUS) on abdominal pain, bowel urgency, and the impact of bowel urgency on pts’ lives.

Methods

Pts were randomized 3:2 to receive IV GUS 200mg or placebo (PBO) at Weeks (Wks) 0, 4, and 8. Abdominal pain and bowel urgency were evaluated at baseline and Wk12 using items from the Inflammatory Bowel Disease Questionnaire, where pts rated trouble with abdominal pain, symptoms of bowel urgency, and the impact of bowel urgency over the past 2 wks using 7-point scales (1=all of the time to 7=none of the time). A ≥2 point increase from baseline was clinically meaningful improvement. All analyses were prespecified but not multiplicity controlled; all p-values are nominal.

Results

At baseline, percentages of pts with abdominal pain (GUS 77.7% and PBO 77.9%), symptoms of bowel urgency (GUS 86.0% and PBO 83.2%), and impact of bowel urgency (GUS 70.8% and PBO 70.4%) at least a little of the time (score ≤5) were similar between groups. GUS-treated pts showed greater improvements at Wk12 in these outcomes compared with PBO (Table 1). For abdominal pain, 52.0% of GUS-treated pts had clinically meaningful improvements from baseline at Wk12 vs 33.0% in the PBO group (p<0.001), and 21.1% vs 12.3%, respectively, of those with abdominal pain at baseline had resolution at Wk12 (p=0.004; Fig. 1A). For symptoms of bowel urgency, 58.6% vs 33.0%, respectively, had clinically meaningful improvements (p<0.001; Fig. 1B), and 24.0% vs 9.8%, respectively, of those with symptoms of bowel urgency at baseline had resolution at Wk12 (p<0.001). Similarly, 57.7% vs 33.0%, respectively, had clinically meaningful improvements in the impact of bowel urgency (p<0.001; Fig. 1B), and 32.4% vs 13.1%, respectively, of those impacted at baseline had resolution at Wk12 (p<0.001). Symptoms and impact of bowel urgency were combined into a bowel urgency score; of pts with symptoms or impact scores ≤6 at baseline, 19.7% versus 8.2%, respectively, had resolution of both at Wk12 (p<0.001; Fig. 1B).

Conclusion

Pts receiving GUS showed clinically meaningful improvements in health-related quality of life measures related to abdominal pain and bowel urgency, including both the symptoms of bowel urgency and impact on pts’ lives.Read more P1158 Comparison of comorbidities, and lifestyle habits between IBD patients, IBD patients with suspected SpA, and controlsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), is a complex condition with systemic implications. Recent research emphasizes the connection between IBD and spondyloarthritis (SpA), sharing genetic and clinical traits. This cross-sectional case-control study investigates comorbidities and lifestyle habits in three groups: IBD patients, IBD patients with suspected SpA, and control group from the general population.

Methods

We obtained data from the Swedish National Quality Registry for Inflammatory Bowel Disease (SWIBREG) for 1,032 IBD patients (592 UC and 440 CD) and selected a control group of 16,756 individuals from the 2018 Swedish National Public Health Survey. Questionnaires covered comorbidities, self-perceived health, smoking, alcohol, and physical activity. Modified criteria for ASAS and AMOR was used to define SpA. Risk factors in patients with IBD for SpA were explored by logistic regression.

Results

IBD patients have higher rates of comorbidities such as hypertension (34.4%), asthma (15.6%), and diabetes (8.3%) compared to the control group.(Table 1). Notably, those with suspected concurrent SpA had even higher rates: hypertension (41.3% in axial SpA, 43.6% in peripheral SpA), asthma (22.4% in axial SpA, 21.5% in peripheral SpA), and diabetes (10.2% in axial SpA, 10.5% in peripheral SpA). Smoking habits differ, with a greater proportion of former smokers in the IBD group (38.3%) and a higher percentage of individuals who had never smoked in the control group (64.6%). Encouragingly, IBD patients demonstrated increased physical activity, with 70.3% engaging in 150 minutes of activity per week. Logistic regression analyses revealed associations between specific factors and the presence of SpA in IBD patients, including female gender (1.815, SD 1.325–2.488), BMI (1.073, SD 1.034–1.113), asthma (1.628, SD 1.038–2.553), gastritis (1.694, SD 1.070–2.683), and current/former smoking (1.359, SD1.004–1.840).

Conclusion

The prevalence of hypertension, asthma and diabetes were higher in patients with IBD compared to the general population. A higher proportion among the controls had never smoked but patients with IBD had lower alcohol consumption and were more physically active. This study sheds light on the IBD-SpA relationship and its impact on comorbidities and lifestyle. The findings aid clinicians in holistic patient management, emphasizing tailored care for specific comorbidities and lifestyle factors.Read more P747 Assessment of a microlearning programme for patients with Inflammatory Bowel Disease (The ADEII project) on ansiety/depression status and illness perceptionWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Information and communication technologies (ICTs) represent a novel approach to chronic disease management. However, their use in Inflammatory Bowel Disease (IBD) is lacking and their results as far unknown, because no specific tools are available, The prevalence of anxiety and/or depression in IBD ranges from 30-35% in clinically inactive phases. Furthermore, negative perceptions of the disease in the dimensions of consequences and emotions have been related to depression and anxiety. We aim to evaluate the outcomes of a novel microlearning programme for IBD patients in.anxiety/depression status and illness perception.

Methods

Prospective cohort study in adult patients with IBD (18 to 70 years old) who underwent a microlearning programme over a 2-month period, throught 4-minute videos organised in individualised video pathways that were sent via mobile phone using a Telegram bot. All patients received the 4-video main pack, consisting of 2 videos with information about their disease (ulcerative colitis or Crohn's disease), 1 video on adherence and another one on steroid treatment. To these were added as many videos as the number of drugs used by the patient to control IBD. Before starting the programme and at 6 months, patients completed the Hospital Anxiety and Depression Scale (HADS) and the Brief Illness Perception Questionnaire (BIPQ).

Results

Between June and October 2022, 1226 videos were sent to 200 IBD patients: 51.5% female (103), UC 52.5% (105), mean age 46.1 (13.2) years (Table 1). Median number of videos per patient was 6 (6-7). Attendance to ADEII programme ranged between 78% and 90%.The median score on the HAD anxiety subscale was 8.1 (4.3), while the median score on the HAD depression subscale was 6(4-8), Initially, anxiety was diagnosed in 60 patients (30%) and depressión in 16 (8%) as subescales scores>11. We found significant differences between the pre-intervention versus post-intervention medians and IQR in anxiety score 8(5-11) vs 7(4-11) (p=0.008) but no in depression. Regarding BIPQ test post -intervention there were significant decreases in P8 negative emotions 6(3-8) vs. 5(3-7) (p=0,003) and P5 identity 6(4-8) vs 5(3-7) (p=0,003) as well as a significant increase in P7 comprehensibility of disease 7(5-9) vs. 8(7-9) (p=0,003).

Conclusion

An ICT-based educational program was widely accepted by IBD patients and showed a decrease in anxiety and negative emotions and representations, along with improvement in the understanding of disease.Read more P1194 Single-cell analysis reveals clonal expansions of pro-inflammatory tissue-resident memory Th17 cells in Crohn's diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Crohn's disease (CD) is a chronic inflammatory disorder affecting the bowel wall. Tissue-resident memory T (Trm) cells are implicated in CD, yet their characteristics remain unclear. We aimed to investigate the transcriptional profiles and functional characteristics of Trm cells in the small bowel of CD and their interactions with immune cells.

Methods

Seven patients with CD and four with ulcerative colitis as controls were included. Single-cell RNA sequencing and paired T cell receptor sequencing assessed T cell subsets and transcriptional signatures in lamina propria (LP) and submucosa/muscularis propria-enriched fractions (SM/MP) from small bowel tissue samples.

Results

We identified 58,123 T cells grouped into 16 populations, including the Th17 Trm, CD4⁺ Trm, and CD8⁺ Trm clusters. In patients with CD, we identified Trm cells with a Th17 signature (termed Th17 Trm) in the bowel, demonstrating significantly increased proportions of the Th17 Trm cluster in both the LP and SM/MP areas. The Th17 Trm cluster demonstrated heightened expression of canonical tissue-residency marker genes (ITGAE, ITGA1, and CXCR6) along with elevated levels of IL17A, IL22, CCR6, and CCL20. The clonal expansion of Th17 Trm cells in CD was accompanied by enhanced transmural dynamic potential, as indicated by significantly higher migration scores. CD-prominent Th17 Trm cells displayed an increased interferon gamma (IFNγ)-related signature linked with STAT1 activation, inducing chemokines (i.e., CXCL10, CXCL8, and CXCL9) in myeloid cells.

Conclusion

Our findings underscored the elevated Th17 Trm cells throughout the small bowel in CD, contributing to disease pathogenesis through IFNγ induction and subsequent chemokine production in myeloid cells.Read more P784 Efficacy of ustekinumab in biologically naïve patients with Inflammatory Bowel DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

In recent years, there are several new treatment options for inflammatory bowel disease (IBD). Tumour necrosis factor α inhibitors have been joined by novel advanced therapies (vedolizumab, ustekinumab (UST) and Janus kinase inhibitors). These drugs are mostly used as second-line treatments after tumor necrosis factor α inhibitors, with subsequent poorer efficacy. There are few data available on the efficacy of first-line treatment with UST. The aim of our study was to assess efficacy of UST in biologically naïve patients with IBD.

Methods

All patients older than 18 years who had a confirmed diagnosis of IBD, treated in a tertiary IBD centre (University Medical Centre Ljubljana, Slovenia), who started first-line treatment with UST, were included in this retrospective cross-sectional cohort study. Demographics, clinical characteristics of patients, treatment persistence of UST, clinical disease activity scores, C-reactive protein (CRP), faecal calprotectin (FC), UST concentrations, and endoscopic scores were collected retrospectively in medical files. We determined a Kaplan-Meier curve of treatment persistence.

Results

We included 71 patients, 11 of which had ulcerative colitis and 60 had Crohn’s disease. Persistence of treatment with UST in biologically naïve patients is 88% at one year (Figure 1). Clinical remission was achieved in 57.7% of patients. Biochemical remission was achieved in 77.6% (CRP<5mg/ml) and 71.1% (FC<100mg/kg) of patients. Endoscopic remission (Mayo endoscopic score <2 in ulcerative colitis or absence of ulcers in Crohn’s disease) was achieved in 50.0% of patients. There was no significant difference (P>0.05) between the median serum concentrations of UST in the group of patients who achieved remission (clinical (5.86μg/ml), biochemical (5.93μg/ml based on CRP, 5.63μg/ml based on FC) and endoscopic (7.14μg/ml)) and who did not achieve remission (5.31μg/ml, 3.25μg/ml, 4.47μg/ml and 4.64μg/ml, respectively).

Conclusion

Treatment of UST in biologically naïve IBD patients shows high treatment persistence with high biochemical and endoscopic remission rates. It appears that UST is more efficacious if used as first-line therapy compared to the use after other advanced therapies. Further prospective data are needed to confirm our findings.Figure 1.Kaplan-Meier curve of treatment persistence, combined for both IBD types.Read more P952 Why do patients with Inflammatory Bowel Disease Take Part in Pharmaceutical Clinical Trials? A qualitative study of Clinical Trial ParticipantsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Recruitment rates to clinical trials in inflammatory bowel disease (IBD) continue to decline. A better understanding of motivations to participate as well as recommendations to reduce barriers to enrolment from a patient perspective may assist in design of future clinical trials.

Methods

We developed a 32-item electronic questionnaire to explore motivations, experiences and recommendations of patients with IBD, who have participated in pharmaceutical clinical trials in a tertiary centre in Canada.

Results

We distributed a total of 82 emails with surveys based on the patient details available to the study team. Using the DillMan Total Design Survey method, participants were followed up one week after the initial email with a reminder phone-call and we received 46 responses (56.1% response rate). Participants were mostly, male (58.7%), non-Hispanic white (93.5%), with a mean age of 45.5 years (SD 10.9). Most participants decided to participate in a clinical trial to benefit future patients with IBD (63.0%). Self-reported knowledge of the possibility of being assigned to placebo on a scale from 0 (no knowledge) to 100 (extremely knowledgeable) was a median of 100 (IQR 100-100) (Table 1). Half of participants (50.0%) reported they were worried about the possibility of receiving placebo, although the majority (63.0%) understood they could improve on placebo. The most challenging aspect reported was the number and length of questionnaires (32.6%), as well of the number of colonoscopies (30.4%). Strategies to increase enrolment recommended by participants were reduction in the chance of receiving placebo (43.5%), facilitating inclusion of patients who have failed multiple therapies (43.5%), allowing virtual visits (39.1%), including subtypes of disease that have traditionally been excluded in clinical trials (e.g., ostomies, fistula) (34.8%), and improving outreach to underrepresented populations (28.3%) (Figure 1). The vast majority (80.4%) reported their experience of participation to be better than expected and would recommend taking part in a clinical trial to other patients with IBD (97.8%).

Conclusion

Patients with IBD who took part in pharmaceutical trials reported a high level of satisfaction overall. The top three recommendations from patients to improve clinical trial design were reducing the chance of receiving placebo, allowing inclusion of patients who have failed multiple therapies and allowing for virtual visits to reduce travel burden to the clinical trial site. These results should help inform the design of patient centric clinical trials in IBD.Read more P1195 Identification of immune cell infiltration and potential candidate biomarker in anti-IL 12/23 treated Crohn’s disease patients by integrated bioinformatics analysis and machine learningWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Variations existed in patients' responses to ustekinumab (UST) treatment in Crohn's disease (CD), but the underlying cause remains unknown¹. Our objective was to investigate the involvement of immune cells and identify potential biomarkers that linked to the response to IL 12/23 inhibitors in patients with CD.

Methods

The analysis utilized the GSE207022 dataset, which consisted of 54 non-responders and 9 responders to UST in CD cohort (Table 1). Initially, differentially expressed genes (DEGs) were identified. Subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were peformed. LASSO regression was used to further screen the most powerful hub genes². ROC curve analysis was employed to evaluate the predictive performances of these genes. CIBERSORT was used to estimate the proportion of immune cell types. These significantly altered genes were further subjected to clustering analysis into immune cell-related infiltration. To validate the reliability of the candidates, patients prescribed with UST as the first line biologics in our center were included as an independent dataset.

Results

A total of 99 DEGs were obtained from the integrated dataset. Analyses of GO and KEGG revealed a significant enrichment of immune response pathways in CD patients. We identified nine hub genes (SOCS3, CD55, KDM5D, IGFBP5, LCN2, SLC15A1, XPNPEP2, HLA-DQA2, and HMGCS2) that were primarily associated with the response versus non-response patients. These nine genes accurately predicted treatment response with an area under the curve (AUC) of 0.96. Non-response individuals exhibited a relatively high Th1 cell polarization. Both LCN2 and KDM5D genes showed positive correlations with Th1 cells and the Th1/Th2 ratio. Furthermore, we validated LCN2 and KDM5D genes as effective predictive markers using independent validation datasets (Figure 1).

Conclusion

Th1 cell polarization was an important cause of non-response to IL-12/23 agents in CD patients, and LCN2 and KDM5D could be used as predictive markers to identify non-response patients effectively.1. Newman AM, Liu CL, Green MR, et al. Robust enumeration of cell subsets from tissue expression profiles. Nat Methods. 2015;12(5):453-457. doi:10.1038/nmeth.3337.2. Feagan BG, Sandborn WJ, Gasink C, et al. Ustekinumab as Induction and Maintenance Therapy for Crohn's Disease. N Engl J Med. 2016;375(20):1946-1960. doi:10.1056/NEJMoa1602773.Read more P750 Endoscopic balloon dilation associated with biological therapy in Crohn's Disease strictures: a single center experienceWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Symptomatic luminal stricture in Crohn’s Disease (CD) occurs in up to 20% of patients at the diagnosis and in more than 50% during their lifetime. A considerable percentage of patients often require further surgery for post-operative CD recurrence, with a consequent increased burden of short bowel syndrome. In this scenario, combining biological therapy with endoscopic balloon dilation (EBD) could potentially reduce this risk. Our study aimed to evaluate the efficacy of EBD combined with biologic therapy in symptomatic gastrointestinal strictures in CD patients.

Methods

We conducted a retrospective study including consecutive CD patients who underwent EBD for low gastrointestinal strictures from December 2015 until November 2022 at our tertiary IBD Center. Subsequent subocclusive/occlusive episodes, the need for steroids, and surgery due to CD stenosis were evaluated during a follow-up period of 6 and 12 months.

Results

A total of 52 patients treated with EBD with an overall number of 55 strictures were included. The mean age was 46,8 (18-77) years. The median of disease duration was 9 (0-42) years. Among the total of 55 studied strictures: 14 (25%) in patients with active smoking, 21 (38%) with increased CRP values at the time of dilation, 43 (78%) had evidence of moderate or severe endoscopic disease activity with ulcerative lesions at stricture site. Anastomotic strictures accounted for 26 (47%) of all 55 strictures. The remaining 29 (53%) were de novo stricture: 8 (15%) ileal, 11 (20%) at ileocecal valve, 4 (7%) colonic, and 6 (11%) anal . Forty-two patients (76%) were under biologic therapy at the time of EBD and 2 (4%) started after EBD. EBD technical success was reported in 60% of the procedures, and no adverse events were recorded. After 6 months from EBD, at univariate analysis, increased CRP at the time of dilation resulted in a risk factor for the need for steroids (OR 14,63, IC 2,690 to 71,50; p-value = 0,0006, Table 2). Concomitant biological therapy, active smoke, and the presence of ulcerative lesions did not show a significant correlation with considered outcomes. After 12 months from EBD, concomitant biological therapy resulted in being a protective factor for surgery (OR 0,06; IC 0,005 to 0,502; p-value=0,0047), while subocclusive and occlusive events were less frequent in anastomotic strictures than ileal stenosis (OR 0,07; IC 0,005 to 0,651; p-value=0,0152).

Conclusion

In patients with CD undergoing EBD for intestinal CD stricture, concomitant biological therapy reduces the risk of surgery for CD stenosis recurrence. Further prospective and controlled studies are underway to confirm these observations.Read more P981 Risankizumab, but not ustekinumab or vedolizumab, downregulates IL-23-induced mucosal pathogenic Th17 cells in patients with Crohn’s diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

We recently described an interleukin(IL)-23-inducible pathogenic subset of CCR6⁺CXCR3^-CCR5⁺ mucosal T helper (Th)17 cells (pTh17) infiltrating Crohn’s disease (CD) inflamed mucosa and specifically activated in response to Adherent-Invasive Escherichia Coli. pTh17 cells are functionally and phenotypically distinct from CCR6⁺CXCR3^-CCR5^- Th17 cells (cTh17) and from IL-12-induced CCR6⁺CXCR3⁺ Th1/17 subset. Here, we investigated pTh17 cells' recirculation into the bloodstream, localization into the intraepithelial lymphocyte (IEL) compartment, and in-vivo modulation by different biological therapies.

Methods

Adult patients with active CD initiating either vedolizumab as per clinical practice or ustekinumab and risankizumab during the SEQUENCE trial were prospectively recruited at Fondazione IRCCS Cà Granda, Ospedale Policlinico di Milano. In vedolizumab-treated patients, peripheral blood and intestinal biopsies were collected at baseline and at the end of induction. In ustekinumab- and risankizumab-treated patients, intestinal biopsies were collected outside study protocol assessments at baseline and week 24. Endoscopic response was defined as a greater than 50% decrease in the Simple Endoscopic Score from baseline. Peripheral blood mononuclear cells, lamina propria mononuclear cells (LPMC), and IEL were isolated and analyzed through flow cytometry.

Results

Overall, 34 CD patients were assessed. Demographic and baseline disease characteristics are summarized in Table 1. At baseline, as compared with cTh17, pTh17 cells: 1. are rarely found in the peripheral blood and express low levels of CCR9 and α4β7, 2. express high levels of tissue-resident markers CD69⁺CD103⁺ in the mucosa, and 3. infiltrate the IEL layer upon binding of CD103 with E-cadherin. Baseline pTh17 cells were upregulated in patients not achieving vedolizumab-induced endoscopic response. Upon vedolizumab treatment, a selective downregulation of mucosal cTh17 cells but not pTh17 was observed. Remarkably, risankizumab induced a specific downregulation of pTh17 cells, but not cTh17, in both LPMC and IEL layers. Conversely, ustekinumab reduced Th1/17 mucosal subsets, but not pTh17 cells (Figure 1).

Conclusion

pTh17 cells are largely unable to recirculate through the bloodstream, express markers of gut-tissue residency, and infiltrate the IEL compartment. IL-23 neutralization by risankizumab specifically downregulates mucosal pTh17 cells, as compared with vedolizumab and ustekinumab. Our immunologic results might provide mechanistic clues to vedolizumab latency effect in CD, and potentially explain early signs of risankizumab superiority over ustekinumab in the SEQUENCE study in terms of endoscopic response at 24 weeks.Read more P1196 Genomic structural variation and polygenic risk score for Inflammatory Bowel DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Genome-wide association studies (GWAS) of patients with inflammatory bowel disease (IBD) have identified multiple single-nucleotide polymorphisms (SNPs) and genetic variants involving structural changes in the DNA sequence. SNPs and structural variants (SVs) can play a crucial role in IBD pathogenesis. In this study, we evaluated large deletions induced by SVs in patients with IBD. Additionally, we evaluated the ethnic contribution to a polygenic risk score (PRS) for IBD.

Methods

Seventy-five Patients with IBD of Korean ancestry from Seoul National University Bundang Hospital (SNUBH) were subjected to whole-genome sequencing (49 patients with UC and 26 patients with CD). SVs involving large deletions were detected and analyzed by using the Genome Aggregation Database (gnomAD) and AnnotSV. The SVs were prioritized based on a list of 241 IBD-associated SNPs identified in the previous GWAS. The prediction performance of European- and Korean-derived PRSs for IBD was also evaluated. For calculating PRS, we applied previously published models derived from the European and Korean populations, respectively, and used Korean Genome and Epidemiology Study (KoGES) database as the Korean controls.

Results

We found a total of 146 SVs involving large deletions in the IBD cohort. Among them, 10 SVs were annotated as likely pathogenic, according to AnnotSV and American College of Medical Genetics and Genomics guidelines; 24 SVs had the probability of being loss-of-function intolerant (pLI ≥ 0.9). We found that the frequency of large deletions that overlapped with the regions coding NOTCH1, HGF, PTPN2, and SENP7 were rare in the IBD cohort compared to the gnomAD population (Table). The large deletions that overlapped with the regions coding IL2RA, ITGA4, BANK1, and STAT3 were identified in the IBD cohort but not in the gnomAD population. The PRS for IBD in the IBD cohort was significantly higher than that in the Korean controls under the Korean- or European-derived model (Figure A). However, the PRSs for CD or UC were not able to distinguish patients with CD and UC in the IBD cohort (Figure B and C).

Conclusion

Our finding suggests that SVs involving large deletion may be an important genomic variability in predicting the development of IBD. The PRS for IBD can predict IBD development without ethnic specificity.Read more P751 Off-label dose escalation of Ustekinumab in Inflammatory Bowel Disease patients. Safety profil of different patternsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Approved maintenance regimens for UST in patients with inflammatory bowel disease (IBD) are 90 mg subcutaneously every 8 (Q8) or 12 weeks (Q12). In the real world, off-label dose escalation is frequently performed after inadequate response or loss of response, and has been shown to be effective. However, different dosing regimens are used and the best strategy is still unknown. Our aim is to evaluate the safety profile of UST dose escalation in IBD patients.

Methods

We performed an observational cohort study in 2 hospitals in Vigo-Spain. All patients who started UST between 1 June 2017 and 31 December 2022 to control their active IBD were enrolled. The primary endpoints were the rate of serious adverse events (AE) and the need to discontinue UST treatment in off-label dose escalation patients.

Results

173 IBD patients received UST: females 53,8% (93), mean age 49.7(15.5) years, Crohn´s disease 82% (142), previous anti-TNF 93,6% (162) and vedolizumab 22,5% (39) (Table 1). At 16 weeks, subcutaneous UST was maintained Q8 in 110 (63.6%) and Q12 in 60 (34.7%). Dose escalation was performed in 56 patients (32,4%) with different patterns: 30 Q4 (54,5%), 12 intravenous reinduction plus Q4 (21,8%), 7 Q6 (12.7%) and 6 only intravenous reinduction (10,9). In 11 patients (6,4%) a second dose escalation was performed.196 adverse events were reported in 95 patients (54,9%), mostly infections 63 (32,1%) and musculoskeletal disorders 46 (23,5%) (Figure 1). More than one AE was reported in 67 patients (38.7%), showing 2 AE in 41 (23.7%), 3 AE in 12 (6.9%) and 4 AE in 14 (8.1%). Twelve adverse events were considered serious (12,5%) as they lead to hospitalization and in 4 cases to discontinuation of treatment (0.02%). Infections were the most frequent cause of serious AE (50%). With a fmedian ollow-up time of 13,5 (11) months, IBD patients scheduled to off-label UST dose escalation regimens showed no higher incidence of AE or severe AE than standard regimens.

Conclusion

In IBD patients, off-label UST dose escalation showed a good safety profile. Most of the reported adverse events were mild infections that did not change the UST treatment regimen. The schemes of dose-escalation were very heterogeneous between the participants.Read more P1009 Efficacy and safety of 4 years of continuous ozanimod treatment: an interim analysis of the True North open-label extension studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The phase 3 True North (TN) study demonstrated the efficacy and safety of ozanimod (OZA) over 52 wk in patients (pts) with moderately to severely active ulcerative colitis (UC); the ongoing TN open-label extension (OLE) is assessing long-term efficacy and safety. This interim analysis of the TN OLE assessed pts with up to ~4 y of continuous OZA treatment.

Methods

Clinical responders after 52 wk of continuous OZA treatment (0.92 mg/d) during TN who subsequently entered the TN OLE were included in this analysis. Data were analysed up to OLE Week (W) 142, representing up to ~4 y of continuous OZA treatment. Symptomatic response (≥1-point and ≥30% decrease from baseline [BL] in the combined 6-point rectal bleeding subscore [RBS] + stool frequency subscore [SFS] and ≥1-point decrease in RBS or absolute RBS ≤1) and symptomatic remission (RBS=0 and SFS ≤1 [and ≥1-point decrease from BL SFS]) were evaluated from OLE W5 through OLE W142. Clinical remission, clinical response, endoscopic improvement, and corticosteroid (CS)-free remission were evaluated at OLE W46, W94, and W142. Endpoints were evaluated using observed case (OC) and nonresponder imputation (NRI) analyses. Adverse events were monitored throughout TN and the OLE.

Results

In all, 131 pts entered the OLE after achieving clinical response on OZA at W52 in TN. At the data cutoff, 87.0% of pts completed OLE W46, 71.8% completed OLE W94, and 64.1% completed OLE W142. Most (67.9%) pts had left-sided UC disease, 23.7% had concomitant CS use at TN BL, and 32.1% had prior exposure to tumour necrosis factor inhibitors. Symptomatic response and symptomatic remission were observed in 100.0% and 84.4% of pts, respectively, at OLE W5 in the OC analysis (93.1% and 78.6%, respectively, in the NRI analysis). By OLE W142, symptomatic response and symptomatic remission rates were 98.7% and 88.3%, respectively, in the OC analysis and 58.0% and 51.9%, respectively, in the NRI analysis. Rates of clinical and endoscopic endpoints during the OLE are shown in Figure 1A (OC) and 1B (NRI). Of note, 65.3% of TN W52 clinical responders achieved clinical remission and CS-free remission at OLE W142 in the OC analysis (35.9% in the NRI analysis). With this additional year of follow-up in the OLE, there were no new cases of bradycardia, third-degree atrioventricular block, hypertension, herpes zoster, or macular oedema, and no clinically meaningful change in malignancy exposure-adjusted incidence rates (Table). No serious hepatic events occurred.

Conclusion

Clinical responders after 1 y on OZA sustained response for an additional 3 y and achieved clinical remission with continuous OZA exposure. OZA is a safe, tolerable, and durable therapy for pts with UC.Read more P1197 ERAP2 genetic variant rs2248374 is linked to paradoxical skin reactions induced by TNF-alpha inhibitors in Romanian patients with Inflammatory Bowel DiseasesWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The endoplasmic reticulum aminopeptidases (ERAPs) are responsible for trimming protein residues to optimal length for major histocompatibility complex class-1 mediated antigen presentation process. Genome-wide association studies have shown the influence of ERAP1 and ERAP2 genetic variants in disease susceptibility for autoimmune disorders. Their role in inflammatory bowel diseases (IBD) however remains obscure due to literature data paucity. The aim of this study was to evaluate the role of a single nucleotide polymorphism (SNP) rs2248374 (G/A) of ERAP2 gene in disease susceptibility and response to treatment in Romanian population with IBD. This SNP is of particular importance because the G allele produces a truncated ERAP2 transcript undergoing nonsense-mediated decay and therefore individuals with GG genotype have no functional ERAP2 enzyme.

Methods

The study involved 186 IBD patients (87/99 UC/CD, 91M/69F) and 150 healthy controls (77M/73F) all unrelated and of Romanian ethnicity. Extraintestinal manifestations (EIM) were documented in 43 IBD patients (19UC/24BC). Among patients with biological treatment against TNF-alpha (N=113) there were 31 (27.4%) primary non-responders and 13 (11.5%) with paradoxical skin reactions. All subjects were genotyped for ERAP2 rs2248374 (G/A) using TaqMan Allelic Discrimination Assay (C_25649529_10 Real-Time PCR System, Applied Biosystems by Thermo Fisher Scientific, USA). Association tests were performed with OpenEpi online software using Two by Two Table statistics. P-values (2-tail from Mid-P exact test) were considered significant if <0.05.

Results

Controls and patients were in Hardy-Weinberg equilibrium for the investigated SNP. No significant differences were observed in relation with the risk of disease or with the therapy response. The minor allele A frequency was significantly lower in IBD patients with paradoxical skin reactions (27%) versus patients without these manifestations (50%, p=0.02, OR 0.36). The genotype AA, responsible for full ERAP2 expression, had 0% frequency in the group with adverse skin reactions compared with 23.2% in patients without (p=0.04, OR 0.0). The GG genotype which is related with no ERAP2 protein expression was more frequent in the subgroup of patients with EIM (41.8%) than in patients without EIM (26.7%), showing a marginal association (p=0.06, OR 1.97).

Conclusion

Our results point to the fact that ERAP2 rs2248374 AA genotype exerts a protective effect over paradoxical skin reaction induced by TNF antagonist agents, and GG genotype shows marginal association with the presence of EIM in Romanian patients with IBD. We consider these results worthy of replication in larger cohorts of patients.Read more P796 Comparative Effectiveness of First-Line Infliximab and Vedolizumab in Patients with Early Ulcerative ColitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Despite the increasing armamentarium of advanced therapies for the treatment of ulcerative colitis (UC), data comparing the effectiveness of biologics in early disease are scarce. We aimed to categorize selection of patients and assess the effectiveness, therapeutic persistence and safety of biologics used to treat early UC in a bio-naïve patient cohort.

Methods

This single-center, retrospective study included all bio-naïve UC patients who commenced advanced therapy within two years of diagnosis between 2012-2023. We collected demographic, clinical, and laboratory data. Clinical disease activity was assessed using the Simple Clinical Colitis Activity Index; clinical response was defined as a decrease of ≥ 3 points from baseline and clinical remission defined as an SCCAI of ≤2

Results

Out of the 1117 patients with UC who were treated at our center during the study period, 46 bio-naïve patients (mean age 36.7 years (±17)) were treated with either infliximab (IFX) or vedolizumab (VDZ), within 2 years from diagnosis. IFX was the first biologic in 19 (41%) patients and VDZ in 27 (58%) patients. At therapy initiation, 38 (82%) patients were receiving corticosteroids and 7 (15%) concomitant immunomodulators (Table 1). Patients treated with IFX had significantly lower hemoglobin (10.4 (IQR 8.5-11.3) vs 12.1 (IQR 10.8-13.9) g/dL, p=0.007) and albumin (3 (IQR 2.8-3.8) vs. 3.8 (IQR 3.4-4.2) g/dL, p=0.01) and significantly higher C-reactive protein (CRP) (48.5 (IQR 9-119) vs. 2.5 (IQR 2-3) mg/L, p<0.001) compared with patients starting VDZ.Following induction (week 14) clinical response and remission rates were similar in both treatment groups (IFX: 73% and 63%; VDZ: 74% and 67%, respectively; p=0.75). At week 52, clinical response and remission rates were similar in both treatment groups (IFX: 50% for both; VDZ: 50% for both, p=n/s). Corticosteroid (CS)-free remission rates amongst patients receiving CS at baseline (17 patients IFX and 21 patient VDZ) at week 52 were similar in both groups (IFX: 58% vs VDZ 57%, p=n/s). Treatment persistence over 2 years of follow-up was similar between IFX and VDZ (Figure 1). Safety profiles were similar in both treatment groups with no new signals noted.

Conclusion

In these real-world data in patients with early and bio-naïve UC, first line IFX was used in more severe baseline disease as highlighted by lower albumin and hemoglobin levels and higher CRP at baseline. Despite this, IFX showed equal effectiveness in induction and long-term maintenance and showed similar treatment persistence compared with VDZ.Read more P1050 A cost-utility analysis of ferric derisomaltose versus ferric carboxymaltose in patients with inflammatory bowel disease and iron deficiency anaemia in FinlandWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Anaemia is a common extraintestinal manifestation of inflammatory bowel disease (IBD), with iron deficiency being the most common cause. Iron deficiency anaemia (IDA) can be treated with oral iron, but where oral administration is contraindicated, not tolerated, or proves to be ineffective, intravenous (IV) iron is the preferred treatment option, facilitating rapid iron replenishment. Ferric derisomaltose (FDI) and ferric carboxymaltose (FCM) are two high-dose, rapid-infusion, IV iron formulations that have recently been compared in three head-to-head randomized controlled trials (RCTs), with FCM administration resulting in significantly higher hypophosphataemia incidence versus FDI, and phosphate monitoring after repeat FCM infusions is now recommended in the FCM product information (PI). Between 2000 and 2020, Finland has seen the average incidence of IBD increase by 2.4% annually, accompanied by a commensurate increase in sequelae such as IDA. The objective of the present study was therefore to evaluate the cost-utility of FDI versus FCM in patients with IBD and IDA in Finland.

Methods

A published patient-level simulation model was used to evaluate the cost-utility of FDI versus FCM in Finland. The model captured quality of life differences based on SF-36 data from the PHOSPHARE-IBD RCT and differences in the number of FDI and FCM infusions required. A Finnish societal perspective was adopted and the analysis was conducted over a five-year time horizon. Unit costs were obtained from publicly available Finnish sources. Costs were reported in 2022 Euros and a discount rate of 3% per annum was applied to future costs and effects.

Results

Over the five-year time horizon, patients received 3.95 courses of iron treatment on average, requiring 1.63 fewer infusions of FDI than FCM (5.57 versus 7.20). This resulted in iron procurement and administration cost savings of EUR 471 with FDI versus FCM (EUR 2,286 versus EUR 2,757). Differences in health-related quality of life and the number of IV iron infusions resulted in an increase of 0.076 quality-adjusted life years with FDI versus FCM. Further cost savings of EUR 273 over five years were also realised with FDI versus FCM, driven by reduced need for phosphate testing (saving EUR 90) and reduced travel and productivity loss (saving EUR 183). Total cost savings were EUR 745 (Figure) and FDI was therefore the dominant intervention.

Conclusion

Relative to FCM, FDI resulted in improvements in quality-adjusted life expectancy in Finnish patients with IBD and IDA. FDI also resulted in cost savings, arising from reduced infusion frequency, phosphate monitoring, patient travel, and productivity loss. FDI therefore represents the dominant choice of IV iron in Finnish patients with IBD and IDA.Read more P1239 Characterization of Clostridioides strains and antibiotic resistance profile in Inflammatory Bowel Disease patients with Clostridioides infectionWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

There is an increasing incidence of community-acquired Clostridioides difficile infection (CDI), particularly in IBD. Due to a suspected community outbreak in mid-2023, we aimed to investigate the microbiological and antibiotic resistance profile of CDI in an IBD cohort, employing blind central reading, in order to better understand its epidemiology.

Methods

This was a prospective study of a University Tertiary Hospital in collaboration with the Infection Control Unit and a central laboratory at the forefront of Infectious Diseases investigation in Portugal (Instituto Ricardo Jorge [IRJ]). Faecal samples from all IBD-related CDI from Apr to Oct 2023, were analysed at IRJ, including isolation and identification of C. difficile strains and testing for antimicrobial susceptibility. Infectious diseases investigators were blinded to patients’ data.

Results

Eleven patients with IBD (median 42 years, 60.0% female) had at least one episode of CDI, comprising 15 IBD-related CDI cases, which represents 26.3% of all CDI cases in this 6-month period. Moreover, this compares to only 14 cases of IBD-related CDI in the previous four years combined. All patients had UC (66.7% extensive), with a median diagnosis of 11 years. All cases were community-acquired, diagnosed in the context of acute worsening of UC symptoms; 40% required hospitalization. Remarkably, only 2 patients had recent antibiotic therapy, while 3 had a recent visit to the emergency department. No predominant ribotype (RT) was recognised: RT 002/2, RT 017, RT 039, RT 078, RT 106 and RT 839 were identified in similar proportions. There were two new RTs detected, which are under characterization. All isolates were susceptible to vancomycin and metronidazole, but 46.7% were resistant to moxifloxacin, which is higher than ever reported in Portugal. Most cases (n=12) were prescribed vancomycin and followed a taper-and-pulse dosing (n=9). None of the three patients who had a recurrence had received taper-and-pulse dosing. Optimization of UC therapy was performed in all cases, including concomitant immunosuppressive therapy escalation when needed, as recommended. Interestingly, one case, despite having tested positive for C. difficile, had a Clostridioides hathewayi isolated in the culture instead. To our knowledge, this is the first case of C. hathewayi associated diarrhoea resolving upon treatment with vancomycin.

Conclusion

The absence of a predominant ribotype, excluding a community outbreak, demands heightened CDI vigilance in IBD even in absence of traditional risk factors. Alarming moxifloxacin resistance underscores evolving dynamics. A novel C. hathewayi-associated diarrhoea case and the emergence of two new ribotypes adds complexity.Read more P1051 The role of Resection Margins in Crohn`s Disease – A potential risk factor for Disease Recurrence?Wed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Postoperative disease recurrence after ileocecal resection for Crohn`s Disease is a major issue for all disciplines. While adequate therapeutic strategies are lacking, further criteria are necessary to improve the identification of patients at risk for disease recurrence. In line with that, the exact role of positive resection margins as a potential risk factor on disease recurrence remains unclear since current evidence is heterogenous.

Methods

All patients who received ileocecal resection due to localized terminal ileitis Crohn at the Department of Surgery at the University Hospital of Wuerzburg between 2014 and 2021 were evaluated. Primary endpoints were severe endoscopic (Rutgeerts-Score >2) and surgical recurrence (re-operation due to Crohn`s Disease) during follow up. Positive resection margins were identified by two independent pathologists and defined by the following criteria as international consensus: neutrophils localized in the epithelium, cryptitis, and/or plexitis.

Results

214 patients received ileocecal resection at the Department of Surgery. Of those, 159 patients were finally included for analysis with a median follow up of 35 months. Postoperative morbidity was not affected by inflammation at the resection margins. However, positive resection margins resulted in significantly increased rates of severe endoscopic recurrence at six months (2.0% versus 15.6%, p=0.02) and overall (4.2% versus 19.6%, p=0.001). Additionally, positive margins resulted in significantly increased rates of surgical recurrence (0% versus 4.5%, p=0.04).

Conclusion

Positive resection margins in Crohn`s Disease are associated with increased rates of severe endoscopic and surgical recurrence and should therefore be considered as risk factor for postoperative disease recurrence.Read more P797 Assessment of pharmacokinetics and clinical response in patients transitioning from intravenous to subcutaneous vedolizumabWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Vedolizumab is a humanized monoclonal antibody directed against α4β7 integrin used in inflammatory bowel disease (IBS) patients¹. The usual dosage of Vedolizumab is 300 mg intravenously (iv). Recently the subcutaneous (sc) formulation (108 mg every 2 weeks) has been approved, which provides more independence for the patient, avoiding visits to the hospital and possible inconveniences associated with it².

Methods

The aim of the study is to evaluate the clinical and biochemical response of IBS patients treated with vedolizumab, 16 weeks after transitioning from iv to sc. An observational, prospective, single-center cohort study was performed. Patients with IBS and maintenance treatment with vedolizumab, stable for at least 4 months, were offered to switch to sc formulation. At the same time of treatment administration a blood test was performed, with vedolizumab levels and fecal calprotectin. Clinical index as Harvey-Bradshaw Index (HBI)/Simple Clinical Colitis Activity Index (SCCAI) and questionaries (IBDQ-9 and TSQM) were performed on each visit.

Results

43 patients were included, 12 of them (27.9%) chose to transition to sc formulation. Baseline characteristics of both groups are shown in Table 1. 34 (79.1%) patients were prescribed vedolizumab due to previous biologic failure, 7 (16.3%) in first line due to comorbidities and 2 (4.7%) because of adverse effects in prior treatment.All included patients remained in remission during follow-up. At week 16 (w16), no significant differences were found in calprotectin levels in patients on iv treatment (mean 146.6 ± SD 45.9) vs sc (159.26 ± 53.9) (p 0.9). Vedolizumab serum levels at w16 were higher in the sc group (22364.3 ± 5141.6) vs. iv (11425.9 ± 1514.2), with statistically significant differences (p 0.009). At w16, 9 (75%) of the patients in the SC group were highly satisfied with the medication and 11 (91.7%) considered it easy to administer. 1 patient (8.3%) in the sc group returned to iv treatment. 4 patients (12.9%) in iv and 2 (16.6%) in sc treatment presented mild adverse effects. The 2 cases (100%) of the sc group the adverse event was local inflammation at the injection site.

Conclusion

In our experience, vedolizumab sc is a safe and convenient alternative to iv administration. Vedolizumab serum levels in patients who transitioned to sc were higher than iv formulation.1. Smith, Michael A et al. "Vedolizumab: an α4β7 integrin inhibitor for inflammatory bowel diseases." The Annals of pharmacotherapy vol. 48,12 (2014): 1629-35.2. Vermeire, Séverine et al. "Efficacy and Safety of Subcutaneous Vedolizumab in Patients With Moderately to Severely Active Crohn's Disease: Results From the VISIBLE 2 Randomised Trial." Journal of Crohn's & colitis vol. 16,1 (2022): 27-38.Read more P1240 Systematic review with meta-analysis: faecal microbiota transplantation as treatment of chronic pouchitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Pouchitis is inflammation of the ileal pouch-anal anastomosis after proctocolectomy in the surgical treatment of ulcerative colitis. Cohort studies have found evidence that allogenic faecal microbiota transplantation (FMT) can induce short term beneficial effects in patients with chronic pouchitis. Until recently results from randomized controlled trials (RCTs) have been missing. In this systematic review and meta-analysis, we investigated whether FMT treatment was superior to placebo in inducing remission in patients with chronic pouchitis.

Methods

We searched MEDLINE, Embase, and Cochrane Central Register of Controlled Trials from inception to 15^th of November 2023, for RCTs assessing the efficacy of allogenic FMT in the treatment of chronic pouchitis. Autologous FMT or placebo was accepted as control treatment. The primary outcome was the improvement of symptoms as defined by the authors following four weeks.

Results

The systematic literature search identified a total of three RCTs on the efficacy of FMT in chronic pouchitis comprising 62 patients with 32 patients treated with FMT. Both treatments (FMT and Placebo) and definition of treatment response varied between studies (Table 1). Meta-analysis revealed that FMT was not superior to placebo (risk ratio=0,68;95% CI=(0,47-0,99); p=0.35) in improvement of symptoms four weeks following treatment (Figure 1).

Conclusion

FMT was not superior to placebo in inducing short-term beneficial effects four weeks after initial treatment in patients with chronic pouchitis. Whether FMT may induce long-term beneficial effects remains to be established.Read more P1052 High doses of methylprednisolone in inducing remission in acute severe ulcerative colitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Ulcerative colitis (UC), characterized by mucosal inflammation progressing proximally through the colon, is increasing in incidence, including among pediatric populations. UC clinically manifests through symptoms such as abdominal pain, diarrhea, and hematochezia. Treatment aims primarily to induce and maintain remission. For those inadequately responding to 5-aminosalicylic acid, remission may be induced via oral steroids or, in severe instances, intravenous methylprednisolone (1.5mg/kg per day). This retrospective analysis aims to evaluate the efficacy of high-dose intravenous methylprednisolone pulses (30 mg/kg, max 1g per day for 3-5 days) in inducing remission in moderate and severe pediatric UC cases used in patients not responding to standard doses of steroids. In the fields of nephrology, rheumatology, oncology and neurology, the efficacy of high-dose glucocorticoids has been proven.

Methods

From a cohort of 121 pediatric patients (<18 years) hospitalized 2018-2021 due to acute flare of UC, 15 were treated with high doses of methylprednisolone to induce remission. The Pediatric Ulcerative Colitis Activity Index (PUCAI) was used to determine the response to treatment- considering a 20-point reduction or a score below 10 as significant improvement and indicative of remission induction.

Results

The activity of the disease was moderate in 2 children and severe in 13 out of the analyzed group. We observed a clinically significant response in 9/15 patients (60%) with a mean PUCAI decrease of 30±23,4 points. The average duration to clinical remission was 4.06 days. For the 6/15 non-responders to methylprednisolone pulses, treatment was escalated (4 received infliximab, 1 adalimumab, and 1 initiated with cyclosporine followed by infliximab); notably, 3 required colectomy. Adverse effects were not observed during the treatment period.

Conclusion

In conclusion, high-dose methylprednisolone appears to be a viable alternative for inducing remission in pediatric UC. However, due to limitations such as the small patient group and the retrospective nature of this analysis, further prospective studies are essential to validate these findings.Read more P798 Study of the concordance between the enzymatic activity of Thiopurine S-methyltransferase and polymorphisms in the TPMT gene in patients with Inflammatory Bowel DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Thiopurine therapy is associated with an increased risk of serious adverse events in patients with Inflammatory Bowel Disease (IBD). Thiopurine S-methyltransferase (TPMT) is the enzyme responsible for metabolism, and its determination helps identify patients at risk of toxicity. This study aims to explore the level of correspondence between the TPMT genotype and enzymatic activity (phenotype) with the objective of preventing adverse events prior to the commencement of thiopurine therapy.

Methods

Consecutive patients with IBD, Crohn’s Disease (CD) or Ulcerative Colitis (UC), were included. Genotype was conducted for the most prevalent TPMT variants (TPMT*2, TPMT*3B, TPMT*3C), TPMT enzymatic activity assessment, and quantification of 6-thioguanine nucleotide (6-TGN) levels. Adverse effects were documented, along with the administration of biologics, mesalazine, ACE inhibitors or allopurinol. The primary objective was to evaluate the concordance between TPMT genotype and phenotype. Secondary objectives included determining the prevalence of genotype and phenotype within our patient cohort, 6-TGN serum levels, the prevalence of adverse events and identifying potential pharmacological inducers of the phenotype.

Results

A total of 218 patients were included (131 with CD and 81 with UC). Thirteen patients did not initiate thiopurines, and 34.63% (71/205) had discontinued treatment. The most observed adverse events were myelotoxicity (15.12%), gastrointestinal toxicity (12.20%), and hepatic toxicity (5.37%). TPMT activity exhibited a trimodal distribution, with 87.61% (191/218) having normal activity, 11.47% having intermediate activity, and 1% having low activity. Genotypically, 90.83% (198/218) had a wild-type genotype, 8.72% (18/218) had a heterozygous genotype, and 0.5% (1/218) had a homozygous genotype. The concordance index between phenotype and genotype was calculated at 0.57. Significantly, myelotoxicity was associated with the presence of genotypic variants (p=0.004). 6-TGN levels did not correlate with TPMT activity and concurrent medications did not affect TPMT activity .

Conclusion

The proactive assessment of TPMT (phenotype or genotype) before initiating thiopurine therapy effectively mitigates the occurrence of myelotoxicity in IBD patients. Importantly, the level of concordance between TPMT activity and genotype is moderate, with genotyping serving as the more reliable approach for preselecting patients susceptible to myelotoxic reactions.Figure 1:TPMT activity (U/mL RBC) distribution.Read more P1053 Ustekinumab trough concentration could predict the aggravation of endoscopic severity after de-escalation in the sub-analysis of CD-EXTEND studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

De-escalation was a useful strategy for improving patient’s QOL and reduction of medical expenses. However, endoscopic data after de-escalation of ustekinumab (UST) has not been reported. The aim of this study was to elucidate UST trough concentration for the prediction of endoscopic aggravation after de-escalation of UST.

Methods

This CD-EXTEND study was a single-centre prospective observational study approved by the institutional review board of our hospital. Thirty CD patients who selected de-escalate UST treatment after administration of intravenous UST 6 mg/kg and subcutaneous UST 90mg every 8 weeks until 54 weeks were enrolled in this cohort. Endoscopic evaluation was performed at baseline and at one year. Endoscopic aggravation was defied as the increase of SES-CD score. Cut-off values of prediction for endoscopic aggravation was calculated by receiver operating characteristic (ROC) curve.

Results

Endoscopic evaluation could be evaluated in 25 patients. Endoscopic aggravation was recognized in 9 patients. There was no significant differences of patient’s characteristics and biomarkers including CRP, fecal calprotectin (FC) and Leucin-rich alpha-2-glycoprotein (LRG) between aggravated and non-aggravated groups at the baseline. However, trough concentration was significantly higher in aggravated group than non-aggravated group at the base line (1.5 ± 0.7 vs 2.8 ± 1.3 μg/mL, p=0.02). CRP, FC and LRG significantly increased in aggravated group, not in non-aggravated group. However, trough concentration significantly decreased in both aggravated and non-aggravated groups. Trough at one year was significantly lower in aggravated group than non-aggravated group (0.44 ± 0.3 vs 1.0 ± 0.71 μg/mL, p=0.02). Cut-off values of trough concentration of prediction for endoscopic aggravation at base line and at one year were 2.15 and 0.4 μg/mL, respectively.

Conclusion

UST trough concentration was a good prediction marker for endoscopic aggravation.Read more P1241 Distinct gut microbiota in Crohn's Disease between inflammatory B1 and stricturing B2 phenotypeWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The gut microbiome represents a promising avenue to elucidate distinct underlying pathophysiology in Crohn's disease (CD).Our aim was to evaluate the composition of the microbiota in Inflammatory B1 and Stricturing B2 Phenotype.

Methods

We performed 16S ribosomal RNA sequencing on stool samples of 108 patients (64 B1 and 44 B2) included in the Chinese CD cohort and 58 health controls without any inflammatory disorder, in order to explore the structural composition of gut microbiota in different phenotype of CD.

Results

Comparison of gut microbiota between patients with CD and healthy controls, α diversity and β diversity were statistically different. At the genus level, compared with the normal group, the abundance of Blautia, Bifidobacterium, Faecalibacterium, Collinsella, Coprococcus, Gemmiger, Prevotella, Dialister, Roseburia and Clostridium were decreased significantly in the CD group. In contrast, the abundance of Bacteroides, Ruminococcus, Streptococcus, Enterococcus, Dorea, Escherichia, Phascolarctobacterium, Veillonella and Eubacterium increased significantly. Compared with B1 phenotype, Streptococcus, Collinsella, Veillonella, Coprococcus and Gemmiger were significant decreased in B2 phenotype group. However, Ruminococcus, Dorea, Lactobacillus and Dialister were significant increased.

Conclusion

Comparison of gut microbiota between patients with CD and healthy controls, α diversity and β diversity were statistically different. At the genus level, compared with the normal group, the abundance of Blautia, Bifidobacterium, Faecalibacterium, Collinsella, Coprococcus, Gemmiger, Prevotella, Dialister, Roseburia and Clostridium were decreased significantly in the CD group. In contrast, the abundance of Bacteroides, Ruminococcus, Streptococcus, Enterococcus, Dorea, Escherichia, Phascolarctobacterium, Veillonella and Eubacterium increased significantly. Compared with B1 phenotype, Streptococcus, Collinsella, Veillonella, Coprococcus and Gemmiger were significant decreased in B2 phenotype group. However, Ruminococcus, Dorea, Lactobacillus and Dialister were significant increased.Read more P799 Deficits in geriatric assessment are dynamic over 18 months and impacted by therapeutic treatment in older patients with Inflammatory Bowel DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Frailty is a dynamic condition, however most previous studies in patients with IBD measured frailty at one point in time. Therefore, we aimed to study the course frailty, reflected by deficits measured in a geriatric assessment, during 18 months follow-up in older patients with Inflammatory Bowel Disease (IBD). In addition, we aimed to identify factors associated with changes in geriatric deficits over time.

Methods

In a prospective, multicenter cohort study, a geriatric assessment was performed at baseline and repeated after 18 months in 154 older patients with IBD. This geriatric assessment evaluated the presence of deficits in five geriatric domains: the somatic domain, mental domain, social domain, activities of daily living and physical capacity. The number and type of impaired domains at baseline were compared to follow-up. An increase in number of domains suggests worsening frailty, whereas a decrease in number of impaired domains suggests improving frailty. Logistic regression was performed to identify factors associated with change in number of domains. All analyses were adjusted for age, sex, type of IBD and educational level.

Results

During follow-up, 32.5% had increased and 26.0% decreased ≥ 1 in number of impaired domains, compared to baseline. At domain level, the proportion of patients with impaired activities of daily living decreased from 49.4% at baseline to 37.7% at follow-up (p-value=0.001). The proportion with impaired physical capacity increased from 14.3% to 26.0% (p-value=0.001). Use of systemic corticosteroid at baseline and/or the year prior to baseline was associated with an increase in impaired domains (aOR 3.00; 95% confidence interval (95% CI) 1.11-8.08; p-value= 0.030), while initiation of biological therapy was associated with a decrease in impaired domains at follow-up compared to baseline (aOR 4.92, 95%CI 1.41-17.15, p-value=0.013).

Conclusion

Geriatric deficits, reflecting levels of frailty, are dynamic over 18 months in older patients with IBD. Therapeutic IBD management appeared an important determinant for the longitudinal course of frailty. This study provides the first longitudinal data on the course of geriatric deficits, measured in a geriatric assessment, in older patients with IBD.Read more P1242 Pediatric IBD microbiome and microbial profiles formed within the familyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The rise of microbiome-focused research, reveals that the intrafamilial microbiome can be linked to specific genetic traits and be studied for its behavior during dysbiosis. It has been reported that microbiota composition is shared between cohabitating individualsand displays patterns of similarity that differ between families. Based on these observations, this study focuses on treatment-naïve pediatric IBD patients and their immediate families to identify the role of the microbiome in disease onset.

Methods

Families with pediatric IBD were recruited,comprising seven drug-naïve Crohn’s disease (CD) patients and two drug-naïve ulcerative colitis (UC) patients, as well as healthy siblings/parents. Fecal samples were collected for 16S ribosomal RNA gene sequencing and bioinformatics analysis.

Results

Our results elucidate the fact that even though family members share lifestyle and dietary habits, the patients exhibit unique microbiome patterns which could only be attributed to the disease. In addition, we studiedthe impact of the disease on specific microbial taxa and how these could serve as potential biomarkers for early detection.

Conclusion

We found a potential role of maternal factors in the establishment and modulation of the early life microbiome, consistent with the current literature, which may have implications for understanding the etiology and progression of IBD.Read more P730 Edema index as a more sensitive indicator of nutritional status with Crohn’s diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Crohn's disease (CD) often presents with malnutrition due to the impaired mucosal barrier accelerating the loss of protein. The edema index can indicate protein consumption. This study aims to confirm whether the edema index could be a nutritional assessment for CD patients.

Methods

The study was conducted at Xiangya Hospital Central South University between May 2023 and July 2023, including CD patients and the control group. In both groups, bioelectrical impedance analysis was performed, and the edema index defined as extracelluar water/total body water (ECW/TBW) was calculated. The demographic data and body composition parameters were collected through the medical system. The control group consisted of healthy adults, strictly matched for gender, age, and BMI in a 1:1 case-control manner. Univariate analysis and multivariate analysis were used to compare the differences in nutrition-related indicators between both groups.

Results

A total of 128 subjects were included in the final cohort with 50% each of CD patients and healthy individuals. There were no significant differences in gender, age, BMI. Fat free mass, muscle mass, basal metabolic rate (BMR), and visceral fat rating were similar in both groups (P > 0.05). Compared to the control group, CD patients had significantly lower fat mass (9.26 ± 5.38 vs.16.63 ± 10.67, P = 0.006), bone mass (2.16 ± 0.41 vs. 2.52 ± 0.57, P = 0.019), but a higher level of edema index (41.07 ± 2.38 vs. 38.53 ± 5.62, P = 0.015). Multivariate logistic regression analysis revealed that edema index was an independent factor to malnutrition in CD patients (OR: 1.665, 95% CI: 1.158-2.395, P = 0.006).

Conclusion

A higher edema index in CD patients demonstrates their worse nutritional status compared to healthy subjects. The edema index may serve as a more sensitive and noninvasive indicator to assess nutritional status in CD patients.Read more P946 Real life management of patients with active perianal fistulizing Crohn’s disease (ALERT-CD study)Wed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The multitude of medical and surgical treatment options for perianal fistulizing Crohn’s disease (pCD) impels differences in management. This study aimed to assess management of pCD in current clinical practice in the Netherlands.

Methods

Patients with active pCD (i.e. visible external fistula opening or patent fistula tract on imaging) were included in a prospective multicenter cohort study in 41 Dutch academic and non-academic hospitals from September 2022 to March 2023. pCD-related clinical, radiological and surgical data were prospectively collected during a follow-up period of 6 months and retrospectively collected from pCD diagnosis until inclusion. Primary outcome of the study was adherence to the international guidelines on pCD management during the disease course (from pCD diagnosis until end of follow-up). Adequate adherence was defined as (I) imaging for pCD diagnosis using magnetic resonance imaging (MRI) and/or endo-anal ultrasound (EUS), (II) endoscopic evaluation of concomitant proctitis, (III) use of antibiotics for symptomatic response, (IV) initiation of an anti-tumour necrosis factor (TNF) agent for maintenance therapy, (V) fistula surgery aiming at fistula closure in case of surgically amendable disease and (VI) decision making by a multidisciplinary team (gastroenterologist and surgeon)(Figure 1).

Results

449 patients with active pCD (52% female) were included(Table 1). At inclusion, median age and median pCD duration were 37.2 years (IQR 28.8–49.4) and 3.1 years (IQR 1.1–7.1). 54% of patients were treated in a non-academic hospital. 89% of patients were treated with CD medication, which concerned anti-TNF agents in 82% of these patients. As recommended by guidelines, a MRI (99%) and/or EUS (9%) were performed in the vast majority of patients (97%) for pCD diagnosis. Following diagnosis, endoscopy was performed in 81% of patients. During the disease course, antibiotics were initiated in 55% of patients and at least one anti-TNF agent(s) was started in 84% of patients for maintenance therapy (73% infliximab, 53% adalimumab, 26% both agents). Surgery aiming for fistula closure was performed in 38% of patients during the disease course. 60% of patients were discussed in a multidisciplinary team (MDT).

Conclusion

This study demonstrated a high adherence to international guidelines on pCD management concerning imaging at diagnosis, endoscopic evaluation for concomitant proctitis and treatment with anti-TNF agents. Adherence to use of antibiotics for symptoms, performance of fistula surgery aiming at fistula closure and decision making in a MDT is moderate and standardization may optimize pCD management.Read more P731 Relapse rate following withdrawal of anti-TNF therapy in patients with inflammatory bowel disease: A single-center experienceWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Discontinuation of anti–tumor necrosis factor alpha treatment (anti-TNFα) in patients with inflammatory bowel disease (IBD) poses a significant risk for relapse. The aim of this study is to analyze relapse rates and to possibly identify factors associated with relapse in IBD patients after treatment cessation with anti-TNFα.

Methods

This is a prospective study conducted at University Clinic of Gastroenterology in Albania from 2019-2022. IBD patients who discontinued biologic therapy with infliximab (IFX) or adalimumab (ADA) were included. All the patients discontinued therapy due to reimbursement issues. Demographic, clinical,laboratory and endoscopic data were collected for each patient. Relapse rates and predictors for relapse were studied using survival and Cox regression analysis.

Results

A total of 52 IBD patients, mean age 50.8±14.7 years (46 UC and 6 CD), 25(48%) males, were included in the study. Mean follow-up was 29 months. 47.4% were treated with ADA and 51.5 % with IFX. The mean period of biologic therapy was 33.3 months for all patients. Upon treatment cessation, 55.8% of patients were in complete clinical remission, and 30.8% were in partial clinical remission.Cumulative relapse rates at 6, 12, 24 and 36 months were 23.9%, 39.1%, 44.2% and 69.7% respectively for all UC patients while 66.7% of CD patients relapsed within 6 months. The mean time to relapse was 13 months for UC and 5 months for CD patients.Among all IBD patients in complete clinical remission at the time of treatment discontinuation, the cumulative relapse rates at 6, 12, 24 and 36 months, were: 6.9%, 24.8%, 57.7%, and 58% respectively. Significantly higher cumulative relapse rates were found in patients with partial remission, the at the same time points: 37.5%, 50%, 75%, and 81.2% respectively (p=0.01).Multivariable Cox analysis revealed that the only factor associated with lower risk of relapse was mucosal healing (vs nonmucosal healing: HR, 0.322; 95% CI, 1.26 to 6.677; p=0.012).

Conclusion

The majority of IBD patients relapsed within 3 years after anti TNFα discontinuation, Mucosal healing was the only factor associated with a lower risk of relapse. These results emphasise the crucial role of mucosal healing in guiding treatment decisions for IBD patients.Read more P973 Real-world data on the effectiveness on IBD of anti-IL23 drugs prescribed for psoriasis indicationWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

There is a significant association between psoriasis and IBD, which share the pathogenic role of IL-23. In the dermatological field, drugs targeting the p19 subunit of IL-23, such as risankizumab, guselkumab, and tildrakizumab, have been approved for the treatment of moderate to severe psoriasis. However, there are still no real-life data on the efficacy and safety profile of IL-23 inhibitors in patients with IBD.

Methods

A prospective, single center observational study was conducted on patients with IBD and psoriasis from April 2021 to March 2023 at the gastroenterological-dermatological outpatient clinic at “Città della Salute e della Scienza of Turin”, Italy. Patients received a dermatological indication to start drug therapy with IL-23 inhibitors according to the dermatological dosing schedule. They were treated either with guselkumab subcutaneously at a dose of 100 mg every 8 weeks, or with risankizumab subcutaneously at a dose of 150 mg every 12 weeks, or with tildrakizumab 100 mg every 12 weeks subcutaneously. Objectives of this study included evaluating the achievement of clinical remission at 3, 6, and 12 months, defined as disease activity with Harvey-Bradshaw Index (HBI) < of 5 in CD and pMAYO < of 2 in UC.

Results

At 3 months after the start of drug treatment, clinical remission was achieved by 73.3% of patients (p=0.006). This number also remained almost constant at 6 (62.4%, p=0.008) and 12 months (60.3%, p=0.04). In addition, there was a statistically superior steroid-free clinical remission compared to T0 at 3 (15.3% vs 73.3%, p=0.006) and 6 months (7.1% vs 54.1%, p=0.04). No major side effects were reported. Two cases of arthralgias (11.8%) and one case of fever with chills (5.9%) were reported. IL-23 inhibitors appear to be effective in maintaining the steroid-free clinical remission. In addition, there was a reduction in fecal calprotectin values to a median value at 6 months of 81.0 (95%IC= 28.2-249.8; p=0.03) from a median value at T0 of 343.1 (95%IC= 44.8-869.7). The maintenance rate of IL-23 inhibitors therapy at the end of follow-up was 75.8%.

Conclusion

In this study risankizumab, guselkumab, and tildrakizumab appear to be effective in inducing clinical remission and steroid-free clinical remission in patients with IBD. In addition, they appear to be effective in maintaining steroid-free clinical remission. IL-23 inhibitors demonstrated a good safety profile in patients with IBD. Despite the limitations of the study with the need to publish further real-world data on a larger scale and with higher dosing of IL-23 inhibitors, the results obtained are promising as they, for the first time, provide real-life support for the clinical potential of these drugs as treatment for IBD in addition to psoriasis.Read more N29 Patient evaluation of digital IBD care in patient initiated follow up pathway using MyIBD Care app and home calprotectin testWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Remote patient monitoring via web applications has been reported to have benefits with improvement in patient-reported quality of life, medication adherence, and decreased heath care costs. Mobile applications can be used for symptom reporting and this along with home biomarker testing can facilitate patient initiated follow up. There remain uncertainties in the acceptance of digital technologies in routine follow up care among IBD patients. We aimed to survey the pilot users of MyIBD care app and CalproSmart home calprotectin monitoring in an IBD cohort

Methods

Patients participating in the patient initiated follow up (PIFU) cohort in IBD Home digital care pathway at a tertiary IBD referral centre were included in this pilot survey before full roll out of the programme. Patients were given detailed written and electronic information about the pathway before signing up. Predefined survey questions were administered using electronic in app methodology. The survey questions were ranked in Likert scale from strongly agree, agree, neither agree or disagree, disagree and strongly disagree. Data reported as proportion of responses to each category.

Results

132 surveys were collected and analysed. Ninety three percent of responses understood the rationale for their inclusion to the digital pathway. Confidence in contacting the IBD team through digital pathway was reported in 89% of responses and 68% felt more in control of own condition. Eight six percent of patients understood the requirements for completing patient reported outcome measures and home calprotectin test while in the pathway and also felt confident in taking home calprotectin test. However only 44% felt closer to the clinical care team with the pathway.

Conclusion

Digital pathway incorporating a patient initiated follow up and self-monitoring is acceptable to IBD patients in stable remission with high satisfaction scores in all domainsRead more P748 Place of thiopurine monotherapy in the treatment of Crohn's Disease in the era of biologic therapies: results of a long-term tertiary single-center experienceWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Crohn's disease (CD) is a chronic and disabling immune-mediated disease of the digestive tract, and immunosuppressive drugs are a cornerstone in the therapeutic approach, particularly purine analogues which are widely used in the treatment of CD as an agent to maintain remission. Despite their widespread use, adverse effects are frequent and lead to discontinuation of treatment in a significant proportion of patients so the increasing use of anti-TNFα biologics may have had an impact on the use of thiopurines. We present a long-term retrospective experience from a tertiary hospital center aimed at studying the evolution of thiopurine monotherapy use in the era of biologics, based on current therapeutic goals and safety standards.

Methods

We performed a retrospective analysis of all Crohn's disease patients followed up in our hepato-gastroenterology department who received AZA monotherapy at the standard dose (2-2.5 mg/kg/d) or 6-MP (1-1.5 mg/kg/d) at any time during their follow-up between January 2016 and June 2023 and who were still being followed up at that time. Patients who had received prior or concomitant biological treatment were excluded from the analysis. Various socio-demographic and phenotypic data were collected. Failure was defined as discontinuation of treatment due to lack of efficacy or AE. Statistical analysis was performed using SPSS2.0 software. Statistical significance was set at p < 0.05.

Results

A total of 383 patients were included: 46.5% were men and the mean age was 31 years (range 17-65). Median follow-up was 66 months. Indications for thiopurine monotherapy were cortico-dependence (306 patients, 80%) or prevention of postoperative recurrence (77 patients, 20%). Overall, 147 patients (38%) failed. The observational study of our patients showed that 74 patients (18.4%) discontinued AZA due to an adverse event (most of which occurred during the first month of treatment), 73 (19%) due to lack of efficacy. Among the main indications for AZA we note: prevention of postoperative recurrence, male gender gave better results than steroid dependence (p =0.001); perianal fistulization of CD and grecal localization gave worse results (p = 0.002).

Conclusion

In our experience, a significant proportion of CD patients on thiopurine monotherapy failed. Although IS monotherapy remains useful for CD in the era of biologics, current clinical practice is moving towards anti-TNFα biologics in an increasing proportion of patients.Read more P974 Incidence of Perianal Complications in Clinical Trials for Therapies for Moderate to Severe Inflammatory Bowel DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Crohn’s disease (CD) and ulcerative colitis (UC) are chronic inflammatory bowel diseases (IBDs) with distinct clinical consequences. Distinct from patients with UC is that nearly 25% of patients with CD patients have or will develop perianal disease. Predictors for the development of new perianal disease or complications from existing perianal disease are not well described but such occurrences are included as adverse events (AEs) in clinical trials for IBD. We performed a systematic review and meta-analysis of perianal AEs in pivotal trials of therapies for IBD.

Methods

We conducted a search of PubMed, EMBASE, MEDLINE, Medline Plus, and CDSR library databases for registry and pivotal Phase II-III clinical trials of therapies for IBD. Safety data from clinicaltrials.gov was reviewed to identify incidence of perianal AEs using the terms "abscess" and "fistula." Reported perianal AEs included the following: anal abscess, fissure, fistula; perianal abscess, fistula; perineal abscess; perirectal and rectal abscess; subcutaneous (gluteal) abscess.

Results

Perianal AE incidence across all trials reviewed was 0.47% (91/19,327 patients). Perianal AEs were more likely to occur in patients with CD (0.77%, 70/9,046) than UC (0.20%, 21/10,281). Perianal AEs occurred more frequently in populations of drug-exposed patients than in patients exposed to placebo. In drug-exposed patients with UC, 0.22% (16/7,415) of patients experienced a perianal AE vs 0.17% (5/2,935) of patients exposed to placebo. In drug-exposed patients with CD, 0.76% (55/7,271) of patients experienced a perianal AE vs 0.61% (15/2,465) of patients exposed to placebo. The results are summarized in Table 1.

Conclusion

We found that perianal AEs occur in pivotal UC and CD clinical trials. Expectedly, the frequency of perianal AEs was higher in trials of CD than those for UC. However, the development of perianal AEs in trials of UC suggests that these patients may have been misclassified and have CD. Available data do not allow distinction between development of a perianal AE in a patient with known perianal disease or progression of undiagnosed clinical or subclinical perianal disease, nor does it allow for distinction in a patient not responding to the experimental agent. The finding that perianal AEs occurred more frequently with drug exposure than placebo may be due to fistula healing with consequential abscess formation or unique mechanistic effects that worsen perianal disease. These results highlight a probable rate of misclassification of patients with UC in pivotal trials, and suggest the possibility of subclinical perianal disease in some patients. Further clarification and study of these AEs and their implications are warranted.Read more N30 Development and implementation of a microlearning programme for patients with Inflammatory Bowel Disease. The ADEII projectWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Information and communication technologies (ICTs) represent a novel approach to chronic disease management. However, their use in Inflammatory Bowel Disease (IBD) is lacking, as no specific tools are available. Microlearning is a pedagogical concept that facilitates learning by breaking down concepts into micro-contents, which can be easily integrated into everyday activities. We aimed to develop a microlearning programme for IBD patients and implement it in clinical practice.

Methods

Prospective cohort study in patients with IBD (18 to 70 years old) who underwent a microlearning programme over a 2-month period, Four-minute videos recorded by IBD unit´s own staff, and organised in individualised pathways.were sent via mobile phone. The interaction with the user was maintained through a Telegram bot that uses methods from the Django REST API for content sequencing. The basic sequencing consists of a video followed by 4 quiz questions. Depending on the answers, the user receives more questions, additional content on the same topic or moves on to the next video. We conducted a final survey about the information shown in the videos.All the contents can be found on the website: https://adeii.webs.uvigo.es/ This QR links to the promotional video of the ADEII project (Figure 1).

Results

We recorded 24 videos about IBD and treatment and another 2 about patients´personal experiences. Between 1 June and 31 October 2022, 1226 videos were sent to 200 IBD patients: 103 females (51.5%), mean age 46.1 (13) years, 105 ulcerative colitis (52.5%), and time from IBD diagnosis 13 (10) years. (Table 1). All patients received by their smart-phone the 4-video main pack, consisting of 2 videos with information about their disease (ulcerative colitis or Crohn's disease), 1 video on adherence and another one on corticosteroids.To these we added as many videos as the number of drugs that each patient used to control IBD. Mean number of videos per patient was 6 (1), range (5-9) and their distribution is shown in Figure 1. Seven patients declined to participate in this course because of fear of information and one left the study. Altogether 156 patients (78%) attended this microlearning programme, 117 fully (58,5%). A telephone contact, planned to solve technical incidents or doubts, rose the attendants to 170 (90%), 152 (76%) fully. After the course, 72,5% of the participants (145) answered correctly more than 83% of the questions based on the IBD information included in this programme.

Conclusion

A microlearning ICT-based course was widely accepted by IBD patients, and can increase the knowledge about their disease. However there are acceptance and technological barriers that must be taken into account when approaching it.Read more P749 Comparison of bowel preparations for colonoscopy in inflammatory bowel disease- A systematic review and network meta-analysis of randomized trialsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Colonoscopy is important in the management inflammatory bowel disease. Adequate bowel preparation (IBD) is a prerequisite for colonoscopy and may be difficult to achieve in setting of IBD

Methods

We performed a systematic review and network meta-analysis of randomised trials of various bowel preparations used before colonoscopy in IBD. Various electronic databases were searched to identify eligible studies. A frequentist network meta-analysis was done to compare the effectiveness of various bowel preparations. Risk of bias was assessed using Cochrane risk of bias tool 2.0. Other outcomes were assessed qualitatively.

Results

We included 7 trials including 960 patients. All bowel preparation had a similar effectiveness of bowel preparation as compared to 4 litres of polyethylene glycol (PEG) (OR when compared with PEG4L: OSS- 1.1043 95% CI 0.6553-1.8610; PEG/Ascorbate 2L- 0.9838, 0.6519-1.4848; PEG 1L -1.0011, 0.5522-1.8150; PEG2L plus bisacodyl -1.0864, 0.7130-1.6554; PEG 4L plus simethicone -1.0069, 0.6721-1.5084; PEG/SPMC 1.5L -0.9966, 0.5569-1.7835; SPMC 2L -1.0996, 0.6123-1.9745 had a similar effectiveness. Low-volume preparations had better compliance, tolerance, and acceptance, and willingness to repeat. No difference in additional outcomes like change in disease activity after colonoscopy, procedure-related outcome after colonoscopy like cecal intubation rate, and change in electrolyte levels were found.

Conclusion

Various bowel preparations had similar effectiveness in respect to colonoscopy preparation in IBD patients. Low-volume preparations have better compliance, tolerance, and acceptance. The systematic review was limited by a small number of included RCTs.Read more P975 Monitoring Inflammatory Bowel Disease (IBD) by intestinal ultrasound decreases time to treatment change and time to remission in comparison to conventional management: Analysis of patients with IBD on multiple IBD therapiesWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Intestinal ultrasound (IUS) is a non-invasive, repeatable, and accurate disease monitoring modality that can provide real-time assessment of inflammatory bowel disease (IBD). We previously demonstrated that IUS shortens time to treatment change and time to remission in patients receiving upadacitinib and monitored by IUS compared to conventional management (ACG 2023). Here, we aim to assess the impact of IUS on management and outcomes of our pts with IBD receiving any IBD therapy.

Methods

We performed a retrospective analysis of patients who completed induction therapy (per individual drug label) but have active disease as measured by SCCAI >2 or HBI >4 between October 2021 and October 2023. We assessed for the time to treatment change (time from a positive clinical index to the time of a medical decision made), and time to clinical remission (time from a positive clinical index to the time of normalization (SCCAI ≤2, HBI ≤4 of the clinical index) and compared those between patients monitored by IUS and those managed with a conventional approach. Patients were matched by their provider and disease type. Active disease by faecal calprotectin (FCP) (FCP >150 mcg/g) and endoscopy (Mayo endoscopic score (MES) >0) were assessed ± a month before a positive clinical index was collected. An abnormal IUS was considered bowel wall thickness (BWT) >3 mm in the colon or terminal ileum and any hyperemia by colour Doppler signal (CDS) (modified Limberg score >0). Chi square analysis was performed, with p<0.10 significance.

Results

54 patients (63 encounters) were included in this analysis (33 in the IUS cohort, 30 in the conventional management cohort) from 3 different providers. At inclusion, 9 (27%) pts in the IUS group and 10 (33.3%) in the conventional group had elevated FCP, and 5 (15.2%) pts in the IUS group and 29 (96%) had endoscopic disease. In the IUS group, the average time-to-treatment change was 2.2 (±1.2) days compared to conventional management 25.6 (±14.5), p=0.050. A total of 44 patients achieved clinical remission (22 IUS; 22 conventional management). The average time to remission in the IUS group was 128.1 days (±22.3) vs 230.6 (±38.2) days in the conventional management group, p=0.035). Drug class did not affect time to treatment change or time to remission (Table 1). The most significant reason for delay in the conventional group compared to the IUS group was awaiting endoscopy and FCP results.

Conclusion

Using IUS to assess disease activity in IBD is associated with earlier treatment changes and shorter time to remission compared to conventional approaches to disease monitoring, independent of therapy choice. Ongoing dissemination and incorporation of IUS in the management of IBD are warranted.Read more P762 Risk of Infection After Acute Severe Ulcerative Colitis in East Asia and Australia/New Zealand: AOCC and ANZIBDC collaboration studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Infection is one of the concerns in the treatment of inflammatory bowel disease, and advanced age and immunosuppressants are known to be risk factors for infection. However, there has been no studies on infection after acute severe ulcerative colitis (ASUC) and its associated factors. The aim of this study was to investigate infection and associated factors in ASUC patients, as well as differences in infection risk between regions of East Asia and Australia/New Zealand (ANZ).

Methods

We retrospectively analyzed patients with ASUC diagnosed according to Truelove Witt criteria from January 2015 to September 2022. We identified the overall incidence of infection and related risk factors, and then analyzed the differences by two regions.

Results

A total of 676 ASUC patients (329 in East ASIA, 347 in ANZ) were enrolled. Overall infections within 1 year after ASUC occurred in 65 patients (9.6%). Clostridioides difficile (C. diff) infection (17/65, 26%), CMV colitis (14/65, 21%), and pneumonia (7/65, 10%) were most common infections. Risk factor associated with infection was combination therapy with anti-TNF agent and thiopurine at discharge (hazard ratio [HR] 5.225, 95% confidential interval [CI] 2.469-11.059, P<0.001). The group with infections exhibited worse outcomes, including a higher readmission rate (39.3% vs. 92.2%, p < 0.001), readmission due to ulcerative colitis (UC) (16.3% vs. 31.3%, p = 0.004), UC-related mortality (0.9% vs. 9.6%, p < 0.001), and overall mortality during the follow-up period (1.1% vs. 13.8%, p < 0.001, Table 1).In comparative analysis between East Asia and ANZ, there was no difference in the incidence of infection (7.6% vs 11.5%, p=0.083) and infection related mortality (1% vs 0.3%, p=1.000) within 1 year after ASUC. CMV colitis (10/25, 40%) and C. difficile infection (6/25, 24%) were common in East Asia while C.difficile infection (11/40, 27%) and skin infections (7/40 17%) occurred frequently in ANZ. The risk factors for infection in East Asia were anti TNF at discharge (HR 3.684, 95% CI 1.434-9.465, P=0.007) and CMV infection (HR 3.587, 95% CI 1.136-11.333, P=0.03), but the risk factors for infection in ANZ were combination therapy with anti TNF and thiopurine at discharge. (HR 7.911, 95% CI 3.397-11.333, P=<0.001, Figure 1).

Conclusion

The incidence of infection within 1 year after ASUC is 9.6%, and combination therapy of anti-TNF and thiopurine at discharge is a risk factor. Infections were associated with poor prognosis including mortality. There was no difference in the incidence and mortality rates of infections between East Asia and ANZ while the types of infections and related risk factors were different.Read more P1071 Patient preferences for adalimumab in inflammatory bowel disease: a nationwide study from the GETAIDWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Several adalimumab preparations are now available on the market for patients with inflammatory bowel disease. Comparative satisfaction and tolerability are unknown. The aim of this study was to investigate inflammatory bowel disease patient satisfaction with approved adalimumab biosimilars and their originator.

Methods

In this cross-sectional study, we included 941 consecutive adalimumab-treated patients with inflammatory bowel disease across 45 centres affiliated with the GETAID who completed a satisfaction questionnaire comprising four items each rated by a 10 points-scale. The differences in responses were performed using one-way analysis of variance followed by Tukey's Honest Significant Difference test.

Results

The most commonly used drugs at inclusion were Humira® (436/941, 46.3%), Amgevita® (177/941, 18.8%), and Hulio® (105/941, 11.2%). Mean overall satisfaction rate with adalimumab was 8.5 [standard deviation 1.8]. Overall satisfaction was significantly higher in patients treated with Humira® (8.6 [1.5]), Hulio® (8.6 [1.8]) or Amgevita® (8.5 [1.4]) (p<0.05). Satisfaction with the subcutaneous injection form was higher for patients treated with Yuflyma® (9.0 [1.4]), Humira® (8.9 [1.3]) and Hulio® (8.9 [1.7]) (p<0.05). A total of 299 patients (31.8%) described injection site reactions. Two hundred twenty-three patients (23.7%) reported that they were previously treated with another adalimumab of which (32/223, 14.3%) discontinued treatment due to side effects.

Conclusion

In this real-world setting, patients with inflammatory bowel disease had a high level of satisfaction with adalimumab treatment, with some differences in terms of overall satisfaction and satisfaction with the injection device.Read more P976 Treatment with exclusive enteral nutrition (EEN) impacts the peripheral blood mononuclear cell profile of paediatric patients with Crohn’s diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Background: Despite its established clinical efficacy, the immunological effects of exclusive enteral nutrition (EEN) in Crohn’s disease (CD) are yet to be elucidated. This study investigated the impact of EEN on circulating peripheral blood mononuclear cells (PBMCs) and how any effects observed varied according to clinical response to treatment.

Methods

Methods: Children with active CD received EEN for eight weeks as their sole induction treatment. Blood and faecal samples were collected prior to EEN and upon EEN completion. PBMCs were isolated, stained and analysed using flow cytometry. Differences in PBMCs types were compared during EEN. Faecal calprotectin was measured with ELISA. Absence of gluten immunogenic peptide (GIP) in faeces was used as a proxy marker of EEN compliance.

Results

Results: Nine participants were recruited (Table 1), three of whom initiated azathioprine during their course of EEN. Following treatment with EEN a decrease in the relative number and frequency of circulating effector memory CD8⁺ T cells re-expressing CD45RA (TEMRA) was observed with a corresponding increase in the frequency of circulating central and effector memory CD8⁺ T cells (Fig. 1). When we excluded participants that commenced thiopurines during their course of EEN a decrease in the relative number of circulating TEMRA CD8⁺ T cells persisted and a decrease in naïve CD8⁺ T cells in the blood was also observed. Participants who demonstrated a decrease in faecal calprotectin 50% following treatment with EEN (n= 5) also demonstrated an increase in the frequency of circulating central memory CD8⁺ T cells. When focussing on participants (n=7) within our cohort who demonstrated a high-level of compliance (undetected GIP in faeces) during EEN, we again observed a decrease in number of TEMRA CD8⁺ T cells in blood alongside an increase in the frequency of circulating central and effector memory CD8⁺ T cells.

Conclusion

Conclusion: We observed significant changes in CD8+ T cell populations in the peripheral blood of children following treatment with EEN. These changes were observed irrespective of background immunomodulator use and persisted in participants which achieved >50% decrease in FC or demonstrated compliance to EEN. Our observed changes in CD8+ T cell populations, particularly the consistent increases in circulating effector and memory CD8+ T cells, are likely a consequence of the actions of EEN in decreasing the diversity and composition of the gut bacteria, therefore reducing the recruitment of effector/memory cells from the blood into the intestine.Read more P763 Rare and severe adverse events in pediatric inflammatory bowel disease: identification of safety signals through the international prospective PIBD-SETQuality Safety RegistryWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Rare but severe adverse events (AEs) can occur in pediatric inflammatory bowel disease (PIBD) due to ongoing inflammation, secondary to immunosuppressive drugs or as coincidental finding. These events can lead to significant disability or even death. Limited prospective research hampers the understanding of the incidences, risk factors, and outcomes associated with these events.

Methods

As part of the ongoing international PIBD-SETQuality Safety Registry, participating pediatric gastroenterologists prospectively reported the occurrence of any of 10 listed rare and severe AEs in their PIBD patient population (<19 years) via monthly electronic surveys since October 2016. Additionally, physicians could report ‘other rare and severe AEs’. Participants received an annual denominator survey, to report the number of PIBD patients under their care. Incidence rates (IRs) were calculated for each AE using Poisson regression models and were compared between countries. Upon reporting AEs, participants received specific follow-up forms to collect patient and IBD characteristics, as well as complication details (diagnosis, risk factors, management, outcome).

Results

Over a 77-month study period (October 2016 to April 2023), 222 pediatric gastroenterologists from 167 centers across 36 countries actively contributed to the registry, completing 7,975 monthly surveys with a median response rate of 86% [IQR 82%-88%]. On average, participants contributed for 53 months [IQR 25-72]. They covered 30,192 PIBD patients, with 114,528 patient-years (PY) of follow-up. In total, 285 listed complications were reported, alongside 117 uncategorized ‘other rare and severe AEs’. The highest IRs (95%CI) per 10,000 PY were found for VTE (IR 5.50 [2.74-4.99]), renal failure (IR 3.67 [2.67-4.89]), opportunistic infections (IR 2.88 [2.01-3.98]), and cancer (IR 2.71 [1.86-3.77]) (Figure 1). The lowest IRs (95%CI) per 10,000 PY were found for liver failure (IR 0.35 [0.11-0.81]) and HLH (IR 0.52 [0.21-1.06]). Combined IRs of the listed AEs did not differ among the five countries with the highest contribution of PY (p=0.18).

Conclusion

Through international collaboration among a large network of PIBD specialists, the Safety Registry has confirmed the increased incidence of several AEs in PIBD, including VTE, cancer and renal failure. Clinical characterization of these events may lead to a better understanding of their underlying etiologies and outcomes. This improves patient care by providing guidance for management development, facilitating well informed clinical decision making and may lead to prevention of these rare and severe events.Figure 1.Incidence rates (95%CI) of rare and severe adverse events in pediatric IBD reported to the Safety RegistryRead more P1084 Persistence and efficacy of Ustekinumab in Crohn's disease after antiTNF failure. May the response of the second biologic therapy be better than the first one?Wed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

After antiTNF failure, a second antiTNF in Crohn's disease (CD) is effective to achieve and maintain remission, but only50% remain with the drug after 12 months of treatment. Ustekinumab (UST) has a better persistence as second-line treatment and is effective to induce and maintain long-term remission.

Methods

Retrospective and observational study retrieved from a prospective database of Crohn's disease patients treated with UST, after approval of Research Ethics Committee. Data were collected at the beginning of treatment and after 4, 8, 16, 24 weeks, 12, 24, 36, 48, 60 months and at the end of follow-up (UST discontinuation or March 2023 if treatment continues).

Primary Objective

evaluate the persistence with UST and clinical (Harvey-Bradshaw index (HBI)<4) and biological remission (C-reactive protein (CRP)<5 mg/dl and/or fecal calprotectin (FC)<250 mg/kg) in each period of follow up.Clinical remission in perianal disease was defined as absence of drainage both spontaneous and after soft pressure. Persistence of the first biologic therapy, reasons of treatment change, dose optimization, surgery, hospitalizations and adverse events were also evaluated.

Results

68 patients were included (Table 1).Median survival of antiTNF is 1.65 years (IC95% 1.18-2.56). 72.06% patients receive antiTNF 1 year, 45.59% 2 years, 30.88% 3 years and only 8.82% are treated during 10 years.Persistence with UST was longer than with antiTNF. 93.2% of patients receive UST 1 year, 89.4% 2 years and 86.1% 3 years.There was a significant reduction of fecal calprotectin values during follow-up (p=0.0002).7 patients with perianal disease achieved clinical remission (70.00%) and 4 complete fistula healing in magnetic resonance enterography (40.00%) at the end of follow-up.60.29% patients received 90 mg every 8 weeks, but 36.76% required dose optimization (23.50% 90mg sq/4 weeks and 13.24%130mg/4 weeks ev).86.76% continue UST at the end of follow-up, with a mean duration of treatment of 27.65 months (SD 18.27). 9 patients (13.24%) stopped treatment (1 primary non response, 5 loss of response, 3 adverse events).11 patients (16.18%) needed surgery and hospitalization during follow up; 63.60% of them had stricturing disease.

Conclusion

Persistence with UST as a second line therapy was superior to antiTNF in first-line. 86.76% continued treatment with UST after 2 years. UST achieved early and long-term clinical remission in approximately two thirds of patients. 36.76% of patients required dose optimization. UST was effective in perianal disease after antiTNF failure.Figure 1 shows clinical remission in patients with basal HBI>4.Read more P1022 One-year safety and effectiveness of ustekinumab in patients with Crohn’s disease: The K-STAR studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

We aimed to investigate the safety and effectiveness of ustekinumab (UST) for Korean patients with Crohn’s disease (CD).

Methods

Adult patients with CD treated with UST were prospectively enrolled in the K-STAR (Post-MarKeting Surveillance for Crohn’s Disease patients treated with STelARa) study from April 2018 to April 2022. After single intravenous infusion of UST ~6 mg/kg, UST 90 mg subcutaneous injection was followed at week 8 and then maintenance treatment with subcutaneous UST 90 mg every 8 or 12 weeks were given, following up to week 52 to 66. Both adverse events and clinical effectiveness of UST therapy were analyzed (ClinicalTrials.gov Identifier: NCT03942120).

Results

Of the 464 patients enrolled from 44 medical centers across South Korea, 457 and 428 patients (Crohn’s disease activity index 150 or over) were included in the safety analysis and effectiveness analysis set, respectively (Table 1). At week 16–20 after starting UST, rates of clinical response, clinical remission and corticosteroid-free remission were 75.0% (321/428), 64.0% (274/428), and 61.9% (265/428), respectively (Figure 1A). At week 52–66, rates of clinical response, clinical remission and corticosteroid-free remission were 62.4% (267/428), 52.6% (225/428), and 50.0% (214/428), respectively (Figure 1B). Combined effectiveness (clinical response + biochemical response) was achieved in 40.0% (171/428) and 41.6% (178/428) of patients at week 16–20 and week 52–66, respectively. Bio-naïve patients exhibited significantly higher rates of combined effectiveness than bio-experienced patients (50.3% vs. 30.7% at week 16–20, p<0.001; 47.7% vs. 36.0% at week 52–66, p=0.014) (Figure 1A;1B). No additional benefits were observed with the concomitant use of immunomodulators. Using a multivariable analysis using backward selection, colonic involvement (vs. ileal involvement, odds ratio [OR], 0.32; 95% confidence interval [CI], 0.12–0.89; p=0.028), ileocolonic involvement (vs. ileal involvement, OR, 0.45; 95% CI, 0.23–0.89; p=0.021), baseline C-reactive protein levels (OR, 0.90; 95% CI, 0.84–0.97; p=0.009), and the exposure to two or more biologics (vs. bio-naïve, OR, 0.38; 95% CI, 0.20–0.73; p=0.003) were inversely associated with achieving clinical remission at week 52–66. Any adverse events and serious adverse events were observed in 28.2% (129/457) and in 12.7% (58/457), respectively with no new safety signal associated with UST treatment.

Conclusion

UST was well-tolerated, effective, and safe as induction and maintenance therapy for patients with CD in Korea. The results from this study enhance our understanding of the role of UST in managing CD patients with diverse characteristics and may help inform clinical decisions.Read more P813 A questionnaire-based study on fatigue and associated factors in Inflammatory Bowel DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Although fatigue is common in patients with inflammatory bowel disease (IBD), it often goes unrecognized and untreated. We investigated the degree of fatigue, and associated factors, in patients with IBD.

Methods

A multicenter study involving 147 IBD patients was conducted at five academic hospitals from August 2019 to December 2021. Demographic, clinical, and laboratory data were collected. Disease activity was assessed by the Mayo score or Crohn’s Disease Activity Index, as appropriate. Fatigue was evaluated using the validated Korean version of the Multidimensional Fatigue Inventory (MFI-K). Anxiety and depression were measured using the Hospital Anxiety and Depression Scale

Results

Among 97 ulcerative colitis and 50 Crohn’s disease patients, the mean total MFI-K score was 59.0 ± 5.5. Age, sex, body mass index, disease duration, anemia, hypoalbuminemia, and use of steroids did not affect the total MFI-K score. The anxiety and depression scores did not correlate with the fatigue score. Moderate and high disease activity significantly increased the MFI-K general and physical fatigue subscale scores compared to remission and mild disease activity (17.6 ± 1.7 vs. 16.7 ± 2.0, P = 0.009), while the use of biologics significantly decreased the total MFI-K score (57.3 ± 5.0 vs. 59.5 ± 5.5, P = 0.031). Multiple linear regression showed that fatigue was significantly increased by a history of surgery for IBD and decreased by the use of biologics.

Conclusion

The degree of fatigue in patients with IBD is high, and disease activity is the most important contributing factor.Read more P814 Empowering IBD communities worldwide: The global impact of www.ibd-eii.com in disseminating evidence-based information and educational supportWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

In recent decades, the volume of inflammatory bowel disease (IBD) research has surged, presenting a challenge for health care professionals to be updated. This is even more complicated for professionals in countries with low IBD prevalence and for registrars, fellows and other healthcare professionals.

Methods

IBD-EII website was launched the 8th February 2023 and serves as a comprehensive, unfunded and free platform offering up-to-date IBD evidence-based data. To highlight the impact, analyzing its first 8 months (data extracted via Google Analytics as of October 26, 2023) and using a google form questionnaire that was sent to subscribers in August 2023.

Results

The website encompasses over 300 trials and study summaries, along with 22 evidence-corner summaries, 102 guidelines from 12 scientific societies, 19 infographics featuring classifications and scores, 65 Cochrane meta-analyses and 13 network meta-analysis.Over the study period, there were 151,736 visits from 139 countries, with an average of 8.29 visits per user. The top-engaged countries were the United States, United Kingdom, Spain, Russia, and India (Figure 1). The site garnered 1058 subscriptions, with 10 (0.9%) individuals unsubscribing during the study period.Of the 850 invited users, 81 (9.5%) filled the questionnaire. Of them 53 (65.4%) were female. There were 49 (60.5%) healthcare professionals, 35 (43.2%) patients/family members of a patient, 4 (6%) were IBD researchers/ pharma industry workers, working for patients organization or both doctor and patient. Among healthcare professionals, 22 (44%) were IBD specialists, 14 (28%) general gastroenterologists, 4 (8%) trainees/ med school, 12 (24%) were IBD nurses/dieticians or pharmacists, 3 (6%) others. Most people have heard of the website in social media 66 (81.5%), by colleagues recommendation 8 (9.9%), congresses 7 (8.6%), or other 5 (6%). Website impact: 80 (98.8%) thought it was useful, 80 (98.8%) recommended to be subscribed. The most valuable sections were "evidence corner" 56 (69.1%) followed by guidelines 48 (59.3%) and timeline 35 (43.2%).

Conclusion

The data highlights the significant global impact of www.ibd-eii.com in disseminating evidence-based information to a diverse international community of healthcare professionals and patients. The website stands as a novel resource, fostering collaboration and empowerment within the global IBD community.Read more P1023 Variability in Mesalazine Management for Ulcerative Proctitis Include Doses, Route of Administration and Use of Fecal Calprotectin: Insights from Clinical Practice Across Spain Beyond Clinical GuidelinesWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Despite universal use of mesalazine in ulcerative colitis treatment, many aspects of clinical practice remain unclear or are not even addressed in clinical guidelines, leading to significant variations in mesalazine management among clinicians. We aimed to gather different approaches of mesalazine use in ulcerative proctitis (UP).

Methods

After discussion of a clinical case, a predefined questionnaire was anonymously answered throughout a series of meetings held at 10 different locations in Spain. Results were categorized according to experience levels and inflammatory bowel disease (IBD) focus.

Results

259 IBD treating gastroenterologists were engaged; 84% had <10 years of experience and 25% had a specific focus on IBD.Most participants (84%) manage UP based on clinical symptoms (i.e. fecal urgency). In case of a clinically moderate-severe UP, 81% would initiate treatment with high dose of combined mesalazine, while 11% proposed only suppositories. 60% of participants would assess response at 4 weeks. If clinical remission achieved, 85% would use fecal calprotectin (FC) to assess deep remission.Upon initial failure of combined mesalazine treatment at standard dose, 59% attempt optimizing mesalazine doses, while 38% add beclomethasone dipropionate. Younger physicians without specific focus on IBD prefer modifying mesalazine doses (70.5% vs 37.1%), (P=0,006), whereas more experienced physicians with monographic dedication prefer adding beclomethasone dipropionate (60% vs 29.4%), (P=0,006).For maintenance therapy (oral or topical mesalazine) the most important drivers in therapeutic decision-making were severity of the initial flare (40%) and patient preferences (36%). After a moderate-severe flare of UP, 80% would recommend maintenance therapy with high dose oral mesalazine and 3 suppositories/week.For monitoring, less experienced physicians and those not working in IBD units more frequently relied only on clinical parameters (26.6% vs. 8.7%, p=0.01), using FC to a lesser extent (73% vs. 88%, p=0.1) compared to more experienced and IBD focused physicians. In the case of elevated FC in asymptomatic patients, 49% would prefer to scope, while 47% increase mesalazine dose directly.The preferred high dose of mesalazine was 4g (55%) or 4-5g (44%). 73% would not reduce the dose upon achieving remission. Only 75% actively investigate therapeutic adherence.

Conclusion

Management of mesalazine in UP patients is highly heterogeneous, and clinical guidelines do not address all issues arising in clinical practice. Nevertheless, clinicians in our setting often use high oral and rectal mesalazine doses for both induction and maintenance and they commonly monitor patients using FC.Read more P1101 Patient-reported physical activity of IBD patients is of concern when weighed with the international physical activity questionnaire regardless of disease activity and IBD phenotype: barriers and facilitators emerged from the extended "BE-FIT-IBD" cross-sectional studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

As the World Health Organization recommends, regular physical activity (PA) determines quality of life. The qualitative/quantitative characteristics of ideal PA to be suggested for inflammatory bowel diseases (IBD) nor the relationship with disease activity are not yet well defined. This study aimed to weigh PA levels and barriers/facilitators to PA in a cross-sectional group of patients with IBD.

Methods

Consecutive Italian non-severe IBD patients (assessed with partial Mayo score for and Harvey-Bradshaw index) received an anonymous online questionnaire to assess PA levels using the International Physical Activity Questionnaire (IPAQ), disease activity as Patient-Reported Outcomes 2 (PRO-2), and finally habits, beliefs, and barriers in conducting regular PA. Clinical, anthropometric, and demographic data were also collected. PA was processed as continuous units of resting metabolic rate in minutes/week (Met min/wk). Three PA groups were identified: inactive (< 700 Met min/wk), sufficiently active (700-2500 Met min/wk) and Health Enhancing PA (i.e., HEPA active, > 2500 Met min/wk) patients.

Results

The 219 patients enrolled exhibited overall PA levels of 834.5 Met min/wk, with a large proportion (94, 42.9%) classified as inactive. Only a minority (9, 4.1%) resulted as health-enhancing PA. Patients with a non-dyslipidaemia metabolic profile (p < 0.0001) or on biologics therapy (p=0.022) showed better IPAQ scores in moderate activities. PRO-2 correlated negatively with IPAQ intense activities scores (τ= -0.156, p=0.038) in ulcerative colitis patients. PRO-2 did not show notable sensitivity/specificity in predicting IPAQ inactivity (AUC < 0.6). IPAQ showed no notable differences when related to disease activity categories according to PRO-2 (p > 0.05). Physically active patients were more willing to discuss their PA with their IBDologists. Several barriers (e.g., diagnosis of IBD and fear of flare-ups after PA) are firmly rooted in physically inactive patients. Evacuation urgency (rectal syndrome) is the IBD-related barrier most physically inactive patients reported. Some fears about PA were worse felt in the absence of a stable partner (i.e., fear of worsening or recurrence of IBD, p < 0.05).

Conclusion

Many Italian IBD patients show a worrying rate of physical inactivity, depriving themselves of the multidimensional benefits that regular PA can bring. There is a need for IBDologists to act by removing barriers to PA and engaging in a regular discussion on the importance of PA with IBD patients. IPAQ has shown good feasibility and patient acceptance in this setting.Read more P815 Infliximab drug monitoring: proactive or reactive: a North West England NHS 3 trust retrospective studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Therapeutic drug monitoring (TDM) plays a vital role in the management of patients on Infliximab. (1) The British Society of Gastroenterology (BSG) recommends TDM assessment ideally takes place 2-4 weeks after the initial loading doses, however the European Crohns and Colitis Organisation (ECCO) do not make particular proactive or reactive recommendations for TDM. (1,2,3)

Methods

Three North West England NHS trusts retrospectively collected data on 75 patients who had Infliximab trough and antibody levels done within a 12 month time frame. The aim was to establish if collectively TDM was done proactively or reactively and the overall outcomes from the monitoring.

Results

The demographic profile gave us 37 females and 38 males with the disease distribution predominantly Crohns disease ( N=53). There were more participants in the 18-50 age range (N=53) with 22 patients being 31-40 years of age, less participants in the 51-70+ age range ( N=22). Dual therapy with either Mercaptopurine or Azathioprine accounted for 49 out of the 75 participants with a majority favouring Azathioprine. Clinical management and routine use of TDM was seen in 40.5% ( N= 54) of patients indicating proactive use of monitoring in this study. TDM was undertaken after induction and annually in 48 patients whilst the remaining 27 patients received monitoring as ‘maintenance’, this is similar to the BSG recommendations and in a study by Sagar et al in 2021 ( 4).

Conclusion

Although the three participating trusts may use differing assays for the TDM, the outcomes show that it is used proactively for the majority of patients after induction and annually in keeping with BSG recommendations (3). From the data collected a further examination of results regarding subcutaneous versus intravenous TDM outcomes is proposed as the trusts move towards providing patients with both modes of administration of Infliximab.Read more P1024 The current role of Tofacitinib in acute severe ulcerative colitis in adult patients: A systematic review and pooled analysisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Despite rescue therapy, acute severe ulcerative colitis (ASUC) is associated with high colectomy rates, while treatment options remain limited. Tofacitinib, a rapidly acting Janus Kinase (JAK) inhibitor, could be an effective treatment option for managing acute severe ulcerative colitis, contributing in parallel to avoiding colectomy.

Methods

A systematic in-depth literature search in the PubMed and Scopus databases until 20 October 2023 was undertaken for all available studies of adult patients with ASUC treated with tofacitinib. Finally, we included 18 articles from a total of 705 articles resulting from our initial search. The primary outcomes were the pooled colectomy rate and the 90-day and 6-month colectomy-free rate.

Results

Overall, one retrospective study, three observational studies, nine case series and five case reports incorporating 264 patients who received tofacitinib in ASUC (preferably defined according to the Truelove ad Witts criteria) identified with a follow-up period ranging from 30 days to 14 months. In total, the pooled colectomy rate was 20.4% (95% CI 15.7-25.1). The pooled 90-day and 6-month colectomy-free rates were 85.6% (95% CI 81.1-90.1) and 82.1% (95% CI 77.6-86.6), respectively (Figure). The most common side effect was infections, with C. difficile infection being the most frequent adverse event among them.

Conclusion

Tofacitinib may be an alternative promising option for the treatment of ASUC. Furthermore, it should be mentioned that tofacitinib could be considered a safe treatment option, taking into account that adverse effects occurred in a small amount of the patients studied. Nevertheless, randomized clinical trials are required to estimate the efficacy and safety of tofacitinib in cases of ASUC.Read more P1116 Risk of fractures in children and adults with inflammatory bowel disease: A report from the epi-IIRNWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Both adult and pediatric patients with inflammatory bowel disease (IBD) are at risk of osteopenia and osteoporosis, nevertheless, whether patients with IBD are subjected to a higher risk for bone fractures is debated. Thus, we aimed to assess the risk for bone fractures, osteopenia and osteoporosis in IBD vs non-IBD patients, using the epi-Israeli IBD Research Nucleus (IIRN) data.

Methods

Data of patients with IBD and non-IBD matched controls (approximately 3 non-IBD controls per case) were retrieved from the epi-IIRN cohort (January 2005- June 2020) that maintain data on all patients with IBD from the four Israeli HMOs. Data included demographics, osteoporosis medications, fracture data and IBD related characteristics. Patients were stratified by age group (0-17,18-49, and ≥50). Patients with known osteopenia or osteoporosis before IBD diagnosis were excluded.

Results

We included 32,263 patients with IBD and 89,423 non-IBD controls [48% female, 56% Crohn’s disease (CD)]. Time to first fracture was significantly shorter in female pediatric patients (p=0.01), in both female (p=0.0004) and male (p=0.003) adult and elderly patients (p<0.0001) (Figure 1). Time to diagnosis of osteopenia/osteoporosis in patients with IBD was significantly shorter in all age groups and genders. Rate of fractures was significantly higher in patients with IBD versus controls for all groups, and rate of osteopenia/osteoporosis was also higher in patients with IBD in all groups (Table 1). In a subgroup analysis, fracture rate did not significantly differ between CD and ulcerative colitis (UC) for all age groups, but osteopenia and osteoporosis were significantly higher in CD compared to UC in all age groups. The hazard ratio for fractures in the pediatric IBD population was 1.02 (0.88-1.16) for males and 1.17(0.95-1.44) for females, in adults 1.08 (0.99-1.16) for males and 1.12 (1.02-1.21) for females, and in the elderly 1.2 (1.08-1.32) for males and 1.19 (1.08-1.31) for females. Arthritis was significantly associated with fracture risk [HR: children 1.47 (1.15-1.88); adults 1.3 (1.17-1.44); elderly 1.19 (1.07-1.30)]. In adults and elderly, older age at diagnosis, chronic obstructive pulmonary disease, diabetes and long-term proton pump inhibitors usage were also associated with a significant increase in fracture risk.

Conclusion

In this large nationwide cohort, patients with IBD had significantly higher risk for bone fractures than matched controls in almost all age groups, with no difference between CD and UC. Additionally, the rate of osteopenia and osteoporosis was higher in patients with IBD, suggesting that further efforts need to be invested in bone health of this at-risk population.Read more P816 Baseline disease severity of patients with Ulcerative Colitis influences rapid symptom relief under filgotinib treatment: post hoc analysis of the phase 2b/3 SELECTION studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Filgotinib (FIL) is an oral, once-daily, Janus kinase 1 preferential inhibitor approved in Europe and Japan for the treatment of ulcerative colitis (UC). A recent analysis of SELECTION trial data (NCT02914522) showed rapid and sustained improvements in UC symptoms with FIL 200 mg (FIL200) treatment in patients with moderate-to-severe UC.¹ Here we assess symptomatic remission rates over time with FIL200 induction treatment according to baseline UC disease severity (partial Mayo Clinic Score [pMCS]).

Methods

SELECTION was a phase 2b/3 randomized, double-blind, placebo-controlled study. Patients aged 18–75 years were randomized (2:2:1) to receive FIL200, FIL 100 mg or placebo once daily for 11 weeks in induction study A (biologic-naive patients) or induction study B (biologic-experienced patients). In this post hoc analysis, proportions of patients with symptomatic remission (Mayo rectal bleeding sub-score of 0 and Mayo stool frequency sub-score of ≤ 1), from days 2 to 15 and weeks 2 to 10 of the induction study, were analysed at each timepoint by baseline pMCS (pMCS ≥7 and pMCS <7 [cut-off previously used for severe and moderate disease, respectively]²). Symptomatic remission rates were compared between the pMCS ≥7 and pMCS <7 groups within the FIL200 and placebo arms using a Cochran–Mantel–Haenszel test adjusted by study randomization stratification factors. Nominal p values <0.05 were considered statistically significant.

Results

At day 2, symptomatic remission rates with FIL200 treatment were significantly higher in patients with baseline pMCS <7 than in those with baseline pMCS ≥7 (8.4% vs 1.1%, p=0.009 [induction study A]; 8.8% vs 0.7%, p=0.004 [induction study B]) (Figure A and B). From days 2 to 15, symptomatic remission rates increased in both groups and, except for day 7 for induction study A and day 9 for induction study B, continued to be significantly higher in those with baseline pMCS <7. From week 2, symptomatic remission rates with FIL200 treatment generally continued to increase in both pMCS ≥7 and pMCS <7 groups (Figure C and D). By week 10, symptomatic remission rates with FIL200 treatment were no longer significantly different between those with baseline pMCS <7 and those with baseline pMCS ≥7 (54.8% vs 43.3%, p=0.124 [induction study A]; 39.5% vs 26.4%, p=0.099 [induction study B]).

Conclusion

Symptomatic response to FIL200 occurs more rapidly in patients with lower UC disease severity than in those with higher UC disease severity. However, converging response rates over 10 weeks of treatment leads to symptomatic remission regardless of baseline UC disease severity.References1. Danese S et al. Am J Gastroenterol 2023;118(1):138–472. Panés J et al. J Crohns Colitis 2019;13:1148–57Read more P1025 Analysis of the Clinical Characteristics of Elderly-onset Crohn's DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The prevalence of Crohn's disease in the elderly is increasing today. The purpose of this study was to analyze the clinical characteristics of elderly-onset patients with Crohn's disease and compare with non-elderly-onset adult patients.

Methods

All Crohn's disease patients with onset aged 60 years and older at our Inflammatory Bowel Disease Center in recently ten years were retrospectively included. The elderly were compared with adult patients aged 18-59 at the time of onset, who were matched according to diagnosis time and gender by a 1:3 ratio of propensity score matching. After matching, the clinical data were recorded and analyzed to compared between the two groups of patients.

Results

A total of 68 patients were included, including 17 patients in the elderly-onset group and 51 patients in the non-elderly-onset adult group. The mean age of diagnosis in the two groups was 30.3±8.7 years and 63.9±4.24 years, and the mean course of disease was 30.3 months and 63.9 months, respectively. According to the Montreal classification, most elderly patients presented with L3 (70.6%) and B1 (58.8%), no cases involving the upper digestive tract or multiple lesion sites, showed mild disease activity (76.5%). The elderly group had fewer intestinal complications and parenteral manifestations. The medication types of elderly are 5-aminosalicylates (52.9%), traditional immunosuppressive agents (45.6%) and enteral nutrition preparations (29.4%) being the more frequent types of medications used, and glucocorticoids and biologics being used less frequently. Exposure to two or more IBD medications was 31.4% and 52.9% in the non-elderly onset adult group versus the elderly onset group, respectively (p=0.110). During follow-up, symptoms such as diarrhea (11.8 vs 5.9%), abdominal pain (35.3% vs 17.6%) and weight loss (11.8% vs 3.9%) were more common in the elderly-onset group. Elderly patients had more hospitalizations on average (0.22 vs. 1.12). 40.7% of elderly patients underwent CD-related surgery during the duration of their disease, with 50.0% of patients undergoing reoperation.

Conclusion

Compared with non-elderly-onset adult patients, elderly-onset patients with Crohn's disease are more common in women, and the lesion mainly in the ileum and ilecolon; the disease behavior is mainly B1; nearly half of the patients have intestinal complications The elderly have atypical clinical manifestations, basically haven’t family history of IBD, take longer to diagnose, have more underlying diseases, more hospitalizations on average, and are more likely to have complications. They are more likely to receive conservative treatment, but with more frequent medication adjustments and a higher likelihood of undergoing CD-related surgery.Read more P862 Effects of induction and maintenance therapy with risankizumab on health-related quality of life outcomes in patients with moderately to severely active ulcerative colitis: A post-hoc analysis of Phase 2b/3 trialsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Ulcerative colitis (UC) has a detrimental impact on patients’ health-related quality of life (HRQoL).¹ Long-term treatment goals for patients with moderately to severely active UC include restoration of HRQoL. This post-hoc analysis evaluated the effect of induction and maintenance treatment with risankizumab (RZB) on HRQoL outcomes.

Methods

Data from two Phase 2b/3 clinical trials (INSPIRE induction: NCT03398148 and COMMAND maintenance: NCT03398135) were evaluated. Patients received RZB 1200 mg intravenous (IV) or placebo (PBO) induction treatment at weeks 0, 4, and 8. Patients with a clinical response per Adapted Mayo score to RZB IV were randomised 1:1:1 to subcutaneous (SC) RZB 180 or 360 mg, or placebo (PBO [RZB withdrawal] SC) every 8 weeks for 52 weeks of maintenance. The proportion of patients achieving a meaningful within-person change (MWPC) for each HRQoL outcome was reported. HRQoL outcomes included Functional Assessment of Chronic Illness Therapy-Fatigue, disease-specific instruments such as Inflammatory Bowel Disease Questionnaire (IBDQ) and Ulcerative Colitis Symptom Questionnaire (UCSQ), as well as generic quality-of-life questionnaires like Work Productivity and Activity Index-Ulcerative Colitis (WPAI-UC), 36-Item Short-Form Survey (SF-36), and EuroQoL 5 Dimensions 5 Levels. MWPCs were measured from baseline to induction Week 12 and to maintenance Week 52. Estimated differences in proportions with 95% confidence intervals and p-values between RZB and PBO were compared using the Cochran-Mantel-Haenszel test adjusting for baseline strata.

Results

For RZB 1200 mg IV (n=650) versus PBO IV-treated (n=325) patients, a greater proportion of patients achieved MWPC across all HRQoL outcomes at Week 12 of induction (p<0.01; Table). At Week 52 of maintenance, a greater proportion of patients treated with RZB 180 mg SC (N=179) versus PBO (withdrawal) SC (N=183) achieved MWPC across all HRQoL outcomes (p<0.05), except for absenteeism from WPAI-UC (p=0.33). For RZB 360 mg SC (N=186) versus PBO (withdrawal) SC, a greater proportion of patients achieved MWPC for UCSQ, IBDQ, and SF-36 physical component summary (all p<0.05).

Conclusion

In this analysis, a greater proportion of patients treated with RZB versus PBO achieved MWPC on various HRQoL outcomes after completing 12-week induction IV therapy. HRQoL improvements were sustained up to Week 52 of treatment. This suggests RZB has the potential to help patients achieve restoration of HRQoL as a long-term goal of treatment in patients with moderately to severely active UC.1. Mavroudis G. Therap Adv Gastroenterol. 2022;15:17562848211062406.Read more P1062 Effectiveness and safety outcomes beyond five years of IBD patients treated with vedolizumab. The LONG-LIVE IG-IBD studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Long-term real-life data on vedolizumab (VDZ) are scarce. In this study, we aim to evaluate the long-term outcomes of patients (pts) with inflammatory bowel disease (IBD) who received VDZ.

Methods

The LONG-LIVE is the long-term extension (LTE) of the LIVE study, including IBD pts who had started VDZ from 04 to 06/2017 at 47 Italian centres affiliated with IG-IBD, prospectively followed-up to 06/2019. Data on therapy withdrawal, clinical and endoscopic activity, need for surgery/hospitalizations, deaths, and serious adverse events (SAEs) were retrospectively extracted from 07/2019 up to the last available follow-up (fup).

Results

782 (70%) pts were enrolled in the LTE (394 CD, 388 UC), 316 (40%) of whom had already definitively discontinued VDZ; 43% were female, mean age was 53±16 years, mean disease duration was 17±9 years, 76% of patients were bioexposed to anti-TNFα therapy. Among the 466 still receiving VDZ, 204 (44%) subsequently suspended VDZ permanently and 9(2%) temporarily: mean VDZ therapy duration was 113±92 and 311±60 weeks among those who suspended and those who continued VDZ, respectively. Mean therapy persistence was 195±5 weeks (no differences between CD and UC); longer mean persistence was observed in bionaive vs bioexposed CD pts (214±16 vs 178±8 weeks, p<0.05), while no such difference was observed in UC pts. Among pts who continued VDZ throughout the entire LTE, 74% and 50% were in clinical and endoscopic remission, at the last fup. During the LTE, 153(20%) pts (83 CD, 70 UC) received IBD-related surgery after a mean time of 136±87 weeks from VDZ start; 85 (11%, 54 CD, 31 UC) pts underwent IBD-related hospitalization for nonsurgical reasons. New or recurrent cancers were reported in 17 pts, 3 of which localized in the gastrointestinal tract: mean interval between first VDZ administration and cancer diagnosis was 214 (±95) weeks; 20 non-oncological SAEs were recorded in pts receiving VDZ, the most common being infections (n=7), mostly pneumonia. Finally, 15 deaths were reported: 5 due to infections and 5 due to cardiovascular diseases.

Conclusion

About one-third of pts were still receiving VDZ after a fup of more than 6 years, with the majority of them being in clinical remission and more than 50% also having quiescent endoscopic activity at the last observation; bionaive CD patients had longer persistence compared to bioexposed ones. Most IBD-related hospitalizations were due to the necessity of surgery. SAEs were observed in a minority of patients and predominantly consisted of infections; the rates of cancer diagnosis are seemingly in line with those of the general population. Our study strengthens the notion that VDZ is associated with long-term real-life durability in terms of effectiveness and safety.Read more P1117 Molecular and clinical characterization of metabolic associated steatotic liver disease in the setting of immune-mediated inflammatory diseases: a link with cancer risk in IBD?Wed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Growing evidence suggests an increased prevalence of metabolic associated steatotic liver disease (MASLD) in the context of immune-mediated inflammatory diseases (IMIDs). The risk of incident extrahepatic cancers is higher in MASLD. We aimed to clinically and mechanistically characterize IMID-MASLD patients compared to classic-MASLD, and its relation to cancer risk in IBD.

Methods

Ambidirectional, case‒control study including a prospective cohort of IMID patients (IBD, psoriasis, hidradenitis, and spondyloarthritis). MASLD and advanced-MASLD was established by the controlled attenuation parameter and transient elastography, respectively. Controls from the general population were age-, sex-, type 2 diabetes-, and BMI-matched in a 1:2 ratio. Liver biopsies were collected when significant liver fibrosis was suspected. Total RNA was obtained from freshly frozen cases and analyzed by RNA-seq. Differential gene expression was performed with‘limma-voom’. Gene set enrichment analysis was performed using the fgsea R package with a preranked “limma t-statistic” gene list. Data on global cancer prevalence was retrospectively collected on a multicenter IBD cohort.

Results

1435 IMID patients and 2918 controls were initially included. Advanced-MASLD prevalence was significantly higher among IMID patients than controls(p<0.0001). In multivariate analysis, concomitant IMID was an independent and the strongest predictor of advanced-MASLD (adjusted OR 2.587; < 0.001).Transcriptomic data was obtained in 109 patients and showed 87 significant genes differentially expressed between IMID- and classic-MASLD. IMID-MASLD cases displayed an enriched expression of genes implicated in pro-tumoral activities or the control of the cell cycle concomitant with a negative expression of genes related to metabolism (figure 1). A comparable transcriptomic signature was observed in IBD-MASLD, involving genes as IGFBP2, PLEKHA4, or metallothioneins, all of them associated to pour prognosis in renal cell carcinoma (RCC). In the multicentre IBD cohort (n=1905; female 50.5%; mean age 50.7 years, mean follow up: 13.3 years) we observed a global cancer prevalence of 9.0%, with a higher-than-expected RCC prevalence (table 1). Whereas RCC represents 3.2% of all cancers in the general population, it accounts for 8.7% in our IBD cohort, in agreement with our molecular data.

Conclusion

Advanced MASLD has a disproportionately high prevalence in IMID populations. Both conditions can trigger a protumoral condition that can lead to an accelerated form of MASLD independent of classic metabolic pathways and a higher cancer risk, as is the case of RCC in the IBD population.Read more P863 Prospective outcome following ustekinumab treatment in a real-world cohort of inflammatory bowel disease patientsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Therapeutic drug monitoring (TDM) serves as a valuable tool for improving efficacy and reducing rates of drug toxicity .However, the utility of TDM with non-anti-TNF agents (such as Ustekinumab-UST) is less well defined, although it may be useful in optimizing UST posology and improving efficacy. In this study, we aimed to evaluate clinical outcomes and UST plasmatic concentration in real-world IBD patients.

Methods

A prospective study was conducted including IBD patients who initiated UST therapy between August 2020 and June 2023. Clinical outcomes were prospectively collected (clinical remission as Harvey-Bradshaw Index (HBI) <4 or partial Mayo score (pMS)≤1; biochemical remission as fecal calprotectin (FC)<150 g/kg); physician global assessment (PGA) (active/ not active) and patient-reported outcome (IBDQ-9)) and UST plasmatic concentration was assessed by ELISA every 8 weeks for 12 months. The need for drug escalation, surgery, hospitalization, or discontinuation of treatment at the end of the follow-up (September 2023) was recorded.

Results

A total of 91 patients were included (population described in Table 1). After a median follow-up of 12 (9.6-10.7) months, clinical remission was observed in 90.4% of CD and 66.6 % of UC patients, 52.7% presented biochemical remission and 61.5% of IBD patients were inactive by PGA. 81% of patients showed a good quality of life as measured by IBDQ-9 >60 points. 9.9% needed IBD hospitalization and only 1 (1.09%) patient required IBD surgery. UST-dose escalation was indicated for 33% of patients, mainly in UC patients (UC 46.1% vs CD 28.1%; p=0.42). Treatment discontinuation was required in 13.2% (12/91) of patients after a median follow-up of 15 (14.8-19) months, due to loss of response in 66.6% of these patients (Figure 1A).The mean UST concentration at induction (8 weeks) was significantly higher than at maintenance (16 weeks) (9.2 (7.7-10.7) µg/ml vs 4.8 (3.9-5.7); p>0.0001); no differences in UST concentration were found during the maintenance treatment (Figure 1B). UST concentration was not related to age, sex, body mass index, type of IBD, or previous exposure to biological agents. In multivariate analysis, UST concentration >7 µg/ml in maintenance (16 weeks) showed an independent predictive value for IBD hospitalization (OR 7.6, 95% CI 2.5-23.1) and UST-dose escalation (OR 4.1, 95% CI 1.4-11.9) in the next 12 months.

Conclusion

Ustekinumab (UST) is an effective treatment, bringing about clinical remission and an enhanced quality of life for individuals with inflammatory bowel disease (IBD). In our prospective cohort, UST concentration at maintenance serves as a predictive indicator of IBD outcome.Read more P1063 Comparison of all paediatric patients and young adults with Crohn’s Disease treated with ustekinumab in the REALITI Real-World Evidence Effectiveness StudyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Treatment of paediatric patients (pts) with Crohn’s disease (CD) can offer some challenges to providers. There is an urgent need to inform prescribers about paediatric efficacy, safety, and dosing. REALITI evaluated the effectiveness and safety of ustekinumab (UST) routine clinical care in paediatric pts (age 2 to <18) regardless of disease severity or baseline corticosteroid use. Reference data are shown for young adults (age 18 to 25) with CD, for whom UST is approved. Data were obtained from the ImproveCareNow (ICN) Registry.

Methods

Data from pts from ICN with CD initiating treatment with UST between 10 January 2010 and 29 February 2020 were evaluated. A supplemental, retrospective chart review collected data not in ICN. The primary endpoint was clinical remission (Short Paediatric CD Activity Index [sPCDAI] score ≤10) at Week (Wk) 52. Data were summarized descriptively, and the proportion of pts achieving clinical remission and associated 2-sided 95% confidence intervals (CI) were calculated along with rates of inflammatory bowel disease (IBD)-related hospitalization and surgeries and serious/opportunistic infections.

Results

Overall, 479 pts in ICN with CD were treated with UST. We report an analysis of paediatric pts (n=348) compared to young adults (n=131). Most paediatric pts (98.9%) and young adults (95.4%) had received prior biologic therapy, with approximately half (47.1% and 50.4%, respectively) receiving corticosteroids at baseline. Slightly higher proportions of pts had moderate to severe disease (sPCDAI ≥30) among paediatric pts (49.7%) vs young adults (44.8%). Clinical remission at Wk52 was achieved in 30.2% of paediatric pts (105/348; 95% CI: [25.6%, 35.2%]) vs 28.2% of young adults (37/131; 95% CI: [21.2%, 36.5%]) (Figure 1A). Clinical remission rates decreased slightly over time from Wk 20-52 (Figure 1B); discontinuation rates through WK 52 remained low and were similar between groups (21.0%, 22.9%, respectively).Overall, 31.9% of paediatric pts and 19.8% of young adults had IBD-related hospitalizations; IBD-related surgery was reported in 16.1% and 9.2% of pts, respectively. Serious infections occurred in 7.5% of paediatric pts and 3.8% of young adults. Rates of opportunistic infections were low (1.4%, 0%, respectively).No events of tuberculosis, malignancy, or anaphylaxis requiring UST discontinuation occurred. One death, deemed by investigators as unrelated to IBD or UST treatment, was reported among paediatric pts; no deaths were reported among young adults.

Conclusion

Using real-world data from the ICN Registry, the remission rates for using UST to treat CD were found to be generally comparable between paediatric pts and young adults. No new safety signals were identified.Read more P1138 Long-term Epidemiological Trends in Emergency Hospital Admissions and Hospitalizations of Patients with Inflammatory Bowel Diseases in one of the biggest metropolises in western Poland in years 2010 to 2021Wed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

A worldwide significant dynamic shift in the incidence and clinical course of Inflammatory Bowel Diseases (IBD) has been observed in the past years. One key indicator that embodies this variability is the necessity for urgent hospitalisation due to exacerbations of Crohn's Disease (CD) and Ulcerative Colitis (UC). The objective of this study was to assess this phenomenon in the Poznan Metropolis, one of the biggest metropolises in western Poland, over a 12-year timeframe.

Methods

Using the National Health Fund's database, urgent hospitalisations of patients with CD or UC from 2010-2021 were identified, and defined as unplanned admissions to emergency departments and inpatient units in Poznan Metropolis hospitals, which required hospitalisation. The ratio of emergency to planned hospitalisations were compared in two identical timeframes: 2010-2015 vs. 2016-2021 and, additionally, during the COVID-19 pandemic years 2020-2021 vs. 2018-2019. The data were analysed and compared according to diagnosis, age, gender and length of hospitalisation.

Results

The numbers of urgent and planned hospitalisations in regard to predefined time periods are shown in Table 1. The rate of acute to planned hospitalisations from 2010-2015 vs. 2016-2021 was 27% (809/3006) vs. 44.5% (1131/2540) (p <0.0001). It increased significantly in all defined categories, except for patients over 60 years of age, where an insignificant decrease from 79% to 71% (p=0.4) was noted. Lower hospitalisation rates were observed among men compared to women (2010-2015: 28% vs. 46%; 2016-2021: 25% vs. 43%). The COVID-19 pandemic posed a paramount challenge to global healthcare systems. However, a statistically significant decrease in the rate of urgent to planned hospitalisations was only found in CD patients (47% vs. 34%; p=0.02; Figure 1). No impact on hospitalisation duration was observed during the COVID-19 pandemic as compared to 2018-2019.

Conclusion

Despite ongoing therapeutic advances, IBD remains a substantial challenge to healthcare systems, as evidenced by the increasing trend in urgent hospitalisations over time, regardless of the diagnosis, particularly among women. The COVID-19 pandemic significantly triggered global economic and healthcare crisis. However, the repercussions on the treatment of IBD patients in our Metropolis were inconsequential.Read more P864 The Effect of Ustekinumab on Mucosal Inflammation in Paediatric Crohn’s Disease: The REALITI Real-World Evidence Effectiveness StudyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Crohn's disease (CD) research using real world evidence (RWE) has been hampered by lack of validated endoscopic outcome measures. The recently validated Simplified Endoscopic Mucosal Assessment of CD (SEMA-CD) provides a reliable way to evaluate mucosal inflammation in paediatric CD patients (pts), making it suitable for use in clinical practice and relevant to real world data. REALITI is a RWE study of the effectiveness and safety of ustekinumab (UST) in paediatric pts.

Methods

REALITI used data from pts with CD in the ImproveCareNow (ICN) registry. Colonoscopy reports (reports) from 2010-2020 identified by chart review were redacted and uploaded to the registry. Central endoscopy readers underwent SEMA-CD training and were randomly assigned to score reports. No reader reviewed reports from their own institution. Three readers independently scored reports blinded to each other’s scores and to clinical information. Demographic and clinical data, prospectively recorded in ICN, were summarized and compared between pts with and without endoscopy. Clinical remission was defined as Short Paediatric CD Activity Index (sPCDAI) ≤10 and endoscopic remission as SEMA-CD ≤1.

Results

Analyses of mucosal inflammation by SEMA-CD in 114 pts age 2 to <18 yr with moderate-severe CD (sPCDAI ≥30) and body weight ≥40 kg at UST initiation (baseline) and after 52 weeks (wk) of treatment are reported. Overall, 77/114 pt had ≥1 report during the study and 20 had a report at Wk 52. Baseline median age of all pts was 16 yr (interquartile range [IQR] 15-16). Pts with endoscopic assessments (N=77) vs pts without (N=37) were more often female (56% vs 41%) and had more ileocolonic disease activity (73% vs 54%), perianal disease (39% vs 35%), and stricturing phenotype (B2; 10% vs 5%), respectively. No pts had B2/B3 phenotype. At baseline, median sPCDAI for all pts was 40 (IQR 35-50; N=114) and median SEMA-CD was 8.5 (IQR 5-13; N=38). At Wk 52, 4/20 pts (20% [95% CI, 8.1%, 41.6%]) were in endoscopic remission. Despite small sample sizes, there appears to be lower clinical remission rates at Wk 52 in pts with baseline endoscopic assessments (17/77; 22.1% [95% CI, 14.3%, 32.5%]) vs without (10/37; 27.0% [95% CI, 15.4%, 43,0%).

Conclusion

Use of SEMA-CD to assess mucosal inflammation in paediatric pts with moderate-severe CD treated with UST demonstrated rates of endoscopic remission similar to clinical remission at Wk 52. Endoscopy was performed more often in sicker pts, with a greater proportion of pts who did not undergo endoscopy achieving clinical remission. Future routine SEMA-CD assessment of mucosal inflammation in clinical practice may improve analyses in observational and retrospective studies.Read more P1064 Upadacitinib is safe and effective in Ulcerative Colitis patients with prior exposure to TofacitinibWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Upadacitinib is a novel selective Janus Kinase (JAK) inhibitor which has recently been approved for use in ulcerative colitis. Clinical trials have rigorous criteria and excluded patients with prior exposure to JAK inhibitors. Given limited real-world effectiveness data we examined outcomes of patients treated with upadacitinib for ulcerative colitis in a real-world population, with a focus on prior tofacitinib exposure.

Methods

This retrospective, multi-centre study recruited patients commencing upadacitinib for moderate-to-severe ulcerative colitis from September 2022 until March 2023 from 13 Inflammatory Bowel Disease centres across Australia. Clinical, biochemical, endoscopic and intestinal ultrasound outcomes were recorded at baseline, week 8 and week 16.The primary outcome was a comparison between clinical remission using PRO2 definitions (STRIDE II guidelines) in those with prior Tofacitinib exposure compared with Tofacitinib-naïve. Secondary endpoints included clinical response, corticosteroid free clinical remission (CFCR), biochemical response and transmural remission assessed by intestinal ultrasound (IUS). Adverse events in both cohorts were also recorded.

Results

152 patients were identified and included (Table 1) – 42 tofacitinib-exposed and 110 tofacitinib-naïve. Complete clinical data was available for all patients at baseline, week 8, and week 16.For the overall cohort, the rate of clinical remission was 20% (30/152) at baseline, 78% (119/152) at week 8 and 85% (129/152) at week 16. In patients with prior tofacitinib exposure, the rate of clinical remission was 23% (10/42) at baseline, 72% (30/42) at week 8 and 86% (36/42) at week 16. In tofacitinib-naïve patients, the rate of clinical remission was 19% (21/110) at baseline, 78% (86/110) at week 8 and 84% (92/110) at week 16 (Figure 1). There was no statistically significant difference in rate of clinical remission at baseline (p=0.23), week 8 (p=0.13) or week 16 (p=0.67).There was no statistically significant difference in clinical response, CFCR, biochemical response or transmural remission by IUS between the cohorts.Adverse events were seen in 40 (26%) patients over the course of 16 weeks follow-up. Most common were acne (12%), rash (4%) and nasopharyngitis (4%). No venous thromboembolism, systemic infection or cardiovascular events were observed. These events were spread evenly among both groups (p=0.37).

Conclusion

This is the largest real-world study to show that upadacitinib is effective and safe for patients with moderate to severe ulcerative colitis and prior tofacitinib exposure.Read more P1139 Lymphocytic Colitis: A large case series in the United KingdomWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Lymphocytic colitis, a type of microscopic colitis, was previously thought to be a rare condition. It is a histological diagnosis characterised by chronic loose stools and normal findings on endoscopy. It is now thought that it could be implicated in up to 10% of people with chronic diarrhoea, and has traditionally been associated with certain medications. We conducted a retrospective case analysis of patients diagnosed with the condition on histology between January 2018 till December 2022.

Methods

A list of patients who had undergone colonoscopy and biopsy for chronic diarrhoea, with no evidence of inflammatory bowel Disease (IBD), was generated. The patient’s electronic health records were then manually analysed, and data was collected using certain parameters including presence of autoimmune disease, faecal calprotectin levels/QFIT, smoking status, medication use (NSAIDS, PPI, Statins or SSRIs), colonoscopy findings, treatment choice and treatment outcomes. 121 patients were eligible based on histopathology consistent with a diagnosis of lymphocytic colitis.

Results

The median age was 63, with a 3:2 split of female to male patients. 63% reported painless, chronic diarrhoea lasting more than 6 weeks. 10.7% had painless and bloody diarrhoea, 23% had diarrhoea with abdominal pain. 25.4% had evidence of autoimmune disease. 43% were taking a PPI, 6.6% and NSAID, 41% a statin and 25.6% an SSRI. 27% were active smokers at the time of presentation. 62.8% of patients had a normal colonoscopy report, with the rest having ‘’abnormal reports” due to polyps. Faecal calprotectin levels ranged from 20-954. QFIT was positive in 35% of patients. 34% of patients were treated under a gastroenterologist. Of those who received budesonide only: 46% recovered with no relapse, 20% had relapsed in under 6 months, 16% relapsed after 6 months, 16% did not present again. Of the patients who received loperamide only, 66% reported resolution of symptoms. All histology demonstrated lymphocytosis in the lamina propria, 16% had expansion of the subepithelial collagen band, often termed ‘incomplete Microscopic colitis’.

Conclusion

Use of PPIs, statins and SSRIs are highly represented in the data, compared with general population usage. Treatment with either budesonide or loperamide generally lead to better symptom control, indicating patients should be referred to gastroenterology upon diagnosis. Clinicians should judiciously prescribe the above medications with clear indication and avoid prescribing indefinitely.Read more P865 Screening for low-processed breads - compositional analysis of food additives used in commercially available breadsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Ultra-processed food (UPF) intake has been associated with the development of inflammatory bowel diseases (IBD), particularly Crohn’s disease (CD). Of UPF subgroups, commercially available breads showed greater risk, possibly due to the increasing presence of food additives (FA) like emulsifiers. As bread is a staple food worldwide, often consumed daily, we aimed to screen the ingredients and FA used in bread industry and to assess the availability of low processed breads.

Methods

We consecutively screened breads available at supermarket and health food store chains popular and widely distributed in Israel. Breads, pita breads and buns (excluding products without food labels), were analyzed by dietitians and categorized into one of three categories according to their processing level and FA types. Low processed category included ingredients used in traditional, home-made breads; medium processed category included FA like malt and added fibers; high processed category included FA like emulsifiers and preservatives, previously associated with impact on microbiota composition or implications on IBD.

Results

A total of 233 breads were screened, 160 are available at the supermarket, 56 at the health food store, and 17 in both. We categorized 195 (84%) as highly processed, 9 (4%) as medium processed and 29 (12%) as low processed. We identified 36 different types of FA and ingredients used. Most breads contained emulsifiers- 178 (76%) and –preservatives-189 (81%). The most used emulsifier was sodium stearoyl-2-lactylate (SSL, E-481), present in 86 breads (37%), followed by mono- and diglycerides of fatty acids (E-471), DATEM (E-472e) and carboxymethyl cellulose (CMC, E-466), found in 22%, 16% and 2% of breads, respectively. Interestingly, the emulsifier E-481, previously shown to induce microbial alterations, was found in 86 breads (52%) sold in the supermarket compared to none of the breads available in the health food store. Out of the 5 common preservatives, most of the breads contained calcium propionate (E-282) found in 112 (48%) and potassium sorbate (E-202) found in 42 (18%). Additives like enzymes were present in 159 (68%), gluten was added to 148 (64%) and 88 (38%) breads had added fibers. A greater portion of the breads contained yeast (85%) compared to sourdough (47%), with 30 (13%) containing only sourdough.

Conclusion

Most of the commercially available breads in Israel are highly processed. The use of emulsifiers, preservatives, added gluten and fibers is very common, yet low processed breads are available. These may be more recommended to patients with IBD. Further understanding of the role of FA in IBD etiology may potentially guide dietary recommendations for specific food choices.Read more P1065 Endoscopic Submucosal Dissection for High-Risk Colorectal Colitis-Associated Neoplasia in Inflammatory Bowel Disease: a Real-World Multicenter StudyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Inflammatory bowel disease (IBD) patients have a 2-3-fold increased risk of developing colorectal cancer. High-risk colorectal colitis-associated neoplasia (HR-CAN), including non-polypoid lesions and large non-pedunculated colon polyps, are often not amenable to conventional resection techniques. Aim of this study was to evaluate effectiveness and safety of endoscopic submucosal dissection (ESD) of HR-CANs.

Methods

In this real-world, multicenter, retrospective study, we included consecutive IBD patients referred to nine Tertiary Italian Endoscopy Centers (January 2014 - April 2023) to undergo an ESD or a hybrid-ESD (hESD), for HR-CANs. The primary outcome was rate of en bloc, R0 resection and adverse events (AEs). The secondary outcome was rate of local recurrence, metachronous lesions, and post-dissection surgery.

Results

96 HR-CANs (89.6% non-polypoid, 79.2% left-side colon, 34.8 mm ± 16.2 mm, 15.6% invasive pit-pattern) in 91 patients with colonic IBD (58.2% male, 60.8 ± 12.2 years, 83.4% ulcerative colitis, disease duration of 183 ± 104 months, 14.3% endoscopic activity) were included. ESD and hESD were performed in 82.3% and 17.7% of cases. The final histopathological diagnoses were serrated sessile lesions in 14.6%, low-grade dysplasia in 32.3%, high-grade dysplasia in 38.5%, adenocarcinoma in 14.6%. Overall, en bloc and R0 resection were achieved in 95.9% and 85.4% of cases. AEs occurred in 12.5% of cases, all managed endoscopically and conservatively. After a mean follow-up of 23.4 months, local recurrence and metachronous lesions occurred each in 3.1% (n=3) of cases. Post-dissection surgery was required in 11.5% (n=11) of cases (7 for histopathology, 2 for recurrences, 2 for refractory IBD). At univariate analysis the left site was identified as a predictor of higher rate of en bloc resection (OR 0.07; 0.007-0.77; p=0.02), while the female sex as a predictor of lower rate of AEs (OR 0.17; 0.03-0.81; p=0.02). Further, the invasive pit pattern was associated with higher rate of post-dissection surgery (OR 6.25; 1.6-24.3; p=0.008).

Conclusion

Our findings showed that ESD of HR-CANs, when performed in Tertiary Endoscopy Centers, was effective and safe in patients with colonic IBD. However, further prospective studies including a long-term follow-up are still required to highlight the impact of ESD for IBD patients’ dysplasia-free survival.Read more P1159 Gene and environment interactions in inflammatory bowel disease: a systematic review of human epidemiologic studiesWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Complex gene-environment interaction for Inflammatory Bowel Disease (IBD) remains elusive. This systematic review aims to summarize the current evidence of gene and environment interactions in IBD.

Methods

PubMed, EMBASE, Web of Science and Scopus were systematically searched from inception through July 20, 2022 to identify publications examining the interaction effect of genetic variants and environmental factors in IBD. Two investigators independently screened the title/abstract and full text according to the predefined criteria. All eligible studies were graded using STREGA guideline. The protocol was registered on PROSPERO (CRD42023443071).

Results

4,305 publications were identified and screened, resulting in 36 eligible studies. 17 studies reported statistically significant interactions.The interaction effect of NOD2 and smoking was most frequently investigated and showed variant-specific interaction at rs2066847 regrading risk of Crohn’s disease (CD). Gene-smoking interactions were further identified in 1) other IBD risk genes (ATG16L1, IL23R, CALM3), as well as the IBD-genetic risk score (GRS), 2) detoxification genes (GSTP1 and ΗΜΟΧ1), 3) smoking-associated genes (CHRNA3, CHRNA5, PPP1R3C, BDNF), as well as the general smoking-GRS, and 4) the inflammation cytokine gene (IL-1β) using the candidate gene approach. Using the Illumina immune-focused Chip, another 64 smoking interacting variants were identified.Gene-diet interactions were reported across different nutritional measures, including the intake of fatty acids with CYP4F3 and FADS2, serum level of selenium with SEPHS1and SEPSECS, dietary intake of potassium with IL21, alcohol consumption with IL12B, dietary heme iron intake with FcgRIIA and serum level of 25-hydroxyvitamin D with VDR. No genome wide environment interaction studies (GWEIS) of IBD have been conducted to date, while this strategy holds great potential to unravel the missing heritability influenced by environment factors for IBD.

Conclusion

While past studies have increased insights into potential gene-environmental interactions in the pathophysiology of IBD, current evidence is limited and inconclusive due to lack of replication of presented results, and limited study power. Further research, including GWEIS and clinical trials, is needed for future recommendations on lifestyle and dietary modification, based on individual genetic backgrounds.Read more P699 Identification of A Novel Activated NK-Associated Gene Score Associated with Diagnosis and Biological Therapy Response in Ulcerative ColitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Natural killer (NK) cells are associated with the pathogenesis of ulcerative colitis (UC), while their precise contributions remain unclear. The present study sought to investigate the diagnostic value of activated NK-associated gene score (ANAG score) in UC and evaluate its predictive value in biological therapy response.

Methods

Bulk RNA-seq datasets were obtained from the Gene Expression Omnibus (GEO). GSE11223, GSE87466, and GSE92415 were integrated for diagnosis value analysis. GSE206285 and GSE92415 were used to analyze the prediction of response to ustekinumab (UST) and golimumab (GLM), respectively. The immune infiltration landscape was estimated by single-sample gene set enrichment analysis (ssGSEA) and CIBERSORT. Differentially expressed genes (DEGs) correlated with activated NK cells were identified as activated NK-associated genes (ANAGs). Key ANAGs were screened by protein-protein interaction (PPI) analysis and least absolute shrinkage and selection operator (LASSO) regression.

Results

The immune infiltration analysis revealed a higher abundance of activated NK cells in non-inflamed UC tissues. 54 DEGs correlated with activated NK cells were identified as ANAGs. PPI analysis and LASSO regression were utilized to screen out 4 key ANAGs (SELP, TIMP1, MMP7, and ABCG2). ANAG score was established with the following formula: ANAG score = 0.628 * SELP + 1.574 * TIMP1 + 0.740 * MMP7 - 0.361 * ABCG2 – 18.940. The ANAG scores were significantly higher in inflamed tissues, as well as in biological therapy non-responders (NR) tissues before treatment. The ANAG score demonstrated excellent diagnostic value (AUC = 0.979). Furthermore, according to quartile stratification, patients with a higher ANAG score before treatment were more likely to experience lack of response to ustekinumab and golimumab.

Conclusion

This study established a novel ANAG score with the ability to precisely diagnose UC and distinguish the efficacy of biological treatment.Read more P943 Real world Effectiveness and safety of tofacitinib in patients with Ulcerative Colitis: 6 months follow-up of the French TOFAST studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

TOFAST is an observational, prospective, multicenter cohort study aiming to describe the real-life clinical benefit of tofacitinib in moderate-to-severe Ulcerative Colitis (UC).

Methods

We report the results of the interim analysis after 6 months of follow-up, describing patient's characteristics, effectiveness, including change in daily PRO2 scores [RB and stool frequency (SF)] during the first 14 days and the median time to relief, and safety.Clinical response was defined as a decrease in partial Mayo score (PMS) (≥ 3 points and ≥30%) from inclusion with a concomitant decrease in rectal bleeding (RB) subscore ≥ 1 point (absolute subscore of 0 or 1). Clinical remission was defined as PMS ≤2 with no subscore >1.Symptomatic relief was reported by patients as the time in days from initiation of tofacitinib to improvement of their symptoms. Safety has been been reported as the % of Adverse Events (AE), serious AE and AE of special interest.

Results

88 patients were included in the safety analysis (one patient was excluded from the effectiveness analysis as he did not meet the eligibility criteria) with a median exposure duration of 11.7 [Q1; Q3: 6.0; 22.1] months. Of these patients, 67 completed a 6-month follow-up visit by 15/07/2023 and were included in the effectiveness analysis.At inclusion 59.8% of patients were male with a mean (± SD) age of 37.5 ±13.2 years, a median disease duration of 5.9 years [Q1; Q3: 2.7; 13.1]. 46.5% of patients had pancolitis. The mean total Mayo Score was 8.1 ±2.4. 94.3% of patients had previously received at least one anti-TNF agent, 67.8% vedolizumab and 35.6% ustekinumab.Tofacitinib was initiated at 10 mg b.i.d, in combination with corticosteroids for 35.6% of patients.At 6 months, 53 (77.9%) patients were still treated with tofacitinib, 58.5% at 10 mg BID dose. Corticosteroids were ongoing in 22.9% of patients.Clinical response and remission were observed in 64.2% and 61.2% of patients, respectively.For the 68 (78.2%), patients who reported improvement the median time to relief was 7 days [Q1; Q3: 3.5 ;14.5].PRO2 scores normalization during the first 14 days is shown in the figure.84.1% of patients reported at least one adverse event (AE) and 21.6% reported at least one serious AE. Seventeen (19.3%) infections and 3 (3.4%) cases of herpes zoster were observed as well as one non-invasive low-grade urothelial carcinoma. No major cardiovascular or venous thromboembolic event, nor malignancy or death were observed (Table).

Conclusion

In this real-life cohort of patients with refractory UC, tofacitinib induced a clinical response and remission in over 60% of patients, with symptoms relief observed as early as the first two weeks. AEs were consistent with the known tofacitinib safety profile.Read more P1161 Prevalence of undernutrition in patients with inflammatory bowel disease and improvement after nutritional adviceWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The prevalence of undernutrition ranges from 25% to 70% and severe undernutrition from 1% to 30% among individuals with active inflammatory bowel disease (IBD). The aetiology of malnutrition is multifactorial. There are not many studies that have assessed nutrition after therapy modification and dietary advice.

Aim

To study the prevalence of undernutrition in IBD and the change after nutritional advice.

Methods

In this single-centre prospective cohort study, 218 consecutive patients with IBD were screened. Patients with associated diseases that could lead to undernutrition were excluded (N=18). Nutritional assessment was done as per the European Society for Clinical Nutrition and Metabolism (ESPEN) definition: BMI <18.5 kg/m² or unintentional weight loss >10% were defined as undernutrition and the Malnutrition Inflammation Risk Tool (MIRT) score was calculated. Obesity was defined as per the WHO Asian BMI classification: grade 1 (BMI 25-29.9 Kg/m²) and obesity grade 2 (BMI >30 Kg/m²)¹. Patients were given nutritional advice and therapy was optimized as per disease activity. BMI and MIRT were calculated on subsequent visits to assess response to nutritional advice.

Results

Of 200 patients (median age 39 [IQR 28-53] years; 96 females), 105 had ulcerative colitis (UC), 93 Crohn’s disease (CD), and 2 IBD-unclassified. Fifty-four (27%) patients had undernutrition (28 UC, 25 CD, and 1 IBD-U). Sixty-one (30.5%) patients were obese. At follow up (median duration 24 months), of 37/54 patients with BMI <18.5 Kg/m², BMI increased in 24 (64.8%) and decreased in 13 (35.1%); of 17 patients with >10% unintentional weight loss, 5 (29.4%) had increased weight on follow-up. MIRT score decreased in 24/54 patients (44.4%), remained same in 14 (25.9%), and increased in 16 patients (29.6%). Of the 24 patients with decrease in MIRT score, 7/24 (29.1%) received only dietary advice, 10 (41.6%) received dietary advice and optimization of IBD treatment, and 7 (29.1%) received only optimization of IBD treatment.

Conclusion

The prevalence of undernutrition and obesity in patients with IBD was 27% and 30.5%, respectively. After dietary advice and therapy optimization, nutrition improved in 53.7% while MIRT score decreased in 43.3% of patients.References:1. Girdhar S, Sharma S, Chaudhary A, et al. An epidemiological study of overweight and obesity among women in an urban area of north India. Indian J Community Med. 2016; 41:154-7.Read more P700 The efficacy of adalimumab combined with surgery for rectovaginal fistula in Crohn's disease：a single-center retrospective studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

To assess the efficacy of adalimumab(ADA)combined with surgery in the treatment of Crohn's disease patients with rectovaginal fistulas.

Methods

A single-center retrospective study. The baseline data of patients with Crohn’s rectovaginal fistulas who visited the Anorectal Department of the Affiliated Hospital of Nanjing University of Chinese Medicine from January 2020 to July 2022 and accepted ADA combined with surgery treatment were included. Crohn’s disease Activity Index(CDAI), perianal disease activity index(PDAI) and inflammatory parameters, including Erythrocyte sedimentation rate(ESR) and C-reactive protein(CRP), were statistically analyzed at weeks0, 48. Follow-up was performed every 8 weeks. The outcomes included clinical response, clinical remission, fistula response, fistula remission, fistula remission under MRI, endoscopic response and endoscopic remission.

Results

A total of 43 RVF patients were included, 53.4% (23/43) patients were treated with Seton,44.1% (19/43) patients were treated with Advancement flap and 2.3%(1/43) patient was treated with Fecal diversion, with a median follow-up of 11.0 (2.5-15.0) months. After 48 weeks of treatment, CDAI[325(262,397)vs.197(134,396)], PDAI[8(6,9) vs. 5(3,6)], ESR[31(8,50) mm/h vs. 10(4,28)mm/h]and CRP[4.62(0.85, 14.45)mg/L vs.0.5(0.5,2.14)mg/L] were significantly lower than 0 week (Table 1) . CDAI, PDAI, ESR and CRP at the 48th week of treatment were significantly lower than those before treatment (p<0.05). At the last follow-up, 62.7%(27/43) patients achieved clinical response, 30.2%(13/43) achieved clinical remission. Meanwhile 69.7%(30/43) of patients achieved fistula response,32.5%(14/43) achieved fistula remission(Table 2),and 25.5%(11/43) achieved fistula remission under MRI; A total of 37 patients completed endoscopic re-examination, including 54.0% (20/37) of patients with endoscopic response and 24.3%(9/37) with endoscopic remission.

Conclusion

ADA combined with surgery is effective in the treatment of patients with Crohn’s rectovaginal fistulas.Read more P944 Ustekinumab in refractory Ulcerative Colitis: single-center, real-world experienceWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Ustekinumab, an anti-interleukin 12/23 agent, was approved by the European Medicines Agency in 2019 as a treatment for moderate-to-severe ulcerative colitis (UC). Limited real-world data is available regarding the utilization of ustekinumab in UC, particularly medication persistence and escalation, which are indicators of medication performance in real-world settings. Our aim was to describe our experience with ustekinumab in refractory UC patients.

Methods

This was an observational single-center study on UC patients who received at least one intravenous dose of ustekinumab 16 weeks before data analysis due to active UC (Simple clinical colitis activity index (SCCAI)>5). Data regarding disease activity prior to and post-induction were analyzed. Patients were followed up until the last ustekinumab administration. Clinical response to therapy was assessed at 16, 24,52 weeks, and the end of follow-up. Response was defined as SCCAI<4, and remission as SCCAI≤2. Dose adjustment or IV maintenance was considered part of the treatment regimen. Patients who discontinued ustekinumab due to lack of therapeutic effect or worsening of UC were considered failures. When available, colonoscopy data was analyzed.

Results

Forty-seven patients who received ustekinumab for refractory UC were included. Thirty-eight percent were female, and 34% were former smokers. Median age was 46 [37.5-61.5]; 62% had extensive disease, and 15% had perianal disease. Ninety-three percent received at least one biologic before ustekinumab, and 24% had received a JAK inhibitor. Thirty-eight patients required dose escalation, and 11 were on maintenance IV. Clinical response at week 16 was achieved in 74% and remission in 46%. At 24 and 52 weeks, 65% and 61% were in remission, respectively. At the end of follow-up, 59% of patients had endoscopic remission (Endoscopic Mayo score ≤ 1). Sixty percent continued treatment during a mean follow-up of 12 months [6-21]. No variable was associated with risk of discontinuation. No serious adverse events were reported. Discontinuation of treatment was due to treatment failure in all cases.

Conclusion

Ustekinumab was effective for induction and maintenance in our cohort of UC patients, although a significant proportion required dose escalation. Drug persistence was higher than 50% during the follow-up. The safety profile of ustekinumab was similar to that in controlled studies and other real-world studies.Read more P1186 Unveiling the reality of Collagenous colitis: Beyond its Benign FaçadeWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Microscopic colitis is a cause of chronic watery, non-bloody diarrhoea diagnosed mainly on histology after taking biopsy from essentially normal colonoscopy. Thereby mainly two subtypes can be identified: Lymphocytic and collagenous colitis. So far, no biomarkers for the diagnosis of microscopic colitis have been identified. Hower, despite being benign nature of this disease .it often trigger Two weeks wait (cancer path way) of the in the UK.

Methods

In this study, we analysed all cases of collagenous colitis diagnosed from 2018-2022 in the Northeast London from 5 different teaching hospitals. 104 cases were identified and their electronic health record from hospital and from the primary care physicians (GP) were manually reviewed.

Results

In this cohort, 24% male, 76% female with ratio of (1:3), with mean age of 65 years. Forty percent were active or ex-smoker.Painless watery diarrhoea was the main cause for referral in 90% of cases, 7% had painless bloody diarrhoea, whilst 3% complaint painful bloody diarrhoea. Abdominal pain noted in only 39% cases. Thirty-five (35%) cases noted to have history of weight loss. Among these patients, 27% had Haemoglobin < 130g/L, including 7% had <105g/L. Twenty nine percent had Faecal calprotectin (FCP) > 50 microgram/gm of stool and 14% had FCP >200. Seventeen percent had serum inflammatory marker raised CRP (normal 0-10).Thirteen percent (13%) of these patient trigger two weeks pathway referral as they had positive Faecal immunochemical test (FIT) which used for bowel cancer screening test,Twenty-seven (27%) presents did not require any treatment, got better after stopping suspected medication as a cause, while 73 % require treatment, of whom 5% require treatment with immunomodulator/ Biologics.

Conclusion

In this large series of collagenous colitis, we found that, despite being benign condition, it can present with alarming features which both health care provider and patient should be aware of, in order to avoid unnecessary anxiety. Further studies are needed to identify biomarker of this condition.Read more P740 Results at 52 weeks of Intravenous Ustekinumab as Maintenance Treatment in Patients with Loss of Response to Subcutaneous Doses: A Multicenter Retrospective Observational StudyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Ustekinumab (UST) is indicated for the treatment of Crohn’s Disease (CD) and Ulcerative Colitis (UC). Despite having shown clinical effectiveness in the real world,some patients may lose response over time or need a higher dose to achieve it. In this context, UST intravenous (IV) maintenance has been proposed. The primary endpoint of our study was to evaluate the efficacy and safety of maintenance IV UST treatment in Inflammatory Bowel Disease (IBD) patients who present with partial response or loss of response to subcutaneous UST.

Methods

We performed a multicenter observational retrospective study including patients with active IBD on maintenance treatment with IV UST. The study conducted at 2 hospitals in Andalusia.The clinical response and remission was analyzed at week 12 and 52, defined as either Harvey-Bradshaw Index (HBI) ≤4 for CD or partial Mayo Score (pMS) ≤2 for UC. The reduction of objective markers of disease activity, fecal calprotectin (FCal) and C-reactive protein (CRP) was evaluated. Moreover, UST trough levels were measured pre-and post UST IV maintenance, drug persistence at the end of the follow-up and any adverse events were assessed.

Results

A total of 59 patients were included in the study, with a median age of 41 years [IQR32-52]. 84.7% (50/59) had Crohn's disease (CD). 91.5% (53/59) had previously received at least one biologic or JAK inhibitor treatment. 58.6% (34/59) werepreviously on subcutaneous UST every 4 weeks (Table 1).In patients with CD, the median baseline HBI value was 9 (IQR 6-12), which decreased to 5 (IQR 4-7) at week 12 and 4 (IQR 3-6) at week 52 (p<0.001) (Figure 2A). In patients with ulcerative colitis (UC), the median baseline pMayo value was 8.5 (IQR 6.5-9.0), which decreased to 5.5 (IQR 4.3-6.0) at week 12 and 3 (IQR 2.0-4.8) at week 52 (p=0.017) (Figure 2B). The median baseline FCal was 800.2 μg/g, which decreased to 520 μg/g at week 12 and 220 μg/g at week 52 (p<0.001). Regarding CRP, the median baseline was 7.1 mg/L, which decreased to 4 mg/L at week 12 and 3 mg/L at week 52 (p<0.001).The median UST levels with subcutaneous maintenance treatment were 3.1 mcg/mL (IQR 1.1-7.4) compared to 12 mcg/mL (IQR 9-20) with intravenous treatment (p<0.001) (Figure 2C).Clinical remission at week 12 and 52, was achieved by 47,5% and 64,3% of the patients respectively. At the end of the follow-up, 96.6% of the patients continued with intravenous UST (Figure 2D). No adverse events were recorded in any patient for the duration of the study.

Conclusion

Intravenous UST for maintenance is able to rescue up to 64% of patients who have failed on subcutaneous doses. 97% of patients continue intravenous UST treatment after one year with an excellent safety profile. UST levels increase fourfold.Read more P969 Unveiling the molecular mechanisms of the combination of vedolizumab with JAK inhibitors in Crohn’s Disease through a systems biology and artificial intelligence-based approachWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Clinical evidence supports the combination therapy of vedolizumab (a gut-selective, anti-lymphocyte trafficking drug inhibiting α4β7-integrin) with JAK 1, 2, 3 inhibitors (JAKi) for Inflammatory Bowel Disease. However, the mechanistic explanation for the improved outcomes in Ulcerative Colitis patients treated with vedolizumab plus JAKi remains unknown and even more in Crohn's Disease (CD). In this study we used an unbiased in silico systems biology and artificial intelligence approach to gain a holistic view of the mechanisms that may underpin the potential benefits of the mentioned combination therapy in the treatment of CD.

Methods

The drugs under study -vedolizumab and JAKi- and CD were characterized at protein level by compiling data from extensive literature search. Through it, human protein interaction networks focused on CD protein effectors were generated and used to construct mathematical models using Therapeutic Performance Mapping System (TPMS) technology (Anaxomics Biotech, Barcelona, Spain). Sampling-based methods were employed to assess the impact on CD of the combined therapy vedolizumab plus JAKi and to describe underlying molecular mechanisms.

Results

Characterization of CD allowed identifying 4 pathological processes (referred to as motives-M) underlying the manifestation of the disease: intestinal barrier disruption (M1), increased innate immune response (M2), chronic inflammation and Th1/Th17 adaptive immune response (M3) and tissue remodeling (M4) and the molecular effectors or proteins involved in each motive. The combination of vedolizumab and JAKi induced a high degree of reversion of the effectors altered in CD (54.76%), higher than the percentage reverted by the individual drugs. Combined vedolizumab plus JAKi therapy mainly modulated M3, where both drugs mostly converge although by distinct mechanisms, thus providing additional individual benefits. The combination therapy reverted a great percentage of M3 effectors, for example, CCR9 and FASLG which were increased in CD, were reverted (or downregulated). In addition to M3 modulation, the combination therapy also modulated M1 and M4. In M1, vedolizumab is the one that would provide more complementary mechanisms apart from those that already converge in both drugs. Regarding M4, it seems that main contribution comes from complementarity pathways of the different mechanisms of action of each individual drug.

Conclusion

The constructed in silico models reveal that the combined vedolizumab plus JAKi therapy could modulate a high array of effectors altered in CD, more than any of the therapies alone, by enhancing the effects of the individual drugs, and provide a mechanistic rationale for employing the combination of these drugs as potential therapy for CD.Read more P741 Characterisation of endoscopic improvements with risankizumab treatment in patients with moderately to severely active Crohn’s diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Endoscopy is used to objectively evaluate disease severity in patients with Crohn’s disease (CD), and endoscopic remission is a target for disease control. Ulcer size is associated with longer-term endoscopic remission, so evaluating ulcers may inform longer-term outcomes. Risankizumab (RZB) is an interleukin 23p19 inhibitor approved for adults with moderately to severely active CD. In phase 3 trials, greater proportions of patients with CD achieved endoscopic outcomes including ulcer-free endoscopy with RZB induction and maintenance therapy vs placebo (PBO).^1,2 We further investigated the effect of RZB on endoscopic outcomes by evaluating improvements in Simple Endoscopic Score for CD (SES-CD) components during these phase 3 trials.

Methods

This post hoc analysis used data from the phase 3 induction studies (ADVANCE [NCT03105128] and MOTIVATE [NCT03104413]) and phase 3 maintenance study (FORTIFY [NCT03105102]). Patients received intravenous (IV) doses of RZB (600 mg or 1200 mg) or PBO for 12 weeks, and clinical responders to IV RZB received RZB maintenance therapy (180 mg or 360 mg subcutaneously [SC]) or PBO (withdrawal) for 52 weeks. This analysis evaluated change in SES-CD subscores (size of ulcers, affected surface, and ulcerated surface) at induction week 12 and maintenance week 52 across ileocolonic segments (rectum, left colon, transverse colon, right colon, and ileum); analyses of improvement were based on a nonresponder imputation for patients with baseline subscores > 0 in the specific ileocolonic segment. Data from the induction studies were pooled for analysis; results for RZB 1200 mg IV induction are not reported. Shift data were from patients with available values.

Results

During the induction and maintenance studies, a numerically greater proportion of patients treated with RZB compared with PBO experienced improvements in any ileocolonic segment in SES-CD size of ulcers, ulcerated surface, and affected surface subscores (Figure). In general across each segment, a numerically greater proportion of patients treated with RZB induction and maintenance therapy compared with PBO experienced improvement from baseline SES-CD size of ulcer subscores of 2 or 3 (diameter 0.5–2 cm or diameter > 2 cm, respectively) to subscores of 0 or 1 (none or diameter 0.1–0.5 cm, respectively) at weeks 12 and 52 (Table). Similar patterns were observed for SES-CD ulcerated surface and affected surface subscores. Safety data for the phase 3 studies have been reported previously.

Conclusion

Patients treated with RZB experienced greater improvements in SES-CD components compared with PBO during the induction and maintenance studies.References1. D’Haens G, et al. Lancet. 2022;399:2015–30.2. Ferrante M, et al. Lancet. 2022;399:2031–46.Read more P1187 Persistence of Advanced Therapies in Patients with Inflammatory Bowel Disease: Retrospective cohort study using large healthcare claims database in JapanWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Inflammatory bowel disease (IBD) is a lifelong disease and strategically utilizing advanced therapies is essential. Few studies exist to inform the drug utilization of biologics or JAK inhibitors in Japan. The objective is to describe persistence of index and subsequently used biologics or JAK inhibitors in patients with Crohn’s disease (CD) or ulcerative colitis (UC) in Japan.

Methods

This retrospective cohort study used the Japan Medical Data Center database, which contains claims data from 14 million individuals in Japan. Patients who were diagnosed with CD or UC, and received advanced therapy, including biologics and JAK inhibitors, between January 1, 2010 and September 30, 2022 were included. Patients aged at least 15 years old were required to have no treatment with advanced therapies within 6-month prior to the initiation of index treatments of interest: adalimumab, infliximab, vedolizumab, golimumab, ustekinumab and tofacitinib for CD and UC in Japan. Persistence was defined as having continuous treatment with each therapy over a specified follow-up period (i.e., 6 months, 12 months, 18 months, or 24 months since the index date), without the presence of a pre-defined treatment gap, i.e., 1.5 times the number of days covered by the prior day’s supply.

Results

The numbers of eligible patients with CD and UC during the study period were 1,115 and 1,942, respectively. Among patients with CD, the distribution of index treatment for adalimumab, infliximab, ustekinumab and vedolizumab was 41.4%, 37.4%, 18.2%, and 3.0%, respectively. Among patients with UC, the distribution of index treatment for infliximab, adalimumab, vedolizumab, golimumab, tofacitinib and ustekinumab was 33.6%, 24.8%, 17.5%, 11.2%, 7.3% and 5.6%, respectively. For CD cohort, persistence of ustekinumab was numerically highest in all periods (94.7% at 6 months, 91.3% at 12 months, 88.2% at 18 months and 80.4% at 24 months), followed by infliximab (94.1%, 87.7%, 82.0% and 76.8%, respectively). For UC cohort, highest persistence was observed in ustekinumab through all periods (95.1% at 6 months, 84.0% at 12 months, 81.6% at 18 months and 75.0% at 24 months), followed by vedolizumab (82.0%, 69.7%, 64.2% and 59.4%, respectively). As subsequent treatments, persistence of ustekinumab and infliximab were comparable for CD while the highest persistence was observed for ustekinumab through all periods for UC.

Conclusion

Persistence of advanced IBD treatments available in Japan was investigated. As an index treatment, ustekinumab maintained high persistence through 2 years from the index date both in CD and UC. This data provides valuable information on the management of patients living in Japan with IBD under real-world setting.Read more P970 Iatrogenic adrenal insufficiency on discontinuation of glucocorticoid treatment in children and adolescent patients with inflammatory bowel disease: to screen or not to screen?Wed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Glucocorticoids are a mainstay of inflammatory bowel disease (IBD) treatment, with oral tapering courses frequently used to induce remission or limit flares. Iatrogenic adrenal insufficiency (AI), due to suppression of the hypothalamic-pituitary-adrenal (HPA) axis is an established side effect of exogenous glucocorticoids. The rate of AI in this population is unknown. There is no standard guidance to suggest routine screening in paediatric IBD (pIBD). This study aimed to better understand the rates of AI with a screening and management protocol developed for pIBD patients given glucocorticoid therapy (GT)

Methods

All patients with IBD under 18 years treated with GT (prednisolone) for 3 weeks or longer from March 2022 to August 2023 were identified. Patients on other GT were excluded. Patients were screened for AI by serum early morning cortisol (Vitros Ortho Clinical Diagnostics immunoassay) and ACTH, and if indicated underwent standard short synacthen(SST) testing. Adrenal axis function was divided into normal allowing cessation of GT, or impaired response requiring hydrocortisone maintenance therapy (see figure1). A serum morning cortisol >250nmol/l indicated a normal adrenal axis; whereas dynamic adrenal axis testing was recommended for cortisol of 175-249 nmol/l. Those with cortisol <175nmol were diagnosed with AI and started on maintenance hydrocortisone. Repeat testing with SST was performed 3 monthly to reassess the adrenal-axis. Patients with an abnormal SST at the 6-month mark were referred to endocrinology

Results

14 subjects were identified (8 male),7 with Ulcerative colitis, 4 with Crohn’s disease, 1 with IBD-U,2 with early-onset IBD. Median age at diagnosis was 10 years (range 8 months -14 years). Duration of GT was for an average 3 months (range 6 - 16 weeks). 42%(n=6) initiated GT with IV methylprednisolone before switching to 2mg/kg oral prednisolone (maximum 40mg) for 2 weeks, weaning 5mg every week. At the end of initial GT, morning cortisol was deficient in 42% (n=6), insufficient in 35% (n=5) requiring SST. Of those undergoing a SST at this stage, 60% (n=3) had a normal response, 40% (n=2) demonstrating AI. Overall, 57% (n=8) had significant AI at the end of initial treatment. Repeat adrenal axis testing was offered at 3 months (5 of 8) and at 6 months (4 of 4). AI was noted in 100% and 75% at 3 and 6-month respectively. No child suffered an adrenal crisis during the study period

Conclusion

AI following glucocorticoid therapy is common in this small cohort. Screening for AI should be considered in pIBD patients receiving conventional doses of glucocorticoids longer than 3 weeks, with appropriate advice given. The incidence and risks of iatrogenic adrenal insufficiency (AI) requires further investigationRead more P684 Using a pharmacokinetic simulation model to determine the optimal infliximab intensification strategy to address loss of response in inflammatory bowel diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The optimal dose intensification strategy to address loss of response associated with low infliximab levels remains uncertain. Favorable associations between higher infliximab levels and objective endpoints imply that post-intensification trough and treatment targets may have utility. This simulation study aimed to identify intensification strategies capable of achieving post-intensification trough thresholds associated with aspirational treatment targets in Crohn’s disease (CD) and ulcerative colitis (UC).

Methods

A previously published infliximab pharmacokinetic model, applied to 200 simulated patients, identified those with subtherapeutic(<3.00mg/L) trough levels after 30-weeks of standard dosing, and subsequently applied ten dose intensification strategies (Figure 1) over a further 32 weeks. The proportion of simulations achieving infliximab trough thresholds associated with endoscopic remission (CD >9.7mg/L; UC >7.5mg/L) was the primary outcome, with clinical improvement (CD >7.0mg/L; UC >3.7mg/L) and perianal fistula healing (CD >10.1mg/L) representing secondary outcomes. Outcomes were stratified by intensity of dose intensification, with five deemed intensive (>10mg/kg 8-weekly). The impact of pre-intensification antibodies to infliximab (ATI) on post-intensification trough levels was also evaluated.

Results

The median pre-intensification infliximab trough level was 0.91mg/L (IQR 1.31). Intensive intensification strategies were more likely to achieve infliximab trough concentrations associated with endoscopic remission (UC: 34.76 v 10.56%, CD: 25.80 v 4.92%), clinical improvement (UC: 61.40 v 34.52%, CD: 39.58 v 12.12%) and perianal fistula healing (24.70 v 4.50%, all p<0.01) than standard intensification strategies (Figure 2). When controlling for cumulative (mg/kg) infliximab dose over 32 weeks, strategies that concurrently dose increased and interval shortened achieved the highest trough levels (all p<0.01). Patients simulated to have ATI prior to dose intensification had lower median infliximab trough levels at weeks 30/32 (3.38 mg/L, IQR 5.52 mg/L) compared to those without ATI (3.89 mg/L IQR 6.14 mg/L) across all dose intensification strategies (p=0.015).

Conclusion

This simulation-based analysis highlights the potential of using post-intensification trough level targets to guide dosing strategy and intensity. Combined high-dose, interval-shortened strategies appear to achieve higher infliximab levels, which may be important in the pursuit of stringent endpoints such as endoscopic remission and fistula healing. These findings require validation across real-world cohorts.Figure 1:Infliximab dose intensification simulation protocolsFigure 2:Infliximab trough concentrations stratified by dose intensification strategyRead more P971 The relapse rates and dynamics of disease severity of inflammatory bowel disease after forced biologic treatment discontinuation: Taiwanese multicentre retrospective studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The reimbursement regulations in 2011 for inflammatory bowel disease (IBD) in Taiwan require patients (pts) to discontinue biologic treatment after using the medication for one year and pts can be retreated after ≥ 6 months of forced discontinue. This study aimed to evaluate relapse rates, predictors of relapse and dynamics of disease severity under Taiwan reimbursement policy.

Methods

This was a multicentre retrospective study using electronic medical record (EMR) database to identify the association between clinical variables and relapse after forced discontinuation in the real-world setting. Pts aged ≥ 20 years old with at least 6 months of biologic treatment were further analyzed to identify the disease severity prior to biologic treatment (closest endpoint before receiving 1^st biologic), 1^st forced discontinuation, 2^nd biologic and 2^nd forced discontinuation. EU PAS register number: EUPAS48289.

Results

We identified 455 newly diagnosed IBD pts from February 2008 to March 2020 in Taiwan. The percentage of relapse after biologic discontinuation was 47.0% (N=353), 41.4% (N=87), and 40.0%(N=15) for 1^st, 2^nd and 3^rd biologic treatment cycle (TxC), respectively.Among pts in the 1^st biologic ST, 353 pts were identified who received at least 6 months of biological treatment. Only 87 (24.6%) pts were able to be re-treated for the 2^nd biologic TxC under reimbursement criteria after forced biologic discontinuation.Prior to biologic treatment, the use of anti-diarrheal symptom control treatment (HR: 1.452, p = 0.0186) and IBD-related surgery (HR: 1.434, p = 0.0216) were factors associated with an increased risk of relapse on 1^st biological TxC. Pts who received the 1^st biologic TxC and 2^nd biologic TxC with a long biologic treatment duration at the end of treatment (HR: 0.998, p <0.0001); (HR: 0.998, p =0.0003) were less likely to experience relapse. Consistent results were found in the 3^rd biologic TxC (HR: 0.963; p =0.0292) long biologic treatment duration was a protective factor against relapse.The percentage of severe pts prior to biologic treatment was 43.7% and dropped to 11.4% after receiving the 1^st biologic treatment. However, the percentage of severe pts increased to 32.0% at 1^st forced discontinuation and further rose to 35.7% at 2^nd forced discontinuation.

Conclusion

The predictors of relapse could assist physicians in clinical decision-making especially when pts faced with discontinuation. Proportion of moderate to severe disease severity decreased after receiving each TxC and due to forced discontinuation, half of the pts exhibited moderate to severe disease severity after forced discontinuation, suggesting that one year of treatment time was insufficient to reach the desired therapeutic goals.Read more P1188 Epidemiology and direct healthcare costs of patients with Inflammatory Bowel Disease (IBD) in an Asian cohort in the first year following diagnosisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Inflammatory Bowel Disease (IBD) is a chronic condition requiring multi-disciplinary care with significant investigation and treatment burden. Indeed, the global treatment market has exceeded US$ 20 billion and is expected to exceed 27 billion in 2030. We aim to study the epidemiology and direct healthcare costs of newly diagnosed IBD patients in their first year of diagnosis in Singapore General Hospital (SGH) and identify factors associated with high direct healthcare costs.

Methods

The study included patients identified from a prospectively maintained IBD registry of SGH. We enrolled patients newly diagnosed with IBD from 2015 to 2022. Patients who received prior treatment or investigation at other institutions were excluded. Data on clinical characteristics and direct costs (investigations, medications, clinic visits, hospitalisations and surgeries) were collected.

Results

A total of 199 patients were enrolled across 2015 - 2022. 96 patients had Ulcerative Colitis (UC) and 103 had Crohn’s disease (CD) (Table 1).There were 26 (20-28) new cases of IBD diagnosed at SGH yearly. Direct healthcare costs of patients in their first year of diagnosis remained steady with an overall 7.1% change in total expenditure from 2015 through 2022. A drop in expenditure happened in 2020 and 2021 due to COVID outbreak and country lockdown. (Fig 1A)The mean cost per patient-year (PPY) was US$12995 for CD US$104345 for UC. 10 (8-11) patients required admission within the first year of diagnosis, with a mean hospitalisation cost PPY of $269717 (± 73771). Overall, inpatient costs accounted for 39.3 % (IQR 34.8 - 44) of yearly expenditure (Fig 1B). A median of 16.7% (14.6-22.1) of patients were started on biologics within the first year of diagnosis.Patients with CD had significantly greater mean expenditure than those with UC on imaging ($1036 vs $328, p = 0.001) and biologics ($1535 vs $603, p = 0.033).Patients above the 75^th percentile of mean cost PPY were defined as having high healthcare cost. This was $12265 and $15957 for UC and CD respectively. Factors associated with high costs were hospitalisation (p < 0.001), biologics (p = 0.001), surgery (p = 0.01) for both UC and CD. UC extent, CD behaviour, history of smoking and age> 40 were not predictive of high costs.

Conclusion

Patients with CD have greater expenditure compared to patients with UC in the first year following diagnosis. Biologics use, surgery and hospitalisation are significant drivers of costs. The proportion of newly diagnosed patients requiring admission and their corresponding costs have remained consistent during our period of study. These findings encourage early identification of at-risk patients with institution of treatment to minimise hospitalisation and surgical burden.Read more P707 Real-world Long-term efficacy of ustekinumab in the treatment of Perianal Fistulizing Crohn's disease: Results from a single-center retrospective studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The efficacy of ustekinumab (UST) in treating perianal fistulizing Crohn's disease (PFCD) remains inconclusive. This study aimed to investigate the long-term efficacy and prognostic factors of UST in the treatment of PFCD patients.

Methods

This is a retrospective single-center analysis of PFCD patients who had at least one year of follow-up and began UST treatment between November 2020 and September 2022. The primary outcome was fistula clinical remission at any time point. Secondary outcomes included fistula clinical response, intestinal clinical remission, and response. Factors associated with long-term fistula clinica remission were screened using the univariate analysis, LASSO regression and extreme gradient boosting (XGBoost) model, and visualized using SHAP.

Results

A total of 131 patients were included in the study, the mean follow-up was 70.39 weeks. Among these patients, 51 (38.9%), 72 (55.0%), and 82 (62.6%) achieved clinical fistula remission at weeks 24, 52, and the last follow-up, respectively. 111 patients (84.7%) achieved intestinal clinical remission and 119 patients (90.8%) achieved intestinal clinical response. Ninety-one patients (69.5%) had prior exposure to other biologics. This study did not ascertain a significant difference in the outcome of UST for CD between biologics Naïve and biologics Exposure patients. The XGBoost model integrated eight independent variables: Montreal L3, Montreal A2, CDAI, PDAI, ESR, body mass index, simple fistula, and re-operation events. The model revealed a favourable discrimination ability with AUC was 0.798 in the internal cohorts.

Conclusion

This study defined the effectiveness and eight risk factors of UST in long-term clinical fistula remission in PFCD patients, which is helpful for early identification of UST beneficiaries.Read more P972 Short and long-term outcomes after acute severe ulcerative colitis in children: A Canadian single centre experienceWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The short and long-term course of ulcerative colitis (UC) following an episode of acute severe UC (ASUC) in children is insufficiently characterized. We aimed to assess contemporary outcomes in children hospitalized with ASUC.

Methods

This was a retrospective cohort study of children aged 2-17 years hospitalized with ASUC between 2010 and 2022 at a tertiary center in London, Ontario, Canada. All data were recorded using standardised Case Report Forms, de-identified, and entered into a central database registry using Research Electronic Data Capture (REDCap) Steroid non-response was defined as requirement of medical rescue therapy or colectomy.

Results

A total of 58 children hospitalized with ASUC were included (male: 55.2% [n =32], mean age at admission: 12.2 ± 3.5 years). The majority had extensive colitis (82.4% [n = 42]) at the time of diagnosis. 74% (n = 43) presented within one year of symptom onset and 31% (n = 18) had ASUC as their index presentation with UC. 15.5% (n = 9) of patients had prior purine analogues and 20.7% (n = 12) had received biologics prior to ASUC presentation. Median Pediatric Ulcerative Colitis Activity Index (PUCAI) score on admission was 65.0 (IQR: 60.0 – 75.0). After intravenous corticosteroid therapy 68.9% (n = 40) responded to steroids. Of the patients with steroid non-response (31% [n = 18]), 3.4% (2/58) underwent colectomy and 27.6% (16/58) patients received infliximab rescue therapy. Median PUCAI score was significantly lower on day 3 between steroid responders and steroid non-responders (37.5 vs 60, p <0.01). The short term (3 months following discharge) and long-term (3-12 months following discharge) colectomy rates following discharge were 7.4% (4/54) and 8% (4/50) respectively. Short term and long-term hospitalization rates for UC exacerbation following discharge was 25.9% (14/54) and 16% (8/50) respectively. Similar rates of long-term colectomy and hospitalizations were observed between steroid responders and non-responders. On univariate analysis, no statistically significant factors associated with steroid non-response were identified.

Conclusion

17% of patients hospitalized for ASUC required colectomy within 12 months of presentation. Despite a high initial response to corticosteroids, long term colectomy rates and re-hospitalization rates are still high. Future research should focus on earlier identification and treatment of children at high risk of exacerbation to prevent complications.Read more P708 Multiple Biosimilar Infliximab Switching is Not Associated with Adverse Outcomes in Inflammatory Bowel Disease: A Real-World Effectiveness Analysis in a National U.S. CohortWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Infliximab (IFX) biosimilars are available for inflammatory bowel disease (IBD). Many options of IFX biosimilars exist, however there is a paucity of data on the safety and efficacy of switching between multiple IFX biosimilars. The goal of this study is to evaluate the safety and outcomes in patients who received multiple IFX biosimilars in a National U.S. Cohort of patients with IBD.

Methods

We conducted a retrospective cohort study of IBD patients on maintenance IFX originator from 2017- 2019 in the national Veterans Affairs (VA) healthcare system. Crohn’s disease (CD) and ulcerative colitis (UC) patients were identified using a previously validated algorithm. Cases, exposures and outcomes were confirmed by chart review. Patents on IFX originator were identified by dispensed medication from the VA Corporate Data Warehouse. Patients were classified as no-switch (NS)- receiving originator but no biosimilar during study period, Single Switch (SS)- switch from originator to one biosimilar, or Double Switch (DS)-switch from IFX originator to two different biosimilars. Primary outcome was IBD flare, defined as escalation of steroid, IBD-related Emergency department visit or hospitalization within 12 months. Secondary outcomes were immunogenicity, serious infection, and infusion reaction. Event rates of the DS group were compared to NS and SS groups using univariate and multivariate (MV) logistic regression models adjusting for patient and non-patient factors.

Results

789 patients (487 CD, 298 UC) on maintenance IFX originator were identified. Of these, 410 patients were categorized as NS, 249 as SS, and 130 as DS. Overall, the rate of flare within 12 months was 19.9% (22.2% NS, 15.3% SS, 21.5% DS, p= 0.08), rate of infection was 11.2% (11.5% NS, 8% SS, 16.2% DS, p= 0.056). No statistically significant differences in rates of immunogenicity or infusion reaction were identified between the DS and NS or SS groups. In MV logistic regression including age, race, gender, medication, comorbidity and VA priority status, no significant differences in flares at 12 months was observed between DS (ref) and NS (aOR 1.12, 95% CI 0.68-1.84), or SS groups (aOR 0.64, 95% CI 0.36-1.12). In MV analyses, SS was associated with lower rate of infection compared to DS (aOR 0.41, 95% CI 0.21-0.82).

Conclusion

In a national U.S. cohort of patients with IBD, multiple IFX biosimilar switching was not associated with flare at 12 months compared to patients continued on IFX originator or with a single IFX biosimilar switch. However, DS was associated with increased odds of infection compared to single switch. These findings provide reassurance that multiple IFX biosimilar switching for IBD is effective but further study on infection risks may be warranted.Read more P1189 Clinical features and surgical necessity rate of fistulising perianal disease in newly diagnosed patients with Crohn's disease: Interim analysis of inception cohort registry study of patients with Crohn's disease (iCREST-CD)Wed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Fistulising perianal diseases (FPD) are common in patients with Crohn's disease (CD) in Asia, but the treatment pattern and the proportion of patients who develop new FPD after diagnosis are not clear. An interim analysis of a large registry study was performed to evaluate the difference in prognosis between patients with and without FPD at diagnosis of CD and the incidence and timing of onset of FPD in patients without FPD at diagnosis of CD.

Methods

iCREST-CD is a prospective, non-interventional, longitudinal, observational registry study conducted at 19 tertiary centres in Japan. Patients newly diagnosed with CD from June 2016 to June 2020 based on the diagnostic criteria of the Japanese Guidelines, aged ≥16 years at the time of informed consent with no prior exposure to biologics were enrolled. Patient demographics, clinical data, disease activity and medical treatment record up to June 2022 were used. FPD were defined as a perianal abscess and/ or perianal fistula.

Results

Of the 662 patients with newly diagnosed CD for whom with or without FPD were recorded, 236 patients [35.6%] had FPD at diagnosis (Group A). Of the 426 patients who did not have FPD at the time of diagnosis, 32 patients developed FPD during the observation period (Group B), and 394 patients did not develop it (Group C). The mean age [SD] at the time of CD diagnosis in Groups A, B, and C was 25.0 [8.6], 31.6 [15.5], and 31.7 [14.4] years, respectively. The proportion of female was 21.2%, 34.4% and 37.8%, respectively; L2 disease location was 14.6%, 23.3%, and 18.0%, respectively; and B2+B3 disease behaviour was 27.5%, 53.1%, and 40.6%, respectively. The mean CRP (mg/L [SD]) was 28.5 [33.8], 42.4 [43.6], and 27.1 [36.3], respectively. For disease activity based on HBI score, the proportion with moderate (8≦HBI≦16) and severe (16<HBI) activity was 17.6%, 36.8%, and 24.0%, respectively (Table).The rate of patients who developed FPD was 4.5% (19 patients) by 12 months and 6.5% (28 patients) by 24 months, respectively (Figure).In Group A with a mean observation period (month [SD]) of 27.9 [8.8], 12.3% and 17.3% of patients needed perianal surgery at 12 and 24 months, respectively. In Group B with a mean observation period of 29.7 [7.7], 7 FPD patients [21.9%] subsequently underwent perianal surgery, all within 12 months of FPD onset.

Conclusion

Patients who did not have a perianal abscess or fistula at the time of their CD diagnosis but later developed these problems tended to have numerically higher CD activity at the time of diagnosis and were more likely to require perianal surgery. These results suggest that patients with highly active CD are at risk of developing new FPD and should be carefully monitored.Read more P1005 Dose escalated Infliximab in Inflammatory Bowel Disease - Crohn's Colitis Cure (CCC) Data Insights ProgramWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Infliximab (IFX) is a monoclonal antibody targeting TNF-α and remains a cornerstone of management of Inflammatory Bowel Disease (IBD). A significant number of people with IBD on standard IFX therapy have persistent disease activity and require dose escalation (DE). In Australia and many other healthcare systems, funding through pharmaceutical benefits schemes is only available for standard dosing. We aim to evaluate the role of DE IFX and patient outcomes in a real-world cohort.

Methods

We performed a cross-sectional observational study using data from Crohn’s Colitis Care, a cloud-based IBD specific electronic medical record used in routine care in Australasia. Data were extracted in November 2023 from 14 private and public care centres. DE was defined as dosing interval <8 weeks and/or dosing >5mg/kg. We examined IBD outcomes prior to and 12 months post DE.

Results

A total of 1725 people received IFX, with DE in 762 (44.2%); 65% had Crohn’s Disease (CD), 33% had ulcerative colitis (UC) and 2% IBD-Unclassified (IBD-U), with a relatively even gender distribution (52.5% male). In the DE cohort, median age was 37 years (IQR 27-49); median age at diagnosis was 23 years (IQR 16-32) and median disease duration 11.6 years (IQR 5.8-17.3). DE and standard dose cohorts did not differ by IBD classification, gender, disease duration, age or age at diagnosis. Median drug level was higher 12-months post DE (8.16μg/ml vs 3.65 μg/ml).Faecal calprotectin (FCP) remission rate (FCP <250μg/g) was higher 12 months post DE, as was endoscopic remission rate and patient reported outcome remission (Table 1). The rate of systemic corticosteroids was lower 12 months post-DE than pre-DE. In the DE-IFX cohort, measures of healthcare utilisation were lower 12-months post-DE; hospitalisation (56 vs 146; p<0.001), surgical interventions (41 vs 61; p=0.040), endoscopic procedures (210 vs 397, p<0.001) and radiological investigations (243 vs 343; p<0.001).

Conclusion

Within a large Australasian IBD cohort, many individuals on IFX required DE. DE IFX was associated with improved measures of remission as well as a reduction in several measures of healthcare utilisation. These data will be used to undertake formal health economic analysis to determine the price points at which DE is cost-effective; additional data on quality of life and indirect healthcare costs will be important to include for a robust holistic assessment of value in care.Read more P732 Lack of concordance between patient-reported, physician-reported and objective criteria-based identification of suboptimal control in IBD patients: IBD PODCAST study resultsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Crohn’s disease (CD) and ulcerative Colitis (UC) are inflammatory bowel diseases (IBD) characterized by chronic inflammation of the digestive tract. Increasing evidence highlights the unmet need, the burden of disease, the progressive nature of the disease and subsequent intestinal damage, limited efficacy of current treatments and suboptimal disease management. The IBD-PODCAST study estimates the proportion of patients with CD and UC with suboptimal disease control (DC) in a real-world setting. Criteria for suboptimal control were largely based on STRIDE-II and modified by an expert panel (Tabel 1). We previously reported that a large proportion of patients were identified with suboptimal DC. The aim of the current analysis was to compare the patients’ and physicians’ opinion to these objective criteria of suboptimal DC in this cohort.

Methods

A non-interventional, cross-sectional, multi-center study was conducted. In total 2185 patients were recruited across 103 sites in 10 countries. Details on the subjective evaluation of DC from patients and physician questionnaires were compared to the objective disease criteria identifying patients with suboptimal DC.

Results

While 52.2% and 44.3% of patients with suboptimal DC in CD and UC, respectively, were identified based on objective criteria; only a limited proportion of patients with CD (10.9%) and UC (13.0%) reported their DC as suboptimal. Similarly, a suboptimal DC was identified by a low rate of physicians (15.7% in CD and 17.9% in UC). Impaired QoL was the main reason for suboptimal DC among CD (46.1%) and UC (51.9%) patients. Conversely, lack of biochemical lab parameter normalization was the main reason for suboptimal DC for physicians (46.6% in CD and 51.8% in UC). An aligned definition of suboptimal DC between physicians and patients was found in a quarter of patients with CD (22.3%) and in a third of cases with UC (33.0%). A concordance of suboptimal DC between patient-reported, physician-reported and objective criteria based on STRIDE-II was identified in 7.5% of CD and 12.0% of UC patients (Figure 1).

Conclusion

There is a high percentage of suboptimally-controlled IBD patients in this large multinational real-world cohort suggesting a large disease burden in IBD patients. There is a disconnect between objective criteria for suboptimal DC and the evaluation by the patient and the physician. Objective criteria (incl regular disease monitoring) may be essential to improve alignment in disease management and treat to target approaches. There is a strong need to improve patient-physician communication and to standardize the definition of disease control in order to improve patient management, patient-physician communication2 and the patients’ quality of life.Read more P1226 Determination of oral and gut mucosal microbiome profiles of patients with treatment-naïve ulcerative colitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The oral microbiome in ulcerative colitis (UC) patients and its role in the pathogenesis of the disease are still poorly understood. Although there are studies investigating the composition of oral microbiome in UC, there are no studies on concomitant analyses of oral and colonic mucosal samples in treatment-naïve patients. In this study, the oral and mucosal gut microbiome of UC patients and oral microbiota of healthy individuals (HC) were compared.

Methods

Sixty patients with newly-diagnosed active (mild-moderate severity) UC patients (n=30) and HC (n=30) were included in the study. Dietary habits were stable in the last three months of participants (checked by dietary recall questionnaires) and co-morbidities affecting microbiota profiles were excluded. Multiple colonic mucosa biopsies were obtained from inflamed areas before treatment in UC group. Simultaneously, subgingival plaque samples were analyzed. All samples were identified through next-generation DNA sequencing analysis, evaluated using bioinformatic tests.

Results

The potential signature bacterial species associated with UC were determined by examining of both gut and oral microbiomes. According to the Microbiome Lefse analysis, Prevotella copri emerged as the prominent common species in the colonic mucosal and subgingival plaque biopsies of UC group. Oral microbiome comparison between UC and HC patients revealed increased Haemophilus parainfluenza and Corynebacterium durum species and decreased F. prastnutzii and Akkermansia muciniphilia in the UC group (p<0.022). Comparative Boxplot analysis of bacterial abundance and alpha-diversity, as indicated by the Shannon index data, revealed that the HC group exhibited higher bacterial abundance and diversity in subgingival plaque samples than the UC group. We found significant association of Bacteroides vulgatus, Prevotella copri, Bacteroides fragilis, Parabacteroides merdae in both colonic mucosal and subgingival plaque samples (oral microbiome) of UC patients (p<0.044).

Conclusion

Our study is the first to show the oral and colonic mucosal microbiome relationship in UC. The presence of oral dysbiosis associated with UC in our study supports the hypothesis that UC could be associated not only with gut dysbiosis, as previously observed, but also with an imbalance in the oral microbial communities. Interestingly, we could not detect previously reported species of Streptococcus, Oribacterium, Rothia, Neisseria and Porphyromonas in the oral microbiome samples of the UC group. However, oral and gut microbiome profiles share some common microorganisms such as Prevotella copri and Bacteroides fragilis. Further studies are required for determining the potential role of oral dysbiosis is disease severity.Read more P733 Long-term effectiveness and acceptability of switching from intravenous to subcutaneous infliximab in patients with inflammatory bowel diseases treated with intensified doses: the REMSWITCH-LT studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

We recently demonstrated that switching from intravenous to subcutaneous infliximab is safe and well-accepted at short-term in IBD patients including those with intensified IV regimen. However, the long-term risk of relapse in these patients remains unknown.We assessed the long-term effectiveness and acceptability of switching from intravenous to subcutaneous infliximab in patients with inflammatory bowel diseases (IBDs) treated with or without intensified intravenous regimen.

Methods

In this prospective multicenter observational study, IBD patients in clinical remission (partial Mayo score ≤ 2 or Harvey-Bradshaw index ≤ 4) were switched to a unique dose of subcutaneous infliximab (120 mg every other week). Pharmacological and biological data were collected at baseline, 6 months and at last follow-up (median follow-up : 18 [15-20] months). Relapse was defined as clinical relapse or fecal calprotectin increase ≥ 150 mg/g compared with baseline.

Results

Among 184 eligible patients, 72.3% (n = 133/184) agreed to switch. At M6, a relapse occurred in 10.2% (n = 6/59), 7.3% (n = 3/41), 16.7% (n=3/18), and 66.7% (n=10/15) (P < .001) of patients receiving 5 mg/kg every 8 wks, 10 mg/kg every 8 wks, 10 mg/kg every 6 wks, and 10 mg/kg every 4 wks, respectively. At 18 months, the rate of relapse was 13.6% (n=8/59), 17.7% (n=7/41), 33.3% (n=6/18), and 86.7% (n=13/15) (P < .001) of patients receiving 5 mg/kg every 8 wks, 10 mg/kg every 8 wks, 10 mg/kg every 6 wks, and 10 mg/kg every 4 wks, respectively.Dose escalation led to recapture clinical remission in 82.1% (23/28) of the patients, including 83.3% (15/18) and 80.0% (8/10) in those receiving 240 mg every other week or 120 mg every week, respectively.Infliximab serum levels increased after the switch (P < .0001) except for patients receiving 10 mg/kg every 4 wks. In multivariable analysis, 10 mg/kg every 4 wks regimen (OR= 61.0; [6.0-600.1], p <0.001) and 10 mg/kg every 6 wks regimen (OR=4.7; [1.1-20.2], p = 0.039) had a higher risk of relapse at 18 months as well as reduced (58.3%) or stable (52.6%) infliximab serum levels between baseline and visit 1 compared with increased serum levels (19.7%) (P = 0.006 and P = 0.008, respectively).Patients’ acceptability (10-point scale) was improved by the switch (6.9 ± 1.6 for IV vs 8.6 ± 1.4 at V1 after the switch; P < .0001) and did not decrease over time during SC maintenance regimen 8.8 ± 1.3 at 6 months and 8.8 ± 1.3 at 18 months. No severe adverse event was reported.

Conclusion

Switching from IV to SC infliximab 120mg eow is safe and well-accepted leading to a low long-term risk of relapse in IBD patients. Tight monitoring and escalated dose should be recommended for patients receiving 10mg/kg/6 weeks and 4 weeks, respectively.Read more P1006 Assessing sexual health care needs in patients with inflammatory bowel diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Optimal care of inflammatory bowel disease (IBD) should encompass both physical and mental health. Sexual health is often overlooked, despite contributing significantly to patient quality of life. This study aims to further characterise the impacts of IBD on sexual health using an IBD specific scale and assess patient interest in accessing relevant expertise.

Methods

An electronic survey was emailed to patients with IBD at a tertiary public hospital using REDCap. Assessment of disease severity was based on clinical disease indices: Harvey Bradshaw Index (HBI) for patients with Crohn’s disease (CD); and the Simple Clinical Colitis Activity Index (SCCAI) for patients with ulcerative colitis (UC). The survey also contains de-identified demographic data, basic information about the participant’s IBD and questions derived from both the validated IBD-Specific Female Sexual Dysfunction and IBD-Male Sexual Dysfunction Scales. Comparisons of patient responses from those with clinically active versus inactive disease were made using Fisher’s exact test. Analysis was exploratory and no correction for multiple comparisons was made.

Results

A total of 101 participants took the survey, including 53 females and 48 males which comprised of 38 patients with UC, 57 with CD, three with indeterminate colitis (and three unsure of diagnosis). Age ranged from 18 to 81 years old with a median of 38; 90% of patients had a disease duration of at least 2 years. Patients with CD recorded a median HBI of five (interquartile range three to nine). Patients with UC recorded a median SCCAI of two (interquartile range one to four). Patients with clinically active CD trended toward more significant sexual dysfunction than those in remission across all domains in the sexual dysfunction scale. Patients with active CD were more likely to report that their disease had prevented engagement in sexual activity in the past year (p=0.04) and more likely to be afraid to participate in sexual activity (p=0.01) compared to those in remission. Patients with active UC were more likely to report that pelvic pain affected sexual activity (p=0.03) compared to those in remission. Regarding seeking additional support, 47% of all patients expressed interest in gaining assistance though only 20% have attempted to seek this advice. 36% of participants would wish to be contacted by their treating team if a sexual health service became available at their hospital.

Conclusion

Patients with more active IBD were more likely to report that their illness negatively impacts their sexual health. 74% of participants reported interest in accessing expert advice regarding sexual health, highlighting the need for services specifically addressing sexual health for IBD patients.Read more P734 Super-responders in patients with moderate-to-severe Crohn’s disease treated with subcutaneous infliximab maintenance therapy: A post hoc analysis of the LIBERTY-CD studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The LIBERTY-CD study demonstrated a broad level of benefit for subcutaneous (SC) infliximab (IFX) maintenance therapy compared with placebo in patients (pts) with moderate-to-severe active Crohn’s disease (CD) who responded to intravenous IFX induction. Characterising subgroups of pts with different levels of response could help to better position SC IFX therapy.

Methods

This was a post hoc analysis of 231 pts from the CT-P13 SC arm of the randomised, parallel-group, placebo-controlled LIBERTY-CD study (NCT03945019). Unsupervised group-based trajectory modelling (GBTM) was conducted to deconvolute cohort-level data into response trajectories. Longitudinal patient reported outcomes (PRO-2: abdominal pain and stool frequency) were used to investigate whether pts who received SC IFX maintenance therapy cluster into response trajectories. Efficacy endpoints (clinical remission, endoscopic response and remission, corticosteroid-free remission and comprehensive disease control [CDC] rate) were analysed and compared between different trajectories. Trough levels of IFX (TLI) were evaluated by trajectory throughout the treatment period. Baseline characteristics were analysed in a descriptive manner to explore predictors for super-response.

Results

Four distinct trajectories were clearly separated and stabilised around Week (W) 10–14 (Figure): rapid and sustained improvement (super-responders, n=61), rapid, but slightly less drastic than super-responders, then sustained improvement (fast responders, n=56), gradual then sustained improvement (slow responders, n=63) and partial improvement during the maintenance phase (limited responders, n=51). Super-responders had the highest rates of W54 clinical remission (73.8%; p=0.002), endoscopic response (63.9%; p=0.009), corticosteroid-free remission (63.6%; p=0.007), endoscopic remission (42.6%; p=0.094) and CDC (37.7%; p=0.013) among trajectories (Table). Super-responders also maintained the highest TLI from W10 throughout the maintenance period. Super-responders showed a trend towards lower baseline body weight, body mass index and oral corticosteroid use, but higher Crohn’s Disease Activity Index score and prior biologic/Janus kinase inhibitor use compared to other trajectories.

Conclusion

Distinct subpopulations with different levels of responses were detected by GBTM using data from a large group of pts with moderate-to-severe active CD who were treated with SC IFX for 1 year. Super-responders with rapid and sustained improvements during SC IFX therapy had a higher likelihood of achieving desirable long-term outcomes, with substantial individual benefit (CDC). Baseline characteristics and TLI were associated with super-response.Read more P1227 Revealing lower capacity of microbial metabolism of flavonoids and associated metabolic changes in Crohn’s diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Recent studies highlight the role of interplay between oxidative stress, gut microbiota, and immune response in the etiology of Crohn’s disease (CD). Polyphenols are natural antioxidants which are mainly metabolized by gut microbiota and could modulate the composition of gut microbiota. However, it’s yet reported whether there is difference in polyphenol-degradation capacity of gut microbiota in CD and healthy controls (HCs).

Methods

A comprehensive literature search was conducted on microbial metabolic pathway of polyphenols and the responsible organisms and genes were recorded. The polyphenol-degrading genes were quantified using shortBRED in three clinical cohorts (the First Affiliated Hospital of Sun Yat-sen University (FAH) cohort, PRISM cohort, and HMP2 cohort). Microbiota abundance was analyzed in FAH and PRISM cohort. Polyphenol intake and serum metabolites were assessed in the FAH cohort. Enterotype analysis was performed in FAH cohort. Correlation analysis among polyphenol intake, gene abundance, serum metabolites and bacterial abundance was conducted.

Results

Phylogenetic tree revealed that reported polyphenol-degrading bacteria were mainly distributed to Actinobacteria and Firmicutes. The abundance of flavonoid degradation related genes (mainly flavone reductase, chalcone isomerase and phloretin hydrolase) was significantly decreased in patients with CD in FAH cohort, but not in PRISM and HMP cohort. Difference in abundance of polyphenol-degrading bacteria was observed between CD patients and HCs in FAH and PRISM cohort. In addition, lower polyphenols intake and serum hippuric acid (HA) level were detected in CD patients. Enterotype analysis revealed that CD patients were mainly distributed to Enterobacteriaceae- and Bacteroidaceae-dominated enterotype while HCs were mainly distributed to Ruminococcaceae- and Prevotellaceae-dominated enterotype. Serum HA level was higher in healthier enterotypes (Ruminococcaceae and Prevotellaceae dominant) and positively correlated with flavonoid-degrading organisms and butyric acid-producing organisms. No positive correlation between abundance of polyphenol-degradation genes and polyphenols intake was detected.

Conclusion

The current study summarized the polyphenol metabolic pathway mediated by gut microbiota and quantified genes responsible for polyphenol degradation. Our comprehensive analysis of diet-microbiota-gene-metabolite data revealed a lower capability of flavonoid degradation in gut microbiota and lower HA level in CD patients. Finally, our findings provide a foundation for future work exploring the polyphenol or polyphenol-degrading microbiota interventions in preclinical models of CD.Read more P1008 Efficacy and safety of retreatment with upadacitinib after treatment interruption in ulcerative colitis: Data from the phase 3 open-label extension study U-ACTIVATEWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Upadacitinib (UPA) is an oral reversible Janus kinase (JAK) inhibitor designed to preferentially inhibit JAK1 approved for the treatment of moderately to severely active ulcerative colitis (UC). UPA may be temporarily discontinued for many reasons including adverse events (AEs) and lack of efficacy.¹ As clinical consequences of discontinuing and restarting UPA are yet to be characterised, here, we assess the efficacy and safety of UPA retreatment in patients (pts) who lost response following UPA treatment withdrawal.

Methods

Pts with a clinical response to 8 weeks’ (wks) UPA 45 mg once daily (QD; UPA45) induction therapy in the Phase 3 U-ACHIEVE or U-ACCOMPLISH studies were re-randomised to placebo (PBO), UPA 15 mg QD (UPA15) or UPA 30 mg QD (UPA30) for the 52-wk maintenance phase of U-ACHIEVE. Pts randomised to PBO who lost response could enter the long-term extension (LTE), U-ACTIVATE, and be retreated with UPA15. Efficacy was analysed (i) at wk 4 of the LTE and (ii) at wk 48 of the LTE among pts with an inadequate response to UPA15 who dose escalated to UPA30 between wks 2 and 36. Exposure-adjusted event rates (EAERs) of treatment-emergent AE (TEAE) were assessed throughout.

Results

Of 223 pts with a clinical response to UPA45 induction randomised to PBO during maintenance, 112 (50.2%) lost response (mean [standard deviation (SD)] days to loss of response: 135.4 [84.6]) and 110 subsequently entered the LTE. Pts with loss of response vs those without were more likely to have a history of inadequate response, loss of response, or intolerance to ≥1 biologic (57.1% vs 46.8%, respectively) or corticosteroid use at baseline (42.0% vs 33.3%). After 4 wks of retreatment with UPA15, 75/108 (69.4%) and 39/108 (36.1%) pts achieved clinical response and remission, respectively (Figure A). In total, 38 (34.5%) pts dose escalated to UPA30 (mean [SD] days to escalation: 80.3 [57.8]); 30/31 (96.8%) and 22/31 (71.0%) achieved clinical response and remission at wk 48 of retreatment, respectively (Figure B). For safety during maintenance, 225 pts with 128.7 patient-years (PYs) of exposure (loss of response [n=112], 42.6 PYs; no loss of response [n=113], 86.1 PYs) were analysed. Generally, the EAERs of serious TEAEs were numerically lower in patients with vs without loss of response. However, patient years of exposure were low, restricting interpretation. During the LTE, EAERs were generally similar in pts who underwent dose escalation vs all pts.

Conclusion

In pts who experience loss of response following UPA withdrawal, efficacy can be recaptured following retreatment with UPA15 and UPA30. No new safety signals were identified.Reference1. Sandborn WJ, et al. Gastroenterology. 2020;158(8):2139−2149.e14.Read more P735 JAK inhibitors and S1P receptor modulators for the treatment of antibiotic refractory chronic pouchitis: an ECCO CONFER Multicentre Case SeriesWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Data regarding effectiveness and safety of JAK inhibitors and S1P receptor modulators in chronic antibiotic refractory pouchitis (CARP) are lacking. This ECCO-CONFER project collected cases of CARP treated with JAK inhibitors or S1P receptor modulators.

Methods

This retrospective multicentre study collected cases across Europe through the ECCO-CONFER project, including patients with ulcerative colitis (UC) diagnosis who underwent proctocolectomy with ileal pouch anal anastomosis (IPAA), treated with JAK inhibitors or S1P receptor modulators for CARP and at least three months of follow up. Main outcomes were steroid and antibiotics-free clinical response at three months (T3) for each drug, defined as clinical part of modified Pouchitis Disease Activity Index (mPDAI) reduction by ≥1 points, steroid and antibiotics-free clinical response at 1 year (T12) assessment, defined as mPDAI reduction by ≥2 points, steroid and antibiotics-free clinical remission (mPDAI=0) at T3 and T12, endoscopic response at T12 (improvement in PDAI Endoscopic Inflammation subscore reaching <3) and endoscopic remission at T12 (endoscopic PDAI ≤1). Non-response imputation was applied.

Results

Seventeen treatments with small molecules of CARP in 15 patients were collected from nine centres in seven countries. Eight patients were treated with tofacitinib; steroid and antibiotics-free clinical response at T3 was achieved in six patients (75%) and steroid and antibiotics-free clinical remission was achieved in five patients (62.5%). One patient discontinued tofacitinib for loss of response after eight months. Of the patients with at least 12 months of follow-up, steroid and antibiotics-free clinical response was achieved in 50.0% of patients, steroid and antibiotics-free clinical remission in one patient (16.7%), endoscopic response in 50.0% and endoscopic remission in 50.0%. One patient was treated with filgotinib, neither steroid and antibiotics-free clinical response nor steroid and antibiotics-free clinical remission were achieved. Six treatments with upadacitinib were collected: at T3 steroid and antibiotics-free clinical response was achieved in 33.3% and steroid and antibiotics-free clinical remission was achieved in 16.7% of cases. Two cases were treated with ozanimod. At T3 steroid and antibiotics-free clinical response was achieved in one patient (50.0%) and steroid and antibiotics-free clinical remission was not achieved. No side effects were reported. Baseline characteristics and results are summarized respectively in figure 1 and table 2.

Conclusion

In a multiple biologic-refractory population, small molecules might be a suitable treatment option for CARP. Based on current limited data, the use of JAK inhibitors should be further investigated.Read more P1228 The EISER Study: Identifying Microbial Factors Associated with Subclinical Gut Inflammation in Psoriatic Arthritis Patients Who Develop Inflammatory Bowel DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Nearly 8% of patients with spondyloarthritis (SpA) manifest symptoms that are compatible with active inflammatory bowel disease (IBD). It is well established that microbial dysbiosis is associated with different immune-mediated diseases. We therefore hypothesized that the gut microbiome could be a modulator of intestinal inflammation and factor in the pathogenesis of IBD in SpA patients.

Methods

As part of the EISER study, we selected a subset of 193 subjects diagnosed with psoriatic arthritis (PsA), a form of SpA, who had no prior diagnosis of IBD. The presence of subclinical symptoms compatible with IBD was evaluated at time of enrollment. For patients with fCAL levels of 80 µg/g or higher, colonoscopy was performed and histological analysis of biopsies collected during the procedure were used to diagnose IBD. Capsule endoscopy was performed on those patients with a negative colonoscopy result. Stool samples were collected from all participants, and microbial DNA was extracted for shotgun metagenomic sequencing using the Illumina HiSeq platform. Sequenced data was processed using MetaPhlAn 4 to estimate taxonomic composition, MMEDS for overall microbiome analysis, and R for additional statistical analyses.

Results

Twenty-five out of 193 subjects in our cohort (12.95%) had symptoms that were compatible with subclinical IBD (sIBD) and five patients (2.6% of total) were confirmed to have clinical IBD (cIBD). The use of nonsteroidal anti-inflammatory drugs (NSAIDs) resulted in significant differences in overall alpha (Shannon entropy, p=0.03) and beta microbial diversity (PERMANOVA, p=0.043), while the use of proton-pump inhibitors (PPI) resulted in significant differences in beta diversity (PERMANOVA, p= 0.036). Patients with cIBD had significantly higher abundance of taxa including Prevotella copri and Prevotella stercorea. P. copri, P. stercorea and fCAL were all significantly elevated in cIBD patients (Wilcoxon’s p=0.0278, 0.0007, 0.0161), although with a larger effect size in P. copri and P. stercorea (Cohen’s D: P. copri = 1.074; P. stercorea = 1.269; fCAL= 0.629). fCAL was also significantly elevated in patients who used PPIs (p= 4.456e-11), while P. copri and P. stercorea abundances were not impacted (Wilcoxon’s p: P. copri = 0.2394; P. stercorea = 0.0643).

Conclusion

Microbiome composition was impacted by the use of NSAIDs and PPI. We identified taxa differentially enriched in cIBD patients, including Prevotella copri and P. stercorea. Importantly, while fCAL was significantly higher in cIBD patients, its discriminatory power was not as strong as that of P. copri and P. stercorea, suggesting that these taxa could be potentially used as biomarkers of co-morbid IBD in patients with PsA.Read more P936 Ultrasound Transmural Remission in Crohn's disease: Different Rate between First and Second Line of Biological TherapyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Ultrasound transmural remission in Crohn’s disease (CD) has been associated with improved long-term clinical outcomes including reduced hospitalization, surgery, escalation of treatment, and a decrease in clinical relapse over endoscopic remission alone. Albeit transmural remission rate (TRR) in CD patients treated with anti-TNF drugs in first line has been well explored, data on TRR using vedolizumab (VDZ) or ustekinumab (UST) as second-line therapy for CD are still limited. The aim of this study was to evaluate the TRR in CD patients in maintenance treatment, comparing adalimumab (ADA) in first line with VDZ/UST in second line.

Methods

From 2018 to 2022 we performed a real world observational longitudinal study evaluating the TRR in all consecutive CD patients in a 2-years maintenance treatment with ADA in first line compared with those treated by VDZ or UST in second line. HBI, fecal calprotectin (FC), SES-CD, and bowel wall thickness (BWT) at ultrasound were analyzed in all patients at the baseline (T0) and after 2 years of maintenance treatment (T1). Clinical remission was defined when HBI was <4. Endoscopic remission was defined when SES-CD was <2. Transmural remission was defined when BWT was <3 mm at a "per-patient" analysis. In accordance with recent literature, laboratory remission was defined when FC was <94 ug/gr.

Results

One hundred and sixty-one CD patients (78 ADA, 41 VDZ, 42 UST) were included in the study. At T1, TRR was recorded in 39.7% of CD patients treated in first line with ADA, and in 17.1% and 21.4% for VDZ and UST, respectively, in second line (ADA vs VDZ/UST: p<0.05; VDZ vs UST: p 0.6). Endoscopic remission rate was 50% for patients treated in first line with ADA, and 31.7% and 35.7% for second line VDZ and UST, respectively (ADA vs VDZ/UST: p<0.05; VDZ vs UST: p 0.7). Laboratory remission rate was 53.8% for patients treated in first line with ADA, and 29.3% and 35.7% for VDZ and UST in second line, respectively (ADA vs VDZ/UST: p<0.05; VDZ vs UST: p=0.5). Clinical remission rate was 58.9% for patients treated in first line with ADA, and 43.9% and 47.6% for second line VDZ and UST, respectively (ADA vs VDZ/UST: p=0.09; VDZ vs UST: p=0.2).

Conclusion

Our findings showed that in CD patients in maintenance treatment with biologics, ADA in first line showed a higher TRR compared with VDZ/UST in second line. Moreover, VDZ and UST showed similar TRR and other outcomes when used in second line.Read more P780 Persistence of Health-related Quality of life decline in IBD patients after the COVID-19 outbreakWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Inflammatory bowel disease (IBD) affects many aspects of a patient’s life and impairs their health-related quality of life (HRQoL). We previously showed that there was a negative impact of the COVID-19 outbreak on the HRQoL of IBD patients in remission. This study aimed to assess if IBD patients in stable, clinical remission could recover their pre-outbreak HRQoL once the global emergency for COVID-19 ended. We also compared their self-perceived stress scores during and after the outbreak.

Methods

We carried out a prospective, observational study on IBD patients with biological treatment and stable clinical remission who had participated in the previous study. Patients filled in the IBDQ9 and the Perceived Stress Scale (PSS) electronically. The results of the IBDQ9 pre-, during, and post-COVID-19 outbreak were compared to determine any changes. PSS scores during and after the outbreak were also compared.

Results

Ninety-three patients in clinical remission were included, with a median age of 43 years; 40% were female, and 78% had Crohn’s disease. Median pre-COVID-19 IBDQ9 was 54 (50-59) and decreased to 50 (46-58) during the outbreak, and post-outbreak was 49 (44-56) (p<0.01). PSS score improved after the outbreak, with a median value of 10 (8-18) during the outbreak and a score of 14 (9-19) after the pandemic. There was a significant negative correlation between the PSS (during the outbreak) and post-outbreak IBDQ9 (r=-0.76, p<0.001). Regression analysis showed that the PSS score during the outbreak was independently associated with a lower post-outbreak IBDQ-9 (p<0.05).

Conclusion

During the COVID-19 pandemic, there was a negative impact on the HRQoL of IBD patients in remission that persists after the outbreak, with higher self-perceived stress scores during the pandemic associated with a lower post-outbreak QoL. The results of this study underscore the long-term impact that unexpected situations can have on IBD patient's HRQoL. Unforeseen circumstances are mostly non-predictable, as the COVID-19 outbreak has shown, and measures to provide high-quality health care, including access to mental care, will hopefully be implemented for IBD patient care.Read more P781 Mirikizumab administration experience from Ulcerative Colitis patients and healthcare providers: Survey data from the LUCENT clinical programWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Mirikizumab (MIRI) is an anti-IL-p19 antibody approved for moderately-to-severely active ulcerative colitis (UC). The recommended dose regimen has 2 parts: MIRI administration begins with intravenous (IV) infusion every 4 weeks (Q4W; 3 total) followed by subcutaneous (SC) injections (2 injections per dose) Q4W (Figure 1). Self-injection of SC MIRI is allowed after patient training. This study explored differences between healthcare provider (HCP) perspectives of UC patients’ experiences and patients’ actual experiences regarding MIRI administration during the LUCENT program. It also assessed HCPs’ own experiences with MIRI administration.

Methods

The study involved two cross-sectional, 30-min, web-based surveys including one for patients and one for HCPs. Patients were eligible if they were enrolled in LUCENT-3 having entered from LUCENT-1 or -2 phase 3 studies or AMAC phase 2 study. HCPs from LUCENT-3 sites were eligible if they administered or oversaw MIRI IV infusions or SC injections during LUCENT-1, -2, -3, or AMAC. Survey questions had responses based on 5-point Likert scales. Outcomes included satisfaction with and acceptability of MIRI administration (Table 1). The survey was completed during LUCENT-3; MIRI SC injection experience at the time of survey varied from >2 to ≥3 yrs.

Results

The surveys were completed by 93 patients from 11 countries and 42 HCPs (gastroenterologist/physician 31.0%, nurse 40.5%, other [coordinator] 28.6%) from 9 countries. Most patients were satisfied or very satisfied with IV infusions (82.8%) and SC injections (91.4%), which was lower than HCPs’ perspectives of patients’ experiences (IV, 92.9%; SC, 100%), but generally similar to HCPs’ own experiences (IV, 81.0%; SC, 95.2%). Consistent with patients’ actual experiences (SC Q4W, 97.8%; two injections, 96.8%), most HCPs thought that patients felt that receiving SC injections Q4W (100%) and receiving 2 SC injections for each dose (92.9%) were somewhat or completely acceptable. Patients (97.8%) were satisfied or very satisfied with MIRI administration overall and 90.3% agreed or strongly agreed that treatment benefits outweighed any administration dissatisfaction. These patient perspectives were similar to both HCP perspectives of UC patients’ experiences (95.2%; 88.1%) and HCPs’ own experiences (97.6%; 95.2%).

Conclusion

Most patients and HCPs were satisfied or very satisfied and acceptable or completely acceptable of MIRI IV and SC administration. Patients’ experiences were similar to HCPs’ perspectives of patients’ experiences as well as HCPs’ own experiences, although there was a tendency for HCPs to perceive patients’ satisfaction to be very satisfied at a higher rate than patients’ actual responses.Read more P1229 The Role and Niche-Specific Adaptation of Malassezia in patients with Ulcerative colitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Accumulating evidence has underscored the role of gut fungal microbiota (mycobiota) in the development of inflammatory bowel disease. We aimed to isolate a Malassezia strain directly from the human intestine mucosal surface from the patients with ulcerative colitis (UC) and investigated its genome and virulence in comparison with the same fungal species isolated from the human skin.

Methods

Mucosal lavage samples were collected separately from colonic areas with and without inflammation in patients with UC. Samples from healthy individuals (HT) were obtained in the same manner as from patients with UC at sigmoid or descending colon. Skin samples were taken from HT in our previous work. DNA was extracted from these lavage samples, and fungal isolation was conducted using PCR amplification with ITS4 and ITS5 primers. Comprehensive analysis and comparison of the genomes, transcriptomes, and virulence between M. globosa gut isolates and those of M. globosa strains isolated from the skin were performed. To determine the contribution of M. globosa gut isolates to exacerbating inflammation, 110⁷ fungal cells were orally gavaged to DSS-induced colitis mouse model for three days.

Results

Total 56 and 11 intestinal water-lavage samples from 29 UC patients and 11 HT were obtained respectively. The α- and b-diversities of mycobiota showed no significant differences between the groups, patients with UC vs. HT or the sites with inflammation vs. non-inflammation of the patient with UC. Malassezia was the fifth most frequently found fungal genus throughout the samples, and live fungal strains belong to 28 and 7 different species were isolated from the patients with UC and HT, respectively. The patients with UC tend to have higher frequency of M. globosa and M. restricta than HT in their gut mucosal surface with inflammation. Whole genome sequencing showed no specific genomic characteristics between gut-isolated M. globosa and skin-isolated M. globosa. However, gut-isolated M. globosa were suffered more from the higher oxygen levels than the skin isolates in different oxygen concentrations. In a mouse model, gut-isolated M. globosa exhibited a more pronounced exacerbation of DSS-induced colitis and elevated production of inflammatory cytokines, including TNF-a, IL-6, IL-12p40, IL-1b, and IL-18, while the skin isolates showed no difference compared to the negative control (Figure).

Conclusion

Our data shed new light on the pivotal role of M. globosa in the pathogenesis of UC, highlighting the potential influence of niche-specific adaptations on the virulence of this fungus. These findings provide critical insights into the complex interplay between the member of the gut mycobiota and host health.Read more P951 Efficacy and safety of tofacitinib for the treatment of moderate- severe ulcerative colitis in biologic naïve patientsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

To assess the rates of clinical response at week 8, biochemical response, steroid-free clinical remission, endoscopic healing and safety data at week 26 of tofacitinib in biologic naive patients with moderate-severe ulcerative colitis (UC).

Methods

This was a retrospective analysis of prospectively collected data extracted from the notes of biologic naïve patients with moderate-severe UC who were treated with tofacitinib in the last 3 years in 5 Greek IBD centers and who had a follow up of at least 26 weeks after initiation of treatment. Tofacitinib was administered at a dose of 10 mg bid for 8 or 16 weeks followed by a maintenance dose of 5mg bid thereafter. Week-8 or -16 clinical response was defined as the reduction in the partial Mayo score of at least 2 points, without concomitant use of any steroid preparation [budesonide, prednis(ol)one, or methylprednisolone]. Steroid free clinical remission at week 26 was defined as a partial Mayo score of ≤1 points without concomitant use of any steroid preparation. Biochemical response at week 26 was defined as any reduction in fecal calprotectin or plasma C-reactive protein concentrations as compared to their baseline levels.Mucosal healing at week 26 was defined as Mayo endoscopic sub-score of ≤1. A safety list of all reported adverse events was completed. Treatment discontinuation due to adverse events was considered as treatment failure, whereas patients needing escalation of the maintenance dose were also considered as non-responders.

Results

Overall, 41 patients (26 males), aged (mean, SD) 35.2 (12.7) years and disease duration of mean (SD) 6.5 (4.8) years were included. UC was extensive in 22, left-sided in 17, and proctitis in 2 patients. Clinical response was seen in 31 (75.6%) and 34 (82.9%) patients at week 8 and 12 respectively.Biochemical response and steroid free clinical remission at week 26 were seen in 35 (85.4%) patients. Endoscopic healing was seen in 29 (70.7%) patients. Adverse events,which did not lead to treatment discontinuation, occurred in 5 patients (hyperlipidemia n=3, elevated liver enzymesn=1, herpes zoster n=1).

Conclusion

In this retrospective real-world ongoing cohort study, tofacitinib demonstrated clinical response at week 8 or 16 and steroid free clinical remission at week 26 in more than 75% of biologic naïve patients with moderate-severe UC with a good safety profile.Read more P782 Comparison of accelerated and standard infliximab induction regimens in Acute Severe Ulcerative Colitis using propensity score: A retrospective multicenter study in a Chinese cohortWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The optimal regimen of infliximab salvage in acute severe ulcerative colitis (ASUC) patients remains controversial. This retrospective multicenter study aimed to compare accelerated and standard infliximab induction in a Chinese cohort of ASUC patients, and to explore risk factors associated with poor prognosis.

Methods

Data were collected retrospectively from steroid-refractory ASUC patients who received infliximab induction as rescue therapy at seven tertiary centers across China. Accelerated infliximab induction was defined as receiving two doses of infliximab on or before day 13 and/or receiving intensified doses of ≥ 7.5 mg/kg. Outcomes including colectomy and clinical remission (Mayo score ≤ 2 and every subscore ≤ 1 at day 14) rates were compared using propensity score adjustment for potential confounders. The variables in propensity score model was determined by logistic regression analysis for accelerated induction.

Results

A total of 76 patients were included: 29 received standard induction and 47 received accelerated induction. The overall disease severity was significantly higher in patients of accelerated group (Table). The 30-day colectomy rates did not differ between two groups (4.3% vs. 0%, P=0.522). However, the accelerated group had a higher 90-day colectomy rate (17.8% vs. 0%, P=0.019) and lower clinical remission rate (27.7% vs. 65.5%, P=0.001). (Figure. A) After adjusting with propensity score and institution, there was no significant difference in colectomy (P=0.20) or no clinical remission (P=0.48) hazards. Dose-effect curves plotted by restricted cubic splines (adjusted for propensity score and institution) showed decreased colectomy hazard with higher cumulative infliximab dosage within 5 days, while no improvement was observed for increasing cumulative infliximab dosage within 28 days. (Figure. B) Multivariate logistic regression analyses revealed female gender (OR=7.69, 95%CI: 1.96-33.33) and C-reactive protein (CRP) >10 mg/L at infliximab initiation (OR=5.00, 95%CI: 1.27-24.34) as independent risk factors for no clinical remission. (Figure. C)

Conclusion

After adjusting for confounders, there were no significant differences in colectomy or clinical remission rates between accelerated and standard infliximab induction among steroid-refractory ASUC patients. Elevated CRP at infliximab initiation indicated more intensive treatment or earlier surgery to be considered. And it would be better to give early intensified dosage within 5 days if needed.Read more N13 Sexual satisfaction and its associated factors among patients with inflammatory bowel disease in JapanWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Patients with inflammatory bowel disease (IBD) frequently experience fatigue and depression, which can lead to difficulties in their sexual lives, such as decreased motivation for sexual activity. Despite indications of sexual dysfunction and dissatisfaction, few studies have explored these issues. This study aims to clarify sexual satisfaction among patients with IBD and its related factors and to determine the percentage of respondents who were unwilling to answer the question about sexual satisfaction and their characteristics.

Methods

We consecutively recruited 500 patients from the specialized IBD clinic, of which 492 (206 with Ulcerative colitis and 286 with Crohn’s disease) valid responses were used in the study. To assess sexual satisfaction, we employed a 5-point scale using the "I am satisfied with my sex life" item from the Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-F). We collected information on patient characteristics (sex, age, occupation, marital status, disease duration, and sleep deprivation status). Additionally, we obtained data from the FACIT-F regarding non-response to sexual satisfaction, emotional well-being (EWB), and the Fatigue subscale (FS). Furthermore, we collected information on disease severity from the medical records, including the partial Mayo Score (pMayo) and Crohn's Disease Activity Index (CDAI).

Results

Out of 492 patients who participated in the study, 319 (64.8%) provided responses, while 173 (35.2%) did not respond to the sexual satisfaction question. The distribution of responses was as follows: “not at all” (11.0%), “a little bit” (9.7%), “somewhat” (24.7%), “quite a bit” (12.2%), “very much” (7.1%). In the bivariate analyses of sexual satisfaction and related factors, four variables showed a significant relationship: age (rs=-0.19, p=0.001), sleep deprivation status (p=0.003), EWB (rs =0.30, <0.001), and FS (rs =0.34, p<0.001). Multiple logistic regression analysis of the factors influencing non-response preferences revealed that female gender (OR=2.41, 95%CI= 1.55-3.75) and older age (OR=1.04, 95%CI=1.02-1.06) were statistically significant.

Conclusion

Chronic conditions, such as depression, fatigue, and sleep deprivation, can affect the sexual satisfaction of patients with IBD, even during periods of remission. A substantial percentage of respondents were unwilling to answer questions regarding sexual satisfaction among Japanese patients with IBD. Hence, healthcare providers should consider offering support for sexual issues, recognizing the discomfort some individuals may feel in discussing such intimate matters.Read more P925 Predicted inflammatory status and Inflammatory Bowel Disease among Korean adults: a Multicentre case-control studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), is a complex disease attributable to an anomalous immune response to intestinal microbiome antigenic stimulation, but there are limited studies on the overall implication of diet and lifestyle factors in the development of IBD, particularly among East Asian. This study assessed the association of pro-inflammatory predicted high sensitivity C-reactive protein (hs-CRP) scores (derived from diet and lifestyle factors) with IBD among Korean adults.

Methods

From July 2017 to September 2023, 912 subjects who underwent gastrointestinal endoscopy at eight tertiary medical centres and completed a food frequency questionnaire were used in this study. The study included subjects with IBD and matched them in a 1:1 ratio (using propensity score matching) with normal control; subjects without colonic inflammation or cancer. Pro-inflammatory predicted hs-CRP score was derived from sociodemographic, lifestyle, and dietary information and multivariable-adjusted conditional logistic regression model was used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) of IBD by tertile distribution of predicted hs-CRP scores (adjusting for age, sex alcohol intake, smoking, education, physical activity and energy-adjusted dietary energy intakes) at a two-sided P<0.05.

Results

Overall, 127 patients with IBD and 127 healthy controls were included in the study after propensity score matching. Of 127 IBD cases, 59 (46.5%) presented with CD and 51 (40.2%) were females. The prevalence of alcohol use was higher in the healthy control group compared to IBD patients (70.1% vs. 48.0%, p < 0.05), while a BMI ≥ 23 was more common in IBD patients (58.3% vs. 35.4%, p < 0.05). Smoking, age, sex, physical activity, and energy intake differed insignificantly between the two groups. Overall, the median (interquartile range) of the predicted hs-CRP was -2.6 (-3.0, -2.2), and multivariable-adjusted ORs and 95% CIs for IBD by tertiles of the predicted hs-CRP score were 1.00, 1.00 (0.44, 2.25), 8.67 (2.24, 33.51; P trend = 0.004) in males and females combined. When the association was stratified by IBD subtype, the association remained for UC but not CD.

Conclusion

Pro-inflammatory predicted hs-CRP score (derived from diet and lifestyle characteristics) was associated with higher odds of IBD, particularly among IBD cases presenting with UC. Promoting lifestyle modification to avoid pro might be promising for the primary prevention of IBD.Read more P783 Exploring the impact of JAK Inhibitors on cholesterol levels in Patients with Inflammatory Bowel Disease: A Real-World Data AnalysisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Janus Kinase (JAK) inhibitors represent a significant therapeutic advancement for individuals with inflammatory bowel disease (IBD). Previous research indicates an increase in total cholesterol (total-c) upon the initiation of JAK therapy.¹The precise mechanisms remain unclear, but studies suggest that inflammation can lower lipid levels. Therefore, by addressing inflammation through JAK therapy, there may be a subsequent elevation in lipid levels. This study seeks to evaluate the impact of initiating JAK inhibitors on total cholesterol levels in patients with IBD, utilising real-world data for analysis.

Methods

A multi-site retrospective analysis was conducted on a cohort of patients with ulcerative colitis and Crohn’s disease who had been initiated on either filgotinib, tofacitinib or upadacitinib. Statistical analysis was applied to examine alterations in total cholesterol levels (total-c) before and after the initiation of JAK inhibitor therapy.

Results

A cohort of 49 patients was identified, with pre and post total-c levels available for 33 individuals included in the analysis. Utilising paired data and the Student's t-test, we examined whether initiating a JAK inhibitor led to increased total cholesterol levels. Patients commenced on tofacitinib and upadacitinib exhibited statistically significant increases in cholesterol (p=0.016, p=0.0001). Patients in the filgotinib group, although demonstrating rises in total-c in most cases, did not reach statistical significance (p=0.21). Graph 1 demonstrates the range and spread of the results. Upadacitinib increased cholesterol levels by the most on average (0.82), compared to tofacitinib (0.64) or filgotinib (0.3). Elevated cholesterol persisted beyond 12 weeks in some patients, but long-term data for all patients was not available. Notably, only one patient initiated a statin, resulting in lipid normalisation at the next assessment. No cardiac events were identified in this cohort.

Conclusion

This analysis of real-world data underscores a potential influence of JAK inhibitors on the cholesterol profiles of individuals with inflammatory bowel disease (IBD). Gaining insights into the interplay between JAK inhibitors and lipid metabolism within the realm of IBD treatment is essential for enhancing patient care and proactively addressing potential cardiovascular risks linked to these therapeutic interventions.1.Herrera-deGuise C, Serra-Ruiz X, Lastiri E and Borruel N (2023) JAK inhibitors: A new dawn for oral therapies in inflammatory bowel diseases. Front. Med. 10:1089099. doi: 10.3389/fmed.2023.1089099Read more P926 Improved standards of colonoscopy for Inflammatory Bowel Disease through implementation of key performance measures - A quality improvement initiativeWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Improving the quality of colonoscopy in inflammatory bowel disease is expected to improve clinical outcomes for patients. The European Society of Gastrointestinal Endoscopy (ESGE) recently published key performance measures for IBD colonoscopy assessment. This study aimed to assess the impact of implementing key performance measures and assess for sustainable improvement through a multimodal education intervention.

Methods

A baseline retrospective analysis was performed in patients with established IBD between June and August of 2022 at a tertiary hospital. The key performance measures included 1) pre-procedure metrics including indication, consent, and safety checklist (target of 100%) and 2) bowel preparation score, photo-documentation, disease activity scores, adequate biopsies, use of high-definition endoscopy and chromoendoscopy. There were six proceduralists involved and data was collected from electronic medical records including endoscopy and histopathology results. The ESGE performance measures were used to set minimum standards and we have adopted overall standards for our unit based on the ECCO and SCENIC consensus guidelines. Over 12 months, proceduralists and endoscopy nursing staff were engaged with educational interventions including didactic teaching for one hour and diagrammatic reminders in the endoscopy suites of the ESGE key performance measures. A post-implementation analysis was conducted at 1 year from baseline, from August to November of 2023.

Results

Baseline standards showed suboptimal performance in the use of disease activity scores and chromoendoscopy. Educational interventions were implemented and after 12 months, a repeat analysis of 50 consecutive patients showed significant improvement in all performance measures (see Table 1).

Conclusion

Quality metrics are important and underrecognised components in colonoscopy for IBD patients and form an integral part of improving patient care. Our study demonstrated that the implementation of the ESGE key performance measures is effective in improving the quality of colonoscopy assessment in IBD patients, identifying areas requiring further development and increasing the dysplasia detection rate. Acknowledging quality attrition over time, we recognise that regular teaching and education are required in addressing the challenge of sustainable long-term improvement.Read more N14 The IBD nurse's role in screening for iatrogenic adrenal insufficiency in children with inflammatory bowel disease on discontinuing glucocorticoid therapyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

With a wide range of medical treatment on offer, ensuring patient safety by monitoring and or preventing side effects is a key part of holistic care.Glucocorticoids are widely used in inflammatory bowel disease (IBD) treatment to induce remission or treat flares. Iatrogenic adrenal insufficiency (AI), due to suppression of the hypothalamic-pituitary-adrenal (HPA) axis is an established side effect of exogenous glucocorticoids. Symptoms of AI can range from life‐threatening adrenal crisis to more subtle chronic symptoms including fatigue, abdominal pain and diarrhoea. The rate of AI in this population is unknown. There is no standard guidance or recommendations to suggest routine screening of paediatric IBD (pIBD) patients. This study aimed to report our experience on set up a monitoring pathway to manage pIBD patients coming off glucocorticoid therapy(GT).

Methods

A database was created to capture all IBD patients under the age of 18 who had received GT for IBD between March 2022 and July 2023. At the time of starting treatment, predicted last day on GT was identified and patients were booked in for testing serum early morning cortisol (Vitros Ortho Clinical Diagnostics immunoassay) and ACTH. After tapering, patients remained on the lowest dose of GT until results review. Evaluation of the adrenal-axis response was then assessed by a protocol piloted by this study – see figure 1. The patients needing treatment for AI were seen in the Nurse led clinic for prescribing, education and training. The training included IM injection training, sick day training and safety netting. To ensure safe evidence based training, the IBD nurse had received training form the endocrine nurse before the pilot.

Results

Following the initial screening, 9 patients were seen in the clinic with AI ( 8 prednisolone and 1 Budesonide). Of these 9,8 (88%) were followed up by the IBD nurse and 1(11%) was followed up by a local paediatrician with an endocrine interest. Treatment with hydrocortisone was commenced and follow up 3 months blood tests organised.The school was notified of the risk of Adrenal suppression and emergency kits provided. Repeat adrenal axis testing was offered at 3 months (5 of 9) and 6 months (3 of 9). AI was noted in 3 patients and 2 patients at 3 and 6-month respectively. At the 6 month mark, patients were discharged from the clinic if they had returned to a normal adrenal axis or referred to the endocrine team for further follow up. Patients were discussed in a multi-displinary meeting at every point on the pathway and no child suffered an adrenal crisis during the study period.

Conclusion

AI following GT is common in this small pIBD cohort. The IBD nurse can play a critical role in providing safe care for these patients.Read more P849 Bayesian network meta-analysis of the efficacy of advanced therapies for patients with moderately to severely active ulcerative colitis naïve to advanced therapyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Etrasimod is an oral, once-daily, selective sphingosine 1-phosphate (S1P)_1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC). In the absence of head-to-head randomised controlled trials (RCTs), network meta-analyses (NMA) offer insight into the comparative effectiveness of treatment options. NMA were conducted to examine the relative efficacy of etrasimod vs other advanced therapies (AT) with licensed dosing (European Medicines Agency) for the treatment of UC in patients naïve to biologic agents and/or Janus kinase inhibitors.

Methods

A systematic literature review (SLR) was performed on 15 November 2022, and covered all available records without time limit, using NICE DSU and PRISMA guidelines. NMA were conducted under a Bayesian framework, and a multinomial fixed-effect approach was used to model outcomes, clinical response and clinical remission, in the induction phase and among induction phase responders in the maintenance phase, in patients naïve to AT. Reported outcomes from trials with a treat-through design, such as ELEVATE UC 52, were recalculated to mimic those of a responder re-randomisation design; only responders in the induction phase were analysed in the maintenance phase. Data are presented as median relative risk (RR) of the treatment vs its comparator, along with corresponding 95% credible intervals (CrI). Prespecified sensitivity analyses were performed.

Results

Of 81 studies identified from the SLR, 21 and 11 RCTs were included in the induction and maintenance networks, respectively. For induction and maintenance phases, all therapies demonstrated benefit over placebo, consistent with phase 3 clinical trial data. In the NMA for clinical remission in the induction phase, etrasimod 2 mg had a statistically significant benefit over adalimumab 80/40 mg and 160/80 mg (RR [95% CrI] for treatment vs etrasimod 0.49 [0.29–0.78] and 0.67 [0.50–0.92], respectively), filgotinib 100 mg (0.55 [0.37–0.84]) and placebo; conversely, upadacitinib 45 mg had statistically significant benefit vs etrasimod (1.47 [1.07–2.03]; Table). There were no statistically significant differences for etrasimod vs other comparators. Similar results were observed for clinical response. In the maintenance phase, there were no statistically significant differences between etrasimod 2 mg and other treatments for clinical remission and clinical response (Table).

Conclusion

With respect to clinical remission and clinical response during induction and maintenance phases, etrasimod efficacy was similar to most comparators as a first-line AT. Differences in trial design and risk-benefit profiles of AT should be considered when interpreting NMA results.Read more P945 Crohn´s disease response to ustekinumab measured by bowel ultrasoundWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

After the STRIDE-II update for patients with Crohn’s disease (CD) one of the new possible adjunct treatment goals was transmural healing, yet its assessment is still not fully cost/risk-benefit proven. A valuable tool to assess this adjunct goal is bowel ultrasound. For this reason, our aim was to evaluate the bowel ultrasonographic response to ustekinumab at one year.

Methods

Retrospective, observational, single center study was designed. All adult patients with CD who were treated with ustekinumab and had a bowel ultrasound just before the induction dose with ustekinumab and who repeated the bowel ultrasound one year after it were included. Examination was done by ultrasound machine (Hitachi Avius) with low frequency curved-array (1-5 MHz) and high-frequency linear-array (5-13 MHz) transducers. The measured bowel ultrasonographic variables were: wall thickness, Doppler activity (Limberg index) and fatty striation. Ultrasonographic response was defined as a reduction in wall thickness of at least 25%, 2mm or 1mm plus 1 Doppler sign. Remission was defined as wall thickness less than 3mm plus absent Doppler sign. Patient demographics and disease characteristics were also collected: age, sex, extension of CD, previous biologic treatments and ustekinumab trough levels. Demographic and clinical characteristics were compared using χ² analysis (or Fisher’s exact test), Student’s t test or Spearman correlation. All statistical analyses were performed using the STATA Statistical Software.

Results

A total of 41 patients (56.1% female) with a mean age of 57.9 years (SD ±2.7) were included. 63.4% had ileal disease and 36.6% ileocolonic involvement. Ustekinumab was first line of biologic treatment in 7.3%, second line in 61.0%, third line in 29.3% and fourth line in 2.4% of patients. 63.4% of patients were on ustekinumab 90mg subcutaneous every 4 weeks at one year with a median trough level of 8.6 (range 7.9-10.6). The median wall thickness measured by bowel ultrasound before induction was 5.5 mm (range 5.0-6.4) and after one year it was 5.0 mm (4.1-5.7) (p=0.47) Figure 1. Before treatment Limberg index was 3 in 26.8% and after treatment it was 3 in 4.9% (p=0.052). Fatty striation was present in 90.2% of patients at the beginning of treatment and in 63.4% at one year (p=0.013). Ultrasound response was achieved in 36.6% of patients while transmural remission was achieved in 12.2% of patients in the first year. No association between ustekinumab trough levels and response/remission were found (p=0.70/p=0.83)

Conclusion

Treatment with USK was related with an ultrasonographic response in one third of patients with refractory CD at one year. No association between ustekinumab trough levels and ultrasonographic response/remission were foundRead more N15 Developing a Tool for educating newly diagnosed Patients with Inflammatory Bowel Disease based on a Quality Database IndicatorWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

There is evidence that education improves quality of life and empowers patients with chronic diseases including inflammatory bowel disease(IBD).Education also indicates a better use of ressources enabling relevant treatment to be started earlier.Education meets an increasing wish from patients to be involved.ECCO recommend patient education and state that this is well handled by specialist nurses.When establishing Danish Quality Database for Inflammatory Bowel Disease(DANIBD) the steering committee agreed that education for the newly diagnosed patients with IBD should be an indicator of quality.This was a new task and a big challenge for many clinics and also it was unusual for nursing to stand out so clearly in a database.The tool aims at 1.- supporting the clinics in implementing the new task into clinical practice 2.- securing uniformity in the education in relation to fulfilling the indicator and 3.- improving quality of patient education and nurse consultations to patients with IBD.

Methods

In the IBD group of the Danish Nursing Association(DSR) it was decided to develop a tool that would serve as an inspiration or could be used directly by the clinics.The tool should ensure that the demands in the indicator was met but should also contain inspiration for other subjects regarding patient education and nurse consultations.Based on literature and the experience of the group members a list of subjects were made and distributed among the group members for developing slides and notes.At plenary meetings all this was put together, structured and edited.In order to get a professional product a collaboration with an art director was established.Financing was secured by donations from the pharmaceutical industry.

Results

There now are two powerpoint presentations - one for Crohn's disease and one for ulcerative colitis.each presentation is split in two parts. Part one meets the database and part two is an inspiration for covering other subjects relevant for patient education and nurse consultations.The presentations encourages the dialogue with the patient and can be customized by the individual clinics or the individual nurses.The presentations contain additional notes and links to further information.In order to help implement the tool two nurses from each clinic in Denmark were invited to one day of training in using the tool and in communication.The presentations were put on the webpage of the IBD group from where it can be downloaded and used by everyone interested.

Conclusion

Developing a quality indicator within the database has started an engaging process focusing on the patient and on improving nursong for patients with IBD.It is expected that the tool will help support and empower patients in their lives with IBD.Read more P685 Effectiveness of a second-line anti-TNFɑ agent compared to a different mechanism of action after first anti-TNFɑ failure in ulcerative colitis: CambiaCU StudyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Ulcerative colitis (UC) is a chronic and relapsing disease for which the number of biological therapies available are increasing over the years. Data comparing the effectiveness of a second anti-TNFɑ (aTNF) and the switch to a different mechanism of action (MoA) such as Ustekinumab (UST), Vedolizumab (VDZ), Filgotinib or Tofacibinib (JAK) is lacking.

Methods

We performed a multicenter and retrospective study (6 Andalusian sites) in which patients diagnosed of UC who had failed a first biological therapy with an aTNF and started a second-line biological therapy with another aTNF or a different MoA (UST, VDZ, JAK) were included. Clinical response and remission were assessed at weeks 16 and 52. The aim of our study was to evaluate the effectiveness of a second-line biological therapy with aTNF compared to a different MoA after a first aTNF failure.

Results

185 UC patients were included. There were no differences in the demographic data except for disease duration (9 years with MoA vs 13 years in aTNF, p=0.02). As first aTNF, infliximab (IFX) was the most common in both groups (49% MoA group, 56% second aTNF), followed by adalimumab (ADA) (48% MoA group, 33% second aTNF). In the second aTNF group, immunomodulators were significatively more used (60% vs 38%, p=0.003). There were no differences in the concomitant use of steroids. 80 patients received a different MoA (37 VDZ, 24 UST, 7 JAK) and 105 a second aTNF (34 IFX, 60 ADA, 11 golimumab). At week 16, 52% of patients were in clinical response (70% with another MoA vs 54% with second aTNF, p=0.07; IFX 65%, ADA 53%, VDZ 68%, UST 71%, JAK 74%, p=0.07), being 15.6% more likely to achieve response with another MoA. Clinical remission at week 16 was obtained by 36% (39% with another MoA vs 33% with second aTNF, p=0.6; IFX 47%, ADA 30%, VDZ 35%, UST 46%, JAK 37%, p=0.1). At week 52, 48% achieved clinical response (51% with another MoA vs 45% with second aTNF, p=0.8; IFX 50%, ADA 42%, VDZ 49%, UST 54%, JAK 53%, p=0.5) and 39% were in clinical remission (40% with another MoA vs 38% with second aTNF, p=0.53; IFX 50%, ADA 32%, VDZ 35%, UST 38%, JAK 53%; p=0.06) (figure 1). When the effectiveness is analyzed by first aTNF used, independently of the aTNF, subsequent use of a different MoA achieves better results although not significant compared to a second aTNF. Partial Mayo and calprotectin showed a significant decrease at weeks 16 and 52 in both groups. Hemoglobin and albumin levels remained similar during follow-up in both groups.

Conclusion

Second-line biological therapy is effective regardless of biological therapy used in UC, but switching to a different MoA tend to achieve better results in terms of clinical response and remission compared to a second aTNF.Read more P1039 RECtal OUtcomes in Paediatric Ulcerative Colitis (RECOUP-UC): An International Clinical Practice Survey of Paediatric GastroenterologistsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Ulcerative Colitis (UC) in childhood is associated with a higher risk of developing acute severe colitis and colectomy compared to adult populations. Following subtotal colectomy, the rectal remnant is typically oversewn and remains in-situ until ileal continuity surgery is undertaken. Access to such surgical expertise determines the timing of restorative surgery, which may range from months to years. There is a paucity of data regarding residual rectal activity during this interval, its medical management and clinical outcomes.

Methods

An electronic survey (SurveyMonkey) of clinical practice was disseminated to the paediatric inflammatory bowel disease (PIBD) community internationally. Data collected included treating centre demographics, local colectomy practices, expert opinion on rectal cuff assessment and management. Clinicians were asked to rank order the symptoms and signs considered most relevant to determining disease activity. They also ranked the clinical features they believed most important to patients. Descriptive statistics were used to present findings.

Results

Responses were collated from over 10 countries, including Ireland, Sweden, UK, Australia, Israel, Canada, Iran, Finland, UAE and Austria. Centre sizes were categorised based on total PIBD population. There was heterogeneity across centres - 16% of respondents were from small volume centres in the range of 0-100 patients, 45% were from medium sized centres (101-300), 25% were from large volume centres (301-500) and 12% treat >500 patients which we categorised as very large volume. Despite variation in centre volume majority of respondents (75%) diagnose >20 new cases of UC annually.Over 90% of respondents reported having no formal guideline for managing rectal disease. Most centres’ patients (60%) waited at least 3 months post-colectomy for restoration surgery. Mild intermittent symptoms were expected to continue by 60% of respondents. Of these symptoms, 45% ranked haematochezia as the most important in determining severity. There was no consensus on the best assessment tool to use; 30% use the PUCAI. Most (80%) use blood markers and endoscopy routinely to assess rectal activity. Favoured treatments include rectal therapy (80%) followed by oral steroids and surgical referral. All respondents agreed that additional research was needed.

Conclusion

International management of the rectum following subtotal colectomy in children is characterised by variable clinical practises, and a lack of guidelines or validated assessment tools. Additional research in the field is needed to address current literature deficits and improve care for children.Read more P1077 Patients’ and Gastroenterologists’ Preferences on Outcomes and Medication Attributes for Ulcerative colitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Gastroenterologists’ perceptions regarding importance of treatment outcomes and medication attributes for ulcerative colitis (UC) may differ from inflammatory bowel disease (IBD) patients’ preferences. The objective of the study was to explore and compare patients’ and health care professionals’ attitudes in the decision-making process for available UC treatments.

Methods

A qualitative study was conducted using patients’ focus groups and gastroenterologists’ interviews. Participants who had been diagnosed with ulcerative colitis were recruited for the purposes of this study. Gastroenterologists (GIs) were identified from the Hellenic Group for the study of IBD. Focus groups discussions and interviews were audiotaped and transcribed verbatim. Thematic analysis was used to identify patients’ and clinicians’ important outcomes.

Results

Eight gastroenterologists and 23 individuals with IBD participated in semi-structured interviews and focus-group discussions, respectively. Categories that emerged from the data analysis included outcomes related to UC, the impact of UC on daily life, drug-related attributes, and the patient-doctor relationship. Within these themes, divergences between the opinions of GIs and patients were observed on two primary issues. In terms of UC-related outcomes, physicians aimed for clinical remission and focused on long-term objectives such as mucosal healing defined by endoscopic improvement and histologic remission. In contrast, patients' expectations were of shorter term and focused on symptomatic response, defined as early and sustained relief of the symptoms and improvement in quality of life. Regarding specific drug attributes, patients were mainly focused on the impact on daily life, considering factors such as route of drug administration, dosage, and the need for daily hospitalization. In contrast, GIs appeared more concerned about drug adverse events and the risk of losing responsiveness.

Conclusion

Individuals receiving healthcare and healthcare providers may have varying views on the significance of different treatment outcomes and features of medications. Patients often prioritize factors that directly impact their quality of life. It is crucial to address these concerns and preferences in clinical discussions when determining the most suitable treatment approach for ulcerative colitis.Read more P686 Comparison between therapeutic sequences starting with IV induction-biologic versus SC-induction biologic in bionaïve-patients with ulcerative colitis: results from the APPETISER studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Recent data suggest that infliximab and vedolizumab would be more effective than subcutaneous anti -TNF as 1st line-biologic, leading therapeutic sequencing challenging.We compared the effectiveness of a strategy starting with a first-line bologic with IV induction (IFX or VDZ = IV group) compared to a biologic with SC induction (adalimumab or golimumab = SC group) to induce and maintain steroid-free clinical remission during the first 24 months.

Methods

From a database of IBD referral center, all consecutive UC patients ≥ 18 years-old who started a first line of biologic (IFX, VDZ, ADAor GLM) for active UC with follow-up > 6 months were included. Prior colectomy or severe acute colitis were excluded.The primary endpoint was remission defined according to PRO2 (PRO2-remission) as the absence of bleeding, normalization of transit (Mayo stool frequency subscore = 0) and no steroid. PRO2-remission was defined as a binary criterion each month (the statistical unit being the month and not the patient).The secondary endpoints concerned the analysis by patient and were CFREM (partial Mayo score ≤ 2 without steroid) and endoscopic remission (CFREM + score Endoscopic Mayo ≤ 1) at week 12 .All comparisons were adjusted using propensity scores on potential confounders. Analysis by month was performed using mixed models to account for repeated data.

Results

Overall, 130 patients were included including 60 patients in the IV group (IFX= 50 and VDZ= 10) and 70 in the SC group (ADA= 48 and GLM= 22). The populations had similar characteristics at baseline apart from concomitant immunosuppressant more frequent in IV group (55.9% vs 21.7%). 2nd line treatment was started in 26.7% of patients in IV group (ADA in 48.8%, VDZ 25.5% and ustekinumab 18.8%) and 87.1% of patients in SC group (IFX in 54.1%, VDZ 31.1%).After adjustment, the rate of CFREM at week 12 was significantly higher in the IV arm (70.8%) than in the SC arm (33.0%) (p < 0.001). The rate of endoscopic remission at W12 was 22.1% and 10.0% in the IV and SC arms, respectively (p =0.18).In this study, 3350 months were analyzed (1180 in the IV arm and 1175 in the SC arm). The percentage of months spent in PRO2-CFREM in the first 24 months (primary endpoint) was greater in the IV arm than in the SC arm (74.2% vs 46.6%; p<0.001). The percentage of months spent in CFREM was higher in the IV arm in the first 6 months (60.4% vs 18.9%), but also between M7 and M12 (73.1% vs 38.6%), M13 and M18 (79.9% vs 57.0%) or M19 and M24 (83.3% vs 64.6%) (p < 0.001 for all comparisons).

Conclusion

A therapeutic sequence starting with IV induction biologic (IFX or VDZ) was more effective than starting with a SC induction anti-TNF (ADA and GLM ) to induce and maintain remission at short and long-term in UC.Read more P927 Long-term outcomes of risankizumab in Crohn’s disease: a multicenter GETAID StudyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Risankizumab is approved for moderate to severe Crohn’s disease (CD). The GETAID recently reported the real-world effectiveness of risankizumab as induction therapy for refractory CD. The aim of this study was to assess the long-term effectiveness and safety of risankizumab maintenance treatment in a large real-world cohort of patients with CD.

Methods

From May 2021 to August 2023, all consecutive CD patients treated with risankizumab in 25 GETAID centers have been retrospectively included. Only patients who received risankizumab 600 mg IV at week 0,4 and 8 as induction and SC 360 mg every 8 weeks as maintenance treatment were included. The primary outcome measure was steroid-free clinical remission (Harvey Bradshaw Index (HBI) <5) at week 52. Secondary outcomes included clinical response (≥ 3-point decrease of HB score and/or (HB) score < 5), endoscopic (no ulcers) and/or radiologic remission (normal intestinal ultra-sound or MRI), need for CD-related surgery, and adverse events.

Results

All patients had received at least three biologics and 108 (62%) had previous intestinal resection. Of the 174 patients included, 172 (99%), 162 (93%), and 167 (96%) had been previously exposed to anti-TNF, vedolizumab, and ustekinumab, respectively. Respectively 66 (38%) and 24 (14%) patients were on corticosteroids and immunosuppressants at risankizumab initiation. Median follow-up was 13.7 (10.0-18.1) months. The rates of steroid-free clinical remission and clinical remission at 52 weeks were 46% (60/131) and 50% (65/131), respectively. Absence/mild abdominal pain with normal stool frequency was observed in 48% (54/112) of patients at week 52. Among the 79 (45%) patients who had an endoscopic (n=67) and/or radiological (MRI, n=56 and IUS, n=15) evaluation during follow-up, response and remission were observed in 27 (34%) and 17 (22%) patients, respectively. Risankizumab persistence rates were 94%, 89%, and 79% at weeks 12, 26, and 52, respectively. At the end of follow-up, 45 (45/174, 26%) patients had discontinued risankizumab (loss of response, 42%; primary failure, 37%; intolerance, 13%). Thirty-six patients (36/174, 20.9%) were hospitalized and 22 (22/174, 12.6%) required intestinal resection. No factors were associated with steroid-free clinical remission at week 52. Twenty-five (14%) patients had an adverse event and 26 (15%) serious adverse events (CD flare, n=17). One death (myocardial infarction) and one cancer (papillary thyroid carcinoma) were observed.

Conclusion

This is the first real-life study to report long-term outcomes in patients with refractory CD treated with risankizumab. Half of the patients achieved steroid-free clinical remission after one year, and the safety profile was consistent with the literature.Read more P703 Comparison of infliximab and adalimumab therapies Persistence in patients with Ulcerative Colitis: Results from a Single Tertiary Turkish IBD Center CohortWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

In the last 25 years, the introduction of biological therapies has been a significant milestone in the management of inflammatory bowel diseases. Despite the recent emergence of new biological therapies and small molecules, Anti-TNF agents still play a crucial role in treatment. In a number of countries, anti-TNF agents are still reimbursed as a first line treatment following either a failure or intolerance to conventional therapies such as thiopurines and aminosalycilates. Many studies have been conducted previously to compare the efficacy of these drugs, but a clear conclusion could not be reached. In this study, we aimed to compare the persistence of infliximab (IFX) to adalimumab (ADA) in the treatment of ulcerative colitis at a tertiary IBD center in Turkey.

Methods

This was a retrospective cohort analysis of patients with ulcerative colitis either received adalimumab or infliximab as a first line biologic treatment. A total of 234 patients were included to this analysis. Demographic information such as gender, age, montreal classification, smoking and prior medications were noted from patients electronic medical records. Weighted Kaplan-Meier and Cox models were used to assess the outcomes.

Results

Out of the 234 patients included in the study, 116 had used infliximab, and 118 had used adalimumab as a first-line treatment. Age and gender of the patients in both groups did not differ from each other statistically. 88% of the patients treated with adalimumab and 84% of the patients treated with infliximab were thiopurine experienced. Montreal classification did not differ between two groups (in IFX group, 73% of the patients had Montreal E3 involvement where as in ADA group, 66% of the patients had Montreal E3 involvement, p>0.05). Primary non-response rates were not different between IFX and ADA group, 13.6% vs 13.4% respectively. In addition, clinical response rates after first year were 60% and 53% respectively. Drug persistency rates of adalimumab and infliximab in moderate to severe ulcerative colitis patients were not statistically different from each other (Figure 1).

Conclusion

Neither clinical efficacy rates nor drug persistency rates of adalimumab and infliximab in ulcerative colitis treatment were not different from each other. Factors such as age, gender, location of involvement, concomitant therapies, and smoking did not alter the outcome.Read more P1083 Patient preferences for Inflammatory Bowel Disease treatments: an international survey using a discrete choice experiment in partnership with EFCCAWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

As the therapeutic landscape for inflammatory bowel disease (IBD) continues to expand, this international patient preference study aimed to quantify IBD patients preferences for treatment and disease-related attributes.

Methods

A survey incorporating a discrete choice experiment (DCE) comprising 14 attributes with a partial profile design was disseminated globally among IBD patients. The survey design was informed by a prior literature review, qualitative research, and expert discussions. Multinomial logit models were used to estimate DCE attribute weights and assess potential interactions.

Results

A total of 1272 IBD patients across 37 countries completed the survey (Table 1). All parameters had the expected negative signs, meaning that the side effects or negative disease related outcomes in the survey had a negative impact in the patients’ utility. Additionally, they were significant predictors (p<0.05) of patient choices. Among the different attributes, the severity of abdominal pain and cramps (11.35%) was considered the most important attribute, followed by urgency and pain of having to go to the toilet (11.91%), and severity of fatigue (10.62%). The lowest importance was assigned to the treatment mode of administration (2.56%), onset of action (3.22%), and endoscopic disease activity (3.57%) (Figure 1). Differences in patient's attribute weights were found between patients with Crohn’s disease and ulcerative colitis, with the former attaching more value to frequency of having to go to the toilet (p<0.01), urgency and pain of having to go to the toilet (p<0.001), risk of surgery (p<0.001), and physical changes (p<0.01). Interactions with age in the model showed that older patients attached less importance to treatment and disease-related attributes. Furthermore, females attached more value to severe infections (p<0.001), physical changes (p<0.001), and skin problems (p<0.01). Some differences in preferences of patients in Northern, Eastern, Southern, and Western Europe were identified, with for example patients in Western Europe attaching more value to fatigue (p<0.001), psychological impact (p<0.001), sleeping problems (p<0.001), and skin problems (p<0.001) compared to patients in Eastern Europe.

Conclusion

Gastrointestinal problems were considered very important to IBD patients next to other quality of life-related attributes affecting IBD patients' physical, mental, and psychological health. Noteworthy, characteristics that distinguish the different treatments from each other (such as mode of administration and onset of action) seem less important to patients. Observed differences in patients preferences as revealed in the DCE emphasize the imperative role of shared decision making in treatment selection.Read more P928 "Metabolism and Response to Stress" (MARS) gene signatures reveal heterogeneity in patients with Ulcerative Colitis and identify characteristics of patients with increased response to therapyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Ulcerative colitis (UC) therapies lead to variable remission in participants in clinical trials likely due to interindividual variability, differences in active biological pathways, feedback, and/or resistance mechanisms. We sought to characterise these differences using mucosal biopsy transcriptomics datasets from two recent UC clinical trials.

Methods

Two clinical trial datasets including patients with moderate to severe UC with mucosal biopsy RNA-Sequencing analysis were used: a phase 2/3 study of andecaliximab (anti-matrix metalloproteinase-9, NCT02520284) and a phase 3 study of ustekinumab (anti-interleukin-12/23, UNIFI, NCT02407236). Samples were scored for enrichment of ~5200 MSigDB signatures using Geneset Variation Analysis and were evaluated for correlation to the sample Robarts Histopathology Index (RHI) (Figure).

Results

From the andecaliximab baseline and follow-up samples, 11 Reactome pathways were specifically selected that were moderately correlated with RHI (r=~0.4) and had low correlation to each other (r<0.7). The 11 genesets, called Metabolism and Response to Stress (MARS) signatures, can generally be sorted into 2 categories: 5 metabolism-related and 6 related to stress response. Clustering of baseline andecaliximab samples scored with MARS signatures revealed 3 major sample groups (baseline and follow-up samples). Group 1 had low metabolism/high stress scores, group 2 had high metabolism/low stress scores, and group 3 had a mixture of samples that had high metabolism/low stress and low metabolism/high stress. Group 2 was associated with a lower proportion of current smokers (p=.04), and group 3 had a higher proportion of immunomodulator failure (p=.03), but not associated with disease duration or prior biologic use. Group 2 had lower Geboes score for epithelial neutrophils (p=.02), lamina propria neutrophils (p=.002), and inflammatory infiltrate (p=.03), while eosinophils increased (p=.01). To evaluate prediction of response to therapy, we evaluated the UNIFI dataset baseline samples using the MARS signatures and identified 4 groups. Group 2 had low metabolism/high stress response, group 3 had high metabolism/low stress response, and groups 1 and 4 had a mixture. The mucosal healing response rate was 3- to 4-fold lower for group 2 than other groups (5.3% [group 2] and 19%, 23%, and 21% for other groups, p=.0009).

Conclusion

We describe the MARS signatures which characterise the heterogeneity of participants with UC clinical trials and identify participants most likely to respond to ustekinumab at baseline. These signatures may be generally useful to predict patient response, match therapeutics to patient profiles, or identify pathways to target in difficult-to-treat patients.Read more P704 Safety of Immunosuppression in A Prospective Cohort of Inflammatory Bowel Disease Patients with a HIstoRy of CancEr: The SAPPHIRE RegistryWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

For patients with inflammatory bowel disease (IBD) and a history of cancer, retrospective studies have failed to find evidence suggesting that exposure to biologic and/or immunomodulator (IMM) agents was associated with new or recurrent cancer. The SAPPHIRE Registry was developed to prospectively examine this issue.

Methods

Patients with IBD who had a confirmed first (index) cancer 5 years prior to enrollment were recruited from centers affiliated with the New York Crohn’s and Colitis Organization (NYCCO) since 2016. Patients receiving chemotherapy or radiation therapy at enrollment or recurrent cancer within the last five years were excluded. The primary outcome was the development of an incident cancer stratified by IBD therapy exposure and adjusted for index cancer stage, index cancer type, sex, smoking history, and age at index cancer in a Cox proportional hazards model.

Results

302 patients were analyzed. Median age at IBD diagnosis was 31.5. Patients were 47% male, 88% white, and 61% never smokers. Index cancers were solid organ (138; 46%), dermatologic (100; 33%) GI (34; 11%), hematologic (27; 9%), or of other types (3; 1%); most index cancers (excluding non-melanoma skin cancer) were diagnosed as Stage 1. Following the index cancer, 90 (30%) patients were not exposed to any immunosuppression, and the other 212 were exposed to immunosuppressive therapy: 142 biologic monotherapy (anti-TNF, anti-integrin, anti-IL12/23, anti-IL23; 47%), 13 anti-metabolite monotherapy (mercaptopurine, azathioprine, methotrexate; 4%), 41 biologic + anti-metabolite combination therapy (14%), and 16 exposed to small molecules (JAK inhibitors, ozanimod; 5%). During follow-up, 46 (15%) patients developed subsequent cancers (25 new, 21 recurrent): 22 (48%) dermatologic, 15 (33%) solid, 7 (15%) GI, and 2 (4%) hematologic malignancies at a median age of 63.5. Patients not exposed to immunosuppression experienced incident cancer at a rate of 2.58/100 person-years (PY, Table). Those exposed to immunosuppression had a rate of 5.12/100 PY, representing an additional 2.54 cancers/100 PY (95% CI: 0.22, 4.85). In a time-varying Cox proportional hazards model adjusting for clinical and demographic characteristics, the adjusted hazard ratio for incident cancer for patients exposed to immunosuppressive therapy compared to unexposed patients was 1.36 (95% CI: 0.73, 2.52). Excluding non-melanoma skin cancer, the adjusted hazard ratio was 1.38 (95% CI: 0.66, 2.91).

Conclusion

In this ongoing prospective study, we have thus far found no association between immunosuppressive IBD therapy and risk of developing new or recurrent cancer. Ongoing enrollment and follow-up, specifically for individual drug classes and cancer types, are required to confirm these findings.Read more P1100 A multivariate time-dependent proportional hazard model to predict development of intestinal failure from Crohn’s DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Intestinal Failure (IF) is a rare but severe complication of Crohn’s disease (CD). Advancement in therapy has not eliminated incident IF from CD (CDIF), and risk factors for developing IF from CD are not well characterised. The Copenhagen Intestinal Failure Database contains one of the largest, comprehensively described adult CDIF cohort¹ from 1973 to 2018, which can be linked with a Danish nationwide CD cohort² to explore healthcare utilisation patterns associated with developing IF from onset of CD.

Methods

CDIF patients from Copenhagen Intestinal Failure Database and a nationwide CD cohort without IF were followed from CD diagnosis until IF, death, or censoring on 31/12/2018. Hospital contacts, surgeries, medication use and employment status were extracted from multiple Danish population-based registries. Unplanned hospitalisation or emergency department attendance (inpatient-contact), CD-related abdominal surgery, and stopping work for 6 months or more (in working-age CD patients, excluding full-time study and parental leave) were considered time-dependent covariates and tested for significance (p<0.05) in univariate proportional hazard models. Significant covariates were then modelled together with additional non-time-dependent clinical and demographic variables in multivariate proportional hazard models. Backward variable selection was performed to derive a final predictive model.

Results

175 CDIF and 22845 CD patients from whom data was available were followed for 2283.1 and 293536.5 patient-years, respectively. Univariate time-dependent proportional hazard models showed that every instance of unplanned IBD inpatient contact, CD-related abdominal surgery, and stopping work was significantly associated with increased hazard of developing IF, with a hazard ratio of 4.91 (95% CI 3.54-6.80, p<0.001), 29.79 (95% CI 9.70-91.48, p<0.001) and 1.61 (95% CI 1.15-2.26, p=0.005). In multivariate analysis, earlier decade of IBD onset, unplanned IBD inpatient contacts, length of stay of the inpatient contact, CD-related abdominal surgery, complicated surgery, number of previous admissions and surgeries and previous median-long term unemployment increased the rate of developing IF (Table), whereas age and comorbidity level at CD onset, non-IBD inpatient contacts, type of surgery, biologics use, and current employment status were not found to be significantly associated with IF development.

Conclusion

This is the first study to demonstrate significantly increased risks of developing IF from CD from increased healthcare utilisation patterns.References:1. Brandt et al.JPEN 41(4),566-574. https://doi.org/10.1177/01486071156120402. Lo et al. Scand.J.Gastroenterol.55(10),1171-1175. https://doi.org/10.1080/00365521.2020.1807598Read more P947 medical cannabis increases appetite but not body weight in patients with inflammatory bowel diseasesWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Medical cannabis (MC) is prescribed to improve appetite and nutritional status in patients with inflammatory bowel diseases (IBD) despite no supporting evidence. We aimed to describe the effect of MC on appetite and dietary intake among patients with IBD.

Methods

An observational prospective cohort study, among patients with IBD, initiating treatment with MC for disease related symptoms, at the IBD clinic of a tertiary referral medical center. Patients' demographics, anthropometric measurements, medical history, cannabis use history, and medical treatment were documented and an appetite questionnaire (SNAQ), and food frequency questionnaire (FFQ) were filled before MC initiation and throughout 6 months of treatment.

Results

Of patients enrolled in the study (n=149, age 39.0±14.1 years, 42.3% female) and treated with MC for disease related symptoms, on top of their routine therapy regimen, while 33.6% received MC for increasing appetite and improving nutritional status. Among patients treated for raising appetite and improving nutritional status, 34.0% experienced a significant increase in appetite after 3 months. None the less, all patients experienced a modest increase in appetite (P<0.05), a trend which was more profound among patients treated with high THC/CBD ratio (SNAQ score 27.0±4.1 at 3 months vs. 25.2±3.6 at baseline, P=0.021). Nonetheless, this increase in appetite throughout the study did not result in increased energy, macronutrient intake or in BMI following MC treatment. Among patients without a significant increase in appetite by 3 months of MC therapy, a significant decrease in BMI was noticed at 6 months (24.1±3.7 at baseline vs. 23.4±3.6 at 6 months, Pv=0.010).

Conclusion

Use of MC, and specifically THC, may be a potential strategy to improve appetite among some patients with IBD. This increase in appetite was not associated with an increase in caloric intake or in BMI at follow-up.Read more P705 Assessment of age on the efficacy and safety among patients in the etrasimod ELEVATE ulcerative colitis clinical programmeWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Etrasimod is an oral, once-daily (QD), selective sphingosine 1-phosphate (S1P)_1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC). Previous work has shown age can impact treatment safety and efficacy in patients with inflammatory bowel disease.¹ This post hoc analysis investigated the impact of age on the safety and efficacy of etrasimod in patients with UC in the phase 3 ELEVATE UC clinical programme.

Methods

Data pooled from the ELEVATE UC 52 (NCT03945188) and ELEVATE UC 12 (NCT03996369) trials were analysed in patients receiving etrasimod 2 mg QD and placebo. ELEVATE UC 52 had a treat-through design comprising a 12-week induction period followed by a 40-week maintenance period. ELEVATE UC 12 was a 12-week induction trial. Proportions and incidence rates (IRs) per 100 patient-years from pooled data of treatment-emergent adverse events (TEAEs) and events of interest were stratified by age (<40 years, 40–59 years, ≥60 years) and analysed in patients who received ≥1 dose of etrasimod or placebo. Efficacy analyses were evaluated in patients with baseline Modified Mayo score (MMS) 5–9 for the primary efficacy endpoint (clinical remission) and select secondary endpoints at Week 12 (both trials) and Week 52 (ELEVATE UC 52) stratified by age.

Results

There were 787 patients enrolled in the ELEVATE UC programme, of whom 420 (53.4%) were aged <40 years, 276 (35.1%) were aged 40–59 years and 91 (11.6%) were aged ≥60 years. The proportions and IRs of TEAEs and events of interest were mostly similar between age groups and treatment arms (Table). IRs of arthralgia, fatigue, hypertension and pyrexia were higher in older age groups, regardless of treatment arm. Serious AEs and AEs leading to treatment discontinuation were low and consistent across all age subgroups. Serious infections and infection events of interest were balanced across age groups and treatment arms. Regardless of age subgroup, significantly more patients treated with etrasimod 2 mg QD vs placebo achieved the primary and select secondary efficacy endpoints at Week 12 and Week 52 (Figure).

Conclusion

The safety profile of etrasimod 2 mg QD in the UC population was consistent across age groups, and with no new risks other than the estimated risks associated with increasing age.² Patients receiving etrasimod in the ELEVATE UC programme showed significant clinical benefit as assessed by clinical remission, symptomatic remission and endoscopic improvement compared with placebo, regardless of age.References1. Lichtenstein GR et al. Inflamm Bowel Dis 2023; 29: 27–41.2. Luo J et al. JMIR Med Inform 2016; 4: e30.Read more P1114 Integral care of the non-Spanish speaking migrant population in inflammatory bowel disease unitsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

In recent years, given the change in the paradigm of management of Inflammatory Bowel Disease (IBD), the different societies have been working to ensure continuous, homogeneous, multidisciplinary social and health care with the patients and their autonomy as the central axis; promoting the creation of Integrated Care Units for IBD patients (ICU-IBD).In the latest analyses of our ICU, attention was drawn to the progressive increase in the demand for care from non-Spanish-speaking migrant patients. This prompted us to carry out this study, with the aim of finding out how this population uses our unit and how it responds to their needs.

Methods

A retrospective longitudinal descriptive observational study with analysis of demographic, clinical and care variables of all non-Spanish-speaking migrant patients followed in the ICU-IBD of our centre until 30 June 2023.

Results

Thirty patients of 14 different nationalities were included, with Moroccan being the most frequent (43.3%); only one of them (3.3%) was fluent in Spanish. Other clinical and demographic characteristics of note were: mean age at follow-up of 43.2 years, predominantly female (66.6%) and predominantly Crohn's disease (63.3%) (Table 1).A total of 86.7% of the patients were referred to our ICU-IBD from the Emergency Department, which they attended due to symptoms related to flare-ups of their intestinal disease.After the initial assessments, we observed that 73.3% did not attend for check-ups, 83.3% of the patients attended the emergency department in the event of a clinical flare-up, and 93.3% showed irregular adherence to treatment. In the subsequent follow-up, we observed a significant change, 76.7% regularly attended consultations, 76.7% consulted the unit in the event of an outbreak and 60% followed treatment regularly (Figure 1). These changes coincide with a socio-health intervention carried out by the specialised nurse; in which patients and their environment were provided with information regarding their disease, treatment and use of the UAI-EII; as well as addressing socio-health problems in order to facilitate their wellbeing and integration into the community.

Conclusion

In view of our results and the data published in other studies, we suggest that the language barrier, the social and healthcare culture of the country of origin, the socioeconomic situation and integration into the new social environment are factors to be taken into account in order to achieve adequate comprehensive care for this migrant population.The role of the IBD nurse is fundamental in the daily work of offering individualised, continuous and comprehensive care to both the patient and their environment; even more so in this population with marked socio-cultural barriers.Read more P948 Hand Grip Strength is a useful objective measure associated with fatigue and impaired quality of life in patients with inflammatory bowel diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Hand grip strength (HGS) is a recognised tool for diagnosis / screening of muscle impairment and sarcopenia, however it remains underutilised in IBD cohorts. The aim of the study was to measure the prevalence of muscle impairment by HGS and association with quality of life in a cohort of UC patients in disease remission.

Methods

Potential subjects were prospectively identified for selection from the Gastroenterology Department in St. Vincent’s University Hospital Outpatient Department. All patients had a confirmed diagnosis of UC for >3 month with stable, quiescent disease (no escalation of medical therapy in the previous 3 months with a documented Faecal Calprotectin (FCP) <100 μg/g). Along with anthropometry data, HGS measurements were performed using the Jamar®Plus+Dynamometer. Quality of life scores were measured using 36-item Short Form Survey (SF-36), Short Inflammatory Bowel Disease Questionnaire (SIBDQ), and Short Health Scale questionnaires were measured. Linear regression was used to calculate standardised β-coefficients for correlation analysis. Non-parametric data was analysed using algorithms including Kruskal-Wallis and Wilcoxon rank-sum test.

Results

60% (n=18) of subjects had a HGS outside the lower limit of the 95% confidence interval of age and sex matched normative values, indicative of impaired grip strength. This was significantly more prevalent in subjects with normal BMI than BMI>30 (p=0.035). Prevalence of fatigue was 43.3% according to SIBDQ question 2a and ’Energy/Fatigue’ scores of SF-36 were significantly lower compared to normal Irish population data (51.0 v 64.8, p = 0.0002). Composite scores of fatigue in both SIBDQ (question 2a) and SF-36 were compared, resulting in a standardized β-coefficient of 0.52 of statistical significance (p value = 0.003).Significant correlation was demonstrated between predicted HGS and ’Energy/Fatigue’ SF-36 scores (standardised β-coefficient = 0.4, p value = 0.027).

Conclusion

HGS is a convenient means of measuring muscle function in an IBD population and correlates significantly with ’Energy/fatigue’ SF-36 scores. These results suggest sarcopenia as a potentially important contributor to fatigue in patients with IBD and suggest HGS is an objective, easily applied objective measure which merits validation as an outcome measure for intervention studies to improve fatigue in patients with IBD.Read more P756 Efficacy and safety of medical therapies for maintenance of surgically induced remission in Crohn’s disease: A systematic review and network meta-analysisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Approximately half of patients with Crohn’s disease (CD) undergo surgical resection in first decade after diagnosis. Majority experience disease recurrence following surgery requiring further intervention. There is limited evidence on efficacy of medical therapies in this setting. We performed a network meta-analysis to evaluate comparative efficacies of medical therapies for the prevention of clinical and endoscopic relapse after surgical resection.

Methods

We searched MEDLINE, Embase, and Cochrane Central Register of Controlled Trials between inception and October 2023 for randomised controlled trials (RCTs). Outcomes assessed were clinical relapse, endoscopic relapse, and safety outcomes including adverse events (AE), withdrawal due to AE, and serious AE. We performed random-effects network meta- analysis using a frequentist approach, and estimated relative risk (RRs), 95% CI values and used GRADE to ascertain certainty of evidence.

Results

A total of 37 RCTs comprising 4411 patients were included. On network meta-analysis of clinical relapse outcome, there was moderate certainty of evidence favouring adalimumab (RR 0.14, 95% CI [0.03-0.7]) over placebo with number needed to treat (NNT) of 3. There was low certainty of evidence supporting 5-amainosalycilates (RR 0.81, 95% CI [0.71-0.92]; NNT of 13) and purine analogues (RR 0.82, 95% CI [0.72-0.93]; NNT of 14) but the effect size was trivial (Figure 1). Whereas for endoscopic relapse outcome, vedolizumab (RR 0.23, 95% CI [0.07-0.8]) and adalimumab (RR 0.32, 95% CI [0.17-0.62], low certainty) and infliximab (RR 0.63, 95% CI [0.48-0.82], low certainty) were the only agents superior to placebo but not purine analogues (RR 0.87, 95% CI [0.7-1.08], very low certainty), 5-ASA (RR 1.04, 95% CI [0.85-1.26], very low certainty), antibiotics (RR 1.13, 95% CI [0.83-1.53], very low certainty), probiotics (RR 1.15, 95% CI [0.94-1.39], very low certainty), vitamin-D (RR 0.9, 95% CI [0.62-1.31], very low certainty) and curcumin (RR 1.17, 95% CI [0.73-1.87], low certainty). On analysis of total adverse events outcomes, all therapies were safe.

Conclusion

On network meta-analysis, adalimumab had a large magnitude of effect size for preventing clinical and endoscopic relapse (low certainty), vedolizumab a large magnitude for preventing endoscopic relapse (low certainty) and 5-ASA a small magnitude result for preventing clinical relapse (low certainty). Overall certainty of evidence is very low to low suggesting need for further research in this field.Read more P985 Efficacy and safety of de-escalation from 50 mg to 25 mg of oral, once-daily, obefazimod for the third and fifth year of open-label maintenance treatment in patients with moderately to severely active ulcerative colitis (UC): An interim analysisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Obefazimod is an investigational, oral, once-daily, small molecule which enhances expression of microRNA-124 and is currently in phase 3 clinical trials for the treatment of patients with ulcerative colitis (UC) [1]. Obefazimod demonstrated efficacy and safety in patients with UC at week-8 in a Phase 2a and Phase 2b, double-blind, placebo-controlled induction trials [2] and their subsequent open-label maintenance (OLM) studies [3].

Methods

Patients with UC who received 50 mg of oral, once-daily, obefazimod for approximately four years in the Phase 2a OLM study and approximately two years in the Phase 2b OLM study, provided they met the eligibility criteria (Mayo Endoscopic subscore = 0 or 1), were given the option to transition to a subsequent open-label maintenance study in which they were administered a daily dose of 25 mg of obefazimod for up to 2 years. This interim analysis, conducted with cut-off date of July 31, 2023, reports the findings of a cohort of patients who completed their week 48 visit.

Results

As of the cut-off date, there were 71 eligible patients, of whom 8 (11%) discontinued prior to week 48 and 63 (89%) completed their 48-week visit. An as observed analysis indicated a disease control rate of 84% (defined as a stable or improved Modified Mayo Score) (Table 1).The levels of fecal calprotectin were <250 and <150 µg/g for 93% (42/45) and 82% (37/45) of patients with available FCP values, respectively.In total, 39/76 subjects (51.3%) reported at least one treatment emergent adverse event (TEAE). The most frequent TEAEs (≥ 5%) were COVID-19 (7.9%) and ulcerative colitis (6.6%). No new safety findings were identified over these 48 weeks.

Conclusion

One year after dose de-escalation to a daily regimen of 25 mg of obefazimod, favorable outcomes in disease control were observed among patients with UC who demonstrated endoscopic improvement (ES<1) after 2-4 years of 50 mg od. No new safety signals have emerged for a duration of up to five years of treatment with once-daily obefazimod.References:1. Vermeire S, et al. J Crohns Colitis. 2023; doi: 10.1093/ecco-jcc/jjad067; 2. . 2021; 3. Vermeire S, et al. The Lancet Gastroenterology & Hepatology. 2022.Read more P757 Patient attitudes, perceptions, and beliefs on the role of diet and nutrition in inflammatory bowel diseases. A scoping reviewWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Despite substantial evidence implicating diet in the development and management of inflammatory bowel disease (IBD), we still lack widely agreeable recommendations for dietary therapy. As a result, patients often self-manage their disease symptoms following a range of dietary regimes, including elimination diets and specific nutrient supplementation. The aim of this in-depth scoping review is to characterise the perception of patients in the role of diet in IBD.

Methods

An extensive literature search was undertaken on PubMed (inception to August ‘23), including MeSH terms ("Inflammatory Bowel Disease" OR IBD OR Crohn's OR Colitis) AND (belief OR perception OR opinion OR views OR attitude) AND (diet OR food OR nutrition). Eligible studies included primary research exploring attitudes, perceptions, or beliefs of adults and children with IBD and/or their carers towards the role of diet in IBD onset, progression or management. We excluded animal, in vitro and non-English articles (Table 1).

Results

1,649 records were identified. After full-text review of 162, 42 papers fulfilled eligibility criteria. Another 6 papers were identified after cross-checking reference lists from included papers, resulting in final inclusion of 48 articles. All articles described that diet perceptions relate with behaviour. In 17 studies a significant percentage of participants considered diet an initiating factor for their IBD diagnosis (Median,IQR: 32%,28%-45%). In 39 studies, patients listed foods they perceived to trigger or benefit their symptoms or inflammation. Most of these studies listed foods affecting the disease for IBD in general (n=29), while fewer studies described trigger and beneficial foods for Crohn’s disease (n=13) and ulcerative colitis (n=16), separately. Spicy food, dairy, alcohol, and coffee were the most perceived as disease-trigger foods, whereas rice, chicken, gluten free products and fish were perceived as beneficial (Fig 1A). Interestingly, 23 studies described patients’ most frequent sources of diet and nutrition information for IBD management (Fig 1B). The top-ranked being patient’s own experience with diet(82%), gastroenterologists(40%), other physicians(35%) and internet(35%). Only 25% of participants reported dietitians as their source of information.

Conclusion

There is a strong belief among patients with IBD that diet is important in disease development and management. It is possible that such beliefs translate to disease management practices, hence increasing restrictive eating, diminish quality or life, including food related quality of life. Until further evidence is produced to pinpoint the exact role of diet in IBD management, it is imperative that HCPs initiate such discussions and advise their patients accordingly.Read more P1115 Characteristics and management of pyoderma gangrenosum and erythema nodosum in patients with inflammatory bowel disease: PIONOSO multicenter studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Inflammatory bowel disease (IBD) is a chronic condition of the gastrointestinal tract. Around 20% of patients develop at least one extraintestinal manifestation, the most frequent being articular, followed by cutaneous and ocular. Among those involving the skin, erythema nodosum (EN) and pyoderma gangrenosum (PG) are frequently observed.

Methods

Our aim was to describe the characteristics of PG and EN in both ulcerative colitis (UC) and Crohn’s disease (CD), and provide a detailed description of their treatment, prognosis and their impact on IBD management. This was a retrospective, multicenter study including all patients with a diagnosis of EN or PG between 01/2013-02/2023. Patients were identified from the ENEIDA registry, a prospectively-maintained database supported by GETECCU. Demographic and clinical characteristics (subtype, date of diagnosis, number of cutaneous lesions, distribution, and location), along with therapeutic requirements and prognosis were registered. Descriptive statistics were used, followed by non-parametric comparisons by chi-square tests.

Results

A total of 542 patients (401 EN, 141 PG) were included among 52,555 IBD patients included in the ENEIDA registry.EN was usually observed in women (77%), mean age of 47 years (SD 15) and CD (76%), mostly located in the lower limbs (97%), followed by upper limbs (Figure 1); lesions were frequently multiple (75%) and bilateral (65%). EN modified the management of IBD in 18% of cases. Steroids were the most frequently used drugs (73% oral, 17% topical, 13% iv); 18% of patients were treated with biologicals, mostly anti-TNF. After 8 weeks, partial response was observed in 19%, and remission in 77%. Recurrence rate of EN was 21%, with 60% developing multiple episodes.PG was mainly seen in women (60%), mean age 52 years (SD 14) and UC (52%), usually located in the lower limbs (75%), followed by arms, thorax or periostomal (Figure 1). The most common type was classic (77%), followed by pustular (19%). Multiple lesions were observed in 56% and unilateral distribution in 62%. PG modified the management of IBD in 29% of cases. Oral steroids were commonly used (54%), followed by biologics (38%) and oral antibiotics (27%). After 8 weeks, 49% of patients showed partial response and 43% achieved complete remission. Recurrence rate of PG was 21%, with 55% developing multiple episodes.

Conclusion

Up to 1% of patients in the ENEIDA registry developed EN and/or PG, usually in the lower limbs and with multiple lesions. Steroids are the mainstay of their treatment, being anti-TNF the main biological agents. EN and PG modify the management of IBD in 21% of cases. Clinical remission rates are higher in EN than in PG, although recurrence occurs in one fifth of patients.Read more P758 Effectiveness and tolerability of methotrexate monotherapy in Crohn’s disease patients: A multicenter observational studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Methotrexate monotherapy is recommended as a maintenance therapy for Crohn’s disease (CD). However, long-term follow-up data are scarce. We aimed to examine the effectiveness and tolerability of methotrexate monotherapy in 94 CD patients from three IBD Clinics in Korea.

Methods

Patients with active CD treated with methotrexate monotherapy were included. Clinical characteristics, laboratory indicators, endoscopy indices were evaluated at baseline, 6, 12, and 24 months. Independent factors associated with long-term clinical and endoscopic outcomes were determined.

Results

Methotrexate was administered orally (70.2%) or parenterally (29.8%). The mean methotrexate induction dose was 15.3 ± 0.4 mg per week, and the mean duration of therapy was 26.2 months. Of 76 patients who were treated for >6 months, the clinical remission rates were 76.3%, 74.6%, and 80.0% at 6, 12, and 24 months, respectively, by per protocol analysis. The mean CRP levels were 7.5 ± 1.3, 5.3 ± 1.2, 3.8 ± 0.7, and 2.6 ± 0.5 mg/L at 0, 6, 12, and 24 months, respectively. Of 31 patients who underwent follow-up endoscopy after 27.5 months, the endoscopic remission rate was 38.7%. Baseline hemoglobin level < 10 g/dL was a significant independent factor negatively associated with clinical remission at 6 (odds ratio [OR]: 0.023, 95% confidence interval [CI]: 0.003-0.206, p = 0.001) and 12 (OR, 0.079; 95% CI: 0.009-0.699, p = 0.023) months. Parenteral administration was a significant independent factor positively associated with clinical remission (OR: 11.231, 95% CI: 1.027-122.811, p = 0.047) and endoscopic remission (hazard ratio: 4.711, 95% CI: 1.398-15.874, p = 0.012) at 12 months.

Conclusion

Methotrexate monotherapy was effective and tolerable as a maintenance therapy in CD patients.Read more P902 Subcutaneous infliximab (CT-P13 SC) as maintenance therapy for Crohn’s disease: 2 years results of the LIBERTY-CD studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

CT-P13 subcutaneous (SC) infliximab formulation showed superiority over placebo as maintenance therapy at Week 54 in Crohn’s disease (CD)¹ and ulcerative colitis². The LIBERTY-CD study¹ included an extension phase up to Week 102, the results, of which, are reported.

Methods

Patients who completed the maintenance phase up to Week 54 and, in the opinion of the investigator, would benefit from continued treatment could continue the open-label extension phase from Week 56 to Week 102 and received CT P13 SC 120 mg regardless of the previous assigned arm of maintenance phase. Patients who had received the adjusted dose of CT-P13 SC 240 mg during the maintenance phase continued receiving the same doses in the extension phase. At Week 54 and Week 102, clinical remission, clinical response, endoscopic remission, endoscopic response, clinical remission (alternative definition) and corticosteroid-free remission were assessed for patients who were treated CT-P13 SC during the extension phase (Figure 1.A) or who were treated CT-P13 SC during the extension phase and had valid efficacy results at the visit of interest (Figure 1.B). Patients with dose adjustment to CT-P13 SC 240 mg prior to Week 54 were considered as non-remitter/non-responder. Safety was evaluated through the extension phase.

Results

A total of 180 patients in the CT-P13 SC arm (assigned arm at the maintenance phase) entered into the extension phase. Overall, 85.6% (154/180) completed extension phase. Compared to the Week 54 results, efficacy results in the CT-P13 SC arm based on the non-responder imputation for missing or invalid data (i.e., patients who had missing or invalid data were considered as non-remitter/non-responder) were generally maintained in clinical remission, clinical response, endoscopic remission, endoscopic response, clinical remission (alternative definition), and corticosteroid-free remission at Week 102 (Figure 1.A). The efficacy results based on the no imputation for missing or invalid data (i.e., observed data) at Week 54 and Week 102 were similar (Figure 1.B). There was no new safety issue reported during the extension phase (Table 1). No death was reported during the extension phase.

Conclusion

Efficacy of CT-P13 SC was maintained through the extension phase. No new safety concerns were observed during the extension phase. These results show that CT-P13 SC provides both a long-term clinical benefit and safety with the convenience of SC administration for moderately to severely active CD patients.[1] Colombel et al., Journal of Crohn's and Colitis, 2023.[2] Sands et al., Journal of Crohn's and Colitis, 2023.Read more P759 Understanding how patients with moderate-to-severe Crohn’s disease describe the spectrum of bowel urgency definitions: Results from qualitative researchWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The objective of this study was to understand how adult patients with moderately-to-severely active Crohn’s disease (CD) describe bowel urgency (BU) remission and “no or minimal” BU.

Methods

Qualitative phone interviews were conducted with adults with HCP-confirmed moderately-to-severely active CD. The interview included open-ended questions that elicited participant (pt) perceptions of BU remission, “no or minimal” and “normal” BU. Pts indicated which score on the 11-point Urgency Numeric Rating Scale (Urgency NRS; 0 [no urgency] to 10 [worst possible urgency] (24hour recall period)) they would use to describe “no or minimal” and “normal” BU. Pts were recruited from 6 clinical sites based in the US. ATLAS.ti was used to organize the data. Descriptive statistics were used for sociodemographic and clinical characteristics.

Results

21 pts with moderately-to-severely active CD participated in this study. Pts had a mean age of 45.4 years, 71% were female, 91% were white, and 48% were employed full-time. All pts had experienced BU and 86% (n=18/21) confirmed they had experienced a BU-related accident in the past. The majority of CD pts (n=18/21; 86%) defined BU remission as a state of normalcy, where there are normal or fewer bowel movements and BU is either gone or less frequent (Table 1). The impact of BU remission included the ability to partake in social/leisure activities and feeling less anxious overall.Pts selected scores from 0 to 6 on the Urgency NRS to describe “no or minimal” level. The highest proportion of pts (n=7/21; 33%) selected “0 to 2,” with “0 to 3” (n=5/21; 24%) and “0 to 1” (n=5/21; 24%) also being commonly chosen ranges. The majority of pts (n=17/21; 81%) described “no or minimal” BU as having no impact on their life—thus allowing them to feel close to “normal,” and offering them the ability to live an improved life free of worry or panic. Pts were also asked to indicate the highest score on the Urgency NRS at which they could still consider their BU to be “normal” and 29% of pts (n=6/21) selected 4 or 3 (n=5/21; 24%) as the highest score that they would still consider as “normal.”

Conclusion

These interviews provided evidence that among pts with moderately-to-severely active CD, BU can still be considered “no or minimal”, “normal” or in “remission” even when some amount of BU is present. In general, responses of “0” to “6” on the Urgency NRS were considered to correlate to “no or minimal” or “normal” BU.Read more P1134 Incidence of invasive fungal diseases in inflammatory bowel disease patients: a nationwide study in South KoreaWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Limited reports exist regarding invasive fungal diseases (IFDs) in inflammatory bowel disease (IBD) patients. This study aims to investigate the incidence and risk factors of IFDs, specifically invasive candidiasis, aspergillosis, and pneumocystosis, in IBD patients in South Korea using nationwide data.

Methods

A population-based retrospective cohort of 42,913 IBD patients between January 2010 and December 2018 was evaluated using the Health Insurance Review and Assessment database. The primary outcome was the incidence of IFDs, including invasive candidiasis, aspergillosis, and pneumocystosis, while the secondary outcome involved analyzing the risk factors associated with each specific infection.

Results

The study included a total of 42,913 IBD patients, with 29,909 (69.7%) diagnosed with ulcerative colitis (UC) and 13,004 (30.3%) diagnosed with Crohn's disease (CD). IFDs occurred in 166 IBD patients (0.4%), with 93 cases in UC patients and 73 cases in CD patients. The incidence rates of invasive candidiasis, aspergillosis, and pneumocystosis in IBD patients were 0.71 per 1,000 person-years (PYs), 0.15 per 1,000 PYs, and 0.12 per 1,000 PYs, respectively. The cumulative incidence of invasive candidiasis (adjusted p-value < 0.001) and pneumocystosis (adjusted p-value = 0.012) was found to be higher in CD patients than in UC patients. Each IFD had different risk factors, including IBD subtypes, age at diagnosis, anti-tumor necrotic factor agents, or the Charlson comorbidity index.

Conclusion

Based on nationwide data in South Korea, this study shows that IFDs occur consistently in patients with IBD, albeit with a low frequency.Read more P903 Persistence, efficacy and tolerance of subcutaneous Infliximab after switch from intravenous infliximab in IBD patients in remission: one-year results from a multicenter prospective cohortWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Prospective data after switch from intravenous infliximab (IV-IFX) to subcutaneous (SC-IFX) in Inflammatory Bowel Disease (IBD) is needed. The aim of this prospective multicenter cohort was to describe SC-IFX persistence, efficacy and tolerance after switch from IV-IFX.

Methods

IBD patients in steroid-free clinical remission (defined by a Harvey Bradshaw index (HBI) ≤ 4 for Crohn’s disease (CD), and partial Mayo Score (PMS) ≤ 2 with no subscore >1 for ulcerative colitis UC)) for at least 6 months on IV-IFX, were enrolled in this prospective cohort if they switched to SC-IFX.Clinical (HBI, PMS), biological (CRP, fecal calprotectin (FC)) and pharmacokinetic evaluations were performed at 3, 6, 12 and 24 months from switch. In case of clinical or biological relapse, as per physicians’ judgement, SC-IFX dose could be increased, or drug changed.Primary endpoint was SC-IFX persistence at week 48 (W48). Secondary endpoints comprised steroid-free clinical remission at W48, proportion of patients who switched back to IV-IFX, HBI and PMS changes and FC, CRP and infliximab serum level changes. Statistical comparisons were performed using Fisher’s exact test. Survival without treatment discontinuation was analysed using a Kaplan-Meyer curve.

Results

426 patients were included (72.4% CD, 45.1% female, median age 37 years), with a median time from diagnosis of 143 months in CD, 154 months in UC. At baseline, 74% were on IV-IFX standard dose (5mg/kg every 8-week) and 68 (16%) received combination therapy with an immunosuppressant.Among patients with complete data until W48, SC-IFX persistence was 95.3% (CI, 93.2-97.5). 319/367 (89.9%) were on steroid-free clinical remission.From baseline to W48, median HBI and PMS scores were 0, CRP did not change significantly, median FC rate decreased significantly from 52µg/g to 36 µg/g (p=0.015). Mean Infliximab trough level at inclusion was 7.97µg/mL, while it reached 17.96µg/mL at W48 (p<0.0001).23 (5.4%) patients had an increase of SC-IFX dose and 22 (5.2%) stopped SC-IFX, of which 6 patients switched back to IV-IFX. SC-IFX persistence was significantly higher among patients treated with SC-IFX monotherapy (98.8%) as compared to those on combination therapy (90.0%) (HR=0.14 [0.04-0.53]).Adverse events were reported in 181/426 patients (42.4%), 12 led to treatment discontinuation. Nine severe adverse events (2%) were reported. Three patients (0.7%) had IBD-related surgery and 8 (1.9%) IBD-related hospitalization.

Conclusion

In this large multicenter prospective cohort of IBD patients in remission, one-year persistence of SC-IFX after switch from IV-IFX was 95.3%, supporting excellent efficacy and tolerance of SC-IFX.Read more P809 VARIETY BEACH: Real-world treatment patterns for vedolizumab intravenous and subcutaneous maintenance dosing observed over 1 year in studies from Belgium, Austria and SwitzerlandWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Vedolizumab (VDZ) is approved for moderate to severe ulcerative colitis (UC) and Crohn’s disease (CD) as intravenous (IV) or subcutaneous (SC) formulations. Real-world data on VDZ treatment patterns in patients (pts) with inflammatory bowel disease (IBD) comparing VDZ IV or SC maintenance are still scarce.

Methods

Three prospective, non-interventional, observational studies following an umbrella protocol enrolled pts in Belgium (NCT04959851), Austria (NCT04890262) and Switzerland (NCT04989907) from Aug 2021 to Jun 2022. Adults initiating VDZ IV induction per the product label or continuing VDZ IV maintenance with the option to switch to SC administration, were eligible. The primary endpoint was VDZ treatment persistence at 1 year. Administration route, dosing frequency, reasons for regimen change and safety endpoints were also assessed. Non- responder imputation was applied for pts discontinuing treatment, discontinuing the study or lost to follow-up. A descriptive analysis was performed.

Results

Of 377 pts enrolled, 373 (UC=218, CD=155) were included in this interim analysis. At enrolment, 287 (77%) (UC=159, CD=128) already received VDZ IV maintenance for median 2.8 (0–12.6) years and 86 (23%) (UC=59, CD=27) started VDZ induction (baseline pt characteristics summarized in Table 1). For pts enrolled on VDZ IV maintenance, 12 discontinued vedolizumab, 34 discontinued the study and 14 were lost to follow-up; resulting in a VDZ persistence rate at 1 year of 79% (227/287). Of pts in this cohort persistent on VDZ at 1 year (n=227; UC=124, CD=103), 39% (88/227) switched from VDZ IV maintenance to SC during the study. For pts initiating VDZ induction, 10 discontinued VDZ, 16 discontinued the study and 3 were lost to follow-up; resulting in a VDZ treatment persistence of 66% (57/86). Of pts from this cohort persistent on VDZ at 1 year (n=57; UC=43, CD=14), 56% (32/57) switched to VDZ SC during the study (Figure 1). Overall, the most common reasons for administration route changes were pt decision 98/161 (61%; UC=56%, CD=67%), end of induction (planned switch: 10%; UC=14%, CD=5%) and disease adequately controlled (6%; UC=7%, CD=3%). Adverse events (AEs) occurred in 48 pts (13%) (UC=20, CD=28) and serious AEs in 6 pts (2%) (UC=3: Budd-Chiari syndrome, death cause unknown, UC worsening; CD=3: bronchopneumonia, gastroenteritis, recurrent urinary tract infection).

Conclusion

Real-world data from prospective observational studies in Belgium, Austria and Switzerland reported high persistence of VDZ IV and SC maintenance treatment over 1 year. Decisions on route of administration change were most frequently driven by patients. Safety results were consistent with the known safety profile of VDZ.Read more P1135 Increased prevalence of migraine in women with inflammatory bowel disease: a cross-sectional studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Data on a possible comorbidity between migraine and inflammatory bowel disease (IBD) are controversial. Our aim was to determine the prevalence of migraine in a cohort of IBD patients.

Methods

We performed a cross-sectional study in a cohort of IBD patients at our IBD Unit. After informed consent, consecutive IBD patients aged 18-64 years were interviewed. Those who admitted a history of headache in the last year were asked to answer the three questions of the id-Migraine validated questionnaire. Those who answered "yes" to the three of them were classified as "definite" migraine and those who answered "yes" to two were classified as "probable" migraine. For all patients we collected demographic data, IBD subtype, disease duration, hospitalizations or surgeries and medical treatments. Migraine prevalence data of IBD patients were compared with reported local migraine prevalence data at 18-65 years of age (Cephalalgia 2011; 31: 463-70). Statistical analysis was done with SPSS®.

Results

We interviewed 283 consecutive IBD patients aged 20-65 years. Main characteristics of this population are described in table 1.Headache was present in 176 (62.2%) patients. Of those, 59 (20.8%; 95% CI 16.1-25.5%) met migraine criteria either definite (n= 33; 11.7%; 95% CI 8-15.4%) or probable (n=26; 9.2%; 95% CI 5.8-12.5). When divided by gender, 12 men (9.6%; 95% CI 4.4-14.) and 47 women (29.8%; 95% CI 22.7-36.9%) met migraine criteria.The prevalence of migraine was significantly increased in IBD patients (20.8%) versus that reported for our general population (12.6%; p= 0.0001). By sex, these differences remained significant in women (29.8% in IBD versus 17.2% in our general population; p=0.0001), but not in men (9.6% in IBD vs 8.0%; p=0.45) (Figure 1).By IBD subtypes, there were no significant differences between CD and UC in migraine prevalence (20.7% vs 19.6% respectively; p=0.58). Regarding IBD characteristics, men with total migraine had higher biologic treatment (66.7% vs 44% p=0.032), and immune mediated inflammatory diseases or extraintestinal manifestations of IBD (33.3% vs 9.6% p=0.0016), but the number of men with migraine was low (12). These associations were not significant for women, nor overall population (p>0.05). Additionally, we did not find any significant association in total migraine patients in the use of mesalazine, disease duration, immunomodulators, surgeries or hospitalizations, neither in total number of patients nor stratified by sex.

Conclusion

Migraine prevalence is higher in patients with IBD than general population, which is a further example of the bidirectional gut-brain interaction. The fact that this association was stronger for women suggests an influence of sex-related factors.ISCIII PI20/01358 and FEDER.Read more P810 Fecal microbiota transplantation in Ulcerative rectocolitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The objective of this work was to carry out a systematic review of the literature to evaluate interventional trials that compare fecal microbiofa transplantation (FMT) with a control group and evaluate the incidence of remission of ulcerative colitis as an outcome.

Methods

The search was conducted using the database from PubMed, from February 2021 to April 2023. In all, 303 articles were found. After reading the titles, 43 articles were selected for the abstract reading. After all the analysis with inclusion and exclusion criteria, 7 articles were fully analyzed in the present study. Of the 7 selected studies, 71% (5/7) performed clinical trials.

Results

In all the studies, a total of 352 patients were submitted to the FMT, with a average of 63 participants per study. The age of the participants vary from 18 to 75 years old, with all the studies having an average age in the third or fourth decade. All articles included patients with clinical disease activity, and 85.7% used the Mayo severity index. Regarding the stool administered, in 71.4% of the studies the participants received frozen stool and the preparation was carried out with saline solution. The infusion was performed with colonoscopy on 85% (6/7) of the studies, however there was no standardized approach to the transplant protocol or preparation of the patients before the FMT. The association between the FMT and the clinical remission has been positive in 85% (6/7) of the studies. 4 of the 5 articles that evaluated the clinical response pointed to an improvement of the patients submitted to the transplant over the placebo group. The endoscopic remission were analyzed in all the 7 studies showing positive results in 43% (3/7) of them. The laboratory were performed in just 1 of the studies and they reported substantial improvement of the evaluated parameters of the FMT group. There was no significant difference between the risk of developing adverse effects between the FMT and the placebo groups.

Conclusion

The FMT has been shown to be effective on the induction of clinical remission of Ulcerative Colitis, however, clinical studies with greater scientific impact are needed to implement this new therapeutic modality.Read more P923 Haematological abnormalities during treatment with Janus kinase inhibitors in patients with Ulcerative Colitis: a post hoc analysisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Janus kinase inhibitors (JAKi) are used for Ulcerative Colitis treatment and could lead to haematological abnormalities, such as anaemia. In this post hoc analysis, we evaluated whether treatment with tofacitinib or filgotinib is associated with anaemia and other haematological laboratory abnormalities.

Methods

Data from randomized clinical trials [OCATVE 1 (NCT01465763), OCTAVE 2 (NCT01458951), OCTAVE Sustain (NCT01458574), and summary-level data from SELECTION (NCT02914522)] evaluating the efficacy of filgotinib and tofacitinib were used in this post hoc analysis. Adult patients with moderate-to-severe Ulcerative Colitis received induction therapy with filgotinib, tofacitinib, or placebo. After induction, patients in remission were re-randomized to receive either filgotinib 100 mg QD, filgotinib 200 mg QD, tofacitinib 5 mg BID, tofacitinib 10 mg BID, or placebo. We evaluated and compared the proportions of patients with anaemia, leukopenia, neutropenia, lymphopenia, and thrombocytopenia at baseline, after induction therapy (i.e., 8–10 weeks), and after 52–58 weeks of maintenance therapy in these treatment groups.

Results

At least a third of patients across all treatment groups had anaemia at baseline, the proportion of those who recovered from anaemia after induction did not differ (Table 1): 29.9% in the tofacitinib 10 mg group, 25.6% in the filgotinib 200 mg, and 30.7% in the filgotinib 100 mg group (P = 0.571). The proportion of patients who developed anaemia after the induction phase also did not differ: 16.7% in the tofacitinib 10 mg group, 17.3% in the filgotinib 200 mg, and 12.1% in the filgotinib 100 mg group (P = 0.880), as presented in Table 1. In contrast, 3.1–5.6% of patients in the tofacitinib groups vs. 7.1–14.5% in the filgotinib groups developed anaemia after 52–58 weeks of treatment (P = 0.036); however, the difference was not statistically significant after correction for multiple testing. Other haematological laboratory abnormalities, except lymphopenia, either did not occur or occurred infrequently across all treatment groups. Data regarding lymphopenia was available only from the OCTAVE trials; after 52 weeks of maintenance therapy, approximately 22% of patients in the tofacitinib groups had lymphopenia compared with 3.8% in the placebo group (P = 0.008).

Conclusion

Heterogeneous data limited this post hoc analysis. Haematological laboratory abnormalities, except for anaemia and lymphopenia, were infrequent. Therapy with JAKi was not associated with an increased occurrence of anaemia. However, since lymphopenia occurred more frequently in patients under treatment with tofacitinib, close monitoring is advisable to manage the risk of infection in these patients.Read more P1153 Hospital surgical volumes and outcomes in ileocaecal resection for Crohn’s disease in Sweden 2000-2019: A national cohort studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Intestinal resection for Crohn’s disease (CD) is often complex and remains associated with significant postoperative morbidity. In several other types of complex surgery, increased case volumes have been associated with better outcomes. In surgery for CD, such an association has not yet been demonstrated.

Methods

In this nationwide cohort study, we used the National Patient Register to identify all CD patients who underwent their first (primary) ileocaecal resection in Sweden 2000-2019 at age 15 years or above. Hospitals were grouped into low, middle, and high-volume centres based on the number of intestinal resections for CD the previous calendar year (1-24, 25-36 and ≥37 resections, respectively). Length of hospital stay, severe postoperative complications and deaths during the first 100 days after the date of index surgical admission were compared between groups, and adjusted for sex, age, duration of disease, preoperative corticosteroid therapy, and year of surgery. Rates of surgical reintervention were used as a measure of severe postoperative morbidity.

Results

In the 20-year study period, 3396 patients underwent primary ileocaecal resection for CD in Sweden; 2371 (69.8%), 527 (15.5%) and 498 (14.7%) in low, middle, and high-volume hospitals, respectively. Median age at surgery was 41, 39 and 34 years, respectively, and the proportion of patients with a diagnostic record of perianal disease was 9, 10 and 16%. Sex, extraintestinal manifestations and preoperative medical therapies and hospital admissions did not differ between hospital types. Laparoscopic surgery was performed in 351 (15%), 126 (24%) and 122 (24%) patients, respectively. Surgical reintervention within 100 days was performed in 117 (4.9%), 19 (3.6%) and 13 (2.6%) patients in the three groups (adjusted odds ratios 0.72 (95% confidence interval 0.43-1.15) for middle-volume and 0.52 (0.28-0.89) for high-volume hospitals, compared to low-volume hospitals, Figure). There were no differences in the length of index admission hospital stay or mortality.

Conclusion

In primary ileocaecal resection for CD, high-volume hospitals had lower odds of early surgical reintervention, compared to low-volume hospitals. This finding may inform considerations of subspecialisation and centralisation in surgery for Crohn’s disease.Read more P811 Age as a Predictor of Serum Tumor Necrosis Factor Antagonist Drug and Anti-drug Antibody Concentrations in Inflammatory Bowel Disease; A Nationwide Retrospective StudyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Tumor necrosis factor antagonists (anti-TNFs) are effective for the induction and maintenance of remission in inflammatory bowel disease (IBD). Several factors have been shown to be associated with anti-TNF treatment failure. We aim to investigate the relationship between age and serum anti TNF drug and Anti-drug Antibody Concentrations

Methods

This was a multicenter retrospective cohort study. Chart review was conducted by evaluating patients' charts from July 2018 until September 2023. The impact pf age on anti-drug antibodies and serum drug concentration in patients with IBD across seven hospitals was investigated. Logistic regression was performed to explore the relationship between age and serum anti TNF drug and Anti-drug Antibody Concentrations (ADAbs)

Results

1093 patients were included, of which 911 (83.3%) were above the age of 16. Mean age was 30.1 years old and 574 (52.2%) were males. 461(42.2%) patients were on infliximab and 632 (57.8%) patients were on adalimumab. In patients receiving infliximab, there was a significant association between older age and increasing ADAbs levels (p =0.036). Whereas in patients on adalimumab, there was no significant relationship between older age and ADAbs levels (p=0.771). Additionally, there was a significant association between older age and decreasing infliximab serum concentration (p = 0.02). Finally, there was no significant relationship between age and adalimumab serum concentration (p = 0.54).

Conclusion

In patients receiving infliximab, anti-drug antibodies were higher in older patients. Consistent with this, serum drug concentrations were lower in older patients on infliximab. There was no difference in anti-drug antibody and serum drug concentrations among patients receiving adalimumab.Read more P924 Function and outcomes of ileal-pouch anal anastomosis in patients with connective tissue disordersWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Ileal-pouch anal anastomosis (IPAA) is a widely preferred surgical intervention for patients with medically refractory ulcerative colitis, familial adenomatous polyposis, and indeterminate colitis. Concerns have been raised regarding the impact of connective tissue disorders on the outcomes of IPAA due to potential alterations in collagen metabolism. To date, there is a lack of studies assessing the feasibility, long-term viability and pouch function of IPAA in patients with connective tissue disorders. We hypothesized that the presence of a connective tissue disorder might be associated with a higher rate of pouch complications and failure.

Methods

Data were collected from a prospectively maintained pouch database and chart reviews. Patients with connective tissue disorders were propensity score matched in a 1:5 ratio with control pouch patients without connective tissue disorder. A comparative analysis of demographics, long-term complications, functional outcomes, and quality of life was conducted.

Results

A total of 19 patients with connective tissue disorders were matched to 95 control pouch patients. The postoperative diagnoses were ulcerative colitis (82.5%), indeterminate colitis (7%), constipation (5.3%), Crohn's disease (4.4%), and familial adenomatous polyposis (1%) Connective tissue disorders identified, included unspecified diffuse connective tissue disorders (26.3%), Ehlers-Danlos syndromes (15.7%), Sjogren's syndromes (15.7%), and others. Patients with connective tissue disorders were more likely to experience pouchitis (79% vs. 56%, p=0.04). Differences in rates of pouch prolapses (10.5% vs. 4.2%, p=0.26) and of pouch failure (26.3% vs. 13.7%; p=0.17) were present but failed to achieve statistical significance. Functional outcomes, and quality of life were similar in both groups.

Conclusion

IPAA remains a feasible surgical option for patients with connective tissue disorders, offering comparable functional outcomes and quality of life. Physicians treating patients with these disorders should be aware of a potentially elevated risk of pouchitis, pouch prolapse and pouch failure.Read more P812 Whole Food and Antioxidants Consumption Linked to Lower Risk of Inflammatory Bowel Disease in TaiwanWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The incidence of inflammatory bowel disease (IBD) rapidly increases in Asia, and western dietary pattern is suspected to be the major risk factor. Despite this, there has been a lack of studies analyzing the relationship between dietary patterns and IBD in Taiwan. This study examines the dietary habits of Taiwanese individuals with and without IBD to inform clinical dietary recommendations for IBD patients.

Methods

A comprehensive survey utilizing structured questionnaires to collect baseline characteristics and dietary information from both IBD patients and healthy controls from February and August 2022. The dietary habits of IBD patients in this study were focused on the three months leading up to their IBD diagnosis. Numerical data were presented as mean ± standard deviation, while categorical data were expressed as absolute numbers and percentages. Statistical analysis involved the Mann–Whitney U test for continuous variables and the chi-square or Fisher's exact test for categorical data. Statistical significance was defined as p < 0.05, and all analyses were performed using SPSS version 22.0.

Results

Our study included 98 IBD patients, with 46 diagnosed with Crohn's disease and 52 with ulcerative colitis, along with 184 healthy controls. Notably, in terms of baseline characteristics, the IBD group exhibited a significantly higher prevalence of cigarette smokers compared to the control group (29.5% vs. 12.6%, p = 0.001). Regarding dietary habits, IBD patients reported consuming significantly fewer natural food categories compared to the control group. These differences included lower consumption of rice products (p = 0.005), cereal products (p < 0.001), mixed-grain products (p < 0.001), mushrooms (p = 0.004), burdock (p = 0.001), poultry (p = 0.049), and milk (p < 0.001). Intake of red meat, seafood, and nuts was comparable. Concerning processed food products, IBD patients also reported less frequent consumption of soymilk (p = 0.017), mock meat (p = 0.012), and tea (p = 0.043). In terms of dietary supplements, IBD patients were less likely to use vitamin supplements (C or E) compared to healthy controls (25% vs. 42.4%, p = 0.004), and they also reported lower consumption of soybean lecithin (1% vs. 7.6%, p = 0.02). The baseline characteristics, frequency of natural foods, processed foods and dietary supplement consumption were summarized in Table 1.

Conclusion

The findings of our study suggest that a diet rich in whole foods and antioxidant may be associated with lower risk of IBD in Taiwan. However, it’s important to note that further research with a larger sample size is necessary to confirm these observations and provide more robust insights into the relationship between dietary factors and IBD.Read more P1080 Real-world Study on Early Predictors of Infliximab Treatment Efficacy in Crohn's diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Infliximab (IFX) can effectively induce and maintain the clinical remission of Crohn's disease (CD). However, a substantial number of CD patients experience primary or secondary nonresponse to IFX during treatment. Therefore, it is essential to identify early predictors of IFX treatment efficacy.

Methods

This study included 147 CD patients. Based on clinical outcomes, patients were categorized into IFX nonresponse and response group. We collected and compared laboratory data on blood routine examination, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), fecal calprotectin and post-induction IFX drug concentration and antibody levels in both groups. Logistic regression models were employed to identify potential factors associated with the risk of IFX nonresponse. Machine learning using random forest analysis was utilized to quantitatively assess the predictive features for IFX treatment efficacy and ROC curves was used to evaluate the model’s accuracy. Additionally, we performed HE staining and double immunofluorescence staining for CD64 and CD206 on intestinal biopsy tissues obtained before IFX treatment to compare the difference of macrophage subtypes between the nonresponse and response groups.

Results

Data from both cohorts revealed that patients in the IFX nonresponse group had lower drug concentration (P < 0.001), higher antibody levels (P < 0.001), and increasing ESR during the induction therapy (P < 0.001). Univariate and multivariate Logistic regression models demonstrated that IFX drug concentration and the ratio of ESR before and after induction therapy were associated with the risk of nonresponse. After the induction period, for each unit increase in drug concentration (1 μg/ml), the risk of IFX nonresponse decreased by 23% (RR= 0.77, 95% CI = 0.68-0.89), while each doubling of the ESR ratio after induction was associated with a 1.43-fold increase in the risk of nonresponse (RR= 2.43, 95% CI = 1.48-4.00). After combining data from the two cohorts, random forest machine learning analysis revealed that drug concentration below 1.5 μg/ml and an increase in ESR during induction could predict IFX nonresponse, with ROC curve areas of 0.740 and 0.651, respectively. Furthermore, immunofluorescence staining of intestinal mucosal biopsy tissues before IFX treatment showed a higher proportion of M1-type macrophages in the nonresponse group compared to the response group (P < 0.05).

Conclusion

Our study suggests that lower post-induction IFX drug concentrations and an increase in ESR during the induction phase are predictive of IFX nonresponse. Additionally, a higher proportion of M1-type macrophages in the intestinal mucosa before IFX treatment is associated with IFX nonresponse.Read more P1003 Dietary pattern can influence the level of fatigue in patients with Inflammatory Bowel Disease in remissionWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

It is well known that dietary pattern can play an important role in the onset of inflammatory bowel diseases (IBD). In patients with established disease, they can influence the risk of relapse and the disease course.The aim of the study is to explore the impact of dietary patterns on health-related quality of life (HR-QoL), fatigue, anxiety and depression in patients with IBD in corticosteroid-free clinical remission.

Methods

A total of 96 consecutive patients diagnosed with IBD that were in corticosteroid-free remission for at least 12 weeks were enrolled in this observational, cross-sectional study.During an interview, patients were asked about their dietary patterns. Twelve categories of foods were identified, 6 of them being considered "healthy" (vegetables and fruits >4 portions/day, cereals >3 portions/day, seeds >4 portions/week, cheese >1 portion/day, yoghurt >1 portion/day, fish >2 portions/week) and the other 6 "unhealthy" (fatty red meat >1 portion/day, sweetened beverages >1L/day, cured meat >2 portions/day, fried food >1 portion/day, chips >1 portion/day, mayonnaise >1 portion/day) (see Figure 1).An "unhealthy" dietary pattern was considered if the proportion of "unhealthy" food categories from the total food categories consumed by the patient exceeded 50%.HR-QoL, fatigue, anxiety and depression were evaluated using the following self-administered questionnaires: IBDQ-32, FACIT-Fatigue and HADS.

Results

Out of the 96 patients included, 60 (62.5%) were men. The median patient age was 38 years (IQR 31.5 – 45.5). Sixty patients (62.5%) were diagnosed with CD, and 36 (37.5%) with UC. Most of the patients were treated with biologics (93.8%).An unhealthy dietary pattern was identified in 58 (60.4%) patients.Patients with an "unhealthy" dietary pattern experienced significantly more fatigue compared to patients with a "healthy" dietary pattern (mean FACIT-F score 40.3 vs. 44.4 points, p=0.02). Even though not statistically significant, patients with "unhealthy" dietary pattern had a trend towards a lower HR-QoL (mean IBDQ score 187.3 vs. 192.8, p=0.24). Anxiety and depression were less frequent among patients with "unhealthy" dietary pattern, but the differences were not statistically significant (anxiety: 24.1% vs. 31.6%, p=0.57; depression: 13.8% vs. 21.2%, p=0.51).

Conclusion

Patients with an "unhealthy" dietary pattern experience significantly higher levels of fatigue compared to patients that are eating "healthier" food. There is also a trend towards lower HR-QoL in this category of patients.Read more P870 Effectiveness and safety of adalimumab as first line biological treatment in Ulcerative ColitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The increase in licensed therapies for ulcerative colitis (UC) is revolutionizing its treatment but making first line choice more challenging. Adalimumab (ADA) is inexpensive but, anecdotally, is sometimes regarded as less effective than other first line advanced therapies. We aimed to evaluate the results of first line ADA in UC.

Methods

We performed a single centre retrospective analysis of UC patients started on ADA between January 15 and March 2022 in an IBD referral hospital. Clinical remission was defined as SCCAI <2 points, endoscopic remission as a UCEIS <2 points and treatment failure as the need for colectomy or second biological line

Results

A total of 79 patients were included (Table 1). Median follow-up was 19 months (2-91); 78.5% were followed >6 months. At 6 months, 80.3% (61/76) and 37.3% (22/59) of the patients were in clinical and endoscopic remission, respectively. 54.3% received combination treatment with immunomodulators (50.6% thiopurines, 3.7% methotrexate). Dose intensification to weekly treatment occurred in 27.8% after median 9 months (4-48 months).During follow-up 51% received corticosteroids at some point (26% topically-acting oral corticosteroids, 10% oral corticosteroids, 15% both). Of patients who received steroids, 55% (22/40) were able to continue adalimumab therapy. 2.5% of patients were hospitalised for a disease flare. 5.1% had an infection recorded during follow up, none discontinued the treatment. No other major adverse events were recorded.In 22.8% (18/79) of patients, ADA was stopped due to treatment failure, mean 15 months after starting the drug (4-56 months), (Figure 1). None of these patients underwent colectomy at the time of stopping the drug; in 17/18 a second biological therapy was started (10 tofacitinib, 1 filgotinib, 1 upadacitinib, 2 ustekinumab, 2 vedolizumab, 1 golimumab). TDM was performed using a drug-sensitive ELISA, which is only able to detect antidrug antibodies when drug levels are low or absent. Drug levels at the time of stopping the drug were <5 µg/mL in 22% of patients (in 2 antibodies were detected), 5-8 µg/mL in 11% and >8 µg/mL in 67%.

Conclusion

In a real-world UC cohort, ADA appears to be an effective well tolerated first-line advanced therapy with the vast majority of patients reaching clinical remission and a significant proportion achieving mucosal healing.Table 1. Cohort characteristics (N 79, frequency and %).Figure 1: Kaplan-Meier survival analysis of time to ADA discontinuation.Read more P1004 Proportion of agents for refractory ulcerative colitis and the efficacy of immunomodulator in 5-aminosalicylic acid intoleranceWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

5-Aminosalicylic acid (5-ASA) is effective for ulcerative colitis (UC), yet several patients exhibit intolerance to this medication. Although biologics and immunomodulators are often employed in cases of 5-ASA intolerance in UC, reports on their induction rates and effectiveness are sparse. This study aims to ascertain the proportion of therapeutic agents for refractory UC and evaluate the efficacy of immunomodulators in patients intolerant to 5-ASA.

Methods

We conducted a retrospective chart review of 182 consecutive UC patients treated for refractory UC at our tertiary referral hospital from 2014 to 2023. The 5-ASA intolerance group comprised patients who initiated oral 5-ASA therapy, discontinued one or more oral 5-ASA treatments within 6 months due to adverse effects, and were unable to continue oral 5-ASA therapy for over 6 months. Those who had been on oral 5-ASA for more than 6 months were categorised as the 5-ASA tolerance group. We compared the types of agents for refractory UC (immunomodulators, calcineurin inhibitors, anti-TNF-α agents, vedolizumab, ustekinumab, JAK inhibitors), disease duration, and clinical background (age at diagnosis, history of acute severe UC [ASUC], disease extent) between the groups. Additionally, we examined the discontinuation rates due to adverse effects and the continuation rate of immunomodulators.

Results

Among the patients treated with agents for refractory UC, 19 belonged to the 5-ASA intolerance group and 163 to the 5-ASA tolerance group. The time to initiation of treatment for refractory UC was significantly shorter in the 5-ASA intolerance group compared to the 5-ASA tolerance group (median 69 days vs 1431 days, p < 0.001). The induction of immunomodulators occurred in 78.9% of the 5-ASA intolerance group, versus 38.0% in the 5-ASA tolerance group (p = 0.001). Anti-TNF-α agents was not used in the 5-ASA intolerance group, while 33.7% of the 5-ASA tolerance group received it (p = 0.001). 15 patients in the 5-ASA intolerance group and 53 in the 5-ASA tolerance group were introduced to immunomodulators to maintain remission. Discontinuations due to adverse effects were noted in 33.3% of the 5-ASA intolerance group and 18.9% in the 5-ASA tolerance group, but the differences were not significant. The one-year cumulative continuation rate of immunomodulators, excluding patients who discontinued due to adverse effects, was 93.3% in the 5-ASA intolerance group and 77.4% in the 5-ASA tolerance group, with no significant difference observed.

Conclusion

Immunomodulators are frequently introduced in cases of 5-ASA intolerance. No significant difference was found in the discontinuation rate of immunomodulators, with a high cumulative continuation rate observed in the 5-ASA intolerance group.Read more P1082 A comparative analysis of persistence of advanced therapies among patients with Inflammatory Bowel Disease in TaiwanWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The prevalence of inflammatory bowel disease (IBD) has been rapidly increasing in Asia. Advanced therapies have significantly improved outcomes for moderate to severe cases of IBD. With the expanding availability of advanced therapies, the selection of the most suitable treatment option has become crucial. Among various factors, treatment persistence holds paramount importance. We present the first study in Asia that compares real-world persistence rates among advanced therapies in IBD patients in Taiwan.

Methods

In this retrospective cohort study, we enrolled patients with IBD who were treated with five advanced therapies: infliximab (IFX), adalimumab (ADA), vedolizumab (VDZ), ustekinumab (UST), and tofacitinib (TOF) at Linkou Chang Gung Memorial Hospital between October 2017 and April 2023. UST followed a standard maintenance dosing frequency of every 12 weeks, while TOF was permitted for use only as a second-line treatment option for UC in Taiwan. We compared baseline data and drug persistence rates within the first 52 weeks for the overall group, biologic-naïve patients, and biologic-experienced patients.

Results

A total of 432 IBD patients were included, with 173 (40%) having ulcerative colitis (UC) and 259 (60%) having Crohn's disease (CD). The majority of patients were male, with a mean age of 43.6 years and a mean BMI of 22.6. UST showed the highest rate of dose escalation (22%). Across all five drugs, the primary reason of discontinuation was secondary loss of response, with IFX having the highest discontinuation rate due to side effects (20%). Other baseline characteristics were presented in Table 1.Kaplan-Meier analysis revealed that all biologics exhibited a persistence rate of over 50% within the initial 52 weeks. UST demonstrated the highest 52-week persistence rates in overall (87.88%, p < 0.001, Figure 1a), biologic-naïve (96.55%, p = 0.002, Figure 1b) and biologic-experienced CD patients (80.56%, p=0.043, Figure 1c). Although no statistically significant differences were observed between advanced therapies in overall UC patients and other subgroup analyses (Figure 1d-1f). VDZ showed highest 52-week persistence in overall (69.05%, p=0.078, Figure 1d) and biologic-experienced (60.87%, p=0.751, Figure 1f) UC patients. UST had highest 52-week persistence in biologic-naïve UC patients (100%, p=0.329, Figure 1e).

Conclusion

In this pioneering real-world comparison of advanced therapies across one year in Asia, UST exhibited superior 52-week persistence rates in CD patients. However, the rate of dose escalation in UST was also the highest among these therapies. The study's limitations include its single-center nature and relatively small sample size.Read more P683 Economic impact of achieving mucosal healing on UC-related hospitalisations and work productivity in patients with moderately to severely active UC: A post-hoc analysis of risankizumab Phase 2b/3 trialsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The value of endoscopic-histologic healing is incompletely understood, and definitions are variable. We assessed the clinical and economic value of achieving mucosal healing in patients with ulcerative colitis (UC) by evaluating the relationship of histologic-endoscopic mucosal improvement (HEMI) and subsequent UC-related hospitalisation and work productivity, and associated costs in the United States (US); United Kingdom (UK); and France, Germany, Italy, and Spain (EU4).

Methods

Data from the risankizumab (RZB) INSPIRE induction (NCT03398148) and COMMAND maintenance (NCT03398135) studies were analysed. The number of UC-related hospitalisations was compared in patients who achieved HEMI or no HEMI using a chi-square test. The mean percent changes in Work Productivity and Activity Impairment (WPAI)-UC domains from baseline to induction week 12 and maintenance week 52 were compared in patients who achieved HEMI or no HEMI using analysis of variance test. Hospitalisation and work productivity differences during induction and maintenance were converted to annualised costs based on average earnings and hospitalisation cost inputs from US, UK, and EU4.

Results

UC-related hospitalisations were significantly lower in patients who achieved HEMI at induction week 12 than those who did not (0% vs 2.9%, p≤0.05). A similar result was found at maintenance week 52, but the difference was not significant. In patients who achieved HEMI vs no HEMI, a greater mean change in activity impairment, impairment while working, and overall work impairment from baseline to induction week 12 was observed (p≤0.001). Improvements were sustained at maintenance week 52 for patients who achieved HEMI vs those who did not. Estimated annualised cost benefits from maintenance data for UC-related hospitalisations in patients who achieved HEMI was $490 in the US, £29 in the UK, and €28–€58 in EU4. Greater monetised benefits accrued from work productivity gains, where estimated annualised cost savings were $5,085 in the US, £3,507 in the UK, and €3,240–€4,456 in EU4.

Conclusion

These findings demonstrate that patients treated with RZB who achieved HEMI had fewer UC-related hospitalisations and greater improvement in work productivity and ability to perform daily activities than those who did not, which results in moderate direct cost savings and substantial indirect cost savings to healthcare systems in the US, UK, and EU4.Read more P1096 Increased incidence of IBD over 22 years in an Argentine cohortWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

A considerable variation of IBD epidemiology around the world has been observed with certain regions showing a notable predisposition. The association between IBD and industrialized nations is well-known. However, a global increase of the incidence of such pathologies has been described, even in those regions with low incidence such as developing countries. Few data exist concerning the incidence of these pathologies in Argentina and Latin America during the last decades. Our objective is to determine the trend of incidence of IBD during a long term in an Argentine cohort.

Methods

A trend incidence study on a retrospective cohort was conducted. The study population comprised of affiliates of the Italian Hospital Medical Care Program (IHMCP), a prepaid health maintenance organization (HMO) with over 180,000 affiliates, of an urban area of Buenos Aires, Argentina. Patients with a diagnosis of IBD established between January 1st 2000 to December 31st 2022 were included. Data were extracted from the Institutional Registry of IBD (IRIBD) on a RedCap platform. Adjusted and raw cumulative incidence of IBD was calculated annually, using as denominator yearly affiliates to the IHMCP. Direct standardization was done considering the World Standard Population according to World Health Organization. Incidence was calculated over 100,000 persons with 95% confidence interval (95% CI). We evaluated the trend of incidence of IBD between 2000 and 2022, using a joinpoint regression analysis. The annual percentage change (APC) with 95% CI was calculated to detect increasing or decreasing trends according to an APC statistically different from zero (alpha 0,05), using Joinpoint Regression Program 4.5.0.1.

Results

Out of 530 affiliates of the IHMCP included in the IRIBD, 286 were diagnosed with IBD during the study period. One hundred and sixty two were women (56,6%). Mean age at diagnosis was 45,3 years (SD 22,2); 26 patients were diagnosed during pediatric ages (9%). Regarding the subtype of IBD, 78% were Ulcerative Colitis, 17% Crohn's disease and 5% IBD unclassified. Adjusted incidence rates of IBD over 100,000 persons per year are detailed in table 1, showing an incidence of IBD of 4,3 (95% CI 0.02 - 8.6) by 2000 and 11,8 (95% CI 5.9 - 17.7) by 2022. The adjusted trend of incidence of IBD showed an annual increase with a calculated APC of 6,4% (95% CI 0,9 – 12,2; p=0,023) (Figure 2).

Conclusion

Our study shows an increasing incidence of IBD with a sustained trend over the last 22 years in an argentine population. One of the strengths of this study is the long term analysis of a known cohort belonging to a centralized HMO. The detected increase in incidence reinforces reported evidence of a changing epidemiologic scenario of IBD in Latin America.Read more P1042 Serum N-glycan Biomarkers Predict Patient Response to Biologics for Crohn’s DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Several therapeutic antibodies are approved to treat Crohn’s Disease (CD), for example, Vedolizumab (anti-α₄β₇), Ustekinumab (targets IL-12 and IL-23), Adalimumab and Infliximab (anti-TNF). Glycosylation alterations have been associated with CD, but have not been thoroughly investigated as potential predictors of disease remission¹. A comparison of serum N-glycan profiles between responders and non-responders prior to each therapy was used to detect potential biomarkers to response. The N-glycan composition after treatment was used to distinguish the different mechanisms of the biologics. In addition, a comparison of glycomic profiles across the different therapies could highlight the distinct biological pathways involved in response.

Methods

Serum samples, before (t1) and after (t2) treatment, were taken from 166 patients, containing the four sub-cohorts of patients under different biologics with CD. Treatment response, observed in 100 patients, was assessed by a combination of clinical and endoscopic outcomes. Firstly, the Serum N-glycans were detected by hydrophilic interaction liquid chromatography to produce a 62-peak chromatogram. Followed by quantifying the relative area of 62 glycan peaks via HappyTools². Logistic regression was used to determine which glycan peaks at t1 are predictive of response (p-value <0.05) and which are markers of response (p-value<0.05). 5 fold cross-validation tested on a variety of classifiers was used to derive the optimal predictor of response. The glycomic profiles across the four biologics, at both t1 and t2, were compared through the Kruskal test. The significant peaks (p-value < 0.05) were then combined to generate a multiclass model to predict response in each therapeutic.

Results

The N-glycan classification models for all four sub-cohorts under different biologics, Ustekinumab (0.78 AUC), Adalimumab (0.82 AUC), Infliximab (0.75 AUC), Vedolizumab (0.75 AUC), performed moderately well at predicting therapy response prior to treatment(figure 1A). In turn, patients could be identified as responders after treatment by N-glycan based classification models, Ustekinumab (0.70 AUC), Adalimumab (0.86 AUC), Infliximab (0.85 AUC), Vedolizumab (0.84 AUC). Prior to treatment, patients who responded were strongly distinguished by the therapy type (0.96 AUC) through a combination of 13 significant glycan peaks (figure 1B).

Conclusion

This study has demonstrated multiple N-glycans are potential predictors of biological response, with the possibility to guide clinicians in the most appropriate form of treatment. These results require the integration of mass spectrometry and validation by larger cohorts.Read more P706 Tofacitinib in Moderate to Severe Ulcerative Colitis patients naïve to biological therapy: A prospective real world analysis of efficacy and safetyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Tofacitinib is an oral non-selective Janus Kinase inhibitor approved for Ulcerative colitis (UC) after the failure of biological therapy. Tofacitinib as first line therapy in biologic naive patients has not been evaluated.

Methods

We conducted a prospective study to assess the safety and efficacy of Tofacitinib as first line therapy in biologic naive moderate to severe UC. Tofacitinib was given at a dose of 10mg BD for 8 weeks followed by de-escalation to 5mg BD maintenance in responders. Dose escalation was done for relapses. Demographics, disease characteristics, concomitant medication, adverse events, severity and time to relapse were recorded. Clinical response and remission (defined as partial Mayo score: PMS decrease ≥2 and PMS ≤1 respectively) were measured at 4 weeks, 8 weeks, 24 weeks and 52 weeks. Endoscopic response (UCEIS score decrease ≥2) and remission (UCEIS 0-1) were assessed at 1 year. Time to event analysis was done to evaluate the cumulative rate of clinical response.

Results

176 patients (136 biologic naive, 58% male; median age 40y [IQR:31-48y]) were included. Median baseline PMS and UCEIS score were 5 (IQR: 5-7 and 4-6 respectively) (Table 1). Of the biologic naïve cohort, clinical response was achieved in 68.4% and 79.4% at 4 and 8 weeks respectively. Clinical remission was achieved in 45.6%(4-weeks) and 55% (8-weeks). Maintenance of remission was seen in 44.1% and 32.4% in 24 and 52 weeks respectively (Fig1A). There was a significant reduction in PMS from baseline to end of 8-weeks (p<0.001) (Fig 1B). Corticosteroid-free clinical remission was achieved in 64.8% at 24-weeks. 106 patients (77.9%) maintained response till last follow-up. 11 relapsed after dose de-escalation (median time of 5m [range 3-22m]. 7/11 responded to dose escalation to 10mg. Endoscopic response was noted in 62.5% and remission in 33.9% with significant reduction in UCEIS from baseline to 52-weeks(p<0.001) (Fig 1B). Severe and minor adverse events were noted in 4 and 3 patients respectively (Table 1). Overall 1/3 of patients discontinued therapy at 24-weeks (14%) and 52 weeks (10%).No significant difference in proportion of clinical or endoscopic remission was observed between the biologic naïve and those with history of prior biologic usage (n=31, median time from withdrawal of biologics to Tofacitnib initiation=9 months).

Conclusion

Tofacitinib was effective in induction of clinical remission in more than half of biologic naive, moderate to severe UC . Three-fourth of these patients continued to be in remission at one year with few serious adverse events. Tofacitinib can be considered as upfront oral therapy after failure of conventional management.Read more P1118 High Crohn’s Disease burden but disproportionally low use of biologics in Crohn’s Disease patients with Intestinal Failure: a longitudinal comparative study from 1973-2018Wed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Patients with Crohn’s Disease (CD) complicated by Intestinal Failure (CDIF) are considered to be among those with the most severe form of CD. Their clinical course before IF onset has not been well characterised. We aimed to describe and compare CD-specific natural history, disease burden and treatment between CDIF patients and CD patients without IF over a 40-year period.

Methods

CDIF patients from Copenhagen Intestinal Failure Database (1973-2018) and a Danish nationwide CD cohort without IF (1977-2018) were followed from onset of CD until IF, death, or 31/12/2018. Hospital contacts, surgeries, prescription dispensation, employment and mortality data were extracted from multiple population-based registries. Groups were compared using logistic regression for proportions and Poisson regression for rates. Standard mortality ratio (SMR) was calculated against age, gender and year-matched Danish population references, and an adjusted mortality rate ratio between CDIF and CD patients was obtained from Cox models.

Results

182 CDIF and 22845 CD patients were followed for 3035.7 and 293536.5 patient-years, respectively. At CD diagnosis, CDIF patients were younger (median age 24 years vs 35 years, p<0.0001), from earlier decades (71.5% vs 16.5% before 1991, p<0.0001), and had fewer comorbidities (6.9% vs 20.4%, p<0.0001). The 10-year cumulative incidence of IF declined from 2.7% in patients diagnosed with CD prior to 1980 to 0.2% in patients diagnosed after 2000, but the number of new CDIF patients has not declined over the decades (Table). A greater proportion CDIF patients received at least 1 course of steroids (70.8% versus 59.8%, p=0.02) and immunomodulators (59.3% vs 48.7%, p=0.03), had IBD-related hospital contacts (98.2% vs 55.2%, p<0.0001) and abdominal surgeries (94.9% vs 47.6%, p<0.0001), and stopped working for >6 months (65.8% vs 57.8% of working-age patients, p=0.05). However, in the biologics era (after 2000), CDIF patients were not treated with biologics more often (20.4% vs 21% had any biologics, p=ns). In those who were treated, CDIF patients had less cumulative time on biologics (3.9 years vs 11.2 years per 100 patient-years, p=0.001). CDIF and CD patients had a SMR of 3.7 (97.5% CI 2.79,4.72) and 1.7 (97.5% CI 1.61, 1.72), respectively. After adjusting for age, sex and co-morbidity, CDIF patients were at 3.42 times risk of dying compared to CD patients.

Conclusion

The incidence of CDIF has reduced in newly diagnosed CD patients, however the number of new CDIF patients has not yet declined due to increasing CD prevalence. Despite CDIF patients experiencing a significantly higher burden of CD before the onset of IF, they were not more likely to receive biologics. They also appear more refractory to biologics.Read more P1043 Immunomodulator and advanced therapies for prevention of clinical relapse and loss of response during maintenance phase in Crohn’s disease: A systematic review and network meta-analysisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Several effective advanced therapies have been approved for the treatment of Crohn’s disease (CD) in the past two decades. Given lack of adequate head-to head clinical trials it is challenging to position these therapies in the management algorithm. Therefore we performed this network meta-analysis to inform therapeutic decisions.

Methods

We searched MEDLINE, Embase, and Cochrane Central Register of Controlled Trials between inception and October 2023 for randomised controlled trials (RCTs). Outcomes assessed were clinical relapse (loss of clinical remission), loss of clinical response, adverse events (AE), withdrawal due to AE, and serious AE. We performed random-effects meta-analysis and network meta-analysis (using a frequentist approach), and estimated relative risk (RRs), 95%CI values. We used GRADE to ascertain certainty of evidence.

Results

A total of 32 RCTs comprising 10,924 patients were included in the analysis. On network meta-analysis of 15 interventions based on prevention of clinical relapse, combination of infliximab (IFX) and azathioprine (AZA) (RR 0.31, 95%CI [0.17-0.56]), IFX (RR 0.62, 95%CI [0.5-0.76], moderate certainty), and adalimumab (RR 0.68, 95%CI [0.55-0.84], moderate certainty) were the only agents that were effective compared to placebo (Figure 1). Methotrexate (RR 0.57, 95%CI [0.32-1.03], low certainty) and azathioprine (RR 0.82, 95%CI [0.62-1.1]), very low certainty) were not effective. On analysis based on prevention of clinical response for nine interventions, there was high certainty evidence for ustekinumab (RR 0.73, 95%CI [0.61-0.86]), upadacitinib (RR 0.64, 95%CI [0.57-0.72]), and moderate certainty of evidence for infliximab (RR 0.71, 95%CI [0.59-0.84]), adalimumab (RR 0.68, 95%CI [0.61-0.75]), certolizumab (RR 0.57, 95%CI [0.47-0.7]), CTP13 (RR 0.46, 95%CI [0.38-0.57]), vedolizumab (RR 0.82, 95%CI [0.68-0.99]), natalizumab (RR 0.54, 95%CI [0.43-0.68]). Tofacitinib was not effective and there was no data available for immunomodulators and combination therapies for this outcome. On analysis of serious adverse events advanced therapies were of no difference to placebo (very low certainty).

Conclusion

On network meta-analysis immunomodulators and advanced therapies for maintenance phase, combination of anti-TNFs and immunomodulators followed by anti-TNF monotherapy had large effect size with moderate certainty for prevention of clinical relapse. There was moderate to high certainty evidence to suggest newer advanced therapies are effective in prevention of loss of clinical response.Read more P655 The ileorectal anastomosis after a total colectomy is a feasible and valid surgical alternative in the treatment of inflammatory bowel diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Colectomy is still necessary in some patients with inflammatory bowel disease (IBD). The decision of the technique for the restoration of the bowel continuity depends on the characteristics of the patient and whether it is Crohn’s disease (CD) or ulcerative colitis (UC). The options for the reconstruction are proctectomy with an ileoanal reservoir or an ileorectal anastomosis (IRa).The aim of this study is to evaluate the need of a proctectomy with a definitive ileostomy after an ileorectal anastomosis, the associated risk factors and the need for advanced therapies.

Methods

This retrospective study includes patients with colectomy and IRa from the ENEIDA national registry. Medical treatment offered during the postoperative follow up and the need for a proctectomy and a definitive ileostomy were evaluated according to the type of IBD.

Results

Of the 394 patients who underwent an IR, 37% had UC and 63% CD with a medium age of 58 years (RIQ 48-68) and a median follow-up after the IR of 174 months (RIQ 70- 266). 17% of UC’s patients and 42% of CD’s patients had associated perianal disease (p<0.001). The cumulative probability for a definitive ileostomy in UC’s patients was 1%, 2%, and 6% at 5, 10 and 20 years respectively and 1%, 3%, and 11% at 5, 10 and 20 years respectively for the CD (p=0.035). Postoperative maintenance treatment with biologicals was left in 45% (44% UC and 47% CD; p=0.28). During follow-up, the probability of starting biological treatment was 8%, 17%, 35% at 2, 5 and 10 years in CD and 3%, 12%, 28% at 2, 5 and 10 years in UC (p=0.59).

Conclusion

The probability of requiring a definitive ileostomy/proctectomy after an IR is low, although is more frequent in patients with CD than with UC. Because of this low probability an IR is a valid alternative to the reservoir or even to the proctectomy with a definitive ileostomy in selected patients, keeping in mind one third of the patients would need advanced therapies.Read more P656 Plasma Inflammation-related Proteins Predict the Therapeutic Effect of 5-ASA in Patients with Ulcerative ColitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

5-aminosalicylate acid (5-ASA) is the first line therapy for mild to moderate ulcerative colitis (UC). However, up to 56% of patients on 5-ASA treatment could not achieve mucosal healing, which is the therapeutic target of UC. At present, predictors for patients’ response to 5-ASA are lacking. Our aim was to identify circulating markers to predict the therapeutic effect of 5-ASA in patients with UC.

Methods

Plasma samples were collected from patients with active UC at baseline and analyzed using the OLINK panel (Target 96 Inflammation). Effective therapy was defined as achieving clinical remission within 8 weeks or mucosal healing within 1 year of 5-ASA treatment. Orthogonal Projections to Latent Structures Discriminant Analyses (OPLS-DA) were implemented to correlate patient groups to plasma proteins in linear multivariate models. Machine learning models (ML) were constructed to predict ineffective therapy in UC patients.

Results

Among the 36 UC patients involved (media age 38.5 years old, men 61.6%), 18 patients belonged to the effective group and the ineffective group, respectively. In multivariate analysis, circulating inflammatory protein profiles could distinguish the patients who did not respond well to 5-ASA treatment (Figure 1A). Elevated levels of Axin 1 (p=0.012), sulfotransferase 1A1 (ST1A1) (p=0.032) and interleukin 15 receptor subunit alpha (IL-15RA) (p=0.022), and decreased level of interleukin 2 (IL-2) (p=0.036) were observed in UC patients refractory to 5-ASA therapy (Figure 1B). Receiver operating characteristic curves (ROC) for predicting the therapeutic efficacy of 5-ASA were constructed. The areas under ROC (AUC) of Axin 1, ST1A1, IL-15RA and IL-2 for the prediction of ineffective 5-ASA therapy were 0.744 (p=0.012, sensitivity 83.3%, specificity 72.2%), 0.710 (p=0.031, sensitivity 94.4%, specificity 55.6%), 0.704 (p=0.037, sensitivity 88.9%, specificity 50%) and 0.704 (p=0.037, sensitivity 77.8%, specificity 61.1%), respectively (Figure 1C). Combination of the four protein markers improved the performance of prediction (AUC 0.860 to 1.000, sensitivity 72.2%-100%, specificity 83.3%-100% across all machine learning classifiers) (Figure 1D).

Conclusion

We identified four plasma inflammation-related proteins associated with the therapeutic effect of 5-ASA in UC. The ML models demonstrated excellent performance in predicting the therapeutic effect of 5-ASA, which could help clinicians identify UC patients who are refractory to 5-ASA in the early course of disease and timely initiation of treatment escalation.Read more P871 A modified Crohn’s disease exclusion diet in a multi-ethnic Asian settingWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Crohn’s disease exclusion diet (CDED) has been shown to be well-tolerated and effective in adults with active Crohn’s disease (CD). There is limited data on using CDED in Asian setting. We performed this study to evaluate the feasibility and tolerability of using CDED as a nutritional intervention in Asian adults with CD.

Methods

We performed a prospective single centre observational study using 12-weeks of CDED as a nutritional intervention in adults with CD. The original CDED was adapted to foods commonly eaten in Asia. Patients with active CD were offered CDED as monotherapy or as an adjunct treatment to drug therapy. Dietary counselling was done by a dietitian and all food was prepared by individual participants or their family members. Participants were seen at baseline, week 6 and week 12. Dietary compliance was monitored by physician using direct questioning and, modified Medication Adherence Rating Scale (MARS) questionnaire. In addition, dietitian monitored compliance using 24-hour dietary recall and 3-day food journal. We monitor the disease activity using Harvey Bradshaw Index (HBI), C-reactive protein (CRP) and faecal calprotectin (FC). (Figure 1) The primary endpoint was tolerance to CDED; secondary endpoints were compliance to CDED and biomarker normalization. Intolerance was defined as refusal to continue with CDED and withdrawal from study. This study was approved by Singhealth Institutional review Board. Informed consent was obtained from all participants.

Results

A total of 6 participants were recruited from November 2022 to May 2023. Most participants were young. Four patients were on biologics (1 infliximab, 1 adalimumab, 1 vedolizumab, 1 ustekinumab). Two patients had CDED as monotherapy. (Table 1). All participants were able to tolerate 12 weeks of CDED and were mostly compliant to CDED. (Table 1) 5 of 6 patients had downward trend of CRP at week 12 compared to baseline and 4 of 6 had Two patients who received CDED as monotherapy had biomarker normalization at week 12. All patients were continued on CDED for another 12 weeks (maintenance phase).

Conclusion

Dietary intervention using CDED is well-tolerated among Asian adults with CD. More data is required to confirm the efficacy of CDED, both as monotherapy and in combination with drug therapy.Read more P673 Accelerated intravenous ustekinumab dosing as rescue therapy in Moderate- Severe Ulcerative ColitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Ustekinumab (UST) is an accepted treatment for patients with moderate- severe Ulcerative Colitis (UC) following failure with corticosteroids and/or anti-TNF. Some studies suggest that intravenous (IV) administration, in an accelerated schedule, could improve outcomes in this difficult-to-manage group with a high risk of colectomy.

Methods

We conducted a retrospective analysis in patients with moderate-severe UC who received UST (IV) as rescue treatment, following failure with corticosteroids and infliximab. UST was administered intravenously, with an initial dose of 6mg/Kg followed by 130mg every four weeks. Clinical activity was determined by the Partial Mayo Score (PMS), and endoscopic activity by the Mayo Score (SM). Clinical Remission (CR) was defined as PMS<2, and Clinical Response (CRp) as a reduction in activity of ≥30%.

Results

The study included 17 patients, 8 (47%) women, 9 (52.9%) of whom were hospitalized at baseline, and 11/17 required transfusion or intravenous iron. According to PMS, clinical activity was severe in 16 (94.12%) and moderate in one. Endoscopic activity according to SM was severe in 13 (76.4%). Clinical remission and response were as follows: 1 (5.8%) / 7 (41.1%) patients respectively at week 4; 8 (47%) / 16 (94.1%) patients at week 12; and at week 26, 15 patients had completed the study, 10 (66.6%) in CR, and 12 (80%) in CRp. Ustekinumab was withdrawn in one case due to an infusion reaction, and one patient underwent colectomy. No independent predictors of response to UST were found in this study.

Conclusion

Intravenous ustekinumab in an accelerated dosing schedule is effective in moderate-severe UC, achieving clinical response in more than two-thirds of patients at week 26.Read more P891 Comparative Effectiveness and Safety of Infliximab and Tacrolimus in the Treatment of Acute Severe Ulcerative ColitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Acute severe ulcerative colitis (ASUC) affects approximately 20% of patients with ulcerative colitis (UC). Patients failing initial corticosteroid therapy receive salvage therapy with either infliximab (IFX) or calcineurin inhibitors, cyclosporine (CYS) or tacrolimus (TAC). We aimed to compare the effectiveness and safety of IFX and the oral calcineurin inhibitor, TAC, in this setting.

Methods

This retrospective cohort study included consecutive patients with ASUC, based on the Truelove and Witts criteria, admitted to Tel Aviv Medical Center between 2017 and 2022 and treated with salvage therapy. Demographic, clinical, and laboratory data were retrieved. The primary endpoint was successful salvage therapy defined as clinical response resulting in discharge without colectomy. Secondary endpoints included the colectomy rates at 90 days and the safety profile of the treatments.

Results

During the study period 96 patients with ASUC were admitted to our center. Of these, 40 patients received salvage therapy – 21 patients received IFX and 16 received TAC and were included in the analysis; 3 patients received CYS and were excluded from the study. Demographic data are detailed in Table 1. Disease duration was significantly longer in patients receiving TAC (mean (±SD) 9.7 years (±7.1) vs 4.5 (±5.9), p=0.04). In addition, patients receiving TAC had significantly greater prior exposure to advanced therapies (14 (87.5%) vs 6 (28.6%), p<0.001) and 12 (75%) patients had previous exposure to IFX. Baseline markers of disease severity including disease extent, hemoglobin, C-reactive protein (CRP), albumin and body mass index (BMI) were similar between the treatment groups (Table 1). Therapeutic success was similar between treatment groups (IFX: 18 (86%) vs TAC: 15 (94%), p=0.62). The 90-day colectomy rate (IFX: 4 (19%) vs TAC: 2 (12.5%), p=0.68), CRP upon discharge (median (IQR) IFX: 15 mg/L (3.3-27) vs TAC: 11 mg/L (5.4-25, p=0.64) and length of hospitalization (mean (±SD) IFX: 23.5 days (±19.46) vs TAC: 17.56 days (±5), p=0.19) were similar between the groups. Safety profiles were similar between the treatment groups with mild electrolyte disturbances treated conservatively in both groups and no observed infections, deaths or other adverse events.

Conclusion

This real world, retrospective study shows that IFX and TAC have similar effectiveness and safety in the setting of ASUC. In this study, patients receiving TAC had significantly longer disease duration and advanced therapy exposure than those receiving IFX and still maintained excellent effectiveness highlighting TAC’s value in this setting.Read more P674 Real-world experiences of switching to subcutaneous formulation in IBD patients on maintenance vedolizumab treatmentWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Usability of subcutaneous vedolizumab (SC VDZ) in inflammatory bowel diseases (IBD, ulcerative colitis [UC], Crohn’s disease [CD]) have proved via clinical trials, while real-world data collection is ongoing. Experiences of Central-European population and assessment of patient’s perspectives are lacking. Our study aimed to evaluate the real-world efficacy, safety and patient’s preferences of SC VDZ maintenance treatment after switching from intravenous (IV) formulation in a Hungarian IBD cohort.

Methods

In this prospective, multicenter cohort study, IBD patients on maintenance IV VDZ treatment were enrolled, who switched to SC administration. Baseline was the day of the switch, while 52-week follow-up was set. Clinical and demographic data were collected, while serum VDZ level and CRP was measured at baseline and at w52. A non-validated questionary was filled by patients who were on drug at w12 recording patient’ satisfaction. Primary outcome was the drug survival rate at one year, while secondary outcomes were change in corticosteroid-free clinical (CSFR, based on physicians’ global assessment score PGA < 1), and biochemical remission (BR, 5 mg/l > CRP) rates to w52, safety issues and patients’ preferences and change in serum drug levels.

Results

In total, 37 IBD patients were followed (Table 1., 15 CD and 22 UC, male/female ratio 45.9 %, median age 42.0 [IQR 34-49] years). In CD group, 66.7 % were in CSFR and 60 % in BR, while in UC group 63.6 % were in CSFR and 68.2 % in BR (p = 0.55 and p = 0.61). Overall, 29.7 % of patients ceased SC VDZ treatment after a median of 20 (IQR 6-26) weeks. Cessation was due to secondary response losing in 3/6 and 4/5 patients in CD and UC group. In case of 2 and one patients, SC treatment was terminated due to local reactions. One patient was fear of needle. Severe adverse event did not occur. Factors associated with discontinuation did not identify. The mean serum VDZ level has higher at w52 compared to baseline in CD and UC patients (CD: 8.9 ± 6.9 to 30.6 ± 17.8 ug/mL, p = 0.047; UC: 13.6 ± 13.8 to 33.6 ± 17.6 ug/mL, p = 0.001, Figure 1.), while disease activity was stable. 84 % of the patients who filled the questionnaire were satisfied with injection, while only one patient found it difficult to inject.

Conclusion

Transition from IV to SC maintenance VDZ treatment is effective at one year, the overall survival rate is high presumably due to the elevated serum drug levels. Severe safety issue did not raise. Satisfaction of switched patients is high, which may improve treatment adherence and save resources.Read more P906 The drug-survival of low-dose thioguanine in patients with inflammatory bowel disease. A retrospective observational studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Thiopurines are commonly used to treat inflammatory bowel disease but withdrawal due to side-effects are common. Thioguanine has been suggested to be better tolerated than conventional thiopuries. We aimed to study drug-survival of low-dose of thioguanine in real-life clinical practice in comparison to conventional thiopurines.

Methods

All patients born in the year 1956 and later, and who at least once started thiopurine treatment between the years 2006-2022 were included. A medical chart review was performed that noted drug-survival for every thiopurine treatment attempt. Mantel-Cox rank test was used to test differences in drug-survival for different thiopurines. Blood chemistry analysis and faecal calprotectin levels was registered the first five years of treatment.

Results

In the study population there was 379 initiated thiopurine treatments (210 for Crohns disease and 169 for ulcerative colitis) in 307 patients with IBD. Low-dose thioguanine (median dose 11 mg; 25-75^th percentile 7-19 mg) had been initiated in 31 patients. Overall, when including all thiopurine attempts, the median time on treatment for the different thiopurine treatments were for azathioprine 24 months (25^th-75^th percentile 3-59 months), for 6-mercaptopurine 15 months (3-59 months), for azathioprine/allopurinol 22 months (1-25 months) and for thioguanine 33 months (11-64 months). Thioguanine had longest drug-survival (Mantel-cox rank test: thioguanine versus azathioprine p=0.014; thioguanine versus 6-mercaptopurine (6-MP) p<0.001). For second line thiopurine treatment, the median time on treatment for 6-mercaptopurine were 13 months (2-69) and for thioguanine 33 months (11-64). Thioguanine had longer drug-survival than 6-MP (Mantel-Cox rank test: p=0.006) (Figure). At 60 months, 86% of the patients who started low dose thioguanine was still on treatment compared to 42% of the patients who started 6-MP (p=0.022). The median 6-TGN levels in patients treated with thioguanine was 364 pmol/8x10⁸. Patients on thioguanine treatment showed significantly lower values of median mean corpuscular volume at follow-up than patients treated with azathioprine and 6-MP. Patients treated with 6-MP had signficantly lower levels of F-calprotectin at year three and year four compared to patients treated with azathioprine. Overall there was a similar response on inflammatory markers the first five years from starting treatment with thioguanines compared to conventional thiopurines.

Conclusion

Treatment with a low-dose of thioguanine is well tolerated in patients with IBD and have a significantly higher drug survival than conventional thiopurines.Read more P693 Care needs and reasons for (not) seeking care among fatigued patients with Inflammatory Bowel Disease: A qualitative studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Fatigue is one of the most prevalent and burdensome symptoms experienced by patients with inflammatory bowel disease (IBD), even when the disease is in remission. Many patients report dissatisfaction towards fatigue-related care and uptake of available interventions is often low. This study aims to explore reasons why IBD patients do or do not engage in professional fatigue-related care and their needs regarding type of care and how to offer care.

Methods

We conducted a qualitative study, taking a phenomenological methodological approach. Sixteen adult IBD patients with disease in remission and severe fatigue (i.e., Checklist Individual Strength – subjective fatigue ≥ 35) were recruited from an academic hospital. We performed semi-structured interviews. Data were analysed using template analyses.

Results

We identified six themes regarding reasons why to (not) seek care for fatigue: 1) cognitions about fatigue and coping (e.g., a need to deal with fatigue alone), 2) perceptions of fatigue-related care and previous care experiences (e.g., perceiving that nothing can be done about fatigue), 3) knowledge and behaviour of the healthcare provider (e.g., fatigue complaints are not taken seriously), 4) somatic factors (e.g., physical symptoms of IBD), 5) social factors (e.g., feeling misunderstood by others) and 6) practical factors (e.g., time and money). Furthermore, we identified needs regarding how to offer care, i.e., proactive screening and active offer of care by healthcare providers, a holistic and person-centred approach and practical needs taken into account. Finally, regarding what care to offer, patients suggested a broad range of options, including information provision on fatigue management, eliminating physical causes of fatigue, discussing medication options, lifestyle support, psychological support, peer support and practical support.

Conclusion

IBD patients’ perceptions, coping and knowledge, as well as healthcare professionals’ behaviours play a major role in seeking fatigue-related care. Findings emphasize the importance of discussing IBD-related fatigue actively and taking a holistic and patient-centred approach to treat fatigue, targeting a broad range of physical- and psychological factors. These findings yield a better understanding of factors that hinder and facilitate care seeking in fatigued IBD patients and hereby provide ways to optimize the uptake of care.Read more P919 Crohn’s Disease Exclusion Diet as add-on therapy in refractory pediatric patientsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Despite the accumulating body of evidence of the efficacy and tolerability of Crohn’s disease exclusion diet (CDED) combined with partial enteral nutrition (PEN), there is still a paucity data regarding its use in combination with other medical treatments. We aimed at assessing its efficacy in re-inducing remission in pediatric CD patients experiencing disease relapse while on other maintenance therapies.

Methods

This was a single-center, retrospective, observational study conducted at an Italian national referral pediatric IBD center. Incident patients who received CDED coupled with PEN in the setting of the loss of response to other maintenance therapies from January 1st, 2020 to June 30th 2023 were included. Clinical remission at the end of each phase was defined by a weighted Pediatric Crohn’s Disease Activity Index (wPCDAI) below 12.5. Biochemical remission was defined by a c-reactive protein (CRP) lower than 0.5 mg/dL. A FC lower than 150 mg/kg was used as a surrogate of mucosal improvement (MI).

Results

25 patients (52% males) met inclusion criteria and were included in the analysis. Median disease duration at CDED+PEN initiation was 31 months (Q1-Q3: 8.4-13.8). The most frequent disease location was ileocolonic (64%), 3 (12%) patients had isolated colonic involvement. 9 (36%) patients had stricturing/penetrating phenotype. 16 patients (68%) were being treated with an anti-TNF-alpha agent, whereas 5 (20%) patients were receiving ustekinumab (Table 1). wPCDAI, CRP and FC significantly decreased after the firs 8 weeks of treatment (22.5 vs 2.5, 1 vs 0.2, 640 vs 360, p<0.001, p=0.019 and p=0.007, respectively). At the end of phase I, 19/25 (76%) of the patients achieved clinical remission, 15 (60%) patients had CRP levels within normal range and 7 (28%) of them had normalized FC. 18/25 patients (72%) had received Exclusive Enteral Nutrition (EEN) for the induction of remission at diagnosis. Patients who achieved clinical remission with the EEN course (i.e.: a wPCDAI of < 12.5 after a complete course of EEN) were more likely to achieve clinical remission when receiving CDED + PEN (11/13 vs 1/5, p=0.022).

Conclusion

CDED coupled with PEN is a valid treatment strategy in the setting of secondary loss of response to maintenance treatments in children with CD. A previous successful course of EEN was associated with higher rates of clinical remission at the end of phase I, thereby possibly identifying a subset of “nutritional responder” patients.Read more P694 Age is a strong of predictive risk factor for anti-TNF therapy related adverse events in IBD patientsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Anti-TNFα is the first class of biologics approved for treatment of moderate-to-severely active Inflammatory Bowel Disease (IBD). More than two decades on, anti-TNFs remain one of the most commonly used biologics for both Ulcerative Colitis (UC) and Crohn’s Disease (CD), and often as first-line therapy. Although effective, they cause several adverse events (AEs), sometimes requiring withdrawal of therapy. We aimed to record AEs and understand factors that could predict risk of AEs.

Methods

All IBD patients exposed to anti-TNF therapy were identified from EMR at two centres of a large tertiary hospital between January 2009 and June 2022. All relevant demographic and clinical data were collected for those patients with well recorded AEs and follow-up. Data on cumulative AEs directly attributed to anti-TNFs that ranged from mild reactions to serious AEs (defined as those requiring review/withdrawal of anti-TNF), were collected. Adverse events (AEs) were recorded as per relevant systems involved e.g.- haematological, cardiac etc., including infections and malignancies as separate categories. All analysis (normalization, hypothesis testing, and visual reports were performed using R software package Version: R 4.2.1.

Results

A total of 844 IBD patients (Male =408) were included with an age range of 18-75yrs. Majority were Caucasian in ethnicity (514) and more patients with CD [605(71%)] were exposed to anti-TNF than UC. The age profiling analysis was performed across ethnic groups (Asian, Caucasian and Others). Age associated AE was reported across all the groups (data not shown). It must be mentioned that though not significant, Caucasian patients were more susceptible towards AE as compared to Asian.

Conclusion

· Patient age above 50yrs has a strong predictive risk factor for AEs related to anti-TNF therapy for IBD.· In our cohort, more than half of patients >50yrs reported at least one AE in UC, and the age was lower in CD.· Although Caucasians were more vulnerable to AEs, this was not statistically significant.· Clinicians should consider and discuss this risk before selecting patients for anti-TNF therapy.· With multiple biologic choices currently available, another class could be considered where possible, for the >50yr patient cohort.Read more P717 Evaluating the performance of Large Language Models in responding to patients' health queries: A comparative analysis with medical expertsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Patients with chronic diseases exhibit a heightened interest in seeking health information, and access to high-quality information can positively impact clinical outcomes. While previous research on static internet text/video information has highlighted concerns about low-barrier creation leading to low-quality content, it remains uncertain whether similar issues persist in responses generated by Large Language Models (LLMs). Assessing the ability of LLMs in responding to medical queries provides valuable insights for their application in healthcare settings.

Methods

In alignment with open science principles, we utilized real patient queries from the China Crohn's and Colitis Foundation (CCCF) series "Questions and Answers on Ulcerative Colitis and Crohn's Disease." The dataset comprised questions posed by patients and corresponding answers from medical professionals, collected from outpatient visits and online social media. In September 2023, 263 patient questions were sequentially input into ChatGPT-3.5 (August 3, 2023 version), and the resulting responses were compiled alongside the original medical professional responses, forming 263 modules. Three Inflammatory Bowel Disease (IBD) specialist physicians and three IBD patients were invited to assess each module. Evaluators were instructed to: 1) choose their preferred response version, and 2) provide a multidimensional Likert 5-point subjective assessment using a crowdsourcing strategy. Additionally, the CRIE 3.0 team conducted an automated objective analysis of Simplified Chinese readability.

Results

Mann-Whitney U tests on text readability levels (median: 7th grade for both medical professionals and ChatGPT responses; Q1: 6th grade; Q3: 8th grade) revealed no significant difference (p=0.87), suggesting ChatGPT's performance align well with recommended literacy levels for popular science publications and is comparable to the average education level in China.

Conclusion

Cautiously interpreting our findings, ChatGPT's preliminary performance appears comparable to specialized IBD physicians, indicating its potential utility in patient community Q&A. Integrating ChatGPT or similar LLMs into the drafting or refinement stages of health texts is feasible. However, due to the presence of AI hallucinations and the consensus in most experimental conclusions, direct use of large language models for patient Q&A services is not recommended. Recognizing the variability in health information understanding between medical professionals and patients can enhance patient education efforts.Read more P920 Efficacy and Drug Adherence Rates of Anti TNF Drugs in patients with Crohn's Disease: A Single Tertiary IBD Center CohortWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

In the last 2 decades, the introduction of biological therapies has been a significant milestone in the management of inflammatory bowel diseases. Despite the recent emergence of new biological therapies and small molecules, Anti-TNF agents still play a crucial role in treatment and still being used as first line biologic treatments rather than anti-integrins and anti-cytokines in quite a number of countries.Although many studies have been conducted previously to compare the efficacy of these drugs, there is still not a clear conclusion. In this study, we aimed to compare the persistence of infliximab (IFX) to adalimumab (ADA) in the treatment of Crohn's at a tertiary IBD center.

Methods

This was a retrospective cohort analysis of patients with Crohn's disease either received adalimumab or infliximab as a first line biologic treatment. A total of 411 patients were included to this analysis. Demographic information such as gender, age, montreal classification, smoking and prior medications were noted from patients electronic medical records. Weighted Kaplan-Meier and Cox models were used to assess the outcomes.

Results

Out of the 411 patients included in the study, 165 had used infliximab, and 246 had used adalimumab as a first-line treatment. Age and gender of the patients in both groups did not differ from each other statistically. 87% of the patients treated with adalimumab and 84% of the patients treated with infliximab were thiopurine experienced. Montreal classification differed between two groups (in IFX group, 60% of the patients had either sticturing or penetrating behaviour where as in ADA group, only 46% of the patients had either sticturing or penetrating behaviour, p<0.05). In ADA group, only 48% of the patients were receiving concomitant azathioprine treatment where as in IFX group, 60% of the patients were receiving concomitant azathioprine treatment. Primary non-response rates were not different between IFX and ADA group, 4.5% vs 4.6% respectively. In addition, clinical response rates after first year were 73.8% and 72.8% respectively. Drug persistency rates of adalimumab and infliximab in moderate to severe ulcerative colitis patients were not statistically different from each other (Figure 1).

Conclusion

In conclusion, it seems that there is no difference in drug persistence rates and in efficacy rates of the medications between infiximab and adalimumab treated moderate to severe Crohn's disease patients. Although disease character and concomitant treatment presence differ between two groups, these differences did not show any significant effect.Read more P718 Observational real-world evidence on the efficacy and safety of Janus Kinase inhibitors (JAKi) in the treatment of moderate to severe Active Ulcerative Colitis (UC)Wed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Janus kinase inhibitors (JAKi) are the first orally administered treatment for Ulcerative Colitis (UC). The JAK family comprises of four intracellular tyrosine kinases inhibitors (JAK1, JAK2, JAK3 and Tyrosine Kinase 2). Inhibition of the JAK kinases lead to dampening of the inflammatory cytokines which drive Inflammatory Bowel Disease (IBD).Tofacitinib was the first generation pan-JAKi. This was followed by second generation JAKi: Filgotinib and Upadacinib which preferentially inhibit JAK1.We report on the real-world evidence on the efficacy and safety of JAKi in the treatment of UC in a tertiary IBD treatment centre.

Methods

Patients attending the IBD clinic at weeks 8-12 of initiation of therapy were included. Baseline demographics, disease activity and previous therapies were recorded. Clinical response was measured using the SCCAI and biochemical response was measured using calprotectin and CRP.We defined clinical response as ≥3 points reduction from baseline SCCAI, and clinical remission as SCCAI Score of <2.5, and / or biochemical remission as a CRP of less than 5 mg/L and a calprotectin level of < 250 mg/g. We also assessed treatment persistence, and the reasons for treatment cessation.

Results

The UC populations are shown in Table 1. 52 patients were included and an additional 24 patients who discontinued therapy early on were assessed to review secondary outcomes. Table 1 summarises the comparative outcomes of the JAKi. 81% and 63% of patients achieved clinical and biochemical remission respectively. Overall, 31% discontinued treatment due to lack of efficacy or adverse events. 60% of patients reported adverse events (AEs), 25 % of patients discontinued treatment due to AEs and 84% of patients continued treatment despite reporting AEs. The most common AEs were hypercholesteremia and cold and flu like symptoms and the most common AEs related with treatment discontinuation were recurrent infection or persistent deranged liver functions contributed to patients’ history of primary sclerosing cholangitis. No Serious Adverse Events were reported. 60% of patients on tofacitinib developed side effects and persisted with therapy, which included hypercholesteremia (67%), shingles (11%), flu like symptom (11%) and hair loss (11%). 53% had side effects with Filgotinib; hypercholesteremia (25%), cold like symptoms (25%), chest infection (13%), shingles (13%), acne (13%). 68% developed side effects with Upadacitinib; reports of acne (20%), cold and flu (33%), shingles and mood swings (7%) and high cholesterol (67%).

Conclusion

In this real-world cohort of UC patients, JAKi was effective in inducing remission and had an acceptable safety profile. The observed safety profile was as expected compared to clinical data results.Read more P939 Ozanimod-Exposed Patients with Ulcerative Colitis Undergoing Total Colectomy Exhibit Unique Histologic Changes in Lymph NodesWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Ozanimod regulates lymphocyte egress from the spleen and lymph nodes into the systemic circulation. The histologic changes which occur in the lymph nodes of patients on these therapies is unknown. We describe histologic changes in lymph nodes from patients with UC who were treated with ozanimod and underwent subsequent colectomy due to treatment-refractory disease.

Methods

This retrospective study included patients with UC undergoing total colectomy for treatment-refractory disease who were treated with ozanimod within the 2 months prior to colectomy and a cohort of patients with UC undergoing colectomy who did not have ozanimod exposure. Histology of the lymph nodes from the mesentery of colectomy specimens were reviewed blindly by a hematophatologist (JXC) and an expert GI pathologist (CRW). Histopathological parameters were scored and demographic and clinical data were recorded.

Results

Of forty-five patients treated with ozanimod at our center, 6 (13%) required surgery for treatment-refractory disease. Colectomy specimen data were available for 5 patients (1 patient had surgery at an outside center). Lymph node specimens from 6 control patients with UC who had colectomy were also examined. Demographic and clinical data are summarized in Table 1. The duration of ozanimod therapy prior to surgery ranged from 6 to 24 weeks. Lymph nodes from patients treated with ozanimod had significantly greater extent of sinus dilatation than control patients (1.5 vs 0.67, p=0.022), they also had significantly more sinus histiocytosis (2.67 vs 1.67, p=0.03) (Figure 1). There was a tendency towards more Castleman-like angiotrophic hyperplasia (1.5 vs 1, p=0.34), plasma cell infiltration (1.5 vs 0.67, p=0.26) and subcortical interfollicular expansion (1.5 vs 0.83, p=0.1) in ozanimod treated patients. Patients treated with ozanimod and controls showed similar amounts of monomorphic lymphoid cells (1.3 vs 1.5, p=0.7), follicular hyperplasia (1 vs 1.1, p=0.8) and vascular proliferation (1.5 vs 1.5, p=1).

Conclusion

This study identifies unique histologic changes in the lymph nodes of patients with UC treated with ozanimod. These changes could be in keeping with the known mechanism of action of ozanimod and suggests that other inflammatory pathways were driving their disease activity in these patients. The significance of the changes, particularly the Castleman-like features, needs to be further investigated.Table 1: Demographic and clinical data of patients treated with ozanimod and control patientsFigure 1: Representative images of lymph nodes from patients with UC treated with ozanimod and control patients showing significant sinus dilatation in patients receiving ozanimodRead more P719 Vitamin and micronutrient excess in patients with Crohn’s disease under oral ambulatory exclusive enteral nutritionWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Exclusive enteral nutrition (EEN) is recommended for preoperative nutritional optimization (PNO) in adult Crohn's disease (CD) patients. However, during ambulatory oral EEN, a lack of routine monitoring for vitamins may occur, with a potential risk of hypervitaminosis-related toxicity, which remains unexplored. This study aims to assess the serum levels of vitamins and micronutrients in CD patients undergoing EEN and to examine its potential impact.

Methods

Complicated phenotype CD patients followed at a University Tertiary Hospital who were started on oral EEN June 2021 - June 2023 were prospectively included. EEN composition was determined and modified by an IBD nutritionist according to patients’ nutritional status and needs and laboratory values. Compliance was monitored daily, both for in- and outpatients. Patients’ weight and serum values (albumin, C-reactive protein [CRP], iron, folic acid, and vitamins B1, B6, B12, A, D, E and K) were monitored weekly.

Results

Nine patients (median age 29 years, 55.6% female) received a median of 24 (IQR 14.5-25.0) days of EEN, for PNO of symptomatic stricturing (7, 77.8%) or abdominal penetrating disease (2, 22.2%). All patients were discharged while on EEN, which was maintained until elective surgery (4, 44.4%) or the planned start of advanced medical therapy (5, 55.6%), with EEN successfully avoiding emergent surgeries. Patients were started on a combination of hypercaloric-hyperproteic and hypercaloric-normoproteic ready-to-drink concentrated polymeric formulas, providing 30 kcal/kg/d and 1.2-1.5g/kg/d of protein. EEN daily volume ranged from 1000 to 1400mL. Compliance was 100%, requiring flavour adjustments for tolerance. Table 1 illustrates changes over time in patients' weight and serum levels of interest. Resolution of anaemia and hypoalbuminemia was achieved, while weight was maintained . Hypervitaminosis cases were remarkably detected: 5 (55.6%) for vitamin B1, 4 (44.4%) for A, 2 (22.2%) for E, and 3 (33.3%) for K, with increasing trends over time. However, no symptoms related to hypervitaminosis were reported.

Conclusion

Our study on PNO EEN in CD uncovered a gap in routine monitoring for essential vitamins during EEN. While achieving significant clinical improvement, our findings revealed subtle and asymptomatic cases of hypervitaminosis in short-term EEN courses. These results underscore that vitamin monitoring is advisable during EEN, especially in prolonged EEN protocols due to possible hypervitaminosis-related toxicity.Read more P940 A glance into paediatric Inflammatory Bowel Disease in Australasia – Crohn’s Colitis Cure (CCC) data insights programWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Around 10% of people with inflammatory bowel diseases (IBD) are diagnosed in childhood¹. Clinical manifestations are known to differ in children compared to adults^2,3. This study aims to describe the real-world characteristics of children with IBD.

Methods

Crohn’s Colitis Care (CCCare) is an IBD-specific electronic medical record (EMR) used at IBD centres across Australasia. Data feed into a de-identified clinical quality registry (CQR), which was interrogated in November 2023. All children (<18 years at time of extract) under active care (encounter within 14 months) were included.

Results

Clinical data from 162 children across 14 centres were available for analysis. Of these, 64.8% (n=105) had Crohn’s disease (CD), 31.5% (n=51) ulcerative colitis (UC) and 3.7% (n=6) IBD-unclassified. There was a roughly equal split in gender (male=55.0%), with a minority aged <10 years (9.9%, n=16). The mean recorded body mass index was 20.5kg/m² (n=101 with BMI data), with 78.2% in the ‘normal’ range (18.5-24.9kg/m²). Five patients (5.0%) were ‘underweight’ (<18kg/m²), and 16.8% (n=17) were overweight or obese (>25kg/m²).Only 7.4% (n=12) were currently receiving steroids, and over half (55.6%, n=90) had received an advanced therapy (biologic or small molecule). Few reported incontinence (n=5, 3.1%), and 6% (n=9) had an IBD-related surgery recorded. Around 20% (11/56) had current or previous fistulising CD. On most recent data, the mean faecal calprotectin was 637μg/g, C-reactive protein 6.1mg/L and ESR 9.4mm/hr. In those with UC, 43.7% had either moderate (S2) or severe (S3) disease activity at last assessment (Figure 1). In those with CD, 31.1% had either stricturing (B2, 21.5%) or penetrating intra-abdominal disease (abscess/perforation/phlegmon, B3, 10.6%).

Conclusion

This study provides a detailed real-world overview of IBD in children in Australasia, demonstrating the ability of CCCare to help collate data at scale across a large geography. Data show clear changes in phenotype over time. Such data allow for the tracking and benchmarking of outcomes over time across centres, thus promoting evidence-based care improvements. Ongoing real-world data collection is crucial in optimising management strategies and improving care outcomes.1 - Burgess CJ et al. Paediatric Patients (Less Than Age of 17 Years) Account for Less Than 1.5% of All Prevalent Inflammatory Bowel Disease Cases. J Pediatr Gastroenterol Nutr. doi: 10.1097/MPG.0000000000002842.2 - Seyedian SS et al. A review of the diagnosis, prevention, and treatment methods of inflammatory bowel disease. J Med Life. doi:10.25122/jml-2018-00753 - Moon JS. Clinical Aspects and Treatments for Pediatric Inflammatory Bowel Diseases. Pediatr Gastroenterol Hepatol Nutr. doi:10.5223/pghn.2019.22.1.50Read more P720 Exit interviews exploring Crohn’s disease patients’ experience of changes in their bowel urgency during the mirikizumab Phase 3 clinical trial in adult patients with moderate to severe Crohn diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The objective of this study was to explore the clinical trial experience of patients with Crohn’s disease (CD), including perceptions of the Urgency Numeric Rating Scale (Urgency NRS) and meaningful within-patient change (MWPC).

Methods

Qualitative, 90-minute exit interviews were conducted with patients who had moderate to severe CD and completed the VIVID-1 phase 3, multicentre, randomized, double-blind, placebo and active-controlled, mirikizumab clinical trial in the past 3 weeks. The semi-structured interview guide included cognitive debriefing to explore the content validity of the 11-point Urgency NRS (0=No urgency to 10=Worst possible urgency in the past 24 hours). Interview transcripts were analysed using qualitative directed content analysis and framework analysis.

Results

Interviewed participants (N=62) were from the US (n=29), Czech Republic (n=10), Poland (n=8), Germany (n=7), Canada (n=4), Australia (n=3) and the UK (n=1). Participants (age 22–75 years, 55% female, 53% high school education or lower) were diagnosed with CD for 1–54 years. Most participants understood the Urgency NRS as assessing the severity of feeling an immediate need to go to the bathroom and used it accurately and without difficulty. Participants interpreted the Urgency NRS as ranging from “no urgency” [0] to an “immediate, sudden need or loss of bowel control” [10]. Participants reported that a ‘good day’ or ‘remission’ would feature reduced or no or minimal bowel urgency and permit adequate time to find a bathroom, feature no accidents and allow participation in daily/leisure/social activities and work away from home. Participants considered Urgency NRS scores ≤3 as a ‘good day’ (n=45/59) and ≤2 as ‘remission’ (n=41/57). Most reported that the bowel urgency improvement they experienced was meaningful (n=51/55; Table 1) because it improved their quality of life. A 3-point Urgency NRS improvement was identified as the smallest meaningful change (n=40/54; Table 1). Most participants associated bowel urgency with CD severity when responding to a Patient Global Rating of Severity (PGRS; n=42) and a Patient Global Impression of Change (PGIC; n=32). Most participants related Urgency NRS scores of 0 to None, 2 to Very Mild, 4 to Mild, 6 to Moderate, 8 to Severe and 10 to Very Severe on the PGRS (Figure 1). Urgency NRS improvements of 3-10 points were considered Much better or Very much better on the PGIC (Figure 1).

Conclusion

The Urgency NRS was well understood and a ≥3-point improvement in Urgency NRS score was considered a MWPC. Participants with CD who had completed the mirikizumab clinical trial perceived a meaningful change in bowel urgency to feature reduced or minimal bowel urgency enabling improved daily functioning.Read more P967 Allogeneic bone marrow-derived mesenchymal stromal cell therapy for complex perianal and rectovaginal fistulas in Crohn´s disease: a retrospective single-centre studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Perianal fistulising Crohn´s disease (CD) is associated with a high burden of disease and treatment of fistulas remains challenging. Promising data on short-term efficacy of bone marrow-derived mesenchymal stromal cell (bmMSC) treatment emerged in the recent past, but there is limited data regarding long-term efficacy and safety.

Methods

Between February 2013 and January 2016, patients with non-active CD (Harvey-Bradshaw Index < 5) and draining complex, treatment-refractory perianal or rectovaginal fistulas underwent local bmMSC therapy as compassionate use. After curettage of the fistula tract, patients received three local bmMSC injections biweekly with 20 million cells each. In case of incomplete clinical and radiological healing 3 to 12 months after the first treatment, up to six additional injections with 40 million cells each were administrated, resulting in a maximal cumulative dose of 300 million bmMSC (table 1). We retrospectively analysed patient records for disease course and documentation of adverse events. Clinical remission was defined by closure of external fistula openings without discharge at digital pressure. The modified Van Assche index was assessed before bmMSC treatment as well as in short- and long-term MRI follow-up.

Results

Six female patients (median age 35 years, range 19 – 46 years) with two or three complex fistulas each were included. In total, 13 fistulas (9 transsphincteric, 2 extrasphincteric and 2 rectovaginal) underwent local bmMSC application (table 1). Median radiological and clinical follow up was 80 months (range, 44 – 98 months) after first local bmMSC injection. 8 of 13 fistulas (62%) exhibited complete closure at last observation. For rectovaginal fistulas, long-term remission was 50 % (1 of 2). Excluding rectovaginal fistulas, 4 of 6 patients (67%) showed long-term closure of all other fistulas. Pelvic MRI showed a decrease in modified Van Assche index from baseline (median score 7.8, range 6.2-9.7) to long-term follow up (median score 2.1, range 1.5-11.7). No immediate adverse events related to bmMSC injections were observed. One patient (p1) was diagnosed with a local adenocarcinoma of the rectum (pT1, pN0, R0) 106 months after first bmMSC injection. MRI control 11 months prior showed complete fistula remission. The tumor exhibited a female karyotype, while bmMSC had been derived from a male volunteer.

Conclusion

More than 60% of all treatment-refractory CD perianal fistulas showed long-term remission up to 8 years after local allogenic bmMSC therapy.Read more P768 Appropriateness of small molecule agents for patients with IBD of childbearing age – a RAND appropriateness panelWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Many women of childbearing age with IBD require advanced therapies. While biologics are largely low risk during pregnancy, the novel small molecules Tofacitinib, Filgotinib, Upadacitinib and Ozanimod (TFUO) have shown concerning reproductive results in animal studies. Therefore, their use in women of childbearing age needs careful consideration.

Methods

We convened a RAND appropriateness panel of 6 gastroenterologists, 2 IBD nurses, 1 IBD pharmacist and 3 expert patients. Following a literature review, 13 statements were drafted and voted upon in 2 rounds.

Results

13 statements were voted on in two rounds. All statements were deemed appropriate after one round of revisions. Here we present a selection of key statements:1. Women with IBD of childbearing age who wish to commence therapy with TFUO, need to use effective contraception. Counselling regarding the risk of TFUO in unplanned pregnancies should be provided.2. For women using contraception while on JAK therapy, we suggest the preferred use of progesterone-only or non-hormonal long-acting contraception over combined oestrogen-progesterone formulations to reduce the risk of venous thromboembolism.3. TFUO are contraindicated during pregnancy due to serious teratogenicity concerns.4. Regardless of physical wash out periods, we recommend that women currently receiving TFUO cease therapy with enough time to establish clinical remission ideally for at least 3 months prior to conception. This window allows to safely establish whether the alternative (or no) therapy can maintain remission.5. Therapies other than TFUO should be considered as first line therapy in women with IBD of childbearing age, with the exception of select individual social or medical circumstances, or women who have completed family planning and agree to use effective contraception.6. TFUO may be appropriate choices for women of childbearing age after failure of, intolerance of or contraindications to one biological agent licensed for IBD.7. In women who wish to have children in the future, a minimum treatment period for TFUO should be considered. Where the wish to start a family is less than 1 year in the future it is recommended to consider agents other than TFUO.8. TFUO are contraindicated during breastfeeding.9. If a woman conceives while taking TFUO, the medication should be ceased, she should receive counselling about potential known and unknown maternofoetal complications, and alternative IBD therapy may be commenced if required.

Conclusion

We developed 13 practice statements derived from a RAND appropriateness panel of clinicians and patients to guide decision making for women of childbearing age regarding TFUO small molecules therapies for IBD.Read more P968 Influences of Sequential Introduction of Thiopurine on Long-Term Efficacy of Infliximab in Patients with Inflammatory Bowel DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

As one of the biological agents for the treatment of inflammatory bowel disease (IBD), infliximab (IFX) has gradually become a cornerstone drug over the past two decades. While there is still a non-negligible loss of response rate, which may be explained by immunogenicity. A coping method is adding immunomodulators, among which thiopurine (TP) is the most common choice. However, combination therapy may lead to an increased risk of infection and malignancy, and how to introduce immunosuppressive agents properly to maximize benefits remains a controversial dilemma. Therefore, this study aims to assess the impact of sequentially introducing TP on the long-term effectiveness of IBD patients receiving concurrent IFX treatment.

Methods

A retrospective analysis was conducted at a tertiary hospital between June 2013 and January 2022. Primary outcomes encompassed drug sustainability and biological switching. Multivariate analyses were employed to examine factors influencing these outcomes.

Results

Among 787 consecutive patients, 500 were included in the final analysis. Of these, 166 received IFX monotherapy and 334 were on IFX-TP cotherapy (173 were prior TP exposure, 59 initiating TP post 3 months of IFX treatment and 102 with de novo combination). A total of 152 (28.94%) patients discontinued the IFX regimen within 18.2 months. Additionally, 119 (22.67%) patients switched to alternative biologics within a median of 18.1 months, with higher switching rates in the monotherapy and early exposure groups (P = 0.027). Antibodies to infliximab (ATI) were detected in 36.7% patients within a median of 5 months. The monotherapy group exhibited higher cumulative rate of ATI development, ATI concentrations, and lower trough levels (TLs), while the de novo combination group demonstrated the lowest ATI development and highest TLs.Only the order of introduction of TP therapy (HR 0.698, 95%CI 0.597-0.815, P <0.001) and ATI formation (HR 1.009, 95%CI 1.003-1.014, P =0.004) were associated with drug sustainability. Both the de novo (HR 0.367, 95%CI 0.263-0.512, P <0.001) and the late combination group (HR 0.53, 95%CI 0.359-0.782, P =0.001) had relatively higher drug retention when compared to the others.In terms of biological switching, combination therapy (HR 0.41, 95%CI 0.19-0.88, P =0.023) and the order of introducing TPs had a significant effect (HR 0.391, 95%CI 0.183-0.836, P =0.015). Moreover, the de novo combination group demonstrated fewer clinical flares (P = 0.043).

Conclusion

Initiating TPs de novo may improve drug sustainability and offer better long-term efficacy for IBD patients receiving IFX therapy.Read more P650 Optimization through iv maintenance with ustekinumab in Inflammatory Bowel Disease. Efficacy and adjusted regimen in real worldWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Ustekinumab (UST) is an effective treatment for Crohn's disease (CD) and ulcerative colitis (UC). However, some patients do not respond to conventional subcutaneous (SC) doses and lose response at follow-up. The use of maintenance intravenous (IV) UST could play a role in these patients.

Methods

The aim of the study was to evaluate the effectiveness of IV maintenance UST in patients with failure to subcutaneous UST. Single-center study performed in consecutive patients included in a prospective database. The reduction of activity markers such as C Reactive Protein (CRP) and fecal calprotectin (FC), UST trough levels pre- and post IV maintenance as well as clinical indices of activity were evaluated. IV dose adjustments and their effect on levels were collected. We defined biochemical remission as the percentage decrease FC ≥ 80% and/or final FC ≤ 250.

Results

Of 335 patients in our center under treatment with ustekinumab, 31 patients (9.25%) were included. Baseline characteristics of patients are shown in Table 1. Mean age at the start of UST IV 42.49 years ± 13.23. CD 77.4%; UC 22.6%. Up to 2/3 of patients with CD had a complicated phenotype (B2/B3) and 50% perianal disease (PD). All included patients were bio-exposed and 61.3% had carried ≥ 2 biologics.The major indication for initiation of UST was secondary failure to previous biologic therapy (74.2%). The most used induction IV dose was 390mg and subsequent SC maintenance was every 8 weeks in 76% (60% were later intensification cases). Re-induction was performed in 36.7% of patients. The median time from drug initiation to IV maintenance was 10.23 [IQR 30.7] months. In 54.8% a higher dose was administered in the first IV maintenance infusion. The most common maintenance regimen was 130mg (64.5%) every 4 weeks (54.8%). Baseline FC decreased significantly (Figure 1) at the end of follow-up (median [IQR]: 809 µg/g [2256] vs 333 µg/g [508], p =0.001). Basal Harvey index was reduced compared to HBI at 24 weeks (mean ± SD: 6.5 ± 4.3 vs 4.1 ± 3.1, p =0.019). Drug levels at the start of IV maintenance were 1.4 µg/ml [IQR 2.3] vs. 4.8 µg/ml [IQR 3.9] at week 24 (p< 0.001) after dose adjustment in 35.5% of patients during IV maintenance.At the end of follow-up 54% went into biochemical remission. The presence of PD was associated with lower biochemical remission (70.6% vs. 27.3%, p =0.025). The median IV UST maintenance time was 8.55 [IQR 23.9] months. 96.6% are continuing treatment. No serious infections or malignancy were documented.

Conclusion

The use of maintenance IV UST appears to be an effective and safe strategy that can be evaluated as a salvage treatment especially in highly bioexposed patients or with complex CD phenotype.Read more P997 New Objective Assessment of perianal Crohn’s disease, Perianal Lesion Index; PLIWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

In the previous survey, decisions of biological treatment (Bio) success for perianal Crohn’s disease (pCD) were made by the patient’s subjective improvement and physician’s assessment, so it lacks objectivity. Moreover, physicians, surgeons, and proctologists are related to treating pCD. This aspect is the difficulty of the treatment of pCD. We need a common assessment for each area’s doctor. We aimed to develop a new objective assessment of pCD, including endoscopic findings, and assess the efficacy of the newly launched Bio except anti-TNFα agents for pCD.

Methods

Usually, perianal abscesses and fistula are derived from ulcers in the lower rectum and anal canal, so we adapted SES-CD to the location and checked discharge and needs of setons, and finally scored it (Table 1). We named this assessment Perianal Lesion Index; PLI.We retrospectively evaluated 20 pCD patients who received Ustekinumab (UST) and Vedolizumab (VDZ) from March 2017 to March 2023 at our institute. We checked each patient’s PLI, CRP, LRG, and CDAI and compared them before starting Bio and eight weeks after initiation of Bio using a paired T-test. Finally, we used the Pearson correlation coefficient to examine the correlation between PLI and conventional serum biomarkers and CDAI.

Results

The male-to-female ratio was 4.0, the average age at the treatment initiation was 35. Eighteen patient’s diseases were located in the small and large intestines, 10 patients were penetrating type, and 2 patients were stenotic type. We used UST for 16 patients and VDZ for 4 patients. Seven patients were naïve for Bio, 8 patients were treated by one Bio, and 5 patients were treated by two Bio.PLI was positively correlated with CRP (r=0.59, p<0.001) but not correlated with LRG (r=0.77, p=0.077) and CDAI (r=0.35, p=0.07). The pretreatment average PLI was 8.5 and significantly decreased to 3.9 (p<0.001) 8 weeks after Bio initiation. There was a significant change in CRP (3.1 to 0.9, p =0.03) but not CDAI (193 to 147, p=0.2). There were significant PLI changes in each treatment group; the UST group’s PLI change was 8.3 to 3.1 (p<0.001), and the VDZ group's PLI was 9.5 to 8.0 (p=0.02) (Figure 1).

Conclusion

PLI seems to be an objective assessment for pCD, and it was positively correlated to CRP. We could assess each drug’s efficacy for pCD. Further investigation is needed to establish PLI’s accuracy, and we hope this assessment will contribute to the choices of Bio for pCD and the evaluation of its efficacyRead more P651 A randomised controlled trial of IBD-BOOST, a digital cognitive behavioural self-management programme for fatigue, and/or pain, and/or faecal incontinence in inflammatory bowel diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Many people with IBD experience fatigue, pain and faecal incontinence (FI), impacting quality of life (QoL). We developed an interactive digital online self-management intervention (IBD-BOOST) based on a theoretically informed logic model and cognitive behavioural techniques, to treat these symptoms. We aimed to assess if IBD-BOOST, alongside health care professional (HCP) support and care as usual (CAU), provides greater relief from symptoms and improvement of QoL compared with CAU alone.

Methods

We conducted a pragmatic multi-centre two-arm parallel group randomised controlled trial (RCT) recruiting patients from clinics and national registries who rated the impact of fatigue and/or pain and/or FI as ≥5/10. Those in the IBD-BOOST arm received 6 months access to the 12-session IBD-BOOST programme, a 30-minute telephone support call with a trained HCP after session 1 and weekly in-site email messages from the HCP for 3 months. The UK Inflammatory Bowel Disease Questionnaire (UK-IBDQ) and global rating of symptom relief (GRSR) at 6 months were dual primary outcomes (alpha=0.025 was considered statistically significant as there were two primary outcomes). Other secondary outcomes, including individual symptoms, were measured at 6 and 12 months. Complier-averaged causal effects (CACE), sensitivity and pre-specified subgroup analyses were conducted.

Results

780 participants were randomised (Figure 1), 432 with Crohn’s disease, 348 with ulcerative colitis or other IBD; 520 (66.7%) were female, mean age 49 years. At 6 months, both UK-IBDQ and GRSR were similar between the BOOST and CAU arms, p=0.19 for IBDQ and p=0.39 for GRSR (Table 1). Adverse events were similar between groups. FI score and EQ5D utility score (secondary outcomes) were significantly in favour of IBD-BOOST at 6 months, but pain and fatigue were no different. 57% of the intervention group completed a pre-defined minimum “dose” of 4 sessions (i.e. compliers). The CACE analysis suggested that compliers were more likely to report better QoL (p=0.03). Subgroup analysis of those meeting criteria for irritable bowel syndrome (IBS), showed that IBD-BOOST was more effective in improving IBDQ and GRSR at 6 months when compared with CAU for the IBD-IBS group (p_interaction=0.015 and 0.046, respectively).

Conclusion

This large RCT found that IBD-BOOST did not improve IBDQ and GRSR in patients with IBD and fatigue and/or pain and/or FI relative to CAU. Participants reported less FI at 6 and 12 months. Those who complied with the intervention showed a more pronounced IBDQ treatment effect. Those with IBD-IBS at baseline improved more than those without, suggesting a possible for further effectiveness research on IBD-BOOST.Trial registration: ISRCTN71618461Read more P1011 Methotrexate polyglutamates in paediatric inflammatory bowel disease: Novel tool for therapeutic drug monitoring?Wed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Methotrexate (MTX) is increasingly prescribed in paediatric inflammatory bowel disease (IBD), but therapeutic drug monitoring (TDM) is currently not feasible due to its characteristic pharmacokinetics and short half-life in plasma, which amounts to approximately 2.5-6.5 hours. Because of this, plasma MTX is no longer detectable shortly after administration. However, MTX-polyglutamates (PG_1-5) are formed intracellularly and accumulate over time. Recently, we developed a technique for targeted erythrocyte MTX-PG analysis with the potential for TDM. Data in paediatric IBD with this technique are lacking so far. Here, we aimed to identify the potential of erythrocyte MTX-PG analysis to measure MTX levels in paediatric IBD.

Methods

In this observational cross-sectional study, we determined MTX-PG concentrations in erythrocytes retrieved from blood samples of paediatric IBD patients on low-dose MTX maintenance therapy, defined as exposure to a stable dose of MTX for at least twelve consecutive weeks. MTX-PG concentrations were determined by stable-isotope dilution liquid chromatography mass-spectrometry. Furthermore, we evaluated the effects of route of administration (oral versus subcutaneous), MTX dosage, and anthropometric data on MTX-PG concentrations.

Results

Fifty-two paediatric IBD patients on MTX maintenance therapy were included. The predominant subspecies was MTX-PG₃ (mean 30.5 nmol/L, SD ± 20.0) and the mean MTX-PG_total concentration was 88.6 nmol/L (SD ± 52.6). A higher dose was linearly associated with significantly higher MTX-PG₃ (r = 0.56), MTX-PG₄ (r = 0.52), MTX-PG₅ (r = 0.48) and MTX-PG_total (r = 0.49) levels. When adjusted for body surface area, MTX dose was also linearly associated with significantly higher MTX-PG₃ (r = 0.51), MTX-PG₄ (r= 0.39), and MTX-PG_total (r= 0.40) concentrations. A reliable comparison regarding route of administration was not possible in this cohort, due to the small number of patients receiving subcutaneous MTX (n=3).

Conclusion

We observed high inter-individual variability in the reached erythrocyte MTX-PG concentrations. Body surface adjusted or unadjusted MTX dosage showed a positive linear correlation with erythrocyte MTX-PG concentrations in children with IBD. This is a prerequisite for TDM and provides a strong basis for further research into the relation between TDM of MTX, effectivity and toxicity.Read more P671 Patient perspectives on symptoms and impacts in Crohn’s disease: Results from qualitative researchWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Patients’ perspectives on their Crohn’s disease (CD) symptoms and the impacts of CD on their daily lives can be used to inform clinical care and treatment development. This study aimed to elicit in-depth qualitative information on the symptom burden of CD and to quantify which symptoms patients considered most bothersome and most important to improve.

Methods

Individual, web-based interviews were conducted in adults and adolescents (aged 15–17 years) with moderately to severely active CD. Participants were asked open-ended questions to elicit their experiences with CD and CD-related impacts on their daily lives. Participants were then probed about symptom- and impact-related concepts of interest that they did not spontaneously report. Participants were asked which symptoms they considered most bothersome and which symptoms they considered most important to improve. Interview transcripts and field notes were analyzed using a standard thematic analysis approach.

Results

17 adults and 3 adolescents participated between May and July 2023. Participants were 17–60 [mean=38] years old; 70% were female [n=14]; 70% were White [n=14]. Participants had been diagnosed, on average, 10 (range: 0.5–29) years ago. Over half (n=13, 65%) reported moderate CD severity. Nearly all participants reported fatigue (n=19, 95%), bowel urgency (n=18, 90%), diarrhea (n=18, 90%), abdominal pain (n=17, 85%), and frequent bowel movements (n=15, 75%). About a third reported nausea (n=7, 35%), bloating (n=6, 30%), joint pain (n=6, 30%), or blood in their stool (n=6, 30%). In total, nine different most bothersome symptoms or treatment priorities were reported across participants (Figure 1). Participants most commonly reported abdominal pain (n=6, 30%), bowel urgency (n=4, 20%), and diarrhea (n=4, 20%) as their most bothersome symptoms; these were also the symptoms most commonly reported as the most important to improve (abdominal pain: n=7, 35%; bowel urgency: n=5, 25%; diarrhea: n=4, 20%) (Figure 1). All participants reported that CD hinders their daily activities, and nearly all reported that CD affects their mood or emotions (n=19, 95%), social activities or relationships (n=19, 95%), work or school (e.g., loss of productivity) (n=18, 90%), and sleep (n=15, 75%) (Table 1). Participants described "feel[ing] left out", "want[ing] to stay home", and having to cancel or leave activities because of their CD. Several participants indicated that they "plan their day around [their CD]".

Conclusion

Patients with moderately to severely active CD were burdened by a variety of symptoms. Patients commonly considered abdominal pain, bowel urgency, and diarrhea symptoms to be the most bothersome and the most important to improve.Read more P672 Occurrence of malignancy among infliximab biosimilar and bio-originator initiators in Canada: a comparative population-based analysisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Infliximab (INF) downregulates the immune system. Given the immune system's role in deleting pre-cancerous cells, malignancy is a potential concern. Still, relatively few real-world data analyses have compared biosimilar versus bio-originator INF in terms of malignancy incidence. We aimed to compare malignancy occurrence among initiators of infliximab biosimilar (INF-B) and originator (INF-O).

Methods

We used data from the National Prescription Drug Utilization Information System (NPDUIS), containing pan-Canadian (except Quebec) claims-level data on prescription dispensations paid from public drug programs linked to comprehensive day surgery and inpatient care (Discharge Abstract Database, DAD) and hospital-based and community-based ambulatory care (National Ambulatory Care Reporting System, NACRS). We studied adults (≥18 years) initiating INF between January 2015 and December 2019 with no history of malignancy, HIV or organ transplant (1-year pre-baseline). Follow-up began 365 days after treatment initiation (lag period) and continued until the first cancer diagnostic code (ICD-10 C00-C97), treatment discontinuation + 365 days, or end of study period. We compared INF-B and INF-O using Cox regression models, adjusting for potential confounders/ effect modifiers: sex, age at treatment initiation, prior use of other biologics or prednisone, province (Ontario versus others), and calendar year.

Results

New users of INF-B (2,019) and INF-O (5,183) were about half female (52%), with a median age (interquartile range) of 45 years (28-62). Overall, the malignancy incidence rate was 10.2 (95% confidence interval, CI, 8.7-11.8) events per 1,000 person-years. Comparing INF-B to INF-O, the adjusted hazard ratio for malignancy was 0.97 (95% CI 0.63-1.48).

Conclusion

In this real-world dataset, we were unable to identify clear differences in malignancy comparing INF-B and INF-O. Limitations include the inability to control for residual confounders (e.g., disease severity), potential outcome misclassification, and selection bias.Read more P1012 Dose escalated Ustekinumab in Inflammatory Bowel Disease - Crohn's Colitis Cure (CCC) Data Insights ProgramWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Ustekinumab is a human monoclonal antibody targeting interleukin-12 and 23 with established efficacy in inflammatory bowel disease (IBD). Many people receiving ustekinumab do not achieve adequate or sustained response to standard dosing and require dose escalation (DE). We aimed to investigate the frequency and outcomes of escalated dosing regimens in an Australasian cohort.

Methods

Crohn’s Colitis Care (CCCare) is a cloud-based IBD-specific electronic medical record used in routine care across Australia and New Zealand. Data feeds continuously into a de-identified clinical quality registry (CQR). Data were interrogated in November 2023 comparing outcomes and healthcare utilisation prior to and at 12 months post ustekinumab DE. DE was defined as maintenance dosing >90mg subcutaneously Q8 weekly and/or additional induction doses.

Results

A total of 790 people received ustekinumab, with 43.4% on DE therapy. Most of the cohort had Crohn’s disease (86.1%), followed by ulcerative colitis (11.3%) and IBD-unclassified (1.6%). The median age for the total cohort was 40 years (IQR 30-52) with an even gender distribution (50.3% female). The median age at diagnosis was 25 (IQR 18-38) with a median time to DE of 6 months (IQR 1-15). Age, age at diagnosis and disease duration did not significantly differ between DE and standard dose cohorts. Almost all people with IBD on DE ustekinumab continued on therapy beyond 12 months (84.5%).Rates of faecal calprotectin remission (<250ug/g), endoscopic remission and patient reported outcome (PRO2) remission were higher 12 months post DE (Table 1). Systemic steroid requirements fell significantly 12 months post DE. The number of endoscopies and radiological investigations fell at 12 months post DE, while the rates of hospital admissions did not significantly differ between the DE and standard cohorts. Clinical assessments (per person) reduced from 1.2 pre-DE to 0.9 post DE.

Conclusion

In a large real-world Australasian cohort of people receiving ustekinumab for IBD, close to half required DE. DE led to reduced systemic steroid use and improved endoscopic, PRO2 and FCP remission rates at 12 months. These data can be used to perform health economy analysis to determine the price points at which DE is cost effective, with additional data on quality of life and indirect healthcare costs being important to include for a robust holistic assessment of value in care.Read more P691 Intestinal ultrasonography accuracy in the evaluation of patients with moderate to severe ulcerative colitis starting infliximab therapyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The diagnostic accuracy of detecting active ulcerative colitis (UC) by transabdominal intestinal ultrasonography (IUS) is well described. However, the value of repeated IUS measurements in tight monitoring during treatment remains to be established. The aim of the study is to evaluate the utility of IUS for monitoring biologic therapy in UC. Additionally, to establish the correlations between IUS findings and the endoscopic Mayo score (EMS), as well as clinical and biochemical severity indices.

Methods

In a prospective open-label study, individuals with moderate to severe ulcerative colitis who were initiating infliximab therapy were included, excluding those with proctitis. Patients were evaluated at baseline and after 3 months of biologics induction by means of clinical, biochemical, endoscopic mayo score, and IUS assessments. A Paired Wilcoxon analysis was conducted to compare data before and after therapy induction. The correlation between bowel wall thickness (BWT) and the endoscopic mayo score (EMS), C-reactive protein (CRP), calprotectin, and the Simple Clinical Colitis Activity Index (SCCAI) was analyzed across both visits.

Results

Thirty-two patients were enrolled and completed baseline evaluations and 21 completed follow-up assessments. The median age was 38 years (IQR 29-60), with 53% male, a median disease duration of 7 years (6-9), 41% having left-sided colitis, and 59% with pancolitis. All patients were treated with infliximab. No significant differences were observed at both time points in terms of BWT, EMS, CRP, and calprotectin (5.5 vs 4.4, p=0.2; 2 (2-3) vs 2 (1-3), p=0.4; 9.4 vs 9.6, p=0.4; 979 vs 394, p= 0.1, respectively). The only significant improvement was in terms of SCCAI (7 (4.8-8) vs 3 (1-5), p=0.009). BWT showed significant correlations with EMS (r= 0.43, p= 0.0015) (figure 1), CRP (r= 0.40, p= 0.007), and SCCAI (r= 0.28, p= 0.03), while no correlation was found with calprotectin (r= 0.19, p= 0.25).

Conclusion

Intestinal ultrasonography could serve as a substitute for lower endoscopy in evaluating disease activity.Read more P692 An IBD nurse-led educational programme on safety and efficacy of adjuvated recombinant zoster vaccine can improve vaccine uptake in IBD patients on immunosuppressive treatmentWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Herpes Zoster (HZ) represents one of the most frequent opportunistic infections in IBD patients under immunosoppressive treatment and can be prevented by vaccination. Adjuvated recombinant zoster vaccine (RZV) is the first HZ vaccine approved for immunocompromised persons. IBD patients are less likely to receive appropriate vaccinations compared to the general population. IBD nurses operate as the primary point of contact for patients and this unique position provides a suitable opportunity to positively impact patient care and encourage vaccination. We aimed to improve RZV vaccination rates by a nurse-led education intervention within an on-site RZV vaccination programme.

Methods

IBD patients on immunosuppressive therapies were actively recruited by phone contact, mail and during outpatient clinic or infusion centre attendance. Prior immunization to VZV was collected from medical records. Patients were randomly assigned to receive either standard explanation on the importance of HZ vaccination by the IBD attending physician (group P) or additional education by an IBD nurse (group N). Patients in group N were referred to an IBD nurse for an individual 15 minutes nurse–patient interview. During the interview, disease activity and current treatment, previous immunization to VZV and history of HZ were reviewed; the importance, benefits and safety of HZ vaccination with RZV were discussed with the patient. Patients were then referred to dedicated on-site vaccination clinics where vaccine administration was provided by the IBD nurses running the infusion centre. Reasons for vaccine refusal was also recorded.

Results

From February to April 2022, 164 (80%) out of 205 eligible patients were enrolled (median age 48.5 years, 54.1% male; 48.7% UC, 51.3% CD); 65 patients (39.6%) were randomized to group P and 99 patients (60.4%) to group N. Six months after randomization, 112 (68.2%) had received at least 1 RZV vaccine dose whereas vaccination was completed in 110 patients (67%). Vaccination rate was significantly higher in the nurse-led education intervention group compared to standard clinical care (group N 75.7% vs group P 56.9%,p<0.05). Most common reasons for vaccine hesitancy were concerns about side effects (40.9%), fear of vaccine aggravating the disease (14.7%), considering themselves not at risk (13.3%) and objection to the administration of vaccine (10.1%).

Conclusion

Vaccination recommendations should be responsibility of the IBD patient care team and efforts should be made to reduce vaccine hesitancy. We showed that a simple nurse-led educational intervention on vaccine safety and efficacy was able to improve RVZ vaccination rates in IBD patients on immunosuppressive treatment.Read more P1013 Placebo rates in Crohn's disease: An individual patient data meta-analysis from multiple randomised controlled trialsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Estimating placebo rates and their determinants is essential for designing efficient randomised clinical trials (RCTs) in inflammatory bowel disease. We conducted an individual patient data (IPD) meta-analysis of placebo data from RCTs in Crohn’s disease (CD).

Methods

MEDLINE, Embase, and CENTRAL were searched from 01/2010 to 01/2020 for contemporary phase 2 and 3 placebo-controlled RCTs of biologics in moderate-to-severe CD. De-identified IPD from eligible trials that were available through the Vivli and Yale University Open Data Access data-sharing platforms were obtained. Primary outcomes were placebo clinical response and remission. Pooled placebo rates and 95% CIs were estimated using a 2-stage meta-analytical approach. Significant patient-level factors (P<0.05) associated with placebo rates were identified using regression analyses.

Results

Placebo IPD were available from 8 induction (n=1147) and 4 maintenance trials (n=524). Pooled placebo clinical response and remission rates varied based on outcome definition and prior biologic exposure (Figure). In induction trials, overall placebo response and remission rates were 27% (95% CI 23-32%) and 10% (95% CI 8-14%), respectively. Among bio-exposed patients, placebo response and remission rates were 27% (95% CI 16-40%) and 9% (95% CI 6-15%), respectively, compared with 29% (95% CI 24-34%) and 11% (95% CI 8-15%) for bio-naïve patients. Overall placebo response and remission rates in maintenance trials were 32% (95% CI 23%-42%) and 22% (95% CI 14-33%), respectively. Corresponding placebo response and remission rates for bio-exposed patients were 21% (95% CI 8-46%) and 17% (95% CI 11-25%), and 36% (95% CI 28-44%) and 24% (95% CI 15-36%) for bio-naïve patients. Placebo rates were lowest when response was defined as a ≥100-point decrease from baseline in the Crohn's Disease Activity Index (CDAI) score, and when remission was defined using stool frequency (≤1.5) and abdominal pain (≤1) subscores. Higher baseline C-reactive protein concentrations were associated with lower odds of placebo response and remission, while higher baseline albumin levels increased the odds of these outcomes (Table). Increased baseline CDAI and 2-item patient-reported outcome (PRO2) scores predicted higher odds of placebo response in induction trials, yet this reduced the odds of remission in induction trials and of both outcomes in maintenance trials. Prior failure to tumour necrosis factor (TNF) antagonist therapy was more predictive than prior TNF antagonist/biologic exposure for reducing the odds of placebo response and remission.

Conclusion

Placebo rates and the patient-level factors influencing them vary according to study design, clinical outcome measure and outcome definitions.Read more P709 Role of NOD2 single nucleotide polymorphisms on ustekinumab drug durability in adult patients with Crohn’s diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Ustekinumab (UST), a monoclonal antibody targeting the p19 subunit of the pro-inflammatory Interleukins 12 and 23, is a therapeutic option in patients with Crohn’s disease (CD) with high efficacy, although some patients will have to cease therapy with UST due to primary non-response, secondary loss of response, or adverse events. Single nucleotide polymorphisms (SNPs) in the Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) gene have been proposed as a prognostic factor in CD. Whether these NOD2 SNPs have an impact on UST drug durability among adult CD patients remains unclear.

Methods

CD patients were genotyped for the three most common NOD2 SNPs (rs2066844, rs2066845, and rs2066847). Hazard ratios (HR) for risk of NOD2 SNPs on UST durability were calculated using univariable and multivariable cox proportional hazard regression adjusting for age at first UST prescription, previous surgery, Montreal A, L, and B classification, present perianal disease, and previous anti-TNF exposure. Statistical analysis was conducted using SPSS. A two-tailed P value < 0.05 was considered statistically significant. All patients provided written informed consent.

Results

92 CD patients were included in the analysis. Of those, 72 continued receiving UST until the end of the study. In univariable and multivariable analyses, NOD2 SNPs were not independent prognostic factors for UST drug durability (P>0.05 for all three NOD2 SNPs). However, age at first UST prescription (adjusted HR [aHR] 0.96, 95% confidence interval [CI] 0.93-1.00, P=0.028 for all tested NOD2 SNPs) and present perianal disease (aHR 2.65, 95% CI 1.11-6.31, P=0.028 for all tested NOD2 SNPs) were independent predictors of ustekinumab drug durability.

Conclusion

Among adult Crohn’s disease patients being treated with ustekinumab, the presence of NOD2 SNPs did not have a significant impact on ustekinumab drug durability.Read more P1054 Clinical outcomes for ulcerative colitis patients stopping 5-aminosalicylates starting biologics and/or immunomodulator therapy: A Systematic review and meta-analysisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Although 5-aminosalicylic acid (5-ASA), a crucial agent in the treatment of ulcerative colitis (UC), its role in the context of more advanced therapies, including immunomodulators and/or biologics, is not well defined. We sought to perform a systematic review and meta-analysis to assess the pooled consequences of discontinuing 5-ASA in patients with UC undergoing treatment with immunomodulators or biologics.

Methods

We searched MEDLINE, EMBASE, and the COCHRANE library to identify articles analyzing clinical outcomes associated with either discontinuing or maintaining 5-ASA in UC patients receiving immunomodulators or biologic treatments. A meta-analysis was performed using a random-effects model to pool estimates and report hazard ratios [HRs] or odds ratios [ORs], following the data format specified in the individual studies.

Results

A total of 6 studies were identified as eligible for the meta-analysis. In UC patients receiving immunomodulators and/or biologics, stopping 5-ASA was not associated with steroid use (HR 0.86, 95% confidence interval [CI] 0.65-1.14 and OR 0.84, 95% CI 0.47-1.51), UC-related hospitalization (HR 0.92, 95% CI 0.69-1.22), UC-related surgery (HR 0.88, 95% CI 0.65-1.18), one-year clinical (OR 0.93, 95% CI 0.63-1.39) and endoscopic (OR 1.24, 95% CI 0.30-5.08) remission.

Conclusion

The cessation of 5-ASA in UC patients treated with immunomodulators and/or biological agents is not related to worsening of clinical outcomes. This finding suggests a limited role for 5-ASA in the setting of more advanced therapiesRead more P710 Prevalence, Characteristics and Management of Patients with Difficult-To-Treat Inflammatory Bowel Disease: A Cross-Sectional Study From a Tertiary Referral CenterWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Difficult-to-treat (D2T) inflammatory bowel disease (IBD) is defined by lack or loss of response to advanced treatments with 2 or more mechanisms of action (MoA), Crohn’s (CD) recurrence after 2 resections, chronic antibiotic refractory pouchitis, complex perianal CD or by the presence of psychiatric comorbidities impairing IBD management.¹ We aimed to assess the prevalence, characteristics, management, and outcomes of D2T-IBD.

Methods

We retrospectively searched the electronic medical records of patients with IBD followed at San Raffaele Hospital (Milan, Italy) as of October 1st, 2023. Patients enrolled in clinical trials altering disease management were excluded.

Results

In total 679 patients with moderate-to-severe IBD were included (350 CD, 326 UC, 3 IBD-U). 163 patients (24%) met at least one criterion of D2T (25% CD, 23% UC). Of these, 75% did not respond or lost response to 2 or more biologics/small molecules with different MoA, 18% had complex perianal CD, 17% had CD recurrence after 2 or more resections for active CD, the remaining had antibiotic refractory pouchitis or psychiatric comorbidities impairing IBD management. Multiple criteria can coexist. Figure 1.Drug-wise, 54% of patients with D2T-IBD failed 2 MoA, 26% 3 MoA, and 3% 4 MoA, the remaining had other causes of D2T-IBD.Prevalence of D2T varied across phenotypes of CD. The presence of perianal disease doubled the probability of D2T-CD (48 vs 24%); stricturing (B2), fistulizing (B3), and upper gastrointestinal involvement (L4) also increased risk. In UC, 22% of left-sided colitis (E2) and 27% of pancolitis (E3) were D2T, no proctitis was D2T.Patients with D2T-CD had a longer mean disease duration (14 vs 8.7 years; p<0.05) and time on advanced treatments (78 vs 63 months; p<0.05). The same two analyses showed no significant difference for UC (11.6 vs 11.2 years; and 41 vs 50 months; both p>0.05).Differently from bio-naive patients (Figure 2A), patients with D2T-IBD were mostly on ustekinumab, followed by infliximab and adalimumab in CD, and by upadacitinib, infliximab and tofacitinib in UC. Notably, 11 patients with D2T-CD received a combination of advanced therapies. Figure 2BOverall, 61% of patients with D2T-IBD were in clinical remission, 43% in biochemical remission (calprotectin <150 μg/g), and 13% in endoscopic remission (Mayo≤1; or SES-CD≤3 or Rutgeerts i0-i1).

Conclusion

D2T-IBD is heterogeneous but most commonly due to multidrug failure and associated with certain phenotypes of IBD. Ustekinumab was the most common treatment choice for D2T-IBD. The majority of patients with D2T-IBD achieved clinical remission but failed to achieve biochemical or endoscopic remission.1. Parigi et al. Lancet Gastroenterol. & Hep. 2023Read more P1055 Intravenous to subcutaneous infliximab switch may reduce the risk of immunogenicity related treatment failure and can be used to facilitate immunomodulator withdrawalWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Infliximab (IFX) is an effective treatment option for many patients with inflammatory bowel disease. Immunogenicity mediated treatment failure (IMTF) is a common clinical problem usually tackled by addition of an immunomodulator (IMM) and/or IFX dose escalation.Switching stable patients on IV IFX maintenance therapy to SC IFX has been shown to be safe and effective.1 It is hypothesised that SC IFX may reduce the risk of IMTF but there is little data to support this. We aimed to explore whether switching selected patients at risk of IMTF from IV to SC IFX was safe and effective and assess whether this strategy can facilitate treatment de-escalation and IMM withdrawal.

Methods

The local IBD database was used to identify potentially suitable patients at higher risk of IMTF. This included those on escalated doses of IV IFX, those who had developed low level anti-drug antibodies (ADA), and those on combination therapy in whom it was felt desirable to withdraw IMM. Those who agreed to switch were commenced on SC IFX 120mg fortnightly and followed up clinically and with IFX drug levels (DLs) and ADA at week 8, 24 and 52.

Results

29 eligible patients underwent IV to SC IFX switch. Two patients were excluded: one returned to IV IFX and the other stopped IFX completely within 8 weeks of switch.Outcomes for 27 patients were evaluated: 10 with UC, 14 CD, 3 IBD-unclassified. Median age was 38 (IQR 31-49). Median duration of IV IFX was 34 months (IQR 24-54 months). 17 patients were on accelerated IV IFX dosing.All 27 patients remained on SC IFX at one year. Two required a course of steroids for disease flare. Of the 19 patients who had faecal calprotectin (FCP) data available, the mean FCP prior to switch was 66.1 (30-317) and post initiation of SC IFX was 189.6 (30 – 1800), but this did not reach statistical significance (p=0.172).12/27 patients were on IV IFX plus IMM therapy. 9/12 successfully stopped IMM after switch to SC IFX.Mean DL prior to switch was 7.13 (2.7-12.5) and post switch was 12.07 (1.6-14.5). In those who were on accelerated IV IFX dosing, 15/17 saw an increase in DLs post switch. In the 8 patients who had ADAs prior to switch, all saw a reduction, with 6 having no detectable ADAs post switch.

Conclusion

Switching from IV to SC IFX in this cohort was safe and effective. Most patients maintained steroid free remission at one year. All those who stopped IMM were successfully maintained on monotherapy at 1 year. 15/17 people treated with escalated IV dosing were successfully switched to standard SC IFX dosing with improvement in mean IFX DLs and without loss of clinical effect.Read more P711 Outcomes of Outpatient Biologic Exposed Patients Hospitalized with Severe Ulcerative ColitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Up to 20% of patients with ulcerative colitis (UC) will require hospitalization for an acute severe flare. It is unclear whether outpatient exposure to biologics alters the outcomes of inpatient severe UC. We aimed to assess the outcomes of hospitalized severe UC patients exposed to biologics in the outpatient setting.

Methods

This was a multicenter, retrospective study of adult patients hospitalized with severe UC at University of Cambridge, Cambridge, St. Mark’s Hospital, London and Yale University, Connecticut (from 1/1/2012-11/1/2021). We included adult patients (age ≥ 18 years) who were hospitalized for a severe UC flare as determined by the treating clinician. The primary outcome was need for colectomy among outpatient biologic exposed vs biologic naïve patients. Secondary outcomes stratified by outpatient biologic exposure included length of hospitalization and need for rescue medical therapy.

Results

A total of 382 patients (53.2% male) with a median age of 35 years [interquartile range (IQR) 25-53] were reviewed. Outpatient biologic exposure was noted in 23.2% (n=86, 52 exposed to infliximab) while 76.8% (n=284) were naïve to biologics. Median disease duration was longer in the biologic exposed group at 6 years (IQR 2-11) compared to 2 years (IQR 1-8) in the biologic naïve group (p < 0.001). Biologic exposed group was more likely to have pancolitis (70.2% vs. 54.7%; p=0.04). The C-reactive protein (CRP) to albumin ratio was higher in the biologic naïve group was higher at 12.8 (IQR: 3.2-35) vs. 8 (IQR: 1-21.5) (p=0.004).The biologic exposed group was more likely to undergo colectomy at 25% (n=21) vs. 9.3% (n=26) in the biologic naïve group (p<0.001). The median hospital length of stay was 6 days (IQR: 4-9) in both groups (p=0.96). Need for rescue medical therapy 37.7% (n=107) in the biologic naïve group vs. 41.9% (n=36) in the biologic exposed group (p=0.49).Colectomy was associated with outpatient biologic exposure (44.7% vs. 19.9%, p=0.0002), Mayo UC endoscopic sub-score of 3 (81.6% vs. 55.1%, p=0.002), higher median CRP [70.6 (IQR:26.8-126.3) vs. 38.8 mg/dL (IQR: 9.7-94.7), p=0.04], lower median albumin [3 (IQR: 2.7-3.6) vs. 3.5 (IQR: 3-4) g/dL, p=0.0002], and female sex (61.2% vs. 44.8%, p=0.03). On multivariable analysis, only low albumin was independently associated with risk of colectomy (odds ratio: 3.31, 95% confidence interval 1.59-6.87, p=0.0005)

Conclusion

In our multicenter cohort, outpatient biologic exposure was associated with increased risk of colectomy among hospitalized patients with severe UC but on multivariable analysis only low albumin was independently associated with risk of colectomy. Further study of larger cohorts is warranted.Read more P712 Effectiveness of switching from intravenous to subcutaneous infliximab in Inflammatory Bowel Disease patients: A combined analysis of real-world evidenceWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Since approval, numerous inflammatory bowel disease (IBD) patients have been treated with subcutaneous (SC) infliximab (IFX), but real-life data based on a large multi-national population of patients switching from intravenous (IV) to SC IFX is lacking.

Methods

The ASSEMBLE project is an initiative to combine multi-national real-world cohort datasets and analyse the effectiveness and safety of SC IFX therapy. In the ASSEMBLE-1 analysis, three studies from France and the United Kingdom^1-3 were integrated to assess the clinical outcomes up to 6 months (6M) after switching from IV to SC IFX. Clinical remission was defined as Harvey-Bradshaw Index (HBI) or modified HBI (mHBI) <5 for Crohn’s disease (CD) and Simple Clinical Colitis Activity Index (SCCAI) or partial Mayo score (PMS) <3 for ulcerative colitis (UC). Treatment persistence was assessed by Kaplan-Meier survival analysis.

Results

The data of 428 patients were pooled from the three datasets (70.6% CD, 29.4% UC). 85.4% of patients were in clinical remission before switching with median HBI or mHBI of 1 (IQR 0,2) for CD and median SCCAI of 2 (IQR 1,3) or PMS of 0 (IQR 0,0) for UC. 59.6% of patients were treated with the standard dose of IV IFX (5 mg/kg Q8W) before switching and 54.0% of patients were on concomitant immunomodulator therapy. Patients were switched to SC IFX 120 mg Q2W (94.4%) or 120 mg QW (5.6%) regimen. After switching, the overall clinical remission rates were 83.4% and 84.7% at 3M and 6M, respectively. CD patients were associated with higher remission rate (89.8%) than UC patients (71.9%) at 6M (p<0.001). The disease activity scores and the levels of fecal calprotectin and C-reactive protein of the overall population were maintained stable after switching (Table 1). High persistence was observed in both CD (97.3% at 3M, 94.8% at 6M) and UC patients (96% at 3M, 94.1% at 6M), with no significant difference between indications (p=0.47 at 3M and p=0.78 at 6M). Perianal CD patients (n=89) did not have a significantly worse treatment persistence rate than non-perianal CD patients (p=0.30). The most common reasons leading to drug discontinuation were lost to follow-up, consent withdrawal, worsening of disease activity, and worsening of perianal disease (3 cases for each). Two patients discontinued due to injection-site pain.

Conclusion

This pooled analysis of ASSEMBLE-1 confirms that switching from IV to SC IFX is effective and safe for CD and UC patients in clinical practice and that the clinical remission is well maintained up to 6M after switching, with no new concerns in safety profiles. [1] Smith et al. J Crohns Colitis 2022 [2] Buisson et al. Clin Gastroenterol Hepatol 2023 [3] Rahmany et al. Gastroenterology 2023.Read more P1056 T cell responses to repeated SARS-CoV-2 vaccination and breakthrough infections in patients with inflammatory bowel disease on TNF inhibitor treatment, a prospective cohort studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Understanding T cell responses to SARS-CoV-2 immunisation in patients on immunosuppressive treatment is important for future vaccine recommendations. Our aim was to investigate the magnitude and quality of T cell responses following repeated SARS-CoV-2 vaccine doses and COVID-19 (breakthrough infections).

Methods

In this prospective, observational study of responses to SARS-CoV-2 vaccines (Nor-vaC)¹, patients with inflammatory bowel disease (IBD) on TNF inhibitor (TNFi) therapy receiving up to four SARS-CoV-2 vaccine doses, and healthy controls receiving three vaccine doses were included. CD4 and CD8 T cell responses to SARS-CoV-2 peptides were measured by flow cytometry before and 2-4 weeks following vaccination and breakthrough infection. Antibodies to the receptor binding domain (RBD) of the Wuhan-Hu-1 and BA.1 (omicron) strains were measured.

Results

Between March 2, 2021, and December 20, 2022, 118 IBD patients, and 21 healthy controls were included in the study (Table). Following three vaccine doses, the humoral immune response was attenuated in IBD patients compared to healthy controls (median 3954 BAU/ml vs. 6280 BAU/ml, p=0.008). However, both the percentage of spike-specific T cells (CD4 median 0.11% vs. 0.10%, p=0.259, CD8 0.030% vs. 0.046%, p=0,333) and T cell polyfunctionality scores (a measure of quality of vaccine response) (CD4 median 0.403 vs. 0.371, p=0.386, CD8 0.105 vs. 0.101, p=0.871), showed comparable quality in IBD patients and controls following three doses. CD4 T cell responses increased rapidly and plateaued after two vaccine doses whereas CD8 T cell responses continued to improve up to four vaccine doses (Figure). Breakthrough infection in patients following the third or fourth vaccine dose increased CD8 polyfunctionality and generated broad CD4 and CD8 T cell responses against non-spike peptides. There was no difference in T cell responses between patients using TNFi mono- and combo therapy after primary vaccination (three vaccine doses) (p=0.648).

Conclusion

Despite attenuated antibody responses, IBD patients on TNFi treatment demonstrated T cell responses comparable to healthy controls following three SARS-CoV-2 vaccine doses. Repeated vaccination and breakthrough infection increased the quality and breadth of T cell responses, reaching a plateau. Distinguishing between CD4 and CD8 immune compartments and dynamics of activation after SARS-CoV-2 immunisation may provide nuanced understanding of protective cellular responses The study results indicate that IBD patients on TNFi treatment may in future follow the same recommendations for further SARS-CoV-2 vaccines as the general population.¹Clinialtrials.gov NCT04798625Read more P752 Difficult-to-treat inflammatory bowel disease: effectiveness and safety of 4th and 5th linesWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Many patients with inflammatory bowel disease (IBD) have signs or symptoms of active disease despite multiple treatment attempts. This emerging concept is defined difficult-to-treat IBD. The objective of this study was to investigate for the first time treatment persistence, efficacy and safety of biologics or small molecules used in 4^th or 5^th line therapy.

Methods

We reviewed all consecutive patients with IBD treated at Nancy University Hospital between July 2022 and April 2023 with the 4^th or 5^th line treatment for at least three months. The primary outcome was to assess the persistence rate of 4^th and 5^th line therapy.

Results

We enrolled 82 patients with IBD (4^th line: 44; 5^th line: 38). On Kaplan-Meier analysis the duration of risankizumab, ustekinumab or vedolizumab therapy did not differ significantly (p>0.05) as 4^th and 5^th line treatment. The restricted mean survival time analysis showed that persistence rate of risankizumab was the highest as 4^th line therapy (risankizumab vs. vedolizumab: 36.0 and 29.4 weeks respectively, p=0.008; risankizumab vs. ustekinumab: 36.0 and 32.8 weeks respectively, p=0.035). In multivariate regression, Crohn’s disease diagnosis (Odd ratio 4.6; 95% confidence interval 1.7-12.4) was significantly associated with treatment persistence.

Conclusion

In this first real-world setting, risankizumab could have longer persistence rate as 4th line treatment for IBD than other agents. Persistence of biological agents was greater in Crohn’s disease than in ulcerative colitis. More studies are needed to compare treatment efficacy in patients with difficult-to-treat IBD.Read more P1057 Upadacitinib as Salvage Therapy for Acute Severe Ulcerative Colitis: A Single-Center ExperienceWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Ulcerative colitis (UC) often leads to hospitalization and may be resistant to standard treatments, necessitating colectomy. Upadacitinib (UPA), an oral selective Janus kinase 1 inhibitor, offers a novel mechanism and the benefit of rapid and predictable pharmacokinetics which suggest it may be efficacious in acute severe UC (ASUC). However, there are a limited number of cases using different dosing regimens describing the potential of this treatment for ASUC. We describe the efficacy and safety of UPA in hospitalized patients with ASUC at our center.

Methods

We conducted an observational cohort study of patients hospitalized for ASUC treated with UPA 45 mg/d as a rescue therapy after failure or incomplete response to other therapies, including corticosteroids. Patient demographics, disease characteristics, and clinical data were collected. The Simple Clinical Colitis Activity Index (SCCAI) was used to monitor clinical response. Clinical outcomes, including loss of response and colectomy, were collected.

Results

Ten patients (ages 21-78, 40% female) hospitalized for ASUC were treated with UPA (population characteristics and clinical summarized in Table 1). The majority of patients (8/10) had prior exposure to two or more advanced therapies. The median SCCAI score at the time of UPA initiation was 8.5, with improvement in five patients on upadacitinib at week 2 (Figure 1). Six of 10 patients discontinued UPA, 3 of whom underwent colectomy during the same hospitalization due to inadequate response. Two patients underwent surgical intervention after discharge from the hospital. Patients who underwent colectomy had a significantly lower albumin level at the time of UPA initiation compared to patients who didn’t undergo colectomy (3.0 and 4.2 g/dL, respectively; p = 0.005), but not CRP (28.5 and 29.8 mg/L, respectively; p = 0.48). One patient had discontinuation of upadacitinib during the induction phase due to elevated liver enzymes. The median time to discontinuation was 7.5 days. Of the 4 patients on ongoing therapy with UPA after initiation in hospital, 2 have been on the maintenance dose for over 6 months with ongoing remission.

Conclusion

Our experience with UPA 45 mg/d for salvage therapy in ASUC patients demonstrated a higher colectomy rate than reported in earlier studies, which . Although some patients benefited from UPA with an improvement in SCCAI scores by week 2, the colectomy rate highlights the need for further research to identify which patients are most likely to benefit from UPA therapy. Our findings underscore the importance of personalized approaches to ASUC treatment and warrant further investigation in larger, controlled studies.Read more P753 Early perianal abscess recurrence in patients with perianal Crohn's disease on biologic therapy predicts long-term permanent fecal diversionWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Generally, it’s difficult to estimate the efficacy of biologics (Bio) for perianal lesions of Crohn’s disease (CD) and lack of evidence. Sometimes, we experience the recurrence of perianal abscess and need to perform re-drainage even after starting 1^st Bio. When the 1^st bio fails, choosing an accurate 2nd Bio is difficult. The most severe result of this situation is rectal amputation. We wonder if any relationships between recurrence timing and long-term outcomes exist. We reviewed and aimed to know our institute’s perianal CD (pCD) treatment.

Methods

We retrospectively investigated patients' medical charts with pCD from 1988 to 2022 at Kenseikai Nara Coloproctology Center. We excluded the patients without using Bio or starting Bio after rectal amputation. The cases with missing values are excluded, too. We defined "early" as within two years and compared two cohorts, the early recurrence group (ER) and the no or late recurrence group (non-ER). We use the Kaplan-Meier method for calculating the time to fecal diversion.

Results

Eighty patients were recruited. The mean current age is 37.5 years old, and the onset of CD is 22.6 years old. The Perianal lesion’s onset is 24.5 years old. The male is 66, and 19 smokers are included. In this part, perianal lesion means only perianal abscess and fistula. Montreal Classification is shown in TABLE1.The Median follow-up duration was 142.5 months. We performed perianal surveillance (PS) for these patients, including EUA, Abscess Drainage, and seton placement, 3.1 times for each person. After the surgical interventions, we treat them with four Bio. After starting Bio, we experienced 33 early recurrences. We observed eight transient stoma creations, nine rectal amputations, and one anorectal cancer. Among them, we calculate the relationships between early recurrence and rectal amputation and find that early recurrence is a risk factor for permanent fecal diversion (HR 6.84 95%CI 1.48-31.7, p=0.0047 FIGURE1).We needed to switch the Bio for 31 patients during the observational period. To know which way of switching is effective for pCD, we calculate the relationships between the practice of switching and any treatment failure. Same class switching and changing MOA are not different for any treatment failure, which means re-abscess drainage and creation of any stoma (HR 0.40 95%CI 0.10-1.57 p=0.19).

Conclusion

Perianal abscess recurrence as we need to re-incision and drainage within two years after starting Bio treatment are related to permanent fecal diversion. We must pay attention to such kinds of patients, but the types of Bio we change didn’t affect any treatment failure. Further studies are needed in this field.Read more P754 Inadequate Pregnancy Specific Knowledge among Patients with Inflammatory Bowel Disease: A Multi-Center Survey in ChinaWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Perceptions and attitudes of inflammatory bowel disease patients on pregnancy may influence their fertility planning and disease progression. There was data published about knowledge as well as the impact of education in relation to inflammatory bowel disease and pregnancy. However, it is unknown in China. Facing the sharp decline in birth rate, we need to understand the pregnancy-specific knowledge of Chinese gastroenterologists and patients with inflammatory bowel disease and the significance of education.

Methods

A cross-sectional questionnaire, regarding pregnancy-specific knowledge, was carried out among China's 63 inflammatory bowel disease centers. 794 questionnaires were obtained, including 185 from physicians and 609 from patients. Our center then led the educational intervention.

Results

Compared to physicians, patients' knowledge levels of fertility (39.1% vs. 70.8%, p < 0.001), imaging examinations (22.8% vs. 72.4%, p < 0.001), and endoscopy performed during pregnancy (19.9% vs. 71.4%, p < 0.001) and vaccination (16.6% vs. 46.5%, p < 0.001) were significantly lower. There was a lack of knowledge among gastroenterologists regarding the delivery mode (36.8%), medications (36.8%), and emergency surgery (26.5%) during pregnancy in patients with inflammatory bowel disease. The following six aspects were significantly improved after education, including the medication (26.7% vs. 51.7%, p=0.005), fertility (45% vs. 63.3%, p=0.044), heritability (40% vs. 58.3%, p=0.045), indications for emergency surgery (15% vs. 53.3%, p<0.001), imaging examinations during pregnancy (20% vs. 40%, p=0.017) and vaccinations (26.7% vs. 45%, p=0.036).

Conclusion

Pregnancy-specific inflammatory bowel disease knowledge was lacking among certain gastroenterologists and inflammatory bowel disease patients in China. Educational interventions can partially improve the knowledge levels of patients in this area.Read more P880 The real-world use of five-aminosalicylate (5ASA) treatment for Ulcerative Colitis in Australia and New Zealand: Crohn’s Colitis Cure (CCC) data insight’s programWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Five-aminosalicylates (5ASAs) promote & maintain remission in people with ulcerative colitis (UC) and are administered orally or rectally, with combination therapy (oral + rectal) more effective than oral monotherapy, especially when treating flares¹. 5ASAs may be perceived as out-dated and thus neglected. With increasing UC incidence & prevalence in emerging nations, understanding real-world 5ASA use and value is vital.

Methods

Crohn’s Colitis Care is a cloud-based electronic medical record used in Australasia. Data feed into a de-identified clinical quality registry (CQR), which was interrogated in September 2023. People with UC under active care (encounter within 14 months) were included.

Results

Of the 2,522 eligible people, 78.4% resided in Australia & 21.6% in New Zealand (NZ). The median age was 41 years (IQR 31-56), with an even gender distribution (50.3% female). Median disease duration was 9 years (IQR 4.4-16.7). Median duration of follow up was 25.9 months (IQR 13.0-41.4). Overall, 39.2% (n=989) had no documentation of 5ASA therapy (42.0% in Australia, 28.9% in NZ; Table 1). In those with documented 5ASA therapy (60.8%, n=1,534), the average 5ASA treatment duration was 9 years (IQR 4.4-16.7) and women were more likely to receive rectal administration than men (p<0.05). In those who ceased 5-ASA therapy, 782 (44.8%) had a reason documented, with the most common being medication rationalisation and/or deep remission (40.0%) (Figure 1), usually due to up-titration to a more advanced therapy.A total of 608 (39.6%) were recorded as already receiving additional IBD therapy at CQR entry (immunomodulators [IMs]/biologics/small molecules). Of those receiving 5ASAs alone at CQR entry (n=926), 5ASAs were subsequently judged to have failed in 37.8% (n=350). 5ASA failure was defined as the need for additional IBD therapies (99.1%, n=230 for IMs/biologics/small molecules and n=117 for steroids, total n=347); hospitalisation (n=3, 0.9%) or IBD surgery (n=0).

Conclusion

Despite not working for everyone, the long duration of 5ASA therapy indicates they are well tolerated & perceived as beneficial by consumers. There was greater 5ASA utilisation in NZ, possibly due to restricted advanced therapy access. Gender-specific trends in 5ASA administration were identified, raising the question as to why this should be so, given this is not obviously explained by disease phenotype. Further analysis is needed to tease out how such trends interact with other therapeutic access, choices and outcomes.1 - Probert C et a. Combined oral and rectal mesalazine for the treatment of mild-to-moderately active ulcerative colitis: rapid symptom resolution and improvements in quality of life. J Crohns Colitis. doi:10.1016/j.crohns.2013.08.007Read more P755 Long-term need for restart of biologics after withdrawal in patients with Inflammatory Bowel Disease in mucosal healingWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

In patients with inflammatory bowel disease (IBD) on biologic therapy, once remission has been achieved, withdrawal is a frequent issue in clinical practice that generates uncertainty in aspects such as the reduction of adverse effects and costs, but also the risk of recurrence of activity and the need to restart treatment. The aim of this study was to determine the rate of long-term reintroduction of biologics after withdrawal due to mucosal healing (MH) in IBD, the response to reintroduction and the associated factors.

Methods

Observational, descriptive, single-centre, retrospective, descriptive study of 178 cases in 164 patients diagnosed with ulcerative colitis (UC) or Crohn's disease (CD) who were withdrawn from anti-tumor necrosis factor (anti- TNF) therapy once MH had been demonstrated, between July 2009 and February 2022. Demographic and phenotypic characteristics of IBD, characteristics of biologic and immunosuppressive therapy, analytical and endoscopic/histological variables at the time of withdrawal were collected. We analysed the risk of restarting biologics due to clinical relapse and response to reintroduction of treatment. We evaluated possible factors related to the risk of restarting treatment and response to treatment.

Results

We included 178 cases. 123 CD and 55 UC. Most had received infliximab (62.9%) and the main indication was corticodependence (68%). Median follow-up was 78 months (IQR 59-95). Clinical relapse occurred in 69% of cases and 61.2% required reintroduction of biologics, with the probability of retreatment at 1, 3, 5 and 7 years being 19.4%, 50%, 60% and 63.4%, respectively (Figure 1). The response to reintroduction was 86.2%. Only 1.68% required surgery during follow-up. Univariate analysis showed higher risk of re-introduction at younger age at diagnosis (23 vs 30 vs 30, p 0.022) and at withdrawal (32 vs 40, p 0.019) and longer follow-up time after withdrawal (82 vs 71, p 0.026). Multivariate analysis also identified the indication for corticodependence (p 0.046).

Conclusion

The risk of relapse and re-starting treatment is high in the long term after withdrawal of biologic therapy for MH in IBD. Younger age at diagnosis and withdrawal, indication for corticodependence and long-term follow-up are risk factors for poor outcome. Reintroduction of treatment is very effective with low complication rates.Read more P890 Usefulness of subcutaneous Infliximab in patients with Inflammatory Bowel Disease in clinical practice: are increased levels associated with clinical benefit?Wed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Switch from intravenous Infliximab (IFXiv) to subcutaneous Infliximab (IFXsc) in Inflammatory Bowel Disease (IBD) has been associated with an increase in trough levels. However, whether this increase is correlated with additional clinical benefit has not thus far been evaluated in clinical practice.

Methods

Single-center retrospective study of IBD patients who switched from IFXiv to IFXsc (for at least 3 months), between July 2021 and August 2023, due to unfavorable pharmacokinetics (IFX serum levels <3 +/- anti-IFX antibodies). Disease activity was defined as clinically: Simple Clinical Colitis Activity Index (SCCAI) ≥2 for Ulcerative Colitis (UC), Harvey Bradshaw Index (HBI) ≥5 for Crohn´s Disease (CD) or perianal fistulae with active drainage; and biochemical: C-reactive protein (CRP) >5 mg/L and/or fecal calprotectin (FC) >250 µg/g in UC and >150 µg/g in CD. Primary endpoint was to evaluate the effectiveness of IFXsc switch: achieving clinical response (decrease of SCCAI ≥2, IHB ≥3 or ≥50% in fistula drainage) or remission (SCCAI ≤1, IHB ≤4 or absence of active fistula drainage) with biomarkers normalization, or maintenance of remission, in patients with and without previous activity, respectively. Secondary endpoints were to assess IFX levels change and safety of IFXsc switch.

Results

Twenty-five patients (23 CD, 2 UC) were included (Table 1). Previous IFXiv therapy lasted for a median of 55 (20.6-74.1) months (100% with intensified dose and 48% with combined therapy). Median baseline IFX level was 1.7 (0.4-3) μg/mL, with anti-IFX antibodies in two cases. At baseline, 7 patients were in remission and 18 had active disease: 15/18 clinical or both clinical and biochemical (3/15 luminal, 11/15 perianal or 1/15 both), and 3/18 biochemical only. Median follow-up was 15.2 (10.2-19.2) months. After IFXsc switch, an increase of IFX level was achieved in 96% of cases, with a median final level of 12.4 μg/mL (9.2-18) (Figure 1). None of the patients in remission at the beginning relapsed during follow-up. Of patients with previous clinical activity, 66.6% achieved clinical remission (53.3%) or response (13.3%), which was seen in 50% of patients with luminal and 66.7% with perianal activity, after a median of 79 (75-210) days. CRP and FC normalization was reported in 53.3% of patients with previous biochemical activity. Treatment was discontinued only in one patient due to inefficacy. IFXsc was intensified in 8% and concomitant treatment could be withdrawn in four patients. No adverse events we reported.

Conclusion

Switching to IFXsc in patients with previous therapy with intensified IFXiv is not only associated with a more favorable pharmacokinetic profile but also with a greater effectiveness.Read more P788 The effect of etrasimod on faecal calprotectin and high-sensitivity C-reactive protein: Results from the ELEVATE UC clinical programmeWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Etrasimod is an oral, once-daily, selective sphingosine 1-phosphate (S1P)_1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC). Here, we present a post hoc analysis of efficacy data from two phase 3 trials, ELEVATE UC 52 and ELEVATE UC 12,¹ assessing associations with faecal calprotectin (fCAL) and high-sensitivity C-reactive protein (hsCRP) and responses to etrasimod in patients (pts) with UC.

Methods

In ELEVATE UC 52 (NCT03945188) and ELEVATE UC 12 (NCT03996369), pts aged 16–80 years with moderately to severely active UC were randomised 2:1 to etrasimod 2 mg once daily or placebo. Efficacy endpoints of clinical remission, clinical response and endoscopic improvement-histological remission (EIHR) were measured at Wk 12 (both trials analysed separately) and Wk 52 (ELEVATE UC 52). Differences in median fCAL and hsCRP between responders and nonresponders (based on criteria for each endpoint) were assessed. Wilcoxon p values were calculated for responder analyses. Sensitivity and specificity based on fCAL and hsCRP concentrations were presented as receiver operating characteristic (ROC) curves with area under the curve (AUC).

Results

In ELEVATE UC 52 and ELEVATE UC 12, 289 and 238 pts received etrasimod and 144 and 116 received placebo, respectively. Baseline fCAL and hsCRP concentrations were similar across cohorts and levels decreased with etrasimod treatment (median change from baseline at Wk 52 [ELEVATE 52]; -710.56 mg/kg and -0.49 mg/L for fCAL and hsCRP, respectively). Following etrasimod, Wk 12 (both studies) and Wk 52 (ELEVATE UC 52), median fCAL and hsCRP were significantly lower in responders vs nonresponders for all efficacy endpoints (fCAL [ELEVATE UC 52] shown in Table; all endpoints p<0.01). At Wk 4, pts receiving etrasimod who were subsequent responders for efficacy endpoints at Wk 12 had lower median fCAL concentrations vs nonresponders in both trials (all p<0.001; Figure). A similar trend was observed for Wk 4 median fCAL concentrations and responders for efficacy endpoints at Wk 52 (ELEVATE UC 52). Across endpoints in both trials, ROC analyses indicated that both fCAL and hsCRP were consistent in predicting short- and longer-term outcomes, with more pronounced associations at Wk 52.

Conclusion

In phase 3 trials in pts with UC, fCAL and hsCRP levels decreased with etrasimod treatment. ROC analyses indicated association between fCAL and hsCRP and treatment response at all endpoints, and demonstrated significantly lower fCAL and hsCRP values in responders. These data demonstrate the utility of fCAL and hsCRP to predict and monitor disease control in pts with UC treated with etrasimod.Reference1. Sandborn WJ et al. Lancet 2023; 401: 1159–1171.Read more P909 Proactive therapeutic drug monitoring and pharmacogenomics in mercaptopurine therapy for ulcerative colitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

OPTIC was a prospective placebo-controlled trial investigating therapeutic drug monitoring (TDM)-based mercaptopurine (MP) therapy in ulcerative colitis (UC). Although the primary endpoint (corticosteroid-free clinical remission and endoscopic improvement at week 52) favoured patients with TDM-based MP therapy over placebo, drug-related adverse events were frequent and drop-out rates high. This post-hoc analysis was carried out to show the therapeutic implications of proactive TDM of MP.

Methods

UC patients with active disease, despite ≥2 g/day mesalamine, underwent remission induction treatment with corticosteroids and initiated weight-based MP therapy (1-1.5 mg/kg). TDM based optimisations were performed at week 6, 12, 18, 24, 36 and 52 using the Dervieux method, unblinded non-including thiopurine expert physicians (DA, MD and AB) provided dosing advice according to a predefined algorithm, aiming for 6-TGN levels of 600-1200 pmol/8×10⁸ RBC and 6-MMP of <5700 pmol/8×10⁸ RBC. Associations between 6-TGN and 6-MMP levels, MP dose and thiopurine S-methyltransferase (TPMT) polymorphisms were explored.

Results

In total, 29 patients initiated MP treatment (41% female, median age 46 yrs [IQR 26-58], median disease duration 6 yrs [IQR 1-14]). TPMT heterozygosity was found in 4/29 patients (3/4 TPMT*3A, 1/4 TPMT*3C). TDM dose adjustments were required in 22/29 patients: 14/29 started allopurinol and decreased MP dose, 5/29 discontinued MP before the first TDM assessment, 2/29 continued MP at the initial dose up until week 52 and the remaining underwent MP dose adjustments. Most adjustments (71%) were made at week 6, thereafter 6-MMP levels stabilised, while 6-TGN concentrations remained stable (Figure 1). TPMT variant carriers had a higher median 6-TGN concentration compared to non-carriers (1700 [IQR 1625-1850] vs 539 pmol/8×10⁸ RBC [IQR 355-953], P<0.001) and more likely to have leukopenia (P=0.025). Two TPMT heterozygous patients achieved the primary endpoint with dose reductions, two discontinued due to myelotoxicity or hepatotoxicity. Until week 52, 16/29 patients completed the trial, 14/29 reached the endpoint with a median 6-TGN of 585 pmol/8×10⁸ RBC (IQR 428-745) and 6-MMP of 268 pmol/8×10⁸ RBC (IQR 110-1257). MP dose correlated with 6-MMP but not with 6-TGN levels. Independently of allopurinol co-prescription, the initial median weight-based MP dose of 100 mg (IQR 75-125) decreased significantly to 50 mg (IQR 25-100, P=0.041).

Conclusion

Most patients underwent TDM optimisation of MP, half of the patients initiated allopurinol with decreased MP dose. TPMT heterozygosity led to supratherapeutic 6-TGN concentrations and adverse events. Weight-based initial MP dose may need reconsideration.Read more P789 Impact of risk factors for Janus kinase inhibitor use identified by the Pharmacovigilance Risk Assessment Committee on the safety and efficacy of ozanimod in patients with moderately to severely active ulcerative colitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

With the emergence of oral small molecule therapies for ulcerative colitis (UC), there is a need for identification of favourable safety and efficacy profiles for these therapies. The Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency reassessed the benefit–risk of Janus kinase inhibitor (JAKi) use based upon data showing increased risk of major adverse cardiovascular (CV) events (MACE) and cancer with tofacitinib. Accordingly, the PRAC identified criteria for which a JAKi should be used only if no alternatives are available or used with caution. This analysis of the phase 3 True North (TN) study (NCT02435992) evaluated the safety and efficacy of ozanimod (OZA) by the presence of JAKi PRAC criteria in patients with moderately to severely active UC.

Methods

Analyses were performed in TN patients comparing those with ≥1 vs no JAKi PRAC criteria at TN baseline (BL). The criteria included age ≥65 y, history of major CV problems, history of CV risk factors (eg, hypertension, high-density lipoprotein cholesterol <40 mg/dl, diabetes mellitus), current or former smoker, and history of cancer. Safety was monitored through Week (W) 52 and efficacy endpoints were assessed at W10 and W52 in patients receiving OZA or placebo (PBO).

Results

At TN BL, 491 patients had ≥1 JAKi PRAC criteria and 521 had no JAKi PRAC criteria. BL patient characteristics were generally similar across groups, but the ≥1 JAKi PRAC criteria group was older (46-48 y vs 36-37 y), with more male patients (62-72% vs 52-61%) and longer UC disease duration (7-9 y vs 6-7 y) vs the no JAKi PRAC criteria group. Treatment-emergent adverse events (TEAEs) occurring during the induction and maintenance periods are shown in Table 1. Overall, TEAE rates were slightly higher in patients with ≥1 vs no JAKi PRAC criteria; however, rates of serious TEAEs and TEAEs leading to treatment discontinuation were similar. Bradycardia and hypertension rates were slightly higher in patients with ≥1 vs no JAKi PRAC criteria; rates of other CV and thromboembolic events and cancer were similar between groups. At W10, OZA was more effective than PBO for clinical remission and response, with slightly greater treatment differences in patients with ≥1 vs no JAKi PRAC criteria (Figure 1A). At W52, more OZA/OZA pts achieved all endpoints vs OZA/PBO pts, with slightly greater treatment differences in patients with ≥1 vs no JAKi PRAC criteria (Figure 1B).

Conclusion

In patients with UC, JAKi PRAC criteria were not associated with greater rates of MACE or cancer with OZA for up to 52 wk, nor did they affect OZA efficacy, suggesting that OZA is a safe and tolerable oral small molecule treatment option for such patients.Read more P910 Salivary calprotectin as a prognostic biomarker in Early Onset Inflammatory Bowel Disease: a cohort studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Inflammatory Bowel Disease (IBD), including Ulcerative Colitis (UC) and Crohn’s Disease (CD) affects children in 25% of cases. In Early Onset IBD (EOIBD) oral involvement is common and oral manifestations (OM) are frequently the first presenting sign of disease.This study compared salivary calprotectin (SCp) between EOIBD and healthy controls (HC), differentiating patients based on their history of OM. Furthermore, this report correlated salivary and faecal calprotectin (FCp) in EOIBD and assessed the prognostic accuracy of SCp in predicting disease relapses.

Methods

A cohort study was conducted; 9 HC and 27 EOIBD (18 UC and 9 CD) were recruited at the University of Naples Federico II. EOIBD were divided in two subgroups based on the history of OM.A sample of stimulated whole saliva was collected by each participant by spitting. The samples were then processed by ELISA for determining SCp.For each patient clinical disease activity was measured through Paediatric Ulcerative Colitis Activity Index (PUCAI) and Paediatric Crohn’s Disease Activity Index (PCDAI), at baseline and during follow-up (4/8/12 weeks).At baseline, patients provided a stool specimen for FCp determination.SCp levels were compared between groups. In EOIBD SCp was correlated to clinical data and to FCp.

Results

At baseline all the patients were in treatment with immunosuppressive drugs; 19 were in clinical remission (PUCAI/PCDAI <10) and 8 had mild disease (PUCAI/PCDAI<35). 13 EOIBD had an history of OM: 12 suffered from aphthous-like manifestations while 3 reported granulomatous lesions; 10 experienced oral involvement before IBD diagnosis. OM were more prevalent in CD than in UC and were associated to ileocolic, perianal and upper gastrointestinal tract involvement.EOIBD with OM reported significantly higher SCp than EOIBD without OM and HC: 155,79±60,08 pg/mL in EOBD with OM vs 82,95±51,58 pg/mL in EOIBD without OM (P<0,01**) and 98,21±39,67 pg/mL in HC (P=0,21).Despite the systemic therapy and the clinical remission, in 7 EOIBD with OM oral lesions persisted. These patients had higher SCp compared to those who experienced OM remission (P<0,05*).In EOIBD with OM higher SCp was associated to higher FCp (P<0,05*) while in EOIBD without OM this correlation was not described.No correlation was found between SCp values and PUCAI/PCDAI at baseline.EOIBD with OM who reported higher SCp were found to have increased risk of relapse (P<0,05*) while no association was reported in EOIBD without OM.

Conclusion

In EOIBD with OM SCp is significantly higher, mirrors intestinal inflammation and predicts relapses. Our results suggest the use of SCp as a prognostic biomarker in EOIBD with OM although more studies are needed.Read more P790 Assessment of steroid use in patients with active ulcerative colitis who initiated a new Janus kinase inhibitor or tumour necrosis factor inhibitor using data from a United States claims databaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

In 2021, the United States (US) FDA issued a label update limiting the use of Janus kinase inhibitors (JAKi) to after tumour necrosis factor inhibitors (TNFi). We examined the rate of steroid use and treatment failure among patients (pts) with ulcerative colitis (UC) initiating a JAKi vs TNFi using data from a US claims database.

Methods

A database of adjudicated medical and pharmacy claims (IQVIA PharMetrics Plus; 2007–2022) was utilised to select pts with UC starting either a new JAKi/TNFi on/after 30 May 2018. Pts were followed from index date to the end of the study period, event of interest or treatment switch (whichever came first). The study assessed steroid use within 90 days of index date, and also treatment failure over the first 6 months after index date, defined as a composite of any: hospitalisation related to UC/colectomy (inpatient/emergency room)/switch to another advanced treatment (AT)/steroid use ≥90 days after index treatment initiation. Individual components of treatment failure were also analysed. Stabilised inverse probability treatment weights (sIPTW) were calculated using 19 confounders. Cox proportional hazards models with sIPTW were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Additional analyses stratifying by AT-naïve vs AT-experienced pts were conducted.

Results

In total, 6019 pts were included; 763 initiated a JAKi and 5256 a TNFi. More pts initiating a TNFi had prior use of non-biologic conventional treatments and were on concomitant conventional treatments at index date, compared with pts initiating a JAKi. Prior AT was more prevalent among JAKi- (74.3%) vs TNFi- (15.3%) treated pts; baseline steroid use was generally similar across groups (Table). Overall, there was a significantly lower risk of steroid use within 90 days in pts initiating a JAKi vs a TNFi (HR 0.75 [95% CI 0.65, 0.87]), and among AT-naïve and AT-experienced pts (HR 0.79 [95% CI 0.64, 0.97] and HR 0.69 [95% CI 0.59, 0.82], respectively; Figure a). There was a significantly lower risk of treatment failure with JAKi vs TNFi (HR 0.80 [95% CI 0.68, 0.94]; Figure b). A significantly lower risk of steroid use ≥90 days was found amongst JAKi- vs TNFi-treated pts overall and within AT-naïve and AT-experienced subgroups (Figure b–d).

Conclusion

In this large US-based claims analysis, pts with UC treated with a JAKi had significantly less steroid use than those treated with a TNFi; this was consistent in AT-naïve and AT-experienced pts. Limitations included confounding of factors uncontrollable in claims data and inherent bias due to approved use of JAKi in the US only in pts with inadequate response to TNFi.Study sponsored by Pfizer. Medical writing support provided by C Duncan, CMC Connect; funded by Pfizer.Read more P933 Closing the internal opening with a rectal advancement flap increases the effectiveness of mesenchymal stem cell (MSC) injection in the treatment of complex Crohn's disease anal fistulasWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The injection of MSCs into complex anoperineal fistulas of Crohn's disease gives a combined clinical and radiological remission of between 35 and 50% at 12 months. In our department, surgical closure is now done by rectal advancement flap (and no longer with simple stitches) in order to minimize the passage of stools and contamination of the fistula tract.The aim of this study was to compare the remission rate and the quality of life between patients treated with MSC injection using simple stitches versus a rectal flap to close the internal opening.

Methods

This single-center prospective study included all our consecutive patients who had a MSC injection. The first patients of the series who had closure of the internal opening(s) with stitches (2020- 2022) were compared with those who had a flap (2022-2023).Complete clinical remission was defined by complete closure of the external opening(s) without pain or discharge, and complete radiological remission by a Magnifi-CD score equal to 0 (Hindryckx P, et al. Gastroenterology 2019). Quality of Life was assessed by the Crohn's Anal Fistula Quality of Life scale (CAF-QoL) (Adegbola SO, et al. Gut 2021).

Results

We included 68 patients (50% women, mean age: 38 ± 13.8 years). The first 42 had stitches and the following 20 had an advancement flap (6 patients had no procedure due to an anal stenosis). The median follow-up was 12 months [6-24].The overall complete clinical remission was 66.7% at M12: 51.1% [35.5-66.8] in the "stitches" group versus 87.5% [69.7-100.0] in the "flap" group (p = 0.005) (Figure). The difference was noticed early from M1.The mean overall Magnifi-CD MRI score decreased from 15.5 ± 4.7 to 6.5 ± 7.1 at M12 (p < 0.001) with no difference between the 2 groups. However, more patients in the flap group had a Magnifi-CD score of 0: 62.5% versus 38.2%.The CAF-QoL quality of life score improved from 51.3 ± 24.7 to 21.2 ± 20.8 at M12 (p < 0.001) with no significant difference between the 2 groups.The duration of the procedure was longer on average by 19 ± 7 minutes in the "flap" group.There was no difference in the anal incontinence score between the 2 groups.In logistic regression, the advancement flap was significantly associated with complete clinical remission (p = 0.007, HR (95% CI): 2.3 [1.3-4.3]).

Conclusion

Closing the internal opening with a rectal advancement flap improves the effectiveness of MSC injections with a complete clinical and radiological remission rate of 87.5% and 62.5% respectively, without consequences on anal continence.Read more P791 Trends in gender representation in inflammatory bowel disease randomized trials from 1955-2023Wed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Historically women have been underrepresented in the field of gastroenterology and continue to be under-represented in academic scholarship and leadership despite the rising number of female medical graduates in recent years.This study aims to characterize the representation of women in authorship of published clinical trials in inflammatory bowel diseases (IBD) and the trend in gender representation since 1955.

Methods

IBD randomized trials published between 1955 to 2023 were included. Author gender, trial specifics (phase, intervention, population) source of funding were examined.

Results

We included 241 trials with a total of 3,264 authors: 2,418 were men (74.1%), 834 women (25.6%) and 12 (0.4%) had unknown gender. Women authorship representation increased from 0% in 1971 up to 30% in 2023 (0.41% annual increase) Figure 1A. Women were first, second, corresponding and last authors in 36/241 (14.2%), 41/241 (15.3%), 27/241 (10.5%) and 30/241 (11.7%) of published trials, respectively, Figure 1. Statistical differences in authorship by gender were found in all study categories, with women being less represented than men in unicenter vs multicenter trials, adult vs pediatric population trials, different trial phases, type of intervention [standard, advance or other] and source of funding (p<0.0001 for all comparisons) Table 1.From 2000 to 2023, industry-sponsored studies (n=119) included 1,680 authors, with 1,295 (77.1%) men and 379 (22.9%) women. Among these authors, 576 had industry affiliation, and 318 (55.2%) were men and 258 (44.8%) women. Women were first, second, corresponding and last authors in 15/119 (12.6%), 12/119 (10.1%), 11/119 (11.2), 10/119 (8.4%) of these studies.Linear regression analysis revealed an upward trend since 1995 in the total number of authors listed per published trial, but with men consistently outnumbering women authors, the ratio of women to men authors per publication remains low over the years (p<0.0001) Figure 1B.

Conclusion

Our findings underscore persistent gender disparities in published IBD trials authorship. Despite an increase in representation over time, women still make up less than 35% of authors and less than 15% of lead authors with little if any improvement over recent years (Figure 1C, 1D). Recognizing that lead authorship in trials has an impact on research funding and academic promotion, this gender disparity in authorship contributes to the many barriers women face in advancing their career in the field of IBD.Read more P853 Factors associated with intestinal tissue levels of anti-TNF in pediatric patients with Crohn's DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Despite advancements, understanding the tissue pharmacokinetics of Anti-tumour necrosis factor alpha monoclonal antibodies (aTNF) and addressing cases of primary non-response, secondary loss of response, and unexplained treatment failures in some patients pose ongoing challenges.The aim of this study was to investigate factors associated with intestinal tissue levels of aTNF, anti-drug antibodies and cytokines in paediatric patients with Crohn's Disease (CD).

Methods

A prospective study of paediatric CD patients treated with aTNF, who underwent ileocecal resection or colonoscopy between June 2020 and January 2023 was performed. Tissue drug levels of aTNF, anti-drug antibodies and pro-inflammatory cytokines ((TNF alpha (TNF-α), interleukin-17 (IL-17), interleukin-1 beta (IL-1β), interferon gamma (IFN-γ)) were analysed in tissue culture supernatant using ELISA.Logistic regression estimated odds ratios (OR) adjusted for potential confounding from disease localization, way of sampling, presence of inflammation, and type of anti TNF (aOR).

Results

Twenty-seven CD patients (18 females, 66.7%) with a median disease duration of 50 (Interquartile range [IQR] 23 – 69) months were analysed. Fourteen (52%) received adalimumab (ADA), thirteen (48%) received infliximab (IFX), with a median aTNF therapy duration of 17 (IQR 4.5 – 41.5) months. Tissue aTNF detection was 100% in ADA-treated and 81.8% in IFX-treated patients.A positive association between intestinal inflammation and the level of free aTNF in tissue was observed (aOR=3.03, 95% CI=0.82-5.29). The ratio of aTNF level in tissue to serum was higher in the inflamed tissue (aOR=0.21, 95% CI=0.039-0.38).Despite an adequate level of aTNF in the serum, no measurable level was detected in the tissue in 13 patients.When comparing anti-drug antibodies levels in serum and tissue, we found a notable discrepancy, with 19 patients having undetectable serum levels, while tissue levels were measurable.We found higher tissue IL-17 levels in patients who had been treated with aTNF therapy for a longer period (aOR=0.15, 95% CI=0.031-0.274), independent of disease duration and patient age.An association was found between the level of IFN-γ and the duration of follow-up, as well as with the duration of aTNF administration. However, it was not possible to determine which of these associations is responsible for this relationship.

Conclusion

Our study highlights significantly elevated free drug levels in inflammatory tissue compared to non-inflammatory tissue. Our findings also align with recent insights linking aTNF failure to upregulation of mucosal IL17, providing a possible molecular rationale for improved treatment response with treatment targeting the IL-23 receptor after aTNF treatment failure.Read more P934 A delphi consensus on the optimisation of medical and surgical therapy in perianal fistulising Crohn’s disease, targeted at individual TOpCLASS classification groupsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Perianal fistulising Crohn’s Disease (PFCD) is a challenging phenotype of IBD associated with poor outcomes. Classically, fistulae have been classified anatomically and guidelines have been generalised, with a lack of appreciation of disease heterogenicity. The recent ‘TOpCLASS classification system’ (Geldof et al. (2022) - figure below) addresses this and categorises patients based on clinical features and patient goals. There is a need to provide management guidance for PFCD that aligns with this approach, targeting differing PFCD manifestations seen in real-life. We present a consensus exercise delivering that guidance.

Methods

Position statements on ‘optimal’ PFCD management within the TOpCLASS classes were made via a consensus meeting in Apr 2023. The expert panel were members of the TOpCLASS Consortium, a group of PFCD specialists and researchers. This included 15 surgeons and 16 gastroenterologists, from IBD centres in Europe, North America, and Australia. Prior to the meeting, to inform provisional statements: 1) a systematic review of the literature was conducted (Oct 2021), 2) multidisciplinary team responses on the management of fictional PFCD cases from 8 leading IBD centres were obtained, and 3) an open discussion on PFCD management with the expert panel was conducted. Consensus was predefined as ≥80% ‘strongly agree’ [A+] or ‘agree with minor reservation’ [A].

Results

53 position statements were agreed by the expert panel. For Class 1 (minimal, asymptomatic) disease the panel agreed, given the lack of symptoms, there is no role for seton insertion (A+ 50%, A 50%), and no role for routine MRI monitoring in the absence of new fistula symptoms (A+ 46%, A 54%). Regarding Class 2 (chronic, symptomatic) disease, the panel agreed on detailed guidance for when fistulae are suitable for a repair attempt and where differing surgical modalities are best utilised in fistula repair. Additionally, statements on seton removal in PFCD were made, alongside statements on optimised medical therapy in Class 2 patients. Specifically, the panel suggest Infliximab first-line (A+ 80%, A 20%), ideally commenced within 30 days of initial drainage +/- seton insertion (A+ 100%). Statements were also produced regarding second-line options, topical therapy, and loss of response to biologics in PFCD. Specific statements were also developed for Class 2b, 2c-i, 2c-ii, and 4 disease, as well as on the psychological burden of PFCD.

Conclusion

The generated statements come from a highly expert Western group of PFCD specialists. We believe they provide pragmatic advice to gastroenterologists and IBD surgeons managing the full breadth of PFCD encountered in day-to-day practice.Read more P854 Tofacitinib demonstrates preliminary efficacy in induction of remission in chronic pouchitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Pouchitis is common following total proctocolectomy for ulcerative colitis (UC) and ileal pouch-anal anastomosis (IPAA) and generally responds to antibiotics. However, up to 20% of patients develop either antibiotic-dependent or antibiotic-refractory pouchitis, collectively referred to as chronic pouchitis.

Methods

We report our preliminary induction results from a multi-center open label induction with randomized withdrawal trial to assess the efficacy of tofacitinib in chronic pouchitis. All eligible participants received 10mg tofacitinib twice daily for 8 weeks, with an additional 8 weeks of therapy given to patients with an inadequate initial clinical response. The primary endpoint was clinical response (a reduction of clinical PDAI≥2) at week 8. Secondary endpoints included endoscopic response (a reduction of endoscopic PDAI≥2), mPDAI remission (modified pouchitis disease activity index (mPDAI)≤ 4 and a reduction of mPDAI≥2), mPDAI response (a reduction of mPDAI≥2) and improvement in health-related quality of life (HRQoL) using the short inflammatory bowel disease questionnaire (SIBDQ). Serum cytokine levels was analyzed using LEGENDplex human inflammation panel 1. Univariate analysis was performed to identify clinical and biochemical predictors of response to tofacitinib.

Results

A total of 33 patients with chronic pouchitis (Table 1) were included in the preliminary analysis. The clinical and endoscopic response rates at week 8 were 55% and 58% respectively, with a median improvement of 1 (p<0.05) and 3 (p<0.05) respectively (Figure 1). The mPDAI remission rate was 49% at week 8 with an mPDAI response rate of 73%. Endoscopic responders exhibited significant improvements in endoscopic oedema, granularity, friability, and mucous exudate (p<0.05). There was significant improvement in HRQoL, with the median SIBDQ score increasing from 35 at baseline to 54 at week 8 (p<0.05). Eleven patients received a further 8 weeks of therapy with a clinical response rate of 36%, yielding an overall response rate including extended induction of 67%. Univariate analysis did not reveal significant differences in baseline characteristics, clinical, or biochemical markers between responders and non-responders. However, a history of corticosteroid use (p=0.08) and high baseline levels of faecal calprotectin (p=0.15) demonstrated a non-significant association with treatment response. Elevated baseline serum levels of IL-1b, IFN-a and IL-33 were associated with a treatment response at week 8 (p<0.05).

Conclusion

Tofacitinib demonstrated preliminary efficacy in inducing both clinical and endoscopic response in patients with chronic pouchitis who have undergone IPAA for UC.Read more P855 Have biological agents changed the need for abdominal surgery in inflammatory bowel disease over time?Wed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Inflammatory bowel disease (IBD) is a chronic relapsing-remitting inflammatory intestinal disorder with two main categories: Crohn’s disease (CD) and ulcerative colitis (UC). CD patients can develop strictures and penetrating complications over time, that can lead to an increased number of bowel resections which, if extensive, can end up as short bowel syndromes. Aggresive UC is related to an increased colectomy rate. Controlling flares in CD and achieving mucosal healing in UC may decrease the need for abdominal surgery. Irruption of biological agents at the begining of the twenty-first century could be related to the fulfillment of both objectives decreasing number of surgeries. Our aim was to analyze the impact of biological treatment in abdominal surgery among patients with CD and UC.

Methods

We conducted a retrospective two cohort study of patients with IBD and abdominal surgery, using our prospectively collected ENEIDA data base. Patients were included in two periods of time, before and after biological irruption. The first cohort included all the patients operated between 1993 and 1998 (before biologics) and the second one between 2013 and 2018. We analyzed differences in the number of surgeries per patient and time between IBD diagnosis and first surgery, among other variables.

Results

We included 55 patients (89.1% CD and 10.9% UC) in the first cohort and 69 patients (82.6% CD and 17.4% UC) in the second one. 44 patients in the second cohort (63.8%) received biological agents before first surgery. There were no significant differences in the number of surgeries (two or more) per patient in both periods of time (10.9% vs 7.3%, p 0.69). The main indication of surgery was strictures (44.6% vs 46.6%) followed by penetrating complications (25.0% vs 30.1%) and medical refractoriness (21.4% vs 15.1%). No differences were observed in the reason to indicate surgery (p 0.78). The main surgical procedure was ileocecal resection (60.0% vs 54.1%), followed by small bowel resection (11.7% vs 17.6%) and proctocolectomy (10.0% vs 5.4%), without significant differences over time (p 0.67). There were 7 immediate post-surgical complications in both cohorts (11.3% vs 9.5%) without significant differences between them (p 0.94). The median time between IBD diagnosis and first surgery was greater among patients in the second cohort who had received any biological agent (19.0 vs 71.2 months, p<0.05), [image 1].

Conclusion

Biological treatment considerably increases the time between IBD diagnosis and the first surgery. Future research will allow us to determine if this is associated to less surgeries in each patient and a reduction in long-term post-surgery complications (short-bowel syndrome, abdominal adhesions, eventrations, etc).Read more P949 Effectiveness and safety of rectal tacrolimus in patients with ulcerative colitis. TACRO-TOPIC study. A multicenter study from the young group of GETECCUWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Few small studies have assessed the efficacy of topical therapy with tacrolimus in patients with ulcerative colitis (UC). The aim of our study was to evaluate its effectiveness and safety in a real-world setting.

Methods

A multicenter observational retrospective study at 25 Spanish GETECCU hospitals was performed. Adult patients with UC who received topical tacrolimus from January 2009 to January 2023 were eligible. Inclusion criteria were proctitis, left-sided, or extensive colitis with persistent distal colonic activity confirmed endoscopically during the previous 3 months. Clinical and biochemical data were collected at baseline, week 4, 8 and 54. Tacrolimus trough levels were evaluated in week 4 and 8. Primary outcome was clinical response at week 8, defined as a ≥3 points or ≥30% decrease of partial Mayo score with ≥1point reduction in the bleeding score. Mean partial mayo scores were compared using the t-test. A p<0.05 was considered statistically significant.

Results

106 patients, 59 (55.6%) males, median age 48.7 years (IQR:39.9-59.7), received rectal tacrolimus during a median of 9.7 weeks (IQR:5-18.7). Sixty-four patients (60.4%) received suppositories, 41 (38.7%) enemas and 1 patient an ointment (0.9%). Thirty (28.3%) were patients with proctitis, 45 (42.4%) with left colitis and 31 (29.2%) with extensive colitis. At baseline, 54 patients (50.9%) received concomitant biological/small molecules therapy, while 14 patients received immunomodulators. Most common dose was 2 mg (84%) Q24H (71.7%).A significant decrease in mean partial mayo score was observed at week 4 and 8 (figure 1). Clinical response at week 8 was achieved in 63 patients (66.3%) and clinical remission in 42 (44.2%). 32 patients (33.7%) were non-responder at week 8. Clinical response and remission at week 4 were achieved in 56 (57.7%) and 33 (34.4%), respectively. Clinical response at week 8 was similar between the group with concomitant biological therapy and without (64.6.9% vs 68.1%, p=0.8). Clinical response at week 8 was similar among different extensions (proctitis: 55.6%; left colitis: 80%; extensive colitis 57.1%; p=0.052). Clinical outcomes are detailed in table 1.Median tacrolimus trough levels at week 4 was 3.4 ng/ml (IQR 1.5-6.7) and 2.9 ng/ml (IQR 1.5-6) at week 8.Adverse events were detected in 21 patients (19.8%), Thirteen were graded as mild and 8 moderate. Treatment was ceased due to adverse events in 11 (10.4%) patients.

Conclusion

Topical tacrolimus is effective in UC achieving clinical response in more than sixty percent at week 8 with even lower doses than reported in clinical trials. Adverse events reported in nearly 20% of patients were mostly mild.Read more P950 Advancing Precision Nutritional Assessment in Inflammatory Bowel Disease (IBD): Adding Fecal Calprotectin in the Malnutrition Inflammation Risk Tool (MIRT) scoreWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Most of the nutritional assessment tools assess only nutrition. The Malnutrition Inflammation Risk Tool (MIRT) incorporates both malnutrition and inflammation (CRP).1 However, CRP is a less sensitive biomarker than fecal calprotectin for the assessment of inflammation. Adding fecal calprotectin (FC) in the MIRT score may improve the assessment of malnutrition risk. FC level cutoff of < 250 mg/kg in adults correlate with endoscopic remission with good sensitivity and specificity.2 Fecal calprotectin level greater than 800 µg/g is predictive of a need for rescue therapy.3

Aim

To study if adding fecal calprotectin to CRP by improves the yield of MIRT score

Methods

This is a single center, prospective, cohort study including consecutive patients with IBD (Ulcerative colitis {UC} and Crohn’s disease {CD}). Malnutrition was defined as per European society for clinical nutrition and metabolism (ESPEN guidelines): BMI <18.5 kg/m² or unintentional weight loss >10% (indefinite time). MIRT score was calculated with BMI, weight loss and CRP and MIRT-FC by adding FC to CRP with as shown in the table below:

Results

During 2019 to 2021, 200 patients included, median age 39 years (IQR 28-53) (105 UC, 93 CD and 2 IBD-U), 60 (30%) patients had malnutrition (32 UC, 26 CD and 2 IBD-U and 27 (45%) malnourished IBD patients had MIRT score > 3. CRP values were normal in 30 (50%). Adding fecal calprotectin to MIRT score malnourished IBD patients, 46 (76%) malnourished IBD patients had MIRT score > 3 (P=0.005). This modification (MIRT FC) increased the yield of existing MIRT score by 31%.

Conclusion

MIRT-FC score improved the yield of MIRT score. Prospective studies are required to validate this further.References:1. Jansen I, Prager M, Valentini L, Büning C. Inflammation-driven malnutrition: a new screening tool predicts outcome in Crohn’s disease. British Journal of Nutrition. Cambridge University Press; 2016;116(6):1061–7.2. D'Haens G, Ferrante M, Vermeire S, et al. Fecal calprotectin is a surrogate marker for endoscopic lesions in inflammatory bowel disease. Inflamm Bowel Dis 2012; 18:2218-2224.3. Sasidharan S, Sasson AN, Shannon KM, Ananthakrishnan AN. Fecal Calprotectin Is a Predictor of Need for Rescue Therapy in Hospitalized Severe Colitis. Inflamm Bowel Dis. 2022;28(12):1833-1837.ParameterPointsPointsPointsBMI (Kg/m2) >20018·5–20·01 <18·52Weight loss (%)<505-102>23CRP (mg/l) <505-502>503Fecal Calprotectin(ug/g)<2500250-8002>8003Read more P856 Influential factors on the clinical and radiological closure of resistant perianal fistula treated with stomaWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Perianal fistula (PaF) is a debilitating and difficult to treat form of Crohn's disease. Although biological (anti-TNF) treatments are almost always used, long term fistula closure rates are far from being satisfactory. Radiological closure, which should be the treatment goal, is even much rarer. Stoma is one of the last steps in the treatment of resistant fistula. In our study, we examined the patients who underwent stoma, in our series, due to resistant PaF and the factors associated with radiological closure.

Methods

Crohn's disease cohort was retrospectively evaluated for patients with resistant perianal fistula (history of poor response to anti-TNF) who underwent stoma. Demographic, treatment, and clinical characteristics of the patients were evaluated in terms of radiological closure (complete resolution of the fistula tract, disappearance of T2 hyperintensity and absence of contrast enhancement on MRI) of the PaF.

Results

There were 47 patients (11%) who underwent stoma due to perianal fistula among 423 Crohn's disease patients with PaF. The median age in the patient group (at the time of stoma) was 34 years and 47% of the patients were male. Radiological fistula closure was achieved in 42% of the patients and clinical remission (>3 months) was achieved in 66%. Table -1 summarizes the comparison of demographic, clinical and treatment parameters of the study group and patients with and without radiological closure. Radiologic closure and non-closure groups were similar regarding pre-stoma- and during stoma treatment status. Being a never smoker was associated with poor radiological closure and could be an indicator of treatment resistance while ex-smoker status had a favorable outcome. Both recurrent antibiotic treatment (>2/year) need for clinical fistula closure and history of seton replacement were associated with radiological unresponsiveness. During stoma, the early partial radiological response - achieved in the 3rd month of perianal MRI fistulography -was strongly associated with later radiological closure in the follow up. In Kaplan-Meir analysis; anatomically branching fistula had the poorest response, but the number of fistula did not have any influence, mucosal remission was associated with earlier and better radiological response, pre-stoma reccurent antibiotic need was associated with worse outcome Figure 1.

Conclusion

Radiological closure of PaF can be achieved with stoma in nearly half of the patients under already combined conventional treatment. History of seton replacement, recurrent antibiotic need and being never smoker are the indicators of resistance to radiological closure. Third month radiological response – is an important and early sign of radiological complete fistula closure.Read more P977 Combined F18-FDG-PET-MRI-imaging can predict clinical remission in small bowel Crohn’s diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Diagnostics and follow-up of small bowel Crohn’s disease (CD) can be difficult. Combined PET-MRI enterography (MRE) can be used to evaluate intestinal inflammation. Lack of standardized methods and diagnostic thresholds has limited its clinical use in diagnostics and monitoring of small bowel CD. There is no previous data on the use of PET-MRI in follow-up of small bowel CD.

Methods

34 patients with suspected CD in small bowel were recruited from Turku University Hospital’s outpatient clinic. A static PET-MRE was obtained with [18F]-FDG (fluorodeoxyglucose) tracer. CD diagnosis was confirmed with small bowel capsule endoscopy. Patients diagnosed with CD were started with appropriate treatment chosen by clinicians. Endoscopic findings including histopathology, laboratory results (Hb, CRP, serum albumin (Alb) and fecal calprotectin (FC)) and medication data were collected. Patients diagnosed with CD (N=16) went through control PET-MRE median 105 days after initial imaging. Highest SUV_max (standardized uptake value) in small intestine was measured and MRE-images with diffusion weighted imaging (DWI) were analyzed by an experienced abdominal radiologist and severity of inflammation was graded from 1-4. Hb, CRP, Alb and FC were measured from the patients at the time of imaging.

Results

Median SUV_max was significantly lower after three months of medical treatment (3.2 vs. 2.1) (p=0.016). FC was significantly lower at the time of control imaging (p=0.030) (median 725 ug/g vs. 141 ug/g). 10 patients had FC <250 ug/g at the time of control imaging. Using this as a cut- off for clinical response, ROC-curve showed AUC 0.73 for SUV_max and AUC 0.65 for MRE-grading. Sensitivity and specificity were highest at SUV_max 2.4 (83% and 80%).

Conclusion

Decreased SUV_max measured after starting CD medication seems to predict clinical remission and a cut-off level 2.4 could be used in diagnostics. Diagnostic yield was higher for SUV_max compared to MRE-grading. Here we have shown for the first time that PET-MRE can be used for disease activity monitoring in small bowel CD.Read more P857 Effectiveness and safety of subcutaneous infliximab in perianal Crohn's disease: a multicentre cohort studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Infliximab (IFX) demonstrated its effectiveness in perianal CD (pCD) and represents the first-line medical treatment. A subcutaneous (SC) formulation has recently been developed, however so far it has not been specifically investigated in pCD. The aim of our study was to evaluate the effectiveness and safety of SC IFX in pCD.

Methods

We conducted a multicentre retrospective cohort study in the French GETAID, in patients with either active (group 1) or inactive (group 2) pCD who received SC IFX. Inclusion criteria were, for group 1: active pCD in the 6 months prior to initiation of SC IFX; and for group 2: inactive pCD for > 6 months at the time of IV to SC switch, but with a history of seton drainage. The primary endpoint in group 1 was clinical remission at 6 months (absence of anal ulcers, and absence of draining fistula). Univariate and multivariable logistic regression analyses were performed to identify predictors of clinical remission. In group 2, the primary endpoint was perianal clinical recurrence during follow-up.

Results

A total of 192 patients were included in 24 centres. Mean age was 38.9 years, 43.2% were women, 25.1% were smokers. 66 patients were included in group 1, 117 in group 2. In 9 patients, pCD had a > 6 months persistent activity on IV IFX when switched to SC.In group 1, median follow-up was 46 (26.6-64.6) weeks, 51/66(77.3%) patients received combination therapy, surgical drainage was performed in 40(60.6%) patients. One(1.5%), 1(1.5%), 32(48.5%), 20(30.3%) and 12(18.2%) patients received 0, 1, 2, 3 and ≥ 4 IV perfusions respectively before SC switch. At M6, 27/61(44.3%) patients were in clinical remission and 53/61(86.9%) in clinical response. MRI remission or response was achieved in 19/28(68%) patients. In univariate analysis, factors inversely associated with remission were BMI, previous pCD surgery, initial seton drainage, and SC dose optimization. In multivariable analysis, prior exposure to ≥1 biologic (OR 0.248;CI95% [0.071-0.861]p= 0.0243) was predictive of clinical remission.In group 2, median follow-up was 53.6(36.7-67) weeks. The pCD recurrence rate at 6 months was 3.1%. The recurrence-free survival curve is shown in Figure1.Overall, SC IFX was discontinued in 20(10.4%) patients, 8 switched back to IV. Two cases of immunization were observed. Median IFX serum concentration was > 20(17.1- > 20) µg/l. There were 16(8.3%) cases of adverse events related to pain/injection-site reaction: 4 switched back to IV, 1 stopped IFX. There were 5 cases of infection, no case of cancer.

Conclusion

Our results are in line with those reported in the literature on the effectiveness of IV IFX in pCD. The SC formulation appears to be effective and safe for active pCD, and for maintaining remission in inactive pCDRead more P978 Changing therapy to achieve endoscopic healing in asymptomatic patients with IBD: When is perfect the enemy of good?Wed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The treat-to-target strategy for inflammatory bowel disease (IBD) recommends optimising or changing therapy in patients who have not achieved clinical remission and endoscopic healing. In asymptomatic patients, the potential benefit of changing therapy to achieve endoscopic healing is less clear, particularly since <40% typically achieve endoscopic healing with current therapy. We sought to define appropriateness of changing therapy in asymptomatic IBD patients with active endoscopic inflammation.

Methods

Using the RAND/UCLA Appropriateness Method, a panel of 9 IBD specialists considered appropriateness of changing therapy in 16 scenarios of patients with ulcerative colitis (UC) and 96 scenarios of Crohn’s disease (CD), rated on a 9-point Likert scale as inappropriate (1-3), uncertain (4-6), or appropriate (7-9). Patients in all scenarios were asymptomatic with active endoscopic disease; variables included disease extent, behaviour, prior treatment, recent disease progression, and prior disease complications. Current therapy was assumed to be optimised, so the only options were changing therapy or continuing current therapy. An additional 14 scenarios explored patient factors that might influence treatment decision-making. Ratings were collected via online anonymous survey, discussed at an in-person meeting, then finalised in a second anonymous survey using a modified Delphi approach. Disagreement was assessed using a validated index.

Results

Panelists rated it appropriate to change therapy (i.e., expected benefit sufficiently exceeds expected negative consequences) in 96/126 scenarios, generally those with progressive, complicated, and/or extensive disease; 27 scenarios of mild and/or stable disease were rated uncertain, particularly with prior exposure to ≥3 drug classes. Changing therapy in asymptomatic patients was rated inappropriate in 3 scenarios: in Mayo 1 UC previously treated with ≥3 therapy classes with no endoscopic progression in the last year; in any patient who showed endoscopic improvement over the last year; and in any patient with CD who had only scattered aphthous ulcers. Patient age >65 years influenced a decision to change therapy specifically for anti-TNFs and JAK inhibitors; the possibility of pregnancy also influenced decision-making. Despite variability in ratings, the threshold for disagreement was not crossed for any scenario.

Conclusion

Our panel of IBD specialists rated appropriateness of changing therapy to achieve endoscopic healing in asymptomatic patients with UC and CD in a variety of scenarios. Our findings can be used to help guide clinical decision-making in this population until data from ongoing randomised studies are available (NCT05230173).Read more P858 Real World Outcomes of Dual Advanced Therapy in Inflammatory Bowel Disease in Children and Young AdultsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

There is mounting interest in dual advanced therapy (DAT), combining 2 biologics or biologics with small molecules, in patients with refractory disease or partial responders. We evaluated the real-world efficacy and safety of DAT in pediatric and young adults with IBD.

Methods

Single-center, cross-sectional cohort study, conducted between 2018-2023. Primary outcome was DAT remission (clinical (Harvey Bradshaw Index ≤ 4 or partial Mayo Score ≤ 2) and biomarker (C-reactive protein ≤ 5 mg/L and/or fecal calprotectin ≤ 250 ug/g) at first efficacy assessment (T1). Secondary outcomes included remission at T2 if intensification or de-intensification occurred at T1 and T3 remission if re-intensification performed at T2. Failures defined those not achieving remission. Adverse events, surgical and therapy outcomes as of last follow up were evaluated. Descriptive statistics summarized the data.

Results

30 patients were included [43% female, 57% CD, median age of 18.3 [15.1-19.8] years, 46% <18 years, and median IBD duration of 5.2 [4.0-6.9] years at DAT start] (Table 1). Of 11 (37%) treated with TOFA + UST, 100% achieved T1 remission. Of the 10 de-intensified at T1, 6 failed at T2, and all 4/6 that re-intensified achieved T3 DAT remission. Of 9 (30%) TOFA + VDZ patients, 6 (67%) achieved T1 remission and of the 3 T1 failures, 1 had colectomy, and 1 of 2 attempting VDZ intensification achieved T2 remission. All 6 with T1 remission de-intensified, but 5 (83%) failed and only 1/5 attempted re-intensification and failed. Of 4 (13%) VDZ + UST patients, 3 (75%) achieved T1 remission and the 1 T1 failure achieved T2 remission after VDZ intensification. The 2/4 de-intensified failed at T2 and none were re-intensified. Of 5 (17%) UPA + UST patients, 4 (80%) achieved T1 DAT remission and the 1 failure achieved T2 remission after UPA intensification. The 1 who de-intensified failed at T2 but in T3 remission post re-intensification. One (3%) VDZ + OZA patient achieved T1 remission and successfully de-intensified to monotherapy OZA at T2. One TOFA + UST patient developed mild leukopenia and responded to TOFA de-intensification, and 1 developed septic arthritis on TOFA +VDZ on prednisone and resumed TOFA once resolved. At last follow-up, 14/30 (47%) patients were on DAT, 11 (37%) changed therapy, 1 of which underwent colectomy and 5 (17%) were on monotherapy (Figure 1).

Conclusion

The majority of IBD patients treated with DAT achieved clinical and biomarker remission with minimal safety events; however, de-intensification to monotherapy has limited success and supports continuing DAT in more refractory patients. Future studies are needed to guide management.Read more P979 Diet, disease activity and extraintestinal symptoms in IBD outpatientsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Patients with inflammatory bowel disease (IBD) show higher rates of fatigue and symptoms of depression and anxiety. Growing evidence reports a beneficial influence of plant- based diets on IBD as well as psychological disorders. The Mediterranean diet shows favorable characteristics in this regard and is simple to implement. We aimed to examine adherence to a Mediterranean diet as well as its associations with disease activity, quality of life and fatigue or affective symptoms in outpatients with IBD.

Methods

We delivered questionnaires to IBD outpatients, assessing adherence to the Mediterranean diet (MEDAS), symptoms of depression and anxiety (HADS), as well as fatigue (FACIT-F) and quality of life (SHS). Disease activity was measured with HBI or pMS, respectively. Associations between the parameters were determined using spearman correlation.

Results

We collected data of n=281 patients. Adherence to the Mediterranean diet was generally low in our sample with a median MEDAS score of 6 (0-13). The greatest deficit was observed in the regular consumption of fish (10 %) and fruit (16.6 %). However, we found a very high adherence for olive oil as the main source of fat (81.9 %), as well as a preference for white meat over red meat and processed meats (63.7 %). The prevalence of depressive symptoms (HADS-D ≥ 8) was 22.4 %, while symptoms of anxiety (HADS-A ≥ 8) were found in 35.9 % of the participants. Severe fatigue (FACIT < 30) was present in 33.8 % of the patients. Patients with clinically active disease were more likely to experience fatigue (ρ=-.231, p=<.001), symptoms of anxiety (ρ=.132, p=.010), depressive symptoms (ρ=.216 p=<.001), and reduced quality of life (ρ=.359, p<.001), all Figure 1a. There were no significant associations between the MEDAS score and disease activity (ρ=.033, p=.522), fatigue (ρ=-.009, p=.831), anxiety symptoms (ρ=.049, p=.294), or depressive symptoms (ρ=-.035, p=.461). Women showed significantly higher adherence to Mediterranean diet (mean MEDAS score 5.2 vs. 6, p=.003). We found a negative correlation between adherence to Mediterranean diet and level of calprotectin (ρ=-.146, p=.023, Figure 1b).

Conclusion

The preliminary analysis of our sample suggests low levels of adherence to the Mediterranean diet in our patient population. Contrary to our expectation, there were no statistically significant associations between diet and disease activity, quality of life, or psychological complaints. However, the inverse correlation between adherence to Mediterranean diet and level of calprotectin can support the anti-inflammatory characteristics this diet. It remains unclear, to which intent an anti-inflammatory diet can impact the course of disease and clinical symptoms in patients with IBD.Read more P859 Sodium Butyrate supplementation significantly improved clinical outcomes and quality of life in patients with Crohn’s Disease – results from a randomized placebo-controlled studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Butyrate has shown anti-inflammatory effects and plays an important role in maintaining gut homeostasis, providing symptomatic relief when orally supplemented in patients suffering from various colonic diseases.

Methods

In this randomised, double-blind, placebo-controlled study 140 IBD patients in remission or with mild disease (n=60 Crohn's disease, CD and n=80 Ulcerative Colitis, UC) were randomized to oral administration of BLM/placebo for 90 days in addition to conventional therapy. As primary aim: changes in microbiome composition induced by BLM treatment. Fecal microbiota from stool samples was assessed by 16S sequencing. Clinical disease activity assessed by using Harvey Bradshaw Index (HBI) for CD and partial-Mayo Score (pMS) for UC, quality of life assessed by using Inflammatory Bowel Disease Questionnaire 32 (IBDQ-32) and adherence-dietary-raccomandation( WCRF) were evaluated before and after treatment.

Results

Demographics, clinical and dietary characteristics were similar between the two populations. The microbiota sequencing highlighted two different enterotypes in CD population: the first one was characterized by a low F/B ratio (with a genus prevalence of Fusobacteriota, Alistipes, and Blautia). The second enterotype was characterized by a higher F/B ratio (with a genus prevalence of Escherichia-Shigella and Lachnoclostridium)(Fig1). BLM had a more pronounced effect on enterotype-1 where the taxa associated with intestinal comfort, SCFA production, increased after treatment, while the taxa associated with CRC and intestinal inflammation, decreased. After treatment was observed: a)improved quality of life (IBDQ-32: CD: treat. 170/184 vs Pb. 188/197 p<0.001 vs p=0.021; UC: treat.185/195 vs Pb.188/188 p=0.003 vs p=0.4), b)lower disease activity in CD patients (the HBI score, showed a significant improvement for those treated with BLM as compared to placebo (McNemar’s p=0.013 vs p>0.9).c) reduced Calprotectin levels (Table1.) Finally, a significant separation was observed in samples from patients who have undergone minor surgery (ileo-colon), compared to non-surgery patients. The variable "surgery" seems to be associated with the enterotype-1.

Conclusion

Sodium butyrate supplementation significantly improved clinical outcomes and quality of life in patients with CD. Our data showed that the differential response to BLM treatment is based on enterotype, suggesting that Enterotype-1 patients may experience greater clinical benefits and improvements in QoL compared to Enterotype-2 patients in both UC and CD populations.Read more P587 Development and Characterization of a Novel Extended Half-life Monoclonal Antibody Drug Candidate Targeting Integrin ɑ4β7 for the Treatment of IBDWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Antagonism of the interaction between the cellular adhesion integrin ɑ4β7 and endothelial ligand mucosal addressin cell-adhesion molecule-1 (MAdCAM-1) is a safe and effective mechanism to treat Crohn’s disease (CD) and ulcerative colitis (UC). Additional benefit may be gained from an ɑ4β7 antagonist given via the subcutaneous (SC) route at extended intervals (eg, every 8 to 12 weeks) during maintenance therapy.

Methods

The novel humanized monoclonal IgG1 antibody SPY001 binds to the same ɑ4β7 epitope as vedolizumab and includes a YTE modification within the Fc region to increase half-life via increased affinity for the neonatal Fc receptor (FcRn), thereby favoring recycling into the circulation over degradation. Binding affinity of SPY001 to ɑ4β7 was determined by kinetic exclusion assay (KinExA) and flow cytometry, and functional activity was determined by inhibition of addressin-mediated cellular adhesion.

Results

SPY001 binds specifically to ɑ4β7 and not to the related integrins ɑ4β1 and ɑEβ7. In cellular assays, SPY001 binds ɑ4β7 on the surface of RPMI-8866 cells with an affinity matching that of vedolizumab, but it does not bind to Ramos cells expressing ɑ4β1. It demonstrates high affinity for ɑ4β7, with a K_D of 836 pM as determined by KinExA. Functionally, SPY001 potently inhibits MAdCAM-1-mediated cellular adhesion with an IC₅₀ comparable to that of vedolizumab but has no inhibitory activity for VCAM-1-mediated cell adhesion.

Conclusion

SPY001 is a novel humanized monoclonal IgG1 with high affinity for ɑ4β7 and potent inhibition of the ɑ4β7/MAdCAM-1 interaction. It offers the potential for effective and safe treatment of CD and UC with the advantage of infrequent SC dosing. Further preclinical and clinical studies are warranted to demonstrate this potential.Read more P980 Dietary perceptions and practices in patients with Inflammatory Bowel DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Patients with Inflammatory bowel disease (IBD) have a strong interest in the role that diet can play in the disease.However, studies evaluating the perception of diet in Tunisian patients are lacking.The aim of this study was to investigate the dietary beliefs and behaviours of adult patients with IBD.

Methods

We conducted a longitudinal study using a self-administered questionnaire distributed online to the «Association Tunisienne des Maladies de Crohn et de RCH» group. Through 17 items, we collected data assessing the dietary behaviours and beliefs of patients with Crohn's disease (CD) or ulcerative colitis (UC).

Results

A total of 121 patients (CD: 59%,UC 41%)were enrolled, with a mean age of 38.1±11.4 years and a sex ratio of M/F= 0.73.Twenty-three patients were active smokers. At the time of the enrollment, 26.4% of patients had an active disease. Eighty-three patients believed that diet was a trigger for the disease, with a male predominance(80% versus 60.8%, p=0.02) but no difference between the UC and CD groups was found(p=0.61). Fourty-one patients felt that diet was more important than medical treatment for disease control, with equal importance for 47 patients and no impact for 6 patients. Ninety-two patients thought that diet could induce a relapse of the disease, with 86.8% resorting to an exclusion diet, and 76% thought that a change in diet could induce remission of the disease. The most frequently avoided were spices(33.1%),and gluten(17.4%). Spicy foods were considered to be the main responsible for IBD flares by 90.1% of patients,followed by fast foods(75.9%), citrus fruits(70.4%) and legumes(64.7%). Respectively 57% and 34.7% of the patients believed that milk and dairy products could induce or worsen disease symptoms. Around half of our patients thought that pasta had no impact on the disease course, while rice was considered to be the major aliment able to prevent relapse and improve symptoms by 47.7% of patients. On the other hand, 52.2% of patients considered high fiber vegetables to be potentially responsible for relapses. Fourty-two percent of the patients believed that fruits could have a negative impact on IBD while 20.4% thought they have a positive effect. Around half the patients thought that red meats and coffee had no impact on the course of the underlying disease. Fifty-five percent of the patients believed that fasting could prevent relapses, while 53 patients felt that it had no significant effect. Half of our patients had at least once consumed nutritional supplements, with a medical prescription noted in 65.6%.

Conclusion

Our study underlines the importance of a holistic approach to the treatment of IBD, taking into account both traditional medical treatments and appropriate dietary education.Read more P860 Long-term outcomes and predictors of vedolizumab persistence in ulcerative colitis - a six-year follow-up studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Long-term vedolizumab (VDZ) outcomes in real-world cohorts have been largely limited to 1-year follow-up, with few bio-naïve patients or objective markers of inflammation assessed. We aimed to assess factors affecting VDZ persistence including clinical, biochemical and faecal biomarker remission at 1, 3 and 5 years.

Methods

We performed a retrospective, observational, cohort study. All adult IBD patients who had received VDZ induction for UC/IBDU were included. Baseline phenotype and follow-up data were collected via review of electronic medical records.

Results

We included 290 patients (UC n=271 [93.4%], IBDU n=19 [6.6%]) with a median time on VDZ of 27.6 months (IQR 14.4-43.2). At the end of follow-up, a total of 157/290 (54.1%) patients remained on VDZ. Median time to discontinuation was 14.1 months (7.0-23.3). Previous exposure to ≥1 advanced therapy, steroid use at baseline; and disease extension were independent predictors for VDZ persistence (Table 1). Clinical remission (partial Mayo <2) was 75.7% (171/226), 72.4% (157/217) and 70.2% (127/181) at year 1,3 and 5 respectively. Steroid use during maintenance VDZ therapy occurred in 31.7% (92/290), hospitalization in 15.5% (45/290) and surgery in 3.4% (10/291). The rate of serious adverse events was 1.2 per 100 patient-years of follow-up.

Conclusion

VDZ persistence is influenced by previous exposure to biologics/small molecules, disease distribution and steroid use at baseline. VDZ effectiveness is enduring with favourable long-term safety profile.Read more P571 The Effect of NLRX1 Activation on Eosinophils in Ulcerative Colitis and Inflammation: Translational Learnings Across Diseases and from Mouse to HumanWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Although the precise role of eosinophils in IBD is debated, elevated eosinophils may influence response to therapy and clinical outcomes¹. Thus, therapeutic agents which affect both neutrophil and eosinophil recruitment may provide more robust clinical improvement in patients with UC. NLRX1 is an immunometabolic protein which reduces oxidative stress, shifts cellular metabolism, and decreases inflammation in multiple cell types implicated in ulcerative colitis (UC). Studies of NLRX1 agonists (gut-selective NX-13 & systemic LABP-73) in diverse disease models identified novel cellular targets of NLRX1 activation. We compared NLRX1’s effect on eosinophils in 2 disease states, UC and the more prototypical eosinophilic disease, asthma, and evaluated the findings.

Methods

In the 4-week NX-13 Phase 1b, a double-blind trial of 36 patients with active UC (Total Mayo Score 4-10; Mayo endoscopic subscore 2-3) who were randomly assigned to NX-13 250mg Immediate Release (IR), 500mg IR, 500mg Delayed Release (DR) or Placebo QD for 4 weeks, histology was assessed using the Geboes score by a blinded pathologist². For allergic asthma models, mice were immunized with ovalbumin or house dust mite followed by antigen challenge concurrent with LABP-73 or vehicle. Cells isolated from the lung were analyzed by flow cytometry using the BD FACS Celesta/Diva. Data are represented as means (standard error).

Results

In the 1b clinical trial, both the Geboes score and neutrophil subscores were reduced in the IR NX-13 group compared to placebo, consistent with the effects seen in preclinical IBD models. Upon examination, eosinophil infiltration was reduced in both the IR dose cohorts compared to placebo (Fig1A). In the subset of patients with active eosinophil infiltration at baseline (defined as Geboes subscore ≥2A.1), eosinophil reduction was seen in all NX-13 doses (Fig1B). Importantly, a numerically increased clinical response rate (decrease in total Mayo score of ≥3 or ≥30%) was seen in patients that demonstrated effective eosinophil reduction, compared to patients without improvement (75% versus 29%; Fisher’s Exact Test, p=0.08). In two allergic asthma models, NLRX1 activation by LABP-73 significantly reduced the fraction of eosinophils within the lung relative to vehicle control (n=7-8; p< 0.05), confirming NLRX1 activation can regulate eosinophilic inflammation in Th2-mediated responses.

Conclusion

Neutrophil and eosinophil infiltration were reduced in UC patients treated with the gut selective NLRX1 agonist, NX-13, and was coupled with better clinical outcomes. The effect of NX-13 on eosinophils will be evaluated further in the ongoing phase 2 NEXUS trial in patients with UC.1 A Mookhoek, et al. JCC (16).2 L Peyrin-Biroulet, et al. JCC (17) SuppRead more P1014 Faecal loss of vedolizumab is associated with UC severity, lower serum vedolizumab levels and rates of clinical response – Results from the FAVOUR studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Infliximab is detectable in the faeces of patients with active UC and faecal loss is associated with more severe disease and with primary non-response. Detection of vedolizumab (VED) in faeces and its importance in patients with UC has not been investigated. We conducted a prospective, observational study of patients with UC commencing VED to investigate faecal VED loss as well as its impact on serum VED levels (SVL) and association with treatment outcomes.

Methods

The FAVOUR study recruited UC patients with moderate to severe UC commencing vedolizumab between April 2019 and May 2022. Patients were treated with 300mg VED IV at weeks 0, 2, 6 and 14. Trough SVL were measured at weeks 2, 6 and 14. Faecal samples at days 1, 4, 7 and at weeks 2, 6 and 14 were homogenised and centrifuged to produce supernatants which were analysed for faecal VED levels (FVL) using a commercially available ELISA (LISA TRACKER, Theradiag, France).Clinical (SCCAI) and biochemical disease activity (CRP and faecal calprotectin) were measured at each infusion. Endoscopy was performed at baseline and week 14 to measure endoscopic (UCEIS/Mayo) and histologic activity (NHI).Correlations were calculated using the Spearman correlation coefficient (r). Categorical variables were compared using Mann-Whitney U.

Results

36 patients (median age 34 (range 18-73); 13 Female) were recruited, of whom 33 completed induction therapy (3 withdrew early and were considered non-responders). 26/36 (72%) achieved a clinical response (SCCAI≤5 and reduction of ≥2) and 18/36 (50%) achieved endoscopic remission (UCEIS≤2).Faecal VED was detectable in 80/203 (39%) samples. Statistically significant correlations were observed between FVL and markers of clinical, biochemical, baseline endoscopic and histologic disease activity at day 1, and weeks 2 and 6 (table 1). Week 14 clinical non-responders had higher FVL than responders at that time point (median 1.0 vs 0.0ug/mL, p=0.004) but not at other timepoints. A statistically significant negative correlation was observed between week 2 FVL and SVL measured at weeks 6 and 14 (table 1). SVL did not differ significantly between week 14 responders and non-responders at any time point.

Conclusion

Active colonic inflammation results in faecal loss of vedolizumab. This appears to correlate with lower SVL and rates of response to treatment. However, SVL were not observed to directly influence rates of response. It is possible that FVL may be a marker of disease activity or that faecal loss results in lower rates of drug exposure at a tissue level and negatively impacts rates of response by this mechanism.Read more P563 Nutritional screening in patients with inflammatory bowel disease: a challenge in the timely diagnosis of malnutrition and sarcopeniaWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Malnutrition is prevalent in inflammatory bowel disease (IBD) and has been reported in up to 70% in patients with active disease and 38% in patients in remission, being related to sarcopenia, so different tools have been proposed for the nutritional screening of these patients taking into account the importance of early intervention avoiding consequences related to altered body composition such as inadequate response to treatment and poor quality of life, but the evidence in IBD patients is still unclear and there are no studies in Colombian IBD patients. Therefore, the aim of this study is to describe the nutritional status of patients using multiple nutritional screening and assessment tools.

Methods

Descriptive observational cross-sectional study in patients diagnosed with IBD with clinical activity, by applying nutritional screening tools such as the Malnutrition Universal Screening Tool (MUST) and the Malnutrition Inflammation Risk Tool (MIRT) to determine their nutritional status and degree of sarcopenia.

Results

Nutritional screening was performed in 20 patients with Inflammatory Bowel Disease, with mild to moderate clinical activity of the disease; patients in clinical remission were excluded. Sixty percent were men and 40% women; with an average age of 44.5 years, 19 years as minimum age and 73 years as maximum age. Taking into account the Malnutrition Universal Screening Tool (MUST), 30% have a high risk of malnutrition, with a higher percentage in men. On the other hand, the MIRT (Malnutrition Inflammation Risk Tool), which evaluates BMI, showed that 25% have a score greater than or equal to 3, which indicates a risk. In addition, and 40% of the population underwent nutritional status assessment in order to rule out sarcopenia. Muscle strength, muscle mass and muscle function were assessed and 25% of this population were diagnosed with sarcopenia and another 25% with possible sarcopenia.

Conclusion

Patients with IBD are at increased risk of malnutrition, This is the first Colombian study to approach the nutritional assessment of IBD patients with mild to moderate disease activity using nutritional screening tools such as the Malnutrition Universal Screening Tool (MUST) and the Malnutrition Inflammation Risk Tool (MIRT), showing that up to one third of patients are at high risk of malnutrition and 50% have a diagnosis or possible diagnosis of sarcopenia, which is slightly lower than that described in the literature, However, it does raise awareness of the importance of nutritional screening in IBD patients as these alterations have been shown to be associated with increased hospitalisation requirements, number of disease flares and associated complications.Read more P637 Ozanimod efficacy with or without concomitant corticosteroids in 5-ASA–exposed, advanced therapy–naive, immunomodulator-naive patients with ulcerative colitis: a post hoc analysis of True NorthWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Long-term corticosteroid (CS) use is not recommended for patients (pts) with ulcerative colitis (UC). Receiving early advanced therapy (AT) may help limit CS overuse, but there is a need to identify pt populations who may benefit most from receiving early AT as monotherapy. Previous post hoc analyses of the phase 3 True North (TN) study (NCT02435992) demonstrated ozanimod (OZA) efficacy in 5-aminosalicylate (5-ASA)–exposed, AT-naive, immunomodulator (IMM)–naive pts. This analysis further assessed the efficacy of OZA induction therapy with and without concomitant CS in this pt population by baseline (BL) endoscopic disease severity.

Methods

In TN, pts in Cohort 1 (C1) were randomised to OZA or placebo (PBO); pts in Cohort 2 (C2) received open-label OZA through Week (W) 10. Pts were on stable doses of oral 5-ASA and/or CS for ≥2 wk before screening and continuing through W10. 5-ASA–exposed, AT-naive, IMM-naive pts were grouped as moderate (Mayo endoscopy subscore [MES]=2 at BL) or severe (MES=3 at BL). Data were analysed in all moderate and severe pts and by concomitant CS use. Clinical remission, clinical response, endoscopic improvement, mucosal healing, and histologic remission were assessed at W10.

Results

Of the 464 5-ASA–exposed, AT-naive, IMM-naive pts, 237 had moderate (PBO, n=47; OZA C1, n=108; OZA C2], n=82) and 227 had severe (PBO, n=54; OZA C1, n=97; OZA C2, n=76) BL endoscopic disease. BL pt characteristics were generally similar between moderate and severe pts with or without concomitant CS use. Overall, OZA was significantly more effective in moderate pts and numerically more effective in severe pts vs PBO in C1, with numerically greater treatment differences in moderate vs severe pts (Figure 1A). The moderate and severe groups each had 51 pts (~22%) on concomitant CS. In moderate pts, numerically greater OZA vs PBO C1 treatment differences were observed in those without concomitant CS use vs those with concomitant CS use for clinical remission and clinical response; treatment differences were significant for all endpoints in pts without concomitant CS use (Figure 1B). In contrast, severe pts with concomitant CS use demonstrated greater OZA vs PBO C1 treatment differences vs those without concomitant CS use for all endpoints (Figure 1C). Results in OZA C2 were generally similar to OZA C1.

Conclusion

OZA treatment was efficacious in 5-ASA–exposed, AT-naive, IMM-naive pts with UC, with numerically greater efficacy in moderate pts than severe pts. Additionally, the results suggest that concomitant CS may not provide additional benefit over OZA monotherapy in moderate pts. These findings support OZA positioning after 5-ASA, but before CS, in pts with moderate UC.Read more P1015 Subcutaneous infliximab effectively manages clinical outcomes of Inflammatory Bowel Disease independently of various confounding factorsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Since its approval, many inflammatory bowel disease (IBD) patients have been treated with subcutaneous (SC) infliximab (IFX), but the association of various confounding factors with clinical outcomes is still elusive.

Methods

The ASSEMBLE project is an initiative to combine multi-national real-world cohort datasets and analyse the effectiveness and safety of SC IFX therapy. In the ASSEMBLE-1 database analysis, three studies from France and the United Kingdom^1-3 were integrated to assess the clinical outcomes up to 6 months (6M) after switching from IV to SC IFX. Clinical remission was defined as Harvey-Bradshaw Index (HBI) or modified HBI (mHBI) <5 for Crohn’s disease (CD) and Simple Clinical Colitis Activity Index (SCCAI) or partial Mayo score (PMS) <3 for ulcerative colitis (UC). Treatment persistence was assessed by Kaplan-Meier survival analysis. After adjustment with inverse probability of treatment weights (IPTW), the association of various parameters on clinical outcomes was assessed with marginal structural models (MSMs), by comparing the estimated marginal means (EMMs) of remission rates at 6M between patients in each subgroup.

Results

The data of 428 patients were pooled from the three datasets (70.6% CD, 29.4% UC). 85.4% of patients were in clinical remission before switching to SC IFX with median HBI or mHBI of 1 (IQR 0,2) for CD and median SCCAI of 2 (IQR 1,3) or PMS of 0 (IQR 0,0) for UC. The overall clinical remission and persistence rates at 6M after switching were 84.7% and 94.5%, respectively. Pre-switch IV IFX regimens, immunomodulator (IMM) use, age, baseline fecal calprotectin (FC) level, or baseline C-reactive protein (CRP) level were not associated with persistence. Persistence rate was >90% regardless of body mass index (BMI), although it was higher for patients <25 kg/m² BMI (98.1%). Assessment with MSMs indicated that the clinical remission rate of CD, but not UC, was expected to be significantly lower only if patients were treated with escalated IV IFX before switching rather than standard 5 mg/kg Q8W regimen (p=0.01; Table 1). No association with high BMI, IMM use, age, ≥150 μg/g FC, and ≥5 mg/L CRP was found in both CD and UC (Table 1). Perianal disease was not associated with CD remission either.

Conclusion

The ASSEMBLE-1 results confirm that switching from IV to SC IFX is well accepted and effectively manages the clinical outcomes of the disease regardless of various confounding factors in IBD patients. However, further studies are warranted to explore the association of pre-switch IV IFX regimens with clinical outcomes. [1] Smith et al. J Crohns Colitis 2022 [2] Buisson et al. Clin Gastroenterol Hepatol 2023 [3] Rahmany et al. Gastroenterology 2023.Read more P613 Dietary intervention as a novel tool to improve diagnostic accuracy of patency capsule in Crohn’s Disease patientsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Patency capsule (PC) is recommended to confirm the patency of the small bowel before ingestion of video capsule endoscopy (VCE). However, in some patients non-expelled PC could be due to slow transit time and not due to small bowel stricture. We examined if dietary intervention during the PC could improve passed PC rate and reduce false positive results.

Methods

A retrospective study of patients who received diet-modified protocol of PC test, introduced into routine clinical practice on February 2023, compared with standard protocol. Dietary-modification comprised individualized dietary advice on the consumption of personally-conceived laxative foods after PC ingestion. Abdominal X-ray at 30 hours post-ingestion was performed to ascertain passage of PC in patients who did not see an intact PC in stool, followed by low-dose limited computed tomography (CT) in patients with evident PC on X-ray to assure passage to colon.

Results

A total of 52 Crohn's patients who ingested PC were included (median age 32.4, 28.8% with previous intestinal resection). 26 of the patients followed the dietary-modified personalized protocol and 26 followed the standard protocol. In total, 38/52 PC passed and 14/52 (26.9%) failed. Patients on dietary modification had significantly reduced rate of a failed PC compared to patients receiving standard protocol (7.7% versus 46.1%, respectively, odds ratio 0.1, 95% confidence interval 0.02-0.49, P=0.005). 12/14 patients with a failed PC underwent low-dose CT, which showed PC was in the colon (false positive PC) in 11/12 patients (92%, 9/11 in standard group, 2/11 in dietary group). All 11 patients with a passed PC in colon subsequently ingested a VCE without complications.

Conclusion

Majority of failed PC are falsely positive, stemming from slow-transit of PC in the colon. Personalized dietary intervention to promote colonic transit may serve as a novel practical tool to reduce false positive tests and improve the diagnostic accuracy of patency capsule.Figure 1.Percentage (%) of patients with failed PC with dietary intervention versus standard protocol. PC, Patency capsule.Read more P614 Endoscopic Electroincision Therapy for ChildrenWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Anastomotic strictures can be successfully treated by endoscopic balloon dilation (EBD); however, the emerging modality of stricturotomy with electroincision therapy (EIT) and strictureplasty(stricturotomy followed by endoscopic clipping) may achieve superior outcomes. Endoscopic stricturotomy has been shown to have greater efficacy than EBD in adult patients with IBD. While the rate of perforation is lower in EIT as compared to EBD in IBD, stricturotomy has a 4-10% rate of delayed bleeding, with a smaller proportion requiring blood transfusion. EIT can delay the need for surgical intervention and in many circumstances obviate the need indefinitely. This study is to describe the use of EIT for luminal strictures in children.

Methods

Retrospective cohort study of 10 pediatric patients (including 18 procedures) with anastomotic and primary luminal stricture who underwent endoscopic EIT with stricturotomy or strictureplasty. Outcomes and complications were documented.

Results

Among 18 performed, 14 stricturotomy and 4 strictureplasty, 2 patients did not require further intervention and had no stricture recurrence at time of follow-up. 3 patients required repeat stricture therapy but the time duration between interventions, previously EBD, extended. There were 2 procedural complications, tension pneumoperitoneum managed by needle decompression and microperforation, neither of which required surgical repair or resection. There were no episodes of GI bleeding.

Conclusion

EIT for luminal stricture in children may offer an alternative to EBD or surgical resection and re-anastomosis. The relative risk in children remains to be delineated.Read more P1016 Real-world data on sequential therapy in moderate-to-severe UC: Unveiling second-line strategies after anti-TNF failureWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The development of anti-TNFs has brought major advances in the treatment of ulcerative colitis (UC). Yet, a significant proportion of patients do not respond favorably to first-line anti-TNF therapy, which may require the use of second-, third-, or fourth-line biologics or small molecules. Treatment selection and sequencing, however, remains a major unmet need.

Methods

We conducted a multicenter, retrospective study including patients with moderate-to-severe UC who failed first-line anti-TNFs, and received sequential therapy with biologics or small-molecules. The effectiveness of sequential therapy, more specifically second-line agents was determined and compared by treatment persistence and colectomy-free survival up to 3 years post-initiation, and assessed using Kaplan-Meier analyses. Multivariate Cox regression analysis was performed to identify the predictive value of various factors for colectomy and persistence.

Results

683 UC patients were included. The median follow-up time was 62 months (IQR: 36-98), during which 14.2% of patients required colectomy. The probability of colectomy-free survival was 97.5%, 93.9% and 92.3% at 1, 2, and 3 years. Persistence rates increased significantly with the number of therapy lines (P<.0001). The presence of deep ulcers at diagnosis (HR: 0.45; P=.009), prior cyclosporine use (CYA; HR: 0.41; P=.028), and low serum albumin at first-line therapy (HR: 0.92; P=.002) appeared to be predictive for colectomy. Following anti-TNF failure, significantly higher colectomy-free survival rates were observed over 3 years with ustekinumab (UST; P=.014; Figure 1a.), than with vedolizumab or tofacitinib. Second-line UST also showed superior persistence at 3, 6, 12, and 24 months (P=.049; Figure 1b.), but not at 36 months. Neither the risk of colectomy (P=.343), nor the rate of persistence with second-line therapy (P=.19) was influenced by the reason of first-line anti-TNF discontinuation. Prior CYA use (HR: 0.42; P=.047) negatively influenced persistence with second-line therapy.

Conclusion

Despite multiple lines of sequential biological and small molecule therapy we found a low incidence of colectomy and a high rate of persistence. Following anti-TNF failure, regardless of its cause, UST might be the preferred second-line agent in moderate-to-severe UC.Read more P657 Persistence of subcutaneous infliximab after two years of the switch from intravenous infliximab to subcutaneous infliximab in Inflammatory Bowel Disease patientsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Biosimilar infliximab (CT-P13) has been available for subcutaneous (SC IFX) administration since march 2021. It has shown to be equivalent to its every-8-week-intravenous formula (IV IFX), however, we do not have long term efficacy and safety data. Our aim was to evaluate medication persistence, efficacy and safety two years after switching from IFX IV to IFX SC

Methods

Multicentre, descriptive, and observational study, with prospective data collection, of Crohn’s Disease (CD) or Ulcerative Colitis (UC) patients who were going to be changed from IV IFX to SC IFX. All patients were on clinical and biological remission for at least 6 months. Clinical activity, analytical data, trough level determinations and adverse events were gathered. Baseline results were compared with those from week 108 after starting CT-P13 SC. Maintenance of the drug after two years and the reason for removal, if so, or of loss of follow-up, were evaluated.

Results

41 patients were included. 24 of whom had intensified doses while 17 were on standard doses (5 mg/kg every 8 weeks). 51% were male; mean age 40.8. 63,4 % (n = 26) had CD. No PCR differences were observed at baseline (IV IFX) [median 0,17 mg/dL] and week 108 [median0,3 mg/dL]. Fecal calprotectin stayed under 200 ug/mg from baseline to 24 months. No changes in clinical indexes were observed. A considerable increase in drug levels was observed after switching to SC IFX at week 108 (6,8 vs 12.3; p < 0,001). 46% of the patients were also on immunosupressor when they switched to IFX SC, and 52% of these had removed it after 2 years of IFX SC. 85% of the patients were still on IFX SC after two years (only one was removed due to loss of response). There were only 3 adverse events, all of which were mild.

Conclusion

Persistence of IFX SC after two years was observed in 85% of the patients. Switching from IV IFX to SC IFX maintains remission in Inflammatory Bowel Disease (IBD) after a 2-year follow-up. Higher drug levels are obtained with the subcutaneous formulation, despite removing the immunosupressor in over 50% of the patients. Switching from IV IFX to SC IFX is safe in IBD.Read more P615 Clinical efficacy of accelerated 4-weekly vs. Conventional 8-weekly ustekinumab dosing in Inflammatory Bowel Disease: A single centre experienceWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

8-weekly dosing regimen of ustekinumab in the treatment of moderate-to-severe Inflammatory Bowel Disease (IBD) is the current standard of care. Accelerated 4-weekly dosing has been suggested to be efficacious, however not licensed, in ‘non-responders’. The aim of this study is to determine how 4-weekly accelerated dosing regimen in ustekinumab drug levels correlate with response to treatment in patients with IBD.

Methods

Patients for inclusion were identified retrospectively utilising online prescription records at Mercy University Hospital, Cork. Inclusion criteria consisted of IBD patients commenced on ustekinumab with a treatment duration of at least 6 months. Participants were separated into 4-weekly and 8-weekly treatment groups. Faecal calprotectin (FCP) levels/ustekinumab drug levels were recorded from the 12-week check in post initiation and at the 2^nd assessment. Symptoms were scored at these visits and further quantified using the Harvey Bradshaw index for Crohn’s Disease and the partial mayo score for Ulcerative Colitis.

Results

101 patients at the Mercy University Hospital Cork were identified utilising a database of prescriptions and physical charts (4-weekly: 27; 8-weekly: 74). A statistically significant decrease in FCP levels at 2nd assessment was noted in patients with 4-weekly dosing (p=0.028). There was no statistically significant relationship between dosing interval and symptoms (p=0.735). Individual patient factors including age, gender, type of IBD, and concurrent IBD medications did not have a statistically significant effect on faecal calprotectin levels or symptoms.

Conclusion

The greater percentage decrease in faecal calprotectin provides objective evidence supporting the escalated dosing interval at the Mercy University Hospital IBD centre. However, further study is necessary to justify increasing the dosing interval for all patients treated with ustekinumab for IBD.Read more P1017 Upadacitinib as rescue therapy for the treatment of Acute Severe Colitis in an acute care settingWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Inflammatory bowel disease is a chronic, relapsing and remitting inflammatory disorder that despite advances in medical therapy often requires hospitalization for treatment of acute flares with intravenous corticosteroids. Many patients will not respond to corticosteroids and require infliximab or cyclosporine as rescue therapy. If medical therapy fails, definitive surgical management is required. Recently, Janus Kinase inhibitors, including upadacitinib, have been proposed as an alternative rescue therapy given their rapid onset of action. The aim of this study was to evaluate the efficacy of upadacitinib as an alternative rescue therapy for acute severe colitis.

Methods

We conducted a retrospective review of 12 inflammatory bowel disease patients admitted for acute severe colitis who received upadacitinib induction therapy. The rates of surgery, repeat or prolonged steroid use, and re-admission within 90 days of index hospitalization were measured. The need for re-induction with upadacitinib, change in medical therapy, rates of clinical remission, change in 6-point partial Mayo score, and laboratory markers of inflammation were measured as secondary outcomes. Statistical analysis of primary and secondary endpoints was performed with descriptive analysis.

Results

Five patients met the primary composite endpoint including four patients requiring surgery and one additional patient being unable to withdraw steroids within 90 days of hospital discharge. One patient required re-induction with upadacitinib within 90 days and no patients required change in medical therapy within 90 days. Of the patients who did not undergo surgery, 63% were in clinical remission within 90 days and showed clinical improvement with decreased 6-point partial Mayo scores at the post-discharge visit (4.75 during admission vs. 1.25 at post discharge visit, p<0.0001). There were no adverse reactions reported in relation to upadacitinib administration during the study period.

Conclusion

We found that two-thirds of patients treated with upadacitinib 45mg daily for acute severe colitis were able to avoid surgery during the index admission and within 90 days post-discharge. Of the patients who were able to avoid surgery, most were able to taper steroids, did not require readmission within 90 days of index hospitalization and were in clinical remission within 90 days. Upadacitinib may be effective salvage therapy for acute severe colitis, but larger controlled trials are required to validate these results.Read more P667 Benefit of 5-ASA continuation on UC disease outcomes following initiation of a biologicWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

In the era of advanced therapeutics for treatment of ulcerative colitis (UC) the benefit of routinely prescribed concomitant 5-aminosalicylate (5-ASA) compounds is still unclear.

Methods

A single centre, noninterventional retrospective cohort review study was performed on real-life data of adult patients with moderate-to-severe UC who were treated with biologics (infliximab, vedolizumab, ustekinumab) for a minimum of 6 months with or without concomitant use of 5-ASA. The difference in further treatment failure defined as a clinical negative composite outcome (need for steroid rescue therapy, biologic switch, IBD-related hospitalization and/or surgery) in two groups (5-ASA + biologic combination therapy vs biologic monotherapy) was assessed. Participants’ characteristics were assessed using descriptive statistics. Normal distribution was assessed using Kolmogorov-Smirnov and Shapiro-Wilk tests. Categorical variables were analysed using Chi-square test and continuous variables with Mann-Whitney test. Kaplan-Meier analysis and log-rank test were used in order to assess difference in therapy duration between two groups.

Results

Total of 104 patients (47.1% females; smokers 17.6%; concomitant stable dose oral 5-ASA 33%) were included. There were no differences in key baseline characteristics such as age, sex, smoking status, extraintestinal manifestations, serum albumin and CRP as well as fecal calprotectin levels between groups of patients receiving 5-ASA co-treatment and patients without 5-ASA. Median duration of therapy was 21 months (IQR 9-40). Concomitant use of 5-ASA was not associated with improved clinical outcomes; there was no statistically significant difference in the occurrence (χ2(1, N =102)=2.2, p=0.14) or time to develop (χ2(1, N =102)=1.12, p=0.29; Figure 1.) negative composite outcomes.

Conclusion

In our cohort we have failed to detect any benefit of 5-ASA continuation on significant clinical adverse events or hospitalisations in UC following initiation of a biologic.Read more P616 Prescribing practices of tofacitinib and preferences amongst high-risk patients in the UKWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Tofacitinib was licensed for use in patients with ulcerative colitis in August 2018. Because it is administered orally, has a rapid onset of action and is relatively inexpensive, it was quickly adopted in real-world practice. Safety warnings linking high-dose tofacitinib use to venous thromboembolic events (VTE) and death followed. Further warnings were issued linking its use to an increased risk of malignancy and adverse cardiovascular events in patients: over 65 years, with a history of diabetes, current or past smokers, and those with a history of coronary vascular disease. The most recent Medicines and Healthcare products Regulatory Agency (MHRA) statement advised against the use of all commercially available JAKi in this high-risk cohort unless a suitable alternative is unavailable (MHRA 2023).We sought to define the number of patients who had, or were, being treated with tofacitinib who were in this high-risk group and the proportion who opted to switch therapy once we had outlined their risk-status and the MHRA advice to them.

Methods

We conducted a retrospective observational cohort study of 131 patients with UC and IBD-U (61% male [80/131]; median age 43 years [range 16-85]; 46% [60/131] patients had previously had at least one biologic agent) treated with tofacitinib from October 2018 to December 2022 in our centre with at least 3 months follow-up. Patients were categorised as high-risk according to the MHRA statement if they had at least one of the criteria above.

Results

Overall, about one-third, 31.3% [41/131] patients that we had treated with tofacitinib were classified in the MHRA high-risk group.Rates of treatment discontinuation were similar in the high-risk versus no risk group. In the high-risk group ten patients (24.4% [10/41]) had discontinued treatment due to lack of response (4) or an adverse event (6). The most common adverse events were herpes zoster infections (14.6%), malignancy (3.3%) and infections requiring hospitalisation (3.3%). Two patients died while on treatment (one due to complications following cervical spinal surgery and the other due to ischaemic heart disease). There were no incidences of VTE.We clinically reviewed 29 high risk patients who were being treated with tofacitinib after a median of 2.4 years (range 0.6-4.56) of treatment. 25/29 high-risk patients decided on continuing their treatment in spite of the health care warnings and alternative therapies being available.

Conclusion

About one-third of our tofacitinib-treated patients were classified as at high-risk. The majority of high-risk patients opted to continue therapy even though alternative therapies were available.Read more P1066 The real-life use of the Crohn's disease exclusion diet (CDED) in adults with mild-to-moderate Crohn's disease activity: an interim analysis of an open-label randomized controlled trialWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The Crohn's Disease Exclusion Diet (CDED) is a validated dietary intervention characterized by a specific highly restrictive food regime which aim to induce remission and reducing inflammation in Crohn's disease (CD). In a previously randomized control trial (RCT), clinical remission was achieved in a range of 75-85% of patients after 6 and 12-weeks of CDED. We aim to provide an additional real-world evidence-based validation.

Methods

Interim analysis of an open-label randomized controlled trial of CD patients with mild-to-moderate clinical activity assessed by Harvey-Bradshaw Index (HBI) was performed. Demographical characteristics and medical history were collected at enrollment, while weight, body mass index (BMI), HBI, fecal calprotectin and serum inflammatory indices were assessed at baseline and after 12 and 24 weeks. Bioelectrical impedance analysis (BIA) was performed every 12-weeks in CDED group to test the safety. The primary endpoint was clinical remission (HBI<5) and was assessed in the intention-to-treat population.

Results

Twenty-four patients were randomized to receive CDED diet, while 21 were in control group. No significant differences among all parameters considered were observed at baseline. Five patients in CDED group discontinued diet because of intolerance at median of 5 weeks. At week 12, the median HBI was lower in CDED patients than in control patients (3, IQR 1-5 vs 5, IQR 4-6, respectively; p=0.001) resulting in more patients achieving clinical remission (17/24, 70,8% vs 8/21, 38,1%, respectively; p=0.027). No differences in fecal calprotectin and serum inflammatory indices were observed. The administration of CDED was associated with weight loss (72 to 69 kg, p=0.003), although BIA analysis showed a decrease in fat mass (18.2% to 15.5%, p<0.0001), while fat-free mass significantly increased (81.9% to 83.7%, p=0.001). No difference in body cellular mass was observed after 12-weeks of CDED.

Conclusion

The CDED is effective in inducing remission in mild-to-moderate clinical activity CD patients and seems to be safe and well-accepted.Read more P617 Persistent active inflammation may predict non-improvement in bone mass density in patients with Crohn's diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Osteopenia and osteoporosis are associated with Crohn’s disease (CD). Diagnosis is made by dual-energy X-ray absorptiometry scan (DEXA). Pathophysiology of osteoporosis may reflect an interplay between persistent inflammation, steroid usage, as well as risk factors similar to general population. We aimed to identify factors associated with low or deteriorating bone mineral density (BMD) among patients.

Methods

A retrospective case-control study, included patients with CD followed at our IBD clinic from January 2000 to February 2023, with ≥ 2 DEXA scans. The observation started one year before the initial DEXA scan and extended until one year after the second scan. Demographic, clinical and laboratory data as well as medication exposure were collected before and during F/U. Patients were classified into three groups based on change in DEXA results: improved, worsened and no change. Multivariable proportional odds regression model was built to assess independent predictors of change in BMD.

Results

121 patients [60 (49.6%) females, median age 33 years (IQR 23-43), median disease duration 5 years (IQR 0-35), median baseline BMI 22.4 kg/m² (IQR 12.9-39.3), baseline CRP 1.4 ULN (IQR 0.5-4.5), baseline vitamin D 54.2 nmol/L (IQR 40.9-67.5)], were enrolled and followed for a median of 48 (IQR 29-71) months. At baseline, patients with osteoporosis had a lower BMI (18.5 kg/m²) than patients with normal BMD (26 kg/m²) and osteopenia (22.4 kg/m²), p<0.001. During F/U 63%, 59% and 66% of patients were exposed to high dose CS, anti-TNF and thiopurines respectively.At the end of F/U,19 (15.7%) patients had deterioration in BMD status while 78 (64.5%) remained unchanged, and in 24 (19.8%) BMD improved. Baseline vitamin D levels (in nmol/L) were higher in patients with improvement in BMD status at the end of the F/U compared to those with maintained or deterioration in BMD (66, 54.2, 41.2; p=0.001, Figure 1). Active smoking was associated with decline in BMD status (p=0.03). No correlation was found between different types of medication exposure and changes in BMD status. In multivariable analysis, elevated CRP was the only independent variable associated with lower odds of improvement in BMD (OR=0.45 (CI 0.2-1.0), p=0.05,Table 1).

Conclusion

Low BMI, low baseline vitamin D levels, and active smoking were found to be risk factors for low BMD status. Elevated CRP was associated with lack of improvement in BMD during the F/U. No correlation was found between different medications and changes in BMD status.Read more P668 Dashboard-guided anti-TNF induction as an effective proactive strategy in Inflammatory Bowel Disease's treatmentWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Infliximab (IFX) and Adalimumab (ADA) are effective treatments for managing Inflammatory Bowel Disease (IBD) but treatment failure is common. Therapeutic drug monitoring (TDM) of trough serum drug concentrations (C Trough) has been used to optimize treatment induction, mitigate immunogenicity, and ensure appropriate drug exposure. HLA DQA1*05 genotype variants have been identified as predictors of immunogenicity. This study aimed to investigate the impact of dashboard-guided optimized induction dosing strategy on clinical and pharmacokinetics outcomes of anti-TNF, with the goal of analysing the HLA DQA1*05 effect.

Methods

We conducted a retrospective single-centre cohort analysis of IBD patients, Crohn’s disease (CD) and Ulcerative Colitis (UC), who initiated treatment with IFX or ADA between January 2020 and March 2023, using a pharmacokinetic dashboard-guided induction, protocolized with the Pharmacy Department. C Trough measurements were taken at week 2, 6 and 14, first drug intervention based on the model was in week 4. Targeted C Trough levels during induction were set at 10-15 mcg/mL for ADA and > 17 mcg/mL for IFX. Primary objective was to assess clinical remission (CR). Secondary outcomes included treatment failure (TF) and endoscopic remission (ER). We performed a descriptive analysis and generated Kaplan Meier curves to assess drug survival

Results

We enrolled 147 patients, 92 having CD (74 treated with ADA and 18 with IFX) and 55 having UC (36 treated with ADA and 19 CU with IFX). HLA DQA1*05 genotype variant was present in 44,14% of patients. Combined treatment with thiopurine was used in 45,58% and 11,54% had been previously received biologic treatment. After 24 weeks, 91,83% (135/147) of patients achieved CR and 65,81% (77/117) at week 56. ER was observed in 59,84% (76/127) after a year. Anti-TNF drug survival probability was 85% after a year, meanwhile ADA drug survival in UC patients was 75%. A 77,7% of patients were prescribed an accelerated dose in the first year, which was associated with improved drug durability. Only a patient out of 147 developed antibodies to ADA. The HLA DQA1*05 variant was not a statistically significant predictor of adverse treatment or pharmacokinetic outcomes.

Conclusion

Optimizing anti-TNF induction with a Dashboard-guide dosing strategy proves to be a valuable approach to enhance clinical remission and durability rates in IBD patients. The role of HLADQA1*05 variant in immunogenicity appears to be mitigated by the model.Read more P1067 Pan-enteric mucosal inflammation in CD patients treated with vedolizumab assessed by capsule endoscopy– interim results of a prospective observational studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Mucosal healing (MH) is a paramount treatment goal in Crohn’s disease (CD). The vast majority of data pertains to MH in the colon and terminal ileum; nonetheless, proximal small-bowel involvement can be detected in up to 50% of CD patients assessed by capsule endoscopy (CE). Data regarding pan-enteric MH among patients with active CD who were treated with vedolizumab (VDZ) are lacking. We aimed to evaluate the efficacy of VDZ for achieving pan-enteric MH using pan-enteric CE.

Methods

This was a prospective open-label observational study. Patients with CD who have started on VDZ, were included. Patients underwent small-bowel patency-assessment using patency capsule (PC) and were followed by CE (PillCam Crohn’s, Medtronic, USA) before /within 40 days of treatment onset and after 14 and 52 weeks. In patients with exclusive small-bowel involvement, colonic preparation was not performed and colon was not assessed in subsequent CE. Accordingly, Lewis score (LS) and Pan-enteric Pillcam score (PS) were calculated, when available. The primary outcome was pan-enteric MH defined as LS<135 and LS<135 & PS<4 for CE confined to the SB/SB &colon, respectively. The main secondary outcomes were small-bowel MH (LS<135) and colonic-MH (colonic PS<4).

Results

57 patients were recruited, 41 patients were enrolled (median age: 28 [23-45] years, male-44%) and 16 patients were excluded (6- retained PC, 1- technical reason, 2 -did not start VDZ, 7-withdrew consent). Of them, six patients (1- retained PC, 1- multiple strictures, 1- lost to follow-up, 3- clinical flare) and eight patients (4- discontinued VDZ, 2- capsule adverse events, 1- lost to follow-up, 1- clinical flare) were dropped-out before week 14 and week 52, respectively. Pan-enteric MH was observed in 7/39 (18%) patients at week 14, and in 7/30 (23%) patients at week 52 (two patients and 11 patients have not yet reached 14/52-week, respectively). We observed higher rates of both small-bowel MH and colonic-MH during follow-up compared to baseline (Figure 1), and it was consistent with significant improvement at week 14 in both LS (900 [225-900] vs. 450 [0-900], p<0.001) and PS (12 [2-18] vs. 6 [0-14], p=0.001) compared to baseline. Improvement was even more prominent at week 52 (LS- 0 [0-300] PS- 2 [2-6]). No cases of retained capsule were observed during follow-up.

Conclusion

VDZ induces MH in both the small-bowel and the colon among patients with CD, and this effect may persist up to 52 weeks of treatment.Read more P618 Comparison of vedolizumab and ustekinumab treatment persistence in anti-TNF experienced Crohn's Disease patientsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

After the approval of vedolizumab and ustekinumab for the treatment of IBD, discussions continue regarding the prioritization of which drug will be used as the first-line treatment. Despite numerous studies in various indications on this matter, there is still no definitive information. It is known that the success of treatments decreases after the use of Anti-TNF in the first step. In this study, we aimed to compare the drug persistence rates of vedolizumab and ustekinumab used as second-line treatments in Crohn's patients with prior experience with Anti-TNF.

Methods

A total of 171 Anti-TNF experienced Crohn's disease patients were included in this study. Age, gender and other demographical info were recorded from patients electronic medial charts. Drug persistence rates were calculated and compared by using Kaplan-Meier Analysis.

Results

Seventy eight patients who received vedolizumab and 93 patients who received ustekinumab were analyzed. In vedolizumab group, 60% of the patients were male where as in ustekinumab group, 57% of the patients were male. Mean age was 39.4 years in vedolizumab group and 41.2 years in ustekinumab group. All patients were anti-TNF experienced. In addition, 70% of the patients in ustekinumab group was vedolizumab experienced. Concomitant azathioprine use was 56% in vedolizumab group where as 34% in ustekinumab group. Drug persistence was significantly higher in ustekinumab group when compared to vedolizumab group (Figure 1). Interestingly, concomitant azathioprine use did not change drug persistence in ustekinumab group however it increased drug persistence in vedolizumab group.

Conclusion

In anti-TNF experienced Crohn's disease patients, ustekinumab treatment persists more longer than vedolizumab treatment. Ustekinumab persistence was independent from concomitant azathiprine use where as concomitant azathioprine use increases vedolizumab persistence.Read more P630 Identification of specific cell subsets related to treatment response after anti-tumor necrosis factor use in Korean ulcerative colitis patients using single cell RNA sequencing: a preliminary studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The breakdown of the epithelial barrier and mucosal homeostasis plays an important role in the development of ulcerative colitis (UC). Recently, single-cell RNA sequencing (scRNA-seq) has been performed to better understand the gene expression patterns and the characteristics of cells in intestine of UC patients. However, there is a lack of studies focus on Asian UC patients. The aim of this preliminary study was to identify the relevant cellular subsets related to treatment response after anti-tumor necrosis factor (anti-TNF) use in Korean UC patients using scRNA-seq.

Methods

This prospective study was conducted two University hospitals in Korea. We performed scRNA-seq on sigmoid colon tissue samples collected from one healthy control and nine biologic naïve UC patients scheduled to use anti-TNF due to lack of response to conventional therapy. All mucosal biopsies from active moderate to severe UC were collected at baseline (n=9) and at 52 weeks follow-up after anti-TNF use (n=2), at which time treatment response was assessed. Treatment responder was defined as those with sustained clinical remission (a partial Mayo score of ≤2 with no subscore >1 and a rectal bleeding subscore of 0) at 52 weeks.

Results

After processing the scRNA-seq data, 13 clusters were discovered and cell clusters were annotated using colon marker gene. Among nine patients, two patients who underwent response evaluation at 52 weeks after anti-TNF use were treatment responder. The normalized proportion of cluster 1 (stem cell-like cluster) in 52 weeks follow-up tissue samples after anti-TNF use was shown to be decreased significantly (p-value=0.03) from that found in the disease tissue samples. A decrease in the proportion of cell cluster 1 from disease tissue samples’ initial average percentage (30.6%) down to an average of 4.8% in the follow-up tissue samples is quite substantial (p-value=0.03). This decrease signifies a notable change in the composition of this specific cell cluster post-anti-TNF treatment. Moreover, reaching a level close to that of the healthy tissue sample (2.7%) suggests a potential restoration of this cell cluster's proportion towards a healthier state (Figure 1).

Conclusion

In Korean UC patients, this information should be crucial in understanding the impact of anti-TNF treatment on the cellular composition or behavior of this stem cell-like cluster, suggesting a potential effect of anti-TNF treatment on this particular cell population.Read more P1068 Limited long-term efficacy of corticosteroids in microscopic colitis emphasizing the need for advanced therapiesWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Microscopic colitis (MC) is a chronic inflammatory bowel disease, characterized by chronic watery diarrhea, and consisting of 2 subtypes: collagenous (CC) and lymphocytic (LC) colitis. It mainly affects middle-aged adults, although it can occur at any age. The only approved therapy is budesonide, preferably administered in a tapering regimen given the high relapse rates. However, little is known about the long-term natural history of the disease.

Methods

All adult patients diagnosed with MC after clinical and histological assessment at our referral center between 2014 and 2022 were reviewed. Patients with follow-up less than 3 months or in whom no clear description of initiated therapy could be identified by retrospective chart review, were excluded for evaluation of long-term outcomes. Clinical remission was defined according to the Hjortswang criteria as < 3 stools/day or < 1 watery stool/day. Data on relapse rates, subsequent therapies and surgery were collected.

Results

Three-hundred twenty-four patients were included, of whom 198 (CC 38.3%, LC 61.7%) were eligible for long-term assessment (Table 1) with a median follow-up of 3.7 [1.1 – 6.3] years. Median age at diagnosis was 63.4 [51.6-74.7] years. Concomitant diseases occurring in 3% or more included thyroid dysfunction (11.6%), coeliac disease (3.5%) and Parkinson’s disease (5.1%), which numerically was more prevalent in the LC (7.4%) than CC (1.3%) population (p=0.09). A minority of patients had a family predisposition of IBD (5.6%). Spontaneous clinical remission occurred in 37 (18.6%) patients, while 4 (2.0%) patients were treated with 5ASA. Most patients (79.3%) were treated with corticosteroids, resulting in 81.1% clinical remission within 3 months. Eighty-six patients (54.8%) flared upon steroid tapering and/or withdrawal requiring corticotherapy reinitiation, prolongation or dose intensification. Due to steroid resistance or dependency, subsequent treatment options included 5ASA (n=14), cholestyramine (n=11), methotrexate (n=6) and azathioprine (n=8), all with limited effect. More advanced therapies are being used, including anti-TNF agents (n=25), vedolizumab (n=9) and JAK inhibitors (n=8). Eighteen patients (9.2%) are currently on maintenance advanced therapies for MC. Two treatment-refractory patients underwent colectomy.

Conclusion

In this large single-center retrospective analysis, steroids confirmed their first line position to induce clinical remission in MC. However, more than 50% of patients relapsed upon steroid tapering and/or withdrawal, resulting in a substantial need for advanced therapy in this patient population. The long-term efficacy and safety of these advanced IBD therapies in MC should therefore be further investigated.Read more P547 Improved clinical and radiologic healing of Crohn’s perianal fistulas using a novel coordinated care model optimising medical and surgical treatments: A prospective real-world observational studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Despite best standard care, sustained healing rates of Crohn’s perianal fistulas remain low. A novel coordinated multi-disciplinary care model optimising medical and surgical treatment was established with the aim to improve fistula healing rates.

Methods

A prospective real-world observational study evaluated the efficacy of this new care model in adults with Crohn’s perianal fistulas. Patients seen through the new care model were sequentially invited to participate, between March 2021 to April 2022, and included irrespective of disease activity, duration, or prior treatments. Three dynamic stages of care were directed towards patients’ clinical disease activity: stage A, active disease, focused on medical and surgical treatment optimisation; stage B, optimised treatments with a seton in situ, focused on definitive surgical management; and stage C, healed disease, focused on treatment maintenance. Endpoints included: [1] clinical fistula healing after a minimum of 12 months follow-up; [2] changes in radiologic disease activity and fibrosis on serial magnetic resonance imaging; and [3] proportion of patients requiring treatment optimisation.

Results

Sixty patients were included. At baseline, 47% were in stage A, 5% stage B, and 48% stage C. Median age was 40 years (IQR: 32-49), 52% were male, median perianal disease duration was 9 years (IQR: 2-16), and median attendance through the preexisting service was 6 years (IQR: 3-9). After a median of 22 months follow-up (IQR: 16-25), 83% had clinical healing which was significantly higher than baseline rates at study inclusion (83 vs 48%, p<0.001). For patients in stage A at baseline, 68% achieved clinical healing with estimated clinical healing rates of 39% (95%CI: 24-60) and 85% (95%CI: 64-97) at 1 and 2 years, respectively. This paralleled a significant reduction in radiologic disease activity and increase in radiologic fibrosis, with radiologic remission observed in 51% and radiologic response in 47% overall (Table 1). Patients who achieved clinical healing had significantly less radiologic disease activity and greater fibrosis compared to patients with non-healing fistulas. Overall, 53% had biologic dose escalation and 10% switched to an alternative biologic agent with the new care model. Thirty-seven percent underwent a median of two perianal surgical interventions (IQR: 1-3), 15% had closure or ablative techniques performed, and 15% had seton removal only.

Conclusion

A novel coordinated multi-disciplinary care model optimising medical and surgical treatments resulted in high rates of clinical healing and improved radiologic disease activity and fibrosis of Crohn’s perianal fistulas. Controlled-matched studies evaluating treatment optimisation are needed.Read more P642 Effect of prior vedolizumab treatment on ustekinumab time-on-treatment in Crohn’s disease: a targeted literature review and statistical analysesWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Ustekinumab, vedolizumab and anti-TNFα therapies are all biologics that are licensed to treat moderate-to-severe Crohn’s disease (CD). With many new therapies available in moderate-to-severe CD, the question of the optimal sequence in which to administer biologics becomes more pertinent. In this study, we aimed to determine if ustekinumab treatment effectiveness was affected by prior vedolizumab treatment in patients with CD.

Methods

We conducted a targeted literature review to identify evidence for ustekinumab effectiveness both with and without prior vedolizumab treatment. The population of interest was patients with moderate-to-severe CD treated with prior anti-TNFα. Studies were required to report single lines of treatment (e.g., specify second-line or state after one anti-TNF). Ustekinumab time-on-treatment (ToT) Kaplan-Meier (KM) data were recreated using digitisation methods and grouped into 2 categories (based on prior vedolizumab exposure) for subsequent statistical analysis. We compared ToT over a 34-month period (maximum follow-up period observed across all studies). A log-rank test was performed to identify whether there was a statistically significant difference in ToT between to the two groups across the follow-up period and Cox regression modelling was used to identify the direction of trends through estimation of a hazard ratio (HR).

Results

We identified 4 studies (n=495) that reported ustekinumab ToT after 1 anti-TNFα and 2 studies (n=69) that reported ustekinumab ToT after 1 anti-TNFα and vedolizumab. Based on the KM curves pooled across studies, the analysis showed the probability of remaining on treatment for ustekinumab following 1 anti-TNFα and vedolizumab was higher than following just 1 anti-TNFα. The log-rank test demonstrated a statistically significant difference between these two groups (HR=0.523; 95% CI: [0.310, 0.883]; log-rank p-value=0.014).We identified a further 3 studies (n=1,017) that reported ustekinumab ToT after ≥1 anti-TNFα, and a further 2 studies (n=441) that reported ustekinumab ToT after ≥1 anti-TNFα and vedolizumab. Although these studies stated second line treatment of ustekinumab, some patients had received ≥2 prior anti-TNFα, which may have biased ToT results. There was no statistically significant difference in ToT for ustekinumab following ≥1 anti-TNFα and vedolizumab compared to following ≥1 anti-TNFα (HR=1.167; 95% Cl: [0.971, 1.1404]; log-rank p-value=0.098)

Conclusion

Our research shows that prior vedolizumab treatment does not negatively impact ustekinumab ToT in CD, which may have implications for the sequencing of biologics in moderate-to-severe CD and should be considered when deciding on the most appropriate treatment for patients.Read more P580 Iron deficiency anaemia and quality of life in Inflammatory Bowel Disease: Prospective cohort study of ferric derisomaltose on quality of life and work productivity in patients with IBDWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Iron-deficiency anaemia is a frequent complication of inflammatory bowel disease (IBD), affecting approximately 10% of patients at any one time. Quality of life scores in patients with IBD and anaemia are similar to those reported in malignancy. ECCO guidelines recommend assessment and treatment of iron deficiency anaemia, with a goal of normalising haemoglobin and iron stores.

Methods

We conducted a prospective observational cohort study of patients with IBD being treated for iron deficiency anaemia with ferric derisomaltose. Patients were included who were anaemic as per World Health Organisation criteria with a ferritin of <30 µg/L and/or a transferrin saturation of <18%. Variables collected included haematological parameters, the 12-item Short Form survey (SF-12) as a generic health-related quality of life measure, the Work Productivity and Activity Impairment (WPAI) questionnaire and the Short Inflammatory Bowel Disease Questionnaire (SIBDQ) as a disease-specific quality of life measure. Patients were assessed at baseline, 12 weeks and 52 weeks. We present here the outcomes at week 12. Comparative statistics have been conducted using Wilcoxon signed rank tests and Pearson’s correlation coefficient.

Results

We recruited 124 patients given between 700 and 1900 mg of ferric derisomaltose, each as a single infusion. Of these, 60% (74/124) were female and the median age was 43 years (IQR 31 – 58). Just under half (46%) of participants had Crohn’s disease, the remainder had ulcerative colitis (49%) or IBD unclassified (5%). Median (IQR) baseline haemoglobin was 114 (109 – 123) g/L in men and 110 (104 – 116) g/L in women. By week 12, haemoglobin, ferritin, SIBDQ, the WPAI, and both the mental and physical component scores of the SF-12 had improved significantly (all p values <0.0001; see Figure 1). Change in the physical score of SF-12 correlated positively with change in haemoglobin (r = 0.38, p<0.0001), while the change in WPAI correlated negatively with change in haemoglobin (r = -0.30, p=0.013).

Conclusion

Treatment with intravenous ferric derisomaltose in patients with iron deficiency anaemia and IBD was associated with significant improvements in haematological, work productivity, and quality of life parameters.Figure 1Box and whisker plot showing haemoglobin, ferritin, Short Inflammatory Bowel Disease Questionnaire (SIBDQ ), Work Productivity and Activity Impairment (WPAI) and Short Form-12 (SF-12) at baseline and week 12; boxes show median and interquartile rangeRead more P653 Impact of ozanimod on type III collagen turnover biomarkers and the association with ozanimod efficacy in patients with moderately to severely active ulcerative colitis: Results from the phase 3 True North studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Ozanimod (OZA), an oral sphingosine 1-phosphate 1 and 5 receptor modulator, was efficacious and well tolerated for up to 52 wk in adults with moderately to severely active ulcerative colitis (UC) in the phase 3 True North study (NCT02435992). Alterations in the degradation and formation of type III collagens, a major component of the extracellular matrix of the intestinal wall, may play a role in the pathogenesis of UC. The objective of this analysis was to assess the effect of OZA on type III collagen levels and turnover and the association of type III collagen levels with OZA efficacy in the True North study.

Methods

In a 10-wk induction period, patients (pts) in Cohort 1 were randomised to receive oral OZA 0.92 mg (n=429) or placebo (PBO) once daily (n=216) in a double-blind manner and pts in Cohort 2 received open-label OZA at the same daily dose (n=367). At Week (W) 10, pts with a clinical response to OZA in either cohort underwent rerandomisation to receive double-blind OZA (n=457) or PBO (n=69) for 52 wk (maintenance period). Type III collagen biomarker plasma levels were assessed at baseline (BL), W10, and W52. Associations between type III collagen levels and disease activity or efficacy outcomes were assessed using Spearman’s rho correlation and logistic regression, respectively.

Results

At W10, treatment with OZA resulted in significantly decreased collagen type III degradation (C3M) (Figure 1A), increased collagen formation (PRO-C3) (Figure 1B), and decreased collagen turnover (C3M/PRO-C3) (Figure 1C). Significant reductions in C3M and C3M/PRO-C3 were observed in pts with vs without a clinical response in all treatment groups (P<0.001), while significant increases in PRO-C3 were observed in responders vs nonresponders (P<0.001; Cohort 1 only). The significantly greater reductions in C3M/PRO-C3 were observed with OZA vs PBO regardless of prior exposure to biologics or tumour necrosis factor inhibitors. Changes in C3M, PRO-C3, and C3M/PRO-C3 levels from BL to W10 were significantly correlated with improvements in all disease activity scores from BL to W10 with OZA and PBO. These changes in C3M, PRO-C3, and C3M/PRO-C3 continued through W52 (Figure 1D–F) in pts who continued OZA. At W52, significantly greater reductions in C3M/PRO-C3 ratios were observed in responders vs non-responders in pts who continued OZA.

Conclusion

These data show that pts with UC who were treated with OZA had decreased plasma type III collagen degradation and turnover, with greater reductions in OZA responders than nonresponders. This further supports the evaluation of collagen type III fragments as potential markers of treatment response in pts with UC.Read more P1069 One-year clinical outcomes of switching to subcutaneous infliximab in patients with inflammatory bowel disease on maintenance of intravenous infliximab therapy with or without remission: A multicentre cohort studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

An elective switching to the subcutaneous (SC) formulation of infliximab (IFX) has shown effectiveness and safety in patients with inflammatory bowel disease (IBD) on intravenous (IV) IFX maintenance therapy. However, data on long-term outcomes in patients not in clinical remission during maintenance therapy is limited. This study aims to evaluate the long-term outcomes of SC switching in patients who were in clinical remission and not in remission during IV IFX maintenance therapy.

Methods

This retrospective multicentre study was conducted from January 2021 to October 2023. Clinical remission was defined as Crohn’s Disease Activity Index (CDAI) <150 for Crohn’s disease (CD) and partial Mayo score <2 for ulcerative colitis. Biological remission was defined as faecal calprotectin (FC) <250 µg/g and C-reactive protein (CRP) <0.5 mg/dL. The primary outcome measure was 1-year treatment persistence of SC IFX.

Results

Among 127 patients included in the study, 80 (62.9%) had CD, and 47 (37.1%) had UC. At the time of switching, 90 patients (70.9 %) were in clinical remission; whereas, 37 (29.1 %) were in a non-remission state. The treatment persistence rate at 1 year was high at 92.9%. Treatment persistence rates between the clinical remission and non-remission groups did not differ significantly (94.4% vs. 89.2%, p=0.287). In both groups, IFX pharmacokinetics and biomarkers between baseline and 12 months (p<0.01) significantly improved. The median infliximab levels increased from a baseline of 3.3 µg/mL (interquartile range [IQR] 1.3–5.1) to 14.4 µg/mL (IQR 9.4–23.0, p<0.001) at 12 months. Disease activity index was stable in the remission group, and decreased in the non-remission group (partial Mayo score, p<0.001; CDAI, p=0.063). At the one-year follow-up, clinical remission and biological remission were achieved in 86.6% and 60.6%, respectively, an increase from baseline (70.9% and 48.0%, respectively). Biologics exposure before IFX was the only significant variable associated with treatment persistence (odds ratio 5.138, 95% confidence interval 1.150–22.951, p=0.032). The concomitant use of immunomodulators was not associated. The incidence of IFX-related adverse events was 14.2%, with only three patients discontinuing treatment.

Conclusion

Switching to SC IFX from IV IFX maintenance therapy demonstrated high treatment persistence and favourable safety profiles, irrespective of remission status at the time of switching. Patients in both remission or non-remission states showed significant improvement in pharmacokinetics and biomarkers, and/or stable disease activity indices.Read more P581 Age-related patterns in biological therapy use and surgery among patients with IBD: Insights from the Belgian PANTHER cohortWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Inflammatory bowel diseases (IBD) are predominantly diagnosed during the second to third life decade. However, the disease may manifest itself at any age and current understanding of differences in clinical presentation and therapy use among age groups is still limited. We aimed to analyse age-related patterns in biological and surgical treatment among patients with IBD.

Methods

This study utilized data from the PANTHER cohort, a prospective Belgian inception cohort including 473 adult patients with IBD from 3 Belgian referral centres. Patient inclusion took place from 2015 to 2023. Patients were categorized into groups based on the age at diagnosis: 'young adult-onset' (18-39 years), 'adult-onset' (40-59 years), and ‘elderly-onset’ (³60 years). Baseline characteristics and treatments were analysed using Chi square, Mann-Whitney U tests, log-rank tests and/or Cox regression in SPSS.

Results

Baseline characteristics are shown in Table 1. No significant differences were found between age groups in terms of IBD diagnosis, gender, median follow-up duration, and smoking status.Use of biologics differed significantly across age groups with highest uptake in young-adult onset patients (65.8%, P<0.001). Significant differences were found in selection of first biologic with vedolizumab as most frequently selected option in the elderly compared to anti-TNF in the youngest age group (P=0.002). Time to initiation of a biological was earlier in the youngest cohort (P=0.002, Figure 1). Cox regression analysis revealed that older age at diagnosis (HR 0.987, 95%CI [0.98;0.996], P=0.006), UC (HR 0.495, 95%CI [0.50;0.39], P<0.001) and centre of follow-up (Brussels vs Leuven: HR 0.663, 95%CI [0.4;1], P=0.048) were associated with a lower risk of biological initiation. When analysing CD separately, independent risk factors associated with biological use were perianal disease (HR 2.26, 95%CI [1.6;3.2], P<0.001), L3 (HR 1.85, 95%CI [1.3;2.6], P<0.001,) and L4 (HR 12.7, 95%CI [1.6;98.7], P=0.015,) location (compared to L1 location). In UC patients, E2 (HR 7.9, 95%CI [2.8;22.4], P<0.001) and E3 (HR 6.9, 95%CI [2.4;19.3], P<0.001) were related to earlier use of biologics.During follow-up, 19% of CD and 5.1% of UC patients required IBD-related surgery. Univariate analysis showed a higher need for surgery in younger patients (P=0.042), however, this difference was no longer significant when analysing CD (P=0.272) and UC (P=0.09) patients as separate groups.

Conclusion

Analysis of the PANTHER Biobank reveals significant age-related variation in the administration of biological therapies among IBD patients.Read more P654 Assessing patient-perceived burden of disease in Ulcerative Colitis: a novel scoring approach in a real-world Australasian cohortWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The prevalence and burden of inflammatory bowel disease (IBD) including ulcerative colitis (UC) is rising globally. We present a novel score to evaluate patient-perceived burden of disease (PPBoD) in UC, which we applied to a large real-world Australasian cohort.

Methods

The Crohn’s Colitis Care (CCCare) Clinical Registry was interrogated in October 2023. Adults with ulcerative colitis (UC) across 17 IBD centres who had an outpatient encounter in the last 14 months were included. A novel PPBoD score was created for UC, including patient-reported components from the Mayo Score (stool frequency and rectal bleeding) as well as general wellbeing, urgency and nocturnal bowel motions. The PPBoD was calculated as detailed in Figure 1. A score of 0 was defined as no PPBoD, 1-2 as mild, 3-4 as moderate and ≥ 5 as significant PPBoD. The correlation between PPBoD and demographics, disease and treatment factors was assessed.

Results

A total of 2507 people with UC (41.0%) were identified with a clinical assessment in the last 14 months; 92.2% of whom (n = 2311) had adequate data to calculate the PPBoD. In this cohort > 80% had either no or only mild PPBoD (Table 1). Age, gender and BMI did not vary significantly between PPBoD categories. People with lower PPBoD were more likely to be on advanced therapies and had lower rates of steroid use. There was no significant difference in the use of immunomodulators and aminosalicylates across PPBoD categories. The cohort was geographically dispersed across Australia (n = 1786, 77.3%) and New Zealand (n = 525, 22.7%). There was significantly higher PPBoD in New Zealand, but notably those in New Zealand were less likely to be on advanced therapies (p < 0.001). In the subset of 780 people (33.8%) who had a recent faecal calprotectin, people with no PPBoD were more likely to have biochemical remission (faecal calprotectin < 100 μg/g). Data were available for endoscopic and radiological remission in 654 people (28.3%); those with no PPBoD were more likely to be in remission (p < 0.001). Over 98% of people with no PPBoD had no days out of role due to disease, whereas those with higher PPBoD had more days out of role (Table 1).

Conclusion

We present a novel consumer-focused score to evaluate PPBoD in UC. Within this geographically dispersed cohort, the majority had either no or mild PPBoD. Advanced therapies were associated with lower PPBoD, and their health economic value could be evaluated using this tool. Further studies are required to validate this novel score to assess BoD in UC.Read more P874 Impact of immunogenicity on clinical outcomes in patients with Crohn’s disease receiving maintenance treatment with subcutaneous infliximab: A post hoc analysis of the LIBERTY-CD studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The Phase 3 LIBERTY-CD study showed that subcutaneous (SC) CT-P13 was more effective than placebo as maintenance therapy and was well tolerated in patients with moderate-to-severe active Crohn’s disease (CD) who responded to intravenous CT-P13 induction. This post hoc analysis aimed to evaluate the impact of anti-drug antibodies (ADAs) on drug levels and efficacy in patients treated with SC CT-P13.

Methods

This post hoc analysis of the randomised, parallel-group, placebo-controlled LIBERTY-CD study (NCT03945019) evaluated the impact of ADAs on clinical outcomes in patients with CD who received SC CT-P13 maintenance treatment. ADAs were measured using a new generation, highly sensitive, drug tolerant assay. The following clinical outcomes were evaluated at Week (W) 54 according to ADA occurrence: proportions of patients achieving the co-primary endpoints of clinical remission and endoscopic response, mean Crohn’s Disease Activity Index (CDAI) score and mean Simple Endoscopic Score for CD (SES-CD). Sensitivity analyses were conducted using multiple imputation methods. Discontinuation rates up to W54 according to ADA occurrence were examined by survival analysis. Trough serum infliximab concentrations at W54 were assessed according to ADA occurrence.

Results

The analysis included the 231 patients (ADA-positive, n=150; ADA-negative, n=81) who received at least one dose of SC CT-P13 as maintenance treatment. There were no statistically significant differences in clinical outcomes at W54 between the ADA-positive and ADA-negative patients in each group across imputation methods (Table). Based on observed data at W54 in the ADA-negative vs. ADA-positive groups, 79.7% vs. 69.5% of patients achieved clinical remission (p=0.1335) and 65.2% vs. 57.5% had an endoscopic response (p=0.3595); mean CDAI score was 83.6 vs. 86.0 (p=0.8342), and mean SES-CD was 3.37 vs. 3.94 (p=0.3796). In a survival analysis, discontinuation rates were comparable between the ADA-positive and ADA-negative groups (log-rank p=0.95; Figure). Mean trough serum infliximab concentrations at W54 were significantly lower in the ADA-positive group than in the ADA-negative group (11.7 vs. 19.3 μg/mL; p<0.00001), but in both groups, they exceeded the historical therapeutic target concentration of 5 μg/mL.

Conclusion

Despite affecting drug levels, ADA status appeared to have no significant impact on W54 clinical outcomes or discontinuation rates. These findings could be explained by the relatively high trough serum infliximab concentrations achieved by ADA-positive patients. Further studies are warranted focusing on long-term effects of immunogenicity and optimal drug concentrations in patients receiving maintenance therapy with SC CT-P13.Read more P888 Effectiveness and safety of Adalimumab Biosimilars in Bio-naive patients with Inflammatory Bowel Disease: The Galician experienceWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Biological drugs has revolutionized the management of inflammatory bowel disease (IBD). However, its use has led to a significant increase in cost that has strained health systems. Biosimilars will reduce cost related to treatment, allowing access to a greater proportion of patients. However, data on the efficacy and safety of the various ADA biosimilars in IBD patients "naive" to biologics remains scarce.

Methods

We performed an observational cohort study in 9 hospitals in Galicia. All patients with IBD naïve to biologics who started ADA biosimilar between November 2018 and January 2022 for control of their disease were enrolled. The primary endpoints were efficacy defined as clinical remission at week 8 and long term efficacy defined as persistence on drug treatment at the end of follow-up. The other co-primary endpoint was to determine the incidence of adverse events that lead to suspension or discontinuation of the drug or hospitalization of the patient

Results

384 patients (95 CU; 283 CD) with a median age of 47 (34-60) years and a median disease duration of 3.4 (0.8-10.0) years before starting treatment were included. After induction (at 8 weeks) 63.7 % of patients were in clinical remission and 85.0 % achieved clinical response. At this time of follow-up, 14 patients (4.9 %) discontinued treatment mainly due to primary non-response (PNR) (57.1 %) and adverse events (42.9 %). In total, 112 patients discontinued treatment during follow-up (Figure 1). The main reasons for stopping therapy were adverse events (32.1 %), PNR (30.4 %) and secondary loss of response (37.5 %). Clinical remission was maintained in 60.9 % of patients, after a median follow-up of 18 (12-24) months. Drug persistence shown by Kaplan-Meier survival curves were significantly higher in CD patients (p = 0.007) and in the group of patients treated with immunomodulators (IMM) (p = 0.001). Additionally, the rates of clinical remission and clinical response were higher in CD patients and in IMM-treated patients (Table 1). Adalimumab levels were also measured during follow-up, showing a median of 11 (6.8-14) μg/mL. Significantly, drug persistence was higher in patients with adalimumab levels ≥ 7 μg/mL at week 4 (p < 0.001). Regarding treatment safety in this population, adverse events that required treatment suspension or discontinuation were reported in 36 patients.

Conclusion

Adalimumab biosimilars in usual clinical practice are safe and effective in inducing and maintaining remission in Galician patients with IBD. Drug persistence was significantly higher in patients with CD, treated with IMM and with post-induction ADA levels ≥ 7 μg/mL.Read more P687 Ozanimod as a once-daily oral therapy for Japanese patients with ulcerative colitis: results from the induction period of a Phase 2/3 study (J-True North)Wed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Ozanimod is an oral, small molecule sphingosine 1-phosphate (S1P) receptor modulator that selectively targets the S1P1 and S1P5 receptor subtypes. Ozanimod is approved in multiple countries outside Japan for the treatment of moderately to severely active ulcerative colitis (UC) and/or relapsing forms of multiple sclerosis. We herein report the efficacy and safety results during the induction period of J-True North, a multi-centre, randomised, double-blind, placebo-controlled clinical Phase 2/3 study consisting of a 12-week induction period, followed by a 40-week maintenance period and an open-label extension period in Japanese patients with moderately to severely active UC.

Methods

Japanese male and female UC patients aged 18 to 75 years with moderately to severely active UC (defined as Mayo score of 6 to 12, with endoscopic subscore ≥2, rectal bleeding score (RBS) ≥1, and stool frequency score ≥1) were randomised in a 1:1:1 ratio to receive either 0.46 mg or 0.92 mg ozanimod, or placebo capsules orally once daily. All patients had received prior treatment with aminosalicylates or corticosteroids. The primary endpoint was clinical response at Week 12 (defined as a reduction from baseline in the complete Mayo score of ≥ 3 points and ≥ 30%, and a reduction from baseline in the RBS of ≥ 1 point or an absolute RBS of ≤ 1 point), and key secondary endpoints were clinical remission, clinical response, endoscopic improvement, mucosal healing and safety at Week 12 and 52.

Results

Patients were randomised to the ozanimod 0.46 mg group (n=68), 0.92 mg group (n=65), and the placebo group (n=65). At baseline, 36.4% of patients were female, mean age was 42.6 y and mean complete Mayo score was 8.4. The clinical response rate at Week 12 was 52.9%, 61.5%, and 32.3% in the ozanimod 0.46 mg, 0.92 mg, and placebo groups, respectively, demonstrating a statistically significant improvement of ozanimod vs placebo (Figure 1). Similarly, higher improvement rates were observed in all key secondary clinical and endoscopic endpoints in the ozanimod groups compared with the placebo group at Week 12. Frequent adverse events (AEs) observed in the induction period were nasopharyngitis, headache, et.al. (Table 1). AEs observed in the study were similar to those in the global phase 3 True North study with 0.92 mg ozanimod, and there were no new safety signals with ozanimod in the J-True North study.

Conclusion

Ozanimod as a once-daily oral therapy was effective as induction therapy for Japanese patients with moderately to severely active UC, and the safety profile was consistent with the results of previous studies.Figure 1Table 1Read more P582 Combination of granulocyte–monocyte apheresis and ustekinumab: multicentre and retrospective studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Granulocyte–monocyte apheresis (GMA) selectively removes activated leukocytes and immune mediators, and it has shown to be safe and effective in treating ulcerative colitis (UC). Previous reports have also described its combination with biologics, mainly with anti-TNF.

Methods

The aim of our study was to evaluate the clinical efficacy and safety of combining GMA after primary non-response (PNR) or loss of response (LOR) to ustekinumab (UST) in patients with UC. A retrospective, multicentric study was performed in 12 IBD Units, including all patients with refractory UC who received combined GMA plus UST. The number of GMA sessions, its frequency, filtered blood volume and time of each session were compiled, along with the clinical data. Efficacy was assessed 1 and 6 months after finishing the GMA by partial Mayo score, CRP and faecal calprotectin. Data regarding UST intensification, need for new immunomodulators/biologics and surgery were also compiled. Descriptive statistics and non-parametric tests were used in the statistical analysis.

Results

Nineteen patients were included (15 UC, 2 Crohn’s disease, 2 unclassified IBD; median age 48 years (IQR, 36-63); 68% male). At baseline, 78% were receiving steroids and 23% immunomodulators. Most patients (89%) had prior exposure to anti-TNF agents and 53% to vedolizumab. Baseline Mayo score was 6.5 (IQR, 5-7), with a median CRP of 9 mg/L (IQR, 4.8-20.8) and faecal calprotectin 1,612 mg/kg (IQR, 873-4,152). GMA was started mostly after PNR in 83%, the median number of GMA sessions was 16 (IQR, 11-27) and 50% of patients started maintenance GMA. Partial Mayo score significantly decreased 6 months after the last GMA session (p=0.019). During follow-up, 27% started a new biologic therapy and 13% required surgery. 64% of patients under steroids at baseline were able to stop them. Adverse events were reported in 5% of patients.

Conclusion

GMA can safely recapture the response to UST in refractory patients after PNR or LOR to this drug.Read more P898 Hesitancy on COVID-19 Vaccination Among Patients with Inflammatory Bowel Disease in South Korea: A Multicenter SurveyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Despite many clinicians recommending COVID-19 vaccination to patients with inflammatory bowel disease (IBD) due to high susceptibility, COVID-19 vaccine hesitancy was a worldwide phenomenon. Although previous studies to identify the cause of this vaccine hesitancy are being published, few studies have been done on COVID-19 vaccine hesitancy among IBD patients in South Korea. Therefore, the aim of our study was to find out the factors that cause vaccine hesitancy in patients with IBD in South Korea.

Methods

An electronic survey was conducted on IBD patients with receiving treatment at 5 hospitals in Daejeon-Chungchung province from September 2022 to January 2023. Basal characteristics, factors for vaccine hesitancy was evaluated. Survey was designed as a voluntary and anonymous manner.

Results

A total of 272 patients participated in the survey, of which 119 patients had Crohn’s disease (CD) and 153 patients had ulcerative colitis (UC). COVID-19 vaccine hesitancy tended to decrease with age (r=-0.158, p=0.011). In IBD medication, comparing patient group using 5-aminosalisylic acid and using biologics, hesitancy was higher in the biologics group (p=0.017). Hesitancy was high in patients who preferred Moderna (p=0.049). 102 patients answered that the cause of vaccine hesitancy was concern about safety of vaccines, with the largest share.

Conclusion

The study found that the main reason of hesitancy was concerns about the safety of the vaccine. Hesitancy tended to decrease with age and was higher in patients using biologics. This study may be helpful to educate patients with more specific targets to prepare for the current COVID-19 as well as other possible future pandemics.Read more P688 Comparative Effectiveness of Ustekinumab Versus Vedolizumab in Treating Crohn’s Disease After Failure of Anti-TNF Agents: Real-World EvidenceWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Despite effective anti-TNF agents in treating Crohn’s disease (CD), some recipients experience primary or secondary non-responses, requiring alternative options. Ustekinumab and vedolizumab have not been compared in randomized controlled trials (RCTs) among CD population. Thus, we used real-world data to compare ustekinumab and vedolizumab at 12 weeks after failure of TNF inhibitors.

Methods

A retrospective study was conducted at a tertiary hospital in Dammam, Saudi Arabia. Patients with CD who had not responded to anti-TNF agents and had never been exposed to vedolizumab and/or ustekinumab were included. Children ≤ 18 years of age, naïve CD patients, CD patients using only anti-TNF agents, and patients who lost follow up were excluded. Primary endpoints were clinical improvements, which were measured by Harvey-Bradshaw Index scores at 12 weeks, and clinical remission, which was measured as an ordinal outcome. Remission clinically, biochemically, and endoscopically; clinical response; cumulative steroid dose; and corticosteroid-free days were secondary endpoints. Using probabilistic Bayesian models and proportional odds models, we analyzed outcomes, and the posterior distribution was used to calculate the probability of treatment effectiveness. A national institutional review board approved the study.

Results

Five hundred forty-six patients received biological agents for inflammatory bowel disease, of whom 101 received biological agents for CD; 71 patients received ustekinumab, and 30 patients received vedolizumab. The baseline characteristics were similar except for perianal disease, which was frequently reported in ustekinumab arm (P = 0.006). Most of the patients were male (54.5%), with a median age of 32 (IQR: 26.0-38.0). Most patients (51.5%) had stricturing disease in the Ileocolonic site (70.3%). For ustekinumab, the median HBI score was 5 (IQR: 3.0 -8.0) whereas for vedolizumab, it was 5 (IQR: 4.0 -7.0). In table 1, a Bayesian multivariable proportional odds model revealed a 40% reduction in median HBI scores at 12 weeks favoring ustekinumab, with an aOR of 0.60 (95% CI: 0.25 to 1.31) and a probability of effectiveness of 75% for ustekinumab. At 12 weeks, the ordinal outcome scale was 39% lower for ustekinumab arm, with an aOR of 0.61 (95% CI: 0.26 to 1.35) and a probability of effectiveness of 73% for ustekinumab arm. Secondary endpoints showed favorable results for ustekinumab reaching up to a 90% probability of effectiveness.

Conclusion

Among CD patients who failed anti-TNF therapies, ustekinumab was more effective than vedolizumab. To validate these results and determine these treatments’ relative efficacy in managing CD, further investigations, including prospective studies and RCTs, are essential.Read more P583 Infliximab Monitoring in Crohn's Disease and Development of Neural Networks Using Clinical Variables to Predict Disease Activity and ImmunogenicityWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Infliximab (IFX) is a biological drug that inhibits the action of tumor necrosis factor-alpha (TNFα), a pro-inflammatory cytokine enrolled in the pathogenesis of Crohn's disease (CD). Trough-level drug monitoring (TDM) has been increasingly used in clinical practice to optimize biological therapy and improve precision medicine. Therefore, this study aimed to analyze the serum level of IFX and antidrug antibodies (ADA) in active and in remission CD patients and develop prediction models via neural networks using a combination of clinical variables.

Methods

Seventy-five CD patients who underwent IFX therapy in the maintenance phase were included. Disease activity was defined by endoscopic and/or radiological criteria, comprising remission (CDR) and active (CDA) groups. Serum IFX levels were measured by ELISA (Promonitor ^®) and rapid lateral flow test (Quantum-Blue^®). ADA was measured using ELISA (Promonitor ^®). For statistical analysis, a non-parametric test was used, with adopted p≤0.05. To create a prediction model, four sets of neural networks were constructed for the following output variables: remission/activity, presence or not of ADA, therapeutic level according to ELISA, and therapeutic level according to the lateral flow test. The neural networks and ROC curves were designed using the Keras package in Python software. The study was approved by the Research Ethics Committee.

Results

No differences were observed in the IFX level when comparing the CDA and CDR groups in both tests (p> 0.05). There was no statistical difference in IFX levels according to the use of immunosuppressants (IMS) (p>0.05). ADA levels > 5AU/mL were detected in only 11 (14.6%) patients. All patients with positive ADA had infratherapeutic IFX levels in both tests, and 72.7% were on combination therapy with IMS. Of the 4 neural networks developed, two, whose output variables were “remission/activity” and “presence or not of ADA,” showed excellent performance, with AUC ranging from 82% to 92% and 100%, respectively.

Conclusion

The introduction of IFX monitoring may allow more individualized and precise therapeutic management. Regarding the performance characteristics of the neural networks, an AUC >80% was evident in two of them. Through clinical and non-invasive laboratory variables, disease activity was determined. Furthermore, the finding of combinations of variables that determine the ADA level, and at the same time not having demonstrated good models for IFX serum level measurement, means that the latter continues to be necessary for clinical practice. Otherwise, ADA levels, which indicate immunogenicity, can be predicted by non-invasive clinical variables.Read more P713 The introduction of an intestinal ultrasound service significantly reduces diagnostic endoscopy usage in an Inflammatory Bowel Disease service – The SCOPELESS StudyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Endoscopic assessment is the gold standard for monitoring of inflammatory bowel disease (IBD) activity. Intestinal ultrasound (IUS) is increasingly utilised as a non-invasive, alternative disease monitoring strategy. Our study aim was to quantify and compare endoscopy usage for evaluation of IBD disease activity before and after the introduction of an IUS service.

Methods

A retrospective single-centre study was performed. Total numbers of lower GI endoscopies (ileocolonoscopy or flexible sigmoidoscopy) performed for luminal Crohn’s disease (CD) or ulcerative colitis (UC) disease evaluation were collected across two 5-year time periods: the pre-IUS era (2010-2014) and the IUS era (2015-2019). Endoscopies for dysplasia surveillance were excluded. The primary endpoint was a comparison of the cumulative number of endoscopies for IBD disease activity evaluation annually relative to the annual number of patients seen in clinic in the pre-IUS and IUS eras. Secondary endpoints included evaluating the number of endoscopies by individual year within each time period, endoscopies according to diagnosis (CD vs. UC), and the number of IUS performed within the IUS era. Categorical variables were compared using a Chi-squared test. A p value <0.05 was considered statistically significant.

Results

The number of endoscopies performed for IBD disease evaluation decreased from 576 in the pre-IUS era to 474 in the IUS era despite an increase in cumulative annual patient reviews (1985 vs. 3337 patient reviews, respectively). The annual number of endoscopies for disease evaluation per patient in the pre-IUS and IUS eras is illustrated in Figure 1. The proportion of cumulative annual endoscopies relative to patients reviewed across the 5-years reduced from 29 per 100 patients in the pre-IUS era to 14 per 100 patients in the IUS era (OR 2.47, 95% CI 2.15-2.84; p < 0.001). There was a reduction in total endoscopies for CD evaluation from 325 to 264 and UC evaluation from 251 to 210. The proportion of endoscopies performed for CD vs. UC was unchanged between the two eras (56.4% vs. 55.7%; p = 0.81). In the IUS era, a total of 3319 IUS were performed (2673 CD, 646 UC). This included 1467 IUS for assessment of suspected activity (44 per 100 patients/year) and 1852 IUS for objective confirmation of clinical remission (55 per 100 patients/year).

Conclusion

In the 5 years following introduction of an IUS service, the number of endoscopies performed for evaluation of IBD activity per patient was halved. IUS was performed for both assessment of disease activity and objective confirmation of clinical remission. The potential workflow and cost savings of reduced endoscopies for IBD disease activity evaluation are significant.Read more P913 Intestinal Ultrasound in paediatric Crohn’s disease reduces the need for subsequent ileocolonoscopyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Approximately 20% of patients with Crohn's disease (CD) are diagnosed during childhood (pCD). At diagnosis, the vast majority (87%) of patients with pCD demonstrate severe disease activity.(1) Severe disease activity necessitates intensive treatment followed by frequent blood tests, faecal calprotectin tests, and endoscopic procedures. Ileocolonoscopy is burdensome for the patient, as bowel preparation and general anaesthesia are needed, and furthermore, the procedure is costly. In recent European guidelines for pCD management, Intestinal Ultrasound (IUS) is recommended for clinical follow-up. Our objective was to investigate the extent to which patients with pCD underwent subsequent endoscopy after having IUS performed during their follow-up regimen.

Methods

We conducted a retrospective descriptive cohort study, encompassing all patients with pCD at a referral center (Department of Paediatric and Adolescence Medicine, Copenhagen University Hospital, Amager and Hvidovre) who had undergone a minimum of one ultrasound examination over a 2.5-year period (May 1, 2021, to November 1, 2023).

Results

A total of 29 patients with pCD were enrolled in the study. Demographic data can be found in Table 1. The median follow-up since time of diagnosis was 40 months (interquartile range (IQR) 30-57). Time to the first IUS examination after diagnosis was median 28 months (IQR 13-49). The indications for IUS were as follows: Clinical suspicion of disease activity and/or elevated faecal calprotectin levels (66% of cases), evaluation of disease activity after initiating biologic therapy (10%), assessment of disease activity status (14%), suspicion of treatment failure (7%) and other indications (3%). Following the IUS procedure, 10% of patients subsequently underwent ileocolonoscopy, which was performed within 11, 14, or 53 days after IUS. Among the remaining 90% of patients, 14% underwent ileocolonoscopy 8-16 months after the IUS procedure, while 76% never had a repeat ileocolonoscopy performed after a median follow-up of 342 days (IQR 247-441) after IUS.

Conclusion

In 90% of patients with pCD IUS can be used to evaluate disease activity without the necessity for an ileocolonscopy in the subsequent 12 moths of follow up.References:(1) Wewer MD, Langholz E, Munkholm P, Bendtsen F, Benedict Seidelin J, Burisch J. Disease Activity Patterns of Inflammatory Bowel Disease-A Danish Nationwide Cohort Study 1995-2018. J Crohns Colitis. 2023 Apr 3;17(3):329-337. doi: 10.1093/ecco-jcc/jjac140. PMID: 36124895.Read more P584 Complication rates after two-stage vs three-stage restorative proctocolectomy with ileoanal pouch construction in the era of biologicsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Patients with proctocolectomy and ileoanal pouch construction typically undergo a two-stage or three-stage surgical procedure, depending on the general condition and recent immunosuppressive therapy. Our single center database prospectively records all surgeries performed since 2021 and retrospectively of patients before this year. Complications are registered by Clavien-Dindo classification.

Methods

All patients with two-stage or three-stage proctocolectomy and ileoanal pouch construction were identified from the database. The prevalence and severity of complications was analyzed according to Clavien-Dindo, with scores of 3 and above classified as severe complication. Patients were grouped by having either one or more severe complications or none at any surgical procedure.

Results

102 patients were identified from the database, of those 44 (43%) had a two-stage procedure and 58 (57%) a three-stage procedure.In the three-stage group, 25 (43%) patients were on active systemic corticosteroid therapy at the time of the first surgery compared to 0 patients in the two-stage group (p<0.001). Biological therapy within the last 3 months before the first surgery was received by 35 (60%) of the patients in the three-stage group versus 16 (36%, p=0.016 ) in the two-stage group.The three-stage procedure resulted in 11 out or 58 patients (19%) having at least one major complication compared to 3 out of 44 patients (7%) of the group with two-stage approach (p=0.077).

Conclusion

There is a trend towards a higher major complication rate in patients operated by a three- versus a two-stage approach in restorative proctocolectomy. This may be due to a selection bias as patients undergoing a three-stage procedure had significantly more often steroids at the time of first surgery and significantly more often biological therapy three months before the first surgery. Further data collection and then multivariate analysis including further risk factors, need to be done in order to better define the preferable individual surgical strategy.Read more P914 Immunogenecity of Hepatitis B Vaccination in Patients with Ulcerative Colitis on Infliximab Monotherapy : A Prospective Comparative StudyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Hepatitis B virus (HBV) infection has been associated with chronic hepatitis and cirrhosis. Patients with inflammatory bowel disease (IBD) maybe at higher risk of HBV infection, especially those on biologic therapies. There is limited data on the effectiveness of HBV vaccination in patients with IBD receiving different types of IBD medications. This study intends to compare the effectiveness of HBV vaccine in patients with ulcerative colitis (UC) on Infliximab (IFX) compared to those on 5-aminosalicylic acid (5-ASA).

Methods

Patients with UC aged between 18-85 years were prospectively enrolled in the study. The patients were divided into two groups: group 1 ( patients with UC on 5-ASA) and group 2 (patients with UC on IFX). HBV vaccination was administered (20 mcg) following the standard regimen, and Hepatitis B serum antibody (HbsAb) titres were assessed three months after the final dose. The response to HBV vaccines was categorized as 'adequate' immune response (≥10 IU/L) and 'effective' immune response (≥100 IU/L).

Results

In our final analysis of 118 patients with UC, 54.2% were male, and 52.5% had extensive disease. HBsAb titer levels were significantly higher in the 5ASA group (126.7 ± 37.5) compared to the IFX group (55.5 ± 29.4). Stratifying HBsAb levels into two categories (≥10-99 IU/L and ≥100 IU/L) revealed a significantly greater proportion of subjects in the 5-ASA group with levels ≥100 IU/L (76.7%) compared to the IFX group (12.1%). Conversely, the IFX group showed a higher percentage of subjects with levels between 10-99 IU/L (87.9%) relative to the 5-ASA group (23.3%). Logistic regression analysis demonstrated that patients with UC receiving 5-ASA were 23.94 times more likely to exhibit HBsAb levels ≥100 compared to those on IFX (OR 23.94, 95% CI 8.89-64.49).

Conclusion

Immune response to hepatitis B vaccination in patient with ulcerative colitis on infliximab is attenuated compared to those on 5-ASA. Therefore emphasizing the importance of HBV vaccination for patients with IBD before starting anti-TNF therapy, especially infliximab, and advocating for screening is imperative in high risk countries.Read more P585 Effectiveness of Switching to Subcutaneous Infliximab in Ulcerative Colitis Patients Experiencing Intravenous Infliximab FailureWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Studies on elective switching to the subcutaneous (SC) formulation of infliximab revealed comparable efficacy and safety and higher infliximab level than those exhibited by intravenous (IV) infliximab. However, no studies have reported on the effectiveness of SC switching in ulcerative colitis (UC) patients who experienced IV infliximab failure during maintenance treatment.

Methods

This retrospective study included UC patients who had been switched to SC infliximab because of IV infliximab failure, between January 2021 and January 2023. Group A was defined as having clinically and biochemically active UC (secondary loss of response), and group B consisted of patients with stable symptoms but biochemically active UC.

Results

Twenty-three patients met the inclusion criteria: 15 in group A and 8 in group B. The serum infliximab levels significantly increased after SC switching in both groups. Electively switched group also exhibited increased infliximab levels after SC switching. Group A showed improved partial Mayo score with a significant decrease in faecal calprotectin (FC) and C-reactive protein after switching. In group B, the FC level significantly decreased without clinical relapse after switching. A high proportion of patients (≥ 80%) in both groups achieved clinical and/or biochemical response at last follow-up. During the follow-up period, only two patients in group A discontinued SC infliximab, and only one complained of severe injection site reaction.

Conclusion

In UC patients who experience IV infliximab failure during maintenance treatment, switching to SC infliximab may be a promising option because of its efficacy and safety.Read more P714 Immunogenicity and safety of adjuvated recombinant zoster vaccine in IBD patients on different immunosuppressive therapiesWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Aberrant immune regulation and the use of immunosuppressive therapy make IBD patients more susceptible to complications of primary Varicella Zoster Virus (VZV) infection and significantly increase the risk of Herpes Zoster (HZ). HZ can be prevented by vaccination and RZV is the first HZ vaccine approved for immunocompromised persons. Limited data on immunogenicity and safety of RZV in immunosuppressed IBD patients are available. We investigated humoral and cell-mediated response and safety of RVZ vaccination in IBD patients under different immunosoppressive therapies.

Methods

In this prospective single centre study, adult IBD patients were enrolled and vaccinated with 2 doses of RZV between May and July 2022. Different immunosuppressive regimens (anti-metabolites, anti-TNF mono and combination therapy; ustekinumab and vedolizumab monotherapy; mofetyl mycofenolate/steroid combination therapy) were not discontinued and the administration schedule maintained. Immunogenicity was evaluated by quantitative detection of serum IgG anti-VZV antibodies and anti-VZV glycoprotein E (gE) antibodies before and 1 month after vaccination completion using ELISA. Reactogenicity was evaluated by diary cards reporting adverse events for 7 days after each dose. Events were graded from 1 (mild, not interfering with everyday activities) to 3 (severe, preventing normal everyday activities). Disease activity was assessed by SCCAI and HBI before vaccination, 7 and 30 days after each dose.

Results

Vaccination was completed in 104 (98.1%) out of 106 enrolled patients (median age 49.7 years, 59.4% male; 55.7% UC, 44.3% CD). Humoral response was observed in all patients, with a significant increase of anti-VZV antibodies (median UTI 23.8; IQR: 20.2-26.2 vs median UTI 419; IQR: 20.2-26.2, 376-458, p<0.001, median 17.8 fold increase, figure 1) and anti-gE antibody concentration compared to baseline (median OD 0.24; IQR: 0.21-0.26 vs OD 0.53; IQR:0.4-0.6, median 2.3 fold increase, p<0.001, figure 1). Imunosuppressive agents, either in mono or combination therapy, did not influence anti-VZV titre, anti-gE concentration and CMI response. Local and systemic solicited reactions after any dose were reported in 96.2% (grade 3=24.8%) and 88.6% (grade 3=33.3%) of patients respectively, with higher grade of intensity after the second dose. No severe adverse events related to vaccination were observed; 2 patients (1.9%) reported a disease flare.

Conclusion

RZV vaccine is able to induce a robust gE-specific humoral immune response. The type and intensity of immunosuppressive regimens did not influence humoral immunogenicity. RZV vaccination was safe and well tolerated in terms of both reactogenicity and exacerbation of disease.Read more P931 Burden of disease among Ulcerative Colitis patients with isolated proctitis in the United States and EuropeWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Isolated proctitis (IP), or ulcerative proctitis, a subtype of ulcerative colitis (UC), is associated with distressing symptoms such as abdominal pain and bowel urgency. As patients with IP not responding to conventional treatment are understudied and underrepresented in clinical trials, treatment guidance is limited. We aimed to understand disease burden among IP patients by describing patients delineated by disease extension and treatment experience.

Methods

Data were drawn from the Adelphi UC Disease Specific Programme™, a cross-sectional survey of gastroenterologists (GIs) and their consulting patients in France, Germany, Italy, Spain, the United Kingdom and the United States from October 2020 – March 2021. GIs reported patient demographics, disease extension, symptoms, components of the full Mayo score (allowing total scores to be calculated for patients), and treatment profile at time of consultation. Patients with a history of physician-assessed moderate-severe disease were included. Patients were categorised as IP (IP at diagnosis and consultation) or as more extensive UC (MEUC; where disease extended beyond IP at both diagnosis and consultation). According to ECCO consensus guidelines¹, patients are considered refractory if they have failed oral steroids combined with oral and rectal 5-ASA therapy. In this analysis, non-refractory IP patients had only received 5-ASAs and/or steroids; refractory IP patients had received an immunomodulator (IM) and/or advanced therapy (AT; biologics, Janus kinase inhibitors). All analyses were descriptive.

Results

Overall, 221 IP patients (118 non-refractory, 103 refractory) and 1607 MEUC were analysed (Table 1). Among IP, non-refractory IP, refractory IP, and MEUC 49.3%, 55.1%, 42.7%, and 55.4% were male, respectively, and mean age ranged 39.0-40.2 years. Symptoms most reported by IP, non-refractory IP, refractory IP, and MEUC patients were abdominal pain (33.8%, 26.5%, 41.7%, 26.0%), fatigue/tiredness (22.7%, 20.4%, 25.2%, 23.8%) and bowel urgency (22.7%, 25.7%, 19.4%, 23.6%). According to Mayo scores at consultation, 40.3% of IP, 44.9% of non-refractory IP, 34.9% of refractory IP, and 50.4% of MEUC patients were in remission. Since diagnosis, 33.5% of IP, 71.8% of refractory IP, and 69.1% of MEUC cohorts had received AT.

Conclusion

Patients with IP experience a similar symptom burden to the MEUC population, despite currently available treatments for UC. The high AT use and low rate of remission indicates undertreatment of IP patients and a need for therapies with proven efficacy in this population, particularly after conventional therapy use.1. Harbord et al. J Crohns Colitis. 2017 Jul 1;11(7):769-784.Read more P736 Class 4 Fistulizing Perineal Disease after Proctectomy for Crohn’s Disease: A Multicentre StudyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The TOpCLASS International Consortium recently described a paradigm shifting classification scheme for perianal Crohn’s disease, based on the desired patient goals of care. Class 4 perineal fistulizing disease is a CD that persists after proctectomy, and there are limited data defining this entity. We sought to determine the rates of clinical perineal fistulizing disease after proctectomy and to secondarily define the risk factors for recurrence.

Methods

Adult patients with CD who underwent perineal resection with proctectomy or proctocolectomy at three hospitals within our institution’s health network between 2009 and 2021 were retrospectively reviewed. The exclusion criteria included a preoperative diagnosis of ulcerative colitis or indeterminate colitis, and patients who underwent restorative proctectomy. Extracted data included baseline demographic data, preoperative medical treatment for CD, proctectomy indication, clinical recurrence of perineal disease, and resolution of perineal disease.

Results

A total of 405 patients with Crohn’s disease were included, including 190 (46.9%) who underwent proctectomy and 215 (53.1%) who underwent proctocolectomy. The median age was 44 years (IQR 33-58) and 58.8% of the patients were female. Within three months prior to surgery, 36% were exposed to biologic therapy, 29.1% to immunomodulators, and 11.4% to corticosteroids. During a median follow-up of 4 years, clinical recurrence of fistulizing perineal CD occurred in 62 (15.3%) patients, including five patients with perineal-vaginal fistulas and one with adenocarcinoma in the fistula tract. The median time to the development of perineal disease was 6.5 months (IQR 3-23 months). Factors associated with perineal disease included younger age (38 vs. 46 years; p <0.01), female sex (71% female vs. 56.6% female; p=0.03), preoperative corticosteroid use (19.4% vs. 9.9%; p=0.031), and the presence of perianal CD, regardless of the indication for proctectomy (85.4% vs 60.1%; p<0.01). After treatment for class 4 disease, perineal symptom resolution was observed in 40 (62.9%) patients. There were 79 (19.5%) patients underwent examination under anesthesia (EUA) for perineal disease, with a median of 2 EUA’s (range 1-21). Preoperative biological therapy was not associated with recurrent perineal disease (p= 0.29).

Conclusion

Perineal CD after proctectomy is common and frequently requires multiple surgical interventions. Younger age, female sex, preoperative corticosteroid use, and the presence of perianal disease may benefit from a more intensive postoperative review and consideration of the continuation or early initiation of prophylactic post-proctectomy CD medical management with biologics.Read more P586 Influence of HLA-DQA1∗05 on the loss of response to anti-TNF treatment in inflammatory bowel disease. Spanish cohort of real clinical practiceWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The presence of the HLA-DQA1*05 allele has been related to a loss of early secondary response, which could have clinical implications when choosing the first-line biological drug. Although its usefulness as a response predictor variant is not yet clearly established, the determination of polymorphism is common in clinical practice.

Methods

The objective of this study is to determine if there is an association between the presence of HLA-DQA1*05 and the loss of response in the short-medium term in the clinical practice of a real cohort. A retrospective cohort study has been carried out including adult patients with Crohn's Disease (CD), ulcerative colitis (UC) and indeterminate colitis (IC) who have received anti-TNF treatment with Infliximab (IFX) and Adalimumab (ADA) with a period of follow-up from 6 to 48 months.

Results

A total of 102 patients were included (73.52% CD- 75; 25.5% UC- 26; 0.98% IC- 1), of which 54.9% were men (56) and 45.1% were women (46), with a median age of 45 years (IQR 18-83).No statistically significant differences were observed between the HLA carrier and non-HLA carrier groups in age, sex, tobacco consumption, or type of inflammatory bowel disease. No differences were also observed between the location or severity of the disease.From the group of patients treated with Infliximab:• IFX at 6 months: a total of 52 patients were analyzed. Treatment was suspended in 6 patients (11.54%).• IFX at 18 months: a total of 35 patients were analyzed.Treatment was suspended in 4 patients (11.43%).• IFX at 48 months: a total of 26 patients were analyzed. Treatment was suspended in 7 patients (26.92%).From the group of patients treated with Adalimumab:• ADA at 6 months: a total of 50 patients were analyzed. Treatment was suspended in 6 patients (12%).• ADA at 18 months: a total of 31 patients were analyzed. Treatment was suspended in 1 patient (3.22%).• ADA at 48 months: a total of 22 patients were analyzed. Treatment was suspended in 3 patients (13.64%).Therefore, no statistically significant differences were observed in the loss of anti-TNF response between the HLA-DQA1*05 carrier and non-carrier groups for IFX and ADA at 6, 18 or 48 months. Nor were any differences found in the loss of response depending on the type of inflammatory bowel disease that the patients suffered from (CD or UC).

Conclusion

In this Spanish cohort from real clinical practice, the presence of the HLA-DQA1*05 allele in patients with inflammatory bowel disease does not influence the loss of response to anti-TNF treatment in the first 48 months of follow-up. However, more studies with larger samples are necessary to determine the usefulness of the polymorphism in clinical practice and establish its possible predictive implication.Read more P932 Corticosteroid-sparing effect of mirikizumab for the treatment of moderately-to-severely active Ulcerative Colitis: Extended induction subgroup analysis from Phase 3 trialWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Mirikizumab, an anti-IL-23p19 antibody, has demonstrated efficacy and safety in moderately-to-severely active ulcerative colitis (UC) Phase 3 trials (LUCENT-1 and -2; NCT03518086, NCT03524092).¹ A treatment goal for patients with UC is corticosteroid (CS)-free remission. We assessed the CS-sparing effect of mirikizumab among the extended induction patient population receiving CS at induction baseline.

Methods

In LUCENT-1, patients in the modified intention to treat mirikizumab group (n=868) received mirikizumab 300 mg intravenously (IV) at Week (W)0, W4, and W8. Patients receiving mirikizumab on CS at baseline (n=351) remained on their stable baseline dose (prednisone ≤20 mg/day or equivalent, budesonide MMX 9 mg/day, or beclomethasone 5 mg/day) during induction (W0 to W12). Patients not achieving clinical response (≥2-point and ≥30% decrease in Modified Mayo Score from baseline; and rectal bleeding=0 or 1, or ≥1-point decrease from baseline) at W12 (n=272) entered LUCENT-2 open label (OL) extended induction and received 300 mg mirikizumab IV at W12, W16, and W20. Extended induction responders at W24 (n=144) entered OL maintenance and received 200mg mirikizumab subcutaneously (SC) Q4W until W52. CS taper was initiated if clinical response was achieved at W24 or earlier based on investigator discretion if symptomatic improvement was evident. Patients who discontinued CS and remained off throughout the study were considered "discontinued." Descriptive statistics for efficacy outcomes were summarized. Missing data were imputed as non-response.

Results

Of the 272 mirikizumab patients in the extended induction population, 118 received CS at induction baseline. The mean prednisone equivalent dose was 15mg. At W24, among the 62/118 (52.5%) who achieved clinical response and continued with maintenance, 8 (12.9%) discontinued CS, 2 (3.2%) achieved clinical remission off CS, and 8 (12.9%) achieved symptomatic remission off CS. At W52, 43/62 (69.4%) of the extended induction responders discontinued CS, 18 (29.0%) achieved clinical remission off CS, and 37 (59.7%) achieved symptomatic remission off CS. Among patients with non-missing data who completed W52 of mirikizumab treatment, 89.6% had discontinued CS (Table).

Conclusion

Nearly 70% of extended induction responders discontinued CS by W52. CS-sparing effect of mirikizumab in patients with moderately-to-severely active UC is clinically meaningful and aligns with the treatment goal of CS discontinuation.References:1. D’Haens G, et al. N Engl J Med 2023;388(26):2444-2455.Read more P557 Data communication practices for reporting health care outcomes to improve quality of care: A scoping reviewWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Value-based health care (VBHC) aims to improve care quality while minimizing costs. An important mechanism of VBHC involves monitoring and reporting health care outcomes to health care providers (HCPs) through data communication (DC) or data feedback. For complex diseases like Inflammatory Bowel Disease (IBD), unwarranted variation in care practices is ubiquitous. Health care data can be used to improve care by showing insights about achieved outcomes and practice variation to HCPs. While some tentative best practices for DC exist, a comprehensive overview is needed to gain a better understanding of how to effectively report health care outcomes to HCPs. This scoping review addresses this gap by examining the use and effectiveness of DC practices not only within the specific realm of IBD but also drawing insights from other clinical fields.

Methods

Studies that implemented and evaluated DC to engage HCPs with data and improve outcomes with qualitative or quantitative designs were sought. Medline, CINAHL, Scopus, Web of Science, Embase, the Cochrane Register of Controlled Trials and PsycINFO were searched for publications in English between 2010 - April 2023. Two researchers reviewed titles, abstracts and extracted data from eligible full texts.

Results

We screened 5,857 studies and included 239: 51 randomized controlled trials, 28 quasi-experimental, 121 pre-post intervention, and 39 qualitative studies. In 35% of those, feedback was implemented in acute care, 30% in primary care, 25% in tertiary care and 10% in other settings. Most interventions (76%) combined DC with co-interventions targeting HCPs’ intrinsic (providing education, post-feedback discussions) and/or extrinsic motivation (incentives, social influence). Additionally, 80 (33%) studies included nudges as part of co-interventions: action toolbox (n=38), reminders (n=28), posters to visualize compliance (n=12) and commitment messages (n=2). Best practices used in DC design included ‘benchmarking with peers’ (n=131), ‘timely feedback’ (n=141), and ‘active delivery of feedback’ (n=147). Most pre-post studies showed positive outcomes (96%), while only 63% of the studies with controlled designs showed positive improvements in outcomes.

Conclusion

The findings of our study highlight the use of DC (co-)interventions in various clinical fields. Additionally, we identified only few studies with controlled designs. In the future, studies with controlled designs testing the effectiveness of DC strategies and additive effects of different co-interventions are warranted to facilitate targeted improvements, particularly in the care of IBD patients, where care practices vary widely.Read more P737 Poor body image is associated with significant depression, anxiety and self-harm in people with inflammatory bowel diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Body image dissatisfaction is common in inflammatory bowel disease (IBD) and is associated with worse quality of life in this population. In other populations body image dissatisfaction has been associated with psychological distress. We aimed to investigate the relationship between body image and depression, anxiety, and self-harm in an IBD population.

Methods

IBD patients at a tertiary IBD referral centre were sent a pre-clinic survey to be undertaken once a year. This survey included a validated measure of body image dissatisfaction – the body image scale (BIS) – with a BIS >= 10 indicating Body Image Dissatisfaction. Demographic data and measures of depression (Patient health questionnaire 9 (PHQ9), and anxiety (Generalised anxiety disorder-7 (GAD7)) were also obtained.

Results

There was 146 responses to the questionnaire, majority female (64%), median age 42 years interquartile range (29-58), 57% Crohn’s disease. A BIS over >= 10 was seen in 35.3%, with mean (SD) BIS score 8.5 (7.5). Consistent with previous literature BIS score was higher in females (11.3 (1.2) v 3.4 (3.5), p<0.001). BIS score was higher in obesity (11.0 v 7.2, p=0.049), however correlation with weight was poor (-0.044), and overall body weight was not higher in BIS>=10 (77.5 (2.8) v 82.1 (4.8) p=0.37), and similarly no difference seen in BMI (30.0 (1.5) v 28.3 (1.2) p=0.41).BIS score and depression score (PHQ9) correlation was strong (ro=0.56), and similarly for anxiety severity score (ro=0.57). More frequent self-harm was associated with worse body image dissatisfaction (Figure 1 oneway ANOVA). Self-harm or suicidal ideation more than half the days was associated with a BIS score over 10 (p=0.012 Chi2, Odds ratio 4.16 for self-harm given BIS over 10).

Conclusion

Body image dissatisfaction is associated with self-harm, depression and anxiety, In addition to its known relationship with lower quality of life. Consideration should be given to developing body image targeting interventions in IBD populations and future research should consider interventional trials in this area.Read more P953 Establishment and Internal Validation of a Clinical Risk Score to Predict the Efficacy of Adalimumab in Crohn's DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Adalimumab (ADA) plays a crucial role in treating Crohn's disease (CD), but not all patients benefit from it. This study aimed to analyze the factors affecting the treatment effectiveness of ADA for CD and then establish an efficacy prediction model with internal validation.

Methods

Retrospectively collected data from CD patients receiving ADA at Xijing Hospital from October 2020 to February 2023. Collect clinical data of patients and use FITC-labeled ADA to perform immunofluorescence staining on paraffin tissue sections of CD patients before ADA treatment. The data were randomly split into training and validation. Single-factor and multiple-factor logistic regression models were used to analyze the factors influencing the 12-week clinical remission of CD patients treated with ADA in the training, determining the optimal predictive model. A line chart prediction model was established and the model's discrimination and calibration were tested. Finally, the model was internally validated in the validation set.

Results

A total of 68 patients were included in the study. The clinical remission rate of CD patients treated with ADA at 12 weeks was 55.88% (38/68). The results showed that baseline endoscopic stenosis [OR=0.019, 95% confidence interval (95% CI) 0.019-0.993], disease course [OR=0.966, 95% CI 0.940-0.993], and the number of FITC-labeled ADA-positive cells [OR=1.109, 95% CI 1.025-1.201] were factors affecting the therapeutic effect of ADA in CD patients (p<0.05) which used to establish the efficacy prediction model. The AUC of the prediction model in the training and validation were 0.868 (95% CI 0.769-0.977) and 0.802 (95% CI 0.604-1) (p<0.05), respectively. The clinical decision curve analysis showed that the prediction model had significant clinical benefits in both the training and validation.

Conclusion

The prediction model can provide reference for clinicians to make treatment decisions.Read more P738 Response to etrasimod treatment in ulcerative colitis is associated with a reduction of circulating B and pro-inflammatory T cells: a single-cell-based post-hoc sub-analysis of the ELEVATE UC 52 trialWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Etrasimod (ETR) is an oral, once-daily, selective sphingosine 1-phosphate receptor 1,4,5 (S1PR) modulator for the treatment of moderately to severely active ulcerative colitis (UC). The mechanism of action is based on a retention of lymphocytes in lymphatic tissue hindering circulating lymphocytes from entering the gut and causing inflammation. However, the effect of ETR on immune cell function and composition is not well characterized. In addition, it is unknown whether the response of UC patients to ETR treatment is associated with specific immune cell signatures.

Methods

Single-cell RNA sequencing (scRNAseq), mass cytometry (CyTOF) and clinical data integration were used to characterize the effects of 12 weeks of treatment with ETR on the immune composition and function of peripheral blood mononuclear cells (PBMCs) collected from 15 UC patients at weeks 0 and 12 during the ELEVATE UC Phase 3 clinical trial. As an exploratory cohort, PBMCs from 5 UC patients reaching the primary endpoint of clinical remission at week 12 (modified Mayo score <2), 5 UC patients not responding to ETR treatment (modified Mayo score >2) and 5 placebo-treated UC patients were included. 30 samples were processed for scRNAseq; additionally, 28 blood samples were ex-vivo stimulated with ionomycin/PMA for 4 h and cytokine production was assessed by CyTOF. To determine the effects of ETR in UC patients, immune cell function and composition were compared intra-individually between weeks 0 and 12. Subsequent comparisons between ETR responders, non-responders and placebo-treated UC patients were performed to discriminate responders from non-responders.

Results

Significant reductions in T and B cell subsets, along with increases in the abundance of dendritic and monocytic cells, were observed in responders by week 12 of -treatment. Importantly, ETR treatment significantly reduced circulating T cells producing pro-inflammatory cytokines, including TNFα and IFNγ, and S1PR modulation led to a mitigation of naïve and effector memory CD4 and CD8 T cells in ETR-treated UC patients achieving clinical remission. In contrast, patients not responding to ETR treatment had significantly higher frequencies of both naïve and TNFα-producing CD4 T cells by week 12.

Conclusion

In line with the described role of S1PR in lymphocyte trafficking, single-cell analyses of circulating immune cells from ETR-treated UC patients confirmed a significant reduction in B cells and pathogenic T cell subsets after ETR treatment providing an in-depth cellular characterization of S1PR modulation in UC patients thereby contributing to a better understanding of the key mechanism of action of ETR. However, these findings require validation in larger cohorts.Read more P558 Clinical Effectiveness and Safety of Vedolizumab vs. Infliximab in Biologic-Naïve Ulcerative Colitis Patients: A Brazilian Real-World Multicentric Observational StudyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Vedolizumab (VDZ) and infliximab (IFX), are considered first-line agents in the treatment of moderate to severe Ulcerative Colitis (UC). However, there are no head-to-head studies comparing the relative effectiveness of the two agents, and Real-world data on the effectiveness and safety of VDZ and IFX in UC are lacking in the Brazilian population. We aimed to compare effectiveness and safety of VDZ to IFX in Biologic-naïve UC patients.

Methods

We conducted a multicenter retrospective cohort study, including patients with moderate to severe UC (Total Mayo score 6-12, with an endoscopic subscore of 2 or 3) who treated with VDZ or IFX. The primary endpoints were: clinical remission, defined as a partial Mayo score (PMS) ≤2, endoscopic remission (endoscopic Mayo subscore of 1 or 0) and steroid-free clinical remission at week 52. Secondary endpoints included; clinical response at weeks 12 and 26, need for drug optimization, adverse events (AEs), need for hospitalization and colectomy, loss of response and biochemical remission (C-reactive protein [CRP] ≤ 0.5 mg/dl and/or fecal calprotectin [FC] ≤ 150 mcg/g) at week 52.

Results

A total of 174 UC (79 VDZ and 95 IFX) patients were included. Clinical remission and endoscopic remission at week 52 were achieved by 56 (70.8% vs 68.4%, p= 0.44) and 46 (58.2% vs 55.7%, p=0.18) of VDZ and IFX patients, respectively. Steroid-free clinical remission at week 52 was 84.2% and 54.1% in the VDZ and IFX group, respectively (p = 0.03). Clinical response at weeks 12 and 26 was reached in 80.0% vs 76.2%, p = 0.74 and in 71.4% vs 77.3%, p = 0.71 in the VDZ and IFX group, respectively. The need for drug optimization was higher for IFX than for VDZ (36.8% vs. 21.5%, p = 0.03). The incidence of AEs (26.3% vs 12.6%, p=0.03) and need for hospitalization (26.3% vs 11.4%, p=0.02) were higher for IFX than to VDZ patients. Secondary loss of response was similar in the two groups (16.4 % for VDZ and 16.8% for IFX, p = 1.00). Biochemical remission at week 52 was 75.0% for VDZ, and 63.9% for IFX, respectively (p=0,42).

Conclusion

In this real-world study VDZ and IFX had similar efficacy in inducing clinical remission, endoscopic remission, clinical response and biochemical remission at week 52. Compared to IFX, VDZ was superior in inducing steroid-free remission, in addition to having a better safety profile and less need for dose escalation. Both VDZ and IFX were effective treatment options in bio-naïve UC patients.Read more P954 Cumulative response to guselkumab through week 24 of induction in patients with moderately to severely active ulcerative colitis: Results from the phase 3 QUASAR induction studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The Phase 3 QUASAR induction study evaluated efficacy and safety of guselkumab (GUS), an IL-23p19 subunit antagonist, in pts with moderately to severely active UC. At Week (Wk) 12, GUS 200mg IV was more effective than placebo (PBO) in inducing clinical remission and clinical response.¹ Pts not in clinical response at Wk 12 received GUS through Wk 24. Here, we report GUS cumulative efficacy and safety.

Methods

Pts with a modified Mayo score of 5-9 and a centrally reviewed Mayo endoscopy subscore ≥2 at baseline (BL) were randomized 3:2 to receive GUS 200mg IV or PBO at Wks 0, 4, and 8. Pts not in clinical response at Wk 12 received GUS at Wks 12, 16, and 20 (GUS 200mg IV→GUS 200mg SC; PBO→GUS 200mg IV) and were evaluated at Wk 24. Matching IV or SC PBO were used to maintain study blinding. Final safety assessments were conducted through Wk 32 (ie, 12 wks after last dose of GUS).

Results

The primary analysis population consisted of 701 pts. BL demographics were similar among treatment groups, and approximately 50% had a history of inadequate response/intolerance to advanced therapy (ADT-IR).At Wk 12, clinical response was achieved by a higher percentage of GUS- vs PBO-treated pts (61.5% vs 27.9%, respectively; adjusted Δ [95% CI]: 33.8% [26.9%, 40.7%]; p<0.001; Figure). Of GUS-treated pts who were not in clinical response at Wk 12 and received additional GUS treatment (GUS IV→GUS SC), 55% (66/120) achieved clinical response at Wk 24. Cumulative clinical response at Wk 12 or 24 was achieved by 77.2% of pts randomized to GUS at BL. Pts with and without history of ADT-IR benefitted from continued treatment with GUS SC through Wk 24 (51.4% and 60.9% achieved clinical response at Wk 24, respectively). Of PBO-treated pts who were not in clinical response at Wk 12 and received GUS treatment (PBO IV→GUS IV), clinical response rate at Wk 24 (69.7%) was similar to that at Wk 12 for pts randomized to GUS at BL (61.5%). Safety findings through the final safety visit were consistent with Wk 12 results;¹ no new safety signals were identified (Table). The most frequent adverse events among GUS-treated pts (n=586) were COVID-19 (7.2%), anemia (5.1%), and worsening UC (4.6%).

Conclusion

Among pts randomized to GUS IV who did not achieve clinical response at Wk 12, continued treatment with GUS SC allowed 55% to achieve clinical response at Wk 24. Overall, more than three-quarters of pts randomized to GUS IV achieved clinical response at Wk 12 or 24. No new safety signals for GUS were identified.1) Allegretti JR, Peyrin-Biroulet L, Feagan BG, et al. The efficacy and safety of guselkumab induction therapy in patients with moderately to severely active ulcerative colitis: Results from the Phase 3 QUASAR induction study. UEG Journal. 2023;11(58):45-6.Read more P559 Descriptive observational pilot study about the use of Virtual Reality (VR) in patients with Inflammatory Bowel Disease (IBD) and biological treatmentWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Virtual reality (VR) is a neurosensory experience in which simulated images and spaces are created where a person has the sensation of being and being able to function within them. A high percentage of patients with Inflammatory Bowel Disease (IBD) receive intravenous biological treatments in a day hospital (HDD) regime. VR has been used in some fields of medicine, such as Oncology, demonstrating its usefulness in reducing chronic symptoms such as pain or anxiety. However, we don’t have any literature demonstrating the applicability of VR in IBD.

Methods

Descriptive observational pilot study based on an initial cohort of 87 patients obtained from the HDD of the IBD Unit. Satisfaction and acceptance of VR through the use of 3D glasses and the reduction of negative symptoms during intravenous biological treatment in patients with IBD in HDD have been assessed.

Results

43 patients (52.4%) used VR and completed the study. The mean age was 45.3 years. The validated IBDQ-32 questionnaire on quality of life in IBD obtained a mean score of 169 points (range: 32-224). In the comparative analysis of the results of the questionnaires before and after the use of VR, a statistically significant improvement was observed in the patients' view of the ability of VR to achieve a reduction in stress (65% patients improve; p: 0.0021) and pain (VAS, 54% p. improve; p<0.05) during treatment. Likewise, with the applicability of VR in other areas of medicine (53%; p: 0.05) and with the possibility of improving well-being during the stay in the HDD (56%; p: 0.0014). No side effects were reported with the use of the 3D glasses.

Conclusion

The use of VR could be a useful complementary tool to improve the stay of patients with IBD on HDD during treatment with intravenous biologic drugs. To this end, we believe it is appropriate to complete our research and obtain more data through other studies along the same lines.Read more P739 Translating Pharmacokinetic and Efficacy Outcomes of NLRX1 Agonist NX-13: Contrasting a Pig Model and a Human Phase 1b Clinical Trial in Ulcerative ColitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

In rodent models of ulcerative colitis (UC), NX-13 (as an orally active, gut selective NLRX1 agonist) improves disease activity through a novel bimodal mechanism. Subsequently, a pig DSS colitis experiment was performed to generate pharmacokinetic (PK) and mechanistic insights, given pigs can be dosed with tablets and their gastrointestinal physiology, microbiome, and immune system is markedly more similar to humans than rodents are. We here describe the efficacy and PK of NX-13 tablets in pigs compared to phase 1 clinical trials.

Methods

NX-13 immediate release (IR) tablets were used in pig studies and human clinical trials with plasma samples collected at hourly intervals. Stool samples were collected at ~24hrs after last dose. NX-13 phase 1 clinical trials were double blind, randomized and placebo-controlled studies testing multiple IR doses in healthy subjects (1a) or subjects with active UC (1b) ^1,2. NX-13 concentrations were determined by LC-MS/MS and linear regression to standard curve.

Results

In pigs, oral NX-13 treatment dampened colitis development with differences as early as day 2, becoming significant at days 4-6 (Fig. 1A). Consistent results were observed in the human Phase 1b trial, including fast rectal bleeding improvement as early as week 2 (Fig. 1B) and endoscopic improvement at week 4. Nonetheless, the NX-13 PK characteristics differed between pigs and humans. Firstly, NX-13’s low level of systemic exposure peaked 1 hour after dosing in the human studies, whereas T_max in pigs was 7 hours at comparable doses. Secondly, the portion of NX-13 retained in the stool is greater in pigs (250-1000 times greater than plasma levels), compared to humans (150-400 times greater) although both stool and plasma concentrations were greater in pigs (Fig. 1C). This suggests NX-13 is not gut-restricted in humans, but rather gut-selective with low systemic absorption. Interestingly, the stool:plasma ratio was numerically lower in patients with UC compared to normal healthy volunteers (Figure 1C), implying epithelial barrier integrity may affect absorption. Despite these differences in PK characteristics, we see similarly fast onset of action signals in the pig model and the human phase Ib trial, suggesting that sufficient target engagement is achieved locally in both species.

Conclusion

NX-13, a novel NLRX1 agonist, has a low percentage of drug absorbed systemically in both pigs and humans, although there are species specific differences in absorption patterns. The hypothesis of a gut-selective compound with low systemic absorption and PK characteristics of NX-13 will be analyzed in the ongoing NEXUS phase 2 study in patients with moderate to severe UC.1 Leber et al. UEG J (9) Supp.2 Peyrin-Biroulet, et al. JCC (17) Supp.Read more P597 The changing landscape of paediatric Inflammatory Bowel Disease medication in Australia 2015-2021, A population-based studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

There have been significant advancements in the pharmaceutical management of paediatric inflammatory bowel disease (IBD) with cost and clinical implications. The real-world shifts in prescribing habits in Australia have yet to be characterised. As part of the National Inflammatory Bowel Disease Paediatric Quality of Care project, this study sought to examine patterns of IBD-related medication use in the Australian paediatric population from 2015 to 2021.

Methods

We used Services Australia Pharmaceutical Benefits Scheme 10% data to identify prescriptions for paediatric IBD patients from 1/1/2015 to 31/12/2021. In Australia, select prescribers must specify an authorised indication for the government subsidy of authority-required medications (i.e. aminosalicylates (5-ASAs) and biologics), enabling patients to be tagged with Crohn’s disease (CD) or ulcerative colitis (UC). To be included in the analysis, patients must have received at least one prescription of an authority-required medication and be aged between 0 and 17 years at the time of dispensing their first IBD-related medication. Trends over time were assessed for significance with the chi-squared test for trend.

Results

The data identified 2940 UC patients (mean age 14.09 ± 3.15) and 2840 CD patients (mean age 14.20 ± 2.67) across 2015-2021. In 2015, 54.90% of IBD patients were dispensed at least one prescription of corticosteroids (CCSs). Trends showed CCS use to fall dramatically to only 29.27% of patients in 2021 (p < 0.0001). Among CD patients on azathioprine (AZA) treatment, there was a disproportionate decrease in male usage, with the male CD patients on AZA falling from 47% (n=277) in 2015 to 38% (n=167) in 2021 (p < 0.0001). Simultaneously, CD patients on methotrexate rose from 11% (n=130) to 28% (n=330) (p < 0.0001). Biologic use rose continually among both CD and UC patients. CD patients on infliximab (IFX) rose from 34% (n=420) in 2015 to 59% (n=670) in 2021 (p < 0.0001), whilst UC patients on IFX increased from 5% (n=70) to 24% (n=220) over the same time (p < 0.0001). Despite rising patient numbers, the total estimated government expenditure on IFX for CD decreased by over 50% from AUD 7.1 million in 2015 to AUD 3.4 million in 2021.

Conclusion

This study quantifies the temporal trends in prescribing habits for paediatric IBD in Australia, observing a shift towards increasingly biologic-centred therapy. Despite increasing IFX use in CD, government expenditure decreased, suggesting that escalated medication use in paediatric IBD care does not necessarily lead to increased costs over time.Read more P772 Comprehensive disease control in patients with Ulcerative Colitis: refinement of a multi-component endpoint using data from the filgotinib SELECTION trialWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Ulcerative colitis (UC) treatment requires a patient-centric efficacy endpoint to assess treatment benefits, enabling a shift towards a personalized approach. Comprehensive disease control (CDC) is an individual multi-component endpoint based on findings from a patient and expert Delphi consensus on remission assessment in UC. CDC was defined as IBDQ remission, partial Mayo Clinic Score (pMCS) remission, biomarker (faecal calprotectin [FCP]) remission and endoscopic improvement. We evaluated different definitions of CDC, and the contribution of different CDC components to the net treatment benefit (NTB) of filgotinib 200 mg (FIL200), an oral, once-daily, Janus kinase 1 inhibitor approved for UC treatment following the SELECTION trial (NCT02914522).

Methods

CDC was assessed at week 58 (W58) of SELECTION in adult patients with active UC treated with FIL200 or placebo (PBO). The CDC definitions evaluated were: 4-component CDC (CDC4) with FCP <150 µg/g, CDC4-150; CDC4 with FCP <250 µg/g, CDC4-250; 5-component CDC (with histological remission [CDC5]) with FCP <150 µg/g, CDC5-150; and CDC5 with FCP<250 µg/g, CDC5-250. The proportion of patients achieving each combination of components was visualized in UpSet plots. NTB of FIL200 was assessed for each endpoint using generalized pairwise comparisons and is reported here for CDC4-150 (and excluding different components).

Results

At W58, 21.6%, 26.6%, 19.1% and 22.6% of FIL200-treated patients achieved CDC4-150, CDC4-250, CDC5-150 and CDC5-250, respectively. Among patients who did not achieve CDC4-150, 0.5% of patients did not achieve pMCS remission compared with 5.0%, 10.1% and 6.0% who did not achieve IBDQ remission, biomarker remission and endoscopic improvement, respectively (Figure). Positive overall NTB of FIL200 versus PBO was demonstrated with all CDC definitions, including those with histological remission (CDC5). For CDC4-150 at W58, excluding pMCS remission did not substantially change the NTB (Δ −0.33; Table) versus excluding IBDQ or biomarker remission, or endoscopic improvement (Δ 3.87, 6.93 and 3.20, respectively). Similar NTB results were seen for all CDC definitions.

Conclusion

CDC is a stringent, patient-level, multi-component endpoint achieved by ~1/5 of FIL200-treated patients at W58. While CDC4-150 could be the optimal operational definition, the addition of histological remission resulted in similar stringency, potentially allowing for the use of different CDC definitions based on context or resources. Additional NTB of FIL200 was identified in patients when IBDQ or biomarker remission or endoscopic improvement were excluded. Overall, CDC appears to be a suitable endpoint to assess individual comprehensive benefit in patients with UC. Prospective validation is needed.Read more P965 Ulcerative proctitis treated with biologics: is it too hard to treat?Wed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Patients with ulcerative proctitis are widely considered a challenging population because the reported reduced response rate to conventional medical treatment. On the other hand, data on the role of biological therapies in this specific cohort are currently scarce

Methods

We retrospectively evaluated all patients with proctitis (defined as the mucosal inflammation of only the rectum with ulcerative colitis confirmed by histology) treated with biologics (infliximab, adalimumab, vedolizumab -VDZ-, ustekinumab -UST) and tofacitinib (TOFA) at four referral centers in the last 5 years. All patients were treated with concomitant topical mesalamine. We included in this study only patients who underwent colonoscopy at baseline and after 52 weeks of treatment, in order to evaluate therapeutic response in terms of mucosal healing (defined as a Mayo Endoscopic Score -MES- <2), besides that clinical remission (defined as a Partial Mayo Score -PMS- <2 without oral or topical corticosteroid therapy). We collect clinical and demographic data, as well as fecal calprotectin (FC) and C-Reactive Protein (CRP) levels at baseline and after the induction of therapy

Results

Among 64 patients enrolled (age 50.8±16.5 years, 29 [45.3%] women), 33 (51.6%) were treated with anti-TNF), 15 with VDZ, 13 with UST, and 3 with TOFA. Globally, 51 (79.7%) patients achieved clinical remission and 37 (57.8%) patients achieved endoscopic remission at 52 weeks. There were no group differences in age, sex, BMI, disease duration, PMS, MES, drug, or baseline CRP levels between patients achieving or not either clinical or endoscopic remission. Baseline calprotectin levels were lower in patients who achieved endoscopic remission (median [IQ range] 297 [158, 475] versus 442 [230, 1545] µg/mL, p=0.036), but not in those who achieved clinical remission. After the induction phase, lower calprotectin levels were observed in patients achieving clinical (46 [15, 166] versus 553 [72, 1649] µg/mL, p=0.001) and endoscopic remission (38 [15, 112] versus 328 [52, 2171] µg/mL, p=0.0002), compared with non-responders. The effects of post-induction calprotectin levels on clinical remission (β= -0.001, p=0.020) and endoscopic remission (β= -0.007, p=0.006) remained significant in multivariable models adjusted for age, sex, BMI, disease duration, and biological treatment. A cut point of 200 µg/mL post-induction was identified to predict endoscopic remission (sensitivity 92%, specificity 64%, ROC AUC 0.781)

Conclusion

High rates of clinical and endoscopic remission with biological therapies could be achieved in patients with ulcerative proctitis. Fecal calprotectin levels after the induction of biological therapies seem to predict the therapeutic response in patients with ulcerative proctitisRead more P773 Clinical decision support tool for vedolizumab is useful in predicting endoscopic remission in Crohn's disease – a retrospective real-life single-centre cohort studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Early control of inflammation could modify the disease course and improve outcomes in patients with Crohn's disease (CD). Positioning of advanced therapies is becoming more important as treatment options expand. Dulai et al. derived and externally validated a clinical decision support tool (CDST) for predicting response to vedolizumab (VDZ). They noticed that the high probability group, according to CDST, has the highest probability of achieving clinical remission (CR), corticosteroid-free remission (CSFR) and mucosal healing. In contrast, low and intermediate-probability groups are more likely to need surgery.

Methods

We performed a retrospective single-centre cohort study based on the UR-CARE registry. Data for 57 CD patients treated with VDZ from July 2016 until April 2023 were analysed. We stratified patients according to CDST for CD into three response probability groups: group 0 with low (≤13 points), group 1 with intermediate (14-19 points) and group 2 with high (>19 points) probability of response to VDZ. CDST was calculated using five variables: no prior bowel surgery, no prior tumour necrosis factor (TNF) alpha antagonist exposure, no prior fistulising disease, baseline albumin and baseline C-reactive protein (CRP). For analysis of the association between CDST, CR (defined as PRO2 ≤1 with rectal bleeding score 0), CSFR and endoscopic activity (defined as no change in endoscopic activity, endoscopic improvement (EI), or endoscopic remission (ER)) chi² test was used.

Results

In our cohort, 38.6% of CD patients were male, the median age was 34 years at the time of diagnosis, and the median duration of disease until VDZ treatment was 4.1 years. Fistulising disease was present in 33.3%, 24.6% had upper gastrointestinal involvement, 56.1% had prior surgery, and 57.9% had prior anti-TNF exposure. The average follow-up duration was 27.0 (standard deviation = 19.2 months). We found a significant association between the CDST group and endoscopic activity at follow-up endoscopy but no statistically significant association between the CDST group and CR nor CSFR at weeks 14 and 52. The majority (69.2%) of patients stratified into CDST group 0 had endoscopically active disease, while in contrast, 68.8% of patients in CDST group 2 achieved ER. In group 1, EI was found in 45.8% and ER in 41.7% of patients.

Conclusion

In our retrospective study, CDST for VDZ predicted ER and EI in our cohort of patients with CD. We could not confirm the association between CDST and CR or CSFR, probably due to the definition used in a retrospective design, namely PRO2, which does not correlate well with endoscopic activity in CD.Read more P598 Validating and Enhancing Real-time Disease Severity Classification in Ulcerative Colitis: Artificial Intelligence as a Second Opinion TriggerWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Endoscopic ulcerative colitis (UC) severity classification shows high interobserver variance. Our prior study proved AI matches central reading scoring still images. To be clinically useful, assessing longer segments is vital. Our aim: a new model for real-time or video-based severity evaluation and demonstrate the supporting value it might offer.

Methods

Data was Mayo Endoscopic Subscore (MES)-scored using 2561 images and 53 videos from 645 patients to train a convolutional neural network. Through open-set-recognition, the model differentiated scoreable from unscoreable endoscopy sections. The validation included 140 videoclips from 44 UC patients. Six IBD-experts and 16 non-IBD experts independently rated these clips, with the majority IBD-expert score serving as ground truth. We assessed its value as a second opinion for non-IBD experts and conducted an alpha test with real-time endoscopic support on a real-world patient.

Results

The model achieved an overall accuracy of 0.82 and 0.84 for MES 0, 0.81 for MES 1, 0.72 for MES 2, and 0.96 for MES 3. No significant distinction between individual experts or ground truth vs. the AI model was observed (figure 1).When employed as a trigger for second opinions, non-IBD experts' performance improved by 10% (table 1). On average, 26-32 % (range on an individual level: 17-39 %) of the time (depending on the evaluated seniority) the framework disagreed with the primary physician. In those cases, the model was correct in an average of 57-59 % (range on an individual level: 33-76%), and the second physician’s opinion was correct in an average of 64-70 % (range on an individual level: 60-77%) of the time according to the ground truth.The alpha test successfully integrated the model into the endoscopic column for real-time classification. It accurately discerned MES 0 and MES 1 frames, aligning with the endoscopist's assessment.

Conclusion

Our innovative AI model exhibits significant potential for enhancing UC severity classification accuracy, rivalling IBD-experts and notably improving non-specialists' proficiency. It is designed for clinical implementation and has demonstrated clinical feasibility in an alpha test.Figure 1:Table 1:Read more P527 Factors associated with choice of treatment regimen after the induction period in patients with Ulcerative Colitis treated with vedolizumabWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Vedolizumab (VDZ) is a selective, alpha4-beta7 anti-integrin antibody used for treatment of inflammatory bowel diseases. The aim of our study was to investigate factors that influence the decision making and determine further therapeutic regimen after the induction period in patients with ulcerative colitis treated with VDZ and to identify predictors for early response to VDZ.

Methods

A retrospective study conducted at the Clinic for gastroenterohepatology, University Clinical Center Serbia included 89 patients with ulcerative colitis (mean age 47±15; 45 males) treated with VDZ (69 bio-naïve and 20 previously exposed to anti-TNF). Localization of disease, endoscopic score at the beginning of therapy, together with CRP and fecal calprotectin levels before the initiation of therapy and at week 14, and prior exposure to anti-TNF in relation to the treatment regimen at the end of the induction period were analyzed.

Results

After induction therapy total of 55 patients (61.8%) continued with standard dosing regimen, while in 34 patients (38.2%) shortening the interval to 4 weeks as optimization of VDZ treatment was prescribed. Patients whose treatment regimen was optimized at week 14 had had statistically significantly higher baseline CRP levels (p=0.025), as well as CRP levels at week 14 (p=0.002) and fecal calprotectin at week 14 (p=0.000), while there was no difference in the baseline fecal calprotectin between patients in standard and optimized regimen (p=1.000). There was no statistical difference in localization of disease and prior anti-TNF exposure between these two groups of patients (p=0.732 and p=0.449, respectively).

Conclusion

Higher CRP and fecal calprotectin levels at week 14 were determining factors for optimization of VDZ treatment. Higher levels of CRP before biologic therapy was started was associated with the increased need for optimized regiment at week 14. Extensive disease and prior anti-TNF exposure did not correlate with need for optimization of treatment after the induction period.Read more P966 The intra-patient variability of adalimumab clearance during an intensive sampling study of Crohn’s disease patients receiving maintenance therapyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Lower adalimumab (ADA) clearance (CL) is associated with improved outcomes in Crohn’s disease (CD) and may be a superior pharmacokinetic (PK) measure than ADA concentrations. We compared intra-patient variability in ADA CL and concentrations within a 14-day treatment cycle and across two consecutive cycles under maintenance treatment.

Methods

In a previous PK study of CD patients receiving maintenance ADA 40mg fortnightly, samples were collected intensively at 3 visits (day 4-6, 7-9, and 13-14 post dose) across 2 consecutive cycles. Available sera from this cohort were subsequently used to measure ADA concentrations (lower limit quantification: <1.6 µg/mL) and antibody to adalimumab (ATA) status using a drug tolerant homogeneous mobility shift assay, and albumin. Apparent ADA CL (L/day) was calculated incorporating these measure parameters in a nonlinear mixed effect model with Bayesian priors (under steady state assumption) with dose and inter-dose interval with ATA and albumin as covariate. Rates of sustained clinical and biochemical remission (Harvey Bradshaw Index (HBI) score consistently <5 and CRP levels consistently <3 mg/L) were estimated for each patient. Longitudinal changes in PK parameters within-and-across cycles were evaluated using intra-patient coefficient of variation and linear mixed effect models.

Results

Sera was available from 70 study visits in 12 patients (6 males, mean age 36 years). Median ADA concentrations and CL were 8 µg/mL (IQR 6.0-10.4) and 0.374 L/day (IQR 0.29-0.43), respectively, with ATA detected in one patient (#9). Estimated ADA concentrations and CL is presented in the Table. Intra-patient variability in CL was much lower across the two 14-day cycle (9% and 7%, respectively) compared to intra-patient variability in ADA concentration (15% and 13%, respectively). Linear mixed effect models confirmed these findings with no impact of sampling time on CL (intercept=0.46±0.12 L/day; slope estimate=0.002±0.002 L/day; p=0.16) as compared to significant change in ADA concentrations (intercept=10.6±1.2 µg/mL; slope estimate=-0.25±0.03 µg/mL; p<0.01) over inter-dose interval sampling time. Sustained clinical and biochemical remission was achieved in 5/12 patients (42%); none presented with CL >0.8 L/day (a cut-off previously associated with worse outcomes). Of 7 patients without sustained clinical and biochemical remission, two presented with optimal concentrations (> 10 µg/mL), thus suggestive of mechanistic failure, and one developed ATA, lower concentration and higher ADA CL.

Conclusion

CL is subject to less intra-patient variability than ADA concentrations, supporting its assessment at any time point within a 14-day treatment cycle.Read more P774 Less combination therapy and more fistulotomy in perianal fistulizing Crohn’s disease in the elderlyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Prevalence of Crohn's disease (CD) is on the rise in the elderly and perianal fistulizing lesions affect nearly one in five patients over 60. Despite the specificity of luminal disease, few studies have focused on the management of perianal fistulizing CD (pfCD) in this population. This study aimed to describe pfCD in patients operated on after the age of 60 to compare findings (presentation, management, outcome) with those obtained in younger patients operated on during the same period.

Methods

Between January 2012 and December 2022, all CD patients (known or confirmed during follow-up) aged 60 years or older undergoing a first surgical intervention for anal fistula at two medical centers were included. For each older patient, two younger patients (<60 yr) operated on during the same period were matched for comparison.

Results

Among 536 patients who underwent surgery between January 2012 and December 2022, there were 30 (6%) aged ≥ 60 yr at first surgery: 17/30 (63%) reported anal fistula and CD in the same year. Among matched younger patients, 31/60 (52%) reported anal fistula more than one year after CD diagnosis. Colonic involvement was more prevalent in the older age group (70% vs 33%); ileal forms were more common in the younger age group (23% vs 3%) and complex fistulas were predominant (93%) in both age groups. Use of biologics was similar in the two groups: anti-TNF alpha therapy in 96.7% of younger patients and in 86.7% of older patients (p=0.07); other biologics in 40% of patients in both groups. However, in patients over 60, combined therapy and anti-TNF alpha optimization were less frequent (p=0.0002 and p=0.0001), as was use of immunosuppressants (33%), with a vast majority on azathioprine. Older patients had fewer surgical interventions (3 vs 4.5, p=0.008). They also had less frequent sparing surgery (30% vs 58%, p=0.01), while fistulotomy was performed more frequently (27% vs 5%, p=0.003). The rates of anal fistula closure were comparable between the two groups (60% vs 62%).

Conclusion

Synchronous diagnosis of anal fistula and CD within the first year of care is not uncommon in patients over the age of 60, which suggests CD should not be overlooked in older individuals developing an anal fistula. Although there appeared to be age-based differences in overall medical-surgical management, and patients over 60 had more comorbidities, use of biologics was similar in the two groups, and the rates of fistula closure at the end of follow-up were comparable in the two populations.Read more P1001 Predictive factors of colectomy in patients admitted with Acute Severe Ulcerative ColitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Acute severe ulcerative colitis (ASUC) is a life-threatening condition which requires quick decision making and urgent treatment. To facilitate this process, it is essential to identify patients at a high risk of emergency colectomy. The aim of this study is to identify predictors for emergency colectomy in patients with ASUC.

Methods

A retrospective study of 121 patients admitted with ASUC to a single gastroenterology centre between 2010 and 2020 was performed. Clinical and demographic data, laboratory and endoscopic examinations results were analysed as potential predictors of colectomy. Albumin and C-reactive protein (CRP) levels were recorded at baseline and at the 3rd day after intravenous steroids (IVS) initiation.

Results

119 patients initially received IVS, while 2 patients with suspected intestinal perforation underwent emergency colectomy on the first day. 64 (53%) were women, with a median age of all patients of 33 (IQR 27-49) yrs. 15 (12.4%) patients admitted with ASUC underwent colectomy, while mortality rate during hospitalization was 1.7%. During the entire follow-up period, with a median duration of 46.5 months (23-88.25), colectomy was performed in 19 (15.7%) patients. Overall, in the study group, colectomy rate at 1 month, 3 months and 2 years were 12.4%, 12.4%, and 14.0%, respectively. Assessing further outcomes after colectomy, during the follow-up period, 13 (68.4%) achieved clinical remission, 1 died during the operation, and 5 (26.3%) patients still have an active course of the disease requiring immunosuppressive treatment.When comparing patients in the colectomy group (n=13) with patients who avoided colectomy during this hospitalization (n=105), no significant differences were found in age, sex, duration of illness, body mass index, endoscopic activity, the use of prednisolone or azathioprine prior to admission or previous treatment with biologics. The presence of cytomegalovirus and Clostridium difficile infection was also not associated with a higher risk of colectomy. Significant differences between the groups were found comparing the laboratory findings: the strongest predictor of colectomy was the CRP/albumin ratio at day 3 after IVS initiation (median value was 1.26 (0,81-3,26) in colectomy group vs. 0,64 (0,25-1,36) in non-colectomy group, p<0.001). The difference was also observed when comparing albumin (median 26 (24-28) vs. 29 (27-32), p=0.012) and CRP (median 33 (25-83) vs. 16 (8-37), p=0.003) levels separately on the 3rd day, while at baseline there was no significant differences in laboratory findings.

Conclusion

A low serum albumin level, higher CRP and CRP/albumin ratio are predictive factors of emergency colectomy in ASUC patients.Read more P775 Efficacy and safety of risankizumab in children with Crohn’s disease: A preliminary reportWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Risankizumab (RISA) is a selective p19 anti-interleukin (IL)-23 antibody approved for adults with Crohn’s disease (CD) and for children ≥ 16 years in selected countries. Given delays in pediatric approvals, we aimed to assess the real-world effectiveness and safety of RISA in pediatric patients with CD.

Methods

From September 2022 to November 2023, all pediatric patients (<18 years) with refractory CD treated with RISA in 5 centers from US and Israel were retrospectively included. All received a 600 mg RISA intravenous induction at weeks 0-4-8. Patients completing the induction phase were treated with subcutaneous injection of 360mg at week 12 and every 8 weeks thereafter. The primary endpoint was steroid-free clinical remission (SFR) after 3 intravenous infusions (i.e., wPCDAI ≤12.5). Secondary endpoints included clinical response (i.e., >17.5-point decrease of wPCDAI), biochemical remission (CRP ≤ 5 mg/L) and drug sustainability. Adverse events were explicitly recorded.

Results

Included were 23 children [13 (56%) males; mean age at diagnosis 14.1±3.7 years, median disease duration 3.9 (IQR 2.6-7.7) years, 11 (48%) < 16 years of age] with a median follow-up period of 21 weeks (IQR 9.4-44.2) (Table 1). All had failed at least one previous biologic treatment and 18 (78%) failed two, including 15 (65%) with prior ustekinumab treatment. After 3 infusions, SFR was observed in 15 (65%) children, clinical remission in 16 (70%), clinical response in 17 (74%), and CRP remission in 17 (74%). There was no difference in response rate of patients <16 years (64% SFR). In a subgroup analysis of 15 patients with prior ustekinumab exposure, SFR was observed in 11 (73%). Only two patients discontinued RISA during follow-up, one who was in clinical and CRP remission at week 12, due to loss of follow-up and the other due to occurrence of an intra-abdominal abscess. Ten patients completed 6 months follow-up, of whom 8 (80%) achieved SFR by then. Only one disease-related adverse event occurred in one patient (intra-abdominal abscess). No drug-related adverse events were recorded.

Conclusion

While awaiting pediatric registration trials, our preliminary data suggest that RISA is safe and effective in inducing and maintaining remission in children with highly-refractory CD. This includes also children previously failing ustekinumab and children younger than 16 years.Read more P572 Evaluation of safety, pharmacokinetics and efficacy of oral treatment with OST-122 in patients with moderate to severe ulcerative colitis: A Phase Ib/IIa, randomized, double blind, placebo controlled clinical trialWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

OST-122 is an orally administered, GI-targeted and non-systemic JAK3/TYK2 inhibitor. In preclinical models and in healthy volunteers, OST-122 has demonstrated excellent safety and tolerability with minimal systemic exposure, thereby reducing the risk of causing serious systemic toxicities associated with current JAK inhibitors. The aim of this study was to evaluate the safety, tolerability, pharmacokinetics and preliminary efficacy of OST-122 in moderate to severe ulcerative colitis (UC) patients.

Methods

This randomized, double blind, placebo controlled, multicenter proof of concept trial enrolled patients aged 18 to 75 years with moderate to severe UC (Total Mayo score 5-10, Endoscopic score ≥2) and with inadequate/loss of response, or intolerance to conventional (steroids and immunomodulators) and/or advanced therapy (ie. anti-TNFα, anti-integrin, anti-interleukin 12/23) in a 3:1 ratio to receive oral OST-122 400 mg (n=28) or placebo (n=9) for 28 days.The main objective of this study was to evaluate the safety and tolerability of OST-122 in patients with moderate to severe UC over 28 days by assessing the number, severity and type of adverse events. The pharmacokinetic profile was determined to confirm the compound’s low exposure in plasma (Cmax, AUC) previously observed in healthy volunteers and preclinical model. Another objective was to explore preliminary efficacy by assessing clinical parameters including rectal bleeding score and clinical response.

Results

A total of thirty-seven patients, 59.5% males, mean age of 44.8 years were included. The patients in the OST-122 group (n=28) had a mean Total Mayo Score at baseline of 8.1 compared to TMS = 6.7 in the placebo group (n=9).Safety analysis revealed no significant differences in the number of reported adverse events between the two treatment groups, nor did serious adverse events occur (Table 1). There were no clinically relevant changes in vital signs, laboratory values or ECG parameters which raise any safety concerns.After 28 days of treatment, 63% of patients taking OST-122 showed an improvement in rectal bleeding (vs 33% in the placebo group), 44% achieved a clinical response (vs 11% on placebo) and 22% reached clinical remission (Figure 1). Statistical significance was not achieved due to the small study size and patient variability. Pharmacokinetic data indicated minimal plasma concentrations (C_{max,ave. Day28} 0.92 ng/mL) and therapeutically relevant levels in colon tissue (C_ave.,Day28 15.5 ug/g tissue).

Conclusion

GI-restricted OST-122 was well tolerated during the 4-week treatment. Its excellent safety profile, limited systemic absorption and promising trends of clinical activity may provide a safer therapeutic option for patients with moderate to severe UC.Read more P801 Umbrella review of effectiveness of digital technologies for the management of Inflammatory Bowel DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The use of digital technology is increasing significantly world wide, with 67% of the global population (5.1 billion people) having subscribed to mobile internet services in 2018 [1]. Clinical trials assessing commercially available health tools are sparse, with limited evidence-based outcome data. Systematic reviews of the randomized clinical trials (RCTs) on digital health technology in inflammatory bowel disease (IBD) performed so far, provide mixed results from highly heterogeneous studies. This umbrella review aims to investigate the effectiveness of digital health technology for the care of patients with IBD, to identify research gaps and highlight areas where future work should focus on.

Methods

The following databases were searched for systematic reviews published from 2012 to August 2022: PubMed and Medline via OVID, Embase via Ovid, Cochrane Library and Prospero database of systematic reviews, CINAHL via EBSCO, PsycINFO via Ovid, AMED (Allied and Complementary Medicine database) via Ovid. Electronic search results were downloaded into the “Covidence” software and screened by two reviewers independently by titles and abstracts according to the inclusion and exclusion criteria. Standardised extraction forms were established in Microsoft EXCEL. The methodological quality assessment of the included reviews was performed using AMSTAR 2.0. [2]

Results

The literature search identified 65 studies that were uploaded on the “Covidence” software for title and abstract screening. Three duplicates were removed. Of the 62 papers remaining, 32 were excluded based on title and abstract screening. The full text of the remaining 30 was analysed, with a resulting selection of 8 systematic reviews (four including meta-analyses) deemed relevant to this umbrella review. The RCTs on digital health technology in IBD conducted so far have identified aspects of IBD care that appear to benefit from the use of digital technology, including the patients’ satisfaction, their quality of life and quality of care, their adherence to medications and a reduced number of hospital attendances. Existing trials have not, however, been able to prove a direct benefit of using technology to achieve or maintain clinical remission (Table 1).

Conclusion

Telemedicine should be regarded as an important adjuvant to routine clinical practice. Future larger trials with longer follow-up and defined interventions and outcomes have the potential to address unanswered questions in this area and to identify the patients with IBD who would most benefit from telemedicine so that these approaches can be tailored to specific groups.References:[1] Agarwal K, del Hoyo F. J Med Internet Res 2019.[2] Shea BJ, Reeves BC, Wells G. BMJ 2017, 358, j40.Read more P877 A comparison of vedolizumab and ustekinumab treatment in patients with Ulcerative Colitis after failure of treatment with tumor necrosis factor inhibitorWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Data comparing vedolizumab (VDZ) and ustekinumab (UST) in patients with ulcerative colitis (UC) previously treated with tumor necrosis factor inhibitor (TNFi) and followed with regular serum-drug measurements are scarce. In the national pharmaceutical tender system of Norway, VDZ was listed as the first drug of choice after failed TNFi treatment from 2016 to 2019 and UST from 2020 to 2022. We aimed to compare drug persistence, effectiveness, drug dosing and disease activity in patients treated with VDZ or UST after failed TNFi therapy.

Methods

We included patients who had failed at least one TNFi and started either VDZ treatment (years 2016-2019) or UST (years 2020-2022). Patients were followed for one year after initiating the treatment or until discontinuation. Prospectively recorded data were obtained from the electronic patient journal (EPJ) and the local IBD-registry. Clinical remission was defined as 6-point Mayo Score ≤1, and biochemical remission was defined as CRP<5 mg/L and FC<250 µg/g. Patients were followed with regular serum-drug measurements and dose adjustments were made at the discretion of the treating physician based on serum-drug measurements and clinical activity at follow-up visits. Wilcoxon signed rank and Mann Whitney U test were used to assess differences in paired and unpaired data, respectively.

Results

A total of 116 patients were included, 59 treated with VDZ and 57 with UST. At 52 weeks, there was no difference in estimated drug persistence with 85% [73-92] for VDZ and 92% [80-96] for UST. Clinical remission increased significantly in both groups (Table 1), and no difference was found between UST and VDZ for clinical remission at week 0 and 52 (OR=2.1 [0.9-4.5] and OR=0.9 [0.3-2.3]). Contrary to the VDZ group, there was a significant decrease in CRP from week 0 to 52 in the UST group, while FC decreased significantly in both groups (Table 1). The proportion of patients in biochemical remission increased in the UST group while there was no significant change in the VDZ group. Significantly more patients treated with UST received an intensified treatment regime at 52 weeks (interval less than eight weeks) compared to VDZ treated patients (87% (95% CI [74-94]) vs 59% (95% CI [45-72])).

Conclusion

This study demonstrates that one-year drug persistence and clinical remission were high and comparable in both UST and VDZ treated UC patients with previous TNFi failure. Treatment with UST, but not VDZ, was associated with a significant increase in the proportion of patients in biochemical remission from induction to 52 weeks. However, a significantly larger proportion of patients treated with UST received intensified dosing at 52 weeks compared with VDZ treated patients.Read more P573 Simplified MARIA score does not predict long-term outcomes in Crohn’s disease patients undergoing modified side-to-side strictureplasty for extensive ileitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Strictureplasty techniques were developed to limit the risk of short bowel syndrome in Crohn’s disease (CD) patients with affected small intestine. In the setting of extensive small bowel disease, long strictures might be treated with modified side-to-side isoperistaltic strictureplasty (SSIS). We studied long-term outcomes in patients who underwent SSIS and evaluated if radiological features on MR enterography (MRE) predict them.

Methods

This retrospective study included CD patients who underwent SSIS, for whom preoperative and six-month postoperative MRE were routinely performed. Simplified MARIA (MARIAs) score, considering wall thickness, edema, fat stranding and ulcers (score >1 active CD; maximum 5) was used. Improvement in maximal wall thickness was defined as decrease of at least 30% from baseline. Deep remission was defined as absence of symptoms and endoscopic remission (mRutgeerts score ≤i1), and clinical recurrence as occurrence of new symptoms confirmed by endoscopy (mRutgeerts score ≥i2b) or radiology (new strictures/inflammation) requiring treatment. Clinical data were collected from medical records. The correlation between recurrence and features within the MARIAs score was assessed.

Results

Thirty CD patients underwent SSIS and had pre- and six-month postoperative MRE (table). Immediately after surgery, 13 (43.3%) patients were continued or initiated on advanced therapy. Over a median [IQR] follow-up of 7.4 [3.3-9.3] years, 17 (56.7%) patients showed clinical recurrence of whom 6 (20.0%) needed surgical reintervention (figure). Deep remission was observed in 8 (26.7%) patients. Preoperatively, all patients had a maximum MARIAs score of 5. After surgery, the median [IQR] change in MARIAs score was 0.0 [0.0-0.8]. Cox regression analysis showed no association between decrease in overall MARIAs score, nor separate components of this score, with clinical or surgical recurrence free survival. Wall thickness decrease of >30%, observed in 15 (50%) patients, showed a trend for clinical recurrence free survival (p=0.098). Three patients showed normalization of MARIAs score and showed no recurrence thereafter. None of the clinical variables collected showed significant association with recurrence, except for immediate postoperative advanced therapy which had a 70% protection from clinical recurrence [p=0.036 / HR 0.3 (0.097-0.92)].

Conclusion

Long-term follow-up of CD patients undergoing SSIS showed that 57% of patients had clinical recurrence and 20% needed surgical reintervention. The MARIAs score was not predictive of long-term postoperative clinical or surgical recurrence as most features of the score remained unaltered. These shortcomings of the MARIAs score should be addressed when designing improved scoring tools.Read more P802 Impact of early use of immunomodulator on the outcomes of Crohn's disease: A Systematic Review and Meta-AnalysisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Although immunomodulators play a crucial role in the treatment of Crohn's disease, robust evidence regarding the impact of early use of immunomodulators on its outcomes is still limited.

Methods

We searched MEDLINE, EMBASE, and the COCHRANE library to identify articles analyzing clinical outcomes according to the timing of immunomodulator administration in Crohn's disease. A meta-analysis was performed using a random-effects model to pool estimates and report hazard ratios [HRs]. Types of immunomodulators include thiopurines or methotrexate.

Results

A total of 7 studies were identified as eligible for the meta-analysis. Early immunomodulator administration within 1 to 3 years after diagnosis was associated with a lower risk of bowel resection surgery (HRs 0.57, 95% confidence interval [CI] 0.45-0.71), but it was not associated with a lower risk of perianal surgery (HRs 0.62, 95% CI 0.27 - 1.39). In subgroup analyses, early immunomodulators were effective in lowering the risk of intestinal resection in both adults and the young population.

Conclusion

Early administration of immunomodulators in Crohn's patients is associated with a lower risk of bowel resection surgery. This finding suggests that when immunomodulators are administered within an optimal therapeutic window, they possess the potential to alter the disease course in Crohn's patients.Read more P887 Comparative efficacy of JAK inhibitors versus vedolizumab in patients with hypoalbumineamia and Ulcerative colitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The IBD community are seeking ways to personalize medication choices for individual patients. Hypoalbumineamia is a poor prognostic marker in ulcerative colitis (UC) as a surrogate marker of disease activity. Biologic molecules are intermittently dosed using albumin binding to maintain plasma concentration, therefore in low albumin states drug clearance is accelerated. This effect is potentially less significant in regularly dosed, JAK inhibitors (JAKi).

Methods

All patients at our unit taking a JAKi were included. Patients using vedolizumab were selected for inclusion based on the nearest neighbour with respect to medication start date. Vedolizumab was chosen as a second line advanced therapy used regularly in UC. Demographic and disease characteristics were collected. Blood tests immediately prior to starting medication were collected. Outcome measure was response to treatment based based on drug continuation and clinician documentation of treatment success at 6 months.

Results

56 patients were included; 28 receiving a JAKi, 28 patients using vedolizumab. The JAKi group consisted of 8 patients receiving Filgotinib, 12 Tofacitinib and 8 Upadacitinib. Patients receiving JAKi were younger (mean age 44 years, SD 14) compared to vedolizumab (56 years, SD 20). Both were predominantly white (JAKi n=16, Vedolizumab n=22). Chronic liver disease was uncommon in both groups; JAKi n=2 (7.1%) and vedolizumab n=3 (10.7%), none of whom had cirrhosis. More hospital admissions were observed in the year prior to starting treatment in patients who received JAKi (n=16, 57.1%) compared to vedolizumab (n=9, 32%). Hypoalbuminaemia (defined as ≤30g/L) was seen in 5 patients in each group. In patients receiving JAKi 16/23 (69.7%) patients without hypoalbuminaemia responded to treatment at 6 months, compared to 3/5 (60%) with low albumin. (p=0.999). In patients receiving Vedolizumab 18/23 (78.3%) patients responded to treatment at 6 months, compared to 1/5 (20%), (p=0.026).

Conclusion

In patients with hypoalbumineamia, vedolizumab was less effective compared to normal albumin states. A similar effect was not observed in patients receiving JAKi. Numerically the efficacy of both vedolizumab and JAKi was worse in patients with hypoalbuminaemia, as would be expected given the likely reflection of increased disease severity. This data suggests that those patients requiring advanced therapy with hypalbuminaemia might respond better to a JAKi. Further research is needed to investigate this finding.Read more P574 Clinical outcomes in extending of injection period of ustekinumab from every 8 to 12 weeks in patients with Crohn’s disease (CD-EXTEND Study)Wed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

De-escalation was a useful strategy for improving patient’s QOL and reduction of medical expenses. However, de-escalation of ustekinumab (UST) for the patients with Crohn’s disease (CD) has not been reported. The aim of this study was to elucidate clinical outcomes of de-escalation of UST.

Methods

This was a single-centre prospective observational study approved by the institutional review board of our hospital. CD patients who selected de-escalate UST treatment after administration of intravenous UST 6 mg/kg and subcutaneous UST 90mg every 8 weeks until 54 weeks were enrolled in this cohort. Primary endpoint was clinical remission rate at one year, including patients treated with re-escalation. Secondary endpoints were persistency of de-escalation of every 12 weeks and re-escalation effects of every 8 weeks. We also compared backgrounds and biomarkers including CRP, fecal calprotectin (FC) for persistent and non-persistent groups. Cut-off values of prediction for non-persistent was calculated by receiver operating characteristic (ROC) curve. Definition of clinical remission was CDAI<150 for CD.

Results

In total, 30 participants were included in the final analysis. Clinical remission rate at one year was 96.7% (29/30). Persistency of de-escalation at one year was 76.7% (23/30). Persistency after re-escalation was 85.7% (6/7). There was no difference between the backgrounds of persistent (n=23) and non-persistent groups (n=7). CRP titer at week 12 was significantly higher in non-persistent group than persistent group (Median 0.59 vs 0.17 mg/dL, p=0.021). FC titer at week 0, 12 and amount of change at week 24 was significantly higher in non-persistent group than persistent group (Median 660 vs 120 μg/g, p=0.021;1341 vs 61 μg/g, p=0.001; 528 vs 4 μg/g, p=0.04). Cut-off values of prediction for non-persistent from CRP at week 12, FC at week 0, 12 were 0.33 mg/dL, 314 μg/g, 581.5 μg/g, respectively.

Conclusion

De-escalation was feasible strategy for CD patients treated with UST. CRP and FC were good prediction biomarker for non-persistenceRead more P803 iGenoMed-MTT: A prospective multiomic study of response to molecularly targeted therapies in IBDWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

No tools exist to individualize treatment selection in Inflammatory bowel disease (IBD) to optimize outcomes. We prospectively recruited patients prior to initiation of molecularly targeted (advanced) therapy (MTT) to identify predictive biomarkers of response and define pathways impacted by successful treatment.

Methods

Serum was collected before initiation of treatment in all patients, and at visit 1 (V1~16 wks) for a subset of patients. Serum samples were analyzed for >140 protein biomarkers (OLINK) and >1200 lipid metabolites. Whole exome sequencing and GWAS data was generated for all participants. Initial data outline proteomic data.

Results

Of the first 166 IBD patients analyzed, therapies initiated included TNF antagonists (n=85), ustekinumab (n=43), vedolizumab (n=28) and janus kinase inhibitors (n=10). Bio-naïve (n=96) and patients using baseline corticosteroids (n=77) were included. Sixty-three patients achieved remission.In TNF-antagonist initiations, serum TNF concentrations increased between baseline and V1 (p=4E-3), while it decreased for other MTTs (p=0.07). In bio-naïve patients, serum TNF concentration had a strong correlation with CXCL10 (r=0.58, P=3E-10). From the Principal Component Analysis of analytes correlated to TNF in bio-naïve patients, we built a proxy for the level of active TNF.At baseline, compared to TNF antagonist naïve patients, significantly higher serum TNF concentrations existed in patients with prior TNF-antagonist exposure >1-month post-cessation and a markedly high TNF concentration with cessation <1 month prior to baseline (p< 2E-16). In patients with prior TNF-antagonist exposure, serum TNF concentrations did not correlate with other cytokines (incl. CXCL10). In these patients, elevated serum TNF were found at V1, suggesting accumulation of inactive (complexed) TNF with treatment. A similar pattern was observed for IL-12 after ustekinumab treatment (elevated serum IL-12 with recent ustekinumab (p= 8E-13), large increase in IL-12 after ustekinumab (p=9E-5)). Reduced IL-12 concentrations existed in current corticosteroid users, compared to previous users and those who never used (p=4E-8). In baseline samples in bio-naive patients prior to therapy initiation, serum concentrations of six analytes provided a discriminant model of corticosteroid use, whith an area under (AUC) the receiver operation characteristic (ROC) curve showed excellent discrimination (AUC=0.91).

Conclusion

These data uniquely characterize proteomic data in patients with various advanced therapies and will enable development of predictive panels. Unique availability of multiple therapies linked to longitudinal proteomic data may allow personalized panels for treatment selection.Read more P575 Kono-S anastomosis reduces post-op intervention after ileocolic resection for Crohn’s diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Ileocolic resection and anastomosis is the most common intestinal operation for Crohn's disease (CD). However, the choice of anastomosis remains a topic of debate. The SUPRME CD randomized trial demonstrated decreased rates of surgical recurrence after Kono-S anastomosis (KSA). We aimed to compare the long-term recurrence-free survival between KSA and stapled side-to-side (SSTS) anastomosis in a retrospective cohort. We hypothesized that KSA was associated with a lower risk of postoperative recurrence requiring intervention than SSTS.

Methods

We included consecutive patients from a prospectively maintained database who underwent ileocolic anastomosis for terminal ileal CD between 2020 and 2022. Patients with other types of anastomoses were excluded. The short-term postoperative outcomes and interventions for perianastomotic recurrence were compared between the two groups.

Results

Overall, 174 patients underwent ileocolic anastomosis: KSA, 83 (47.7%) and SSTS, 91 (52.3%). In the KSA group, compared to SSTS, median BMI was lower (24.3 vs. 26.4 kg/m², p=0.04), median operative time was longer (186 vs. 146 minutes, p<0.001), and patients were more likely to have mesenteric excision (53% vs. 15.4%, p<0.001). There were no significant differences in the short-term postoperative outcomes. After 12 months, 12 (30%) patients in the KSA group and 14 (35%) in the SSTS group developed endoscopic recurrence with a Rutgeerts score ≥i2 (p = 0.81). Compared with the SSTS group, the KS group received more postoperative biologics (65.1% vs. 39.6%, p=0.001) and more frequent medical therapy for perianastomotic recurrence [18/20, 90%] vs. [15/22, 68%]; p=0.14). On multivariable analysis, the KSA (OR 0.09, 95% CI 0.01-0.95, p=0.05) was associated with a lower risk of perianastomotic recurrence requiring surgical and endoscopic intervention.

Conclusion

We did not observe any statistically significant differences in overall recurrence-free survival between KSA and SSTS. However, the Kono-S anastomosis was independently associated with a decreased rate of endoscopic or surgical intervention for perianastomotic recurrence.Read more P897 The association of HLA-DQA1*05 carriage with immunogenicity to anti-tumour necrosis factor therapy and drug persistence in Asian patients with inflammatory bowel diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

HLA-DQA1*05 carriage increases anti-tumour necrosis factor (TNF) immunogenicity and lowers drug persistence in European inflammatory bowel disease (IBD) patients. There is a paucity of data for Asian patients. We hypothesize that the HLA-DQA1*05 allele is present in our local IBD population and may be associated with similar clinical and pharmacokinetic outcomes as European cohorts.

Methods

A single-centre retrospective study of consecutive IBD patients on Infliximab (IFX) or Adalimumab (ADM) was performed.HLA-DQA1*05 carriage was tested with Sanger sequencing. Serum anti-drug antibody (ADA) levels were analysed at each IFX infusion and per physician discretion for ADM. Concomitant immunomodulator (IM) therapy with Azathioprine or Methotrexate was recorded.Primary outcome was immunogenicity to IFX or ADM, defined as ADA concentration ≥10 AU/ml at any time point. Secondary outcomes were loss of response (LOR), defined as IBD symptom-related treatment intensification, and persistence, defined as anti-TNF continuation at end of follow-up. The effects of HLA-DQA1*05 carriage on outcomes and predictors of persistence were analysed.Results 39 patients (28 Crohn’s disease, 11 ulcerative colitis) were included (mean age 39 years, median disease duration 10 years). 24 patients had IFX as first anti-TNF agent (21 with IM, 3 as monotherapy), 7 of whom had second-line ADM with IM. 15 patients had ADM as first anti-TNF agent (13 with IM, 2 as monotherapy), 2 of whom had second-line IFX (1 with IM). 15/39 (38.5%) patients were positive for HLA-DQA1*05. 42/48 (87.5%) of anti-TNF exposures were on IM.In HLA-DQA1*05 carriers compared to non-carriers, development of ADA (61.1% vs 47.8%, p=0.397) and LOR (42.1% vs 31.0%, p=0.433) was numerically higher but not statistically different. Persistence of first anti-TNF agent was similar between carriers and non-carriers at the end of follow-up (median 28.0 months vs 21.5 months, p=0.364) (Figure 1). ADA development was not associated with LOR (p=0.07) or persistence (p=0.29).19/48 (39.6%) of anti-TNF exposures discontinued treatment at the end of follow-up, 13 of whom experienced LOR. 10/13 (76.9%) of patients with LOR were female. Female sex was significantly associated with anti-TNF non-persistence on univariable (OR 4.82, 95% CI 1.38-16.75, p=0.01) and multivariable logistic regression (OR 7.24, 95% CI 1.35-38.90, p=0.02), after adjusting for HLADQA1*05 carriage, presence of ADA and anti-TNF order (first versus second-line) (Table 1).

Conclusion

In Asian IBD patients, HLA-DQA1*05 carriage may not affect immunogenicity nor treatment persistence, especially with proactive therapeutic drug monitoring and concurrent IM. Female sex negatively affects persistence. Larger prospective studies are needed.Read more P804 Does Crohn's disease extent and behavior have an impact on ustekinumab effectiveness? A real-world multicenter retrospective studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Crohn's disease (CD) presents heterogeneity in clinical phenotypes. Progression of disease and response to therapy have been associated, among other factors, with the extent and behavior of the disease. Real-world data on long term effectiveness of ustekinumab (UST) in CD based on disease characteristics are limited and conflicting^1,2. The aim of this study is to describe real-world UST persistence according to disease distribution and perianal involvement in patients with CD.

Methods

This was a retrospective multicenter study involving adult patients with CD who received, at least, one dose of UST until August 2023, at 5 major hospitals in Athens, Greece. UST effectiveness based on treatment persistence was evaluated using Kaplan Meier curves for survival free of treatment discontinuation among patients with different disease extent and behavior. Log-rank test was used for statistical significance.

Results

A total of 147 adult CD patients who received biological treatment with UST for a median of 34 months (IQR 17-48) were included in the study. Patient baseline characteristics are shown in Table 1. UST treatment persistence rates were 93% (95% CI: 89-98) at 12 months and 87% (95% CI: 81-94) at 36 months. The persistence rate of UST differed significantly between patients with or without perianal disease (p=0.036) (Figure 1), while there was no significant difference based on disease extent (p=0.59) or behavior (p=0.31).

Conclusion

Our study showed that UST treatment persistence is similar in adult patients with CD, regardless of disease localization or behavior. Nonetheless, perianal disease involvement is associated with reduced treatment persistence.References1. Liefferinckx C, Verstockt B, Gils A, et al. Long-term Clinical Effectiveness of Ustekinumab in Patients with Crohn's Disease Who Failed Biologic Therapies: A National Cohort Study. J Crohns Colitis. 2019;13(11):1401-1409. doi:10.1093/ecco-jcc/jjz0802. Iborra M, Beltrán B, Fernández-Clotet A, et al. Real-world long-term effectiveness of ustekinumab in Crohn's disease: results from the ENEIDA registry. Aliment Pharmacol Ther. 2020;52(6):1017-1030. doi:10.1111/apt.15958Read more P552 Clinical factors associated with ustekinumab therapy persistence in a refractory Crohn’s disease cohortWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Ustekinumab (UST) is a monoclonal antibody that binds to the p40 subunit shared by pro-inflammatory interleukins 12 and 23. UST has demonstrated efficacy for the induction and maintenance of remission in patients with Crohn’s disease (CD). A proportion of patients with CD do not respond to UST at the standard dose of 90 mg every 8 weeks.

Methods

A multi-centre retrospective study of CD patient who commenced UST therapy at two specialist tertiary referral centres between October 2012 and March 2021 was performed. Patient demographics, baseline characteristics, medication history and disease behaviour were characterised. Duration of UST therapy and UST dose escalation were documented. UST therapy persistence, was considered a proxy for treatment response, and was expressed as time to discontinuation of UST therapy. The study evaluated whether UST dose optimisation was associated with increased UST therapy persistence; and clinical factors associated with UST therapy persistence. Optimised dosing was defined as a dosing regimen of UST 90mg at less than an 8-weekly interval. Statistical analysis was performed using survival analysis and multivariate cox logistic regression with effect of covariates on outcome expressed as odds ratios (OR).

Results

133 patients commenced UST during the study period (age [mean, range] 39 years, 16-79; 59% female; disease duration [mean, range] 12.4 years, 1-35). 99% of patients had failed at least 1 biologic and 72 patients (54%) required dose escalation during the study period. The mean duration of UST therapy was 74 weeks (range 2-427). 75 (56%) patients were still receiving UST at end of study period. Survival analysis demonstrated that there was no significant difference in UST persistence between patients receiving standard and optimised UST dosing regimens, p=0.58. Patients with early UST dose optimisation (within 6 months of therapy initiation) had increased UST therapy persistence, p=0.003. A multivariate regression analysis demonstrated that early UST dose optimisation (within 6 months of therapy initiation) was independently associated with a longer time to UST therapy discontinuation (OR 0.31 (95%CI 0.15-0.68), p=0.003). Neither disease duration (OR 1.11, p=0.66), male sex (OR 0.91, p=0.83), concomitant immunomodulator use (OR 1.03, p=0.95), perianal disease (OR 1.09, p=0.85), smoking status (OR 1.16, p=0.68) nor previous surgery (OR 1.47, p=0.33) were independently associated with time to UST therapy discontinuation.

Conclusion

UST is an effective treatment for CD patients with prior biologic therapy exposure. Optimised UST dosing regimens are frequently utilised in routine clinical practice. There appears to be an increased likelihood of treatment success with early UST dose optimisation.Read more P915 Multi-Omics Biomarkers for the Prediction of Response to Biologics in Patients with Inflammatory Bowel DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The treatment concept for inflammatory bowel disease (IBD) has been transformed with biologics now recommended as the first-line therapy for moderate-to-severe patients. However, the significant heterogeneity among IBD patients has limited the efficacy of selected biologics based on traditional clinical factors. Therefore, it is imperative to molecularly stratify patients to match them with the most appropriate biologics. In this study, we systematically reviewed baseline omics biomarkers that have the potential to predict response to biological therapies, aiming to facilitate precision medicine in IBD.

Methods

We conducted a comprehensive literature search using PubMed by which we included studies that explore the role of omics biomarkers in predicting the efficacy of various biologics including anti-TNFα, anti-integrin, anti-IL-12/23P40 and anti-IL-23 P19 in patients with IBD.

Results

Our review included 110 studies. Of these, 86 studies focused on anti-TNFα, 17 focused on anti-integrin and 7 focused on anti-IL-12/23P40 and/or anti-IL-23P19. These studies investigated multi-levels baseline biomarkers, including genomics, transcriptomics (bulk RNA and sc-RNA sequence), proteomics, microbiome, and metabolomics (derived from serum, urine, or stool). Furthermore, recent studies already focused on integrating multiple omics analysis and showed that the predictive model based on multi-omics data could significantly enhance their performance. Among the available biomarkers, mucosal transcription of OSM (AUROC = 0.83), IL-13RA2 (AUROC = 0.90), and TREM-1 transcription in mucosal biopsy (AUROC = 0.77) as well as in PBMC ( AUROC varies between 0.78 and 0.94) could accurately predict the response to anti-TNFα. The mucosal IL-23A transcription could discriminate responders from non-responders to anti-IL-12/23P40 with an AUROC of 0.90. OSM, biomarkers of intestinal collagen turnover like C4M, IL-17, IL-22, and TNFα in serum also showed significant potential in predicting the response to anti-TNFα, anti-integrin and anti-IL-12/23P40. In addition, single-cell molecular signatures with sc-RNA sequencing provided more profound insights into predicting the response to biologics. The lack of reproducibility in results across different groups may be due to the disparity in patient selection, methodology, and study designs among different investigations.

Conclusion

Numerous omics markers have shown great potential in predicting the efficacy of biologics. However, it is crucial to explore and validate these novel biomarkers in larger cohorts using harmonized protocols to facilitate their evaluation into actual clinical practice, especially for newer biologics like anti-IL-12/23P40 and anti-IL-23P19.Read more P821 Multi-site analysis of upadacitinib effectiveness in Crohn's Disease patients: A UK perspectiveWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Upadacitinib, a selective Janus Kinase inhibitor, is the newest advanced therapy in our armamentarium for the treatment of Crohn’s Disease (CD). It has been licensed for use in moderate-to-severely active CD. However, we have limited evidence of its effectiveness in a ‘real-world’ setting.

Methods

We undertook a retrospective cohort study on CD patients treated with upadacitinib in 24 UK hospitals. Clinical endpoints were reviewed at 12 weeks compared to baseline. Clinical remission was defined as Harvey-Bradshaw Index (HBI) <4 and response as HBI reduction ≥3 or sustained HBI <4. Biochemical remission using faecal calprotectin (FCal) and CRP was defined as FCal <200 µg/g and CRP ≤5, and response as FCal or CRP reduction of 50% and no increase in either parameter. Corticosteroid or exclusive enteral nutrition (EEN) use was documented.

Results

170 patients (50% male) were included. The breakdown of disease location included 15% ileal, 21% colonic, 61% ileocolonic and 3% upper GI. Prior advanced therapy exposure was seen in 168 patients, with 117 having failed 3 or more agents. Clinically active disease as defined by HBI ≥4 was seen in 133 patients at baseline. Median HBI at baseline was 8 (5-10) and by week 12 this had fallen to 3 (2-6) (p<0.001). 51% received prednisolone and/ or EEN during induction. Of the 128 patients with paired clinical assessment at baseline and 12 weeks clinical remission was achieved in 41% (figure 1A), 96% of whom were in steroid free clinical remission. This also included 39% of those with 3 or more previous advanced therapy failures. A further 40% were noted to have clinical response at 12 weeks. The median faecal calprotectin reduced from 781 µg/g (354-1800) to 255 µg/g (79-655) (p<0.0001) (figure 1B). In a multivariate analysis (table 1), a higher number of previous resections (p=0.031) and use of steroids (p=0.006) increased clinical remission rate whilst disease location/ behaviour, number of prior advanced therapy failures and baseline HBI did not have an effect. There were three significant adverse events noted including: a reported malignancy, zoster reactivation (drug withdrawal required), and thrombosis. Mild lipid, liver function, and full blood count changes were noted in 29 (17%) of patients, not requiring drug withdrawal.

Conclusion

Upadacitinib was effective in inducing clinical response in our cohort of patients with previously refractory CD regardless of the number of previous advanced therapy failures. A higher number of prior resections may represent lower overall disease burden but further investigation into the relationship with remission is required, as well as to review real-world endoscopic response and maintenance of remission.Read more P553 The safety and efficacy of adalimumab 80mg weekly as maintenance therapy in pediatric Crohn’s DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Intensification of adalimumab (ADL) dosing to weekly 40 mg injections, in response to low drug levels, has been shown to provide beneficial outcomes in pediatric patients with Crohn’s disease (CD). Our study aimed to evaluate the safety and efficacy of weekly 80 mg ADL administration in children with CD.

Methods

In this retrospective cohort study conducted across five Israeli centers, we reviewed the medical records of pediatric CD patients who received a high dose of ADL 80 mg weekly injections between 2016 and 2023. Collected data included demographic characteristics, disease features, laboratory studies, and treatment outcomes.

Results

Thirty-two children with CD were included: mean age 15.8 (±1.7) years at intensification, 21 male (66%), 18 (56%) with L3 phenotype. The median time to ADL 80 mg intensification from ADL induction was 48.4 weeks (IQR 23.1-122.5). The mean weighted Pediatric Crohn's Disease Activity Index (wPCDAI) was 28.5 (±16.9) at the time of intensification and the median calprotectin and C-reactive protein levels were 937 μg/g (IQR 540-1410) and 1.3 mg/dL (IQR 0.6-5.2), respectively. Clinically active disease was the main reason for ADL intensification (30, 94%). Baseline ADL levels were available in 30 patients (94%) with a median of 3.8 μg/mL (IQR 2.4-7.2). Among these, 23 children (77%) failed to achieve a target of ≥ 7.5 μg/mL. The median follow-up duration from the intensification dose was 91.2 weeks (IQR 53.6-149.1). Corticosteroids were required in 5/32 (15.6%) children, with a median time of 32.3 weeks (IQR 10.7-51.3) from intensification. There was no statistically significant difference in steroid utilization rates between children who achieved a target baseline drug level of ≥ 7.5 μg/mL and those who did not (p=0.934). Thirteen individuals (41%) discontinued ADL treatment, within a median of 24.7 weeks (IQR 11.7-57.1) from intensification. CD-related exacerbation, hospitalization, and surgery rates were 9 (28%), 4 (13%), and 2 (6%), respectively. No statistically significant differences were found in exacerbation (p=0.406), hospitalization (p=0.322), or surgery rates (p=0.427) between children who achieved a baseline ADL trough concentration level of ≥ 7.5 μg/mL and those who did not. Overall, ADL intensification was safe, but 3 (9%) patients developed new-onset psoriasis.

Conclusion

Our findings support the safety and efficacy of administering ADL at a weekly dosage of 80 mg as maintenance therapy in pediatric patients with moderate to severe CD.Read more P916 Off-label dose escalation of Ustekinumab in Inflammatory Bowel Disease patients. Incidence rate, timing, dosing patterns and outcomesWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

In patients with inflammatory bowel disease (IBD), after intravenous induction,Ustekinumab (UST) is administered as maintenance 90 mg every 8 (Q8) or 12 weeks (Q12) subcutaneously. As with other biological drugs, dose intensification may be effective after inadequate response or loss of response. However, different dosing regimens have been used and the best strategy is unknown. Our aim was to evaluate the incidence and efficacy of UST off-label dose escalation in IBD.

Methods

We performed an observational cohort study in 2 hospitals in Vigo,Spain. All patients who started UST between 1 June 2017 and 31 December 2022 to control their active IBD were enrolled. The primary endpoints were incidence rate and outcomes of UST off-label dose intensification. Secondary endpoints were the timing of dose escalation and the patterns indicated.

Results

1173 IBD patients received UST: females 53.8% (93), mean age 49.7(15.5) years, Crohn´s disease 82% (142), previous anti-TNF 93.6% (162) and vedolizumab 22.5% (39) (Table 1). Subcutaneous UST was maintained Q8 in 63.6% (110) and Q12 in 34.7% (60). Baseline activity data were higher in Q8 patients (p=0.001). At 16 week 23 patients (13.3%) had no response, but 9 (39.1%) became late responders at 6 months. Of the 173 IBD patients included, 38.2% and 30.6 % achieved clinical response and clinical remission at 1 year.Dose escalation was performed in 32.4% (56) with different patterns: 54.5% Q4 (30), 21.8% reinduction plus Q4 (12), 12.7% Q6 (7) and 10.9% only intravenous reinduction (6). The timing of dose escalation was: before 6 months in 19.6% (11), at 12 months 42.8% (24) and at 2 years 73.2% (41). Response and remission were achieved in 28.6% (16) and 41.1% (23) after dose escalation respectively. In 6.4% of the patients (11) a second dose escalation was indicated. Neither previous anti-TNF or vedolizumab nor concomitant use of steroids at starting UST were associated to dose escalation. IBD patients that were initially scheduled to receive subcutaneous UST Q12 needed less dosing escalation (p<0.001).

Conclusion

Off-label UST dose escalation was frequent and effective in achieving response in IBD patients. The schemes of dose-escalation were heterogeneous between the participants. Patients initially scheduled Q12 due to lower inflammatory activity required less dose escalation.Read more P554 Assessment of corticosteroid prescribing trends and appropriateness for management of Inflammatory Bowel Disease in a secondary care centre in New ZealandWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Corticosteroids are commonly used for inducing remission in Inflammatory Bowel Disease (IBD) but are considered ineffective for long-term maintenance¹. Evaluating the appropriateness of corticosteroid usage is crucial in optimising IBD management given their common adverse effects.

Methods

This study aimed to assess the appropriateness of corticosteroid usage for patients with IBD in a secondary centre in New Zealand, using international standards^2,3.A retrospective records’ audit was conducted in 2020, encompassing all IBD patients encountered in Nelson Hospital from 2005 to 2020. Ethical approval was obtained beforehand. The primary outcome measure evaluated was the appropriateness of corticosteroid prescriptions, in accordance with established international standards (UK² and ECCO³). Key criteria included dosage (strength and/or duration), patient counselling on side effects and alternatives.

Results

We studied a group of 613 IBD patients with an average age of 55, comprising 311 males and 302 females. Crohn's Disease was the predominant diagnosis (297 cases), followed by Ulcerative Colitis (252 cases) and Indeterminate Colitis (64 cases). Of the patients included in the audit, 51.4% (315 out of 613) were prescribed steroids during the 15-year study period. Of the 315 total prescriptions, 52.1% (163) were considered inappropriate. Among these, 28.6% (90) were excessively long courses, 23.5% (74) were due to under-dosing or multiple short courses, and 6.3% (20) were because of corticosteroid dependence. Out of a total of 315 prescriptions, Gastroenterologists issued 36.5% (115), while General Practitioners were responsible for 24.1% (76). The remaining prescriptions were divided among General Surgery (9%), General Medicine (6%), and the Emergency Department (5%).

Conclusion

Corticosteroid prescribing for IBD patients in this secondary centre in New Zealand deviated from international guidelines, primarily in terms of dose and duration. It’s vital to adopt accessible, customized guidelines and enhance quality measures to ensure IBD patients receive evidence-based corticosteroid treatment when needed.References1-Ford AC, Bernstein CN, Khan KJ, et al. Glucocorticosteroid therapy in inflammatory bowel disease: systematic review and meta-analysis. Am J Gastroenterol 2011;106:590-599; quiz 600.2- Mowat C, Cole A, Windsor A, et al. Guidelines for the management of inflammatory bowel disease in adults. Gut. 2011;60:571-607.3-Gomollon F, Dignass A, Annese V, et al. 3rd European evidencebased consensus on the diagnosis and management of Crohn’s disease 2016: part 1: diagnosis and medical management. J CrohnsColitis. 2017;11:3-25Read more P937 A Retropective Analysis of Micronutrient Status in Inflammatory Bowel DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Researchers are increasingly focusing on the influence of micronutrient levels on the initiation and prognosis of Inflammatory Bowel Disease (IBD). Earlier investigations have highlighted a connection between deficiencies in zinc and selenium and an elevated risk of IBD development and unfavorable outcomes. This study seeks to investigate the existing micronutrient status among Chinese patients with IBD and assess whether deficiencies in trace elements are associated with disease activity, extent of intestinal involvement, and the use of biological treatments.

Methods

This cross-sectional study included patients diagnosed with Crohn's disease (CD) or ulcerative colitis (UC) who underwent plasma micronutrient testing during outpatient or inpatient visits to the Department of Gastroenterology at Peking Union Medical College Hospital from May 2022 to October 2023. Baseline data, the history of biological agent use, and laboratory inflammation parameters such as hsCRP, ESR, and Alb were extracted from the Electronic Medical Record System. Colonoscopy images were examined to assess the extent of intestinal involvement and endoscopic activity. The distribution of micronutrient deficiency among patients with varying disease statuses was explored using the Pearson chi-square test and Mann-Whitney U-test.

Results

Among the 168 participants with IBD in this study (77 with CD, 91 with UC), a frequent occurrence of deficiencies in copper, selenium, strontium, and zinc was noted. In CD patients in the endoscopic active phase, there was a higher incidence of selenium and zinc deficiencies compared to the remission phase (selenium 0% vs. 11.3%, p=0.17; zinc 4.2% vs. 24.5%, p=0.052). In UC patients during the endoscopic active phase, strontium (14.5% vs. 0%, p=0.053) and zinc (17.7% vs. 3.4%, p=0.094) deficiencies were more likely to occur. CD patients with zinc deficiency and UC patients lacking zinc or selenium showed higher levels of blood hsCRP and ESR but lower levels of serum albumin. UC patients with E3 type involvement were more prone to selenium and strontium deficiencies compared to those with only left colon involvement (selenium 18.5% vs. 2.7%, p=0.025; strontium 14.8% vs. 5.0%, p=0.078).

Conclusion

This study identified a notable prevalence of micronutrient deficiencies in individuals with IBD, particularly during active phases. Specifically, patients with CD in an inflammatory state are inclined to exhibit zinc deficiency. In the case of UC, the absence of selenium, strontium, and zinc signals a higher level of inflammation. UC patients with involvement of the entire colon are more prone to experiencing deficiencies in selenium and strontium. These findings warrant validation through multi-center study and mechanism invetigation.Read more P822 Therapeutic Management And Risk Of Colectomy In Patients With Acute Severe Ulcerative Colitis And Previous Exposure To Anti-Tnf Drugs. A Cohort Study Of GeteccuWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

There are few data regarding the management on acute severe ulcerative colitis (ASUC) flare in patients with previous anti-TNF exposure. We evaluated the medical management, the risk of colectomy and factors associated comparing with a bionaive cohort.

Methods

A retrospective and multicentric study of GETECCU. Patients with ASUC episode between 2010-2020 were included in two cohorts: bio-exposed (cohort 1) and bio-naive (cohort 2). Patients with previous other biologics or JAK inhibitors exposure were excluded. Steroid response was defined as reduction of bowel movements and C Reactive Protein (CRP). Rescue therapy was used after steroid failure and maintenance therapy after steroid or rescue therapy response/remission. Clinical effectiveness of rescue and maintenance therapy was analyzed using partial mayo score (clinical response with decreased of 2-3 points, clinical remission ≤2). Colectomy rate was evaluated at short and long-term using survival analysis and was compared using cox logistic regression.

Results

Finally, 461 patients were included from 33 centres. Basal characteristics and medical management are shown in Table 1. Bioexposed patients received steroid therapy less frequently (82 vs 97%, p 0.001). Comparing with bionaive cohort, there were differences between medical management although steroid response and the use of rescue therapy were similar. However, clinical remission at one year was lower (44 vs 59%, p 0.03). Colectomy rates at 1 and 12 months were of 15 and 17% in Cohort 1, respectively. Comparing with bionaive cohort, there were a higher risk of colectomy at short and long-term, HR 2.46 (1.57-3.87, p 0.001) (Figure 1). There were no factors associated with colectomy at one year. Response to steroids was the only protective factor of colectomy at one year (RR 0.17, 0.07-0.45, p 0.001).

Conclusion

Management of ASUC in bio-exposed patients is heterogeneus and differs from bionaive patients. The risk of colectomy is increased. Although the response to medical treatment is not negligible, special efforts in standardizing therapies are warranted in order to improve prognosis.Read more P555 Switching from intravenous vedolizumab to subcutaneous maintains clinical remission even in intensified patients with Inflammatory Bowel Disease. One year follow-upWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Vedolizumab is a humanized monoclonal antibody. It is indicated for moderate to severe flare of Inflammatory Bowel Disease (IBD). Subcutaneous (SC) vedolizumab, is a major advantage for patients for home administration. This study aimed to analyze the percentage of clinical and biochemical remission at 52 weeks in all IBD patients on treatment with intravenous (IV) vedolizumab after switching to the SC one.

Methods

Single-center, descriptive, observational, and retrospective study. The study included all the IBD patients (19 patients) who were at the moment of inclusion with IV vedolizumab treatment in a tertiary hospital, who underwent a switch from IV vedolizumab to SC vedolizumab. In addition, the relationship between treatment with intensified IV vedolizumab and subsequent drug levels versus patients without intensification for 52 weeks.

Results

Ten patients (22.6%) were diagnosed with Ulcerative Colitis (UC) and 9 patients (47.3%) with Crohn´s disease (CD). The baseline characteristics of the 19 patients are described in Table 1. Reasons for starting IV vedolizumab: there was loss of response to a first anti-TNF in 10 patients (52.6%) and loss of response to two previous anti-TNFs was observed in 3 patients (15.7%). In 4 patients (21%) IV vedolizumab was started as the first line of treatment due to the increased risk of infections and a previous history of neoplasia. Finally, in 2 patients with CD (10.5%) it was started as prevention of recurrence. Up to a total of 8 patients (42.1%) were on an intensified IV vedolizumab before switching to SC vedolizumab. All 19 patients (100%) were in clinical remission and 15 patients (78.9 %) remained in biochemical remission prior to switching to SC vedolizumab. At the end of the follow-up (52 weeks) all of them achieved clinical remission and 17 patients (89.4%) achieved biochemical remission (Figure 1). Therefore, biochemical remission was achieved in 10% more patients after the switch. It was noted that biochemical remission was achieved in 87% of patients on the intensified regimen with IV vedolizumab versus 100% of patients on the non-intensified regimen. No statistically significant differences were obtained between patients who had been on intensified IV vedolizumab and those who had not. At one year of follow-up, SC vedolizumab was suspended in one patient due to muscle pain, and IV vedolizumab was restarted again.

Conclusion

Following the standard dose switch of SC vedolizumab, clinical remission is maintained, achieving biochemical remission in 89.4 % of patients one year with SC vedolizumab with maintained vedolizumab levels, even in previously intensified IV vedolizumab patients.Read more P823 Real-world effectiveness of upadacitinib in Crohn's disease; a UK multicentre retrospective cohort studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Upadacitinib is a Janus kinase inhibitor which has recently been approved for the treatment of Crohn’s disease. There are limited real-world studies on the outcomes of upadacitinib in Crohn’s disease. Our aim was to evaluate the outcomes of upadacitinib in a real-world cohort.

Methods

We conducted a retrospective, multicentre, cohort study. Our primary outcome was treatment persistence at week 24. Our secondary endpoints were corticosteroid-free clinical remission (Harvey-Bradshaw Index ≤4), and biomarker remission (CRP ≤5 mg/L and FCAL <250 µg/g). We measured outcomes at 12 weeks, 24 weeks and at last observation. We recorded adverse events.

Results

We included 74 patients who commenced upadacitinib over a two-year period for analysis, with a median follow-up time of 23 weeks (IQR, 15-39 weeks). All patients had failed anti-TNF therapy, with 78% and 58% additionally failing prior IL12/23 and vedolizumab (Table 1). Treatment persistence was 83.6% at week 12, and 76.6% at week 24 (Figure 1). Reasons for treatment cessation included primary non-response 15% (11/74), secondary loss of response 1% (1/74), and adverse events 12% (9/74). Rates of clinical remission were 58% (32/55) at week 12, 43% (16/37) at week 24, and 52% (35/67) at last observation. CRP remission rates were 45% (27/60) at week 12, 35% (12/34) at week 24, and 44% (30/69) at last observation. FCAL remission rates were 40% (17/42) at week 12, 31% (9/29) at week 24, and 36% (19/53), at last observation. There was a significant reduction in HBI, CRP and FCAL during follow-up (Figure 1). During the maintenance period, 11% (7/61) of the cohort who continued therapy were prescribed corticosteroids. Ten patients (19%) had a hospitalisation due to a Crohn’s flare. Five patients (7%) underwent Crohn’s disease related resectional surgery during the study period. Two were emergency surgeries (3%), and three (4%) were elective surgeries for symptomatic fibrotic strictures, which were present prior to commencing upadacitinib. Thirty-four adverse events were recorded across 29 patients (39%). Serious adverse events occurred in 9 patients (12%), three of which (4%) led to hospitalisation.

Conclusion

Upadacitinib was effective in a real-world, medically refractory, moderate to severe Crohn’s disease cohort with good persistence.Read more P938 Effectiveness and safety of switching from original infliximab to GP1111 biosimilar in inflammatory bowel diseases – prospective, cohort studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Biosimilars are highly similar to the already approved reference biological medication, and are potentially more accessible widespread due to the better cost-effectiveness. However, both the effectiveness and immunogenicity may differ due to structure characteristics. In 2020, non-medical switch was obligated from originator infliximab (IFX) to biosimilar GP1111 amongst inflammatory bowel disease (IBD, Crohns’s disease [CD], ulcerative colitis [UC]) patients in Hungary. As data regarding GP1111 are lacking in IBD, thus we aimed to assess the pharmacokinetics, effectiveness and safety of biosimilar GP1111 following the financial switch.

Methods

This was a real-world, prospective, single-center cohort study enrolling IBD patients who were switched from original IFX to GP1111 biosimilar. Baseline was defined as the day of the switch, and 52 weeks of follow-up was set. Demographic and clinical data were recorded at w0, w8, w16, w24, and w52, while infliximab serum levels were measured at baseline and at w52. Primary outcome was change in serum trough level of IFX, while sustained steroid-free remission, loss of response rates and adverse events were secondary outcomes.

Results

Overall, data of 142 patients were analyzed (median age: 43.1 years [IQR: 32.3 - 49.6]; male/female ratio: 77/65; CD: 97, UC: 42). Mean follow-up period was 46.2 ± 10.3 weeks. Change in serum IFX level was not observed (baseline 3.2 ± 2.3, µg/mL; w24: 3.7 ± 2.7 µg/mL; p = 0.106). Sustained steroid-free remission rates did not alter at w52 (99/142) from baseline (86/142) (p = 0.11). Overall, treatment was ceased in 24 patients. Following dose escalation and intensification, 9/18 patients discontinued treatment due to loss of response. Further treatments were ceased in 15 patients due to allergy (8), paradoxical reactions (3), malaise (1), pregnancy (1), and non-compliance (2). At w52 83.1% of the patients were on drug, and treatment persistence was not associated with the length of prior IFX treatment period.

Conclusion

Our study revealed convincing effectiveness with reassuring safety profile of switching to GP1111 in long-term, with sustained IFX levels. The usage of this particular biosimilar in daily practice may be suggested.Read more P599 An Antioxidant diet in comparison to a Mediterranean diet for children and adults with Inflammatory Bowel Disease: clinical outcomes and nutritional data from OXIBDiet trialWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The multicentre OXIBDiet trial (NCT04513015) has already demonstrated a redox imbalance in IBD children compared to adults and controls. The second part of the study aimed to evaluate the impact of an Antioxidant Diet (AoD) in comparison to a Mediterranean Diet (MD) in IBD patients. Clinical outcomes and nutritional data are reported.

Methods

IBD children and adults with mild symptoms/remission were randomly assigned to AoD (polyphenols intake >650 mg/die) or MD for 12 weeks. In the paediatric sample a Free Diet (FD) group was enrolled. At baseline and at 12 weeks inflammatory, oxidative stress (OS), clinical and anthropometric parameters were recorded. Dietary habits were registered by a validated Food Frequency Questionnaire and nutritional intakes were estimated with Winfood software.

Results

Twenty-five children (10 OD, 10 MD, 5 FD) and 17 adults (9 OD, 8 MD) completed the study. The total antioxidant capacity (Ferric reducing antioxidant power, FRAP) of the total IBD cohort significantly increased only in AoD (p=0.024) group and the Protein Oxidation (AOPP) showed a trend of decrease in AoD group (p=0.065). Stratifying for age, the same results of FRAP emerged only in the paediatric sample, following the AoD (Figure 1).Weight z-score (p=0.04) and BMI z-score (p=0.054) increased significantly in children following the AoD. The AoD groups both in children and in adults showed respectively a significant improved in health status (p=0.016) and in Food Related QoL. Faecal calprotectin (FC) showed a trend toward reduction both in AoD and MD groups and an increase in the FD group. At week 0 dietetic habits and nutrients intakes were similar in children in the AoD and MD groups. Changes in nutrients intakes at week 12 for both groups are reported in Table 1. In AoD group of IBD children a significant positive correlation between FRAP and intake of polyphenols emerged (p=0.015).

Conclusion

Preliminary results showed a significant improvement in OS imbalance and anthropometric parameters in IBD subject following an AoD. Antioxidant micronutrients intakes increased in IBD children especially on AoD, with a positive effect on the total antioxidant capacity. Also, QoL and Faecal calprotectin showed a favourable trend in AoD group, both in children and in adults. Final results of the study will allow to clarify the role of oxidative stress and antioxidants in IBD pathogenesis and treatment.Read more P824 Association between visceral adipose tissue and disease duration, clinical activity, and response to various biological agents in inflammatory bowel diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The relationship between body fat composition and inflammatory bowel disease (IBD) progression, medical response, and prognosis is widely acknowledged. Visceral adipose tissue (VAT) has been shown to be profoundly responsible of most of the obesity-associated metabolic derangements, however it is also related to severity of inflammation. Although VAT can be estimated using computerized tomography, abdominal bioimpedance is a new and reliable technique without expense and radiation exposure. We investigated whether VAT is linked to the disease activity in severe IBD and the short-term response to biological therapies.

Methods

We prospectively evaluated 65 IBD patients, (n=26 with ulcerative colitis (UC) and n=39 with Crohn’s disease (CD) who had moderate-severe disease activity) at baseline before the initiation of biological therapy. We quantified VAT using abdominal bioimpedance (ViScan). VAT and other body fat metric measures (BMI, total and free fat mass, abdominal fat mass) were also analyzed. The response to biological agents was assessed by clinical (Mayo and CDAI) and endoscopical (mucosal healing) scores at 3 months.

Results

Out of the 65 patients, 22 individuals (33.8%) exhibited clinical and/or endoscopic response after 3 months. Among responders and non-responders, there was a comparable approximation of disease location (p=0.321) and behavior (p=0.239). Patients with CD had slightly lower levels of VAT, BMI, and free fat mass compared to those with UC. In non-responders with UC, VAT levels were lower than in responders, whereas in non-responders with CD, VAT levels were higher than in responders. No distinction was observed in the VAT response among other classes of biologics, including anti-TNF, ustekinumab, and vedolizumab.

Conclusion

In summary, VAT parameters using bioimpedance (ViScan) were found to be correlated with the disease activity and reliably identified IBD patients who responded well to various biological treatment in the short-term. Therefore, human fat indices might be novel biomarkers for disease severity and response to therapy.Read more P875 Filgotinib in ulcerative colitis: early real-world multicentre UK experienceWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Phase 3 RCTs recruit a carefully selected population to demonstrate efficacy which may not reflect the population treated in clinical practice. We aimed to describe the use and effectiveness of filgotinib in a large UK real-world cohort of ulcerative colitis (UC) patients.

Methods

A retrospective observational cohort evaluation was conducted across six UK IBD centres. Baseline demographic and clinical data (including risk factors for serious adverse events and prior advanced therapy exposure), clinical (Simple Clinical Colitis Activity Index or Partial Mayo score) and endoscopic activity indices, and laboratory parameters (CRP and faecal calprotectin) were collected at baseline, 8 to 12 weeks after initiation (post induction), and during maintenance (the most recent review).

Results

A total of 216 patients are included in this analysis from May 2022 to November 2023 (mean follow-up period 202 days). The median [IQR] age at filgotinib initiation was 38 [27, 50] years (eight ≥65 years), 139 (64%) were male and median disease duration was 5.3 [1.9, 11.1] years. Disease extent (n=204) was: E1: 23 (11%), E2: 78 (38%) and E3: 103 (50%). 77 (36%) patients were naïve to advanced therapy; 66 (31%), 40 (18%), 25 (11%) and 8 (4%) patients had prior exposure to 1, 2, 3 or 4 advanced therapy modes of action(s) respectively, including 17 (8%) patients with prior exposure to tofacitinib. 48 (22%) patients had at least one risk factor included in the EMA warning. Of 137 patients who had endoscopic assessment at baseline, 56 (41%) and 20 (16%) had moderate or severe disease respectively. The median baseline faecal calprotectin and CRP were 800 [464, 1800] µg/g and 4 [1, 11] mg/L respectively. 82 (49%) were on concomitant corticosteroids at baseline (n=166).Cumulative probabilities of filgotinib persistence were 86%, 76% and 58% at 3, 6 and 12 months respectively (figure 1A). Prior exposure to multiple advanced therapies or tofacitinib did not appear to impact persistence (p=0.3 and 0.08 respectively). Reasons for filgotinib discontinuation are shown in figure 1B. There was a significant improvement in the disease activity scores in patients continuing filgotinib (figure 1C). In the cohort with prior tofacitinib exposure (11 failed to respond or lost response to tofacitinib), 7 remain on filgotinib with a median duration of 281 days.Eight patients discontinued filgotinib due to adverse events including one episode of venous thromboembolism.

Conclusion

In a large real-world cohort of UC patients, filgotinib appears to be effective and well-tolerated.Read more P600 Efficacy of different modalities of faecal microbiota transplantation to induce clinical remission in patients with ulcerative colitis: a systematic review and network meta-analysisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

We aimed to compare the efficacy of different modalities of faecal microbiota transplantation (FMT) to induce clinical remission in patients with ulcerative colitis (UC).

Methods

We performed a systematic review and network analysis (random effects model) of randomized controlled trials including at least one arm of FMT in adult patients with active UC. Primary endpoint, i.e. clinical remission (total Mayo score≤ 2 with Mayo endoscopic score≤ 1), was assessed between week 6 and 12. Results are expressed as relative risk with 95% confidence intervals, adjusted for bowel cleansing and pre-FMT antibiotics therapy. Ranking of FMT modalities for clinical remission was calculated as their surface under the cumulative ranking (SUCRA), which represents the percentage of efficacy achieved by an agent compared with an imaginary agent that is always the best without uncertainty. Heterogeneity among studies was evaluated by τ² (global statistical heterogeneity across all comparisons).

Results

Among the 12 selected studies, patients were exclusively bio-naïve in 4 studies (4/12), while between 9 and 32% had prior biologics exposure in the other trials. Risk of bias was low across all domains in 7 studies. Global heterogeneity was negligible (τ² = 0). After adjustment on bowel cleansing and pre-FMT antibiotics, oral capsule (RR=7.1[1.8-33.3]), lower GI FMT (RR=4.5[1.7-12.5] and combination of both (RR=12.5[2.1-100]) were more effective than placebo to induce clinical remission contrary to upper GI FMT (RR=1.1[0.2-7.7]) and autologous FMT (RR = 0.8[0.2-3.8](Table 1).The combination of lower GI FMT and oral capsule was significantly more effective than upper GI FMT to induce clinical remission (RR=10.7[1.1-104.2]). Combination of lower GI FMT and oral capsule ranked highest for the induction of clinical remission (SUCRA=0.93), followed by oral capsule (SUCRA=0.82) and lower GI FMT (SUCRA=0.72). Autologous FMT ranked lower than placebo (SUCRA=0.12vs0.22). We performed a sensitivity analysis distinguishing single donor FMT and multi-donor FMT (pooled samples from different donors). Combination of lower GI FMT and oral capsule ranked highest for the induction of clinical remission (SUCRA=0.89), followed by single donor lower GI FMT (SUCRA=0.70), multi-donor (pooled samples) lower GI FMT (SUCRA=0.65), multi-donor (pooled samples) oral capsule (SUCRA=0.61), single donor oral capsule (SUCRA=0.60).

Conclusion

In this network meta-analysis, we confirmed the efficacy of FMT to induce clinical remission in patients with UC. The combination of lower GI and oral capsule FMT seems to be the best modality of FMT for patients with UC while upper GI FMT is not suitable. In clinical trials, autologous FMT should be avoided due to a potential detrimental effect.Read more P886 Ustekinumab concentrations in induction are associated with mid-term endoscopic outcomes in patients with inflammatory bowel diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

It is unclear whether ustekinumab (UST) concentrations can predict the clinical course of inflammatory bowel disease (IBD) and guide treatment algorithms during the induction phase. The aim of our study was to assess the association between serum UST concentrations during the induction phase and clinical outcomes at week 24 and to determine the validity of a UST threshold for guiding intensification strategies.

Methods

We conducted a retrospective study including Crohn's disease (CD) and ulcerative colitis (UC) patients who started UST treatment between June 2022 and February 2023. Intensification strategies were determined according to standard clinical practice. UST concentrations were collected at weeks 8, 16, and 24. Quartile analysis and logistic regression were performed to evaluate the association between UST concentrations and treatment targets. Definitions are clinical steroid-free remission as a Harvey-Bradshaw index <5 and a partial Mayo score <2; endoscopic remission as a simple endoscopic score (SES-CD) ≤2 and Mayo endoscopic score (EMS) ≤1; and endoscopic response as a ≥50% reduction in SES-CD and ≥1 point in EMS.

Results

We included 42 patients (CD: 24). At week 24, clinical remission rates of 67% and endoscopic response and remission rates of 57% and 28%, respectively, were achieved. At week 24, the majority of patients continued intensified treatment: 90 mg subcutaneously every 4 weeks in 55% and 130 mg intravenously every 4 weeks in 36%. Patients who achieved an endoscopic response at week 24 had higher UST levels at week 8 (4.1 vs. 2.9 µg/ml, p=0.029). No significant differences between endoscopic remission rates and UST levels at any week were observed. The differences observed in the quartile analysis between the UST concentrations at week 8 and the endoscopic response were not statistically significant (p=0.451). The area under the ROC curve value for UST levels at week 8 to predict endoscopic response was 0.734 (p=0.012). Logistic regression analysis identified prior exposure to vedolizumab and absence of perianal disease as predictors of endoscopic response and remission at week 24 in univariate analysis, but not in multivariate analysis. No association was observed between UST levels and drug persistence rates.

Conclusion

In this real-world cohort, higher UST concentrations at week 8 were associated with higher rates of endoscopic response at week 24. A reliable concentration threshold for predicting endoscopic response and treatment intensification could not be determined, probably due to the insufficient number of patients included in the study and the relatively poor performance of the ROC curve. Prospective, randomized studies are needed to validate these results.Read more P825 Comprehensive dietitian-delivered dietary advice effectively achieves dietary change in adults with Ulcerative Colitis, whereas generalised written dietary advice does notWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Diet is an important consideration in microbial therapy trials. It is unclear whether provision of generalised written dietary advice is sufficient to induce dietary change as part of a therapeutic regimen or whether personalised diet advice is required. This study examines the effectiveness of different dietary advice modes provided in dietary and faecal microbiota transplantation (FMT) studies in adults with mild-moderately active ulcerative colitis (UC).

Methods

This observational study examined before and after dietary intake data from three prospective dietary and FMT studies held from 2018 to 2021 at a South Australian tertiary inflammatory bowel disease service. In all studies, adults ≥18 years with mild-moderately active UC completed 3 or 7-day weighed food diaries measuring habitual diet at 0 and 8 weeks after provision of dietitian-developed dietary advice. In studies one and two, a medical officer provided participants a written UC healthy eating pamphlet. The pamphlet contained generalised dietary recommendations for UC, targeting reduction of total and animal protein and increasing fermentable fibres including resistant starch to recommended serve sizes. In study three, a research dietitian provided a 1-week guided meal plan, diet manual with recipes and verbal personalised dietary counselling advising on the same recommendations and strategies. In all studies, participants were encouraged to eat to appetite. Dietary intake, including key nutrients of interest (protein and fermentable fibres), at weeks 0 and 8 was assessed using Foodworks 10^TM nutritional analysis software and analysed using paired statistical tests.

Results

Across studies one and two, 28 adults with mild-moderately active UC received written dietary advice. In study three, 30 adults received personalised verbal and written dietary advice. Outlined in Table 1, verbal and written advice significantly reduced total protein and animal protein intakes by 20% (p=0.007) and 34% (p=0.002) respectively. Total fibre and resistant starch intakes significantly increased by 64% (p<0.001) and 353% (p<0.001) respectively. Comparatively, written advice alone had no significant change on any key nutrient intakes. Neither dietary advice mode significantly changed energy or micronutrient intakes.

Conclusion

Written dietary advice alone was insufficient to achieve dietary change. In contrast, verbal and written dietary advice with the same intended change on dietary intake, delivered by a research dietitian effectively achieved dietary changes. This emphasises that comprehensive written and verbal dietary education delivered by a dietitian should be included in microbial-modulating study designs where dietary change is an intended outcome.Read more P601 Intestinal ultrasound correlates with clinical, biochemical, endoscopic and histologic biomarkers in patients with Ulcerative Colitis: a cross-sectional studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Intestinal ultrasound (IUS) is emerging as a non-invasive monitoring tool in patients with ulcerative colitis (UC). Our goal was to correlate IUS with clinical, biochemical, endoscopic and histological activity.

Methods

Cross-sectional multicentric study of patients with left (E2) or extensive (E3) UC. Consecutive patients were included and clinical (Patient-Reported Outcome (PRO2) and Simple Clinical Colitis Activity Index (SCCAI)), biochemical (fecal calprotectin (FCal) and C-reactive protein (CRP)), endoscopic (Mayo endoscopic sub-score (sMayo)) and histological (Nancy score) activity were evaluated. IUS activity was characterized by Milan Ultrasound Criteria (MUC). Clinical, biochemical, ultrasonographic, endoscopic and histologic remission were defined as SCCAI≤2, FCal<250 ug/g, MUC<6.2, sMayo=0 and Nancy=0, respectively. All evaluations were performed within 1 month. Pathologist was blinded to endoscopic and IUS results. In patients in IUS remission, the sigmoid colon was considered for analysis.

Results

58 patients with UC were included (55% men, with a mean-age of 38 (+/-17) years, 65% with E2 UC). Clinical, biochemical, ultrasonographic, endoscopic and histologic remission occurred in 53%, 53%, 53%, 31% and 12% of the patients, respectively. The most affected segment by both IUS and endoscopy was the sigmoid colon (34.5% and 41.4%, respectively). In our cohort, IUS activity had a strong correlation with PRO2 (r=0.778, p<0.001), SCCAI (r=0.810, p<0.001) and endoscopic activity (r=0.758, p<0.001), and a moderate correlation with FCal (r=0.517, p<0.001), CRP (r=0.402, p<0.001) and histological activity (r=0.475, p<0.001). We observed a consistent increase in the bowel wall thickness (BWT) and MUC score as the sMayo raised. Accordingly, patients with endoscopic activity presented higher BWT and MUC score, when compared to patients in endoscopic remission (Table 1). On the other hand, patients in IUS remission showed higher rates of clinical (90% vs 10%, p<0.001) biochemical (74% vs 26%, p<0.001) and endoscopic remission (94% vs 6%, p<0.001), with a trend towards higher rates of histologic remission (86% vs 14%, p=0.054).

Conclusion

In our cohort, IUS activity had a moderate to strong correlation with clinical, biochemical, endoscopic and even histologic activity. Additionally, patients with endoscopic activity presented worse IUS activity, suggesting this method as a reliable non-invasive monitoring tool in UC patients.Read more P899 Inflammatory Bowel Disease Patients Show More Recognizable Digestive Symptoms of COVID-19: A Questionnaire StudyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

It's important to manage IBD patients in the era of coronavirus pandemic (COVID-19). However, there is few studies on the clinical symptoms and prognosis of COVID-19 in IBD patients.

Methods

A web-based survey concerning symptoms of COVID-19 in people with or without IBD was designed. A pilot-test was carried out to ensure the feasibility of the questionnaire. Propensity score matching (PSM) was used to compensate for differences in baseline characteristics. Wilcoxon rank-sum test and Chi-square test were used to compare the clinical and prognosis differences between two groups.

Results

A total of 1274 individuals (including 631 with IBD) completed the questionnaire. After the use of PSM, 786 cases including 393 of IBD and non-IBD individuals respectively were included in the analysis. Fever and nasal congestion were the most common clinical manifestations of COVID-19 in our study. As for gastrointestinal (GI) symptoms, more IBD patients presented with new-onset abdominal pain (26.7% vs. 12.7%, p<0.001), diarrhea (22.4% vs. 14.5%, p<0.005) and altered bowel habits (38.7% vs. 24.9%, p<0.001).

Conclusion

COVID-19-related GI symptoms are more common in IBD patients. It is important to rule out COVID-19 infection in patients experiencing recurrence or exacerbation of GI symptoms.Read more P826 Exclusive Enteral Nutrition versus Crohn's Disease Exclusion Diet in pediatric patients with Crohn's DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Crohn's disease exclusion diet (CDED) has emerged as an alternative to exclusive enteral nutrition (EEN) to induce remission in pediatric CD patients. CDED is better accepted by the patients, thus improving adherence, and can represent a long-term strategy, as opposed to EEN. The aim is to compare the outcomes of both diets in our clinical setting.

Methods

We conducted a retrospective and observational study on CD patients who were under follow-up in a pediatric Inflammatory bowel disease (IBD) Comprehensive Care Unit from a tertiary hospital from June to October 2023. We included pediatric CD patients (under 18 years of age) who had received one of these two diets as induction treatment both as monotherapy and in combination with other drugs. Anthropometric values, inflammatory markers and clinical activity indexes were compared in both groups in three different time points: prior to induction (time 0), and three (time 1) and six months (time 2) after the induction. The study was approved by the Ethics Committee of HIUNJ. Data were analyzed with the SPSS software (v.25).

Results

A total of 53 patients were included: 24 in the CDED group and 29 in the EEN group. Up to 48 patients (90,6%) simultaneously started another drug as part of the maintenance strategy. Results are shown in table 1. The decrease of faecal calprotectin (FC) was more striking in the CDED group but kept elevated in both, whereas C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) descended to normal values after both diets (figure 1). However, there were no statistically significant differences regarding anthropometric values, inflammatory markers, or clinical activity indexes between the two groups at each time point (table 1).

Conclusion

Although the concomitant use of other drugs limits the drawing of conclusions, the therapeutic use of both the CDED and EEN diets seem to be useful to achieve clinical, analytical, and anthropometric improvement in pediatric CD patients. Conducting more studies on larger samples would help to confirm the role of CDED as an effective alternative to EEN.Read more P602 Risankizumab levels but not IL22 are significantly correlated and predictive of clinical and biochemical remission in Crohn's diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Risankizumab (RZB) is an anti-IL23 monoclonal antibody blocking the p19 subunit, whose recent Phase 3 trial demonstrated its efficacy in CD. Compassionate use has been possible since December 2019. The aim of this study was to investigate whether RZB and IL22 levels correlated with deep remission.

Methods

Any CD patient receiving RZB (compassionate use) was eligible for the study. All patients were treated with a regimen of RZB (600mg W0, W4 and W8) followed by 360 mg/sc every 8 weeks from W12. Patients with other dosing regimens were excluded. Before each infusion or SC injection, fecal calprotectin, CRP, RZB levels (ELISA ; Theradiag) and IL-22 levels (ELLA automated system; Biotechne). Clinical and biochemical remission was defined by a clinical score (CDAI) < 150 with fecal calprotectin < 250 µg/ml and CRP < 5 mg/l.

Results

28 patients on failure to anti TNF, vedolizumab and ustekinumab (mean age: 44 years, sex ratio M/F: 1.3) with 95 RZB maintenance samples (360mg/sc every 8 weeks) were eligible. For 44 RZB samples (46%), patients were in clinical and biochemical remission . Patients with clinical and biochemical remission had higher mean RZB levels than patients without clinical and biochemical remission (21.6 +/-13.3 versus 7.4+/-6.4 µg/ml; p=0.001). Biochemical and clinical remission rates were significantly higher in the highest RZB quartiles (p=0.01) (Figure 1). Area under the curve analysis (AUC: 0.93; p<0.001) isolated a RZB threshold significantly associated with clinical and biochemical remission: 11.5 µg/mL (sensitivity: 81.8%, specificity: 80.3%, PPV: 78.2%, NPV: 83.6%, accuracy: 81%.) . The progression-free survival curves towards loss of clinical and biochemical remission were significantly more favorable in the group of patients with RZB levels > 11.5µg/mL (p=0.03) . In univariate and multivariate analysis, only RZB level was isolated as a factor associated with clinical and biochemical remission: HR: 1.36 (CI95: 1.05-1.35), p=0.001). Conversely, albumin, CRP, albumin and other patient variables were not significantly associated with deep remission. The IL22 levels are not statistically significantly different between clinical and biochemical remission or not (respectively, 10.4 pg/mL (4.2-17.2) vs 8.6 pg/mL (4.3-16.2); p = 0.73)

Conclusion

RZB levels are significantly higher in clinical and biochemical remission CD. A threshold of 11.5µg/mL predicts clinical and biochemical remission in CD and is associated with significantly better progression-free survival. Conversely, IL22 levels are not associated with clinical and biochemical remission. However, these results are in a limited patient population of those receiving compassionate use therapy.Read more P917 Ustekinumab and immunomodulatory combination therapy is more effective than Ustekinumab monotherapy to prevent relapse in Crohn’s patients classified as low to intermediate-probability responders by UST-CDSTWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Ustekinumab (UST) is a monoclonal antibody that has therapeutic effects on Crohn’s disease (CD) by blocking interleukin 12 and 23. Controversy remains about the effectiveness of the combination of UST and azathioprine(AZA) and the criteria for patients who may benefit from the combination therapy. The aim of this study was to evaluate the effect of combination therapy on relapse in patients with CD and the feasibility of UST - Clinical Decision Support Tool (CDST) as a patient selection tool for combination therapy.

Methods

Patients with moderate to severe CD showed a clinical response after UST induction therapy and observed until the relapse. Kaplan-Meier analysis was performed to evaluate the efficacy of UST with AZA and to investigate the screening ability of UST-CDST for combination therapy selection.

Results

Among 35 patients, 8 (22.9%) experienced a clinical relapse during the median follow-up period of 17.0 months of UST treatment. There was no statistically significant difference in the cumulative relapse rate according to combination therapy in all enrolled patients. (6.7% vs 35%, p=0.063) The cumulative relapse rates were 8.3% in a combination therapy group, and 43.7% in UST monotherapy group among low to intermediate-probability responders according to UST-CDST, showing a statistically significant difference. (p=0.032)

Conclusion

Combination therapy with UST and AZA seems to be helpful prevent relapse, and UST-CDST may be helpful in patient selection who effective with combination therapy.Read more P603 Comparison of the safety and efficacy of ustekinumab and vedolizumab in patients with Crohn’s disease. - A systematic review and meta-analysis of propensity score matched cohort studiesWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Ustekinumab and vedolizumab represent both valid therapeutic options in patients with Crohn’s Disease following anti-TNF failure. Comparison data regarding safety and efficacy between these drugs are indirect, and reports conflicting results. The aim of the study was to assess the safety and efficacy profile of ustekinumab and vedolizumab in patients with Crohn’s Disease who failed prior anti-TNF treatment, including studies that applied propensity score matching to reduce confounding bias.

Methods

We identified 52 reports that compared ustekinumab and vedolizumab after a propensity score match analysis, of which 14 were assessed for eligibility, and finally 8 retrospective studies were included. The main outcomes considered were clinical steroid-free remission at 14±4, 24±4, and 52±weeks, drug discontinuation rate, adverse events, serious infections, and hospitalisation during the first year of treatment.

Results

A total of 3,185 patients were treated with ustekinumab (n=1,906, 59.8%) or vedolizumab (n=1,279, 40.2%). Steroid-free clinical remission was not significantly different between ustekinumab and vedolizumab at 12±4 weeks (OR 1.14, 95CI 0.76-1.72), at 24±4 weeks (OR 0.92, 95CI 0.56-1.51, p=0.73), and at 52±4 weeks (1.07, 95CI 0.73-1.56, p=0.75). Risk of adverse events was not different between the two drugs (OR 0.65, CI95 0.30-1.41, p=0.28). In patients receiving ustekinumab, the rate of infection (OR:0.52, CI95 0.30-0.91, p=0.02) and the need of hospitalisation at 1-year (OR:0.68, CI95 0.57-0.81, p<0.0001) appeared to be lower.

Conclusion

Ustekinumab and vedolizumab do not significantly differ in inducing and maintaining clinical steroid-free remission, while ustekinumab was associated with a lower risk of serious infections and hospitalisation during the first year of treatment.Read more P827 Has opioid use increased among adults with Crohn’s disease? A Swedish Nationwide cohort Study 2008-2020Wed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Chronic opioid use has turned into a global health challenge. Crohn’s disease (CD) patients may experience severe pain requiring opioids which could exacerbate CD symptoms and pose a risk of chronic use. The use of opioids among CD patients has not been explored on a national level. We compared the secular trends of opioid use among prevalent CD patients and matched reference individuals in Sweden.

Methods

This nationwide cohort study included adults with a prevalent CD diagnosis who lived in Sweden for at least 12 consecutive months at some point between 1 January 2008 and 31 December 2020. For each patient, up to 10 reference individuals from the general population were matched on birth year, sex, calendar year, and place of residence. We retrieved the data on dispensed opioid prescriptions (opioid use) from the National Prescribed Drug Register. We defined opioid use as ≥1 filled prescription per calendar year. We also estimated the annual prevalence of ≥1 dispensation of weak (codeine combinations, tramadol, and Dextropropoxifen) and/or strong opioids (Oxycodone, Morphine, Hydromorphone, Fentanyl, Buprenorphine, Tapentadol, and Petidin).

Results

We identified 43,155 adult CD patients and 418,218 reference individuals (Table 1). The prevalence of opioid use was stable from 2008-2016. However, between 2017 and 2020 it decreased from 19.7% (95% CI: 19.2, 20.2) to 16.9% (95% CI: 16.2, 17.7) and from 8.5% (95% CI: 8.4, 8.7) to 6.9% (95% CI: 6.7, 7.1) among CD patients and reference individuals, respectively (Figure 1a). However, between 2008 and 2020, the prescription of strong opioids more than doubled among both CD patients (increasing from 4.3% [95% CI: 4.1, 4.6] to 11.5% [95% CI: 11.1, 11.8]), and reference individuals (increasing from 1.3% [95% CI: 1.3, 1.4] to 5.4% [95% CI: 5.3, 5.5]) (Figure 1b). In 2020, the last year of the observation, compared with males, both female CD patients (20.3% [19.7, 20.8] vs 9.3% [9.2, 9.5]) and their matched reference individuals (15.3% [14.8, 15.9] vs 7.1% [6.9, 7.2]) had a higher prevalence of annual opioid use. The secular trends of overall opioid use and increasing use of strong opioids were similar for males and females (data not shown).

Conclusion

Annual opioid use among prevalent CD patients in Sweden, a country with publicly-funded healthcare and access to modern CD treatment, was two-fold higher than in the general population in the last 13 years. The annual opioid use remained stable from 2008-2016 and slightly decreased from 2017-2020 for CD patients and reference individuals. During the same period, the use of strong opioids more than doubled for CD patients and the general population.Read more P918 Can we rely on HLA to predict resistance to biological therapy in Inflammatory Bowel Disease patients?Wed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Monoclonal antibodies revolutionized IBD therapy, although some patients do not respond or progressively loose response due to antidrug antibodies. Immunogenicity seems to be related with HLA haplotypes, namely HLA-DQA1*05 allele associated with an increased risk of immunogenicity to anti-TNF therapy in CD. There are no data regarding the association between HLA-DQA1*05 positivity in UC patients and other biological drugs.

Objectives

We aim to determine HLA-DQA1*05 prevalence in IBD patients and evaluate its association with loss of response to biological therapy. As a secondary endpoint we aim to evaluate the effect of HLA-DQA1*05 genotype in a composite outcome that encompasses clinical, biochemical, and endoscopic remission at week 54.

Methods

Single center prospective cohort study, including consecutive adult bio-naïve IBD patients followed at IBD consultation, that initiated biological therapy. Data was collected regarding demographic, disease characterization and disease activity at baseline. All patients were screened for HLA-DQA1*05. Pharmacokinetic data was collected, and biological therapy was adjusted based on standardized protocols. Patients were classified as primary non-responders or as secondary non-responders. Response assessment was carried out at week 54 with a composite outcome that encompasses clinical, biochemical, and endoscopic remission. Statistical analysis: Chi-square test; Student’s t-test; Mann Whitney test; Kaplan-Meier survival analysis.

Results

We included 100 patients (67 CD, 33 UC), of whom 33 primary non-responders, 12 secondary non-responders and 55 achieved w54 of treatment. Patients started anti-TNF (72 patients, 51 Infliximab and 21 Adalimumab), Vedolizumab (18 patients) or Ustekinumab (10 patients), and 26 were on combined therapy. 43 (43%) patients were HLA-DQA1*05 positive. Kaplan-Meier survival analysis revealed no statistically significant differences in therapy persistence between HLA groups in all patients. However, a Kaplan-Meier survival sub analysis revealed patients under Vedolizumab had significant lower therapy persistence if HLA-DQA1*05 positive (p<0.001). UC´s patients revealed tendency to lower therapy persistence if HLA-DQA1*05 positive, although not statistically significant (p=0.051). HLA-DQA1*05 negative patients under Vedolizumab achieved our composite outcome (p<0,001) and patients under anti-TNF revealed a higher response to the composite outcome but without statistical significance.

Conclusion

HLA-DQA1*05 genotyping demonstrated no impact in therapy persistence, except in the subgroup of patients treated with Vedolizumab. HLA-DQA1*05 negative patients had a higher response to the composite outcome, but with statistical significance only in Vedolizumab subgroup.Read more P604 Exploring the role of chest X-ray in latent tuberculosis screening in Inflammatory Bowel DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Patients being treated with biologics or JAK inhibitors have an increased reactivation risk of latent tuberculosis infection (LTBI), and this is associated with a more severe infective course. Current ECCO guidance recommends the screening for LTBI by a combination of patient clinical data and epidemiological factors, chest X-ray (CXR), and tuberculin skin test or interferon-gamma release assay (IGRA) prior to starting immunosuppressive treatment. The evidence supporting CXR is categorized at evidence level 5, and information on its use in screening for LTBI originates from two decades ago. Apart from radiation exposure, a single posterior-anterior view has limited diagnostic capabilities.This study aims to determine the relation between CXR findings and IGRA test results in patients undergoing LTBI screening before commencing immunosuppressive therapy for Inflammatory bowel disease (IBD) patients in a low-risk population.

Methods

This is a retrospective analysis whereby IBD patients (≥16 years) on biologics or JAK inhibitors were identified from our local database. The clinical data, epidemiological, CXR and IGRA result were then analysed from the electronic case records. The IGRA test used was the QuantiFERON-TB Gold.

Results

A total of 356 patients were included in the study, with 58.7% (n=209) being male. Among these patients, the majority had Crohn's disease (66.6%, n=236), 30.1% (n=109) had ulcerative colitis, and the remaining 2.8% were classified as having IBD-unclassified. Most patients (97.1%) had been exposed to anti-TNF alpha medications and 13.2% were exposed to multiple biologicals.The mean age of IBD diagnosis was 30.3 years (SD+/-15.7). None of the patients had any clinical suggestion nor any evidence for exposure to TB.None of the CXRs performed revealed any radiological signs of prior TB infection. 93.8% (n=334) of the IGRA results were negative and 4.2% (n=15) were categorized as indeterminate. Among those with indeterminate results, 66.7% (n=10) were undergoing corticosteroid treatment for active disease. The remaining 2.0% (n=7) had a positive IGRA test and were treated for LTBI.None of these patients had TB reactivation when then treated with biologicals.

Conclusion

This research highlights that performing routinely a CXR in individuals with a negative IGRA offers little to no benefit, and subjects patients to unnecessary radiation. It also demonstrates the importance of conducting the IGRA test early, before initiating any immunosuppressive treatment.Furthermore, in patients with a negative IGRA, if chest imaging is required for screening purposes, opting for an ultra-low dose CT might be more prudent than a CXR, as it visualises the lungs better and the radiation exposure is not substantially different.Read more P828 Evaluation of adherence and beliefs about medication in patients with Inflammatory Bowel Disease following a novel microlearning programme (The ADEII project)Wed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Information and communication technologies (ICTs) represent a novel approach to chronic disease management. However, their use in Inflammatory Bowel Disease (IBD) is lacking and their results as far unknown, because no specific tools are available. The rate of non-adherence in IBD ranges from 30 to 40%, with medication concerns being one of the main factors. Our aim was to evaluate the outcomes of a novel microlearning programme for IBD patients in adherence and beliefs about medication.

Methods

Prospective cohort study in adult patients with IBD (18 to 70 years old) who underwent a microlearning programme over a 2-month period, throught 4-minute videos organised in individualised video pathways that were sent via mobile phone using a Telegram bot. All patients received the 4-video main pack, consisting of 2 videos with information about their disease (ulcerative colitis or Crohn's disease), 1 video on adherence and another one on steroid treatment. To these were added as many videos as the number of drugs used by the patient to control IBD. Before starting the programme and at 6 months, patients completed the Medicines Beliefs Questionnaire (BMQ). Adherence was defined as a medication possession ratio (MPR≥80%) at these same dates. MPR values were computed separately for each drug, and patients on combination therapy were considered adherents if they got MPR≥0.8 in every prescribed medication.

Results

Between 1 June and 31 October 2022, 1226 videos were sent to 200 IBD patients: 51.5% female (103), UC 52.5% (105), mean age 46.1 (13.2) years (Table 1). Median number of videos per patient was 6 (6-7). Attendance to ADEII programme ranged between 78% and 90%. Prior to the study, Initial non-adherence was 29.8% (59 patients), decreasing significatively to 18.1% (36) after the programme (p=0.02). Regarding BMQ test, we also found significant differences between the pre-intervention versus post-intervention medians and IQR of General BMQ score 18 (15 -21,8) vs. 17 (13.3 - 20) (p=0,001), BMQ-Overuse score 8 (7 -9) vs. 8 (6 -9) (p=0,027), BMQ-Harm score 10 (8 -12) vs 9.5 (7-11) (p=0,002) and BMQ-Concern score 13,5 ( 11-16) vs 13 (10-16) (p=0,001), with no changes in BMQ Global Specific and BMQ-Necessity scores.

Conclusion

Patients with IBD widely accepted an ICT-based educational program, which improved adherence, along with a decrease in negative ideas or beliefs about medications.Read more P935 Remission rates of biologics and small molecules in extension studies of moderate to severe Ulcerative Colitis; A systematic review and Network Meta-analysisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Ulcerative colitis is a relapsing and remitting inflammatory bowel disease characterised by symptoms of bloody diarrhoea and abdominal pain. In recent years, newer therapies have emerged such as biologics and small molecule therapies. However, these therapies have not been compared head-to-head in the longer term, and the choice in clinical practice is often at the discretion of the clinician. In this study we aim to compare these biologics and small molecule therapies across outcomes such as remission (as defined by the Mayo score) as well as histological, endoscopic and corticosteroid free remission in data beyond 52 weeks of medication administration.

Methods

Medical databases including MEDLINE, EMBASE and Cochrane were searched for phase III and IV randomised control trials examining efficacy of biologic and small molecule therapies in adults with moderate to severe ulcerative colitis beyond 52 weeks. A network meta-analysis was performed using the frequentist model to compare the aforementioned outcomes with pooled relative risk, heterogeneity and P values used to rank treatments.

Results

13 randomised control trials (RCT) were included for analysis from a screen of 2516 abstracts. Of these 13 RCTs, there were 8 treatments directly compared to placebo beyond week 52. In terms of remission as defined by the Mayo score, Upadacitinib 30mg was found to be the best treatment for moderate-severe ulcerative colitis when compared to Upadacitnib 15mg, Vedolizumab and Etrolizumab in consecutive order. In achieving histological remission, Upadacitinib 30mg was superior to Upadacitinib 15mg, Filgotinib (200mg and 100mg) and Etrolizumab. For endoscopic remission, Upadacitinib 30mg was superior to Upadacitinib 15mg, Filgotinib (200mg and 100mg), Vedolizumab, Etrolizumab and Golimumab. For corticosteroid free remission, Filgotinib 200mg was superior to Golimumab, Upadacitinib (30mg and 15mg), Vedolizumab and Etrolizumab.

Conclusion

Large head-to-head trials of biologic and small molecule therapies in the treatment of moderate to severe ulcerative colitis beyond 52 weeks have not been performed. However, our results show Upadacitinib 30mg to be efficacious in terms of remission defined by the Mayo score as well as histologic, endoscopic and corticosteroid free remission when compared to other biologics and small molecule therapies. Whilst these newer therapies show promise, their overall performance over an extended period remains unclear and their use often precludes the efficacy of subsequent biologic or small molecule therapies. As such, the first choice of therapy must be made carefully to increase the probability of remission whilst also balancing the burden of adverse events.Read more P515 Exclusive enteral nutrition downstages complicated Crohn’s disease prior to surgical resection: A feasibility studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Exclusive enteral nutrition (EEN, oral or enteral liquid feeds only) is an established first-line therapy to induce remission in Crohn’s disease (CD) in children, but not in adults where low tolerance has been reported. Recently, smaller studies have suggested advantages of EEN in preoperative optimisation in adults. We hypothesise that in this setting, EEN is feasible and is associated with improved inflammatory and nutritional markers.

Methods

Consecutive patients with small bowel or ileocolic Crohns disease, who started preoperative EEN at two large IBD centres 2020-2023 were retrospectively studied. EEN was part of a 4-6week preoperative optimisation pathway. Outcomes were compliance and serum albumin, c-reactive protein and body weight, respectively. Medians (range) & Wilcoxon tests used.

Results

Thirty-two patients started EEN for stricturing (n=10) or penetrating disease (n=14). Six patients (19%) did not tolerate EEN and received parenteral nutrition (n=2) or reverted to normal diet (n=4), while 26 patients (81%) completed EEN until surgery. This group received EEN during 38 (17-70) days. C-reactive protein concentrations decreased from 8.5 (1-157) to 3 (1-96) mg/L (p = 0.0051), and albumin levels increased from 33.5 (27-44) to 38 (26-42) g/L (p< 0.001), while body weight did not change, from 67 (48.5-107) to 66.6 (48.5-105.7) kg (p = 0.25). 21 (81%) EEN patients underwent minimally invasive surgery, 22 (85%) had a primary anastomosis and 4 a stoma. Median postoperative length of stay was 4 (2-11) days. One patient with a severe complication, no one with an anastomotic leakage.

Conclusion

EEN was well tolerated in this cohort of patients undergoing surgery for complicated CD. EEN was associated with improved systemic inflammation, a maintained nutritional status, and favourable postoperative outcomes despite the complexity of disease in this group of patients. These results align with previous studies that have shown the effectiveness of EEN in reducing disease activity and promoting mucosal healing in CD patients.By reducing inflammation and uphold nutritional status, EEN might help to create a more favourable surgical environment, potentially leading to better outcomes and decreased postoperative complications.Read more P627 Real-world clinical effectiveness and safety of vedolizumab and ustekinumab in biologic-naïve patients with Crohn’s disease by disease location: Results from the EVOLVE Expansion studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Crohn’s disease (CD) location may affect disease course and treatment (Tx) decisions. This analysis compared real-world clinical effectiveness and safety of vedolizumab (VDZ) and ustekinumab (UST) in biologic-naïve patients (pts) by CD location.

Methods

Medical charts of biologic-naïve pts with CD aged ≥18 years initiating VDZ or UST in Australia, Belgium or Switzerland from 2016 to 2021 were analysed in a multicentre, observational, retrospective EVOLVE Expansion study (NCT05056441). Subgroup analysis evaluated outcomes with VDZ vs UST in pts with baseline ileal, ileocolonic and colonic CD (Montreal classification). Data were collected from Tx initiation to the first of chart abstraction initiation, Tx discontinuation, loss to follow-up or death. Inverse probability of Tx weighting (IPTW) was used to balance baseline characteristics between cohorts. Clinical outcomes (clinical response, clinical remission, mucosal healing), as assessed using published algorithms,¹ and Tx persistence during 36 Tx months were analysed in time-to-event analyses (Kaplan-Meier method). Risks of safety (serious adverse events [SAEs], serious infections [SIs]) and healthcare resource utilisation (HCRU; CD exacerbations, CD-related hospitalisations, CD-related surgeries) outcomes with VDZ vs UST during 36 months were also compared.

Results

This analysis included 293 pts with ileal (VDZ:158, UST:135), 185 with ileocolonic (VDZ:91, UST:94) and 121 with colonic (VDZ:84, UST:37) CD. Baseline characteristics after IPTW were similar between VDZ and UST cohorts in all 3 subgroups. Cumulative rates during 36 Tx months were similar between VDZ and UST cohorts in ileal, ileocolonic and colonic CD subgroups for clinical response (p=0.67, p=0.94, p=0.22, respectively), clinical remission (p=0.51, p=0.20, p=0.52), mucosal healing (p=0.29, p=0.60, p=0.71) and Tx persistence (p=0.37, p=0.29, p=0.50) (Figure). There were no differences in the risks of SAEs, SIs, CD exacerbations and CD-related hospitalisations between cohorts across disease location; risk of CD-related surgeries was similar in pts with ileocolonic and colonic CD, and higher in VDZ vs UST cohort (p=0.02) in pts with ileal CD (Table). However, in ileal CD subgroup, CD-related surgeries during 36 months were reported only in 12/158 (7.6%) pts in VDZ and 3/135 (2.2%) pts in UST cohort.

Conclusion

During 36 Tx months, effectiveness, safety and HCRU outcomes were similar between VDZ and UST cohorts regardless of baseline disease location; risk of CD-related surgeries was higher with VDZ vs UST in pts with ileal CD and similar between cohorts in other subgroups. However, the absolute number of pts requiring CD-related surgeries was low.Reference:1. Bressler B, et al. J Crohns Colitis. 2021;15(10):1694-1706.Read more P568 Clinical relevance of baseline and change in Urgency Numeric Rating Scale score for mirikizumab treatment for Ulcerative ColitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Mirikizumab (MIRI), an anti-IL-23p19 antibody, has demonstrated efficacy/safety in moderately-to-severely active ulcerative colitis (UC) Phase 3 trials (LUCENT-1 and -2; NCT03518086, NCT03524092). This analysis evaluated induction and maintenance efficacy of MIRI among patients with different baseline (BL) bowel urgency severity.

Methods

In LUCENT-1, patients were randomized to receive 3 intravenous doses of 300mg MIRI or placebo (PBO); 1 every 4 weeks (Q4W). In LUCENT-2, responders to MIRI induction at W12 were rerandomized to subcutaneous 200mg MIRI or PBO Q4W through W40 (52W continuous treatment). Endpoints: clinical response, clinical remission, endoscopic remission, symptomatic remission at W12 and W52 (definitions in figure legend), Urgency Numeric Rating Scale ([UNRS]: 11-point scale from 0 [no urgency] to 10 [worst possible urgency]). Analysis: Fisher's exact test with non-responder imputation by patient induction BL UNRS score: 0-3, 4-6, and 7-10; score cut-offs based on ≥3 being a clinically meaningful improvement (JPRO 2022;6:114).

Results

Number of patients by BL UNRS score of 0-3, 4-6, or 7-10: W12 – 149, 437, 576 patients, respectively; W52 – 70, 215, 259 MIRI responders. At W12 and W52, a significantly greater proportion of MIRI-treated patients achieved clinical response, clinical remission, endoscopic remission, and symptomatic remission, regardless of UNRS score group at induction BL, for all comparisons except W52 clinical remission score 0-3 (Figure 1). In general, across clinical endpoints and regardless of BL UNRS score, MIRI treatment improved UNRS scores at W12 and W52 for a majority of patients, regardless of achievement of the clinical endpoint, although to a lesser extent when not achieved. MIRI treatment improved UNRS scores at W12 and W52 to a greater extent than PBO treatment regardless of achievement of clinical endpoint (Table 1; clinical remission data shown). Regardless of BL UNRS score, individual-point score shift data (not shown) illustrated that score shifts generally were distributed across lower scores at W12 and W52 than BL. This is relevant since Dubinsky and colleagues (JPRO 2022;6:31) demonstrated that a UNRS 1-2-point change in score can be important to a patient.

Conclusion

Regardless of BL bowel urgency severity based on UNRS score, MIRI is efficacious in achieving symptomatic, endoscopic, and clinical endpoints in UC patients. MIRI improves bowel urgency severity vs PBO even if clinical endpoints are not achieved. Observing shifts in UNRS scores along the UNRS scale, regardless of starting point, may aid in understanding a patient’s efficacy outcomes. These results support MIRI’s efficacy in bowel urgency and the clinical relevance of bowel urgency severity assessment over time.Read more P640 Role of vedolizumab trough levels in predicting clinical response in Inflammatory Bowel Disease: a multicentre prospective studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Medical treatment of Inflammatory Bowel Diseases (IBD) has developed aiming at a target-therapy using molecular-targeted drugs, such as vedolizumab (VDZ), recommended in moderate to severe forms of IBD refractory to conventional therapy. Considering the low rate of clinical remission after 12 months of treatment (about 30%) and its cost, it is important to identify predictors of clinical efficacy: therapeutic drug monitoring (TDM) based on measuring VDZ trough levels (TL) and circulating neutralizing antibodies could be useful in this setting.This prospective study aims at evaluating the association between VDZ TLs at week 24 and clinical and biochemical disease activity at the same timepoint and at week 52, in order to identify if these levels can predict 12-months clinical remission

Methods

The study has included patients who started VDZ treatment from 2016 to 2022 at two IBD centres (Turin and Pisa). Patients were monitored through clinical scores (HBI and PMS) and laboratory tests (haemoglobin, CRP, faecal calprotectin) at the beginning of treatment, at 6, at 12-months; TDM has been performed at month 6; response to the treatment and clinical remission have been defined according to IOIBD criteria after 6 and 12 months

Results

All of 40 patients included (16 CD, 24 UC) have undergone a follow-up at month 6, while only 35 have been to an annual evaluation. At the beginning of treatment the clinical disease activity was moderate (HBI mean 7.5; PMS mean 4.9), it became mild at the second timepoint (HBI mean 3.5; PMS mean 2.5) and was found to be mild or in remission after a year (HBI mean 3.6; PMS mean 1.5). The response rate (77%) and clinical remission rate (63%) at 6 and 12-months have been steady over time. TDM has found a mean of VDZ TLs of 79.3 μg/ml (SD 51.3) and no anti-VDZ antibodies. 12-months clinical remission has been tested through logistic regression in order to identify predictive factors: it was inversely proportional to PMS (OR 0.47; p 0.02) and abnormal CRP levels (OR 0.24; p 0.04) at 6-months and directly associated with haemoglobin concentration at 0 (OR 2.14; p 0.04) and 6-months (OR 1.86; p 0.02). As to TDM, VDZ TLs at the second timepoint were positive predictors of symptoms remission at the next timepoint (OR 1.02; p 0.03): higher concentrations at 43.1 μg/ml were associated with clinical remission (AUC 0.69; p 0.03) and were positively correlated with laboratory tests, such as haemoglobin (r 0.36; p 0.03)

Conclusion

Response to VDZ at the end of the year can be predicted after the first 6 months with clinical evaluation and laboratory tests, as well as TDM: lower PMS, higher haemoglobin, quiescent inflammatory biomarkers together with higher VDZ TLs allow to identify who will achieve clinical remission.Read more P957 Subcutaneous infliximab (CT-P13 SC) for ulcerative colitis: 2-year extension results of the LIBERTY-UC studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Superiority of CT-P13 subcutaneous (SC) infliximab formulation over placebo in maintenance therapy was demonstrated in both ulcerative colitis¹ and Crohn’s disease². LIBERTY-UC study was continued up to Week 102 as an extension phase treatment. We now present the efficacy and safety results up to Week 102 of CT-P13 SC 120 mg group in the LIBERTY-UC study (NCT04205643).

Methods

Patients who completed the maintenance phase up to Week 54 and, in the opinion of the investigator, would benefit from continued treatment continued the open-label extension phase from Week 56 to Week 102.During extension phase, all patients received CT-P13 SC regardless of previous treatment group randomised at the start of maintenance phase. The patients who had received the adjusted dose of CT-P13 SC 240 mg during the maintenance phase continued receiving CT-P13 240 mg in the extension phase. Patients with dose adjustment to CT-P13 SC 240 mg prior to Week 54 were considered as not to achieve each endpoint.At Week 54 and 102, clinical remission, clinical response, endoscopic-histologic mucosal improvement and corticosteroid-free remission were assessed by among patients who entered and treated in extension phase (Figure 1A), and who entered and treated in extension phase and had valid efficacy results at the visit of interest (Figure 1B). Safety was evaluated throughout the extension phase.

Results

A total of 237 patients in CT-P13 SC 120 mg group entered into extension phase. Among them, 208 (87%) patients completed extension phase.Proportion of patients who achieved clinical remission, clinical response, endoscopic-histologic mucosal improvement and corticosteroid-free remission at Week 54 and Week 102 among patients who entered and treated in extension phase (i.e., patients who had missing or invalid data were considered as not to achieve each endpoint) are presented in Figure 1A. Among patients who entered and treated in extension phase based on the no imputation for missing or invalid data, each endpoints are generally well maintained or slightly higher in Week 102 compared to Week 54 (Figure 1B). During extension phase, no new safety signals were observed compared to maintenance phase¹ (table 1).

Conclusion

The efficacy of CT-P13 SC 120 mg in UC patients was generally sustained through extension phase. No new safety concerns were found during the extension phase as well. These results indicate that long term use of CT-P13 SC can maintain clinical benefit as well as safety with the convenience of SC administration for patient with moderately to severely active UC.[1] Sands et al., Journal of Crohn's and Colitis, 2023.17(Supplement_1), i623-i624.[2] Colombel et al., Journal of Crohn's and Colitis, 2023.17.Supplement_1: i161-i162Read more P662 Discontinuation of biologic therapy in Inflammatory Bowel Disease: longer term outcomesWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The National Institute of Health and Care Excellence (NICE) in the UK recommends evaluation of all patients receiving biological therapy for IBD at 12 months, with a view to discontinuation of therapy for those with stable disease in remission. We recently evaluated the outcomes of discontinuation of biologics at our centre and the disease relapse rate at 12 months was 14.5%. Following this, longer-term outcomes were evaluated for patients who did not relapse at 12 months.

Methods

All patients on Biologics therapy who underwent biologics discontinuation were identified via our IBD registry. Retrospective data was collected between January 2015 and January 2022 and these included baseline demographics, disease type, type and duration of biological therapy, when therapy was discontinued and disease relapse initially at 12 months, and beyond. All patients had disease re-assessment prior to discontinuation. Disease relapse was defined as evidence of disease activity requiring steroid, biologic or surgical therapies. Patients with perianal Crohn’s disease were excluded.

Results

A total of 62 patients were included and divided in two groups. 37 (60%) patients had Crohn’s disease (CD) and 25 (40%) had Ulcerative Colitis (UC). Disease extent in the CD group included Ileal (32%), Colonic (53%) and Ileocolonic (15%). In the UC group disease extent included Proctitis (28%), Left sided (56%) and Extensive disease (32%).At 12 months, 14.5% (9) patients had disease reactivation, 13.5% with CD and 16% with UC. The duration of treatment prior to discontinuation ranged between 9 to 74 months (Median 47.5).Beyond 12 months of discontinuation, a total of 48 patients (CD 29 and 19 UC) had their data analysed, with 5 patients excluded due to being lost to follow up. 29% of these patients eventually had a relapse (CD 7, UC 7). The median follow up period was 53 months (range 21-84 months) in the CD group and 42 months (range 24-76 months) in the UC group. The rate of relapse post 12 months of de-escalation was 24% in the CD group and 36% in the UC group.

Conclusion

In this study, the rate of disease recurrence beyond 12 months of discontinuation of biological therapy was 29 % (median follow up in CD 53 months and UC 42 months) compared to 14.5% at 12 months. Despite careful selection of patients with up-to-date disease activity assessment prior to discontinuation, our data suggests that the overall disease recurrence rate was high at 40% (35% in CD and 48% in UC) and recurrence rates increase over time. We would therefore suggest that discontinuing treatment should only be considered after clear discussions with patients about the high risk of disease relapse and based on an individual basis.Read more P569 Persistence and safety of upadacitinib in Crohn’s disease and ulcerative colitis in real life: results from a Spanish nationwide studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Upadacitinib (UPA) has demonstrated its efficacy in patients with inflammatory bowel disease (IBD) in clinical trials. However, these results may differ from those achieved in clinical practice. Thus, persistence and safety should be analysed in a real-world scenario. Main aim: to evaluate the persistence of UPA in real life, both in Crohn’s disease (CD) and ulcerative colitis (UC). Secondary aims: to assess the effectiveness and safety of UPA.

Methods

Multicentre, retrospective study of IBD patients who received UPA for IBD in clinical practice. Persistence was calculated from the date of the first dose to the date of the last dose of UPA. For effectiveness assessment, only patients with active IBD at baseline were considered. Active disease was defined as Harvey-Bradshaw index >4 in CD, and partial Mayo score >2 in UC. Negative imputation method was used to deal with missing data. Cox regression and logistic regression analyses were used to identify predictive factors of treatment persistence and effectiveness, respectively.

Results

One hundred patients from 34 centres were included, 68 with CD and 32 with UC. All patients had been previously exposed to biologics (median 4, IQR 3-4), and 26% to JAK inhibitors (78% in UC); 37% of them were on steroids at baseline. Regarding UPA survival, 81% of patients remained on UPA at month 6, and 66% at month 12 (figure 1). Loss of response was observed in 34% per patient-year of follow-up. Dose intensification was required in 18%, 72% of whom responded clinically. Finally, 23 patients interrupted UPA during the follow-up. Age below 40 at UPA start and CD were associated with higher risk of UPA withdrawal (HR 2.4; 95%CI:1.0-5.7 and HR 3.7; 95%CI:1.0-12.9, respectively). Seventy-eight patients had active disease at baseline and were considered for the effectiveness analysis. Short-term clinical remission was achieved in 51%, 59% and 64% at week 4, 8 and 12; focusing on the type of IBD, clinical remission was achieved in 79% of UC vs. 54% of CD (p=0.03) at week 12. In the long-term, 53% and 42% remained in clinical remission at months 6 and 12. Clinical remission in patients exposed to JAK inhibitors was achieved in 75% and 79% at week 8 and 12, respectively; and in the long-term, in 54% and 55% at months 6 and 12. A total of 41 patients (41%) presented at least one adverse event (Table 1).

Conclusion

In the largest real-life cohort of IBD patients treated with UPA, the proportion of patients maintaining UPA at 12 months seems relatively high, regardless of prior exposure to JAK inhibitors. UPA seems to be effective in inducing and maintaining clinical remission, both in CD and in UC. The safety profile was similar to that previously described.Read more P876 Efficacy and safety of microencapsulated butyrate add-on therapy in induction of remission in patients with mild-to-moderate Ulcerative Colitis - results from multi-center, double-blind, randomized, placebo-controlled clinical studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Butyrate is the most beneficial among short-chain fatty acids (SCFA’s) that plays a key role in intestinal homeostasis by modifying: gut microbiome, gut barrier integrity, and reducing inflammation. There are some evidence of its usefulness in the treatment of Ulcerative Colitis (UC), however the data are not clear. The aim of our study was to assess the efficacy and safety of oral microencapsulated sodium butyrate (MSB) as add-on treatment in induction of remission in active UC.

Methods

100 patients with mild to moderate UC were enrolled in the study and randomized to MSB group treated with 2x300 mg/d of butyrate or placebo group (C); 96 of those patients completed all study protocol. Total Mayo Score (TMS), endoscopic images and fecal calprotectin were investigated to estimate the effect of MSB administration in induction remission, as well as relation between fecal butyrate concentrations (C4) and effectiveness of treatment.

Results

Clinical and endoscopic improvement (p < 0.001 and p = 0.042) and clinical remission (p < 0.001) was observed in MSB group. Accordingly, an improvement in the endoscopic image(defined as Mayo Score (MS) difference ≥ 1) at 8 weeks of follow up was achieved in 26patients (55.3%) in the study group and 16 (32.7%) in placebo group (p=0.042). Clinical improvement (defined as TMS difference ≥ 3) was observed in 39 (83%) study group patients and 15 (30.6%) in placebo group (p < 0.001). Clinical remission (TMS at visit 2 ≤ 2) was obtained in 30 (63.84%) MSB group patients and 11 (22.4%) in control group (p < 0.001). Significant improvement was also expressed as reduction of calprotectin level. In MSB group significant increase of C4 was observed in the group with clinical improvement, clinical remission and endoscopic improvement, and it was significantly higher than among non-responders. (MD =1.35 CI 95 [0.51;3.56], p < 0.001), clinical remission (MD = 1.69 CI 95 [0.44;3.45], p = 0.001) and endoscopic improvement (MD = 1.99 CI 95 [0.84;2.82], (p < 0.001)). In C group the level of C4 was significantly lower, regardless of clinical response. No side effects was observed during treatment.

Conclusion

MSB supplementation increases the fecal butyrate concentration and results in clinical remission and endoscopic improvement in mild to moderate UC. Our study clearly showed that MSB appears to be a beneficial and safe add-on treatment of those patients.Read more P677 The Oxford Anti-TNF Study of Immunogenicity and Sustained Response (OASIS-IBD): Analysis of 40,000 Patient Years of Anti-TNF UseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Anti-TNF therapy is established as a mainstay in IBD management. Recent data raise controversies regarding efficacy of these agents, sustainability of response, and identification of factors that may influence outcomes, including dose escalation and need for long-term concurrent immunosuppression (Lancet Gastro.Hep.2019;4:341).

Methods

We report a retrospective cohort study of 699 IBD patients on anti-TNF at our centre between 2005-2022. Clinical data were obtained from patient records and pharmacy database (TABLE 1). Primary outcomes were overall loss of response (LOR) at any timepoint; and secondary LOR (after an initial clinical response to therapy). Cox regression analysis was performed to identify variables independently affecting outcome. Kaplan-Meyer survival curves were constructed to demonstrate overall response rates (persistence on drug) and secondary LOR (Figure 1a-d). Dose adjustments were made proactively in a Virtual Clinic.

Results

204 patients had a diagnosis of ulcerative colitis (UC), 481 Crohn’s Disease (CD) and 14 IBD-unclassified. 126 patients received both infliximab (IFX) and adalimumab (ADA). Median duration on IFX was 42 months (range 0-204); median duration on ADA was 48.5 months (range 0-180). 48% of patients on IFX underwent dose escalation, as did 40% on ADA. Overall, 58 patients (7.6%) remained on treatment at 120 months.Overall survival rates for IFX at 12 months were 83% (82%CD vs. 82%UC); and at 36 months were 71% (69%CD vs. 74%UC). Overall survival rates for ADA at 12 months were 84% (89%CD vs. 59%UC); and at 36 months were 72% (78% CD vs. 42% UC) (Figure 1a-b).Secondary LOR rates for IFX at 12 months were 6% (5%CD vs. 9%UC); and at 36 months were 16% (15%CD vs.19%UC). Secondary LOR rates for ADA at 12 months were 7% (5%CD vs. 19%UC); and at 36 months were 16% (12% CD vs. 42% UC) (Figure 1c-d). There was no difference in survival analysis for IFX between CD and UC.On Cox regression analysis, for IFX, immunomodulation was associated with reduction in overall LOR (HR=0.48, p=1.07e-05) but not secondary LOR (HR=0.78, p=0.31) (Figure 1e-f). For ADA, outcomes were better for CD vs. UC for both overall LOR (HR=0.35, p=3.29e-07) and secondary LOR (HR=0.35, p=9.99e-05).

Conclusion

We demonstrate encouraging response rates in the first three years of therapy, with a small proportion remaining on therapy beyond 120 months. Survival rates on IFX were similar for UC and CD, but for ADA were significantly lower in UC. Secondary LOR was not affected by immunomodulation. Further analysis of relation to drug levels, dose escalation and genotyping is underway. This work was supported by The Leona M & Harry B Helmsley Charitable Trust.Read more P885 Pharmacokinetics, pharmacodynamics, and immunogenicity of biosimilar infliximab in pediatric patients with inflammatory bowel diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The pharmacokinetics and pharmacodynamics of biosimilar infliximab (IFX-BioS) in pediatric inflammatory bowel disease (IBD) are poorly understood. We examined some factors predicting IFX-BioS trough levels (TLs) in children.

Methods

Children with Crohn's disease (CD) and ulcerative colitis (UC) with an indication to start IFX-BioS in our center were prospectively included (January 2021-June 2022). TLs were measured with an in vitro lateral flow immunoassay (therapeutic range:3-7 microg/mL) at the 4^th and 6^th infusions and correlated with several covariates.

Results

A total of 110 TLs in 55 children (34 UC and 21 CD) were included. The mean TLs were 8.8±7.6 microg/mL and 9.8±6.7 microg/mL at the 4^th and 6^th infusions, respectively. The multivariate linear regression model at the 4^th infusion found a positive correlation between TLs and age at diagnosis (B: 1.950, 95% CI: [0.019, 3.882], p=0.048) and IFX-BioS dose/kg (B: 1.962, 95% CI: [0.238, 3.687], p=0.029), and a negative correlation with clinical scores (B: -0.401, 95% CI: [-0.738, -0.064], p=0.023). At the 6^th infusion, female gender (B: 6.887, 95 CI: [0.861, 12.913], p=0.029), hemoglobin (B: 1.853, 95% CI: [0.501, 3.204], p=0.011), and IFX-BioS dose/kg (B: 1.792, 95% CI: [0.979, 2.605], p<0.001) were found to be positively correlated to TLs. Clinical remission was achieved in 71% (4^th infusion) and 67.2% (6^th infusion) of patients. Logistic regression analysis revealed no significant association between combined clinical and biochemical remission and TLs at the 4^th (OR: 0.010, 95% CI: [0.928; 11.099], p=0.819) or 6^th (OR: 0.017, 95% CI: [0.924; 1.119], p=0.732) infusion, corrected for IFX-BioS dose/kg and interval between infusions.

Conclusion

We discovered some predictors IFX-BioS TLs in IBD children. Understanding the IFX-BioS pharmacokinetics and pharmacodynamics could allow physicians to identify which patients are at higher risk of poor outcomes and adjust treatment accordingly.Read more P570 Efficacy and safety of Adalimumab in Very Early-onset IBD- A Multicentre Study from the Paediatric IBD Porto Group of ESPGHANWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Patients with very early onset inflammatory bowel disease (VEOIBD) often present with severe disease course and require escalation to biologics. Exclusion of pediatric patients from clinical trials lead to scarcity of efficacy and safety data on TNFa antagonists therapy in VEOIBD. We aimed to assess safety and efficacy of adalimumab (ADM) induction and maintenance therapy in patients with VEOIBD.

Methods

This was a retrospective study involving 31 sites affiliated with the IBD Porto Group and IBD Interest Group of ESPGHAN, as well as centers in North America. Demographic, clinical and laboratory data were collected from patients diagnosed with VEOIBD who commenced ADM therapy before 6 years of age between 2014 to 2023.

Results

We identified 77 VEOIBD patients with a median age at diagnosis of 2.6 years (interquartile range [IQR] 1.3–4.1), of whom 29 (38%) were diagnosed at age <2 years (infantile-onset IBD). Thirty-seven (48%) patients were diagnosed with Crohn’s disease, 25 (32%) with ulcerative colitis and 15 (20%) with IBD-unclassified. Five (9%) from those genetically tested were diagnosed with monogenic disease. Median age at initiation of ADM was 4.2 (IQR 2.8-5.1) years. Forty-four patients (57%) were Infliximab experienced, discontinued mainly due to pharmacokinetic (20 [45%]) and pharmacodynamic (13 [30%]) failures. At initiation of ADM, concomitant corticosteroids and immunomodulators were given in 37 (48%) and 29 (37%) patients, respectively. The median wPCDAI and PUCAI scores at baseline were 45 [37.5-60] and 45 [27.5-57.5], respectively. Median follow-up time was 85.4 (IQR 40.4-139.2) weeks. While patients with CD showed significant clinical improvement after 26 and 52 weeks (PCDAI decreased to 10 [0-33.4], p<0.001, and 10 [0-25], p<0.05, respectively), No significant improvement in PUCAI score was observed among patients with UC (Figure 1). Inflammatory markers and calprotectin showed a gradual decrease over time (Figure 1). Weight and Height Z scores did not differ significantly throughout the follow-up period. ADM discontinuation rates after 1 and 3 years were 40% and 65%, respectively, mainly due to primary non-response (14, 29.8%) and loss of response (19, 40.4%). Drug discontinuation rates were not dependent on concomitant immunomodulator treatment or ADM initiation or on age (less or above 3 years). Four patients (5.2%) developed severe infections, including a patient with TTC7A mutation who died following septic shock.

Conclusion

Adalimumab therapy was relatively safe and seemed more effective in young patients with Crohn’s disease, but not in those with ulcerative colitis. Durability was relatively low due to high rates of primary non-response and secondary loss of response.Read more P896 You Can Lead a Horse to Water But You Can’t Make it Drink: A Study on Medication Adherence of Inflammatory Bowel Disease Patients in IrelandWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Medication adherence is important in ensuring adequate treatment of Inflammatory Bowel Disease (IBD). The High Tech Hub (HTH) is an online system used in Ireland to prescribe and monitor the ordering of High-Tech Medication, specifically oral small molecules and subcutaneously-delivered biologics. We aimed to observe compliance rates of treatment in our centre, observe trends between different medication and identify factors associated with adherence.

Methods

We extracted prescribing and medication dispensing information from the HTH database for our centre between May and November 2023. We collected information on patient demographics such as age and gender, patient disease subtype, medication class and duration of prescription given against the duration of prescription collected by the patient with an 85% threshold as a marker of compliance to treatment. Statistical analysis was used to compare differences in adherence between subsets of the population and a multivariate regression model was used to identify factors associated with adherence.

Results

We extracted information from 824 prescriptions from 644 unique patients. The median age was 42 years (IQR 32-52) with 52.2% males. 60.7% (n=391) had Crohn’s Disease, 33.4% (n=215) had Ulcerative Colitis and 3.1% (n=20) had IBD-U. Majority of patients, 77.3% (n=498), were on Anti-TNF medication, followed by 13.2% (n=75) on anti-Interleukins, 6.2% (n=40) on JAK Inhibitors and 3.3% (n=21) Anti-Integrins.6.5% (n=42) of patients required dose optimization during the 6-month observation and 1.7% (n=11) required a change of medication. 9.5% (n=61) of patients collected prescriptions for steroids. Further analysis demonstrated no significant difference in adherence within gender (Male: 61.0% vs. Female 53.6%, p=0.056), age (<25 years: 66.2%, 25-39 years: 55.0%, 40-54 years: 58.6%, ≥55 years: 54.6%, p=0.346), disease type (Crohn’s: 58.6%, Ulcerative Colitis: 56.7%, IBD-U: 50%, p=0.776), medication class (Anti-TNF: 56.4%, Anti-Interleukin: 65.9%, Anti-Integrin: 57.1%, JAK Inhibitor: 52.5%, p=0.378).However, we found significant lower adherence rates in patients who required dose optimization (21.4% vs. 60.0%, p<0.001) and those who required a change in medication (18.2% vs. 58.1%, p=0.008) in the observation window. There was also a lower rate of adherence noted in those who received prescriptions for steroids (45.9% vs 58.9%, p=0.051).

Conclusion

There was a high rate of non-adherence noted in our IBD population, worse in those who ended up requiring dose optimization or change in therapy. Addressing compliance by monitoring the online dispensing of medication may be a useful way to ensure adequate treatment and avoid unnecessary treatment escalation.Read more P519 Assessment of anal sphincter complex in pregnant patients with non-active perianal Crohns diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Pregnant IBD patients are more likely to undergo Cesarean delivery (CS).. Active perianal Crohn’s disease (PCD) is the only Crohns - related indication for CS. The rationale for CS in this group is that active PCD damages the sphincters and therefore a vaginal delivery may exacerbate the damage to the point of fecal incontinence. Pregnant PCD patients with non-active PCD are commonly not offered CS.We suspect that lack of active PCD does not necessarily attest for the physiological function of the anal complex sphincter and that vaginal delivery may exacerbate their condition to the point of incontinence. Therefore, we conducted a prospective trial to examine, prior to delivery, the anatomy and physiology of the sphincter complex in our cohort and weather pregnant patients with non-active PCD suffer from sphincter damageMethodsAll consecutive pregnant patients with Non-active PCD were enlisted. Patients underwent physical examination, anal manometry and Trans Rectal Ultra Sound (TRUS) before conception or during pregnancy before delivery.Active PCD was defined as: Perianal abscess, fistulas with active drainage, severe fissures and stricture.Non active PCD was defined as history of prior PCD, history of surgery for perianal fistula or old scars from previous abscess drainage.

Results

There were 13 patients who were enlisted to our study. Table 1 describes the TRUS, Manometry and pregnancy details. There were 9 patients (69%) with evidence of sphincter damage in our cohort including external and/or internal sphincter of at least 30 degrees of the muscle radius. Of them, 6 had posterior damage and 4 had anterior damage. In Manometry all patients had either normal or satisfying results. Three patients were strongly recommended to choose CS due to the sphincter damage.

Conclusion

patients with non-active PCD and future intent to deliver should be assessed routinely regarding their sphincter complex status. This should include TRUS, manometry and clinical evaluation. We discuss with each patient the advantages and disadvantages of vaginal delivery versus CS, weighing the risk of repeated CS (mainly placenta previa and accreta) against the risk of incontinence. Maternal age, Obstetrical history and estimated fetal weight at delivery are the main factors to consider. Although it is still unclear if detected muscle injury affect clinical incontinence, it is our practice to recommend CS for patients with significant muscle damage. We emphasize our recommendation specifically in patients with anterior damage because potentially delivery damage would be to the same areaRead more P678 Long-term efficacy, safety and health-related quality of life in patients who achieved comprehensive disease control with filgotinib in SELECTION: analysis of ~3 years in SELECTIONLTEWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Filgotinib (FIL), an oral, once-daily, Janus kinase 1 inhibitor, was approved for Ulcerative Colitis (UC) treatment after the phase 2b/3 SELECTION trial (NCT02914522). In SELECTION, a greater proportion of FIL200 mg (FIL200)-treated than placebo-treated patients achieved comprehensive disease control (CDC), a stringent multi-component endpoint. We examined the long-term outcomes of achieving CDC in patients continuing on FIL200 in the ongoing long-term extension (LTE) study SELECTIONLTE (NCT02914535).

Methods

This interim analysis included adult patients with UC who completed SELECTION and received ≤144 weeks of FIL200 in the LTE (up to data cut-off 24/02/22). CDC (biomarker remission, endoscopic improvement, IBDQ remission and partial Mayo Clinic Score [pMCS] remission achieved concurrently) was assessed at SELECTION week 58 (LTE baseline [BL]). Mean pMCS and IBDQ score, use of corticosteroids (CS) and incidence of TEAEs and serious TEAEs in the LTE were compared between SELECTION CDC achievers and non-achievers. A mixed model for repeated measures was fitted on pMCS and IBDQ score, with CDC achiever status, study visit and the interaction between CDC achiever status and study visit as fixed effects; p values were nominal.

Results

We analysed 148 patients (CDC achievers, n=41; CDC non-achievers, n=107). Mean pMCS was stable in CDC achievers (0.44, LTE BL; 0.50, LTE week 144) and decreased in CDC non-achievers (1.49, LTE BL; 0.77, LTE week 144; Figure). Mean IBDQ score was stable in CDC achievers (204.05, LTE BL; 197.21, LTE week 144) and increased in CDC non-achievers (181.55, LTE BL; 196.37, LTE week 144; Figure). There was a significant beneficial effect of achieving CDC on pMCS and IBDQ score overall (pMCS: fixed effect estimate: −0.5542, p=0.0025; IBDQ score: fixed effect estimate: 13.1585, p=0.0042). There was a significant interaction between achieving CDC and study visit for IBDQ score (p=0.0183), with the benefit of achieving CDC lessening by week 144. Generally, a lower proportion of CDC achievers used CS than non-achievers; 2.4–7.3% of CDC achievers used CS vs 1.9–15.9% of CDC non-achievers. Incidence of TEAEs and serious TEAEs were stable over time and similar between CDC achievers and non-achievers.

Conclusion

Follow-up for ~3 years showed high levels of long-term benefit with continued FIL200 treatment. Achieving comprehensive disease control at the end of the randomized trial with FIL200 was associated with long-term efficacy, improved HRQoL and low overall use of CS. This may demonstrate the value of filgotinib-induced achievement of CDC in UC disease course. The safety profile of FIL200 was consistent between CDC achievers and non-achievers, suggesting an acceptable long-term benefit–risk profile.Read more P907 Impact of preoperative use of biologics on 30-day surgical morbidity and mortality in patients with Crohn’s Disease undergoing ileocolectomy: National Surgical Quality Improvement Program database analysisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Preoperative use of biologics has been inconsistently reported to be associated with increased frequency of infectious and surgical anastomotic complications in inflammatory bowel disease patients. We aimed to evaluate the rates of 30-day post operative morbidity and mortality in Crohn’s disease patients exposed preoperatively to biologics.

Methods

Data was collected from the NSQIP (National Surgical Quality Improvement Program) which is a nationally validated, risk adjusted program designed to measure and improve the quality of surgical care. Crohn’s disease patients undergoing open or laparoscopic ileocolectomy were identified using corresponding ICD 10 and CPT Codes from NSQIP PUF (Participant Use Data File) for the year 2021.Patients were divided based on the preoperative use of biologics (group 1) and (group 2) for whom no biologics were used. Univariate analysis was done on SPSS via Chi-squared and Fisher exact test for categorical variables, while independent sample T-test was used for continuous variables. Composite morbidity was defined as the association of any two morbidity events in the database. A multivariate regression analysis was done to predict post operative morbidity while controlling for the following variables: age, BMI, smoking, steroid use, diabetes, hypertension, sepsis, ASA classification, and preoperative transfusion.

Results

A total of 910 patients (female n=473; 52%, mean age of 42.3 ± 16.1) were included. The group1 patients were significantly younger (40.30 years ±15.33) than group 2 (43.58 years ±16.8 p=0.002) and had significantly slightly higher ASA III and IV scores (97.4% vs 97.2%, p=0.004). On the other hand, group 2 had a significantly higher prevalence of hypertension (20.2% vs 12.8%, p=0.003) and chronic obstructive pulmonary disease (2.6% vs 0, p=0.001). No significant difference in remaining preoperative variables, surgical approach (laparoscopic vs open) and comorbidities were found between the two groups. On univariate analysis of morbidity, only a significant prevalence of deep vein thrombosis and thromboembolism was found in patients exposed to biologics (1.1% vs 0 p=0.027). No significant difference was found in surgical site infections, sepsis, infectious complications, anastomotic failure, composite morbidity, or mortality. On multivariate analysis, no significant morbidity was noted between the two groups.

Conclusion

Crohn’s disease patients undergoing ileocolectomy and exposed preoperatively to biologics did not show a significant increase in 30-day postoperative morbidity and mortality.Read more P556 Immunomodulator and advanced therapies for Induction of clinical remission and response in Crohn’s disease: A systematic review and network meta-analysisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Several effective advanced therapies have been approved for the treatment of Crohn’s disease (CD) in the past two decades. Many have used synthesis techniques to study this area, but these rarely consider both advanced and immunomodulator therapy together in the same analysis. Network meta-analysis enables the direct and indirect comparison of these different therapeutic agents, aiding in determining their relative positioning within the treatment algorithm.

Methods

We searched MEDLINE, Embase, and Cochrane Central Register of Controlled Trials between inception and October 2023 for randomised controlled trials (RCTs). The outcomes included were clinical remission and response, adverse events (AE), withdrawal due to AE, total and serious AE. We performed random-effects meta-analysis and network meta-analysis (frequentist approach), and estimated relative risk (RRs), 95%CI values. We used GRADE to ascertain certainty of evidence.

Results

A total of 83 RCTs comprising 19214 patients were eligible. A total of 28 interventions were included in the analysis. Combination of anti-tumor necrosis factor (TNF) and immunomodulators, anti-TNF monotherapy (adalimumab [ADA], infliximab [IFX], BI695501), IL-23 antagonists (ustekinumab [UST], guselkumab, risankizumab [RIS], mirikizumab), anti-integrins (vedolizumab, natalizumab) and upadacitinib were effective in inducing clinical remission compared to placebo (Figure 1). There was moderate certainty of evidence for combination of ADA and azathioprine (AZA) (RR 3.1, 95%CI [2.0-4.8]; risk difference [RD]: 40.1%), IFX+AZA (RR 2.5, 95%CI [1.7-3.8]; RD: 28.9%), ADA (RR 2.5, 95%CI [1.8-3.5]; RD:28.5%), and UST (RR 2.0 95%CI, [1.6-2.5]; RD: 19.2%) in induction of clinical remission compared to placebo. For induction of clinical response, there was moderate certainty of evidence for IFX+AZA (RR 2.8, 95%CI [1.6-4.8]), ADA (RR 2.5, 95%CI [1.7-3.9]), IFX (RR 2.8, 95%CI [1.6-4.8]), RIS (RR 1.9, 95%CI [1.3-2.6]). On analysis of serious adverse events all therapies were of no difference to placebo (very low certainty). On sensitivity analysis, the impact of concomitant immunomodulator use and the biological naivety of patients had little effect on these results.

Conclusion

On network meta-analysis, combination of anti-TNFs and immunomodulators followed by anti-TNF monotherapy had large effect size with moderate certainty for the induction of clinical remission. More novel therapies appear to have examples of similarly important effect sizes, but are currently limited due to the imprecision of the limited evidence base at present and future research should target these therapies in study.Read more P697 Short- and long-term outcomes following biologic use before non-conventional stricureplasty for Crohn’s JejunoileitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Non-conventional strictureplasties, specifically the Finney and Michelassi technique, are bowel-preserving surgical techniques for diffuse jejunoileal Crohn’s Disease (CD). We investigated the association of biologic use during non-conventional strictureplasty for Crohn's jejunoileitis and its short- and long-term outcomes.

Methods

We conducted a retrospective review of all patients with CD who underwent non-conventional strictureplasty at our centre, e.g., side-to-side antiperistaltic strictureplasty (SSAS) according to the Finney or modified Finney technique, or side-to-side isoperistaltic (SSIS) according to the Michelassi or modified Michelassi techniques from January 2000 to October 2022. Patients were categorized into BIO and NoBIO groups based on their uninterrupted use of biologics until the moment of surgery. Our outcomes of interest were: (a)30-day complications; and (b)surgical recurrence. Statistical analysis was performed using R version 4.3.1.

Results

A total of 71 patients underwent non-conventional strictureplasty: 80 SSAS and 14 SSIS. Group 1 had 17 patients in which 15 SSAS and 3 SSIS were performed. Group 2 had 54 patients in which 65 SSAS and 11 SSIS were performed. Most patients also underwent concurrent Heineke-Mikulicz strictureplasty in 49 patients (69%) and concurrent small bowel resection in 53 patients (74.6%). The patients in the BIO and NoBIO groups had similar baseline characteristics (Table 1). No differences were observed in perioperative outcomes (Table 2). No difference was observed when comparing surgical recurrence rates, but a longer median time to recurrence was observed in the BIO group (4.7 vs. 4.4 years, p=0.004).

Conclusion

Biologic use at the time of non-conventional strictureplasty for diffuse jejunoileal Crohn’s disease is safe and is associated with a longer median time to recurrence.Read more P538 Platelet-rich stroma during surgery for treatment-refractory perianal fistulizing Crohn’s disease: long-term outcomes of a pilot studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Platelet-rich stroma (PRS), a combination of stromal vascular fraction and platelet-rich plasma, proved to be safe and feasible for the treatment of treatment-refractory perianal fistulizing Crohn’s disease (pCD). This study aimed to assess the long-term outcomes in patients with pCD treated with PRS.

Methods

Long term results from adult patients with pCD, who underwent fistula curettage, closure of the internal fistula opening and PRS injection, included in an earlier conducted pilot study (n=25) were assessed up to October 2023. The primary outcome was complete clinical closure at long-term follow-up (closure of all treated external opening[s]). Secondary outcomes comprised complete radiologic closure (absence of fluid-containing tracts on MRI), partial clinical closure (closure of ≥ 1 treated external opening[s]), recurrence (reopening of the external opening after complete clinical and/or radiological closure) and the need for unplanned re-intervention(s).

Results

The majority of the patients was female (56.0%)(mean age 34.4 years [SD: 0.9], and mean follow-up 3.7 years [SD: 0.6])(Table 1). 68% of the patients were concomitantly treated with a biological. During follow-up, ≥1 unplanned re-intervention(s) were necessary in 44% of the patients which were minor (e.g. incision and drainage) in the vast majority (83%)(Table 2). Complete clinical closure at long-term follow-up was reached in 88%. Complete radiologic closure was reached in 75% of patients. Partial clinical closure was reached in all patients (100%). Recurrence was reported in 8% of patients, all whom reached (partial/complete) clinical closure, whereas no recurrence was experienced in patients with complete closure on MRI. All patients with complete radiologic closure achieved clinical closure. Vice versa, patients with clinical closure achieved complete radiologic closure in 82% of the cases.

Conclusion

In this pilot study with treatment-refractory pCD patients treated in a tertiary referral center, all patients had benefit from surgical treatment and an additional injection of PRS. At long-term follow-up, treatment with PRS injection during surgery is promising as complete clinical and radiological closure is achieved in the majority of these patients. In addition, complete radiologic closure seems a valuable prognostic parameter for long-term success for fistula closure. Future (randomized) research is warranted to further assess the effectiveness of PRS in patients with pCD.Read more P908 Real-life effectiveness and safety of tofacitinib and vedolizumab as a second-line therapy in anti-TNFs experienced patients ulcerative colitis: preliminary results of an IGIBD study (VE2TO-UC)Wed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Drug positioning in ulcerative colitis (UC) patients refractory to anti-tumor necrosis factor (TNF) is still debated. We aimed to compare the real-life effectiveness and safety of tofacitinib and vedolizumab as second-line therapy in anti-TNFs experienced UC patients.

Methods

In this Italian multicenter cohort study, we retrospectively included consecutive UC adult patients exposed to ≥ 1 anti-TNF agent starting tofacitinib or vedolizumab. Clinical remission (defined as partial Mayo score (PMS) <3 and no subscore >1) and corticosteroid-free clinical remission (CFREM) were assessed at week 26. Patients who discontinued treatment due to a primary or secondary non-response, adverse events, or intolerance were considered as treatment failure and classified as non-responders. The primary outcome was to compare clinical remission in tofacitinib- and vedolizumab-treated patients at week 26. Propensity score with inverse probability of treatment weighting (IPTW) was used to adjust for confounding, including sex, age at drug initiation, age at diagnosis, smoking habit, disease extension, use of immunosuppressant and steroids at baseline, disease activity at baseline by PMS, reason for anti-TNF discontinuation. Multiple imputation was used for missing data. Venous thromboembolism event, herpes zoster reactivation, major cardiovascular adverse event, severe lymphopenia, initiation or escalation of cholesterol-lowering drugs, hospitalization, surgery, dysplasia or colorectal carcinoma, and death were assessed for the safety profile.

Results

Overall, 99 tofacitinib- and 230 vedolizumab-treated patients were included. Baseline characteristics are summarized in Table 1. The groups were comparable except that tofacitinib-treated patients were younger and of pediatric onset, with lower comorbidities and cardiovascular risk factors. Of note, 22 patients were excluded due to a lack of sufficient follow-up. After IPTW analysis, no difference between tofacitinib- and vedolizumab-treated patients in terms of clinical remission 1.23 (0.68 – 2.23) and CFREM 1.27 (0.71 – 2.29) was observed at week 26. Similar results in terms of clinical remission 1.13 (0.60 – 2.14) and CFCR 1.16 (0.62 – 2.20) were obtained when analyzing patients with a baseline PMS ≥ 2 (Figure 1). No difference was observed in terms of adverse events in the two groups.

Conclusion

Our preliminary results suggest no difference in terms of clinical remission and CFREM of tofacitinib and vedolizumab as second-line therapy in anti-TNFs experienced UC patients at the 26^th week. Safety was consistent with known tofacitinib and vedolizumab profiles.Read more P698 Effectiveness and Safety of Ustekinumab for Ulcerative Colitis: A Brazilian Multicentre Real-World Observational StudyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Real-world data on the effectiveness and safety of ustekinumab (UST) in ulcerative colitis (UC) are lacking in Latin America. In this study, we aimed to describe the effectiveness and safety of UST in a real-world multicentre cohort of Brazilian patients with UC.

Methods

We conducted a multicentre retrospective observational cohort study, including patients with moderate to severe UC (Total Mayo score 6-12, with an endoscopic subscore of 2 or 3) who received UST. The co-primary endpoints were clinical remission, defined as a total Mayo score ≤2 at 1 year, with a combined rectal bleeding and stool frequency subscore of ≤1, and endoscopic remission (endoscopic Mayo subscore of zero) within one year from baseline. Secondary endpoints included clinical response between weeks 12-16, endoscopic response within one year of starting UST, steroid-free clinical remission at week 52, and biochemical remission at week 52. We also evaluated UST treatment persistence and safety.

Results

A total of 50 patients were included (female, n=36, 72.0%), with a median disease duration of 9.2 years (1-27). Most patients had extensive colitis (n=38, 76.0%), and 43 (86.0%) were steroid-dependent at baseline. Forty patients (80.0%) were previously exposed to biologics (anti-TNF drugs, n=31; vedolizumab [VDZ], n=27). The co-primary endpoints of clinical remission and endoscopic remission at 1 year were achieved by 50.0% and 36.0% of patients, respectively. Clinical response at weeks 12-16 was 56.0%, endoscopic response, steroid-free clinical remission, and biochemical remission at week 52 were 68.0%, 67.4%, and 50.0%, respectively. The UST treatment persistence rates at 24 months was 73.7%. During the follow-up, 10 patients (20.0%) were hospitalized, mostly due to disease progression, and three patients required colectomy. Nine patients (18.0%) discontinued the drug mainly due to a lack of effectiveness. Twenty-six adverse events (AEs) were reported, 15 of which were considered as serious AEs.

Conclusion

This is the first real-world experience study to report the effectiveness and safety of UST specifically in a Latin American population. In this real-world cohort of difficult-to-treat UC patients, UST was associated with improvements in clinical, biochemical, and endoscopic outcomes. The safety profile was favorable, consistent with the known profile of UST.Read more P873 Ustekinumab Real World Evidence Study (UndieS): Assessing the suitability of patients treated in routine clinical care for participation in the pivotal phase 3 clinical trialWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Phase 3 randomised controlled trials (RCTs) are recognised as the gold standard for measuring the efficacy of new medicines and are essential for licensing new products. To maximise internal validity, RCTs recruit a highly selected, carefully defined group of participants, whereas patients treated in routine practice are much more heterogeneous. We set out to describe the real-world use of ustekinumab and assess the proportion of treated patients who would have been eligible for the relevant registration studies.

Methods

UndieS is a UK-based, multicentre, prospective, observational study investigating the effectiveness of ustekinumab in 593 Crohn’s disease patients. Objective evidence of active Crohn’s disease (biochemical or endoscopic) and/or failure or intolerance to another therapy were the only entry criteria. Within the limits of the study, we compared participants’ characteristics with the eligibility requirements of the UNITI clinical trial programme. The pragmatic modified Harvey-Bradshaw Index (mHBI), shown to correlate to CDAI score, was used in UndieS. No endoscopic follow up information was collected.

Results

82% of patients treated in this real-world study would not have been eligible for participation in the UNITI programme. Eight RCT eligibility criteria would each be expected to exclude at least 10% of the real-world patient population (figure 1). A low disease activity score was the eligibility criterion most frequently expected to render UndieS participants ineligible for the UNITI programme with 61% of predicted CDAI scores (i.e. estimated from mHBI) falling below the threshold for RCT eligibility, despite 80% of those treated having objective evidence of inflammation and 55% failed/ were intolerant to an alternative therapy. Only 13% of participants were using corticosteroids at baseline. 59% of UndieS participants had previously failed or been intolerant to at least one anti-TNFα medication. For those who would have been ineligible for the RCT based on laboratory tests, an elevated ALT was the commonest abnormality among UndieS participants. The requirements for multiple venepunctures and pregnancy avoidance were the most relevant impediments for UndieS patients, with 28% of females of childbearing potential not willing to agree to the specified conditions.

Conclusion

Within the limitations of this study, we have demonstrated a significant disparity between participants in phase 3 RCTs and patients treated in routine clinical care. This questions the applicability of efficacy studies to real world clinical practice. Data from high quality, observational studies should complement findings from RCTs to support decision makers. Future work will investigate whether outcomes differ according to RCT eligibility.Read more P539 Assessment of VEdolizumab aNd Ustekinumab in Elderly patients with Crohn’s disease (CD): the IG-IBD AVENUE studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Comparative data regarding ustekinumab (UST) and vedolizumab (VDZ) effectiveness and safety in elderly inflammatory bowel disease (IBD) patients are limited. The aim of the present nationwide multicenter cohort study was to compare persistence and safety of these drugs in elderly versus non-elderly Italian IBD patients.

Methods

Data from 20 Italian centers were retrospectively collected. Based upon age and treatment, IBD patients aged ≥65 years were allocated to group 1 (G1) and group 3 (G3) (cases) if treated with UST or VDZ, respectively, and to group 2 (G2) and 4 (G4) (controls) if they were aged < 65 years and treated with UST or VDZ, respectively. The primary outcome was drug persistence at week 52. Propensity score analysis was performed for primary outcome using the inverse probability of treatment weighting method. Secondary outcomes included: steroid free remission (SFR) at week 52 and frequency of adverse events (AEs) at the end of follow-up.

Results

A total of 439 patients (176 elderly and 260 non-elderly) were included in the study. Among elderly patients, 93 and 83 were included in the group G1 and G3, respectively. Among non-elderly patients, 147 and 116 were included in the group G2 and G4, respectively. Baseline characteristics are represented in Table 1. No differences were found in terms of persistence between G1 vs G3, G1 vs G2 and G3 vs G4 (Figure 1). Higher baseline Harvey-Bradshaw Index (HBI) (OR=2.09, 1.15 – 3.78; 0.015) and baseline steroid therapy (OR=1.10, 1.04 – 1.15; p<0.001) were identified as predictors of a lower drug persistence at Cox model. Steroid free remission at week 52 was achieved by 80% and 77% of elderly patients in G1 and in G3 (p=0.63), respectively. Similarly, no differences for SFR were found between G1 and G2 (p=0.73) and between G3 and G4 (p=0.68). Incidence rate for AEs were G1 and G2 were 7.85 and 7.90 respectively; for G3 and G4 IR were 5.81 and 12.50 respectively. No differences were found in the UST groups (IRR=0.99; p=0.98) while in VDZ-treated patients, non-elderly had a higher rate of AEs (IRR=0.46; p=0.006).

Conclusion

These data confirm that ustekinumab and vedolizumab are highly effective drugs in patients with IBD, associated with a good safety profile in both elderly and in non-elderly IBD patients.Read more P628 Vedolizumab in Indian patients with Inflammatory Bowel Disease: Interim results from a prospective, multicentre, open-label, phase 4 studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Although anti-tumour necrosis factor (TNF)-α agents have revolutionised the management of ulcerative colitis (UC) and Crohn’s disease (CD), they have demonstrated a therapeutic ceiling with numerous safety concerns. Vedolizumab (VDZ) has consistently demonstrated safety and efficacy in patients with UC and CD in pivotal clinical trials, but its efficacy and safety data are very limited in the developing world where infectious diseases predominate.

Methods

This prospective, multicentre, open-label, single-arm, phase 4 study (Clinicaltrial.gov: NCT04804540) included patients (aged 18-65 years [yrs]) with moderate-to-severe active UC and CD who were non-responsive to available conventional therapies and/or anti-TNF agents. Patients received VDZ 300 mg through intravenous infusion for induction (Week [W]0, W2, W6) and maintenance (W14, W22, W30, W38, and W46) treatment phase. This interim analysis included data collected till the last patient completed W14 visit. Safety endpoints including incidence of adverse events (AE), serious AEs (SAE), adverse drug reactions (ADR), and adverse events with special interest (AESI), and efficacy endpoints including clinical response and clinical remission were analysed.

Results

Of 215 patients screened, 150 were eligible (UC, 102 [68.0%], median age: 39 yrs; CD, 48 [32.0%], median age: 31 yrs). Median VDZ treatment duration was 155 days in UC and 143 days in CD groups. Overall, 71 (47.3%) patients (UC, 49 [48.0%]; CD, 22 [45.8%]) experienced ≥1 AE; of these, 40.7% patients had mild AEs (UC, 40.2%; CD, 41.7%). Forty-six (45.1%) patients with UC and 22 (45.8%) patients with CD had ≥1 treatment-emergent AE (TEAE); 5 (4.9%) patients with UC had treatment-related TEAEs. Seven (4.7%) patients (UC, 6 [5.9%]; CD, 1 [2.1%]) had ≥1 SAE (2 [1.3%] were treatment-related), 5 (3.3%) had ≥1 ADR, and 4 (2.7%) had ≥1 AESI. One patient (0.7%) each reported pulmonary tuberculosis and tuberculous pleural effusion as ADR/AESI. Anaemia and small intestinal obstruction were the frequently reported TEAE and SAE, respectively. Most of the AEs were resolved and no AE-related death was reported during study (Table 1). Overall, 90 (60.0%) patients (UC, 56 [54.9%]; CD, 34 [70.8%]) at W14, 37 (63.8%) patients (UC, 29 [61.7%]; CD, 8 [72.7%]) at W30, and 4 (57.1%) patients (UC, 4 [66.7%]) at W46 had the clinical response. Similarly, 62 (41.3%) patients (UC, 40 [39.2%]; CD, 22 [45.8%]) at W14, 23 (39.7%) patients (UC, 19 [40.4%]; CD, 4 [36.4%]) at W30, and 3 (42.9%) patients (UC, 3 [50.0%]) at W46 had the clinical remission (Figure 1).

Conclusion

Treatment with vedolizumab was safe and effective in Indian patients with moderate-to-severe active UC and CD as per this first multicentre prospective study on vedolizumab from India.Read more P576 Fecal calprotectin could predict clinical and endoscopic response to ustekinumab therapyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Ustekinumab (UST) is one of the most used biologic drugs for the treatment of Crohn’s Disease (CD) and Ulcerative Colitis (UC). However, not all patients achieve clinical remission and even less mucosal healing. There is currently scarce knowledge about the early markers of therapeutic response in this setting, with particular regard to mucosal healing. The aim of this multicenter study was to evaluate the role of fecal calprotectin (FC) as early predictor of mucosal healing.

Methods

We enrolled consecutive patients with CD or UC treated with UST for at least 48 weeks at four referral centers in the last 5 years. Therapeutic response was evaluated in terms of clinical remission (defined as a Partial Mayo Score <2 for patients with UC and as Harvey Bradshaw Index <5 for patients with CD, without concomitant corticosteroid therapy) and mucosal healing (defined as a Mayo Endoscopic Score <2 for UC and as the disappearance of ulcers for CD). We collected clinical and demographic data, as well as fecal calprotectin (FC) and C-Reactive Protein (CRP) levels at baseline and at week 24.

Results

Among 196 patients enrolled (73 [37.2%] women), 167 were affected by CD, whereas 29 by UC. Globally, 128 (65.3%) patients achieved clinical remission and 83 (42.3%) endoscopic remission at 48 weeks of treatment. There were no group differences in age, sex, BMI, baseline clinical and endoscopic indexes, or baseline CRP levels between patients achieving or not either clinical or endoscopic remission. Baseline calprotectin levels were lower in patients who achieved endoscopic remission (median [interquartile range] 391 [103, 1050] versus 825 [317, 1800] µg/mL,p=0.002). At week 24, lower calprotectin levels were observed in both the groups who achieved clinical (160 [50, 426] versus 439 [146, 1000] µg/mL,p<0.0001) and endoscopic remission (114 [43, 265] versus 392 [139, 912] µg/mL,p<0.0001) compared with non-responders. The effects of week-24 calprotectin levels on clinical remission (β= -0.003,p<0.0001) and endoscopic remission (β= -0.004,p<0.0001) remained significant in multivariable models adjusted for age, sex, and BMI. A cut-point of 268 µg/mL was identified as the optimal threshold of week-24 calprotectin for predicting clinical remission (sensitivity 65%, specificity 67%, ROC AUC 0.689), while a cut-point of 309 µg/mL was identified to predict endoscopic remission (sensitivity 79%, specificity 59%, ROC AUC 0.712).

Conclusion

Our data suggest that FC assessment after 24 weeks of treatment with UST could represent a promising early marker of response, even in terms of mucosal healing, in both CD and UC.Read more P884 Patient satisfaction and experience after a switch to an adalimumab biosimilar with high concentration and citrate-free: results from a multicentric prospective real-life studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Switching from a reference product (RP) to a biosimilar (BS) aims at generating cost savings. Patient adherence after a switch is linked to overall experience that can be impacted by patient or treatment characteristics. This study aimed to analyse patient-experience after a switch from an adalimumab (ADA) to CT-P17¹ (ADA BS high concentration, HC, citrate-free).

Methods

YU-MATTER (NCT05427942), a multicentric prospective observational study included patients with inflammatory bowel disease (IBD) or chronic inflammatory rheumatic disease (CIR), treated with ADA: either the RP (HC: 100mg/ml) or a BS with low concentration (LC: 50 mg/ml). Patients were switched to CT-P17 and followed-up for 3 months (M). Clinical characteristics were collected at M0, including beliefs (BMQ questionnaire²), patient-experience via 5 self-questionnaires designed in collaboration with patient associations to explore satisfaction regarding the injection (Likert 7), discomfort (pain [NRS 0-10], redness [Likert 4], itching [NRS 0-10], and haematoma [Likert 3]). Satisfaction and overall injection tolerance (pain < 4 AND absence of redness AND itching < 4 AND absence of haematoma) were assessed between M0 (just before switch) and M3 (3 months after switch). Factors associated with satisfaction improvement (Likert) were explored through multivariable logistic regression.

Results

Of the 232 patients analysed, 167 had IBD (CD =136); mean age 44±15 years; median IBD duration 9 years ([Q1; Q3]: [5; 15]) and 50.9% were men. The median differential score necessity-concern was of 5 [3; 7] suggesting that the perceived necessity of the treatment was higher than its concerns. 119 (51.2 %) patients were switched from a BS (45 with citrate) and 113 (48.7%) from the RP. At M3, 175 patients (75.4%) were satisfied with the injection and 145 (62.5%) had a stable or improved satisfaction versus the previous ADA. Among patients receiving a BS, the presence of citrate was significantly associated with an improvement of satisfaction after switching to CT-P17 (58.3% vs. 30.0%, p=0.006). Overall injection tolerance significantly improved after switching from 28.9 % at M0 to 57.7 % at M3 (p<0.0001). A significant decrease of pain related injection was observed after the first injection of CT-P17 (median -2 [-4; -1]) for patients switched from a BS and remained stable for patients switched from the RP (median 0 [-1;1]). In multivariable analysis, the switch from a LC ADA was an independent factor of satisfaction improvement (vs from the RP, odds ratio=3.03; p=0.003; Table).

Conclusion

The global experience of switching to CT-P17 was positive with an overall improvement in injection tolerance. Injection volume was an independent factor associated with a successful experience.Read more P638 Efficacy of Induction upadacitinib Therapy in Chinese Patients with Moderately to Severely Active Crohn’s DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Upadacitinib (UPA) is the 1st oral, reversible, selective Janus kinase inhibitor that approved in China for moderately to severely active Crohn’s disease (CD) treatment. UPA demonstrated significantly greater efficacy compared with placebo (PBO) in phase 3 global multicenter, double-blind, PBO-controlled induction U-EXCEL and U-EXCEED studies. This analysis reports the efficacy and safety results on a sub-analysis of Chinese from the combined 2 induction studies.

Methods

Eligible patients with an average daily very soft/liquid stool frequency (SF) ≥4 and/or abdominal pain score (APS) ≥2, plus a Simple Endoscopic Score for CD (excluding the narrowing component) ≥6 (≥4 for isolated ileal disease) were randomized (2:1) to UPA 45 mg or PBO for 12 weeks. Patients receiving corticosteroid at baseline began a steroid taper at week 4 per protocol. This analysis included Chinese subjects from global population. The 2 induction studies were combined for each analysis set. Clinical remission per PROs was defined as average daily very soft or liquid SF ≤ 2.8 and average daily AP score ≤1.0 and both not greater than baseline. Endoscopic response was defined as decrease in SES-CD>50% from baseline (or for subjects with an SES-CD of 4 at baseline, at least a 2-point reduction), as scored by central reviewer.

Results

Of the 1021 patients enrolled in the 2 induction studies, 120 from China were included in the analysis. Baseline demographic and characteristics were mostly similar with a few exceptions. A significantly higher percentage of Chinese patients who received UPA 45mg QD than those received PBO had clinical remission per PROs at week 12 (70.9% vs 22.0%, p<0.0001). At week 4, clinical remission per PROs was achieved by a numerically greater proportion of patients receiving UPA (51.9%) than PBO (17.1%). At week 12, in patients taking corticosteroids for CD at baseline, a numerically greater proportion of patients receiving UPA (72%) discontinued corticosteroid use and achieved clinical remission per PROs than did patients receiving PBO (30%). A significantly higher percentage of Chinese patients who received UPA than those received PBO had endoscopic response at week 12 (64.6% vs 12.2%, p<0.0001). The rate of adverse events (AEs) in the UPA group was comparable to PBO group. There were no treatment-emergent deaths in either group. In the Chinese population, AEs of special interest occurred at similar rates between PBO and UPA group. No malignancies, adjudicated major cardiovascular events, or venous thromboembolic events were reported.

Conclusion

Similar to global population, Chinese patients treated with UPA 45mg achieved clinical and endoscopic outcomes at higher rates than did patients receiving PBO, with a tolerable safety profile.Read more P647 Effectiveness of combined treatment with two biologics or advanced molecules in inflammatory bowel diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Treatment with a combination of biologic drugs or advanced molecules represents a seldom-used therapeutic option for inflammatory bowel disease (IBD). Data on the effectiveness of these combinations of treatment are limited.The objective of this study is to assess the effectiveness of combination therapy in IBD patients.

Methods

A retrospective, single-center observational study was conducted. Patients with IBD treated with a combination of biologic drugs or advanced molecules from January 2020 to September 2023 were analyzed.Clinical, demographic, and therapeutic variables were collected. The clinical response rate was evaluated using the Harvey-Bradshaw Index for Crohn's disease (CD) and the partial Mayo score for ulcerative colitis (UC) at the initiation and 6 months into treatment.Bivariate analysis was performed to identify variables associated with clinical response.Long-term treatment survival was studied using Kaplan-Meier curve.

Results

A total of 9 patients were included: 7 (77.8%) with CD and 2 (22.2%) with UC. The majority (66.6%) had received more than two biologic treatments. Patient characteristics are described in Table 1. Combination treatment was initiated due to partial response to monotherapy in 2 patients (22.2%) and monotherapy failure in 7 (77.8%). The most commonly used combination was ustekinumab-vedolizumab (n=6, 66.6%). Three patients (33.3%) had a clinical response at 6 months, with one patient achieving clinical remission.In the bivariate analysis, partial response to monotherapy as an indication for a second biologic and elevated PCR at the start of treatment were associated with a higher clinical response (p=0.03 and p=0.04, respectively).The median survival of the combination treatment was 309 days (±109) (Fig. 1). At the end of the follow-up, 2 patients (22.2%) continued with combination treatment (average of 251 days). In 4 cases the treatment was switched to a JAK inhibitor, one patient required surgery and, finally, two patients needed surgery and treatment change.

Conclusion

The combination treatment have a low long term effectiveness in patients refractory to conventional treatment, although it may be a valid option for that subgroup of patients showing a partial response to monotherapy.Read more P577 Histological Remission Leads to Less Endoscopic Flare-up in Moderate-to-Severe, Biologics Experienced Ulcerative Colitis Patients: A Comprehensive Retrospective Cohort StudyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

In the management of inflammatory bowel disease (IBD), adopting a treat-to-target strategy has proven beneficial. Current therapeutic targets primarily focus on achieving endoscopic remission. However, the significance of histological remission as a potential target. However, it remains underexplored in Asian populations. We aimed to investigate the role of histological remission in clinical outcomes among ulcerative colitis (UC) patients already in endoscopic remission.

Methods

In this retrospective cohort study, we enrolled moderate to severe, biologics experienced UC patients with endoscopic remission, defined as endoscopic Mayo subscore 0 point during June 2017 and September 2023 in Chang Gung Memorial Hospital, Linkou. Then the patients were divided into histological remission (HR) and non-histological remission (non-HR) groups according to histological Nancy index (NI). HR was defined as NI 0 point, and others belonged to non-HR group. Comparative analyses were performed between two groups regarding baseline characteristics, one year follow up and end of follow-up clinical outcomes. The location of biopsy was active inflammatory lesion, if no active lesion, we performed routine biopsy over rectum, 15cm level from anal verge. We took at least 4 pieces biopsy over each location.

Results

We enrolled 42 moderate-to-severe, biologics experienced UC patients (HR group, 23 patients and non-HR group, 19 patients) with endoscopic remission. The average follow-up duration was 17.6 months. In non-HR group, NI scores were categorized as follows: 1 point (42.1%), 2 points (31.6%), 3 points (21.1%), and 4 points (5.3%). Baseline characteristics showed no significant differences between the two groups. In terms of outcomes, the HR group demonstrated a significantly lower endoscopic relapse rate (26.1% vs. 68.4%, P=0.006) and better results in Kaplan-Meier survival analysis (log-rank P=0.015) at the end of the follow-up period. The HR group also exhibited a reduction in clinical relapses, emergency department visits, and hospital admissions. Although these differences did not attain statistical significance, this phenomenon is likely attributable to the study's constrained sample size.

Conclusion

In moderate-to-severe UC patients who are biologics-experienced and in endoscopic remission, achieving histological remission is associated with a reduced rate of endoscopic relapse.Read more P895 Analysis of the efficacy of intravenous ustekinumab maintenance treatment in patients with refractory Inflammatory Bowel DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Ustekinumab (UST) is a monoclonal antibody that inhibits the p40 subunit of IL-12 and IL-23, approved for the treatment of Crohn's Disease (CD) and Ulcerative Colitis (UC). Its administration is intravenous during induction and subcutaneous during maintenance. Several studies have assessed the efficacy of reinduction and intensification of this treatment in patients with loss of response. However, there are few studies evaluating the effectiveness of intravenous UST for maintenance.The aim of the study is to evaluate the efficacy and safety of maintenance with intravenous UST in patients with Inflammatory Bowel Disease (IBD).

Methods

Observational, retrospective, and single-center study. All patients receiving maintenance with intravenous UST until June 2023 were reviewed. Clinical response was evaluated with Harvey-Bradshow Index for CD and partial Mayo for UC. Biochemical response was evaluated with calprotectin and C-reactive protein.

Results

A total of 29 patients with IBD (24 CD and 5 UC) were included. The mean follow-up of patients was 449 days (74-948). The cohort's characteristics are summarized in Table 1.In all cases, intravenous maintenance was performed with UST 130mg/4 weeks. In 4 cases (13.8%), maintenance was initiated directly with intravenous UST. In 9 (31%) patients due to primary failure to UST and in 16 (55.2%) patients due to secondary failure.The clinical response to intravenous UST maintenance in patients with CD at week 8 and 16 and at one year of follow-up was 87.5% (n=21/24), 83.3% (n=20/24), 73.3% (n=11/15) respectively. For UC, the response was 60% (n=3/5) at week 8 and 16 and at one year. The drug survival was 723 days (± 74) (Figure 1). No predictive variable for treatment response was identified. Two patients (both with CD) experienced recurrent respiratory infections as an adverse effect, without the need to discontinue UST.

Conclusion

Maintenance treatment with intravenous UST can be useful and safe in patients with severe IBD and/or failure of subcutaneous UST maintenance.Read more P578 CDST (Clinical Decision Support Tool) is predictive of steroid-free clinical remission in patients with Crohn's disease treated with vedolizumab in a specific manner which is mainly driven by the serum level of albuminWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The CDST (Clinical Decision Support Tool) was developed to predict response to vedolizumab in Crohn’s disease to identify a subgroup of super responders (SR).We aimed to 1) confirm that prediction of CDST is specific to vedolizumab versus ustekinumab, 2) to determine the weight of each item included in CDST to predict the response to vedolizumab in order to explain its specificity.

Methods

From the VENUS cohort, all patients with CD treated with ustekinumab (UST) or vedolizumab (VDZ) after exposure to at least one anti-TNF were included consecutively in two referral centers. The primary endpoint was corticosteroid-free clinical remission (CFREM) defined by a CDAI < 150 at W 54. CFREM was also assessed at W 14.All analyzes were adjusted using propensity scores based on patient and CD characteristics, concomitant treatments and disease severity.To understand the weight of the items, CDST was calculated only with the clinical items, by adding the CRP (CDST 4 items) and full CDST (CDST 4 items + 0.4 x albuminemia). Patients were considered as super responders (SR) if 3-items CDST > 3, a 4-items CDST > 3 or a complete CDST > 19.

Results

Overall, 312 patients (UST = 224 and VDZ = 88) were included. After adjustment, UST was more effective than VDZ in achieving CFREM at W54 (50.6% vs 40.6%, p=0.047) with no difference at W14 (56.1% vs 56.7%, p=0.99).The 3-item CDST was not predictive of CFREM with VDZ at W14 (52% vs 56%, p = ns) or W54 (41% vs 41%, p = ns) in non-SR or SR patients, respectively, while it predicted response to UST at W54 (44% vs 60%, p < 0.01).The 4-item CDST was associated with CFREM with VDZ at W14 (46% vs 67%) and W54 (38% vs 54%) and with UST at W14 (51% vs 73%) and W54 (44% vs 70 %) (p<0.05 for all comparisons). The rate of CFREM was not different between UST and VDZ in non-SR or SR (at W14 andW54).Full CDST was predictive of CFREM at W14 in pts treated with VDZ (50% vs 71%, p<0.05) but not at W54 (41% vs 50%, p = ns). CDST did not predict UST efficacy. In SR patients according to full CDST, VDZ seemed more effective to achieve CFREM at W54 than UST (50% vs 33%), contrary to non-SR (46% vs 36% in favor of UST). The same trend was observed for CFREM at W14: 66% vs 71% in SR and 55% vs 50% in non-SR with UST and VDZ, respectively.In VDZ group, albumin level at baseline was associated with CFREM at W14 (33.7 ± 6.0 vs 39.4 ± 5.3; p = 0.033), contrary to the UST group (37.7 ± 5.5 vs 37.4 ± 9.3; p = 0.54).

Conclusion

CDST is predictive of CFREM with vedolizumab but not with ustekinumab. The specificity of CDST to vedolizumab is mainly driven by albuminemia. The impact of albumin level on vedolizumab is not fully explained by drug clearance and suggests an increased need for albumin to transport vedolizumab to its target.Read more P663 Efficacy of jak inhibitors in inflammatory bowel disease patients with extraintestinal manifestations– Retrospective studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

JAK inhibitors have demonstrated efficacy in ulcerative colitis (UC), Crohn’s disease (CD), and inflammatory arthritis. However, limited data exist on their effectiveness in treating extraintestinal manifestations (EIM) in patients with inflammatory bowel disease (IBD) in real-world scenarios. This multicenter, retrospective study aims to assess the efficacy of JAK inhibitors (JAKI), specifically tofacitinib or upadacitinib, in IBD patients with EIM.

Methods

This was a retrospective multicenter cohort study. Inclusion criteria included IBD patients with active EIM documented before JAKI treatment initiation, with a follow-up up to 52 weeks. EIM Clinical response was defined as either improvement or remission of EIM complaints, as subjectively described by the patient or taken from the treating physician’s assessment.

Results

Eighty-six patients from eight centers were included, with 64% having UC (n=55). Women constituted 60% of the patients (n=51). Tofacitinib and upadacitinib were administered to 63% (n=54/86) and 36% (n=32/86) of patients, respectively. Eleven patients (13%) were biologically naïve, all treated with tofacitinib. Arthralgia was the predominant complaint, affecting 55% (n=30/54) of tofacitinib-treated and 44% (n=14/32) of upadacitinib-treated patients. Patient characteristics, including EIM distribution, are detailed in Table 1.At 3 months, 86% (n=72/83) achieved EIM clinical response, with tofacitinib responders at 94% (n=49/52) compared to 74% (n=23/31) for upadacitinib (p=0.01). Seven percent (n=6) discontinued treatment due to lack of response. Peripheral arthralgia improved or achieved remission in 86% (n=32/38) of patients, while 68% (n=13/19) with axial arthropathy experienced clinical response.At 6 months, EIM clinical response was achieved by 76% (n=44/75), with tofacitinib at 86% (n=44/51) and upadacitinib at 54% (n=13/24) (p=0.004). Twelve percent(n=10) discontinued treatment due to loss of response. Peripheral arthralgia responded in 86% (n=31/36), and axial arthropathy responded in 42% (n=8/19).At 12 months, 65% (n=44/68) of patients improved or had remission, with tofacitinib responders at 73% (n=35/48) and upadacitinib responders at 45% (n=9/20) (p<0.05). Eighty-eight percent (n=23/26) with peripheral arthralgia and 50% (n=5/10) with axial arthropathy achieved clinical response.

Conclusion

This study demonstrates the effectiveness of JAK inhibitors in treating EIM, with a high percentage of responders. Tofacitinib appears more effective than upadacitinib, possibly influenced by a higher proportion of biologically experienced patients and differences in IBD subtype distribution between the two groups, with upadacitinib mainly used in CD patients and tofacitinib in UC patients.Read more P911 Development and Characterization of SPY002, a Novel Extended Half-life Monoclonal Antibody Drug Candidate Targeting TL1A for the Treatment of IBDWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Tumor necrosis factor (TNF)-like ligand 1A (TL1A) mediates a broad spectrum of pro-inflammatory and fibrotic effects and is implicated in the pathogenesis of several immunologic disorders. Blockade of the interaction of TL1A with its cognate receptor, DR3, has been shown to ameliorate disease activity patients with Crohn’s disease (CD) and ulcerative colitis (UC). SPY002 is a novel, extended half-life fully human IgG1 monoclonal antibody (mAb) that binds soluble TL1A with high affinity and specificity, and potently inhibits TL1A-mediated signaling.

Methods

SPY002 was evaluated in multiple in vitro and ex vivo assays compared to other clinical anti-TL1A mAbs (PRA023/MK-7240, RVT-3101, and TEV-48574). Binding affinity to soluble TL1A was determined by surface plasmon resonance (SPR) and binding to membrane-bound TL1A was confirmed by flow cytometry (FACS). Competitive blockade of TL1A binding to cell-surface DR3 was determined by FACS, and competition against the decoy receptor, DcR3, was evaluated by ELISA. The binding epitope of SPY002 was determined using cryogenic electron microscopy. TF-1 cell apoptosis and a primary human whole blood-based assay measuring IFNg secretion were used to assess functional blockade of exogenously added TL1A. Half-life extension was measured via pharmacokinetic analysis in both Tg276 transgenic mice (hemizygous for human FcRn) and cynomolgus monkeys given a single bolus of SPY002 by intravenous and/or subcutaneous administration.

Results

SPY002 binds specifically to monomeric and trimeric TL1A and not to related TNF super family proteins TNF, FasL, TRAIL, or LIGHT. SPY002 demonstrates sub-nanomolar affinity for soluble TL1A and binds to TL1A over-expressed on the surface of human embryonic kidney (HEK) cells. SPY002 potently inhibits both TL1A-induced apoptosis of TF-1 cells and TL1A-induced secretion of IFNg in human whole blood, with IC₅₀ values comparable to those of RVT-3101 and TEV-48574, and a substantially lower IC₅₀ than that of PRA023/MK-7240. The half-life of SPY002 is significantly extended in Tg276 mice compared to RVT-3101. In cynomolgus monkeys, the half-life of SPY002 is at least 18 days, compared to an observed half-life of 9-12 days for RVT-3101 and PRA023/MK-7240.

Conclusion

SPY002 exhibits high selectivity and affinity for TL1A, demonstrates effective blockade of the TL1A interaction with DR3, and potently inhibits downstream cellular signaling. With an extended half-life in NHP, SPY002 demonstrates therapeutic potential for effective and safe treatment of CD and UC with the advantage of infrequent SC dosing. Further preclinical and clinical studies are warranted to demonstrate this potential.Read more P664 Anti-TNF exposure is associated with an increased risk of urgent and one-year colectomy in Acute Severe Ulcerative ColitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Acute severe ulcerative colitis (ASUC) affects up to 25% of patients with UC and is significantly associated with an increased risk of colectomy. Despite improvements in medical management, individual patient prognostication and risk stratification in ASUC remains clinically challenging. We explored clinical, biochemical, and endoscopic factors as potential predictors for colectomy in patients hospitalized with ASUC.

Methods

A retrospective analysis of patients with ASUC as defined by Truelove and Witts criteria admitted to the Mount Sinai Hospital between 2011 and 2020 was conducted. Patients with well-documented data on disease history, medication use, clinical symptoms, and laboratory results during admission for ASUC were included. Colectomy risk during hospitalization and within one year was assessed. Multivariable logistic regression analyses were performed to identify clinical, biochemical, and endoscopic parameters associated with colectomy risk in patients with ASUC.

Results

Out of the 158 patients included, 34 (21.5%) underwent colectomy during hospital admission, and 41 (25.9%) within one year after admission. On multivariable analysis, adjusting for age, sex, body mass index (BMI), and disease duration, prior anti-TNF exposure (odds ratio [OR] 4.59, 95% confidence interval [CI] 1.57-13.4, P=0.005) and the use of biologics (any type) at admission (OR 3.31, 95%CI: 1.14-9.63, P=0.028) were associated with an increased risk of 1-year colectomy. Conversely, the use of mesalamines at admission was associated with a decreased risk of 1-year colectomy (OR 0.31, 95%CI: [0.13-0.72], P=0.006). Furthermore, recent UC-related hospitalization (within one year of admission) (OR 2.72, 95%CI: 1.15-6.43, P=0.022) and increased number of bowel movements after 3 days of treatment (OR 1.18, 95%CI: 1.04-1.34, P=0.011) were associated with higher risk of 1-year colectomy. Biomarkers measured at admission including hemoglobin and albumin were associated with a decreased risk, while CRP was associated with an increased risk of urgent and 1-year colectomy. Patients with deep ulcerations observed at endoscopy tended to have an increased risk of urgent colectomy, although this was not statistically significant (univariable OR 3.36, P=0.081). Finally, treatment of ASUC with anti-TNF was strongly associated with a decreased risk of urgent (OR 0.30, 95%CI: 0.13-0.73, P=0.007) and 1-year colectomy (OR 0.31, 95%CI: 0.14-0.73, P=0.007).

Conclusion

In patients with ASUC, anti-TNF treatment is associated with a reduced risk of both urgent and 1-year colectomy. Conversely a history of anti-TNF exposure is linked to a higher risk of both urgent and 1-year colectomy. This data emphasizes the need for alternative therapies.Read more P579 Dietary beliefs, barriers, and acceptability of diet in IBD patients – a multi-centre survey from the Asia-Pacific regionWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Dietary beliefs and behaviors in IBD patients may affect both clinical outcome and psychosocial aspect of patients’ lives. New emerging studies have shown varying efficacy of different diets in inducing and maintaining remission in IBD patients. This study aims to investigate the dietary beliefs, barriers, and acceptability of diet among IBD patients in the Asia-Pacific region.

Methods

A multi-centre survey was conducted across 4 countries in Asia-Pacific. An anonymized online electronic survey was disseminated at 10 participating IBD centres. Patients were asked to rank acceptability of IBD-related diets on a Likert scale of 1 to 5, with 1 being strongly unacceptable and 5 being strongly acceptable. The survey is currently still ongoing and preliminary results from the initial 3 months are reported below.

Results

A total of 402 responses were recorded. Patient demographics and disease characteristics are shown in Table1.Most patients received dietary advice from their doctor (n=279,69.4%) and social media (n=150,37.3%). 168 (41.7%) patients believe that diet plays a role in the development of IBD. Conversely, 107(26.6%) did not believe so, and 128(31.8%) were unsure. Most patients (n=336,83.6%) patients would avoid certain foods during a flare. Diet modifications were attempted by 188 (46.8%) patients and the most common dietary modifications were the low fibre diet (n=106, 56.4%), followed by the Exclusion diet (n=69, 36.7%), and gluten free diet (n=54,28.7%). 100 (24.9%) patients are currently on an IBD-related diet.The barriers to the acceptance of IBD-related diet were identified and the two most common reasons cited were difficulty in meal preparation (n=196,48.8%) and interference of social life (n=176,43.8%). Acceptance of IBD-related diets would increase if the diet is effective in inducing remission or reducing symptoms (n=315, 78.4%) and easy to prepare (n=284,70.6%). Patients were most accepting of the low fibre diet (n=260, 64.7%) and Mediterranean diet (n=189,7.1%). Exclusive enteral nutrition (n=71,17.7%) and low FODMAP diet (n=109,27.1%) were the least acceptable.Type of IBD, duration of disease, current use of steroids and small molecules were not associated with previous dietary modification. Use of biologics, current use of more than one medication, the belief that diet can induce remission and reduce flare were independently associated with previous attempted dietary modification (p< 0.05).

Conclusion

Exclusive enteral nutrition has the lowest acceptance despite its role in inducing remission. Future IBD-related diet studies should consider the aforementioned barriers to make it more widely acceptable among IBD patients.Read more P912 A Real-World Evidence Study of Dose Escalation and associated costs of advanced therapies for Ulcerative Colitis in France and United KingdomWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Dose escalation to optimize advanced therapies is common practice in ulcerative colitis (UC) to avoid intra-class or inter-class drug switching and maintain clinical response. Dose escalation also has impact on healthcare resource utilization (HRU) and costs. However, there are limited data available on real-life dose-escalation. Study aim was to understand real-world dose escalation/de-escalation UC advanced therapy drugs patterns in two European countries (France, United Kingdom [UK]).

Methods

This retrospective study analysed data from the THIN®/CEGEDIM database to identify adult patients with moderate-to-severe UC who were naïve to advanced UC therapies or had not received any of the UC advanced therapy drugs of interest (adalimumab [ADA], golimumab [GOL], infliximab [INF], tofacitinib [TOF], ustekinumab [UST], or vedolizumab [VED]) for at least 12 months prior first prescription (and/or dispensation for France) between January 2017 and February 2022. A dose increase of ≥20% during the maintenance period compared to lowest Summary of Product Characteristics recommended dose was considered dose escalation. Proportions of patients with dose escalation after maintenance date were estimated using Kaplan-Meier (KM) survival analyses. Clinical response (defined as absence of: UC-related hospitalization or colectomy, treatment switch or addition of another UC advanced drug, systemic/rectal corticosteroids exposure), and direct (consultations, hospitalisations, diagnostic tests, UC drugs, complementary therapy) and indirect costs related to UC by treatment cohort were also analysed.

Results

1663 patients fulfilled the selection criteria, of whom 619 had information on dose patterns. Overall, 89% of patients (range 33% [INF] to 100% [GOL, TOF, and UST]) had dose escalation within the first 24 months after start of maintenance, with a median % dose increase ranging from +15% [VED] to +198% [GOL] (Table). Median (95% CI) time to first dose escalation was 2.1 (1.8-2.4) months (range 0.7 [UST] to 4.6 [VED]). Clinical response ranged from 56.3% (ADA) to 77.0% (INF). Direct annual HRU costs related to UC ranged from 3,085 (INF) to 16,527 (UST) EUR in France and from 1,857 (INF) to 4,104 (VED) GBP in the UK. Mean direct HRU costs in France were 25% higher in escalated patients compared to de-escalated patients (range: +4.2% GOL to +61.9% UST).

Conclusion

Dose escalation of advanced therapies for UC is a common strategy to avoid treatment-switching. Despite dose escalations and their cost to the system, a proportion of patients fail to achieve clinical response, highlighting the need for more efficacious and durable treatments for patients with moderate-to-severe UC.Read more P530 Early Intestinal Ultrasound changes to predict treatment response to anti-TNF therapy in paediatric Inflammatory Bowel Disease; a pilot studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

In paediatric Inflammatory Bowel Disease (IBD) selecting the right treatment in the early stages of disease is key to prevent disease progression and to prevent unnecessary exposure to ineffective treatment. Intestinal ultrasound (IUS) is increasingly used to monitor disease activity in response to therapy. However, little is known about the early transmural changes during anti-tumour necrosis factor (anti-TNF) therapy in paediatric IBD. The aim of this study is to assess the early changes in IUS parameters and to evaluate the very early predictive value of IUS for therapy response in paediatric IBD treated with anti-TNF-α therapy.

Methods

In this pilot study children (aged 3-18 years) starting with anti-TNF therapy (infliximab or adalimumab) were enrolled prospectively if ultrasound at baseline showed bowel wall thickness (BWT) ≥ 2,5mm. IUS was performed at baseline and the most affected bowel segment was identified. Subsequently IUS was repeated in this segment at week 2 and week 13. Response to therapy was determined at week 13.Response and remission was defined as follows.- Therapy response: a ≥50% decrease in faecal calprotectin (FCP) in combination with a decrease in PUCAI (≥20 points or normalisation) /PCDAI (≥12.5 points or normalisation), or normalisation of FCP (<250mg/kg))- IUS response: decrease in BWT by 25% OR decrease in BWT by >2.0 mm of the most severely affected segment compared to baseline- IUS remission/Transmural healing: BWT<2.0 mm and no Doppler signal(Limberg score) and no mesenteric fat proliferation

Results

Eleven IBD patients (aged 7 to 12 years; 64% female) were enrolled. IUS response was observed in 5/11 patients at week 2 (decrease in BWT -25% in all). Doppler signal decreased in 3/11(one point in Limberg score in all). After 13 weeks 4/11 patients showed therapy response and 3/11 showed IUS remission.

Conclusion

Transmural changes were detected by IUS as early as 2 weeks after initiating anti-TNF therapy. This pilot study observed mainly reactivity in BWT, in contrast with previous studies that initially noted changes in Doppler signal.IUS has the potential to predict therapy response at an early stage. A larger sample size is needed to accurately assess its predictive value at week 2 for treatment response.Read more P681 Preliminary data from the Biologic and Partial Enteral Nutrition in Crohn’s Disease Study (BIOPIC)Wed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Biologics such as adalimumab (ADA) are used to induce clinical remission (CR) in individuals with active Crohn’s disease (CD) but around 50% of patients actually achieve clinical remission. Exclusive enteral nutrition is also an effective induction treatment, but tolerability limits its use, especially in adults. This study aimed to assess the efficacy and tolerability of partial enteral nutrition (PEN) in combination with ADA compared to ADA monotherapy.

Methods

In this multi-centre (n=8) RCT (NCT04859088), adults with active CD (Crohn’s Disease Activity Index, CDAI ≥ 150) due to start ADA as their first-line biologic were randomised to either continue their habitual unrestricted diet (UD) or to replace half of it with PEN during their first 6 weeks of induction treatment Primary outcome clinical efficacy (i.e., clinical response, CDAI baseline decrease of ≥ 70 or CR, CDAI score <150) was assessed after 12 weeks of ADA initiation. Secondary outcomes included changes in inflammatory markers (faecal calprotectin, (FCAL), CRP) and quality of life (SIBDQ), at 3 (only FCAL), 6 and 12 weeks. To calculate adherence to PEN, used/unused tins were returned and compared to number provided. Analysis was performed using intention-to-treat analysis.

Results

32 participants (13 UD, 19 PEN) have completed the study; 29 (13 UD, 16 PEN) of whom completed the full 12 weeks of the study. Adherence rate to PEN was high (~96%). Clinical efficacy (response & remission) was UD: 92% vs PEN: 84%, p=0.490 at 6 weeks and UD: 85% vs PEN: 58%, p=0.11 at week 12. FCAL data was available for 22 participants (9 UD, 13 PEN). FCAL (g/g) significantly decreased after 12 weeks in patients receiving PEN (mean difference 189, p=0.009) but this effect did not quite reach statistical significance (p=0.052) in the UD group (Fig 1). Proportionally more patients from the PEN group had FCAL <100 mg/kg compared to the UD group (3, 6, 12 weeks, PEN: 62%, 69%, 69% vs UD: 33%, 33%, 56%) during the study course. CRP (mg/L) significantly decreased at week 6 and 12 in patients receiving PEN (week 6 & week 12, p<0.0001) and in patients continuing their UD (week 6, p=0.001, week 12, p=0.007). SIBDQ score increased in both groups (PEN, p=0.023 vs UD, p=0.008).

Conclusion

Preliminary data from the BIOPIC study suggests equivalence in clinical efficacy between the two groups but better responses to blood and gut inflammatory markers when ADA is combined with PEN. High tolerability of PEN suggests it can be a viable option for adult patients with active luminal CD.Read more P929 Relation between Crohn’s disease phenotype and response to ustekinumab in Stockholm – the STOCUSTE studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Ustekinumab, an anti-interleukin-12/23 antibody, has successfully been introduced in the treatment of Crohn’s disease, mainly in patients failing tumor necrosis factor alpha inhibitors (aTNF). As Crohn’s presents with different phenotypes, we hypothesized that response to ustekinumab treatment may differ depending on disease characteristics.

Methods

This retrospective study included 322 unselected patients diagnosed with Crohn’s disease and treated with ustekinumab in Stockholm, Sweden, between 2016 and 2021. The primary outcomes were clinical remission (physician global assessment, PGA =0), response (PGA decrease of ≥1, from baseline), and drug persistence at 3 and 12 months. Subsequently, we calculated odds ratio for drug persistence, clinical response, and clinical remission in relation to several phenotypic disease characteristics.

Results

Disease location was 15% Ileal (L1), 43% colonic (L2), 41% Ileocolonic (L3), and 7% isolated upper GI (L4), in addition, 22% had fistulizing disease. Some patients had a combination of L4 and L1, L2, or L3. The intention-to-treat response rate was 43% at 3 months, and 42% at 12 months. No difference in outcome was observed in relation to disease location or presence of fistulizing disease. Patients who were >17 years at disease presentation had almost three times the odds for response at 12 months, compared to patients who were < 17 years at diagnosis (Table 1). Almost three times lower clinical remission rates were observed in patients exposed to aTNF agents and vedolizumab prior to ustekinumab, compared to patients exposed to aTNF only (OR 0.38, CI 0.18 – 0.79, p-value 0.01). Higher remission rates were related to age >17 years at disease presentation, however this lost statistical significance in the adjusted logistic regression model. Previously operated patients had double the odds to still be on ustekinumab at 12 months compared to un-operated patients (Table 2).

Conclusion

In this Stockholm-based Crohn’s disease cohort, the distribution of disease location was well balanced. Considering isolated ileal inflammation and fistulizing disease as markers for disease severity, a substantial part of the cohort had a high disease burden. Nevertheless, there was no statistically significant difference in any of the outcomes in relation to ileal location or fistulizing disease. These results indicate that ustekinumab is a viable treatment option for all location-related phenotypic expressions, as well as fistulizing character. However, patients who previously failed two biologics, and could be considered difficult-to-treat patients, had a worse outcome on ustekinumab compared to patients who were not treatment refractory before.Read more P531 Long-Term Evaluation of Intensified Ustekinumab in Crohn's Disease: Real-Life ResultsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Dose intensification of ustekinumab (UST) is implemented in clinical practice to rescue patients with loss of response or suboptimal clinical response to the drug. Observational studies, with contradictory results, associate higher UST trough concentration and clinical outcomes in Crohn's disease (CD). The primary outcome was to evaluate the long-term effectiveness of dose intensification of UST in terms of clinical and biochemical remission and its relationship with serum trough concentrations.

Methods

A retrospective, single-center observational study was conducted, including patients with CD treated with intensified UST, analyzed from January 2023 to the present. Demographic data, smoking status, disease pattern and duration, extraintestinal manifestations, perianal disease, and prior exposure to biologics were collected.Laboratory markers (fecal calprotectin (FCP) and C-reactive protein (CRP)), disease activity scores (Harvey-Bradshaw Index (HBI)), and drug serum levels at the time of intensification, at 6 and 12 months, were analyzed to evaluate response. Clinical remission was defined as HBI < 5, clinical response was defined as reduction in the HBI by ≥3 points and biochemical remission as FCP < 150 µg/g. Data were collected from the electronic medical record. Quantitative variables were expressed as median (interquartile range). To analyze the results, a logistic regression was performed.

Results

A total of 35 patients were included. Patients' clinical and demographic characteristics are summarized in Table 1. All were intensified with subcutaneous dose of 90 mg every 4 weeks (31.4% underwent intravenous re-induction).At 6 months after UST intensification, 82.86% (n=29) of the patients presented clinical remission, with a statistically significant decrease in FCP levels (247.78 µg/g vs. 133.55 µg/g (p = 0.0026)). At 12 months, 85.71% had achieved clinical remission, also presenting a statistically significant decrease in FCP levels (370.41 µg/g vs. 200.94 µg/g (p = 0.0200)). Drug levels, classified as >2.2 µg/ml and <=2.2 µg/ml, were not related to remission at 6 months (OR 0.94, 95%CI 0.05-16.35. p=0.97) or at 12 months (OR 0.87, 95%CI 0.13-6.03. p=0.89).

Conclusion

UST intensification proves to be an effective long-term optimization strategy in CD, without an apparent correlation with higher serum drug levels in our series.Read more P682 A Retrospective Comparison of Different Treatment Modalities in Patients with Chronic PouchitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Chronic pouchitis affects ~30% of patients post total colectomy with ileal pouch anal anastomosis (IPAA) surgery. Treatment with anti-TNF, anti-integrin α4β7, anti-IL-12/23, or Crohn's disease exclusion diet (CDED), have shown promise in different studies. We aimed to compare the efficacy of these treatments in a real-world context and to detect factors that can aid in treatment choices.

Methods

A retrospective cohort study encompassing demographic, clinic, endoscopic, histologic and lab values of adult ulcerative colitis (UC) patients post-IPAA surgery with chronic pouchitis, treated with biologics or CDED at the Tel Aviv Medical Center. Data were collected at baseline, 12, 26, and 52 weeks of treatment. Primary outcomes were assessed using the modified Pouchitis Disease Activity Index (mPDAI). mPDAI response was defined as a reduction from baseline of ≥2 points, while mPDAI remission was defined as mPDAI response in addition to mPDAI score ≤4.

Results

Therapeutic interventions among 51 patients included CDED (n=10), vedolizumab (n=21), ustekinumab (n=7) and adalimumab (n=13) [Table 1].At 12 and 26 weeks, overall mPDAI response rates were 52% and 48%, respectively, with no significant difference between groups. At 52 weeks, mPDAI response rates were significantly higher for ustekinumab and vedolizumab (60% and 55%, respectively) compared with adalimumab and CDED (27.3% and 0%, respectively), p=0.043. Fecal calprotectin reduction at week-26 was greatest for ustekinumab (93%), followed by vedolizumab (73%), adalimumab (55%), and CDED (-13%), p=0.003.Treatment persistence over 150 weeks was significantly higher for ustekinumab (100%) compared with adalimumab (46%), vedolizumab (33%), and CDED (20%), p<0.001 [Figure 1]. The predominant cause for treatment discontinuation was secondary loss of response (50%), followed by primary non-response and surgical complications (14.7% each), poor compliance (11.8%), side-effects (5.9%), and development of antibodies (2.9%).Patients without prior biologic or immunomodulator treatment for pouchitis had significantly higher mPDAI response rates at 12 weeks (90%, p=0.016 and 73.3%, p=0.03, respectively). Patients with surgical pouch complications showed a trend towards lower mPDAI-defined response rates at 12 weeks (25% vs. 64.7%; p = 0.064).

Conclusion

Ustekinumab and vedolizumab demonstrate higher likelihood of maintaining long-term clinical and endoscopic response, along with greater reduction in fecal calprotectin compared with adalimumab and CDED. Biologic and immunomodulator therapy-naïve patients achieved higher induction response rates.Read more P930 Rapid symptomatic improvement with subcutaneous infliximab induction treatment for patients with moderate-to-severe Crohn’s disease: first results from the DIRECT-CD studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Subcutaneous (SC) formulation of infliximab (IFX) received regulatory approval for the maintenance treatment of Crohn’s disease (CD) in 2020. DIRECT-CD is an ongoing multicentre trial to evaluate the efficacy of SC IFX induction and maintenance treatment in monotherapy versus combination therapy in CD (EUDRACT 2021-000469-33). Here we aimed to determine the rapidity of symptom improvement during this SC IFX induction regimen.

Methods

Patients with moderate-to-severe CD (Crohn’s disease activity index [CDAI]) >220 and endoscopic ulceration) received fixed SC IFX induction doses of 240 mg at Week 0 and 2, followed by maintenance treatment (120 mg every other week). We analysed diary PRO-2 entries (stool frequency and abdominal pain) through 14 days from the first injections of SC IFX. CDAI was assessed at Week 0, 2, 4 and 8. Changes in biochemical parameters were assessed (C-reactive protein [CRP]: Week 4 and 8; faecal calprotectin [FC] at Week 8). Combined corticosteroid-free remission (CSFR) was defined as CDAI<150 and CRP≤5 mg/L or FC≤250 mg/kg and complete tapering of corticosteroids.

Results

Twenty-five patients completed 8 weeks of treatment (60% female, median age 30 years [IQR 24-45], median weight 66.6 kg [IQR 64.0-89.5], median disease duration 4 years [IQR 1-8], 64% had ileocolonic disease [L3] and 76% exhibited an inflammatory phenotype [B1], 52% were using concomitant immunomodulators, and 28% were on stable dose of steroids). On the first day after the initial dose of SC IFX (240 mg), a significant decrease in PRO-2 was observed compared to baseline (5 [IQR 3-9] vs 8 [IQR 7-10], P<0.001) and this response was sustained throughout day 14 (P<0.001, Figure 1). At all measured time points, CDAI decreased significantly compared to baseline (Week 0: 313 [IQR 271-402]; Week 2: 245 [IQR 140-296], P<0.001; Week 4: 218 [101-258], P<0.001; Week 8: 172 [127-260], P<0.001). Combined CSFR was reached in 30% and 57% of all patients at Week 4 and 8, respectively. Median CRP was lower at Week 4 compared to baseline CRP (2.8 mg/L [IQR 0.7-4.9] vs 7.1 mg/L [IQR 2.1-26.3], P=0.001), a significant drop of FC was observed at Week 8 compared to baseline (77 mg/kg [IQR 37-847] vs 1385 mg/kg [IQR 219-3093], P<0.001).

Conclusion

Induction treatment with SC IFX provided a rapid decrease of abdominal pain and diarrhoea as early as day one. CDAI, CRP and FC decreased significantly at the earliest time point of evaluation (Week 2-8). DIRECT-CD is an ongoing clinical trial.Read more P560 The impact of reactive point-of-care drug level measurement on the medium-term course of inflammatory bowel diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

First generation of biologicals (infliximab (IFX) and adalimumab (ADA)) has revolutionised the treatment of patients with Crohn’s disease (CD) and ulcerative colitis (UC), however, primary resistance or loss of efficacy are serious clinical challenges. Although there is currently insufficient evidence to recommend for or against the use of therapeutic drug monitoring to improve clinical outcomes, the determination of IFX and ADA levels with point-of-care tests (POCT) is fast, simple and can be a helpful tool to guide the therapy. Our aim was to evaluate the impact and duration of IFX and ADA level measurement with POCT on the medium-term course of the disease.

Methods

In our retrospective study we enrolled patients with UC and CD who were treated at our department with IFX or ADA and underwent a reactive drug level (DL) measurement which was carried out with POCT method between October 2021 and May 2023. We examined the types of therapeutical decision (dose intensification, switch or swap) were performed knowing DL and how the changes have affected the half-yearly outcome. Laboratory findings such as C-reactive protein (CRP), iron, albumin, haemoglobin, platelet, stool calprotectin level and calculated disease activity indices, Crohn’s disease activity index (CDAI), Harvey-Bradshaw Index (HBI), partial Mayo score and Simple clinical colitis activity index (SCCAI) were analysed at baseline and after 6 months.

Results

99 patients were enrolled; median age was 37 years (IQR 29-51 years). Baseline characteristics are shown in table 1. In 46 cases the drug level was subtherapeutical while in 53 cases was in normal range. At baseline patients with low drug level had significantly higher CRP (22.09 vs 10.7 mg/l, p=0.026), platelet count (344.6 vs 272.8 G/l, p=0.004) and significantly lower iron level (12.28 vs 15.6 umol/l, p=0.033) compared to patients with normal drug level while there was no difference between the activity indices (CDAI p=0.091; HBI p=0.187; SCCAI p=0.830; pMayo p=0.662) within the two groups. 70% of the patients in the low DL group had a therapeutic change: in 52% dose increase, in 13% switch, and swap in 15%. Changes in the therapy were significantly more frequent in the low DL group (p<0,0001). The difference in baseline CRP and iron level between the two groups was no longer detectable at month 6 (CRP 7.55 vs 8.7 mg/l, p=0.669, iron 14.1 vs 15.6 umol/l, p=0.325). All activity indices were significantly lower in low DL group at month 6 compared to baseline (CDAI p=0.022; HBI p=0.016; SCCAI p=0.047; pMayo p=0.046).

Conclusion

The drug level monitoring with POCT affected the decision-making process and presented beneficial effect for medium-term and helped to achieve stride therapy goals.Read more P955 The effect of appendicectomy on the clinical course of Ulcerative Colitis: Preliminary resultsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Emerging evidence indicates an immunomodulatory role of the appendix in ulcerative colitis (UC). Previous studies have suggested a beneficial effect of appendicectomy in inducing and maintaining remission. Therefore, appendicectomy may be considered as an alternative or adjunctive treatment in UC.

Aim

To evaluate the efficacy of appendicectomy in maintaining remission in UC patients.

Methods

Adult patients with established UC in complete clinical and endoscopic remission (defined as Mayo score <3 with endoscopic subscore of 0 or 1) following medical induction treatment for disease relapse within 12 months prior to randomisation, were enrolled in the Netherlands and United Kingdom. Patients were randomised (1:1) to undergo appendicectomy (intervention group) or continue maintenance medical therapy (control group). The primary outcome was the one-year UC relapse rate (defined as a total Mayo-score score ≥5 with endoscopic subscore of ≥2). To detect a clinically relevant decrease in relapse rate from 40% to 20%, 82 patients per study arm were needed to achieve 80% power. The last patient was included in September 2022, so analysis of the primary outcome parameter is expected to start soon. Trial progress, including the accumulated number of (serious) adverse events (SAE) in both groups, were presented annually to the Data Safety Monitoring Board. Therefore safety data is available.

Results

In total, 99 patients were included in the intervention group and 99 patients in the control group. There were 86 males and 112 females, with a median age of 41 years (IQR 33-52). Baseline characteristics were comparable in both groups, with the majority of patients having proctitis (38.9%) or left sided colitis (35.9%). Three SAEs were reported in the appendicectomy group, 2 of which were related to the surgical procedure (reintervention for obstructive ileus and postoperative hematoma) and one hospitalisation for clostridium infection. One SAE was reported within the first year in the control group (appendicitis). The one-year reported colitis-associated adverse event rate was significantly lower in the appendicectomy group when compared to the control group (46.4% vs. 63.9%, P=0.02). During follow up there were no colectomies in the appendicectomy group, whereas three patients underwent colectomy for therapy-refractory disease in the control group.

Conclusion

Appendicectomy in patients with UC has the possibility to decrease the rate of colitis-associated (serious) adverse events. These results suggest that the final analysis of the primary outcome parameter (relapse rate) could demonstrate that appendicectomy is superior to standard medical therapy alone in maintaining remission in these patients.Read more P701 Evaluation of the effectiveness of vedolizumab in patients with Crohn's disease: a multicenter real-life study from ArgentinaWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Vedolizumab (VDZ) is a gut-selective integrin inhibitor used to treat Crohn's disease (CD). Most of the information regarding real-life data on response to VDZ has been published from North America and Europe cohorts and there is scarce information from Latin America related to effectiveness of VDZ in patients with CD. The aims of this study were: i) to describe the clinical characteristics of patients with CD who received VDZ, ii) to know in which biologic line VDZ was indicated, and iii) to evaluate the clinical response at one year and the persistence of treatment during follow-up.

Methods

A retrospective multicenter study was conducted in 18 Argentinean centers. We included CD adult patients (age ≥18y) who started VDZ between 01/06/2015 and 31/10/2023 and completed at least VDZ induction. Baseline demographic characteristics, response at 12 months (m), need for optimization, and treatment persistence during follow-up were assessed. Logistic regression was used to evaluate predictors for response at 12m and treatment persistence.

Results

A total of 113 CD patients (57% male), mean age 52 years (range 18-87 years) were included. Colonic (47%) and ileal (29%) were the most frequent CD involvement. Inflammatory (68%) was the most frequent phenotype compared to stenosing (23%) and fistulizing (9%). Perianal involvement was present in 9% of patients. VDZ was indicated as first-line in 61 (54%) patients, second-line 31 (27.4%) patients, third line 17 (15%) patients, and fourth-line 4 (3.5%) patients. At 12 m of follow-up, clinical remission was observed in 37 (32.7%) patients and clinical response in 56 (49.6%) patients. Eighteen (15.9%) patients presented a lack of response/primary failure. Adverse effects leading to VDZ discontinuation prior to 12m occurred in 2 (1.8%) patients. Mean follow-up time in those patients that achieved clinical remission/response at 12m was 23 (SD 15) m. Thirty-five (37.6%) of those patients required dose optimization and 69 (74.2%) persisted on treatment during follow-up. Male sex (OR 2.93, 95%CI 1.04-8.26) and inflammatory phenotype (OR 5.37, 95%CI 1.16-24.9) were independent predictors for clinical response/remission at 12m. VDZ in first-line (OR 3, 95%CI 1.05-8.52) and inflammatory phenotype (OR 2.96, 95%CI 1.07-8.22) were independent predictors for treatment persistence in those patients that achieved clinical remission/response at 12m.

Conclusion

This is the first real-life multicenter study on the effectiveness of VZD in CD in Argentina and one of the largest in Latin America. VDZ showed an effective therapeutic option in a real-life setting. A higher efficacy was observed in males, inflammatory phenotype and in biologic-naïve patients.Read more P561 Reasons for low use of topical 5-ASA formulations in patients treated for ulcerative colitis: comparison of doctors and patients perspectivesWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Ulcerative colitis (UC) is a chronic relapsing inflammatory disorder of the colon. In patients with proctitis or left sided colitis, topical application of 5-ASA as suppository, enema or foam preparation has been shown more effective as compared to systemic treatment. In a study conducted 10 years ago, we observed an underuse of topical therapy in patients with UC.

Objectives

to assess the current use of topical 5-ASA for UC and compare it with previous findings. To evaluate perspectives on use of topical therapies, among physician and patients.

Methods

The study had two parts. We first conducted a retrospective cohort data analysis, among adult UC patients included in the SIBDCS. We included patients enrolled since 2012 (not included in our previous study), and to compare the results of the use of 5-ASA therapies from 2021-2021. We then conducted two parallel surveys: with patient and with gastroenterologists. The survey was independent from the cohort data analysis. We assessed potential reasons for low use of topical therapies.

Results

721 patients were included in the retrospective study (329 (45.6%) females, age at diagnostic (median, IQR): 31 (23-42), disease duration: 6 (2-15)). Disease extension at last FU was 18.0% proctitis, 26.3% proctosigmoiditis; clinical activity was low to moderate in 18.6%, and high in 1.8% of patients. 16.4% of patients with proctitis received topical 5-ASA only (5-ASA top+oral (5ASA): 42.2%), 5.9% with proctosigmoiditis (16.6% 5ASA), 0% in left-sided colitis (9.3% 5ASA) (figure 1). Exclusive 5-ASA topical use was lower than observed 10 years ago (23.3%) in proctitis. The survey was completed by 142 patients: 89 females (63%), mean (SD) age 46 (13) and disease duration 15 (10), 15% had proctitis/proctosigmoiditis and 29% left-sided colitis. 63 gastroenterologists participated in the survey; 25% were females, 36.5% had a professional experience up to 10 years, 55% were in single/group practice. 76% of patients reported having ever been prescribed suppositories (S), 74% foam (F), 61% enema (E). Patients-reported top reasons for stopping topical therapy prematurely (1/3 of cases) were unpleasantness (51.3% F/E, 13.9% S), ineffectiveness (41.1% F/E, 60.5% S), and preference for tablets (51.3% F/E, 37.8% S). Physicians’ perspectives on compliance difficulties were unpleasantness (83.7% F/E, 56.3% S), and preference for tablets (76.4% F/E, 63.7% S). 85% of patients were well informed on rectal therapies, 76% of doctors would be open for training/update on rectal therapies.

Conclusion

The use of rectal therapies in UC patients that should benefit from is still low. Reasons for non-compliance were discordant between doctors and patients.Read more P702 Long term outcomes following de-escalation of dose-intensified ustekinumab in patients with Crohn’s diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Data on outcomes following de-escalation of dose-intensified ustekinumab (UST) in Crohn’s disease (CD) have not been reported. This retrospective cohort study aimed to evaluate the failure rates 6, 12, and 24 months after de-escalation from dose-intensified UST to standard dose UST and identify predictors of failure.

Methods

Single centre, retrospective study of consecutive CD patients undergoing de-escalation of dose-intensified UST (90mg 4-weekly) to standard dosing (90mg 8-weekly). De-escalation and post de-escalation decisions were informed by protocolised 6-monthly assessment using Harvey-Bradshaw Index, C-reactive protein (CRP), faecal calprotectin (FCP), drug level and intestinal ultrasound. Failure was defined by re-escalation of UST, corticosteroids, switch out of class, or IBD-related hospitalisation or surgery. Success was defined by continued standard UST dosing. Categorical variables were compared using Fisher-exact and continuous variables using Mann-Whitney U tests between groups.

Results

14 patients underwent de-escalation from April 2020 to March 2023. The median age was 41 years, disease duration 15 years, and duration on dose-intensified UST 34 months. 43% received IV reinduction at time of escalation, 86% had previous exposure to advanced therapies, of which 43% were dose-intensified. 36% were on an immunomodulator (IMM) at de-escalation. In the 6 months prior to de-escalation, the median CRP was 3.5mg/L, FCP 96mg/g, and 91% were in sonographic remission. 5/14 (36%) failed de-escalation at 6 months and 9/14 (64%) failed by 12 months. Of those with 24 months follow up, 9/12 (75%) failed de-escalation. Median time to failure was 8 months (IQR 4.5-13). All patients who failed underwent re-escalation and 2 required surgery. UST drug levels reduced from 3.6 to 1.9mg/mL 6 months post de-escalation. Re-escalation successfully recaptured response in 7/9 (78%). A greater proportion of patients with successful de-escalation at 12 months received concomitant IMM compared to those that failed (80% vs. 11%, respectively; p = 0.02). There were no other significant differences in clinical or disease characteristics between those with failure vs. success at 6, 12, or 24 months, although numbers were small (Table 1).

Conclusion

One-third of patients failed de-escalation of dose-intensified UST at 6 months, two-thirds failed at 12 months and three-quarters by 24 months. Patients considered for a trial of de-escalation need close, objective monitoring as most failure occurs early, and re-escalation is successful in the majority. Concomitant IMM may reduce failure rates and should be considered. Further studies are required to confirm these findings and identify additional predictors of de-escalation failure.Read more P956 Pregnancy outcomes after maternal or paternal exposure in the tofacitinib ulcerative colitis clinical programmeWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Pregnant women with ulcerative colitis (UC) have a higher risk of adverse pregnancy outcomes vs age-matched controls.¹ Tofacitinib is an oral Janus kinase inhibitor for the treatment of UC. There are no well-controlled studies on tofacitinib use in pregnant women. It was shown to be teratogenic in rats and rabbits at approximately 73 and 6.3 times, respectively, the maximum recommended human dose of 10 mg twice daily. Tofacitinib affects female fertility, parturition and peri/postnatal development in rats and was secreted into the milk of lactating rats; it had no effects on male fertility or sperm motility/concentration.

Methods

We report pregnancy outcomes in the tofacitinib UC clinical programme: 4 randomised, placebo-controlled Phase (P)2/3 studies (NCT00787202/NCT01465763/NCT01458951/NCT01458574),^2,3 an open-label, long-term extension study (NCT01470612)⁴ and a randomised P3b/4 study (NCT03281304) were analysed.⁵ Study protocols excluded pregnant women, required females of childbearing potential to use effective contraception and regularly tested for urine β-hCG. Study drug was discontinued in female patients who became pregnant. Pregnancy outcomes after maternal or paternal tofacitinib exposure were identified from Pfizer’s internal safety database up to March 2023 and categorised as healthy newborn, medical termination, foetal death, congenital malformation, spontaneous abortion or lost to follow-up.

Results

There were 40 pregnancies with exposure to tofacitinib: 16 cases of maternal exposure (median age 29.5 [range: 24−41] years), all during the 1^st trimester (10 [62.5%] healthy newborns, 2 [12.5%] medical terminations, 2 [12.5%] spontaneous abortions, 2 [12.5%] lost to followup); and 24 cases of paternal exposure (18 [75.0%] healthy newborns, 2 [8.3%] spontaneous abortions, 4 [16.7%] lost to follow-up). There were no cases of foetal death or congenital malformation.

Conclusion

Most known outcomes for maternal and paternal tofacitinib exposure were healthy newborns, similar to previous analyses in other tofacitinib clinical study populations and the general UC population.^6,7 Limitations included the low number of reported pregnancies and available follow-up. Tofacitinib should not be used during pregnancy unless necessary.References:1. Cornish et al. Gut 2007;56:830−72. Sandborn et al. N Engl J Med 2012;367:616−243. Sandborn et al. N Engl J Med 2017;376:1723−364. Sandborn et al. Aliment Pharmacol Ther 2022;55:464–785. Vermeire et al. J Crohns Colitis 2021;15:1130–416. Mahadevan et al. Inflamm Bowel Dis 2018;24:2494–5007. Selinger et al. Frontline Gastroenterol 2021;12:214–24Study sponsored by Pfizer. Medical writing support provided by S Leneghan, CMC Connect; funded by PfizerRead more P562 Safety and persistence oh the first JAK inhibitor Tofacitinib in patients with ulcerative colitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

A drug safety warning was published in 2021 about the risks associated with tofacitinib, which were found in the Oral-Surveillance study. The European Medicines Agency (EMA) and the Spanish Agency for Medicines and Medical Products (AEMPS) have recommended, due to this warning, some precautions in the prescriptions: It should not be used in patients older than 65 years of age, people who are current or past smokers, or individuals with cardiovascular or malignancy risk factors unless there are no suitable treatment alternatives. The aim fo this study was to assess the safety and treatment persistence of tofacitinib in clinical practice in three Spanish third-level hospitals.

Methods

Retrospective observational multicenter study of patients with Ulcerative Colitis (UC) treated with tofacitinib from January 2019 to October 2023. Sex, age, line of treatment, persistence, adverse events, discontinuations and risk factors associated with the warning were evaluated. Information was collected from the hospital’s information systems.

Results

A total of 56 patients, 53% women, mean age 55 (18-72) years old. Tofacitinib was the first line treatment in 2% of the patients after loss of response to the conventional treatment, second line for 57%, third line for 30% and fourth line for 11% after biological drugs (infliximab, adalimumab, vedolizumab and ustekinumab). 52% of patients needed maintenance with the higher doses (10mg dose) after induction due to the lack of response with the 5 mg dose, with an average of 52 weeks. The mean persistence was 18 months (1-56), with 19,6% discontinuations due to primary failure and secondary failure. It must be noted that one patient, who received tofacitinib for three years, underwent appendicular neoplasia and finally died due to liver metastases. There was not discontinuation due to other adverse events, which were: 3,6% herpes zoster, 46,4% increased total cholesterol level >200 mg/dl (compared with the initial measurement), of which 19% received statins.There were 27 (48%) patients with risk factors associated with the safety warning: 37% cardiovascular risk, 3,7% older than 65 years, 11,1% previous malignancy, 18,5% current or past smokers and 29,6% had several of these risks.

Conclusion

In this multicenter real-world treatment-refractory UC population cohort, tofacitinib was well tolerated in the long term, even in the patients with risk factors related to the warning.Read more P998 Phase 2 basket design study evaluating the efficacy and safety of an anti-TL1A antibody (TEV-48574) in moderate to severe ulcerative colitis or Crohn's Disease (RELIEVE UCCD)Wed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

TEV-48574 is a human antibody that targets tumor necrosis factor (TNF)-like ligand 1A, also known as TNF superfamily member 15 (TNFSF15). TEV-48574 is being evaluated in the first basket design trial in IBD. The basket design is uniquely suited for the efficient assessment of TEV-48574 as evidence suggests that TL1A signaling plays a key role in both ulcerative colitis (UC) and Crohn’s disease (CD). TL1A signaling is not a primary driver but an amplifier of inflammation; thus, targeting TL1A should mitigate excessive immune responses while leaving baseline immunity intact. Originating in oncology trials, the basket trial design has emerged as a new efficient approach for testing treatment efficacy in different disease indications with potentially common molecular mechanisms. The basket design approach allows the evaluation of multiple indications in a single study design that provides adequate support for initiation of confirmatory studies. Additionally, the basket design allows for shared sites and institutional review boards, data collection and analyses under consistent conditions. Herein, we describe the phase 2b basket trial evaluating TEV-48574 in UC and CD (clinicaltrials.gov NCT05499130), currently ongoing along with a long-term extension study (LTE)(NCT05668013).

Methods

In this double-blind placebo-controlled global study, TEV-48574 or placebo is administered subcutaneously to adults (n = 240) diagnosed with moderate-to-severe IBD (UC (n = 120) or CD (n = 120)). Patients who meet pre-specified inclusion/exclusion criteria are randomized to either one of two TEV-48574 dose regimens or placebo in a 1:1:1 ratio (stratified by diagnosis (UC or CD) and previous exposure to advanced IBD therapy(biologics and small molecules)) for 14 weeks. Patients who complete the 14-week induction period have the option to enter the LTE, consisting of a 44-week maintenance period for responders and a re-induction period for non-responders. Primary efficacy endpoints are induction of clinical remission (a modified Mayo Score of ≤2 points for UC), and endoscopic response (a reduction in Simple Endoscopic Score for Crohn's Disease (SES-CD) of ≥ 50% from baseline) for CD, at week 14. A Bayesian approach will be used to compute posterior probabilities for the response endpoints within each indication. Additional endpoints include safety assessments, measures of clinical response, biomarkers, pharmacokinetics, and immunogenicity.

Results

ConclusionTEV-48574 is a potential novel treatment option for patients with UC and CD that may have dual antifibrotic and anti-inflammatory effects. The phase 2 basket study design offers an efficient approach to advance TEV-45874to confirmatory phase 3 studies.Read more P619 Sleep disruption is associated with reduced quality of life in inflammatory bowel disease through its interaction with painWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Quality of life is reduced in people with inflammatory bowel disease. Poor sleep is prevalent in people with inflammatory bowel disease. This study aimed to investigate the influence of sleep on quality of life in people with inflammatory bowel disease.

Methods

An online questionnaire was administered through three tertiary IBD centres, social media and through Crohn’s Colitis Australia. The questionnaire included the EQ-5D-5L measures of health-related quality of including EQ-5D utility score, EQVAS – visual analogue scale from 0-100 of quality of life and domains mobility, selfcare, activities, pain and depression and anxiety. Measures of sleep included the insomnia severity index (ISI), and the Pittsburgh sleep quality index (PSQI). IBD activity was assessed using validated patient reported scores. Demographic data and mental health scores were also obtained.

Results

Quality of life was lower in people IBD than the general South Australian population (utility score mean (SD) 0.79 (0.15) v 0.91(0.14)). Poor sleep and clinically significant insomnia were associated with lower quality of life (utility score 0.77 (0.15) and 0.71 (0.16) respectively, cohort 0.79 (0.15), p<0.0001). Sleep quality scores moderately correlated with EQ-5D domains pain (Ro=0.35), usual activities (Ro=0.32), and depression-anxiety (Ro=0.37) but not domains self-care or mobility. After adjusting for demographic variables, IBD anxiety, depression, and anxiety the pain domain continued to be influenced by sleep quality, sleep disturbance and sleep duration, and the usual activities domain continued to be influenced by daytime dysfunction (see table 1).Clinically significant insomnia was associated with a reduction of 13.6 (10.42-16.91) (univariate regression) in quality of life measured by EQVAS. Following introduction of demographic and IBD activity the reduction in EQVAS for clinically significant insomnia remained significant (10.11 (6.96-13.27)). Health related quality of life scores (EQVAS) were significantly worse in those with clinically significant insomnia and active IBD than with active IBD alone (see Figure 1).

Conclusion

Health related quality of life in IBD is influenced by aspects of sleep quality irrespective of IBD activity and mental health conditions. The presence of insomnia is associated with a significant decline health related quality of life. Consideration should be given to sleep targeting interventional studies in an IBD population.Read more P725 Predictive factors for biologic therapy initiation after ileal pouch-anal anastomosisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Patients with ulcerative colitis (UC) undergoing proctocolectomy and Ileal Pouch-Anal Anastomosis (IPAA) frequently develop long-term complications, such as chronic pouchitis and Crohn’s-like disease of the pouch. These may eventually require biologic therapy. We aimed to identify peri-operative predictors for biologic therapy after IPAA.

Methods

All patients after IPAA followed at Rabin Medical Center pouch clinic and consenting to prospective observational follow up were included. Patients undergoing IPAA due to familial adenomatous polyposis (FAP) and those with ileostomy were excluded. Primary outcome was the initiation of biologic therapy after IPAA. We used Cox proportional hazard models to evaluate the following potential predictors: gender, race, smoking status, BMI category, UC duration until surgery, surgery indication, immediate post-operative complications (bowel obstruction, infection and leakage), and pre-operative treatment with 5-ASA, steroids, immunomodulators, and biologic therapy.

Results

Out of 174 patients in our cohort, 18 were excluded due to FAP and 8 due to ileostomy, leaving 148 for analysis. Prior to IPAA, 52 patients (35%) were treated with biologic therapy. Median follow-up from ileostomy closure to last documented visit was 15.14 years. During this period, 32 patients (21.6%) initiated biologic therapy, including 18 with adalimumab (12.2%), 10 with infliximab (6.7%), 2 with ustekinumab (1.3%), 1 with golimumab (0.6%), and 1 with vedolizumab (0.6%). Median time-to biologic therapy initiation was 10.1 years (IQR 10.0).Significant hazard ratios (HR) for biologic therapy initiation were pre-operative treatment with biologic therapy (HR 4.8, 95% CI; 2.3-10, p<0.001); Arab descent (HR 4.7, 95% CI; 1.6-14, p=0.005); pre-operative treatment with immunomodulators (HR 3.0, 95% CI; 1.3-7, p=0.011); UC duration of less than 10 years before ileostomy closure (HR 2.7, 95% CI; 1.2-6.3, p=0.02); past smoking status (HR 2.6, 95% CI; 1.22-5.7, p=0.013); and immediate post-operative complications (HR 2.0, 95% CI; 1.0-4.1, p=0.05). None of the patients undergoing IPAA due to dysplasia (n=27), required biologic therapy.

Conclusion

Pre-operative treatment with either biologic therapy or immunomodulators, Arab descent, short disease duration prior to IPAA, past smoking status, and post-operative complications were significant predictors of biologic therapy initiation post-IPAA. Patients with these risk factors may benefit from closer post-operative follow-up and earlier initiation of biologic therapy.Read more P726 A phase 2 study investigating the efficacy and safety of dupilumab versus placebo in adults with moderately to severely active ulcerative colitis with an eosinophilic phenotypeWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Ulcerative colitis (UC) is a heterogeneous, chronic inflammatory disease, with many different drivers of pathogenesis, characterised by inflammation of the colon mucosa, relapsing–remitting disease course and variable response to therapy. Around 30–55% of patients with UC are refractory to treatment during the induction phase, despite the availability of molecular targeted agents. Recent studies have investigated a potential link between eosinophilia and increased disease activity, poorer clinical outcomes and response to therapy.Dupilumab is a fully human monoclonal antibody that blocks the shared receptor component for interleukin (IL)-4 and IL-13, key and central drivers of type 2 inflammation in multiple diseases. It is approved for treatment of atopic dermatitis, asthma, chronic rhinosinusitis with nasal polyps, eosinophilic oesophagitis and prurigo nodularis. The phase 2 LIBERTY-UC SUCCEED (NCT05731128) study is designed to investigate the efficacy and safety of dupilumab versus placebo in adults with moderately to severely active UC with an eosinophilic phenotype.

Methods

Approximately 100 patients will be randomised 1:1 to receive dupilumab or placebo treatment for 52 weeks. Key inclusion criteria include age ≥18 years, moderately to severely active UC (modified Mayo score 5–9), biomarker enrichment, and inadequate/non-response, loss of response, or intolerance to standard biologic therapy and/or oral corticosteroids, ASA compounds, immunomodulators or small molecules. Key exclusion criteria include severe extensive colitis (defined by current hospitalisation, requirement for surgery for UC within 12 weeks of screening), prior medical history of eosinophilic colitis, or presence of intestinal failure. Participants who qualify will have the opportunity to receive open-label dupilumab.

Results

The primary endpoint is proportion of patients in clinical remission at Week 24, defined as a modified Mayo score of ≤2 with a stool frequency score ≤1, a rectal bleeding score = 0 and a Mayo endoscopic subscore ≤1 with absence of friability. Higher scores indicate greater disease severity. Secondary endpoints include the proportion of patients achieving clinical response by modified Mayo score at Week 8, 24 and 52, and incidence of treatment-emergent or serious adverse events.

Conclusion

The phase 2 LIBERTY-UC SUCCEED study will evaluate the efficacy and safety of dupilumab therapy in adults with moderately to severely active UC with an eosinophilic phenotype. This will aid in addressing the need for precision medicine approaches to treat UC.Read more P620 A cost-effective Inflammatory Bowel Disease flare management pathway utilising rapid access intestinal ultrasound and nurse-led triage to achieve hospital avoidance with increased patient satisfactionWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Timely inflammatory bowel disease (IBD) flare treatment improves outcomes, but quick differentiation from other symptom causes is challenging. We aimed to reduce unplanned hospital presentations with a novel IBD clinical care pathway (CCP) allowing appropriate early flare management, utilising nurse-led triage and objective assessment with rapid access intestinal ultrasound (RAIUS).

Methods

Prospective data collection from 15 November 2022 until 14 June 2023, including clinical outcomes, pre-specified criteria for healthcare utilisation impact, clinical coding data, and patient satisfaction surveys. A senior IBD nurse assessed patients using a symptom severity-based algorithm, utilising a modified partial Mayo score and Harvey-Bradshaw Index. Standardised blood and stool tests were collected. Based on clinical urgency, patients were discussed with their specialist, referred for RAIUS, or considered for planned hospitalisation if severe symptoms (bypassing emergency department (ED)).

Results

There were 211 episodes of care (EOCs), with 407 initial and follow up encounters. The median patient age was 34 (IQR 25-44), a majority female (66%), 54% with Crohn’s disease, and 61% bio-exposed. Most (78%, n=165) EOCs were for flare symptoms (mild 41% (n=69), moderate 49% (n=80), severe 10% (n=16)) and the remainder for non-flare concerns (n=46). Of those with flare symptoms, 36% (n=59) had medication optimisation for active disease (5% (n=11) started steroids), 41% (n=67) reassured of remission, 12% (n=19) aperients for faecal loading, 5% (n=8) referred for further investigations, 2% (n=4) seen urgently in colorectal clinic for perianal flare, 2% (n=3) electively admitted, and 3% (n=5) seen urgently in IBD clinic. RAIUS was performed in 56 EOCs (27%), showing active disease in 32% (n=18), response/remission in 43% (n=24), and faecal loading in 23% (n=13). After RAIUS, 52% (n=29) had IBD medication optimisation. Based on pre-specified criteria, unplanned hospitalisation was avoided in 10% (n=20) of EOCs, urgent clinic review avoided in 58% (n=123), and no direct impact in 32% (n=68), with a net saving of AUD$146418 (Figure 1). Clinical coding data showed lower hospital presentations (Figure 2). Only 7 patients (3%) had an unplanned hospital presentation within 30 days of CCP engagement (most after-hours) and 5 (2%) were seen urgently in IBD clinic. With the CCP, more survey respondents (n=60) were "satisfied" or "very satisfied" with the IBD service, increasing from 53% (n=32) to 85% (n=51).

Conclusion

Our novel CCP improved IBD care through timely assessment, with high patient satisfaction and cost savings. Better integration of nursing and intestinal ultrasound resources can improve IBD care.Read more P999 First in human treatment of Crohn’s disease with autologous ex-vivo expanded polyclonal, gut-targeted regulatory T cells: Initial results of the TRIBUTE feasibility studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Despite the increase in novel medications for Crohn’s disease (CD), many patients either fail to respond adequately to, or are intolerant of current drugs. Cell therapies have yet to have a significant impact in IBD but represent a potential novel treatment option. Regulatory T-cells (Tregs) play a key role in immune homeostasis, and Treg dysfunction is implicated in the pathogenesis of CD. Their therapeutic potential has not been assessed in humans with CD. We designed a Phase 1b study to explore the feasibility of using novel, autologous, ex-vivo expanded, gut-homing Tregs as a treatment for CD.

Methods

The TRIBUTE feasibility study aimed to treat 4 patients with treatment-refractory, moderate to severe CD (CDAI 220-450 and endoscopic ulceration) with a single dose of 3-5x10⁶ cells/kg of TR004, an autologous cell product comprising CD4⁺CD25⁺CD127^lowCD45RA⁺ Tregs expanded ex-vivo in the presence of an agonist that increases the expression of a4b7, priming the cells for gut homing. Deuteration during expansion allowed for cell tracking. Primary outcomes were dose-limiting toxicity by week 5, feasibility of recruitment to and retention in the study, successful expansion of the cells and successful dosing. Colonoscopy was performed at screening and at week (wk) 8 and disease activity (CDAI and biomarkers) was assessed at wk 0,1,2,3,5 and 8. Safety follow up is planned to wk 104.

Results

5 patients (3 male, median age 36 (range 24-39), median failed advanced therapies 3 (2-4)) were screened. In 1 patient, cells failed at day 21 of expansion due to human error requiring the patient to be replaced.Of the 4 patients with successful expansion of cells, after 23-30 days of expansion, median b7 expression was 98% (92-99%) and cell viability was 91% (84-94%). Median fold expansion was 254 (32-578). 3 patients received a dose of TR004 and attended all study visits, the other patient being withdrawn prior to dosing due to pregnancy after contraceptive failure. No dose-limiting toxicities occurred. 1 patient, with long standing colonic CD and PSC, had dysplasia identified at the wk 8 colonoscopy and underwent colectomy at wk 20. 1 patient started oral prednisolone at wk 6 for active disease. In the 3 patients who were dosed, median CDAI was: wk0: 357, wk1: 295, wk2: 207, wk3: 218, wk5: 200 and wk8: 208. (Figure 1a). SES-CD was unchanged from screening to week 8 (Figure 1b).

Conclusion

In this first in human study we demonstrated that treatment with a novel cell product comprising autologous, ex-vivo expanded, gut-homing Tregs, is feasible in patients with CD. No dose limiting toxicity was identified. Clinical and endoscopic changes should be interpreted with caution in such small numbers of patients. There is a rationale to proceed to Ph2.Read more P727 Clinical efficacy of apheresis in Ulcerative Colitis. The experience of four tertiary centersWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Selective depletion of myeloid lineage leucocytes by adsorptive granulocyte and monocyte apheresis (GMA) with Adacolumn ^® was introduced as a nonpharmacologic treatment for ulcerative colitis (UC) in 2000. It has been reported that GMA may be effective in combination with immunosuppressive treatment in a subset of patients.Τhe purpose of our study is the evaluation of the effectiveness and safety of GMA as a complementary treatment in patients with refractory ulcerative colitis.

Methods

Prospective data collection of a patient cohort with refractory UC receiving Adacolumn ^® as an adjunct to their medical treatment. The therapeutic protocol has 2 phases: The induction phase entails two sessions per week for at least 3 weeks. The maintenance includes one weekly session for one month, one session every 15 days for one the next month, and monthly sessions thereafter. The patients’ medical treatment was maintained during the sessions. As a failure to GMA was considered the need for colectomy, the switch to a different treatment and inability to discontinue steroids. Response was evaluated after completion of at least 6 sessions of GMA.

Results

Ten patients with refractory UC were offered Adacolumn^® between February 2021 and September 2023. Mean age was 39.6 years (22-61years). All patients had failed at least one biologic treatment and two-thirds two biologics. Their treatment which was maintained during GMA was: tofacitinib 10mg bid for 4 patients, ustekinumab 90mg sc every 8 weeks for 3, vedolizumab 300 mg every 8 weeks for 2, and corticosteroids 16mg for one. The median duration of treatment was 5.1 months (2-13 months), while the median number of sessions was 16 (6-45). Clinical and endoscopic remission was achieved in two cases (20%), after 13 sessions for both (in brackets in the Table) whereas two patients (20%) responded clinically according to partial Mayo score. Treatment failure was documented for 6 patients (60%) after 6-45 sessions. Patient number 4 performed 45 sessions in different hospitals because he was reluctant to be operated. Three underwent colectomy and three discontinued due to non-response. No adverse effects were observed. The initial median of partial Mayo score was 6 (5-9) while at the end of the evaluation was 4.5 (0-9). Table 1 summarizes the results of our study.

Conclusion

1) GMA may be beneficial as an adjunct to biologics in refractory to medical treatment UC patients.2) Interestingly, all patients on tofacitinib showed a favorable response after the addition of GMA.This observation may help define a subset of UC patients who may benefit the most.Read more P1000 A meta-analysis and systematic review of 5-aminosalicylates withdrawal in Inflammatory Bowel DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

5-aminosalicylic acids (5-ASA) are the first-line agents in mild-to-moderate ulcerative colitis (UC). They are not recommended for Crohn’s disease (CD) or moderate-to-severe UC. 5-ASAs are the most prescribed medication for all patients with inflammatory bowel diseases (IBD). Its continuous use is associated with significant cost, adverse effects, and delay in treatment escalation. Recent analyses suggest no benefit of 5-ASA use in patients escalated to more advanced therapies. Hence, 5-ASA withdrawal was suggested, but the outcomes remain unclear. We aimed to perform a meta-analysis of 5-ASA withdrawal in patients with IBD and compare the risk of disease relapse in different cohorts of patients.

Methods

A search for articles was conducted in five medical databases, studies were selected, and their quality was assessed. Studies were divided into six clinically relevant cohorts depending on the type of IBD and other treatments used; the relative risk of relapse for individual studies in each cohort was analysed.

Results

1714 studies were identified; 27 were included in the meta-analysis. Withdrawal of oral 5-ASA monotherapy was associated with a 60% increased risk of relapse. Similarly, withdrawal of rectal 5-ASA had a relative risk of relapse of 2.03. When combined with immunomodulators and/or biologics in UC or CD, oral 5-ASA withdrawal was not associated with an increased risk of relapse. Patients on combined oral 5-ASA and immunomodulators had a higher risk of relapse in the 5-ASA continuation group across three studies; this can be attributed to the persistence of oral 5-ASA use in patients with more severe disease, delaying the appropriate escalation to advanced therapies. Two studies reported no increased risk of colorectal cancer when 5-ASA was withdrawn either as monotherapy or when combined with other treatments.

Conclusion

Oral or rectal 5-ASA monotherapy in UC should not be discontinued. 5-ASA withdrawal does not increase relapse in patients with UC or CD escalated to immunomodulator and/or biological treatment. Oral 5-ASA continuation combined with immunomodulators delays escalation to advanced therapy. Available data suggest that 5-ASA withdrawal does not increase the risk of colorectal cancer; however, this must be considered carefully in patients with unmodifiable risk factors.Read more P534 The preference for controlled-release mesalazine formulation of 2 g-granule sachet in patients already experienced 1 g-tabletWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The important factor is a good adherence in the treatment of inflammatory bowel disease (IBD) and the major guidelines recommend that the choice of formulation of mesalazine should consider patient preference and likely adherence. This study was to evaluate the preference for controlled-release (CR) mesalazine 2 g-granule sachet in patients who have been already experienced CR mesalazine 1 g-tablet and its related clinical factors.

Methods

First was treatment with 4 g CR mesalazine a day as two 2 g-granule sachets for 2 weeks in patients with IBD in remission who have already taken 4 g CR mesalazine a day as four 1 g-tablets for more than 3 months in Kosin University Gospel Hospital, Korea. The patients were consecutively enrolled. Second were the patients’ survey with 10 questionnaires about preferences (Table 1) after the 2 week-treatment and medical review of clinical information of patients.

Results

A total of 80 patients (46 in ulcerative colitis and 34 in Crohn’s disease, and 54 of male) were enrolled. Previous use of CR mesalazine four 1 g-tablets a day more than 1 year was in 88.6% of patients. In preference of formulation by ease to swallow, 70.0% of patients answered 2 g-granule sachet was better but just 20.0% of patients answered 1 g-tablet was better. In preference of formulation by next prescription, that is about overall preference, 63.8% of patients answered granule was better but 30.0% for tablet. In the number of 1 g-tablet or 2 g-granule sachet able to be swallowed at once, 46.9% of patients could swallow one or less tablet (1 g or less) and 96.1% of patients could swallow one or two sachets (2 g or more) (Fig. 1). When the patients who chose ‘granule was much better or better in overall preference' are classified as granule preference group and the remaining as others group. Number of tablet able to be swallowed at once in the medication before the granule trial was significantly less in granule preference group compared to others group (1.6 tablet vs. 2.0 tablet) (Fig. 2). However, the other factors including age, sex, body weight, height, body mass index, type of disease, concomitant oral medications, previous duration of 1 g-tablet use, were not associated with the overall preference.

Conclusion

In patients already experienced CR mesalazine 1 g-tablet for a long time, two-thirds of the patients more preferred to be prescribed 2 g-granule sachet and the preference was associated with the ability to swallow 1 g-tablets at once. Not only CR mesalazine 1 g-tablet but also 2 g-granule sachet can be an excellent choice for improving adherence of mesalazine treatment in IBD, especially when it comes to patients who can't take two or more 1 g-tablets at once.Read more P729 Prospective observational study evaluating the effects of GLP1-RA on Inflammatory Bowel Disease (IBD) in patients with Type 2 Diabetes Mellitus (TDM2)Wed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

GLP-1 RA are antidiabetic drugs approved for treatment of TDM2 as second-choice therapy for long-term treatment in patients with TMD2 without previous cardiovascular events or as first-choice therapy in patients with previous cardiovascular events and without heart failure (SID/AMD guidelines).Their beneficial effect is not only associated with glycol-metabolic control, but also with a systemic anti-inflammatory action. In view of this anti-inflammatory action, we wanted to assess whether GLP1-RA could have a possible beneficial effect on IBD in terms of laboratory and clinical parameters. Moreover, these drugs have proven to improve liver function and histology, therefore, liver wellbeing may also be included as a cross-sectional element of evaluation in the possible benefits of these therapies.

Methods

Through the evaluation of 981 medical records of IBD patients followed in the gastroenterology department of the Hospital San Giovanni Antica Sede (SGAS), 71 TDM2 patients were identified. Among these, 21 were recruited for the study. The recruited patients were scheduled for a diabetological examination: GLP-1 RA treatment could then be introduced where indicated. At a 3-month follow-up interval, both the GLP-1 RA treatment group and the subjects that did not have any changes in therapy (control group) underwent re-evaluation of the parameters of interest. All patients in the study were offered the possibility to receive a FibroScan to measure liver stiffness at the start of the study and at the 3-months follow-up.

Results

A prevalence in the IBD population of TDM2 was found to be 7.2% (vs. Piedmont population prevalence 6.2%, p = 0.31). Out of the 21 patients recruited, 6 received GLP-1 RA treatment. At 3 months, an analysis of the results through the Wilcoxon test showed that the GLP-1 RA treated patients had a reduction in faecal calprotectin levels, an improvement in disease scores, an improvement in glycemic balance and a reduction in CAP and FIB4 when compared to the control group; these results did not reach statistical significance. In contrast, the reduction in BMI reached statistical significance. A comparison of the deltas for the variables under analysis between the two groups was also carried out using the Mann-Whitney test. Concordant and positive trends were observed in the GLP-1 RA-treated group: in this case the reduction in HbA1c reached statistical significance.

Conclusion

Treatment with GLP-1 RA in patients with TDM2 and IBD appears safe and seems to show benefits from an intestinal, metabolic and hepatic viewpoint. Studies with a larger number of subjects are certainly needed to effectively confirm the benefit of GLP-1 RA in this specific category of patients.Read more P879 Comparative Efficacy of Biologics and Small Molecule Therapies for the Induction and Maintenance of Endoscopic and Histological Remission in Ulcerative Colitis: A Systematic Review and Network Meta-analysisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Treatment options for moderate to severe ulcerative colitis (UC) are increasing rapidly, but lack of comparative efficacy trials make treatment choices a clinical challenge. We aimed to compare the relative efficacy of biologics and small molecules in achieving endoscopic and histological remission in patients with moderate to severe UC.

Methods

The literature was searched between January 1990 and July 2023. Phase 3 placebo or active comparator randomized controlled trials (RCTs) were included to assess the efficacy of biologics or small molecule drugs as induction or maintenance therapies for patients with UC. The primary outcome was induction and maintenance of endoscopic improvement (Mayo endoscopic score ≤1), whereas secondary outcomes were the induction and maintenance of endoscopic (Mayo endoscopic score = 0) and histological remission. Sub-analysis was performed based on previous exposure to biologic therapy. We used a random effects model and reported data as odd ratio (OR) with 95% confidence intervals (CIs).

Results

We identified 34 studies that met our inclusion criteria, with a total of 12,227 patients with UC. Upadacitinib was superior to most biologics in inducing endoscopic improvement and remission as well as maintaining endoscopic improvement and histological remission. Etrasimod ranked second, after upadacitinib, in maintenance of endoscopic improvement in both biologic naive (80.4%) and experienced (78.9%) patients. Infliximab was superior to adalimumab (OR 1.88, 95% CI, 1.07; 3.29) and vedolizumab (OR1.85, 95% CI, 1.13; 3.03) in inducing endoscopic improvement in overall UC patients. Filgotinib 200 mg (OR 4.76, 95% CI, 1.89; 5.88) and vedolizumab (OR 4.16, 95% CI, 2.94; 6.25) were superior to adalimumab in maintaining histological remission. In biologic naive patients, infliximab was found to be superior to adalimumab (OR 1.80, 95% CI, 1.05;3.07), vedolizumab (OR 5.20, 95% CI, 2.04;7.69), and golimumab (OR 6.30, 95% CI, 3.39;9.71) in inducing endoscopic improvement

Conclusion

Upadacitinib appears to be superior to other therapies in achieving both endoscopic improvement and remission as well as maintaining histological remission. Furthermore, etrasimod, filgotinib and tofacitinib ranked high in achieving these outcomes. This study highlights the role of small molecules drugs as effective alternatives to biologics.Read more P535 Effectiveness of upadacitinib in patients with Ulcerative Colitis: a real-life, multicenter, Italian reportWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Upadacitinib (UPA) is an oral, selective JAK inhibitor, that has recently received approval in Italy for the treatment of Ulcerative colitis (UC). To our knowledge, only few data of real-life studies are available. The aim of our observational data collection is to report the first real-life experiences with UPA in UC in terms of effectiveness and safety.

Methods

These data come from four Italian IBD centers. Adult patients with a diagnosis of UC, who have been prescribed UPA for active disease, after failure of at least one anti-TNF therapy, were enrolled. After an induction period of 8 weeks with a 45 mg daily dosage, treatment efficacy were assessed using the partial Mayo score (pMS) and the fecal calprotectin levels (CP). Treatment-related adverse events were also recorded.

Results

Among 20 patients who started UPA, 12 have completed the induction and were therefore enrolled and evaluated before starting UPA and at the end of the 8 weeks induction period. 83% (10 patients) had previously failed two or more biological therapies, including tofacitinib (3 patients, 25%). 3 patients (25%) were tapering systemic corticosteroids and 3 patients (25%) were receiving topical steroids when they started UPA. In the pre-treatment evaluation, the mean pMs was 5,25 (SD 2,26) and the median CP was 1270 ug/g (411- 3152). At the end of induction (week 8), 10 patients (83%) achieved clinical remission and one patient showed clinical response with a decrease of 6 points of pMS. One patient underwent colectomy after 4 weeks of ineffective therapy. The mean pMS at week 8 was 0 (SD 0,92) (Fig. 1), with a median CP of 88 ug/g (5-4639). Reported adverse events, that however did not cause drug discontinuation, were one case of leukopenia and one case of acne. To the date of the last evaluation, all patients maintained the achieved results, with a mean follow-up period of 92 days. A further analysis excluding the physician global assessment from pMS has been performed, to obtain a sort of patient-reported outcome 2 (PRO-2): the results, in terms of percentage reduction of the scores, were in line with the presented data. Despite the limited number of patients who completed the induction (11), we observed statistical significance in the difference between pretreatment and post-induction values of all the measured variables (Tab. 1, Fig. 1).

Conclusion

With this first Italian report in a real-life setting, UPA showed promising effects in rapidly inducing clinical remission and in normalizing a sensitive marker of intestinal inflammation. Moreover, it seems to be well tolerated. Long-term real-life studies, including endoscopic and histologic evaluations, are needed to confirm efficacy and safety of UPA in maintaining stable remission in UC patients.Read more P764 Darvastrocel in Treatment of 152 Patients with Perianal Crohn's Disease - Observational StudyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Complex perianal fistulas significantly affect quality of life and treatment costs in patient with Crohn's disease (CD). Application of adult allogeneic expanded adipose-derived mesenchymal stem cells (Darvastrocel, Takeda Pharmaceuticals) represents novel treatment modality for this challenging condition.The aim of this study was to examine the long-term effects of Darvastrocel (DVS) in patients with complex perianal fistula associated with Crohn’s disease.

Methods

The study was conducted at two Czech medical facilities (NH Hospital, Horovice and ISCARE, Prague). All consecutive CD patients with complex perianal fistula (up to 2 internal and 3 external openings) treated by the same team with DVS between August 2019 and July 2023 were enrolled into the study and followed prospectively. All fistulas persist despite previous biologic and surgical treatment. The technique of DVS application was based on the ADMIRE CD study protocol and was in accordance with SPC. Fistula tract was curetted, internal opening closed and leak test performed under GA. DVS was applied below the internal opening and along the fistula tract subsequently. Perianal area was then assessed at week 3, month 3 and 6 and then every year postoperatively.

Results

In total, 152 patients (53.9% male, 46.1% female) with median age of 36.6 (20-72) years were enrolled (tab. 1). Primary success rate detected within the period of 19.8 (4.2-50.2) months after application was 80.3% (122 patients). Fistula recurred in 9 patients (at the site of original fistula in 6 and in a new location in 3 cases), resulting in a sustained healing rate of 74.3% (113 patients) observed within average of 27.2 months. The Perianal Crohn's Disease Index was significantly lower 3, 6, and 12 months after application in the healed compared to failed group - 1 (0-9), 0 (0-8) and 0 (0-9) vs. 7 (1-13, 8 (0-12) and 6 (0-12), p<0.005. Postoperatively, 48 patients (31.6%) were prescribed antibiotics due to inflammatory changes in perianal area. Out of 122 healed patients 31 (25.4%) received antibiotics for 17 (5-37) days, while 17 (56,6%) patients with treatment failure were treated for 16 (7-70) days.

Conclusion

This real-life study showed that Darvastrocel is highly effective in treatment of complex perianal Crohn’s disease resistant to conservative and surgical management. Moreover, for some patients (anal stricture, chronic changes in anorectum) this may be the only available therapeutic option. Intermittent antibiotic treatment did not affect long-term outcomes. We consider clinical response (crucial for the patient's quality of life) sufficient for predicting sustained long term remission.Read more P883 Impaired long-term quantitative cellular response to SARS-COV-2 vaccine in thiopurine-treated IBD patientsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

SARS-CoV-2 mRNA vaccine induces a robust immune response in most patients with inflammatory bowel disease (IBD). However, humoral short-term response appears to be reduced in patients receiving anti-TNF agents or tofacitinib, even after booster doses. Data on long-term immune response is limited. We aimed to assess short and long-term humoral and T-cell response to SARS-CoV-2 mRNA vaccine in IBD patients receiving anti-TNF and/or thiopurines.

Methods

A prospective, longitudinal study was carried out in IBD patients receiving thiopurines, anti-TNF mono, or combo therapy. Patients had received between 2 and 4 doses of mRNA SARS-CoV-2 vaccine. Cellular and humoral response to the vaccine was assessed by serum interferon-gamma release assay (IGRA) and antibody SARS‐CoV‐2, respectively. We defined short-term response as humoral and T-cell response six weeks after the second vaccine and long-term response 6 to 12 months after that. Primary outcome was to determine if T-cell immune response differs in IBD patients receiving anti‐TNF versus thiopurines.

Results

We recruited 148 IBD patients, 57 treated with anti-TNF monotherapy, 53 with anti-TNF combo, and 38 with thiopurines. Short-term T-cell and humoral responses were similar between the three groups. However, long-term T-cell concentration was reduced in thiopurine-treated (median 0.7 UI/mL [0.26-2.35]; p<0.05) and anti-TNF-combo-treated patients (median 0.4 UI/mL [0.22-1.13]; p<0.01) when compared to anti-TNF monotherapy (median 2.2 UI/mL [1-4.15]). Multivariate analysis showed that anti-TNF monotherapy (-0.93, p<0.05) and decreased time between vaccination and T-cell response measurement (0.04 [.00005-.078] p=0.05) were associated with increased T-cell concentration long-term when compared to the other groups of patients.

Conclusion

We found a diminished long-term quantitative cellular response in our cohort of IBD patients vaccinated for SARS-CoV-2 treated with thiopurines or combo therapy compared with anti-TNF monotherapy. These findings highlight the recommendation to receive booster doses in IBD patients, specially those receiving thiopurines.Read more P765 A Novel Monoclonal Antibody Drug Candidate SPY001 Targeting Integrin ɑ4β7 for the Treatment of IBD Demonstrates Prolonged Half-Life in Non-Human PrimatesWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Background: Antagonism of the interaction between the cellular adhesion integrin ɑ4β7 and endothelial ligand mucosal addressin cell-adhesion molecule-1 (MAdCAM-1) has proven to be relatively safe and effective in the treatment for Crohn’s disease (CD) and ulcerative colitis (UC). Additional benefit may be gained from an ɑ4β7 antagonist given via the subcutaneous (SC) route at extended intervals (eg, every 8 to 12 weeks) during maintenance therapy.

Methods

The humanized monoclonal IgG1 antibody SPY001 binds to the same ɑ4β7 epitope as vedolizumab and includes a YTE modification within the Fc region to increase its serum half-life via increased affinity for the neonatal Fc receptor (FcRn), thereby favoring recycling into the circulation over degradation. Half-life extension was evaluated via pharmacokinetic analysis in Tg276 transgenic mice (hemizygous for human FcRn) following a single intravenous bolus dose of SPY001 (10 mg/kg, 5 mg/kg, 1 mg/kg) and in cynomolgus monkeys following a single bolus dose of SPY001 (150 mg/kg), given by either intravenous (IV) and subcutaneous (SC) administration. PK simulations in humans were based on allometric scaling of SPY001 clearance observed in cynomolgus monkey and conducted in MATLAB.

Results

In Tg276 mice, the half-life of SPY001 was 10-11 days across all dose cohorts compared to approximately 3 days for vedolizumab. In cynomolgus monkeys, the half-life of SPY001 was 19-23 days following a single IV or SC infusion, a significant increase over the reported half-life of 10 days for vedolizumab in cynomolgus monkeys. Based on allometric scaling of the clearance of SPY001 observed in this study, predictive simulations of SPY001 PK in humans suggested that Q8W-Q12W SC dosing at 300 mg would be able to achieve a C_{6-wks, induction} ≥ 35 mg/mL and C_{trough, ss} ≥ 6 mg/mL for simulated patients covering a large range of body weights and albumin concentrations.

Conclusion

SPY001 is a novel humanized monoclonal IgG1 with an extended half-life over that of vedolizumab in Tg276 mice and cynomolgus monkeys. It offers the potential for effective and safe treatment of CD and UC with the advantage of infrequent SC dosing. Further preclinical and clinical studies are warranted to demonstrate this potential.Read more P564 Surgical treatment of jejuno-ileal Crohn’s disease. Results from the The JejUno Ileal Crohn's disEase (JUICE) international, multicentric, observational studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Crohn’s disease (CD) affecting the upper gastrointestinal (GI) tract is a rare condition, leading to a scarcity of information regarding its diagnosis, surgical treatment, and adjuvant therapy. The JUICE study aimed to conduct a surgical audit of duodeno-jejuno-ileal CD across 11 European IBD Referral Centres.

Methods

The study included all the consecutive, non-selected patients undergoing surgery for upper-GI CD between January 2010 and December 2022. Patients with synchronous ileal and colonic locations were included, while those with previous upper-GI CD surgery or multiple surgeries for ileo-colic CD were excluded. Univariate and multivariate analyses of 120 variables, covering pre-operative characteristics, intra-operative findings, and post-operative follow-up, were conducted.

Results

The study encompassed 279 patients, with a male/female ratio of 2.2. The average age at diagnosis was 30±14 years, and the disease duration was 11±10 years. The Montreal Classification revealed A1 15.4%, A2 61.3%, A3 23.3%; L1+L4 34.4%, L2+L4 4%, L3+L4 26.9%, isolated L4 34%; B1 1.8%, B2 67.4%, B3 30.8%; perianal location 19.4%. BMI averaged 21±3. Preoperative nutritional support was necessary in 50.5%. MRI-enterography was the predominant preoperative examination (86.7%). Comorbidities were present in 24.7%, with 61% having an ASA score >1. In the 30 days pre-surgery, 16.8% used steroids, 41.2% received biologicals, with 24.6% on combined (biologicals + steroids) therapy. Video-assisted approach was used in 70%, with a 5.1% conversion rate. Intraoperative staging revealed 1334 locations treated with 247 resections, 500 strictureplasties, 12 bypasses, and 53 concomitant colonic resections. Entero-enteric fistulas and intra-abdominal abscesses were present in 29% and 14%. Patients with thickened mesentery, wrapping fat, and lymph node enlargement were 50.8%, 38.7%, and 50.8%, respectively. Mortality was 1%, Clavien-Dindo grade 3 and 4 complication rate 11.1%. Hospital stay averaged 10±6 days; 90-day readmission was 3.2%. B3 behaviour, smoking, preoperative malnutrition, and preoperative biological therapy increased postoperative complication risk (p=0.01). 10-year Kaplan-Meier surgical recurrence rate was 23%, reduced to 11% with early and continuous post-op biologic treatment compared to late treatment or suspension (60% - Log-Rank p<0.0001).

Conclusion

This is by far the largest series of upper-GI CD ever studied, depicting a little known, complex, technically demanding sub-group of patients. Preoperative optimization, focusing on preoperative nutritional status and therapy, is crucial to reduce complication risk. Early-onset post-operative biological therapy seems to significantly reduce long-term surgical recurrence.Read more P893 Transition from intravenous to subcutaneous infliximab: effectiveness in a cohort of patients with inflammatory bowel diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Inflammatory bowel disease (IBD), ulcerative colitis (UC) and Crohn’s disease (CD), is a group of chronic inflammatory disorders. Biologics are indicated for patients failing conventional maintenance therapy with moderate to severe activity. Different routes of administration, intravenous (IV), subcutaneous (SC) or oral have been approved. For chronic diseases such as IBD, some patients may prefer self-administered SC dosing to IV dosing as a less time-intensive and more convenient treatment option. This study aims to evaluate evaluate the success of infliximab subcutaneous administration after switching from intravenous administration in IBD patients.

Methods

The transition from IV to SC administration was proposed to 60 IBD patients in clinical remission. Data on medical history and laboratory tests were collected from electronic health records. Moreover, patients filled a paper questionnaire 8 weeks after the switch focused on the level of satisfaction and onset of adverse event (AE).

Results

Overall 60 patients were enrolled for switching from IV to SC therapy. Most of patients (>80%) did not experience any difficulties in handling the device and respected the correct time-table of administration. The switch was a complete success in 50 out of 60 patients (83.3%). Ten patients stopped subcutaneous formulation: five of these switched back to intravenous formulation for adverse event or patient’s preference, four swap or swop to other therapy and one withdraw from biologic. No predictor of loss of response was found at multivariate analysis. Faecal calprotectin and C-reactive protein values significantly improve after the switch at 3, 6 and 12 months (p= 0.03, p= 0.004, p = 0.01 and p= 0.06, p= 0.001, p= 0.007 respectively). About 16.7 % of patients had at least one side effect after switching. Local pain and swelling at site of injection were the most common AEs. The vast majority of AE were mild and lasted only a few days. No serious AEs were reported and no patient was hospitalized.

Conclusion

Effectiveness of switching from intravenous to subcutaneous infliximab administration in IBD patients is confirmed in our real world cohort of patients.Read more P565 Capillary blood based self-collection device for infliximab therapeutic drug monitoringWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Patient friendly new devices may improve therapeutic drug monitoring (TDM) in inflammatory bowel disease (IBD). Our objective was to evaluate an infliximab (IFX) precision guided dosing tool from capillary blood collected using an upper-arm self-collection device amongst IBD patients and compare its performances to gold standard venous blood collected using venipuncture.

Methods

Patients under maintenance therapy with IFX were recruited from a single IBD center and enrolled in the BEST (Bayesian Estimates Sustaining Trough) study. BEST is a prospective real world evidence clinical utility study to establish the value of an IFX Bayesian forecasting tool in the optimal management of IBD. Blood specimens were collected prospectively, at midcycle or at trough. Capillary blood specimens were collected using an upper arm self-collection device (Tasso Inc., Seattle, WA) connected to a serum separator tube. Paired venous blood was collected using venipuncture. IFX concentrations and antibodies to IFX (ATI) status were measured using drug tolerant homogenous mobility shift assay, albumin levels were measured using nephelometry. IFX Clearance was calculated using nonlinear mixed effect model with Bayesian priors. Statistical analysis consisted of Deming regression.

Results

Overall, 27 patients (n=9 with UC, mean age=37 years, weight=79 Kg) were enrolled. Median IFX dosing was 10 mg/Kg, and median dosing frequency every 6 weeks. A total of n=58 serum pairs isolated from capillary and venous blood were tested. PK profiles measured from venous blood were optimal during maintenance with no immune response detected (ATI < 3.1 U/mL) and most patients had IFX concentration at trough above 5 µg/mL (98%, median 15.4 µg/mL IQR: 10.9-28.0 µg/mL) and low Clearance (< 0.294 L/day: 89%; median 0.200 L/day IQR: 0.170-0.248 L/day). IFX concentrations and Clearance levels were comparable between venous and capillary blood with high correlation (R²= 0.975; slope =0.928; and R²=0.978; slope =1.035, respectively) (figure). In capillary blood specimens collected at midcycle (median 14 days before the next infusion, n=12 pairs), median IFX concentration was 38.3 µg/mL (IQR: 31.2-64.7 µg/mL) and declined to 21.9 µg/mL (IQR: 14.1-44.5 µg/mL) at trough. There was a high correlation between forecasted and measured trough concentrations in capillary blood (R²=0.925; Deming’s slope=1.093). Similar results were observed with venous blood pairs (R²=0.983; Deming’s slope=1.024).

Conclusion

IFX therapeutic drug monitoring using patient self-collection of capillary blood performed as well as standard venous blood measurement. This collection method may facilitate the implementation of point of care TDM in clinical practice.Read more P904 Appendectomy for refractory ulcerative colitis: results of prospective observational studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Appendectomy is suggested to improve the course of the disease in many patients with refractory ulcerative colitis (UC). The present prospective observational study demonstrates middle-term outcomes after an appendectomy in 26 patients with refractory UC.

Methods

Between 5/2022 and 2/2023, 26 selected patients underwent appendectomy for refractory UC. Refractory UC was defined as a failure of at least one biologic therapy. Patients with Dysplasia or Cancer were excluded. The appendectomy was performed without the removal of the cecal base. Primary Endpoint of the study was the Mayo clinical score (MCS) at 6 months after the appendectomy. Secondary Endpoint was the “Treatment failure” which was defined as occurrence of one of the following events during the first 6 months after appendectomy: 1) high-dosed steroid treatment, 2) change of biologic treatment, 3) colectomy.

Results

Mean age was 35 years (18 to 59 years) and there were 11 female patients. 15 had a pancolitis (58%). Twelve were taking steroids (46%). Median number of biologic therapies taken by patients prior to surgery was 3 (range, 1-5). One patient underwent surgery for sever acute UC. The appendix appeared to be inflamed histologically in 16 patients (62%). Hospital stay was median 2 days, there was one wound infection at the port site and one postoperative hematoma. A significant improvement of disease symptoms was reported by 21 patients during the first 4 weeks (81%). At 6 months, MCS improved from mean 6.4 to 4.5 (p=0.057). Therapy failure was observed in 15 patients (58%) – two underwent colectomy, 11 needed at least one high-dose steroid treatment and biologic therapy was changed due to refractory symptoms in 9 patients. Intake of JAK-inhibitors at the time of appendectomy was the only factor to be associated with lower probability of treatment failure (30% vs. 75%, p=0.043). The only patient undergoing appendectomy for severe acute UC was free of symptoms 14 months after surgery.

Conclusion

The majority of patients with refractory UC demonstrated rapid clinical response to the appendectomy. After 6 months, more than 40% of patients did not experience disease flares necessitating intensification of treatment.Read more P766 No difference in progression of disability 2 years after stopping infliximab or immunosuppressant vs. continuing combination therapy in patients with CD in sustained steroid-free remission: a subanalysis of SPAREWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

In the SPARE trial, the discontinuation of infliximab (IFX) in patients with Crohn’s disease (CD) in sustained remission under combination therapy (IFX and immunosuppressant therapy), was associated with a significantly higher relapse rate than when continuing combination therapy or discontinuing immunosuppressant therapy. However, a high proportion of patients rapidly recover remission when resuming treatment. The impact of this treatment strategy on functional disability, a major endpoint in assessing CD progression, has been poorly studied. We aimed to compare the evolution of the IBD-disability index (IBD-DI) in patients continuing combination therapy, discontinuing IFX or immunosuppressant therapy.

Methods

The study of the evolution of the IBD-DI in the 3 groups (combination, IFX withdrawal, immunosuppressant withdrawal), between baseline and the end of study (2 years), was a pre-defined secondary endpoint of the trial. Changes in scores (between baseline and the end of study) were compared using Wilcoxon tests between the arms “combination group” versus “IFX withdrawal group” and between “immunosuppressant withdrawal group” versus “IFX withdrawal group”.

Results

IBD-DI was available at baseline and at the end of study for 153 patients out of the 211 randomised in the SPARE trial between November 2015 and April 2019 (46 in the combination group, 55 in the IFX withdrawal group, and 52 in the immunosuppressant withdrawal group) and those were included in the analysis. Table 1 summarizes baseline characteristics of these patients. 30 patients had a relapse (6 [13%] of 46 in the combination group, 19 [34.5%] of 55 in the IFX withdrawal group, 5 [9.6%] of 52 in the immunosuppressant withdrawal group). Of 23 patients who had a relapse and were retreated or optimised according to protocol, remission was achieved in 21 patients (1 of 2 in the combination group, 18 of 19 in the IFX withdrawal group, and 2 of 2 in the immunosuppressant withdrawal group). The median IBD-DI at baseline was 12.5 (IQR, 5.36-21.43), without significant differences between the 3 groups. Figure 1 shows changes in the IBD-DI between baseline and the end of study in the 3 groups. There was no significant difference in terms of changes in IBD-DI between the arms "combination group" and "IFX withdrawal group" (p=0.56), or between the arms "immunosuppressant withdrawal group” and "IFX withdrawal group" (p=0.29).

Conclusion

In patients with CD in sustained steroid-free remission under combination therapy with IFX and immunosuppressant therapy, there was no difference in progression of disability over 2 years between those who continued combination therapy, stopped IFX or stopped the immunosuppressant with the possibility of recycling the medication after a relapse.Read more P566 Maintenance vedolizumab treatment in pediatric IBD: 54-week follow-up of the prospective multicenter VEDOKIDS studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Prospective long-term data on vedolizumab (VDZ) in children with Crohn’s disease (CD) and ulcerative colitis (UC) are lacking. In this prospective, multicenter cohort study, we aimed to evaluate the effectiveness and safety of maintenance therapy with VDZ in pediatric CD and UC.

Methods

Children commenced on VDZ were followed at baseline and 2, 6, 14, 30 and 54 weeks thereafter. Serum for drug levels and stool for calprotectin were repeatedly obtained. The primary outcome was sustained steroid-free remission (SSFR), defined as clinical remission )PUCAI<10 or wPCDAI<12.5) without steroids/EEN at both 30 and 54 weeks, analyzed under the ITT principle.

Results

139 children were enrolled (77 [55%] UC, 62 [45%] CD; age 14.9 years (IQR 12.0-16.6). Of the 119 (86%) children >30kg, 110 (92%) received a dose of 300mg; 20 (14%) weighed<30 kg and received a dose of 8.3mg/kg (IQR 7–10.3). Week-54 remission rate was 52% in UC and 37% in CD; SSFR rates were 42% and 24%, respectively (OR 2.2 [95%CI 1.1-4.7] Figure). SSFR rate was numerically higher in isolated colonic CD than in ileal disease (5/11 [45%] vs 10/49 [20%], OR 3.3 [95%CI 0.8-12.9]; p=0.08). Infusion interval was shortened in 22 children (10 [13%] UC, 12 [19%] CD), of whom none achieved SSFR.SSFR rate was higher in week-6 responders compared to non-responders in UC (51% vs 27%, OR 2.9 [1.1-7.7]) and CD (35% vs 14%, OR 3.4 [95%CI 0.95-12.4]), similar to the week-14 figures (UC: 50% vs 22%, OR 3.6 [1.2-11.1]; CD: 36% vs 8%, OR 6.2 [1.3-30.8]). SSFR was eventually achieved in 49% of UC children having mild disease at week-6 and 14% with moderate-severe disease (OR 5.8 [95%CI 1.2-28.2]); the corresponding rates in CD were 31% and 0% (p=0.02).In multivariable models, the best predictors in CD were lower wPCDAI at baseline (AUROC 0.88 [95%CI 0.79-0.96]; optimal cutoff 25 (sens/spec 76%/80%)) and at week 6 (0.90 [0.82-0.98]; optimal cutoff 17.5 (80%/87%)). In UC, the best predictors were PUCAI at week 6 (0.70 [0.57-0.82]; optimal cutoff 10 (64%/57%)) and at week-14 (0.78 [0.67-0.89]; optimal cutoff 5 (76%/60%; Table).In children <30kg, SSFR was associated with week 6 drug levels >30ug/mL, not reaching statistical significance (3/6 [50%] vs 1/8 [13%], OR 7.0 [95%CI 0.5-97]). By week 54, 197 adverse events were recorded, of which were VDZ-related in 8 (5.8%) children, and in 2 (1.4%) led to stopping VDZ; none were severe. There was 1 lymphoma case judged to be unrelated to VDZ.

Conclusion

VDZ was effective for maintaining remission, more so in UC and in colonic CD. The likelihood of eventually achieving SSFR was very low in children with moderate-severe disease or those not showing response at week-6, particularly in CD.Read more P629 JAK inhibitor safety in Inflammatory Bowel Disease: real-world data comparing the effect of JAK inhibitors on blood parameters and their clinical significanceWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Janus kinase inhibitors (JAKi) licensed for the treatment of inflammatory bowel disease (IBD) now include tofacitinib, upadacitinib and filgotinib. JAKi are known to cause abnormalities in a multitude of blood tests. However, whether there are differences in their effects in a ‘real-world’ setting is not known.

Methods

Blood test results for 118 patients treated with a JAKi were collected. A total of 13 parameters known to be affected were included. Percentage change at 12 and 24 weeks from baseline was calculated and compared amongst the different JAKi. The difference between the proportion of patients with abnormal results at each time-point was also reviewed.

Results

The JAKi breakdown included: tofacitinib-64, upadacitinib-35, filgotinib-18. JAKi treatment was associated with a significant rise in cholesterol, bilirubin, ALP and AST at 12 and 24 weeks (table 1), while rises in triglyceride and LDL cholesterol, and haemoglobin reduction were only apparent at 24 weeks. Other parameters showed transient or non-significant changes. Individual analysis of each parameter highlighted only two significant differences amongst JAKi: upadacitinib significantly reduced WCC (p=0.048) and neutrophil count (p=0.044) within the group at 24 weeks, and when directly compared to tofacitinib (p=0.047). However, no patients were neutropenic at 24 weeks and only 5 patients had a low WCC (upadacitinib: 3, tofacitinib: 2, filgotinib: 1). As per Common Terminology Criteria for Adverse Events (CTCAE), adverse events (AEs) in these parameters were low despite the significant percentage change in multiple variables. 1 patient (1.1%) was found to be anaemic (Hb <80g/L, at 12 weeks which resolved at 24 weeks), 1 (1.4%) was noted to be lymphopenic (lymphocyte count <0.5x10⁹/L, at 24 weeks), and 1 (limited data) with CK >5 times upper limit of normal. No patients had a significant hepatic disorder as per CTCAE, though mild liver function changes above the upper limit of normal were seen in 9% of patients. On comparing the proportion of patients with abnormal results at 12 and 24 weeks to baseline, it was only cholesterol (p=0.027) and HDL-cholesterol (p=0.041) that had a significantly higher proportion of patients within the abnormal range at 12 weeks. This did not persist at 24 weeks (p=0.13 and p=0.37 respectively). Two patients were commenced on a statin during JAKi therapy. No abnormalities in these blood parameters caused drug withdrawal.

Conclusion

In this cohort the majority of changes in blood test parameters were transient and/or mild with no AE-related drug withdrawals during JAKi therapy. No clinically significant differences have been appreciated amongst the three JAKi.Read more P905 Symptomatic remission and IUS improvements in a multi-national real-world cohort of UC patients treated with Upadacitinib - First results from the IBD-DACH study EUROPEWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Upadacitinib (UPA) is an oral, reversible and selective Januskinase-inhibitor (JAKi) that was approved for the treatment of several immune-mediated inflammatory diseases, including moderate to severe ulcerative colitis (UC) (1). While the efficacy of UPA has been demonstrated in clinical trials in UC, real-word (RW) evidence on the effectiveness and safety of UPA in UC remains scarce (2). Here, we shed light on the clinical and sonographic results after 2 and 8 weeks of UPA induction in a large, multinational RW cohort of UC patients.

Methods

EUROPE is an ongoing, prospective, non-interventional, multi-country study in patients with active UC who initiate therapy with UPA. The study assesses the early clinical effectiveness and the predictive value of early disease improvements including sonographic parameters for the long-term outcome after 52 and 104 weeks. For this interim analysis, we report clinical and sonographic results at baseline (BL), week 2 (2W) and week 8 (8W) of 124 UC patients with a visit after 8W until August 2023. For 75 patients, sonographic BL data for the most affected bowel segment was available.

Results

Of the 124 UC patients, most were male (60.5%, n = 75) with a median age and disease duration of 37.5 years (27.5 – 50.9) and 6.58 years (2.40–12.13). Almost half of all patients had a pancolitis (48.4%, n = 60) The vast majority of patients was bio-experienced (85.5%, n = 106), a third had been exposed to ≥ 3 biologicals (28.2%, n = 35). At BL, patients had a median bowel wall thickness (BWT) of 5.0 mm (3.8-7.0) in the sigmoid colon. It was the most affected segment in 44.4% of patients (n = 55). Disease activity per paMayo score was 3.0 (2.0-5.0) points, with 72.6% (n = 90) and 38.8% (n = 48) of patients reporting ≥ 3 more stools than usual/day and blood in most stools or bleeding without stool, respectively.At 2W after UPA induction, stool frequency and rectal bleeding substantially improved as reflected by the rate of patients in symptomatic remission significantly increasing from 16.9% (n = 21) at BL to 43.5% (n = 54) at 2W and to 64.5% (n = 80) at W8 (both p < 0.001 vs. BL, fig.1). BWT was reduced significantly as early as 2W (n = 48; p < 0.001) and was ≤ 3mm in more than half of all patients. Considering the overall population, 156 patients were included in the safety analysis. Of these, 23.7% (n = 37) experienced an adverse event of which most were non-serious.

Conclusion

In this first interim analysis of the EUROPE study, UPA treatment in UC was associated with early clinical and sonographic improvement, with most patients achieving symptomatic remission and/or normalization of BWT by week 8 of treatment.1-SmPC Upadacitinib2-Danese, Vermeire et al. Lancet. 2022 Jun 4;399(10341):2113-2128Read more P567 Impact of recent thiopurine use on ozanimod safety in patients with ulcerative colitis: a post hoc analysis of the phase 3 True North studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Ozanimod, a sphingosine 1-phosphate (S1P) receptor modulator that selectively targets S1P₁ and S1P_5, is approved for the treatment of moderately to severely active ulcerative colitis (UC) in adults based on results from the phase 3 True North study (NCT02435992). Reductions in absolute lymphocyte count (ALC) are expected with ozanimod but not associated with treatment-emergent adverse events (TEAEs). This post hoc analysis explored the effect of recent use of thiopurines on ALC and safety outcomes in patients treated with ozanimod.

Methods

True North was a phase 3 trial of ozanimod induction and maintenance therapy in moderately to severely active UC. Patients in Cohort 1 were randomised to once-daily double-blind treatment with ozanimod 0.92 mg or placebo; patients in Cohort 2 received open-label ozanimod for a 10-week induction period. Patients on concomitant thiopurines were required to stop therapy at study start without a washout period. In this post hoc analysis, patients were stratified by recent prior thiopurine use (within 90 days of ozanimod initiation). ALC was assessed at baseline; ALC, TEAEs, and infectious outcomes were assessed during the induction period at Weeks 5 and 10.

Results

Of the 1012 patients in True North, 796 were treated with ozanimod and analysed (n=57 with recent thiopurine exposure; n=739 without recent thiopurine exposure). At baseline, mean ALC (×10⁹/L [SD]) was slightly lower in patients with than without recent thiopurine use (Table). Both groups had similar baseline incidence of ALC <200 cells/µL (0%) and <500 cells/µL (range 0.0–0.3%). While ALC <200 cells/µL and <500 cells/µL were more prevalent among patients with than without recent thiopurine use (Figure), the reductions from baseline to Week 10 in ALC were similar in both groups (Table). Rates of infection were also similar in patients with recent thiopurine use (14.7% in Cohort 1 and 13.0% in Cohort 2) and without recent thiopurine use (10.4% and 12.5%, respectively). The most frequent infection was nasopharyngitis in both groups: 8.8% in Cohort 1 and 0% in Cohort 2 in patients with recent thiopurine use; 3.0% and 2.9%, respectively, in patients without recent thiopurine use. There were no serious adverse events (AEs) related to ozanimod treatment, and treatment discontinuations were similar in patients with and without recent thiopurine exposure.

Conclusion

Lower ALC was observed in patients starting ozanimod within 90 days of thiopurine use but was not associated with an increased incidence of infection or serious AEs. The findings suggest switching from thiopurines to ozanimod without a washout period may be safe and tolerable.Read more P742 The efficacy of comprehensive multivitamin and mineral supplement to treat symptoms of fatigue in patients with Inflammatory Bowel Disease in remission with immunomodulators and or biological agentsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Patients with inflammatory bowel disease(IBD) very often report feeling tired for no reason. Malnutrition and vitamin or mineral deficiencies are also very common among patients with IBD. The aim of this study was to evaluate the efficacy of a multivitamin and mineral supplement for the treatment of fatigue in patients with IBD.

Methods

Single-centre, randomized placebo-controlled clinical trial to compare a comprehensive over-the-counter multivitamin and mineral supplement (supplemented group) with an identical presented placebo (placebo group) for the treatment of fatigue. Non-vitamin deficient patients with IBD in remission with immunomodulators and/or biological therapy were asked to report score their fatigue on a Visual Analog Scale (0-10) and the validated Chalder fatigue questionnaire (CFQ) at baseline, week 12 and 24. The validated CFQ has a scoring range from 0-33 and 2 subscales physical and psychological fatigue. Patients were considered to be fatigued by the CFQ with a score of 12 or above.

Results

A total of 214 patients reported fatigue at the start of the study. Of these patients 115 and 99 were assigned to the supplement and placebo groups, respectively. In the supplemented and placebo group, 32 (34%) and 18 (21%) patients, respectively, experienced no fatigue according to the CFQ definition at 24 weeks (Unadjusted Odds Ratio (OR): 2.0 (95% Confidence Interval (CI):1 - 3.8). In particular patients with Ulcerative Colitis (UC) and supplement use experienced less fatigue at 24 weeks (OR 5.7 (95% CI:1.3 - 24.1). Improvement of fatigue experienced between baseline and 24 weeks was not statistical different for either the supplemented and placebo group.

Conclusion

Although improvement in fatigue score was limited, a significant number of patients with IBD in remission with immunomodulators, and/or biological therapy using a very comprehensive vitamin and mineral supplement reported improvement of fatigue after 24 weeks of use.Read more P921 Maintenance of clinical, biochemical and transmural remission in inflammatory bowel disease patients switching from intravenous to subcutaneous infliximabWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Subcutaneous (SC) infliximab (IFX) effectively maintains biochemical, clinical and endoscopic remission in inflammatory bowel disease (IBD) with a comparable safety profile to intravenous (IV) formulation. Transmural healing is considered a desirable long-term treatment endpoint in IBD, especially in Crohn’s disease (CD). Whether switching from intravenous to SC-IFX effectively maintains transmural remission in IBD is still unknown.

Methods

This is a preliminary report from a prospective multicentre cohort study on IBD patients in clinical and endoscopic remission on IV-IFX treatment switched to SC-IFX. Enrolled patients were followed-up for 12 months, with fecal calprotectin (FC), C-reactive protein (CRP), infliximab trough levels and anti-drug antibodies (ADAs) measured at baseline, at 3, 6 and 12 months. Intestinal ultrasound (IUS) was performed at baseline and every six months. At month 12 a full colonoscopy was performed for mucosal healing assessment. Remission rates and safety profile were subsequently recorded. T-Test and ANOVA for mean comparisons and Kaplan‐Meier estimates were used for survival curves.

Results

43 IBD patients (69% males) were enrolled, 58% with CD, of whom 52% reported a history of perianal disease. Median disease duration and IFX therapy were 6 (IQR 3-12) and 5 (IQR 2-9) years, respectively. During a median follow-up of 311 (range 122-489) days, clinical remission rate was 98% (Harvey-Bradshaw Index <5 and Mayo score <2). No reactivation of perianal disease was reported. FC and CRP remained stable at each time point (p> 0.05). The median baseline infliximab level was 10.02 ( range 0.1- 41.84) ug/ml. Undetectable infliximab levels (<1 ug/ml) and positive ADAs were found in 6 and 14 patients, respectively; at 3 months, a significant increase in infliximab levels (mean increase 27.5 ng/ml; ± 12.5 SD; p< 0.001) and a progressive decrease of ADAs titer were observed, despite unchanged SC-IFX dose. At baseline, all patients had normal bowel wall thickness (i.e. ileum ≤ 3mm, colon≤4 mm) and a Limberg score ≤1at IUS; reactive lymphadenopathies were reported in 5 patients and a mild abdominal effusion in 1. No significant changes were shown during follow-up. Mild endoscopic activity was found in 2 out 30 patients who performed follow-up endoscopy. Regarding safety profile 12 mild infectious events, 2 mild cutaneous injection site reaction and 1 non-IBD related hospital admission were observed.

Conclusion

Switching from IV to SC infliximab in a selected cohort of IBD patients confirmed to be safe and effective in maintaining clinical, biochemical, and transmural remission. IUS is a useful, non-invasive and low-cost tool for periodic disease assessment in this subset of patients.Read more P510 Relapse rate following withdrawal of vedolizumab and ustekinumab in patients with inflammatory bowel disease. The VEDUST-EXIT studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Approximately half of patients with IBD in clinical remission (CR) flare within 12 months of withdrawing anti-TNF therapy. However, the outcomes of vedolizumab (VDZ) or ustekinumab (UST) cessation in terms of CR in routine practice are unknown. There is a need for more data to establish the relapse rates following treatment cessation.

Methods

This was a retrospective observational multicenter study. We included adult IBD patients who had withdrawn from either VDZ or UST after achieving CR and had available follow-up data for one year following treatment discontinuation or until relapse occurred. The control arm comprised patients discontinuing anti-TNFs after achieving CR. The primary objectives of this study are to assess the clinical relapse rates after discontinuing VDZ or UST and to identify potential predictors of sustained remission and relapse after therapy discontinuation.

Results

A total of 133 patients were included (48.1% Crohn’s disease and 51.9% ulcerative colitis). Sixty out of the 133 (45%) patients discontinued anti-TNF, 54 (40%) VDZ and 19 (15%) UST. All patients were in CR prior to drug discontinuation. The most common cause for drug discontinuations was patients’ preferences (80%) followed by cost and administrative issues. Duration of remission before drug discontinuation was 11 (IQR 7.5-10), 8.5 (6-12.2), and 12 (8-27) months, for anti-TNF, VDZ, and UST, respectively.The median follow-up duration was 14 months (5.5-20), with an overall relapse rate of 78.9% (105/133). Relapse rates in each cohort were 71.6%, 83.3%, and 89.4%, respectively, p=0.5. The median time to relapse was 10 months (3-9), 9 (6-16.5), and 8 (5-16.5), respectively. There was no significant difference in the relapse rates between the different drugs (anti-TNF vs VDZ, anti-TNF vs UST, and VDZ vs UST, (hazard ratio, HR 1.2, confidence interval, CI 95% 0.2-1.8; P = 0.35), HR 1.2, CI 95% 0.9-1.6; p=0.13, HR 1.2, CI 95% 0.6-2.1; P=0.5, respectively). Predictors of relapse after drug withdrawal were a short treatment period (HR 0.98, CI 95% 0.96-0.99; P = 0.04), shorter remission period (HR 0.9, CI 95% 0.95-0.99, P =0.03), multiple prior biologics (HR 1.2, CI 95% 1.04-1.44, P= 0.013), perianal disease (HR 5.5, CI 95% 1.6-1.8, P=0,006) and lower hemoglobin level (HR 1.95, CI 95% 1.1-3.1, P= 0.008). The following factors were not associated with an increased risk of relapse: IBD type, disease phenotype, extraintestinal manifestations, active smoking status, prior IBD-related surgery, elevated CRP or calprotectin, and endoscopic or radiologic signs of active disease.

Conclusion

In IBD patients that discontinue biologics after achieving clinical remission, relapse rates following withdrawal of VDZ and UST are comparable with those of anti-TNF.Read more P922 A multicenter retrospective real-world study to determine the optimal cases of vedolizumab-treated UC patientsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Vedolizumab (VDZ) is a gut-selective monoclonal antibody approved for ulcerative colitis (UC). This real-world study aimed to evaluate the effectiveness of VDZ in the treatment of UC, with the goal of further treatment optimization.

Methods

In this multicenter, retrospective, observational chart review, 370 patients with UC who received at least one dose of VDZ in clinical practice at 16 tertiary hospitals in Japan were enrolled. Comprehensive analyses of predictors of 2- and 54-week remission, drug persistence, and the development of loss of response were performed.

Results

Lower partial Mayo scores and lower Mayo endoscopic subscores were significantly associated with 2-week remission in the multivariate analysis. More 2-week remitters achieved clinical remission at Week 52 than non-2-week remitters. Clinical remission rates were significantly higher in biologic-naïve than in biologic-non-naïve patients across Weeks 2 to 54. Higher clinical remission rates at Week 54 were significantly associated with lower baseline disease severity and no prior anti-tumor necrosis factor alpha (anti- TNFα) treatment. Among patients with prior anti-TNFα treatment, longer duration of anti-TNFα treatment was associated with higher clinical remission rates at Week 54 (28.1%, 32.7%, and 60.0% for ≤3 months, >3 to <12 months, and ≥12 months, respectively, p=0.001 between groups). In addition, clinical remission rate at Week 54 was higher in patients who had loss of response to anti-TNFα treatment than in those who had primary nonresponse (54.4% vs 24.6%; p=0.001). The 54-week persistence rate was 64.5%. Concomitant use of tacrolimus (OR 2.76, 95% CI 1.00, 7.62, p=0.05) and shorter disease duration (median:7.8 years), (OR 0.33, 95% CI 0.13, 0.82 for ≥7.8 years vs <7.8 years p=0.017) were associated with loss of response to VDZ in the multivariate analysis, but prior use of anti- TNFα treatment was not.

Conclusion

This retrospective study confirms favorable outcomes with VDZ in patients without prior exposure to anti-TNFα treatment. However, among patients with history of anti-TNFα- exposure, better outcomes were observed among those who experienced loss of response than those with primary nonresponse, as well as those who had a longer duration of anti-TNFα treatment.Read more P743 A personalised algorithm predicting the risk of intravenous corticosteroid failure in acute ulcerative colitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

An episode of acute ulcerative colitis (UC) represents an important watershed moment in a patient’s disease course. Foreknowledge of a patient's likely response to intravenous corticosteroid therapy has significant clinical utility. Using a large prospectively collected acute UC patient database and machine learning-based techniques we aimed to derive and validate a personalised algorithm for identifying patients at high risk of corticosteroid therapy failure from variables available at hospital presentation.

Methods

A prospectively collected database of 600 consecutive presentations of acute UC was collated at a single referral centre between 1996 and 2022. An AIC-based Elastic Net model was used to select variables on the 419 earliest presentations of acute UC (1996-2017). Two risk-scoring algorithms, with and without utilising additional endoscopic variables, were constructed using logistic regression models. These risk scores were then validated on a separate cohort of 181 acute UC presentations (2018-2022).

Results

The partial risk of rescue (ROR) score included the admission indices of oral corticosteroid treatment; bowel frequency ≥6/24 hours; albumin; CRP ≥12mg/ml and log₁₀CRP. The full ROR score incorporates the same variables with the addition of the Mayo endoscopic subscore and disease extent.The ROC AUCs in the validation cohort were 0.76 (95% CI: 0.69-0.83) and 0.78 (95% CI: 0.71-0.85) for the partial and full ROR scores, respectively. When incomplete cases were excluded, the full ROR score validation cohort ROC AUC increased from 0.78 to 0.80.

Conclusion

These pragmatic personalised risk scores (available at www.severecolitis.com) have comparably strong performance characteristics and usability enabling the identification of individuals at high risk of corticosteroid treatment failure before or after endoscopic assessment. These patients may be suitable for consideration of early treatment escalation or screening for participation in clinical trials.Figure 1.Performance characteristics of the full model for corticosteroid treatment failure: Full risk of rescue (ROR) scoreRead more P511 Short-term real-world effectiveness and safety of granulocyte and monocyte adsorptive apheresis (GMA) in patients with inflammatory bowel disease: GRACE StudyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The clinical efficacy of granulocyte and monocyte adsorptive apheresis (GMA) with Adacolumn in patients (pts) with inflammatory bowel disease (IBD) has been reported in several clinical trials (CT), with significant clinical remission rates. However, evidence on real-world effectiveness of GMA with Adacolumn in ulcerative colitis (UC) or Crohn's disease (CD) pts who were underrepresented in CT is still limited.

Methods

GRACE is a multicentric, prospective observational study conducted at 31 centres in Spain. The study included adults (≥18 years) diagnosed with UC or CD who had been scheduled to receive GMA with Adacolumn in clinical practice. The study consisted of a baseline (GMA initiation) and 3 follow-up visits at 4, 24, and 48 weeks after the last GMA session. The primary endpoint is the steroid-free remission rate at 24 weeks. This interim analysis is focused on clinical characterization of pts and their management and outcome 4 weeks after GMA treatment.

Results

A total of 95 evaluable pts were included at data cut-off date (25 Sept 2023) (median age: 54 years; 50% men: 81% outpatients). Overall, 89.4% (n=84) of pts had UC, being moderate-to-severe in 85.5%; 57,8% had pancolitis, and the median Mayo score was 5 (interquartile range [IQR], 3-6). Out of the 10 pts (10.6%) with CD, all had B1, and 3 pts had L1, 4 L2 and 3 L3. Overall, 17% had extraintestinal manifestations. Regarding IBD-related therapy, 52.6% of pts had previously received anti-TNF agents, 37.9% thiopurines, and 17.8% JAK inhibitors. Overall, 85.3% of pts received concomitant treatment with GMA, most commonly 5-ASA (60%), corticosteroids (51,6%), ustekinumab (20%), vedolizumab (17.9%), and anti-TNF therapy (11.6%). A total of 71 pts reached the 4-week visit after receiving a median of 10 (IQR, 8-10) GMA sessions (weekly: 26.3%, biweekly: 36.8%, and weekly/biweekly: 31.6%). At week 4, clinical remission was achieved by 50.7% of patients (UC: 49.2%; CD: 66.7%), being 50% and 53.3% in patients concomitantly treated with ustekinumab and vedolizumab. Steroid-free remission rate was 26.1% (UC: 22.2%; CD: 66.7%) at week 4. Overall, 11,2% of patients experienced AEs related to GMA, most of them being mild (73%) or moderate (22.4%). Most common AEs were headache and asthenia. No SAEs were observed.

Conclusion

Preliminary data at 4 weeks show that Adacolumn is a safe and effective treatment in a cohort of IBD refractory pts with previous failure to multiple therapies including thiopurines, biologics and JAK inhibitors. Half of pts were concomitantly treated with biologics, and their clinical remission rate was similar to the overall population. Long-term results of this study (48 weeks) are required to confirm these findings.Read more P941 Observational study of tofacitinib in ulcerative colitis in Sweden (ODEN) – Interim analysis of clinical and biomarker dataWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Tofacitinib is a Janus kinase (JAK) inhibitor for the treatment of moderate to severe ulcerative colitis (UC). ODEN is an ongoing Swedish multicentre prospective observational study regarding effectiveness of tofacitinib in UC. In this interim analysis, we aimed to assess the clinical outcomes during the first 16 weeks.

Methods

Patients with active UC were enrolled 2020-2023 when starting tofacitinib as per clinical indication. Inclusion criteria were fecal (F) calprotectin >250 mg/kg or Mayo endoscopic score ≥2. Data were collected using an electronic case report form linked to the Swedish National Quality Registry for Inflammatory Bowel Disease (SWIBREG). Data concerning inflammatory markers, endoscopic activity, partial (p) Mayo, extra intestinal manifestations, health-related quality of life measures, corticosteroid use, and colectomy rates were collected regardless of tofacitinib discontinuation. Information collected at week 8 and 16 is presented here. Intention-to-treat (ITT) analysis was applied and tofacitinib discontinuation was considered as treatment failure (i.e., no tofacitinib-induced clinical or laboratory response or remission). McNemar’s test was used for proportion differences.

Results

The proportion of patients who previously had failed at least one biologic was 95% and at least two biologics, 62%. At inclusion, median p-Mayo was 5 and 39% of patients were on corticosteroids (Table 1a). Patients’ survival on drug is shown in Figure 1a. At week 8 and 16, 42% and 43%, respectively, achieved corticosteroid free clinical remission, Figure 1b. A 50% reduction in F-calprotectin was seen in 54% and 49% at week 8 and 16, respectively. The endpoint of Mayo endoscopic score 0 and/or F-calprotectin <100 mg/kg was achieved by 30% and 38% at week 8 and 16, respectively. Arthralgia frequency decreased significantly from baseline from 29% at inclusion to 13% and 11% at week 8 and 16 respectively. Three patients underwent colectomy the first 16 weeks (Table 1b).

Conclusion

After 16 weeks of treatment with tofacitinib, a substantial proportion of previously treatment refractory UC patients were in clinical and endoscopic corticosteroid-free remission, and a distinct improvement in F-calprotectin levels was observed. In addition, a significant reduction in arthralgia was noted.Read more P776 A Prospective, Multicenter, Single-arm, Observational Study to Evaluate the Safety and Effectiveness of Vedolizumab in Real-world Clinical Practice in China: Interim Analysis of Safety resultsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Crohn's disease (CD) and ulcerative colitis (UC) are categorized as inflammatory bowel disease [IBD] usually treated by corticosteroids, immunomodulators and biologics, etc. Vedolizumab, a gut-selective α4β7 integrin antibody, has been approved in China for IBD patients who are intolerant /lost response to conventional therapies or TNF-α inhibitors. Of late, there is a paucity of data on the safety and effectiveness of vedolizumab in real-world clinical practice in China. This study evaluates the safety and effectiveness of vedolizumab in adult patients with UC or CD Here, we present the first interim analysis.

Methods

In this multicenter, single arm, prospective, observational, real-world study (NCT04872491), adults (aged >18 years) with UC or CD were administered intravenous vedolizumab 300 mg at week 0, 2, 6, and thereafter every 8 weeks. Incidence of adverse events (AEs), serious AEs (SAEs), Treatment-related AEs (TRAEs) and AEs of special interest (AESIs) were the primary endpoints Patients with administration of at least 1 dose of VDZ were included and observed 18 weeks after completion of the study or early termination, up to maximum of 72 weeks. AESIs included infections, malignancies, infusion-related reactions, and hypersensitivity. The secondary endpoints included the effectiveness of vedolizumab in terms of clinical response, clinical remission and endoscopic remission assessed at week 14 and week 54 after vedolizumab initiation.

Results

A total of 307 patients (UC, n=245; CD, n=62) with a median age of 41 years (range: 18-86) were included in the interim analysis. Median duration was 883 days (UC: 1035 days; CD: 731 days) and 105 days (UC: 107 days; CD: 99 days) for IBD and vedolizumab exposure, respectively. A total of 105 (34.20%) patients (UC: 35.92%; CD: 27.42%) developed 225 AEs and the most frequent AEs were infections and infestations (16.61%) followed by gastrointestinal disorders (GID) (14.66%) and general disorders (GD) (4.56%). Colitis and pyeria were the most common GID and GD, respectively occurred in 7(2.28%) patients each (Table 1).Forty-one TRAEs were observed and ten AEs lead to study discontinuation. Total 13 AESIs and 34 SAEs were reported and at least one AESI was reported in 10 patients. No deaths were reported during the study (Table 2).A total of 79.19% (118/149) and 34.48% (10/29) patients with UC and CD respectively, achieved clinical response at week 14 (±4 weeks). Clinical remission and endoscopic remission was achieved by 2/2 and 1/1 patients with UC, respectively at week 54 (±4 weeks).

Conclusion

Vedolizumab demonstrated favorable safety profile and treatment effectiveness among Chinese adult patients with UC or CD in real-world clinical practice.Read more P548 Ustekinumab shows favourable safety profile and drug persistence rates in patients with Crohn’s Disease – results from a tertiary IBD centreWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Patients with Crohn’s disease (CD) often require multiple biological therapies due to loss of response. Anti-TNF drugs are generally used as first-line biologic followed by a switch of class when patients lose response. Ustekinumab (UST), an IL12/23p40 antagonist is used in CD, often after anti-TNF failure. The aim of the study was to report on outcomes of UST therapy with a median follow-up period of nearly 24 months.

Methods

All CD patients who commenced UST therapy were identified from EMR at two tertiary referral centers between January 2017 and December 2021. All relevant demographic and clinical data were collected. Data on clinical response (defined as a downgrade in disease activity based on clinician assessment & biochemical parameters), steroid-free duration, and long-term response to UST at 52 and 104 weeks were recorded. The response was assessed clinically and supported by biomarkers, cross-sectional imaging, endoscopic data, and sustained maintenance of UST. Statistical analysis was carried out using the IBM® SPSS® Statistics software package Version: 28.0.0.0.

Results

A total of 249 CD patients (M=133 (53%); median age 41 years) were included, with a median follow-up period of nearly 24 months (5-79 months). 94 (38%) patients had stricturing (B2), penetrating (B3) and perianal phenotype at baseline and 104 (42%) had undergone previous resection/s. 207 (83%) had documented moderate to severe disease activity and 211 (85%) patients were exposed to at least one biologic prior to treatment with UST. 66 (27%) patients were on concomitant thiopurines at the start of treatment. 224 (90%) patients in our cohort showed clinical response to UST and all remained on treatment at the end of follow-up period. The distribution of patients as per disease activity at baseline, 52 and 104 weeks is illustrated in Figure 1. An improvement in haemoglobin levels was observed post-therapy with UST, which was statistically significant at 104 weeks (p<0.001), with corresponding significant reduction in faecal calprotectin levels (median reduction: 506 mcg/g to 335 mcg at 104w; p<0.001). Only 10 (4%) patients had side-effects which were directly attributed to UST therapy.

Conclusion

UST is an effective therapeutic option in CD for both bio-naïve and previous biologic failure patients. Although our cohort had a large proportion of patients with complicated and refractory disease, clinical response was observed, regardless of their previous exposure status to biologics, and disease phenotype. UST appears to be well tolerated with a reasonable safety profile. UST has good drug-persistence rates making it economically feasible in the long term. Clinicians could safely continue UST for longer durations to manage CD.Read more P777 Is the long-term Budesonide use have any influence on Bone Mineral Density in Inflammatory Bowel Diseases?Wed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Systemic steroid use, and IBD itself, both have negative effect on bone mineral density. Budesonide is a synthetic steroid with high topical glucocorticoid activity and low systemic bioavailability. When compared to systemic steroids, the frequency of side effects of budesonide appears to be quite low, however, there is no documented report about the long term budesonide use on BMD in IBD patients. We also do not know other potential side effects of long term budesonide use. In this study, we aimed to evaluate the long term budesonide use on BMD and its’ other potential side effects, in IBD patients.

Methods

We retrospectively reviewed the files of the patients who had been using budesonide for ≥24 months and had DEXA measurements during the follow-up period (Budesonide group). Patients in the budesonide group were matched 1:1 with patients without a history of budesonide use, in relation to pre or post registry number of each index case under budesonide. Matching between groups has been done, in terms of gender, age, type of IBD, history of resection, concomitant medications, and comorbidities. For the exact matching, move on for the next or further next available patient, pre or post of each index case, was taken as a choice. (Control group). At the initiation and completion of budesonide treatment, DEXA scans were taken, and biochemical parameters and bone fractures were recorded. We also recorded other causes of secondary osteoporosis in patients (such as comorbidities, medications, alcohol, and cigarette use), as well as cumulative steroid doses and durations in those using conventional corticosteroids.

Results

A total of 104 patients were included in the study, with 52 in the budesonide group and 52 in the control group. The mean duration of budesonide use was 46.13 ± 15.4 months (range: 25-94 months), and the mean cumulative budesonide usage dose was found to be 34.9 ± 11.8 g (range: 14-64.8 g) in the budesonide group. Table 1a presents the comparison of the two groups. None of the patients in the budesonide group showed deterioration in BMD during the follow-up (Table 1b and 1c). No other prominent long term side effects, valued for the file recording, was found.

Conclusion

Budesonide treatment seems to be safe in consideration for maintaining long term remission in IBD. Relatively low number of patients, not considering the first two year’s follow up and dropping of the cases with earlier side effects, missed for the long-term judgement under budesonide, may explain the lacking of the other potential side effects (indicated in the literature).Read more P942 Real-world data on outcomes of treatment with ustekinumab in patients with Ulcerative ColitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Ustekinumab (UST), a monoclonal antibody against the shared p40 subunit of IL-12/IL-23, has been approved for the treatment of moderate to severe ulcerative colitis (UC). The aim of this ambi-directional study is to collect and analyze data from a large cohort of Greek patients with UC treated with UST.

Methods

Data from UC patients treated with UST in 15 Greek hospitals were analyzed to evaluate rates of clinical response (CR, 50% reduction in UC-PRO2 compared to baseline) at week 16 of treatment, steroid-free clinical remission (SFCRem, pMAYO score <3 with UC PRO2=0) at weeks 16 and 54, and endoscopic healing (EH, endoscopic MAYO=0 and/or UCEIS=0-1, with 1 allowed only for vascular score) at week 54.

Results

Characteristics of the 132 enrolled patients are shown in Table 1. Most patients, 98/ 74% commenced UST treatment for active disease despite treatment and 92/ 72% had been exposed to biologic agents prior to UST (anti-TNFs, 66/50%, vedolizumab (VDZ) 57/43%). Fifty-three (40%) and 29 (22%) had received a single or two biologics (IFX and VDZ, 18/14%), respectively. By week 54, 19 had discontinued treatment due to no response. A sum of 116 patients have reached week 16, out of whom 104 have enough data to be analyzed. SFCRem was achieved in 49/47% patients. Analysis of patients with active disease at induction (87 in total with adequate data) showed that CR was achieved in 64/74%. Of 49 patients who completed 54 weeks of treatment, 25/51% were in SFCRem. Of 38 patients with adequate endoscopic data 14 /37% achieved EH. Patients who achieved SFCRem at week 16 were more likely to maintain SFCRem at week 54 (OR=3.89 [1.10-13.76], P=0.035). CR at week 16 was not associated with SFCRem at week 54. In univariate analysis SFCRem at week 54 was negatively associated with baseline disease activity (pMAYO score OR=0.78 [0.61-0.99], P=0.047; UCEIS OR=0.55 [0.36-0.85], P=0.007; WBC/1000: OR=0.65 [0.49-0.87], P=0.003), refractoriness to IFX (OR=0.27 [0.08-0.85], P=0.026), and positively associated with concomitant use of 5-ASA at UST initiation (OR=3.69 [1.05-12.96], P=0.041) but not at week 54 (P=0.757). EH at week 54 was negatively associated with refractoriness to IFX (OR=0.13 [0.02-0.71], P=0.019) and VDZ (OR=0.19 [0.05-0.79], P=0.022).

Conclusion

UST is mostly used as 2^nd or 3^rd line treatment for moderate to severe UC. By the end of induction, patients' majority showed CR, while at year 1 SFCRem was achieved in 51% and EH in almost 40% of patients. Negative predictive factors of SFCRem at week 54 included baseline disease activity, WBC count and resistance to prior treatment with IFX, while concomitant use of 5-ASA at baseline had positive effect. Negative predictive factors for EH at week 54 were refractoriness to IFX or VDZ.Read more P549 Liver stiffness assessed with TE-CAP tends to increase with longer duration of disease in Crohn’s disease: A prospective cohort study for the evaluation of hepatic abnormalities in inflammatory bowel diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Intestinal mucosal injury is supposed to cause liver disease and abnormal liver profiles are frequently observed in inflammatory bowel disease (IBD) patients. Therefore, we investigated the hepatic manifestations of IBD in Korea.

Methods

A prospective cohort for the evaluation of hepatic abnormalities in IBD was established at Kosin University Gospel Hospital, Busan, Korea in 2018. From December 2018 to June 2023, patients who diagnosed with IBD were consecutively enrolled and conducted both abdominal sonography and transient elastography-controlled attenuation parameter (TE-CAP) with liver function tests, viral tests, lipid profiles, and fecal calprotectin.

Results

Three hundred twelve (138 Crohn's disease, CD, 174 ulcerative colitis, UC, and 200 men) patients were enrolled. Mean ages (years old) were 46.4 in UC and 37.5 in CD. Mean body mass indexes, BMIs were 23.1 in UC and 21.9 in CD. Mean CAP (dB/m) score was 222.439 (±55.375) [UC 232.408 (±53.476), CD 209.869 (±55.358)]. Mean E (kPa) value was 4.481 (±1.801) [UC 4.496 (±2.028), CD 4.461 (±1.474)]. Mean fecal calprotectins were 982 in UC and 1160 in CD. The mean durations of disease (months) were 36.8 in UC and 44.0 in CD. In abdominal sonography, abnormal findings in gallbladder were found 38/169 (22.4%) in UC and 38/137 (27.7%) in CD (P=0.834). (Table 1) HBs Ag positivity was 7/173 (4.0%) in UC, 5/138 (3.6%) in CD (P=0.847). Anti-HBs was positive in 115/173 (66.4%) in UC and 68/138 (49.2%) in CD (P=0.002). Anti-HBc IgG was positive in 46/112 (29.1%) in UC and 17/130 (13.0%) in CD (P=0.001). Anti-HCV was positive in 0/173 (0.0%) in UC and 3/138 (2.1%) in CD (P=0.051). In UC patients, CAP value was associated with BMI (r=0.498, P<0.0001), triglyceride (TG) (r=0.264, P<0.0001), and low-density lipoprotein (LDL) (r=0.162, P=0.033). E value was related to BMI (r=0.267, P<0.0001). In CD patients, CAP value was associated with BMI (r=0.661, P<0.0001), total cholesterol (r=0.290, P=0.001), TG (r=0.286, P=0.001), LDL (r=0.217, P=0.011) and fecal calprotectin (r=-0.343, P<0.0001). E value was associated with total bilirubin (r=0.369, P<0.0001), ALP (r=0.236, P=0.005), r-GTP (r=0.318, P<0.0001), AST (r=0.384, P<0.0001), ALT (r=0.277, P<0.001) and disease duration (r=0.239, P=0.005). In CD patients with a disease duration of more than 1 year, the E value was confirmed to increase gradually as the disease period lengthened (r=0.346, P=0.004). (Figure 1)

Conclusion

In CD patients, liver stiffness tends to increase with longer duration of disease or active liver inflammation. Both UC and CD patients, fatty liver may occur attributed to abnormal metabolic profiles. In addition, there is a need to encourage HBV vaccination in IBD patients in HBV endemic area, especially in UC patients.Read more P778 The association of drugs and clinical relapse in patients with microscopic colitis. A retrospective observational studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Smoking, the use of non-steroidal anti-inflammatory drugs (NSAID) acetylsalicylic acid (ASA), proton pump inhibitors, serotonin reuptake inhibitors (SSRI) and statins has been associated with microscopic colitis (MC). We aimed to study if these factors were associated with a higher risk of clinical relapse in patients diagnosed with MC.

Methods

All patients with a histological verified diagnosis of MC at our clinic between the years 2006-2022 were identified. Baseline factors and drugs prescribed before and after diagnosis were registered. Risk factors influence on the odds of having a prescription of oral budesonide and the odds of having a second course of budesonide (clinical relapse) were studied retrospectively.

Results

Patients with MC (n=183) with a mean age of 62.3 years (SD 13.3 years) were followed for median 5 years (25^th-75^th percentile 4-10 years) after diagnosis. One-hundred and thirty-eight patients (75%) had at least one prescription of budesonide after diagnosis and 90 patients (49%) had at least one clinical relapse treated with budesonide. The time to clinical relpase in patients with at least one course of budesonide are shown in Figure below. Patients who had been prescribed NSAIDs within one year before clinical relapse had higher odds for clinical relapse (OR 2.88, 95% CI 1.11-7.43) but there was no increased risk for clinical relapse for the use of ASA (OR 0.99, 95% CI 0.43-2.33), PPIs (OR 1.06, 95% CI 0.53-2.14), SSRI (OR 1.29, 0.59-2.80) or statins (OR 0.93, 95% CI 0.46-1.89). No association was seen for being a smoker and/or being prescribed NSAID, ASA, PPI, SSRI and statins at baseline and the odds of having a prescription of oral budesonide within one year after diagnosis.

Conclusion

The risk of a clinical relapse are associated with the use of NSAIDs but not with the use of ASA, PPIs, SSRIs and statins. We suggest that patients with MC use NSAID with caution.Read more P550 Short and long-term outcomes after acute severe ulcerative colitis in adults: A 12 year Canadian experience in the post biologic eraWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Patients with acute severe ulcerative colitis (ASUC) are at increased risk of colectomy following an episode of acute severe exacerbation. Medical rescue therapy in steroid non-responders has reduced the need for emergency colectomy. However, impact of biologics on longer-term colectomy risk is unclear.

Methods

A retrospective cohort study of adult patients aged ≥18 years hospitalized with acute exacerbation of UC requiring hospitalization and managed with intravenous corticosteroids between 2010 and 2022 at two regional hospitals in London, Ontario, Canada. Steroid non-response was defined as requirement of medical rescue therapy or colectomy.

Results

A total of 264 adults hospitalized with ASUC were included in the analysis (male: 51.1% [n=136], mean age at admission: 40.8±17.8 years). The majority had extensive colitis (71.3% [n=169]) at the time of diagnosis. 46.3% (n=118/255) presented within one year of disease onset and 23% (n=61) had ASUC as their first presentation with UC. 25.7% (n=66/257) of patients had prior purine analogues and 23.3% (60/257) had previous biologics prior to ASUC presentation. After admission, 55.7% (n=147) responded to intravenous corticosteroids. Of the steroid non-responders, 37.5% (n=99) patients were managed with infliximab rescue therapy and only one patient received tofacitinib rescue therapy. Median CRP, stool frequency and Lindgren index score were statistically significant between steroid responders and non-responders (Table 1). A higher proportion of steroid non-responders had prior exposure to biologics or tofacitinib compared to steroid responders (31.9% vs 16.3%, p<0.01). On multivariate analysis for various factors predicting steroid non-response, assessment by Oxford criteria on day 3 was the only factor that was statistically significant (odds ratio 4.70 (95% CI 1.06-20.8), p = 0.04). Oxford criteria on day 3 had a sensitivity, specificity of 58.6% and70.8%, respectively for predicting steroid non-response. 8% (n=21) required colectomy during index admission. An additional 13% (n = 32) underwent colectomy within 12 months of discharge, for which there was no difference between steroid responders and non-responders (12.2% vs 14.7%). The short term (3 months following discharge) and long-term (3-12 months following discharge) colectomy rates following discharge were 8% (20/245) and 5.4% (12/223) respectively. Hospitalization with UC exacerbation rate following discharge was 17% (38/223).

Conclusion

8% of patients admitted for ASUC require colectomy during the same admission and additional 13% required colectomy within 12 months of discharge. Despite a high initial response to corticosteroids, long term colectomy rates and re-hospitalization rates remain high.Read more P963 The comparative effectiveness and safety of different biologics in young (<60 years) versus elderly (≥60 years) patients with IBD: results from a real-world experience at a Belgian tertiary centreWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The therapeutic armamentarium for inflammatory bowel disease (IBD) is rapidly expanding as well as the number of elderly patients with IBD. Given the frailty of this subpopulation, it is of increasing importance to have data on the efficacy and safety of different therapies in this cohort. Aim: To assess the efficacy and severe adverse event (SAE) rate of different biologics in young (<60 years (yr)) versus elderly patients with IBD (≥60 yr) in a real-world tertiary cohort.

Methods

A retrospective monocentric study was performed at the Ghent University Hospital. Patients starting anti-TNF, ustekinumab (UST) or vedolizumab (VDZ) from 01/2018 to 06/2021 with follow-up until 12/2022 were included. Co-primary endpoints after induction and after 1 yr of therapy were: clinical response (CRp) and remission (CRm), biochemical response (BRp) and remission (BRm) and endoscopic response (ERp) and remission (ERm). The secondary endpoint was treatment survival. Severe adverse events (SAE) were defined as intestinal resection (IR), IBD-inflammation related hospitalization (IBD-hosp), IBD-treatment related hospitalization (e.g. infections) (treat-hosp), malignancy and death. Multivariate logistic regression (MLR) and Cox regression model (CRM) were applied to assess potential risk factors (RF).

Results

A total of 267 patients were included (33 patients ≥60 yr). Significantly different baseline characteristics are shown in Table 1A. After induction, no differences in CRp, CRm, BRp, ERp or ERm were found between both groups (Table 1B). Only BRm was numerically higher in younger patients, but not statistically significant after MLR (Table 1C). After one year of therapy, no difference was seen for CRp, CRm, BRp, BRm, ERp or ERm (Table 1B). There was no difference regarding treatment survival for both groups (aHR 0.701, [0.346-1.420], P=0.324) (figure 1), as well as for reason to stop biologic (P=0.336). Regarding SAEs, a higher rate was seen for elderly patients (26.9% vs. 45.5%, P=0.028), also after CRM (aHR 1.86, [1.01-3.44], P=0.047), adjusting for type of biologic, use of systemic corticosteroids or immunomodulators, previous IR, disease duration and number of previous biologics used. Regarding different subtypes of SAE, no difference for IR (P=0.503), IBD-hosp (P=0.714), specific IBD related SAE (P=0.480), malignancy (P=0.162) and death (P=1.000) were found. Treat-hosp was higher in elderly patients (5.1% vs. 24.2%, P=0.001), which was confirmed in the CRM (aHR 5.01, [1.92-13.04], P<0.001).

Conclusion

No difference was seen regarding efficacy of different biologics in younger versus elderly patients with IBD. SAE rate was higher in elderly patients.Read more P779 Long term efficacy of azathioprine monotherapy in patients with Inflammatory Bowel DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

ECCO guidelines recommend monotherapy with azathioprine (AZA) as maintenance therapy of patients with inflammatory bowel disease (IBD) mainly in steroid-dependent disease. However, in the era of the new advanced treatments AZA is not considered as a preferable option, mainly because of the referred side effects and its use is limited in combination with biologic agents.

Methods

This is a retrospective observational study using data from the longitudinal, prospective IBD registry of University Hospital of Heraklion, Greece.Our aim was to study IBD patients who started on monotherapy with AZA, the profile of adverse effects they developed, the treatment persistence in monotherapy, as well as the possible related factors of treatment success [including age, gender, smoking status, body mass index, disease type, disease phenotype for Crohn’s disease (CD), history of IBD related surgery and the presence of extraintestinal manifestations].

Results

Of 168 IBD patients treated with AZA, 89 (53%) were under AZA monotherapy [38 (43%) female, 67 (74%) CD, median age (IQR) 47 (32-56) years, mean (±SD) disease duration 17 (±8.4) years, median (IQR) time receiving AZA 72 (7-120) months]. Thirty (34%) patients continue their treatment till now (23 CD, 7 ulcerative colitis-UC), with a median time (IQR) of 108 (81-132) months. Of these, 18 (60%) (15 with CD and 3 with UC) present endoscopic remission and 11 (36%) (8 with CD, 3 with UC) mild endoscopic activity (based on SES-CD Score for CD and Mayo endoscopic score for UC). Of the 59 who discontinued, 33 (37%) experienced adverse events, 5 (5.5%) developed malignancy, 5 (5.5%) did not respond at baseline, 6 (6.5%) had loss of response (at a median of 91 months), 3 (3%) discontinued due to advanced age, 3 (3%) discontinued their medication on their own and 2 because of treatment de-escalation due to deep remission. Using logistic regression analysis, patients who responded to AZA monotherapy were patients without a history of IBD surgery or any extraintestinal manifestation, P=0.001 and 0.004, respectively. In the multivariate analysis, these associations remained statistically significant (P=0.01 and 0.006 respectively).

Conclusion

About one third of patients with IBD under AZA monotherapy experience long term response and about two thirds of them prolonged disease remission. Patients without either a history of IBD surgery or extraintestinal manifestations seem to respond better to AZA monotherapy.Read more P964 Vedolizumab trough concentrations during subcutaneous treatment in patients with inflammatory bowel diseasesWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

An exposure-response relationship has been described for intravenous (IV) vedolizumab (VDZ), but little is known about through levels and real life outcomes of subcutaneous (SC) VDZ treatment. We aimed to study the effect of SC VDZ in a prospective real life cohort and assessed what clinical variables are associated with vedolizumab trough concentrations.

Methods

IBD patients initiating VDZ SC treatment were included in our nationwide, prospective Initiative on Crohn and Colitis (ICC) registry. Adult IBD patients were included if a known trough level during IV and SC therapy was available. Two different assays were used for trough levels measurements : i.e. an enzyme linked immunosorbent assay (ELISA) and liquid chromatography-tandem mass spectrometry (LC-MS/MS). The primary outcome measure was the mean VDZ trough concentration during maintenance treatment (after at least four SC injections). In addition, associations between VDZ serum trough concentrations and corticosteroid-free clinical remission were assessed. A Receiver Operating Characteristic (ROC) analysis was performed to determine the concentration threshold that was associated with corticosteroid free clinical remission after 4 SC VDZ injections (i.e. defined as a Harvey Bradshaw Index (HBI) score ≤ 4 for CD and a Short Clinical Colitis Activity Index (SCCAI) score ≤ 2 for UC).

Results

In total, 24 with Crohn’s disease (CD) and 32 with ulcerative colitis (UC) patients were included. Twelve patients started SC VDZ after a maximum of three VDZ infusions and 44 patients switched to VDZ SC after at least four VDZ infusions. The mean VDZ trough concentration was 34.4 µg/mL (SD 12.9) after 13 (IQR 11-20) weeks of SC treatment. The mean VDZ trough concentration increased from 20.5 µg/mL to 35.2 µg/mL (P < 0.001) in patients who switched from IV to SC VDZ. Biochemical remission (defined as a C-reactive protein (CRP) ≤ 5 µg/mL with a faecal calprotectin (FC) ≤ 250 µg/g) prior to the switch, VDZ measurements using LC-MS/MS and higher VDZ levels during IV therapy were associated with higher VDZ serum levels during SC therapy. Active smoking and prior use of >1 biologic and/or tofacitinib were associated with lower VDZ levels during SC therapy (table 1). A VDZ trough concentration of ≥ 34.5 µg/mL during SC maintenance therapy predicted corticosteroid free clinical remission with a sensitivity, specificity, positive predictive value and negative predictive value of 60%, 75%, 86% and 43%, respectively.

Conclusion

VDZ serum concentrations were significantly higher during SC therapy versus IV treatment. A VDZ trough concentrations ≥ 34.5 µg/mL was associated with corticosteroid free remission.Read more P551 Benefit–risk trade-offs and patient preferences for therapy selection in Ulcerative Colitis: a multi-country preference studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The treatment landscape of ulcerative colitis (UC) is increasingly complex. In the absence of predictive biomarkers and objective parameters, shared treatment decision-making is advocated in clinical practice. This study quantified the benefit–risk trade-offs that patients with UC are willing to make when choosing a treatment. A patient-centric benefit–risk assessment of filgotinib, an oral, Janus kinase 1 preferential inhibitor, was also conducted to show how measured trade-offs can be used.

Methods

Patients recruited through databases, panels, social media and patient associations completed an online discrete choice experiment (DCE). Eligible patients were aged ≥18 years, had a diagnosis of UC for ≥6 months and resided in France, Germany, Italy, Spain or the UK. DCE treatment attributes were identified using a literature review, clinical data and patient interviews. Patients completed the DCE by choosing between a series of two hypothetical treatment options with varying attributes which were systematically varied to ensure trade-offs were made. Data were analysed using a mixed logit model. Relative attribute importance (RAI) scores and maximum acceptable risks were generated. Preference data were combined with SELECTION clinical trial data to evaluate the desirability of filgotinib 200 mg versus placebo from the patients’ perspective.¹

Results

Among 631 patients who completed the survey (8997 patients invited), 75.3% were male and the mean age (standard deviation) was 42.2 (7.7) years. Patients preferred a daily oral pill over self-injection or intravenous treatment, and a treatment that avoided steroid use (Figure). Achieving and maintaining remission (RAI 32.4%; 95% confidence interval [CI] 29.5–35.2%) was considered the most important factor when choosing treatment. To achieve a 20% increase in the chance of remission, patients were willing to accept a 1.4% (95% CI 1.2–1.6%) increase in the risk of blood clots, a 2.0% (95% CI 1.7–2.3%) increase in the risk of serious infections, and a 0.7% (95% CI 0.6–0.8%) increase in the risk of malignancies (Table). Analysing patient preference and clinical data suggests filgotinib has a 70.1% chance of being preferred over placebo (p<0.001).

Conclusion

Treatment preferences of patients were mostly driven by the likelihood of achieving and maintaining remission. To achieve this, they were willing to accept some increase in the risks of blood clots, serious infections and malignancies. Patients also valued avoiding steroids. A patient-centric benefit–risk assessment indicated that patients are significantly more likely to prefer filgotinib over placebo, illustrating how preference data can be used with clinical data to inform decision-making.1. Feagan BG et al. Lancet 2021;397:2372–84.Read more P850 Symptomatic effectiveness of ozanimod in routine clinical care of ulcerative colitis: an interim analysis of the multicentre, prospective, noninterventional COLIBRI studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Ozanimod (OZA) is approved for the treatment of adults with moderately to severely active (MOD/SEV) ulcerative colitis (UC) per results of the phase 3 True North trial. Real-world data are needed to determine treatment effects in a more diverse population in clinical practice. The COLIBRI study (NCT05382715) assesses the use, effectiveness, and safety of OZA and quality of life in patients (pts) with MOD/SEV UC in a routine clinical practice setting in Germany over a period of 52 or 104 weeks. This interim analysis of COLIBRI reports baseline (BL) characteristics and evaluates the symptomatic clinical effectiveness of OZA up to Week (W) 10.

Methods

COLIBRI will enrol up to 380 adults with UC; the study design is shown in the Figure. Adherence to the times of visits and the diagnostic and therapeutic measures are not mandatory and will correspond to the routine processes of the respective facilities. Partial Mayo score (pMS; sum of stool frequency subscore [SFS], rectal bleeding subscore [RBS], and Physician Global Assessment), symptomatic clinical improvement, defined as either symptomatic response (decrease from BL in the combined 6-point SFS + RBS of ≥1 point and >30%, and decrease of ≥1 point in RBS or absolute RBS of ≤1 point) or symptomatic remission (RBS = 0 and SFS ≤1, and a decrease of ≥1 point from BL SFS), and symptomatic remission were assessed at W4 and W10. Data were collected by electronic case report forms and by the study-specific interface of the MyTARGET app (Kiel, Germany) for pt-related outcomes, which were evaluated throughout the study.

Results

Of 83 pts included in this interim analysis (BL and W4, n=58; BL and W10, n=39), the median (interquartile range) age of pts was 40 (29.0–53.0) years, 49 (59.0%) were female and 34 (41.0%) male, 80.7% had prior exposure to advanced therapies (AT), and 48.2% had prior exposure to ≥3 AT. Overall, 67.5% had prior tumor necrosis factor alpha inhibitor and 50.6% had prior vedolizumab use. BL pt characteristics are shown in the Table. In total, 76 pts with BL data had pMS data; the mean (SD) pMS at BL was 5.0 (2.2), and most pts fell within the moderate pMS category (44.9%). Mean (SD) pMS decreased from BL (5.0 [2.2]) to 3.9 (2.6) at W4 and to 3.5 (2.3) at W10. Symptomatic clinical improvement was achieved in 32.8% (19/58) and 51.3% (20/39) of pts at W4 and W10, respectively. Symptomatic remission was achieved in 22.4% (13/58) and 25.6% (10/39) of pts at W4 and W10, respectively.

Conclusion

This interim analysis of the German COLIBRI study showed that refractory pts with MOD/SEV UC receiving OZA achieved symptomatic effectiveness at W4 and W10 in a routine clinical practice setting.Read more P1040 Comparative effectiveness of upadacitinib versus ustekinumab in patients with moderately to severely active Crohn’s disease: a matching-adjusted indirect comparisonWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Upadacitinib (UPA), an oral Janus kinase inhibitor, and ustekinumab (UST), a parenteral IL 12/23 antagonist, are effective treatments for moderately to severely active Crohn’s Disease (CD). In the absence of head-to-head data, a placebo (PBO)-anchored matching-adjusted indirect comparison (MAIC) was conducted to indirectly compare efficacy of UPA vs UST.

Methods

Individual patient (pt)-level data from phase 3 UPA trials and published data from phase 3 UST trials were used. For induction, pts received UPA 45mg daily or PBO for 12 weeks or UST ~6mg/kg IV or PBO IV at week 0 with 8-week follow-up. For maintenance, UPA clinical responders were re-randomized to UPA 15mg, 30mg, or PBO daily for 52 weeks. UST clinical responders were re-randomized to 90mg SC (every 8 or 12 weeks) or PBO SC for 44 weeks. UPA pts had baseline (BL) CD Activity Index (CDAI) 220-450; those with prior UST or vedolizumab exposure were excluded. Treatment effect modifiers, including BL mean CDAI, Simple Endoscopic Score for CD (SES-CD), median C-reactive protein, prior biologic(s) failure, and disease location, from UPA data were weighted to match the UST population. Outcomes assessed were CDAI response (≥100-point decrease or CDAI <150), CDAI remission (CDAI <150), endoscopic response (SES-CD ≥50% decrease), and SES-CD ≤2. Separate MAICs were conducted for induction and maintenance; data reported for induction clinical outcomes are stratified by prior inadequate response to tumor necrosis factor inhibitors (TNFi-IR).

Results

A greater proportion of UPA- vs UST-treated pts achieved endoscopic response (difference 26.3%, P<0.001) and SES-CD ≤2 (difference 9.9%, P<0.05) at the end of induction. In TNF-IR patients, a greater proportion of UPA- vs UST-treated pts achieved CDAI response at the end of induction (difference 18.2%, P<0.05) and at the end of Week 8 (difference 26.0%, P<0.001). CDAI remission rates were also higher at end of Week 8 for UPA- vs UST-treated pts (difference 13.3%, P<0.05). Rates of achieving CDAI response and remission were similar between UPA- and UST-treated pts at the end of induction and Week 8 among bio-naïve pts. Following maintenance treatment, similar rates of SES-CD ≤2, endoscopic response, and CDAI remission were obtained in the total population of UPA and UST-treated pts.

Conclusion

Pts with moderately to severely active CD treated with UPA achieved higher rates of endoscopic (total population) and clinical (TNFi-IR population) outcomes during induction compared to UST-treated pts. Outcomes at the end of maintenance were similar for UPA and UST, however, results should be interpreted with caution due to low sample size.Read more P521 Impact of pouch leaks on quality of life and symptoms in patients after ileal pouch-anal anastomosis surgeryWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Ileal pouch-anal anastomosis(IPAA)is the procedure of choice in patients requiring total proctocolectomy.The reported leak rates after IPAA surgery range from 1-12% with well described significant impact on postoperative morbidity and recovery.However, the long-term impact of salvaged pouch leaks on the broader quality of life outcome and pouch function remains poorly understood.The aim of this study was to compare between patients with and without postoperative leaks after IPAA surgery, hypothesizing that patients with salvaged pouch leaks would have worse long-term quality of life and pouch function compared to matched patients without leaks.

Methods

This retrospective cohort study included patients who underwent IPAA(n=4058) between 1995-2022.Leak was defined as abscess or fistula requiring intervention, who had definitive resolution of their pouch leaks, whether with conservative treatment or after salvage surgery or pouch excision with end ileostomy creation. The Leak group consisted of 194 patients with treated leaks.The No Leak group included 963 patients without leaks,matched 1:5 on sex, age(± 3 years),and surgery date.Questionnaire data were available for 85 of 194 patients with leaks and 614 of 963 without leaks. Quality of life(QoL) was assessed using SF-36, health status using EORTC QLQ-C30(QoH),and life enjoyment(QoE) using a standardized scale.Bowel movements,seepage,and pad usage were recorded.Outcomes were compared using Mann-Whitney U,t-tests, and chi-square tests.

Results

A total of 699 patients with IPAA were included, with 85(12%)in the leak group. The median age was 42 (IQR, 31-53) years, and 54% were male. Median time from surgery to the last QoL assessment was 6.58(IQR: 3.5-11.3) years in the Leak group and 6.05 (IQR: 2.5-11.2) days in the No Leak group. Patients with Leaks reported significantly lower QoL (median 7(IQR:5-9)vs8 (IQR:7-9);p<0.001), lower health status on the QoH scale (median 7(IQR: 5-8) vs 8 (IQR :7-9); p<0.001), and lower life enjoyment on the QoE scale (median 7(IQR: 5-8)vs7(IQR :6-9);p=0.003) compared to the No Leak group. A higher proportion of patients in the Leak group reported daytime (49%vs.20%,p<0.001) and nocturnal seepage (66%vs.38%, p=0.001), along with greater daytime(40%vs.22%,p=0.01) and nighttime pad usage (53%vs.30%,p=0.001). There were no significant differences in the number of bowel movements per 24h (p=0.54), daytime bowel movements(p=0.7), or nighttime bowel movements (p=0.695) between the groups.

Conclusion

In matched cohorts,salvaged pouch leaks were associated with reduced quality of life,health status,and life enjoyment compared with matched patients without leaks.Patients with leaks also had increased rates of seepage and pad usage,indicating worse pouch function.Read more P851 Therapeutic drug monitoring of infliximab and adalimumab versus clinical control during maintenance therapy in patients with Inflammatory Bowel DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Although it is known that the levels of infliximab or adalimumab are correlated with clinical response, there is controversy about the best strategy to follow in patients with Inflammatory Bowel Disease (IBD) in remission and undergoing maintenance treatment.

Methods

We conducted a randomized, prospective, single-blinded, and multicentre trial in patients with Crohn’s Disease (CD) or Ulcerative Colitis (UC) who have remained in clinical remission for at least 12 weeks and are receiving adalimumab (ADA) or infliximab (IFX) as maintenance treatment. Patients were assigned to two groups. In the first group, patient management was done considering therapeutic drug monitoring (TDM). In the second, according to usual clinical practice (CP). The optimal serum range was within 3-7µg/ml and 5-8µg/ml for IFX and ADA respectively, based on the use of Promonitor-IFX, and Promonitor-ADL kits. The primary endpoint was to maintain patients in clinical remission (target >16% between both groups at 12 months) and diminish the frequency of flare-ups.

Results

In total, 209 patients were randomized, 29 UC (27.6%), 76 CD (72.4%) as the clinical practice group, and 24 UC (23.1%), 80 CD (76.9%) as the drug monitoring therapeutic group.Infliximab was administered in 105 patients and adalimumab in 104. Remission at the end of the study was achieved in 98.1% of the proactive dosing group and 90.5% of the clinical practice group (p=0.02), with a difference between both groups of 7.6%. The number of flare-ups was 1.3/10 patient-years in the TDM group and 2.4/10 patient-years in the CP group. The IRR of flare-up throughout the study was 0.71 (95% CI 0.32 – 1.55). In the group with IFX: IRR = 0.56 (95% CI 0.08 – 3.81) and with ADA: 0.78 (95% CI 0.29-2.16). The changes made in the drug dose are shown in Table 1.

Conclusion

Differences were found in favour of the TDM group, with increasing remission rates (7.6%) and half number of flare-ups. However, the pre-established effectiveness remission target (16%) was not met.In the subgroup of patients with Infliximab, management through TDM seems to have an advantage over usual clinical control.Read more P522 Post hoc analysis reveals limited efficacy of induction therapy in ileum only Crohn´s diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Crohn´s disease (CD) can affect any part of the GI tract, although has a predilection for the terminal ileum and colon. Approximately 30% of patients have inflammation restricted to the small intestine, another 30% have disease limited to the colon, and the remainder have a combination of small and large bowel involvement. Despite studies suggesting that ileal and colonic CD may be distinct disease phenotypes and might therefore respond differently to treatment, CD patients are typically enrolled into clinical trials irrespective of the site of gastrointestinal involvement. The aim of this systematic review and meta-analysis was to assess treatment efficacy in patients with small bowel disease.

Methods

Embase and PubMed databases were searched until October 2023 for randomised, placebo-controlled, clinical trials that reported induction efficacy, based on clinical remission (CDAI <150), in ileal-only Crohn’s disease between 2010 and 2023. The following search criteria were employed: Crohn´s disease AND [2010-2023] AND (small bowel OR ileum OR ileal OR L1) AND (CDAI OR clinical remission AND induction AND placebo). Additional studies, not identified through this search strategy were also considered. Resultant studies were systematically reviewed before a random-effects meta-analysis was undertaken to assess induction efficacy, based on clinical remission, in ileal only CD.

Results

A total of 9 studies, involving 709 adult patients, were identified: two via Embase and PubMed; six from supplementary search materials; and one post-hoc analysis of brazikumab data (not published). The studies provided CDAI remission results by disease location subset. The induction treatment times ranged from 6-12 weeks, and both bio-naïve and bio-failure patients were included. The studies were relatively homogenous (I2 = 38.5%, Q = 13.0 (p-value = 0.112)) with a random effect meta-analytic estimate of difference versus placebo in CDAI remission of 2.1% (95% CI -6% to 11%). Two studies used clinical response (defined as ≥ 100 point decrease or score < 150) as indicated in the figure.

Conclusion

This is the first systematic meta-analysis of treatment effects in ileal-only CD. The available evidence suggests treatment effect heterogeneity, with inferior outcomes in ileal disease versus a broader patient population with ileocolonic or colonic involvement. Previous systematic review1 on clinical remission after induction treatment demonstrate placebo adjusted values in the range of 12-20% in a no defined disease site population. This indicates the need for novel therapies with a mechanism of action directly tailored to heal the small intestine in patients with CD.Read more P1041 Coconut water modulates dietary potassium and gut microbiome to induce remission in ulcerative colitis: randomized controlled trialWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

High potassium intake is associated with decreased risk of inflammatory bowel disease(IBD), urinary potassium has been correlated with disease activity in ulcerative colitis(UC), and gut microbiome modulation improves outcomes in UC. We evaluated coconut water as potassium rich diet and gut microbiome modulator in patients with mild-moderate UC.

Methods

This single-center double-blind placebo-controlled trial randomized patients with mild-moderate (simple clinical colitis activity index-SCCAI:3–9) endoscopically active UC (ulcerative colitis endoscopic index of severity-UCEIS>1) in 1:1 ratio to coconut water + standard medical therapy-SMT(CW) vs placebo + SMT. 400ml of coconut water (200-250mg potassium/100ml) was administered for 8 weeks. Primary outcome measure was clinical remission (SCCAI ≤ 2) and secondary outcome measures were clinical response (SCCAI decline ≥ 3) and adverse events at 8 weeks. Microbiome was analyzed at baseline and 8 weeks.

Results

Of 121 patients screened, 95 were included for modified intention to treat analysis(49-CW, 46-placebo)[mean age-37.2 ± 11.2years; males-54.1%; disease duration-48 (IQR:24–90) months; pancolitis - 26.1%; SCCAI-5 (IQR:4 – 6); UCEIS-4 (IQR:3 – 5)]. There was significant increase in dietary potassium and decline in sodium/potassium ratio at 8 weeks in CW. Clinical response [57.1% vs 28.3%, p=0.01, OR-3.4 (95%CI:1.4 – 7.9)], remission [53.1% vs 28.3%, p=0.02, OR-2.9(95%CI:1.2 – 6.7)] and proportion of patients with fecal calprotectin (FCP)<150μg/g [53.6% vs 14.3%, p=0.01, OR-6.9(95%CI:1.6 – 28.9)] were significantly higher in CW. The relative abundance of bacterial taxa which had a significant or trend towards negative correlation with SCCAI, UCEIS, or FCP, increased at 8 weeks in CW. Adverse events were comparable and no patient developed hyperkalemia.

Conclusion

Coconut water increased dietary potassium, modulated the gut microbiome and was more effective than placebo for induction of remission in mild-moderate UC.Read more P852 Metataxonomic and metabolomic profiling to predict response to anti-TNF therapy in Crohn’s DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The composition of the gut microbiota is associated with response to treatments in inflammatory bowel disease¹. We sought to identify gut microbial and metabolomic biomarkers associated with response to anti-TNF therapy in Crohn’s disease.

Methods

Faecal and serum samples collected at baseline and week 14 of anti-TNF treatment in the "Predictors of anti-TNF treatment failure" (PANTS) study were used². Response to treatment (defined clinically and biochemically) was determined at week 14². Faecal samples were processed by GA-map^®, with targeted 16S rRNA PCR sequencing. Serum samples were analysed with targeted liquid chromatography tandem mass spectrometry for bile acids and tryptophan metabolites. Multivariate and univariate analyses, as well as Spearman’s rank test, were performed.

Results

Two-hundred and twenty-four patients with Crohn’s disease commencing anti-TNF therapy were included (54.1% anti-TNF responders, 48.6% female, median age 37.2 (26.5-50.0) years, 56.9% receiving immunomodulator-based treatment). A significantly higher proportion of non-responders received corticosteroid treatment compared to responders at baseline (p=0.0009).Sixty-nine bacterial taxa were identified. Significantly lower abundances of Clostridium difficile and Mycoplasma were identified in responders relative to non-responders at baseline (q-value=0.046 and q-value=0.034, respectively). No significant differences in the abundances of Faecalibacterium prausnitzii, Shigella or Escherichia Coli were found (all q-values > 0.05).Eighteen serum bile acids and thirteen tryptophan metabolites were identified. Significantly higher serum abundances of cholic acid, tryptophan and 3OH-kynurenine were identified in responders at baseline (q-values=0.049, 0.033, and 0.033, respectively). Exploration of microbial–metabolite associations revealed negative correlations between secondary bile acids and several bile salt hydrolase producing bacteria, such as Bifidobacterium (r ≤ -0.50). Positive correlations were also identified between xanthurenic acid and Bifidobacterium and Roseburia intestinalis (r ≥ 0.50). Increased abundances of short-chain fatty acid producing bacteria, such as Bifidobacterium and Bacteroides vulgatus, were noted in responders at week 14.

Conclusion

We have identified baseline differences in the faecal microbiota and serum metabolome of anti-TNF responders and non-responders. These findings require validation in larger cohorts to determine their robustness for potential use in treatment personalisation.References1. Radhakrishnan S. et al., Alimentary pharmacology & therapeutics vol. 55,1 (2022): 26-48. 10.1111/apt.16656.2. Kennedy N. et al., The Lancet. Gastroenterology & Hepatology vol. 4,5 (2019): 341-353. 10.1016/S2468-1253(19)30012-3.Read more P523 The performance indicator of colonic intubation (PICI) in an Irish Inflammatory Bowel Disease (IBD) cohortWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Comprehensive assessment of endoscopic disease activity and mucosal healing is central to therapeutic decision making in IBD. Data suggests that IBD patients may have a poorer experience of endoscopy with a higher burden associated with bowel preparation, higher GI specific anxiety and increased procedure related pain. Existing KPIs may be inadequate in capturing appropriate patient outcomes in IBD patients. PICI is a novel composite endpoint incorporating patient safety and comfort to ensure targets are met without compromising patient safety.

Methods

The aims of this study were to assess the safety, tolerability, and feasibility of colonoscopy in patients with IBD compared to non-IBD patients in Ireland using PICI, defined as successful caecal intubation with nurse assisted comfort score ≤3 and midazolam dose ≤2. We reviewed de-identified national endoscopy procedure data on all colonoscopies performed over a 6 year period in 24 hospitals nationally using the EndoRAAD reporting system. Procedures were categorised into IBD and non-IBD procedures on the basis or procedure indication (IBD surveillance or assessment) or a new diagnosis of IBD.

Results

Procedure data from 261,889 colonoscopies from 2014-2020 were analyzed (IBD: n=18,675; non-IBD: n=243,214 procedures). The Odds Ratio (OR) of achieving PICI was significantly lower in IBD patients compared to non-IBD patients, particularly in patients with Crohn’s Disease (0.74, 0.68-0.81, p<0.001). Male gender was associated with a significantly higher OR of achieving PICI (1.32 (1.29-1.35, p<0.001). Poor bowel prep was associated with reduced PICI (OR 0.78, p<0.001). Additionally, procedures performed by supervised trainees had significantly reduced PICI (OR 0.69, p=0.032). The extent of colonic inflammation had no significant impact on PICI in IBD patients (OR moderate and severe inflammation 1.08 (p=0.66); and 1.06 (p=0.79) respectively). Mean procedure time was slightly longer for IBD patients (28.7 min versus 26.7 min, p<0.001), with 91.1% of IBD patients having mucosal biopsies compared to only 26.3% of non-IBD patients (p < 0.001).

Conclusion

This large retrospective cohort study utilises the novel composite measure of PICI to assess the safety, tolerability, and feasibility of colonoscopy in IBD patients compared to non-IBD patients. We have identified significantly poorer comfort scores and higher sedation rates required to achieve caecal intubation at colonoscopy in IBD patients, particularly in patients with Crohn’s Disease. Further exploration is required to identify factors to improve the safety and quality of endoscopy in IBD patients.Read more P622 Network meta-analysis comparing efficacy between biologics and conventional therapies to prevent endoscopic postoperative recurrence in patients with Crohn's diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

As no direct comparison between IBD drugs to prevent endoscopic postoperative recurrence (POR) In Crohn’s disease (CD) are available, hierarchizing these therapeutic options remains challenging.The objective of this network meta-analysis was to compare the effectiveness of treatments to prevent endoscopic POR of CD.

Methods

We performed a systematic review and network meta-analysis of comparative studies conducted in adults, evaluating a treatment to prevent endoscopic POR after ileocecal resection. The selection of studies was made according to PRISMA guidelines. The primary endpoint was endoscopic POR at 6 months defined as Rutgeerts score ≥ i2.The network meta-analysis was carried out according to a random effects model. The results are presented as odds ratio (OR) with 95% confidence interval, adjusted for risk factors of POR. The risk of bias of the studies was assessed according to the Cochrane risk-of-bias tool for randomized trials and overall statistical heterogeneity between studies was assessed using τ². The SUCRA ranking method (surface under the cumulative ranking) was used to rank the treatments.

Results

Twenty studies were included in this network meta-analysis, including a total of 2414 patients. Overall heterogeneity was moderate (τ²=0.34). After adjustment for POR risk factors, ustekinumab (OR = 0.23 [0.07-0.70]), vedolizumab (OR = 0.17 [0.05 -0.59]), infliximab (OR = (0.18 [0.36-0.88]) and adalimumab (OR = 0.17 [0.07-0.42]) were superior to placebo to prevent endoscopic POR, contrary to 5-ASA (OR = 0.79 [0.42 -1.48]) and thiopurines (RR = 0.52 [0.22-1.24]) (Table 1).Ustekinumab (OR = 0.29 [0.08-0.99]), vedolizumab (OR = 0.22 [0.06-0.85]), infliximab (OR = (0.23 [0.09-0.54]) and adalimumab (OR = 0.22 [0.08-0.59]) were more effective than 5-ASA in preventing endoscopic POR. Adalimumab (OR = 0.33 [0.15-0.74]) and infliximab (OR = 0.34 [0.13-0.87]) were also more effective than thiopurines. We observed no difference in efficacy between the 4 biologics (infliximab, adalimumab, ustekinumab and vedolizumab) (Table 1).The SUCRA ranking identified adalimumab (SUCRA=0.81), infliximab (SUCRA=0.80), vedolizumab (SUCRA=0.79) and ustekinumab (SUCRA=0.72) as the most effective treatments. The likelihood that thiopurines (SUCRA=0.41), 5-ASA (SUCRA=0.24), placebo (SUCRA = 0.16) and antibiotics (SUCRA=0.08) was the best option is very low.

Conclusion

This network meta-analysis confirms the efficacy of anti-TNF agents, vedolizumab and ustekinumab in preventing endoscopic CD POR without any difference between them. When prophylactic therapy is necessary, biologics appear as the best therapeutic option to prevent of endoscopic POR. Due to lower efficacy, the use of 5-ASA and thiopurines should be limited in this situation.Read more P872 PREDICT UC: Optimising Infliximab Induction therapy for Acute Severe Ulcerative Colitis – A Randomised Controlled TrialWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The optimal dosing strategy of infliximab (IFX) in Acute Severe Ulcerative Colitis (ASUC) is unknown. We compared intensified and standard dose IFX strategies in ASUC.

Methods

In this open-label randomised trial (NCT02770040), patients from 13 Australian centres with intravenous steroid-refractory ASUC were randomised to receive a first dose of 10mg/kg or 5mg/kg IFX in a 1:2 ratio. Patients in the 10mg/kg group (intensified induction [II]) received a second dose at day 7 or earlier at time of non-response; all 5mg/kg patients were re-randomised 1:1 to standard (SI) or accelerated induction (AI), which produced three induction groups: II, SI and AI. SI patients received 5mg/kg at week 0, 2 and 6, with an extra 5mg/kg dose before day 7 if non-response. AI patients received 5mg/kg at week 0, 1 and 3, with the week 1 dose increased to 10mg/kg and given earlier if non-response. Primary outcome: clinical response by day 7 (reduction in Lichtiger score to <10, with decrease of ≥3 points and improvement in rectal bleeding and stool frequency to ≤4/day). Secondary outcomes compared induction regimens until month 3. Analysis was by intention to treat.

Results

Between July 2016 & September 2021, 138 patients were randomised; 46 received a first IFX dose of 10mg/kg and 92 received 5mg/kg. Primary outcome: day 7 clinical response was observed in 65% (30/46) of 10mg/kg vs 61% (56/92) of 5mg/kg patients (P=0.76). In the 5mg/kg group, the rate of day 7 response was numerically lower in those with albumin <25g/L vs ≥25g/L [47% (15/32) vs 68% (41/60), P=0.07]. No difference in clinical response was observed in the 10mg/kg group when stratified by albumin [64% (9/14) vs 66% (21/32) P>0.99]. There was no difference in time to clinical response, change in Lichtiger score or CRP from baseline to day 7. Two patients who received 10mg/kg IFX underwent colectomy in the first 7 days vs 0 in the 5mg/kg group (P=0.21). Comparison of induction regimens (II, SI & AI): no difference in clinical remission rates between weeks 2 and 6 were observed. AI and II groups had higher rates of combined clinical and biochemical remission compared to SI between weeks 2 and 6 (P=0.042). At 3 months, there was no difference in rates of endoscopic and steroid-free remission, as well as rates of colectomy (II 7%; SI 12%; AI 19%, P=0.20).

Conclusion

In steroid-refractory ASUC, a first dose of 10mg/kg or 5mg/kg IFX achieved similar clinical response rates by day 7. Patients receiving intensified or accelerated induction achieved clinical and biochemical remission earlier compared to standard induction; however, outcomes at three months were similar. Patients with a lower albumin may benefit from proactive intensified dosing strategies.Read more P517 Endoscopic mucosal resection (EMR) in treatment of colitis associated neoplasia (CAN): a single-centre experience from Leuven, BelgiumWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Endoscopic resection has been recommended as preferable therapeutic approach for colitis associated neoplasia (CAN) in inflammatory bowel disease (IBD) patients. However, endoscopic resection of these lesions can be challenging due to ongoing inflammation, mucosal scarring, and submucosal fibrosis. We report long-term, single centre experience on performance of endoscopic mucosal resection (EMRs) for treatment of CANs .

Methods

Hospital electronic database was searched in order to identify all the patients diagnosed with CANs in period 01.01.2009-30.09.2023. Data on the lesion characteristics, therapeutic approach, treatment outcomes and follow-up were collected and used for the descriptive analysis.

Results

During the study period 32 CANs have been treated with EMR in 19 patients. Mean diameter of the lesion was 18.2±9.09mm (8-50mm). Nine lesions were removed en-bloc (28.1%) while 23 (71.9%) were removed piece meal. One EMR (3.1%) was associated with post-procedural bleeding, which was treated endoscopically by the use of caograsper. Another 2 EMRs (6.2%) were associated with intraprocedural perforations which were resolved by placement of the endoclips. Histopahtological examination disclosed adenomas with low grade dysplasia in 19 lesions (59.4%), adenomas with high grade dysplasia in 7 lesions (21.9%), sessile serrated lesion with high grade dysplasia in one lesion (3.1%) and sessile serrated lesion without dysplasia in 4 lesions (12.5%). One lesion (3.1%) was identified as adenocarcinoma with deep submucosal invasion and patient was referred to surgery. All the other patients were subjected to follow-up, during which 4 cases of local recurrence at the site of resection were observed (12.5%), of which 3 were treated with new EMR while one was referred to surgery. Apart from recurrent lesions, six metachronous CANs were observed during the follow-up in 3 patients (15.8%), all removed by EMR and included in this analysis. All together 2 out of 19 patients (10.5%) included in the study underwent colorectal surgery for CAN treatment.

Conclusion

EMR appears to be safe and effective in treatment of CANs, both in terms of short and long-terms outcomes, as well as need for additional colorectal surgery.Read more P636 Comparison of the real-world efficacy of filgotinib with tofacitinib in patients with refractory ulcerative colitis: A single-center retrospective studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Several Janus kinase inhibitors have recently been launched for the treatment of ulcerative colitis (UC). However, there are few reports comparing the efficacy and safety of each drug in patients with refractory UC, especially with filgotinib (FIL), which was recently launched and can be concomitantly used with thiopurines. We herein aimed to compare the real-world efficacy and safety of tofacitinib (TOF) and FIL in induction therapy for patients with refractory UC.

Methods

Patients with refractory UC, who received either TOF 20mg/day or FIL 200mg/day from May 2018 to October 2023 in Hyogo Medical University Hospital were included in this study. Primary outcomes were clinical response rates at 2, 4, and 8 weeks after administration of TOF or FIL. Clinical response was defined as a decrease of partial Mayo Score (pMS) of ≥2 from baseline and rectal bleeding subscore is ≤1 or a decrease of ≥1 from baseline. Secondary outcomes were cumulative incidences of adverse events during the observation period.

Results

Of the 230 refractory patients with UC, 197 received TOF and 33 received FIL treatment. The median age was 37 [IQR 27–49] and 49 [33–54] years, and the median disease duration was 3 [1–10] and 5 [2–10] years, respectively. Median durations of observation were 118 [52–188] weeks in the TOF group and 41 [29–60] weeks in the FIL group, median baseline pMS were 6 [5–7] and 5 [5–6], and serum CRP levels were 3.8 [1.3–12.3] and 1.8 [0.3–3.3] mg/L, respectively. Thirty-eight (19.3%) patients in the TOF group and 3 (9.0%) patients in the FIL group received systemic steroids, and 8 (24.2%) in the FIL group received thiopurine at baseline. The clinical response rates at 2, 4 and 8 weeks were 58.4%, 59.4% and 62.9% in the TOF group, and 42.4%, 57.6% and 48.9% in the FIL group, respectively, and the rate tended to be higher in the TOF group than in the FIL group at 2 weeks (p = 0.092). Of the patients who did not respond at 4 weeks, the TOF group had a significantly higher clinical response rate (31.3%) than the FIL group (0%) at 8 weeks (p = 0.032). Among 124 patients with prior anti-TNF-α antibody failure, 59.6% (65/109) of patients in the TOF group and 46.7% (7/15) in the FIL group achieved comparable clinical responses at 8 weeks (p = 0.407). Fifteen of 197 (7.6%) patients in the TOF group and 2 of 33 (6.1%) in the FIL group did not continue treatment until 8 weeks due to adverse events, but there were no significant differences between the groups.

Conclusion

Even in patients without a response for up to 4 weeks, TOF treatment may provide a higher clinical response than FIL treatment at 8 weeks.Read more P882 A Phase I/II clinical trial of ex-vivo expanded human bone marrow derived allogeneic mesenchymal stromal cells in adult patients with perianal fistulizing Crohn’s DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Perianal fistulas affect one-third patients with Crohn’s disease with limited therapeutic options. There is dearth of literature on safety and efficacy of bone marrow-derived mesenchymal stromal cells in this population.

Methods

An open-label, phase I/II, single-arm study was conducted involving local administration of human allogeneic bone marrow-derived mesenchymal stromal cells in perianal fistula of patients with Crohn’s disease refractory to standard therapies. Clinical severity and biomarkers were assessed at baseline and periodically till 104 weeks, and MRI at 24 and 104 weeks. Primary and secondary objectives were to assess safety and efficacy respectively. Fistula remission was complete closure of fistula openings with <2cm perianal collection on MRI, and fistula response was decrease in drainage by ≥50%. Change in perianal disease activity index, quality-of-life and Van Assche index on MRI over time was assessed using mixed-effect linear regression model.

Results

Ten patients (male:8, mean age:27.4±12.0years) were recruited. Self-resolving procedure-related adverse events occurred in three patients, with no follow-up adverse events. In intention to treat analysis at week 24, two patients (20%) achieved fistula remission and seven (70%) had fistula response. At week 52, two (20%) patients were in remission and seven (70%) maintained response. At 104 weeks, two (20%) patients maintained response and one (10%) was in remission. Statistically significant decrease in perianal disease activity index(P=0.008), Van Assche Index(P=0.008) and improvement in quality-of-life(P=0.001) were observed over time.

Conclusion

Allogeneic BMSCs are safe and effective for the treatment of PF in CD with significant improvement in clinical severity and radiological healing.Read more P518 Dietary and non-dietary predictors of treatment response to adalimumab in anti-TNFα-naïve adults with Crohn’s diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Biologics, such as anti-TNFα agents, are commonly used in the management of Crohn’s disease (CD). A significant proportion of patients do not respond to treatment, necessitating the exploration of pre-treatment predictors of treatment response.

Methods

Anti-TNFα-naïve adults with active CD (Crohn’s Disease Activity Index; CDAI≥150) participating in an RCT (NCT04859088) were randomised to receive adalimumab monotherapy or adalimumab combination therapy with 50% partial enteral nutrition (PEN). Treatment response (CDAI<150) was assessed after 6 weeks, baseline diet was assessed with EPIC-Norfolk FFQ, alternative Mediterranean diet scores (aMED), and principal component analysis (PCA) with orthogonal (varimax) rotation was used to identify data-derived dietary patterns. Baseline predictors evaluated included PEN use, steroid use, immunomodulator use, age, disease duration, CDAI, C-Reactive protein (CRP), albumin, haemoglobin, Scottish Index of Multiple Deprivation (SIMD) score, adherence to dietary patterns identified, aMED score, smoking status, alcohol consumption, physical activity level, body mass index (BMI), fat mass (kg/m²), fat-free mass (kg/m²), and handgrip strength. Differential analysis between responders and non-responders was carried out with general linear model or chi-square test when appropriate. Random forest model with recursive feature elimination (RF-RFE) was used to identify the most predictive factors of treatment response.

Results

Of 42 participants recruited to the study, 62% (26) responded to treatment. PCA revealed four dietary patterns (Figure 1A). Responders to adalimumab were younger (mean (SD): 36.0 (17.1) vs 50.8 (10.0), P=0.004), had lower baseline CDAI (mean (SD): 228 (62) vs 286 (78), P=0.018), higher CRP (14.5 (19.2) vs 4.6 (5.8) mg/L, P=0.036), were less likely to smoke (31% (5 of 16) vs 8% (2 of 26), and less likely to adhere to a dietary pattern characterised by high consumption of animal products (PC2) (P=0.030). Adherence to PC2 also correlated positively with age (r=0.327, P=0.035). The RF-RFE algorithm highlighted young age, low baseline CDAI and low PC2 adherence as key factors (Sensitivity: 77%, Specificity: 63%, PPV: 77%, NPV: 63%, OOB: 29%, P=0.012) (Figure 1B). Interestingly, exclusion of dietary factors improved diagnostic performance of the model (Sensitivity: 77%, Specificity: 75%, PPV: 83%, NPV: 67%, OOB: 24%, P=0.003) (Figure 1C), indicating potential interactions by other factors like age.

Conclusion

Young age, non-smoking, low baseline CDAI and elevated CRP predict adalimumab response in anti-TNFα-naïve adults. While dietary factors may also play a role, their impact seems confounded by other non-dietary factors. Further research is warranted in this area.Read more P892 Do anti TNF alpha drugs reduce cardiovascular risk in Crohn's disease ?Wed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

We now know that Crohn's disease (CD) is characterised by a higher cardiovascular risk, despite the low frequency of traditional risk factors. Arterial stiffness (AS) and its relationship with chronic inflammation seem to explain this paradox. Given that inflammation plays an important role in AS, reducing it should make it possible to reduce this stiffness. This led us to evaluate the effect of anti TNF alpha on AS

Methods

This was a prospective observational study involving 118 patients with CD, 63 of whom were taking anti TNF alpha (Adalimumab, Infliximab). AS was assessed by pulse wave measurement (aPWV) using a validated Sphingmocor Syndney device at the time of recruitment and during patient follow-up. Statistical analysis was performed using SPSS statistical software and Student's t-test for paired samples.

Results

The mean age was 37 years [19-67], sex ratio = 1.5, 22.2% were active smokers, 62.9% of patients were in a flare and 43.3% had had at least two relapses in the year prior to recruitment, median duration of disease was 30 months. The mean duration of follow-up was 9 months [6-24]. The reduction in aPWV was highly significant for patients on anti-TNF alpha therapy, whether with flexible or rigid arteries: the mean aPWV was 7.67+/-1.4 vs 7.08+/-1.07 for patients on anti-TNF alpha therapy, with a p=2*10^-5. The aPWV was 8.49+/-1.07 vs 7.42+/- 0.44 for patients with rigid arteries with a p= 3*10^-4.

Conclusion

Treatment with Anti TNF alpha appears to slow down aPWV in Crohn's disease, and may therefore be a good way of reducing the cardiovascular risk and the risk of developing cardiovascular disease in Crohn's disease.Read more P644 Body composition does not predict clinical course in patients with acute severe ulcerative colitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Acute Severe Ulcerative Colitis (ASUC) is a life-threatening complication of UC. Previous research has shown that body composition parameters, including sarcopaenia, are associated with outcomes in IBD. However, the relationship between body composition and the clinical outcomes of patients hospitalised with ASUC has not yet been clearly defined. We sought to further evaluate the prognostic role of body composition and further explore predictors of clinical outcome in ASUC.

Methods

We performed a cohort study of hospitalised ASUC patients. Body composition was assessed using fat and muscle segmentation, at the level of the L3 vertebral body, in patients who underwent abdominal computed tomography (CT) during hospitalisation. We defined sarcopenia according to skeletal muscle index (SMI) < 38 cm²/m² in females and < 42 cm²/m² in males. Clinical endpoints included length of hospitalisation, need for rescue medical therapy or colectomy. Between group comparisons were performed and logistic regression was used for risk factor analysis.

Results

We studied 116 patients with ASUC, 51 of whom underwent abdominal CT imaging during their hospitalisation. Median age was 32 years and 64% of patients were female. Sixty-two patients (53.5%) required rescue medical therapy. Rescue medical therapy was successful in 48 patients (77.4%) and 14 patients (22.6%) required an inpatient colectomy. Patients who underwent CT imaging during admission required increased rescue medical therapy (66.7% vs 43.1%, p=0.02) and were hospitalised for longer (11 vs 6 days, p<0.001). Compared to non-sarcopaenic patients, sarcopaenic patients did not require increased rescue medical therapy (60.7 % vs 79 %, p= 0.22) nor longer median hospitalisation (10.5 vs 11.4 days, p=0.69). We observed a trend towards increased rescue therapy failure in patients with sarcopaenia (52.9% vs 33.3%, p=0.31). Higher Mayo score at presentation was associated with increased need for rescue medical therapy (OR 2.18, 95%CI: 1.43-3.33, p<0.001) and an increasing C-reactive protein (CRP) to albumin ratio predicted prolonged length of stay (OR 1.44, 95%CI: 1.18-1.77, p=<0.001).

Conclusion

Sarcopaenia did not predict ASUC outcomes in this cohort. Higher Mayo score and increased CRP to albumin ratio at admission predicted prolonged hospitalisation and need for rescue medical therapy.Read more P470 Crohn’s disease patients with Ustekinumab-induced remission are characterized by high baseline p35 cytokines subunits in LPMC and high IL-23 receptor expression in the lamina propria Th1 cellsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Crohn’s disease (CD) is a chronic relapsing disorder of the gastrointestinal tract characterized by excessive inflammation sustained by the induction and expansion of Th1 and Th17 cells. Ustekinumab (UST), a fully humanized monoclonal antibody, is currently used for the therapy of CD patients. It acts by neutralizing both IL12 and IL23, essential for the maturation and expansion of Th1 and Th17 cells, by binding the common subunit p40. To be effective UST needs, in addition to the expression of target cytokines, the presence of cells responsive to IL12 and IL23, thus cells with IL12 and IL23 receptors.

Methods

This is a prospective, observational, single-center open-label study. All CD patients with clinical indications to receive UST for active luminal disease were enrolled. Patients had baseline endoscopy to confirm disease activity by SES-CD and to collect biopsies to isolate LPMC. Real-time pcr was performed to evaluate IL12 (p40 and p35) and IL23 (p40 and p19) cytokines subunits and IL12 (IL12Rb1 and IL12Rb2) and IL23 (IL12Rb1 and IL23R) receptors subunits expression in remitters (R) and not remitters (NR). Moreover, LPMCs were analyzed by flow cytometry, and IL12Rb2 and IL23R expression in Th1, Th17, and type 1 Innate lymphoid cells (iLC) cells were evaluated. Results were analyzed for clinical remission status (HBI<5) at week 16. Differences between groups were analyzed by Mann-Whitney test and statistical significance was considered for p<0.05.

Results

From April 2019 to November 2022, 13 CD patients were enrolled, whose clinical and demographic characteristics are enclosed in Table 1. At baseline there was no difference in IL12Rb2, ILRb1, and IL23R expression between R and NR (Fig.1). Regarding cytokines subunits, there was no difference in p19 but there was a significantly higher expression of p35 subunits in R than in NR (mean 1,52 vs 0,34; p=0,001) (Fig.1). Flow cytometry showed no difference in Th and ILCs subgroups frequency between R and NR. IL12Rb2 and IL23R were also equally expressed by Th17, Th1/Th17 and ILC1 cells in the two groups. In contrast, Th1 cells, IL23R expression was higher in R group as compared to NR (mean 20,6% vs 6,8; p=0.009) (Fig.2).

Conclusion

In CD patients treated with UST, higher expression p35 in LPMC and higher expression of IL23R in the lamina propria Th1 cells was associated with remission at week 16.Read more P900 A PROOF-OF-CONCEPT, PLACEBO-RANDOMIZED CONTROLLED TRIAL TARGETING ADHERENT AND INVASIVE ESCHERICHIA COLI (AIEC) WITH ANTIBIOTICS IN CROHN’S DISEASE: the TEOREM TRIALWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Adherent-invasive E. coli (AIEC) are found in the ileal mucosa of 21-63% of patients with ileal Crohn’s disease (CD) vs 0-16% of controls. This trial tested the efficacy of antibiotics targeting AIEC in CD patients with ileal involvement, colonized by AIEC.

Methods

Eligible patients had endoscopically active (CDEIS ≥8) ileal or ileocolonic CD and either a clinically inactive, or mild to moderately active disease that responded to budesonide or prednisolone. AIEC search was performed on ileal biopsies, by phenotypical assays. The primary endpoint was the endoscopic overall response at week 12, defined as segmental response in at least 1 segment, and < 20% increase of CDEIS in other segments. Segmental response was defined by decrease ≥ 50% of surface of ulcerations, or loss of deep ulcerations (if any). Secondary endpoints were ΔCDEIS ≥ 50% in at least 1 segment with CDEIS ≥ 8 at baseline, and remission (CDEIS < 6 in all segments). Endoscopic endpoints were assessed by a central, anonymous and blinded scoring of video recordings of colonoscopies at preinclusion and week 12. Patients were randomized 1/1 between oral Ciprofloxacin 500 mg bid + Rifaximin 800 mg bid and double placebo for 12 weeks. In this subgroup of patients selected for AIEC colonization, we were in search of a strong signal of efficacy. We hypothesized that 60% of patients in the experimental arm and 25% of those in the placebo arm would reach the primary endpoint. 31 patients in each arm were planned to demonstrate such a difference.

Results

Between May 2016 and June 2021, 155 patients were screened, of whom 91; 27 were AIEC positive and 24 patients (12 in each arm) were randomized in 10 centres. 17 patients had a clinically active disease. All AIEC strains of randomized patients were sensitive to ciprofloxacin and rifaximin. Clinical and endoscopic characteristics were similar in the 2 arms. 2 patients did not have colonoscopy at week 12 (1 tendinitis and 1 had no colonoscopy during the COVID pandemic). 7/10 patients cleared AIEC at week 12 in the experimental arm, vs 6/12 in the placebo arm. The 3 patients who received antibiotics and remained AIEC+ after antibiotics acquired resistance to ciprofloxacine. Results are displayed in the table. There was no association between AIEC clearance and endoscopic endpoints. A Bayesian, post hoc analysis showed that the probability to obtain a 35% difference in the primary endpoint between the two arms of the trial was of 25%.

Conclusion

Antibiotics were not statistically superior to placebo to achieve endoscopic response and remission in patients with ileal CD colonized with AIEC. There was no association between AIEC clearance and endoscopic endpoints. Differences were numerically in favour of antibiotics.Read more P471 Tight control strategy improves combined histologic and endoscopic remission in ulcerative colitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Increasing evidence suggests that combined histological and endoscopic remission associates with less adverse outcomes (hospitalization and corticosteroid therapy) and predicts a quiescent course of ulcerative colitis (UC). However, few patients can achieve this target with the drugs currently available. A tight control strategy with a proactive treatment escalation based on biomarkers may improve these results.

Methods

Retrospective, single-center cohort study including consecutive patients with UC with severe endoscopic disease (Mayo endoscopic subscore=3) and subsequent endoscopic, histologic and faecal calprotectin (FCP) evaluation. Data concerning demographic, disease phenotype, laboratory findings and treatment were collected. We defined tight control strategy as therapeutic escalation in >50% of cases where FCP≥250ug/g. Therapeutic escalation was defined as the start, switch or dose increment/interval shortening of biologic therapies/small molecules. Endoscopic remission was defined as a Mayo endoscopic subscore ≤1. Histologic remission was defined as the absence of ulcers, erosions and neutrophils in the lamina propria.

Results

One hundred and seven patients were included, 56.0% male and 63.6% with extensive UC. Thirty-four patients (31.8%) were included in the tight control group. During follow up, 52 patients (48.6%) achieved endoscopic remission, 29 (27.1%) histological remission and 27 (25.1%) combined remission. Patients in the tight control group achieved combined remission more frequently (38.2 vs 19.2%, P=0.05). On multivariate analysis including age at diagnosis, duration and extension of disease and therapy received, a tight control strategy was independently related to a higher probability of combined remission: OR 2.768 IC95% 1.056-7.255, P=0.038.

Conclusion

A tight control strategy based on FCP was associated with higher combined histological and endoscopic remission in UC.Read more P660 Serum Leucine-rich Alpha-2 Glycoprotein Can be a Biomarker for Selecting Anti-Cytokine Biologics in Patients with Inflammatory Bowel Disease: A Multicentre Prospective Cohort StudyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Serum leucine-rich alpha-2 glycoprotein (LRG) is a biomarker reflecting endoscopic activity in patients with inflammatory bowel disease (IBD). However, it remains unclear whether serum LRG can predict the effectiveness of anti-cytokine biologics (biologics) in patients with IBD. This study aimed to evaluate whether serum LRG could predict the effectiveness and serum trough concentrations of biologics in patients with IBD.

Methods

This was a multicentre prospective cohort study including patients with IBD (including ulcerative colitis [UC] or Crohn’s disease [CD]) who received the biologics [ustekinumab (UST), anti-tumor necrosis factor (anti-TNF)] from January 2019 to March 2023 at 15 hospitals participating in the Osaka Gut Forum. The effectiveness of biologics was evaluated by clinical remission (CR) at week 8. We defined CR as a partial Mayo score of 2 or lower, with each subscore of 0 or 1 for UC and a CD activity index of < 150 for CD. Factors associated with CR at week 8 such as backgrounds, disease activities and concomitant medications at week 0 were analyzed by Cox proportional hazards model. For each biologic, we compared the effectiveness of biologics in the high LRG group with that in the low LRG group divided by the median serum LRG levels at week 0 (cut-off = 18.2 μg/mL).

Results

A total of 184 patients with IBD (UC, 80; CD, 104) were enrolled (UST/ anti-TNF, 119/ 65; biologic exposure, 31.5%; median disease duration, 6 years [Interquartile range (IQR) 1-14]). Median serum LRG levels at week 0 and serum C-reactive protein levels at week 0 were 18.2 μg/mL [IQR 12.5-28.1] and 0.19 mg/dL [IQR 0.03-0.77], respectively. At week 0, 63 (34.2%) and 64 (34.8%) patients concomitantly received corticosteroids and immunomodulators, respectively. In 184 patients with IBD, multivariate analysis revealed that serum LRG level at week 0 < 18.2 μg/mL was extracted as a significant factor for CR at week 8 (Odds ratio: OR 2.70, 95% confidence interval: CI 1.22-5.96). In patients who received UST, the proportion of CR at week 8 in the low-LRG group (76.9%) was significantly higher than that in the high-LRG group (59.3%, P = 0.038). In patients who received anti-TNF, however, the proportion of CR in the low-LRG group (84.6%) was not differ from that in the high-LRG group (82.1%, P = 0.781). Median serum trough concentrations of UST at week 8 in the low-LRG group (10.9 μg/mL, IQR 6.7-13.4) was significantly higher than that in the high-LRG group (5.3 μg/mL, IQR 2.4-8.3, P < 0.001).

Conclusion

Serum LRG could predict the effectiveness and serum trough concentrations of UST and be a biomarker for selecting biologics in patients with IBD.Read more P901 Extended induction response over time in patients with moderately-to-severely active Ulcerative Colitis treated with mirikizumab in the LUCENT-1 and -2 trialsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The safety and efficacy of mirikizumab (miri), an anti-IL-23p19 antibody, for moderately-to-severely active ulcerative colitis (UC) have been shown in Phase 3 trials (LUCENT-1 and -2; NCT03518086, NCT03524092).¹ Extended induction with 3 additional intravenous (IV) doses of miri induced clinical response at Week (W)24 in more than 50% of patients who did not initially achieve clinical response to induction with miri at W12.² Among the clinical non-responders, some had achieved partial response at W12 (Table 1). We assessed response over time in clinical non-responders at the end of induction who received extended induction with miri for an additional 12W.

Methods

In LUCENT-1, patients (N=1281) were randomly assigned 3:1 to receive miri 300mg or placebo IV at W0, W4, and W8. Patients not achieving clinical response with miri 300mg IV at W12 of LUCENT-1 (n=272) received extended induction treatment with open-label miri 300mg IV at W12, W16, and W20 (LUCENT-2). Symptomatic remission, symptomatic response, bowel urgency (BU) remission, and BU change from baseline at W16 and W20 are reported (definitions in Table 1) in addition to the previously disclosed outcomes at W24. For categorical variables, number and percentage of patients who are responders/remitters were presented. For continuous variables, mean change from baseline with standard deviation (SD) was used. Missing data were imputed as non-response.

Results

Among patients who were clinical non-responders to 12W of initial induction treatment (n=272), 53 (19.5%); 73 (26.8%); 101 (37.1%) achieved symptomatic remission and 144 (52.9%); 169 (62.1%); 197 (72.4%) patients achieved symptomatic response at W16, W20, and W24, respectively. Among miri induction non-responders with Urgency Numeric Rating Scale (NRS) score ≥3 at induction baseline (n=256), 10.9% achieved BU remission at W16, 14.8% at W20, and 19.9% at W24. There was a 1.8±2.4 (mean±SD) point reduction in Urgency NRS scores at W16, 2.1±2.5 reduction at W20, and 2.5±2.7 reduction at W24 (Table 1).

Conclusion

Among patients who were clinical non-responders to induction at W12, more than 50% achieved clinical response after 3 additional induction doses with miri. A proportion of patients benefited earlier from extended induction at W16 and W20, respectively, regarding symptomatic response and remission, and BU outcomes. The results demonstrate continued symptomatic improvement and further support the potential benefit of extended induction treatment.References:1. D’Haens G, et al. N Engl J Med 2023;388(26):2444-2455.2. D’Haens G, et al. J Crohns Colitis 2023;17(Supplement_1):i682-i683.Read more P512 Early proactive therapeutic drug monitoring with ustekinumab therapy in paediatric Crohn's DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

In the treatment of paediatric Crohn’s disease (CD), the youngest (lightest) children have historically been underdosed by standard weight-based dosing. Paediatric data on optimal dosing and drug levels are sparse. We aimed to examine real-world post-induction pharmacokinetic and effectiveness in a prospective multicentre paediatric CD cohort.

Methods

Luminal CD patients 2-17 years old in the Canadian Children IBD Network were eligible if they received UST IV and had a serum UST level measured proactively at week (wk) 8. Wk8 and subsequent UST levels were compared between children <40 and ≥40 kg (Mann-Whitney-U), dosed in accordance with an ongoing phase 3 paediatric trial. We calculated a “dose to exposure ratio” by dividing induction dose by wk8 level. Clinical remission was defined as wPCDAI <12.5 while still on UST. We used ROC curves to define optimal (Youden index) wk8 levels associated with wk16 remission and subsequent UST continuation. Continuous measures are reported as median (IQR).

Results

44 children were eligible from April 2017-April 2023 (70% M; age 13.1 (10.8-15.5) y; disease duration 0.3 (0.08-1.3) y; weight 44.7 (30.4-55.0) kg, 12 <40kg; 75% bio-naïve; L1 18%, L2 23%, L3 52%; SES-CD at diagnosis 17 (11-21)). At UST start, wPCDAI was 27.5 (10-52.5) and albumin was similar between weight groups (p=0.3). Median follow-up was 10 (7-13) months. 68% received 260 mg IV loading dose, 16% 390 mg. All received 90 mg SC q8 weekly maintenance. Induction doses in mg/kg and mg/m² were significantly higher in children <40 kg (Table 1). Despite this, wk8 levels were similar between weight groups, with the same pattern at other times. The dose (mg/kg) to exposure ratio was 1.45x higher in children <40kg, indicating they received more drug per unit increase in serum UST level relative to heavier children. Interval shortening to q4wk occurred in 7 prior to wk16, and in 16 (36%) by 6 months. By wk16, 56% of patients with available wPCDAI were in clinical remission and 60% at 1 year. Overall, 7 (16%) ceased UST. Wk8 UST levels were numerically higher in those who achieved wk16 clinical remission (7.4 (6.2-10.2) vs. 5.5 (2.6-7.1), p=0.094), and numerically lower in those who ceased UST (4.9 (2.6-6.9) vs. 7.3 (5.4-10.7), p=0.087). Based on ROC, the optimal wk8 UST level associated with wk16 clinical remission was 5.8 (AUC 0.68, sensitivity 78%, specificity 57%). The optimal level associated with UST continuation was 7.9 (AUC 0.73, sensitivity 43%, specificity 100%, Figure 1).

Conclusion

Paediatric CD patients weighing <40kg required higher UST doses to achieve comparable drug exposure to those ≥40kg. Positive clinical outcomes were associated with higher UST levels (with optimal cut-offs 6-8).Figure 1Read more P878 Assessment of Ulcerative Colitis Relapse Risk Using RDI (Red Dichromatic Imaging)Wed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

In the management of patients with UC, mucosal healing has been proven to be a therapeutic goal and a factor influencing prognosis. It has been reported that MES 1 has a higher rate of recurrence than MES 0. However, it has been reported that MES 0 also has a relapse rate of approximately 10%. Red dichromatic imaging (RDI) is a new imaging technology that has been closely correlated with the activity index of UC. (Naganuma et al. Endosc Int Open 2017). It also correlates with histological findings and holds promise as a modality that could further stratify MES 0 (Hashimoto et al. Surgical Endosc 2023). However, it is unclear whether RDI findings is associated with UC relapse. The aim of this study was to investigate the predictive ability of RDI for UC relapse.

Methods

This was a single-center retrospective study. A total of 93 clinically remitted UC patients who underwent colonoscopy at our department from May 2019 to October 2021 were enrolled, and at least one RDI and WLI image was taken at each of six sites from the cecum to the rectum. Patient information and still images of RDI and WLI were blinded, and two physicians independently evaluated both images taken using the RDI score of Naganuma et al. Clinical remission was defined as partial Mayo Score (pMayo) 0-1, and relapse was defined as pMayo ≥ 2 and additional treatment.

Results

The median after observation was 1022 days (5-1427 days), and the overall cumulative relapse rate was 24 % (21 patients), The mean of RDI score was 2.02, with 37 patients in RDI score 1, 28 patients in RDI score 2, 17 patients in RDI score 3, and 11 patients in RDI score 4. The relapse rate for RDI score 1 was 0%, 18% (5 patients) for RDI score 2, 47% (8 patients) for RDI score 3, and 73% (8 patients) for RDI score 4.73 % (8 patients).None of the patients with RDI score 1 had a relapse, In contrast, 11% (6 of 54) of MES 0 patients relapsed, and 33% (8 of 24) of MES 1 patients relapsed. 31 patients had RDI score 1 and 17 patients had score 2 in MES 0, which could be stratified within MES 0 by using the RDI.

Conclusion

This study suggested that the RDI score can further stratify MES 0, which is defined as mucosal healing, and may be a more accurate predictor of relapse.Read more P881 Real-life vs trial access to biologic therapy differences: a 2019-2020 experience in an Italian tertiary IBD centerWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Inflammatory Bowel Diseases (IBD) are multifactorial diseases including Ulcerative Colitis (UC) and Crohn's Disease (CD). Up to 50% of IBD patients show a primary or secondary non-response to standard biological therapy. Hence, Randomized Clinical Trials (RCTs) represent a significant therapeutic opportunity for them.This study aims to describe the clinical characteristics of "trial IBD patients" vs. "real-life IBD".

Methods

We prospectively enrolled patients who started biologic therapy from August 2019 to August 2020. We divided patients into 3 sub-groups: (1) "real-life", patients treated according to clinical practice with biologic therapy that did not meet the inclusion and exclusion criteria for RCTs, (2) "real-life suitable for trial", patients potentially eligible in RCTs, but treated with standard of care, and (3) "trial", patients treated with drugs from 14 phases 2b and 3 studies actively recruiting in our center.

Results

We enrolled 134 patients (72 UC, 62 CD). "Real-life" patients were 41 in UC and 38 in CD, "real-life suitable for trial" were 6 in UC and 14 in CD, and "trial" were 25 in UC and 10 in CD.According to the existing inclusion and exclusion criteria, the study showed that 43% UC patients and 39% CD were suitable for enrollment in RCTs, however only 16% of CD were finally enrolled in RCTs. At the enrollment, patients were mainly excluded for topical therapy use, cancer, recent infections, low CDAI (<220) or SED-CD (<6), or presence of complication of diseases in CD or for limited extension of disease in UC.Both "trial" UC and CD patients presented more extraintestinal manifestations of disease, especially the articular ones (p<0,05) and a higher significant concomitant use of systemic corticosteroids (≤20mg/die (p < 0,05)). Percentages of patients treated previously with other biological drugs were superior in "trial" patients compared to "real-life" only in UC (88% vs 29%). We observed different baseline clinical disease activity scores in CD: the HBI of "real-life" patients was 4.8, and the HBI of "trial" patients was 9.1.In addition, patients enrolled in RCTs waited longer before accessing the proposed biological therapy.

Conclusion

This study highlights some differences between clinical practice and RCTs, particularly regarding criteria to start biologic therapy. Globally "trial patients" have more complex diseases that significantly impact their clinical status. Furthermore, RCTs use clinical scores (e.g. CDAI) as determinants for enrollment and decision-making, while endoscopy and radiological imaging are more widely used in clinical practice for decision making. These differences could cover the actual effectiveness of a new drug compared to the theoretical efficacy deriving from registration RCTs.Read more P513 Clinical efficacy and durability of subcutaneous infliximab in patients with inflammatory bowel disease after switching from intravenous in a Korean multicenter prospective cohort studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Subcutaneous infliximab (IFX-SC) has shown comparable efficacy and safety with IV infliximab (IFX-IV) in inflammatory bowel disease (IBD), such as ulcerative colitis (UC) or Crohn's disease (CD), since its launching in 2021. We aimed to investigate the real-life efficacy and durability of IFX-SC after IFX-IV in Korea.

Methods

This multicenter, prospective cohort study included IBD patients who administered IFX-IV maintenance therapy from September 2021 to November 2023. Patients received IFX-SC 120mg after the last IFX-IV administration (Week [W] 0), and every 2 weeks thereafter. Patients who administered IFX-SC less than W8 were excluded. Clinical relapse (CREL) at W26, W50, and one-year drug survival were assessed. Among IBD patients with W0 clinical remission, CREL was partial Mayo score ≥2 points among UC patients, and Crohn’s disease activity index ≥150 points among CD patients. Drug survival was evaluated based on the time of drug persistence from W0 to the last date of IFX-SC administration among drug-off cases. Rate of drug re-switch (from IFX-SC to IFX-IV) was also investigated.

Results

A total of 447 patients (UC with 154, and CD with 287) were enrolled. Enrolled patients included young adults with a male predominance (Table 1). At W0, 77 patients with UC and 185 patients with CD showed clinical remission. Patients with UC showed 15.7% (11 out of 70 patients) of W26 CREL, and 12.1% (seven out of 58 patients) of W50 CREL (Figure 1A). Among patients with CD, rates of W26 CREL and W50 CREL were 5.9% (nine out of 153 patients) and 10% (11 out of 110 patients), respectively. On the other hands, one-year drug survival was also investigated (Figure 1B). Among patients with UC, W26 drug survival rate was 89.8% (95% confidence interval [CI], 0.836–0.937), and W50 drug survival rate was 89.0% (95% CI, 0.827–0.931). Among patients with CD, it showed higher drug survival rate, showing W26 drug survival rate of 97.8% (95% CI, 0.951–0.990) and W50 of 94.9% (95% CI, 0.911–0.971). During the study, 3.4% (15 patients) of serious adverse events were reported. Drug re-switch rate was 5.4%, mainly due to injection site discomfort.

Conclusion

In real-world settings, IFX-SC seems to be a feasible option for the maintenance therapy, following IFX-IV administration. Considering favorable drug survival rate, low relapse rate, and tolerable safety profile, it may facilitate individualized treatment.Read more P661 Ustekinumab in Crohn’s disease: A three-year multicentre prospective study from Hungary - Assessing efficacy, drug sustainability, and safetyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

While randomized controlled trials have shown ustekinumab (UST) as an effective therapeutic option for Crohn’s disease (CD), there is a lack of long-term observational data in real-world CD patient settings. This prospective study seeks to evaluate the clinical effectiveness, sustainability, and safety of UST in a nationwide multicentre cohort of CD patients over three years. The aim is to bridge the gap in our understanding of UST's real-world implications for long-term CD management.

Methods

CD patients undergoing ustekinumab (UST) treatment were consecutively enrolled at nine Hungarian Inflammatory Bowel Disease centers from January 2019 to May 2020. Over a three-year period, comprehensive data on patient demographics, disease characteristics, treatment history, clinical disease activity (measured by the Harvey Bradshaw Index (HBI)), biomarkers, and endoscopic activity (evaluated using the Simple Endoscopic Score for Crohn’s Disease (SES-CD)) were systematically collected.

Results

Involving 148 patients, the cohort comprised 48.9% with complex behavior of CD and 97.2% with previous anti-TNF exposure. Pre-induction remission rates were observed at 12.2% (HBI) and 5.1% (SES-CD). Clinical remission rates (HBI) at the end of the first, second, and third years were 52.2%, 55.6%, and 50.9%, respectively. Criteria for endoscopic remission were met in 14.3%, 27.5%, and 35.3% of subjects at the end of the first, second, and third years. Dose intensification was notable, with 84.0% of patients on an 8-weekly and 29.9% on a 4-weekly regimen by the end of year 3. Throughout the follow-up period, drug sustainability stood at 76.9%, and no serious adverse events were observed.

Conclusion

Our study confirms that ustekinumab is a sustainable, effective, and safe long-term treatment for Crohn's disease patients with a severe disease phenotype and a history of high anti-TNF failure, with the need for frequent dose adjustments.Read more P889 Facilitating equitable IBD care trust-wide: a need for treatment targets in IBD?Wed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Timely biological therapy in IBD is associated with reduced disease progression, especially in CD (Berg et al 2019). However, there are no clear UK standards detailing the timescale in which IBD care should be delivered. We evaluated the time between initial consideration of therapy and first dose in a district general hospital and tertiary referral centre in Barts Health NHS Trust.

Methods

Details of patients receiving biologics for IBD at Newham (NUH) and Royal London Hospital (RLH) (between 2018 – 2022) were obtained from infusion clinics; electronic records were reviewed for 50 recent referrals. The following information was collected: demographics, phenotype, drug, first documentation of consideration of biologic, completion of funding application, onset of therapy.

Results

Demographics:NUH: Age (median(IQR)) = 43.5(30.3 – 50.56) Gender (F:M) = 26:24, CD:UC = 34:16, Biologic: infliximab:vedolizumab:ustekinumab:adalimumab: 29:5:11:5, First biologic: n=34RLH: Age (median(IQR)) = 31.6 (24.6 – 41.1) Gender (F:M) = 27:23 CD:UC = 23:27, Biologic: infliximab:vedolizumab:ustekinumab:adalimumab: 34:12:3:1, First biologic: n=25There was substantially longer time between initial consideration of therapy and first dose delivered at NUH 94.5 days (44 – 174) compared with RLH 35.5 days (23.75 –69) (p<0.01). However, time from completion of funding application to first dose did not differ significantly between sites (43.5 days (30.3 – 50.6) vs 31.6 (24.6 – 41.1), p=0.42). In patients receiving first biologic, there was a trend towards a longer time since diagnosis at NUH (3.2 years (1.0 – 9.1) vs 1.7 years (0.5 – 4.3), p=0.08).

Conclusion

Patients treated in a tertiary referral centre started biologics sooner after consideration, and earlier in disease course. This does not appear due to availability of infusion services, but due to time to complete initial investigations and finalise escalation. This may reflect differences in service set-up; in particular, NUH manages IBD care with a single IBD nurse, and fewer options for fast-track clinic follow up. A clear UK IBD standards framework identifying recommended time frames for establishing biologics is indicated, to ensure equity in care across tertiary and DGH settings.Read more P689 Adaptive steroid tapering impedes corticosteroid-free remissions compared to forced tapering in UC clinical trialsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Protocols for managing steroids in clinical trials of ulcerative colitis (UC) vary. Most trials mandate steroid tapering at the beginning of maintenance phase. Adaptive steroid tapering allows for some discretion on whether to taper steroids for a patient. It remains unclear what impact steroid tapering protocols have on trial outcomes.

Methods

This post-hoc analysis from many clinical trials of advanced therapies in UC (VARSITY, ACT 1/2, PURSUIT, GEMINI1, OCTAVE and ULTRA2) was carried out under protocols with Vivli (00007656) and YODA (20224882). Responders to induction therapy with baseline corticosteroid use were considered as the primary population of interest. Adjustments were made to account for re-randomization designs and treatment exposure. Univariate analyses were conducted to identify baseline variables that had an association with the primary outcome of interest, one-year corticosteroid-free clinical remission (CR). All covariates with a significant univariate association (p < 0.05) were considered for inclusion in the multivariate model. Logistic regression was used to assess the impact of steroid-weaning regimen on the outcome of interest. Secondary outcome of interest was one-year CR.

Results

There was a total of 861 patients from the seven included trials who had achieved clinical response after induction and were using corticosteroids. Within multivariate analysis, patients using adaptive steroid weaning regimens were less likely to achieve one year corticosteroid-free CR (odds ratio (OR) 0.66 (95% CI 0.48-0.92), p=0.015). Patients with higher partial Mayo scores were also less likely to achieve one year corticosteroid-free CR (OR 0.88 (95% 0.8-0.97), p=0.012). Other variables found significant on univariate analysis were no longer significant once considered within the multivariate model (smoking, race, albumin, endoscopic Mayo score). For the secondary outcome of one year CR, patients using adaptive steroid weaning regimens had increased odds for achieving one year CR as compared to those using fixed regimens (OR 1.9 (95% 1.43-2.52), p<0.001). Several other variables were also found to have an association with one year CR within the multivariate model (Table 1).

Conclusion

Among patients with UC on corticosteroids at the time of study enrolment, adaptive steroid weaning regimens were less likely to achieve one-year corticosteroid-free CR but more likely to achieve one-year CR. This may help explain the findings within the VARSITY study, where patients treated with vedolizumab had increased odds for one-year CR but were less likely to achieve one-year corticosteroid-free CR. Consideration should be given to implementing mandatory steroid weaning protocols in future clinical trials of UC.Read more P514 Beyond the First Attempt: A Multi-Centre UK Analysis of Second JAK Inhibitor Use in Ulcerative ColitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Tofacitinib, filgotinib, and upadacitinib are Janus Kinase inhibitors (JAKi) effective in inducing and maintaining remission in moderate-to-severe ulcerative colitis (UC). Limited data exists regarding outcomes in patients on a second JAKi after prior JAKi treatment failure. Here we describe the effectiveness of induction with a second JAKi in a cohort of UC patients.

Methods

In this retrospective cohort study, UC patients from 20 UK hospitals treated with a second JAKi were included. Clinical endpoints, as defined in Table 1, were assessed at week 8. Corticosteroid use, prior advanced therapies, and reason for cessation of first JAKi were documented.

Results

99 patients commenced induction therapy with a second JAKi, 87% of whom had active disease by disease activity index, endoscopy or biomarkers. First JAKi was stopped due to failure or intolerance in 95% of cases. Tofacitinib was the most commonly used first JAKi (72%). Second JAKi was upadacitnib in 77% and filgotinib in 23%. There was no significant difference in the SCCAI (p=0.834) or pMayo (p=0.074) at baseline in those given either drug. Exposure to at least one other advanced therapy was seen in 78 patients, and 49 patients required steroids during induction. Both the median SCCAI and pMayo scores improved from 7 (SCCAI 5-9, pMayo 5-8) at baseline to 2 (SCCAI 0-3) and 1 (pMayo 0-3) at 8 weeks (p<0.001). Paired endoscopy results were available in 27 patients, showing an overall improvement from a median UCEIS 5 (5-6) and MES 2 (2-3) to 1.5 (0-5) and 1 (1-2.5) respectively (UCEIS p<0.001, MES p=0.019). Median faecal calprotectin reduced from 650 (331-1500) to 62 (31-173) in 45 patients (p<0.001) (figure 1B). Of the 82 patients with paired disease activity index at baseline and 8 weeks, 52% achieved clinical remission (figure 1A) of whom 93% (40/43) were in steroid-free remission, 64% (9/14) in endoscopic remission and 88% (22/25) in biochemical remission. There was no significant difference in remission rates depending on disease extent, number of previous advanced therapies, first or second JAKi, or reason for cessation of first JAKi including primary non-response (p=0.99). Serious adverse events were admission for IV steroids, colectomy and VTE (1 each), withdrawal due to adverse event n=1, zoster infections n=3.

Conclusion

on Our results suggest that treatment with filgotinib or upadacitinib following exposure to another JAKi can be effective in inducing clinical remission in UC. Efficacy was similar in our cohort regardless of mechanism of failure of the first JAKi or whether upadacitinib or filgotinib was used as a second JAKi. The observed safety profile was as expected especially with considerable risk of zoster infections.Read more P1034 The Egyptian ICRID-IBDQ: A novel IBD knowledge questionnaire from development and validation to comparison of different patient education modalitiesWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Inflammatory bowel diseases are chronic debilitating diseases whose proper management depends on patients’ good knowledge. It is the role of the physician to ensure good knowledge by tailoring appropriate methods of patient education.

Methods

This study included 105 patients with established diagnosis of IBD presenting to the Integrated Clinical and Research Center for Intestinal Disorders (ICRID) unit, Department of Endemic hepato-gastroenterology and infectious diseases, Faculty of medicine-Kasr Al Ainy Hospital, Cairo university. It included 2 phases: The first was cross-sectional analytical where the Egyptian “ICRID-IBDQ” questionnaire assessing the IBD patients’ knowledge was developed, validated, and used within the study population. This questionnaire comprised questions about the nature of the disease, lifestyle, diet, treatment modalities along with its effect on pregnancy and fertility; and the knowledge level was estimated by the number of correct answers considering scores above 75% as “Good”, 50-75% as “Fair”, and below 50% “Poor”. The second phase was comparative interventional where the patients were randomly allocated to 3 different educational methods: Direct education by physician, by infographic videos, and both combined, with the utility of the three in patient education compared using the ICRID-IBQ.

Results

The estimated patient knowledge of IBD is 26.3%, corresponding to “Poor”. The factors significantly associated with better knowledge on multivariate analysis are higher level of education (college or more) (p value <0.001, OR 8.7), female gender (p value 0.002, OR 4.9) and positive family history (p value 0.042, OR 7.7). All fields had “poor” knowledge, and the field with the most defective knowledge was surgery. All patients receiving education improved, total percentage of improvement measured from 26.3% to 78.9% (p value <0.001). There was no statistical difference between the 3 educational groups: Direct education by physician, infographic video or both combined (p value 0.09).

Conclusion

The importance of patient education has to be seriously addressed and tailored educational programs using combined methods have to be implemented by healthcare facilities to improve IBD patients’ quality of treatment and of life. Infographic videos are valuable tools which may aid in improving knowledge by patient education.Read more P690 Monitoring ustekinumab levels in Inflammatory Bowel Disease in clinical practice: a window of opportunityWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Ustekinumab (UST) is an effective drug in inflammatory bowel disease (IBD). Monitoring Ustekinumab trough levels in μg/mL (UST_TL) can assist in the clinical management of these patients. Our objective was to analyze UST_TL in patients with IBD, establish cutoff points associated with clinical response and remission, and analyze factors related to higher levels.

Methods

Observational, retrospective, and single-center study that included patients with IBD receiving UST treatment with at least one level determination.Before the initiation of UST (baseline) and prior to level extraction (periods 1 and 2), clinical and analytical data were collected as follow: Harvey-Bradshaw Index (HBI) in Crohn's disease (CD), partial Mayo Index (pMayo) in ulcerative colitis (UC), fecal calprotectin (FC) and C-reactive protein (CRP).Median and interquartile range (IQR) were used for quantitative variables, and percentage (%) for qualitative variables. Univariate and bivariate analyses were performed for response and clinical remission rates using ROC curves.

Results

A total of 125 patients with at least one UST_TL determination were included. Figure 1 illustrates their baseline characteristics.In period 1, 62.4% of patients were on subcutaneous maintenance, and the median UST_TL was 3.1 (1.6-5.3). 64% of patients responded to treatment, with higher UST_TL than non-responders [4.1 (2.0-6.2) vs. 2.1 (1.0-4.5); p=0.006]. 42.5% achieved clinical remission with higher UST_TL than those who did not achieve it [4.0 (2.3-5.7) vs. 2.5 (1.2-5.2) p=0.039].Furthermore, patients on subcutaneous maintenance* had lower UST_TL than those on subcutaneous and intravenous intensification [2.2 (1.3-3.5)* vs. 7.4 (5.1-10.8) and vs. 5.3 (3.3-12); p<0.001 and p=0.03, respectively).In the 46 patients with two determinations, statistically significant differences were found between period 1 and period 2 in UST_TL [3.4 (1.9-6.4) vs. 7.2 (4.7-11.7) p<0.001], HBI [8 (4-9) vs. 4 (4-4.3); p<0.001], pMayo [4.5 (3-5) vs. 1 (1-3.3); p=0,042], FC [700 (180-2000) vs. 400 (108-1571); p=0.032), and corticosteroid use (41.3% vs. 26.1%; p=0.024).ROC curves were calculated for response and clinical remission in period 2. The UST_TL cutoff points were 4.25 and 6.025μg/mL for response and clinical remission, respectively (figure 2).

Conclusion

Similar to previously published studies with anti-TNF, high levels of UST_TL are associated with increased clinical remission and response. Patients undergoing UST treatment may benefit from a change in dosage to increase levels and achieve clinical remission. The cutoff point obtained for clinical remission was 6 μg/mL.Therefore, the determination of UST_TL in daily clinical practice is a useful tool for the treatment of patients with IBD.Read more P474 IBD-Disk : Towards validating the classical Arabic version of the questionnaire ?Wed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The IBD-Disk is a validated 10-question, self-administered visual questionnaire used to assess the inflammatory bowel disease (IBD) related disability. It has been translated into several languages and validated in different populations since its emergence. The aim of our study is to explore the internal consistency and item reliability of the IBD-Disk in its classical Arabic version, and to analyze the strength of correlation between each item and the sum of the scale.

Methods

We conducted a monocentric cross-sectional study including IBD patients. All individuals completed the IBD-Disk questionnaire in classical Arabic. The internal consistency of the IBD-Disk was assessed using Cronbach's alpha between item combinations. A value > 0.70 was considered acceptable, > 0.80 good, and > 0.90 excellent. Cronbach's corrected correlation was assessed using Pearson's correlation coefficient.

Results

We included 166 patients, 53.6% were men and 69.3% had Crohn's disease. Median age was 38 years [30 - 48]. The mean total score was 36.4 ± 21.0. The "Energy", "Emotions" and "Education & work" items had the highest scores (4.9 ± 2.9, 4.7 ± 3.1, and 4.4 ± 3.2 respectively). Including the 10 items of the IBD-Disk scale, a value of 0.913 95% CI [0.893-0.932] was observed for Cronbach's alpha, demonstrating good reliability between the different sub-scores. By performing the removal procedure one by one, Cronbach's alpha varied between 0.902 and 0.915, confirming that all items contribute to the construct. In addition, all items showed a Cronbach corrected correlation between each item and the rest of the scale r > 0.4, p<0.001. Energy showed the highest correlation (r=0.751), and joint pain the lowest (r=0.506) (Table 1). Also, Cronbach's alpha was positive for every pair of IBD-Disk items at the start of the study. The item pairs that showed the best correlation were [Abdominal pain - Regulating defecation], [Energy - Regulating defecation] and [Energy - Sleep]. In contrast, the item pairs that were least interconnected were [Abdominal pain - Joint pain], [Interpersonal interaction - Joint pain] and [Body image - Joint pain] (Table 2).

Conclusion

Our work has demonstrated excellent item homogeneity in the classical Arabic version of the IBD-Disk, and a good correlation between each item and the remaining total score. However, a prospective measurement of the intra-class correlation coefficient of the classical Arabic version will be necessary to assess its reproducibility over time.Read more P1035 CT-based radiomics signature of visceral adipose tissue and bowel lesions for identifying patients with Crohn’s disease resistant to infliximabWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Data describing the effect of visceral adipose tissue (VAT) on infliximab treatment response in patients with Crohn’s disease (CD) remains scarce. We aimed to develop and validate a VAT-based radiomics model (RM) using computed tomography (CT) images to identify CD patients at high risk of primary nonresponse to infliximab, and explored whether it can improve the prediction efficacy of an established bowel lesions-based RM.

Methods

This retrospective study included 231 CD patients (training cohort, n=112; internal validation cohort, n=48; external validation cohort, n=71) from two tertiary centers. Machine-learning VAT model and bowel model were developed separately to identify CD patients with primary nonresponse to IFX. A comprehensive model incorporating VAT and bowel radiomics features was further established to verify whether CT features extracted from VAT would improve the predictive efficacy of bowel model. Area under the curve (AUC) and decision curve analysis were used to compare the prediction performance. Clinical utility was assessed by integrated differentiation improvement (IDI).

Results

VAT model and bowel model exhibited comparable performance for identifying patients with primary nonresponse in both internal [AUC: VAT model vs bowel model, 0.737(95% CI, 0.590-0.854) vs. 0.832 (95% CI, 0.750 - 0.896)] and external validation cohort [AUC: VAT model vs. bowel model, 0.714(95% CI, 0.595-0.815) vs. 0.799(95% CI, 0.687-0.885)], exhibiting a relatively good net benefit. The comprehensive model incorporating VAT into bowel model yielded a satisfactory predictive efficacy in both internal [AUC,0.840(95%CI, 0.706-0.930)] and external validation cohort [AUC,0.833(95%CI, 0.726-0.911)], significantly better than bowel alone (IDI=4.2% and 3.7% in internal and external validation cohorts, both P<0.05).

Conclusion

VAT has an effect on IFX treatment response. It improves the performance for identification of CD patients at high risk of primary nonresponse to IFX therapy with selected features from RM.Read more P715 Multiparametric assessment of IBD and SpA-IBD patients to explore disease biomarkers and response predictorsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Immune-mediated inflammatory diseases (IMID) are an emerging problem in Western world. Despite being traditionally considered nosologically distinct entities, two or more IMID can coexist within the same patient and their pathogenesis overlap to a certain extent. Two IMID, inflammatory bowel disease (IBD) and spondylarthritis (SpA), often associate, but their pathogenesis remains unknown and disease biomarkers are not fully characterized. This project aims to investigate pathogenic and predictor markers of response

Methods

A collaborative study, enrolling IMID patients (pts) starting a target therapy, was performed. We focused on 2 cohorts: IBD and IBD-SpA. At baseline, serum (to measure CRP, IL17A, TNFα, and TREM1), intestinal biopsy and stools were collected. Clinical response was assessed at 4 months. The exploratory outcome of this preliminary analysis was to investigate whether serum, immunohistochemical and microbiological markers correlate with each other and with response to therapy

Results

We enrolled 60 pts (36 IBD, 24 IBD-SpA): 61.7% were female, median age was 46 years (IQR 30-57.3). At 4 months, 52.8% and 41.7% of the IBD and IBD-SpA cohorts showed clinical response. A nearly significant correlation between increased intestinal CD68+ cell infiltrate and higher baseline CRP levels (R=0.52, p=0.06), and between increased CD21+ cell infiltrate and CRP drop at 4 months (R=0.47, p=0.09) was observed. Lower baseline TNFα levels correlated with CRP drop at 4 months (R=0.35, p=0.02); higher baseline TNFα levels correlated with a reduced intestinal infiltrate of CD20+ and CD21+ cells (R=0.67, p=0.04; R=0.69, p=0.04). In the IBD-SpA cohort, a trend towards higher mean TREM1 levels was observed in non-responders vs responders (389.0 pg/mL vs 276.4 pg/mL, p=0.09); ROC curve identified a cut-off of 361.0 pg/mL to predict nonresponse (sensitivity 66.6%, specificity 75.0%, p=0.09). IBD patients had a reduced α-diversity compared to healthy controls (HC) and SpA patients; IBD and SpA patients had an increased β-diversity compared to HC. IBD pts had increased Proteobacteria and decreased Bacteroidetes compared to HC. Agathobacteria, Bacteroides, Faecalibacteria and Prevotella genera were significantly decreased in IBD vs HC, whereas Streptococci and Escherichia-Shigella were significantly increased

Conclusion

Baseline TNFα may correlate with specific immune signatures of the intestinal infiltrate. Baseline TREM1 may help predicting response in the specific setting of concomitant IBD and SpA. Gut microbiome composition is altered in IBD pts compared to HC, comprising more pathogenic and fewer protective bacteria. Further analyses will be needed to confirm such observations and explore additional features and predictive biomarkersRead more P475 Potential of molecular remission: tissue neutrophil elastase is better than histological activity for predicting long-term relapse in patients with Ulcerative Colitis in endoscopic remissionWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Growing interest exists in deep remission, beyond clinical and endoscopic remission, to enhance long-term prognosis in patients with ulcerative colitis (UC). Our study aimed to evaluate the risk of relapse according to tissue expression levels of calprotectin and neutrophil elastase (NE) in patients with quiescent UC.

Methods

Rectal biopsies were performed on 218 patients with UC in clinical and endoscopic remission. Histological activity was prospectively scored using the Robarts Histological Index. Tissue calprotectin and NE levels were evaluated using immunohistochemistry. Clinical relapse was defined as the requirement for medical therapy escalation, systemic steroid administration, UC-related emergency room visits, hospitalization, or surgery. Optimal tissue calprotectin and NE cutoffs for relapse were determined using log-rank analysis. A Kaplan–Meier analysis was performed to assess the cumulative incidence of clinical relapse, and a Cox proportional hazard analysis was conducted to identify the risk factors for clinical relapse.

Results

Tissue calprotectin and NE levels were significantly higher in patients with histological activity than in those in histological remission (P < 0.001, respectively). The optimal cutoffs of tissue calprotectin and NE for relapse were 10.61 /mm² and 22.08 /mm², respectively. The 3-year clinical relapse risk was significantly lower in the low tissue NE group than in the high tissue NE group (P = 0.009); however, it did not differ between the low- and high-tissue calprotectin group (P = 0.094) (Figure). In multivariate analyses, a low level of tissue NE expression (adjusted hazard ratio [aHR] = 0.453, 95% confidence interval [CI] = 0.225–0.911, P = 0.026) and maintenance treatment using biologics (aHR = 0.368, 95% CI = 0.141–0.962) were independently associated with a lower risk of 3-year clinical relapse, but previous steroid exposure was independently related to increase the risk of 3-year clinical relapse (aHR = 2.824, 95% CI = 1.298–6.141) (Table). The histological index and tissue calprotectin did not have influence on the 3-year clinical relapse.

Conclusion

In patients with UC who have achieved clinical and endoscopic remission, tissue expression of NE is a better predictor of long-term relapse than histological activity.Read more P716 Efficacy and safety of upadacitinib during induction in Crohn’s disease: Real-world experienceWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Upadacitinib is a selective JAK1 inhibitor that has recently been approved for treatment of moderate-severe Crohn’s disease, with Phase III clinical trials showing positive efficacy and safety profiles. Our aim was to evaluate the real-world experience of upadacitinib in a refractory cohort of Canadian patients with Crohn’s disease.

Methods

This was a two-centre retrospective study looking at 12-week induction data for patients with active Crohn’s disease from McGill University Health Centre and Hamilton Health Sciences. The primary outcome was clinical remission at 12 weeks, with secondary outcomes including clinical response, biochemical remission, and biochemical response. Clinical remission was defined as a Harvey-Bradshaw index (HBI) < 5. Clinical response was defined as an HBI reduction of ≥ 3. Biochemical remission was defined as a c-reactive protein (CRP) < 5 mg/L and/or fecal calprotectin (FCP) < 250 μg/g. Biochemical response was defined as a reduction of CRP or fecal calprotectin by 50% from baseline. These parameters were all evaluated at 8 and 12 weeks. Adverse events were summarized for patients who had follow up data available and included in the efficacy analysis.

Results

There were 28 patients who were treated in total, all of which had multiple biologic treatment failures. Baseline median age was 37, median HBI was 9, median CRP was 9.41 mg/L, and median FCP was 580 μg/g. The median disease duration was 13.5 years. Four patients discontinued upadacitinib due to no response or side effects. For all available data including patients who discontinued upadacitinib, clinical remission was achieved at 12 weeks in eight patients (8/11, 72.7%). Clinical response was achieved in eight patients (8/11, 72.7%), biochemical remission was achieved in four patients (4/11, 36.4%), and biochemical response was achieved in six patients (6/11, 54.6%). Of those that were initially on steroids (n=5), four patients (4/5, 80.0%) were able to wean off steroids and achieved a steroid-free clinical or biochemical response at 12 weeks. Of those who had previously been on off-label tofacitinib (n=5), clinical follow-up data was available for three patients at the end of the 12-week induction period. Two patients achieved clinical remission (2/3, 66.7%) and three patients had a clinical response (3/3, 100%). Among 13 patients with follow-up data, adverse events were observed in three patients (3/13, 23.1%), with two having non-serious infections (2/13, 15.4%) and one having fevers of unknown origin (1/13, 7.69%).

Conclusion

This real-world multicentre Canadian induction study shows favourable efficacy and tolerability of upadacitinib in refractory active Crohn’s disease.Read more P1036 Persistence of biologics and advanced small molecules in 4th, 5th and 6th line of therapy for inflammatory bowel disease: a cross-sectional retrospective studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The choice of treatment for inflammatory bowel disease (IBD) with multiple prior drug failures, also known as difficult-to-treat (D2T) IBD, is an increasing challenge. We assessed the persistence of biologics and advanced small molecules, a surrogate for their efficacy, in patients with Crohn's disease (CD) and ulcerative colitis (UC) overall and in 4th, 5th and 6th lines of advanced treatment.

Methods

We retrospectively searched the electronic medical records of patients with IBD followed at the San Raffaele Hospital (Milan, Italy) up to 1 October 2023. Patients enrolled in clinical trials that changed disease management or receiving experimental drugs were excluded. Drug persistence was defined as the time from initiation to discontinuation of each treatment. Welch's ANOVA and Games-Howell's method for multiple comparisons were used.

Results

A total of 679 patients with moderate to severe IBD were included. 350 had CD, 326 UC, and 3 IBD-U. The mean disease duration was 11 years and 452 (66%) had received 5-aminosalicylates or antimetabolites as first maintenance treatment. Escalation to and changes between advanced treatments over time is summarised in Figure 1A. A greater use of anti-TNF agents was observed in the first lines of treatment whereas newer medications were proportionally more prescribed in refractory patients.In the overall analysis, regardless of the line of treatment, there was no difference in drug persistence between agents at 12 months (p=0.62), with approximately half of the patients having discontinued the drug. Figure 1BIn subsequent lines of treatment, drug persistence decreased significantly in patients with CD (p=0.002). The trend was particularly pronounced from line 2, with a mean duration of 31 months, to line 7, with a mean duration of 11 months.In UC, the reduction was less evident and borderline non-significant (p=0.05), although it suggests a decrease in drug efficacy as the disease progresses. Figure 2 A, BIn patients with D2T IBD, drug persistence in 4th, 5th and 6th line advanced treatment was similar for all agents (all p>0.05), indicating no clear advantage of one drug over the others. Figure 2 C, D, E

Conclusion

In CD, and possibly in UC, the persistence of patients on any advanced drug decreases with subsequent lines of treatment. None of the advanced agents showed a longer persistence time when used as a 4th, 5th or 6th line of treatment.Read more P744 Evaluation of a lifestyle program based on physical activity on quality of life and fatigue in patients with Inflammatory Bowel Disease: a pilot studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Patients with inflammatory bowel disease (IBD) tend to be less physical active, whilst maintaining an active lifestyle has been associated with enhanced disease control, diminished fatigue and improved quality of life. The primary objective was to evaluate the potential impact on physical fitness, fatigue, quality of life and disease control of a specially designed exercise program for IBD patients.

Methods

Patients with IBD, treated at two teaching hospitals in the southwest of the Netherlands, participated in a 16-week exercise program (IBD-Fit) between March until June 2023. The program was designed especially for patients with IBD to sport with peers and was adjusted to a patient's fitness level. Improvement of physical fitness (measured with body composition, grip strength, sit-and-reach test, Y-balance test and 6-minute walk test) was analysed. In addition, patients were asked to fill in validated questionnaires at baseline and at the end of the program (IBD-Quality of life, IBD-Fatigue and IBD-control), to assess the effect of the exercise program on quality of life, fatigue and disease control. For statistical analyses, a paired t-test or Wilcoxon matched paired rank test was used.

Results

A total of 27/32 patients completed the entire exercise program, with a mean age of 50.4 years (SD 12.5), 40.7% were male, 48.1% had Crohn’s disease and 51.9% had ulcerative colitis (table 1). After 16 weeks, body composition, such as BMI and muscle mass improved compared to baseline; fat percentage significantly decreased (32.3 to 29.7%; Z=-2.983; P=0.003). Physical fitness improved significantly, based on the sit-and-reach test (23 to 29 cm; Z=-3.03; P=0.002), the absolute reach distance of the Y-balance test (73.7 to 79 cm; Z=-2.77; P=0.006), and the mean distance during a 6-minute walk test (505.2 to 557.5 m; 95%CI 32.6 – 72.2; P<0.001). Grip strength showed no significant improvement. Quality of life improved on average with 8.0 points on the IBDQ. The Systemic Symptoms domain improved significantly (mean difference 2.7; 95%CI 0.1–5.4, P=0.043). The program significantly improved fatigue scores (Z = -2.296, P=0.022). Disease control showed no significant improvement after the program. Overall, patients were very satisfied with the exercise program. Average rating was 8.6 out of 10.

Conclusion

This pilot study in a small number of patients shows that a specially designed exercise program has a positive effect on IBD patients. These results underline the importance to broaden our standard of care and can be used as a steppingstone to implement the program on a larger scale and ultimately become part of the standard of care for patients with IBD.Read more P1037 Treatment sequences and time on specific treatments in patients with inflammatory bowel disease under advanced treatment – a German claims data analysisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The number of advanced therapies (ADT) approved for the treatment (Tx) of inflammatory bowel disease (IBD) in is increasing, however, yet no guidance on optimal sequencing of treatments is available in Germany (and elsewhere). This study aims to investigate applied Tx sequences of ADT in claims data based on real-world setting across Germany in patients (pts) with IBD.

Methods

A retrospective healthcare claims data analysis was conducted using claims data from approx. 4.5 Mio pts within German statutory health insurance, including pts diagnosed with Crohn’s disease (CD) and ulcerative colitis (UC) from 2014 to 2021. Pts were followed up for at least 6 months after the first prescription of ADT (index date) if not deceased. A pre-index period of at least 12 months was applied to only include pts naïve to ADT. The study assessed Tx sequences and time to next treatment (TTNT) among other parameters. Data was not adjusted to disease severity and only descriptively reflects real world Tx patterns within the database.

Results

The database included 15.041/18.361 pts with CD/UC. Pts with CD/UC starting ADT between 2014 to 2021 received either Adalimumab (ADA: 923/337), Infliximab (IFX: 616/419), Ustekinumab (UST: 113/25) or Vedolizumab (VDZ: 139/248). In an analysis of ADT sequences and TTNT defined as start of first line (1L) Tx to start of second line (2L) Tx we found that during the observation period the majority of pts (71.4%) have not switched to 2L Tx yet. In 1L, ADA was observed as the preferred Tx in CD pts (51.5%) followed by IFX (34.4%), VDZ (7.8%) and UST (6.3%), in UC pts IFX (40.7%) was mostly prescribed as 1L followed by ADA (32.8%), VDZ (24.1%) and UST (2.4%). The proportion (%) of pts not switched to 2L Tx within one year for CD/UC were: ADA (83.6/70.3), IFX (79.0/73.1), UST (93.5/96.0) and VDZ (85.4/86.6). Within three years proportions of pts not switched to 2L Tx changed for CD/UC: ADA (68.1/54.5), IFX (57.8/56.8), UST (82.5/72.0) and VDZ (72.7/73.0) (table1). For pts who had a switch to a different ADT, the switch occurred within one year in over 50% of all pts. Most Tx switches (45.8%) were observed in pts who received IFX as 1L Tx, both in the UC and CD population. The majority of CD pts that received 2L Tx were switched to UST (35.7%), while in UC, a high proportion of pts were switched to VDZ (44.3%). Further Tx pathways and proportions of switches are summarized in Figure 1.

Conclusion

The study found that most IBD pts started ADT with ADA or IFX, but unadjusted time on 1L data may suggest a trend towards superior TTNT of VDZ and UST in UC and CD. Data should be interpreted carefully, as pts for >1L are limited and UST and VDZ were approved during the study period.Read more P520 Preferences towards treatment attributes among patients with Crohn’s disease and ulcerative colitis in Argentina, Australia, Brazil, Saudi Arabia and Taiwan: a discrete choice experimentWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Advanced therapies (ATs) with different mechanisms of action and routes of administration (RoA) are used for inflammatory bowel disease (IBD: Crohn’s disease [CD] and ulcerative colitis [UC]), and patients (pts) play an increasing role in the decision-making process.Pts’ preferences for treatment attributes from 7 European countries have been reported previously; however, evidence from non-European countries is lacking.

Methods

Adult pts with CD or UC on treatment for ≥6 months from Argentina, Australia, Brazil, Saudi Arabia and Taiwan were enrolled in this cross-sectional, self-administered online survey (Oct 2022 to May 2023). Pts’ preferences for IBD treatment attributes are described. In a discrete choice experiment, the relative importance of treatment attributes was estimated using conditional logit models.

Results

Overall, 706 pts with CD and UC (n=353 each) completed the survey. Mean (standard deviation [SD]) ages (years [y]) were 36.8 (9.9) and 37.7 (10.2), 47.9% and 47.6% were female, and mean (SD) disease durations (y) were 4.5 (6.0) and 4.6 (6.7) for CD and UC, respectively; 58.1% (CD) and 56.1% (UC) were exposed to ATs. For pts with CD, the rate of long-term remission on maintenance therapy (MT) was the most important attribute for treatment choice (32.5%), followed by the rate of 1-y remission (25.7%), RoA (24.6%) and risk of serious adverse events (AEs, 11.5%) and mild AEs (5.8%). For pts with UC, the rate of corticosteroid-free remission after 1 y was the most important attribute (30.8%), followed by RoA (27.4%), rate of mucosal healing after 1 y (16.1%), long-term remission on MT (14.9%) and risk of serious AEs (10.0%) and mild AEs (0.8%). Country-specific results are shown in the Table. Compared with intravenous administration every 4–8 weeks, pts with CD preferred subcutaneous (SC) administration every 1–2 weeks (odds ratio [95% confidence interval]: 1.41 [1.27–1.56] P<0.001) or every 4–12 weeks (1.22 [1.08–1.39, P=0.002]), and pts with UC preferred taking a tablet (1.41 [1.25–1.59], P<0.001) or SC administration every 4–12 weeks (1.30 [1.14–1.48], P<0.001) or every 1–2 weeks (1.20 [1.07–1.35], P=0.002). Pts exposed to ATs ranked the importance of RoA lower than that of effectiveness compared with AT-naïve pts, and 49.3% of pts with CD and 50.5% with UC indicated that they wanted ATs to start earlier.

Conclusion

This study highlights the importance of treatment effectiveness, RoA and safety for pts with IBD. Personalised care is crucial given that preferences for treatment attributes may vary across countries and among pts. Patient–physician shared decision-making discussions regarding therapy choice and timing should happen throughout the treatment journey.Read more P745 Assessment of Crohn’s disease patients following risankizumab initiation using intestinal ultrasound: A prospective studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Risankizumab (RIS) is a humanized monoclonal antibody that inhibits interleukin-23 by binding to its p19 subunit. The use of RIS in the treatment of moderate to severe Crohn’s Disease (CD) was approved in December 2022. Intestinal ultrasound (IUS) is an accurate and well-tolerated modality for evaluating response to therapy. Here, we assessed the IUS response at 3 and 6 months following RIS therapy.

Methods

CD patients initiating RIS were recruited and evaluated by IUS at baseline (within 14 days of initiation), 3, and 6 months. Data elements collected at baseline included demographics, medication exposures, surgical history, as well as inflammatory biomarkers. IUS response (decrease in bowel wall thickness (BWT) ≥ 25%)) and transmural remission (TR) (normalization of BWT normalization, color doppler signal (CDS, modified Limberg (ML) score 0), wall stratification, inflammatory fat)) for each segment were evaluated. Paired t-tests were used to compare values at 3 and 6 months relative to baseline.

Results

A total of thirty-three (20, 60.6% female) patients were recruited; 30 completed baseline and 3 month IUS, while 18 patients have also completed a 6 month IUS. Median age was 55 years (IQR 39-63), with a 12 year median CD duration (IQR 5-28). Five had inflammatory behaviour, 19 had stricturing, and 6 had fistulizing behaviour. CD distribution was 18 ileal, 1 colonic, and 11 ileocolonic. Baseline mean CRP (4.1 ± 4.9 mg/L) did not differ at 3 months (5.0 ± 6.8 mg/L, p=0.16), nor at 6 months for patients with values available (6.2mg/L ± 8.3, p = 0.38). Of patients with FC concentrations, 3 month mean FC (129.4 ±70 mcg/g) (9 patients) had significantly decreased from baseline (427.6 ± 271 mcg/g) (p=0.008), and similarly at 6 months (9 patients; baseline 396 ± 299 vs. 129 ± 75, p = 0.02). 80.0% (4/5) patients with colonic BWT > 3mm had IUS response (baseline mean BWT 5.6±1.4mm vs 3.5 ± 0.8mm at 3 months (p=0.011). IUS response was achieved in 20% (5/25) with ileal CD at 3 months (BWT 6.3 ± 2.1mm vs 3 month 6.0 ± 2.5mm (p=0.31). 21.4% (3/14) of ileal CD patients had an IUS response at 6 months. There was a non-significant ileal BWT reduction (5.4 ± 1.6mm) from baseline (6.0 ± 1.7mm) at 6 months. Of the 9 with moderate to severe CDS, 55% (5/9) had reduction to mild CDS by 3 months. TR was achieved by one patient with ileal CD at 6 months.

Conclusion

IUS response was achieved in 80.0% of CD patients with colonic disease at 3 months follow RIS initiation. IUS response was detected for 20% of ileal CD patients at 3 months and 21.4% at 6 months A significant FC reduction by 3 and 6 months was attained. Further prospective patient recruitment and IUS at 6 and 12 months to assess preliminary results and longer-term response is needed.Read more P476 Correlation between fecal calprotectin and inflammation on ultrasound in fibrostenotic Crohn’s DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Fibrostenotic Crohn’s Disease (CD) is a challenging phenotype particularly due to the absence of intestinal anti-fibrotic therapies. Differentiating between strictures that are predominantly fibrotic versus inflammatory remains a diagnostic dilemma. The ability to make this differentiation is critical to inform therapeutic decisions. Fecal calprotectin (FC) is a stool marker reflective of intestinal inflammation. Very few studies have evaluated the relationship of FC concentration in ileal CD strictures and parameters of inflammation on intestinal ultrasound (IUS). Strictures on imaging are defined as 1) increased bowel wall thickness (BWT), 2) narrowed luminal apposition, and 3) pre-stenotic dilation (PSD). BWT and hyperemia (color Doppler signal (CDS)) are the most sensitive markers for CD inflammation on IUS. It is predicted that FC will match CDS in ileal strictures, similar to non-stricture phenotypes. We aim to correlate FC levels with IUS inflammation of ileal CD strictures.

Methods

We performed a retrospective cohort pilot study exploring the relationship between FC levels and IUS inflammatory parameters in ileal strictures. FC levels were obtained ≤ 60 days of index IUS in fibrostenotic ileal CD patients. Individuals who underwent medication changes or experienced a clinical flare during this period were excluded. Inflammation was measured as BWT and CDS using a modified Limberg (ML) score. Pearson correlation for continuous variables, Spearman rank correlation and a Kruskal-Wallis test for FC and Limberg scale were completed.

Results

A total of 25 fecal samples were obtained from 17 patients with ileal strictures (47% male, median age 59 years (range 18-76)) were assessed. Median FC concentrations was 204.9 ug/g, IQR: 250.4. Median ileal stricture BWT was 7.0 mm (range 3.0–10.0). 40% (10/25) had ML1 (short chains in bowel), 32% (8/25) ML2 (long chains in bowel), and 28% (7/25) ML3 (long chains and perienteric fat). There was no correlation between FC and BWT (r=0.02, p=0.92), nor FC with ML scores (r=0.20, p=0.25). In those with ML1, median FC was 232.4, while those with ML2 or 3, had a FC of 155.6 and 469.7, respectively. FC values were significantly different between the ML scores, p<0.0001.

Conclusion

FC levels were not correlated with inflammatory parameters as seen on IUS in ileal CD. This unexpected finding may be due to ML2 scores having lower FC than anticipated, and small sample size. Other imaging factors such as loss of wall stratification need to be taken into account, and are perhaps more reflective of inflammation than BWT and CDS. This study provides the initial data to assess accuracy of FC and hyperemia of ileal CD strictures on IUS compared to histologic measures of inflammation on resected specimens.Read more P746 Real-world Effectiveness and Safety of Advanced Combination Therapy in Patients with Inflammatory Bowel Disease: A Multi-center Brazilian StudyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Advanced Combination Therapy (ACT) involves the concurrent use of biologic agents and/or small molecules and is a viable consideration for patients with concurrent immune-mediated diseases (IMIDs), uncontrolled extraintestinal manifestations (EIMs), or refractory disease. This study aims to evaluate the real-world effectiveness of ACT in a cohort of patients with inflammatory bowel disease (IBD).

Methods

We conducted a retrospective multi-center study, including patients with active IBD initiating ACT within the last 3 years. Collected variables encompassed demographics, prior and current IBD medications, disease activity assessed by the Mayo score for ulcerative colitis (UC) and the Harvey-Bradshaw index (HBI) for Crohn’s disease (CD) at weeks 16 and 24, C-reactive protein levels (CRP), and fecal calprotectin (FC) levels. Primary outcomes were clinical response at week 16, and clinical remission at week 24. Secondary outcomes included variations in CRP and FC levels from baseline, along with the occurrence of adverse events (AE).

Results

A total of 57 patients were included in the study (35 with CD, 22 with UC), with a mean age of 39 years (SD±15.04), and 59.6% were female. The primary indication for initiating ACT was refractory disease in 49 patients, concomitant IMIDs in 8 patients, and both conditions in 3 patients. The mean follow-up was 46 weeks (SD: ±36.14 weeks). Overall, 54 patients (91.43%) had previous exposure to anti-TNF, 35 (61.40%) to ustekinumab (UST), and 24 (42.1%) to vedolizumab (VDZ). The most prevalent ACT regimens were UST + adalimumab (ADA) in 19 patients (33.34%), VDZ+ADA in 9 patients (15.79%), VDZ+UST in 9 patients (15.79%), and VDZ+tofacitinib in 7 patients (12.28%). The rate of clinical response at week 16 was 85.71% for CD and 86.26% for UC, and the proportion of patients in clinical remission at week 24 was 48.57% for CD and 40.91% for UC (Figure 1). Statistically significant differences were observed in baseline CRP levels vs. week 24 levels in CD patients (16.83 mg/dL vs. 6.26 mg/dL; p < 0.0001) and in UC patients (14.5 mg/dL vs. 4.42 mg/dL; p < 0.0147). Similarly, differences in baseline fecal calprotectin levels vs. levels at weeks 16-24 were statistically significant in CD patients (2307.84 mg/g vs. 865.64 mg/g; p < 0.0175) and in UC patients (3309.7 mg/g vs. 971.06 mg/g; p < 0.013). Nine patients (15.79%) experienced mild adverse events (AEs), none leading to treatment discontinuation.

Conclusion

In a population with refractory IBD, ACT demonstrated good tolerability and induced a significant number of patients to achieve clinical response and remission. Larger studies with extended follow-up periods are warranted to further assess the long-term outcomes of ACT in this population.Read more P477 Performance of bowel preparation quality scales in patients with Crohn’s diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The performance of bowel preparation (BP) in patients with Crohn’s disease (CD) is unknown and may be suboptimal due to the presence of mucosal inflammation, strictures, pseudopolyps and bowel resection. We evaluated the reliability and validity of available BP scales in patients with CD.

Methods

Bowel preparation, in colonoscopy videos (N=50) from patients with CD (N=40) that represented a range of bowel preparation quality and endoscopic disease activity, was independently rated twice, separated by at least 2 weeks, by 3 central readers using the Boston Bowel Preparation Score (BBPS), modified BBPS, Harefield Cleansing Scale (HCS), Food and Drug Administration bowel cleansing assessment scale (FDA BCAS), and a 100-mm visual analogue scale (VAS) of bowel cleanliness. Endoscopic activity was assessed with the Simple Endoscopic Score for CD (SES-CD). All assessments were on endoscope insertion and withdrawal and in the ileum, right colon, transverse colon, left colon, and rectum to facilitate evaluation of the relationship between BP and SES-CD scores. Reliability of BP assessment was quantified using the intraclass correlation coefficient (ICC) and interpreted with benchmarks defined by Landis and Koch.¹ Validity was assessed by within-patient correlation between each BP scale and the VAS across segments using mixed effect models. Correlation between BP quality and SES-SD scores by location was assessed using Spearman’s rho.

Results

Substantial (ICC ≥0.61) inter-rater reliability was observed for all BP scales and the VAS during insertion and withdrawal, except for the FDA BCAS, which had moderate (ICC ≥0.41) inter-rater reliability on insertion (Table 1). Intra-rater reliability was similarly substantial for all BP scales and almost perfect (ICC ≥0.81) for the VAS during insertion and withdrawal.Coefficients for the validity of all BP scales based on correlation with the VAS of bowel cleanliness exceeded 0.58 on both insertion and withdrawal. BP and endoscopic disease activity were negatively correlated in the colon, particularly in the left colon, suggesting that lower BP scores in this segment may result in higher SES-CD scores (Table 2).

Conclusion

Existing scales are reliable for the assessment of BP in patients with CD. These results provide a framework for scoring of BP quality in clinical trials for CD and support the inclusion of patients with CD for the evaluation of novel BP agents.Reference:1. Landis J.R. and Koch G. G. Biometrics. 1977:33;159-74Read more P767 Pharmacokinetics of subcutaneous infliximab induction and maintenance in patients with moderate-to-severely active Crohn’s diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Since 2021, subcutaneous (SC) infliximab (IFX) has been available for maintenance treatment of Crohn’s disease (CD) after an induction phase of 2 intravenous administrations of 5 mg/kg. The DIRECT-CD study is an ongoing randomised multicentre trial in which CD patients receive SC IFX also during induction. The applied SC IFX doses in the DIRECT-CD are based on population pharmacokinetics derived during maintenance treatment with SC IFX. We aimed to validate our induction regimen and correlate serum concentrations with clinical efficacy.

Methods

Patients with moderate-to-severe CD (Crohn’s disease activity index [CDAI]) >220 and endoscopic ulceration) received fixed SC IFX induction doses of 240 mg at week 0 and 2, followed by maintenance treatment (120 mg every other week). IFX serum concentrations and CDAI were evaluated at week 2, 4, 8, 14 and 26. Clinical remission was defined as a CDAI ≤150. For this analysis, body weight is defined as low if <80 kg and high if ≥80 kg.

Results

In total, 48 samples of 12 Crohn’s disease patients were analysed (Table 1). During the induction phase (week 2 and 4), observed IFX serum concentrations were lower than expected by the population pharmacokinetic model for all patients (median 15.0 µg/mL [IQR 9.4-20.0]). Moreover, concentrations were significantly lower in patients with a low versus high body weight (median 20.0 µg/mL [IQR 15.0-21.0] vs median 10.2 µg/mL [IQR 4.4-15.8], resp., P=0.004). During the maintenance phase (week 8, 14 and 26), median IFX serum concentrations were also higher in patients with a low body weight compared to patients with a high body weight (17.5 µg/mL [IQR 14.8-19.5] vs 8.9 µg/mL [IQR 5.8-13.8], P<0.001). No patients in the first quartile of IFX serum concentrations (≤7.0 µg/mL) at week 2 reached clinical remission at Week 8, whereas all patients who had an IFX serum concentration at week 2 of ≥15.0 µg/mL reached clinical remission at week 8. At the end of the study (week 26), clinical remission was reached in 67% of patients with a low body weight whereas only 33% of patients with a high body weight reached clinical remission.

Conclusion

These data implicate the importance of body weight in SC IFX dosing strategies. Based on these findings, SC IFX induction and maintenance treatment is changed to a weight-based dosing scheme in the ongoing DIRECT-CD trial.Read more P478 Fatigue, physical fitness, and physical activity in patients with inflammatory bowel diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Fatigue is a common and debilitating symptom in patients with Inflammatory Bowel Disease (IBD) with a great impact on quality of life and work productivity. A better comprehension of the contributing factors to fatigue could potentially pave the way for more targeted and effective strategies for managing fatigue in IBD. Fatigue may be associated with lower levels of physical activity and reduced physical fitness. Yet, the interaction between these factors in IBD, measured with validated tests, is not fully understood. Therefore, this study aimed to investigate the association between fatigue and physical fitness and physical activity in patients with IBD.

Methods

Adult patients with IBD in remission or with mild-to-moderate clinical disease activity with an ASA Physical Status <III were eligible for inclusion. Fatigue was defined as a Checklist Individual Strength-fatigue subscale score ≥35. Patient and clinical characteristics were collected, including age, sex, body mass index, comorbidities, disease duration, disease location and behavior, clinical and biochemical disease activity, smoking status, previous intestinal resection, and medication use. Cardiorespiratory fitness was measured using cardiopulmonary exercise testing to assess the oxygen uptake at peak exercise (VO_2peak). Muscular strength (peak torque at 60°/s) and endurance (fatigue rate as percentage decline in peak torque over 30 repetitions at 180°/s) of the knee extensor and flexor muscles were assessed using an isokinetic dynamometer. Objective physical activity data were collected continuously for seven consecutive days utilizing the MOX accelerometer, with activities categorized into sedentary, standing, light (LPA), moderate (MPA), and vigorous physical activity (VPA) levels.

Results

In total, 50 patients were included, with 17 being classified as fatigued. Fatigued patients had significantly higher BMIs, a higher frequency of clinical disease activity, and a higher prevalence of smoking (Table 1). They also exhibited significantly lower VO_2peak (mean [±SD] 28.1 [±7.9] vs. 36.0 [±9.8] mL·kg^-1·min^-1, p=0.007) and higher knee extensor fatigue rate (mean [±SD] 39.0% [±8.8] vs. 31.1% [±10.4], p=0.010) compared to non-fatigued patients. There was no statistical significant difference in physical activity between fatigued and non-fatigued patients.

Conclusion

Although physical activity did not differ between patients with and without fatigue, fatigued patients exhibited lower cardiorespiratory fitness and knee extensor muscular endurance. A larger population is needed to further investigate the influence of patient and disease characteristics on this relationship to work towards more targeted and effective strategies for managing fatigue in patients with IBD.Read more P792 Real-world evidence comparison of the effectiveness of ustekinumab with anti-TNF or vedolizumab in ulcerative colitis: 1-year maintenance therapy results from the prospective, observational RUN-UC studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Observational real-world evidence (RWE) studies on the effectiveness of ustekinumab (UST) in ulcerative colitis (UC) are needed in addition to RCTs, which may not represent everyday clinical practice. For this reason, the prospective, controlled, propensity score (PS)-adjusted RUN-UC study was conducted on UC patients starting a new biologic therapy with a follow-up period of up to 3 years. The aim of the present analysis was to evaluate the 1-year maintenance therapy effectiveness of UST vs. anti-TNF or vedolizumab (VDZ).

Methods

Between 2020-2022, 507 UC patients starting a new therapy with UST or other biologics were enrolled in 34 IBD-experienced centres in Germany. After the exclusion of patients with a stoma, small molecules and missing outcomes, the final sample consisted of 476 patients. Response modified (reduction in partial Mayo score (pMayo) by ≥3 points from baseline to month 12 and a reduction of at least 30% or achievement of remission at month 12), clinical remission (CR) (pMayo ≤ 1 plus a bleeding subscore=0) and steroid-free remission (pMayo ≤ 1, bleeding subscore=0 and no systemic use of steroids or oral budesonide use in the previous 8 weeks) were considered as outcomes. To reduce the effect of confounders, PS adjustment with inverse probability of treatment weighting (IPTW) was implemented. Health-related QoL was assessed by using the visual analogue scale (EQ-VAS) of the EQ-5D.

Results

A total of 476 UC-patients [147 UST (bio-naïve: 12), 168 anti-TNF (ADA: 32.7%, IFX: 59.5%, GOL: 7.7%) (bio-naïve: 114) and 161 VDZ (bio-naïve: 105)] were included in the analysis. The PS-adjustment eliminated systemic differences in the baseline parameters (UST/anti-TNF/VEDO: 42.2/47.0/50.3% males, 25.2/25.0/19.9% EIMs), in particular, the "bio-experienced" characteristic was also equalised, between the groups. Treatment persistence over 12 months was different between UST (93.9%), VDZ (87.0%) and anti-TNF (75.0%) (Fig. 1). The PS-weighted effectiveness of UST (mITT analysis) in terms of response, clinical and steroid-free remission at month 12 (Tab. 1) was comparable to that of anti-TNF and VDZ, as was also the case without PS-weighting (CR: UST 33.1%, anti-TNF 38.5%, VDZ 38.1%). Patients of all treatment groups showed significant improvements in QoL measured as the EQ-VAS after 12 months of treatment.

Conclusion

In this prospective RUN-UC study with PS-weighted groups, UST showed similar maintenance effectiveness compared to established biologics in UC (anti-TNF and VDZ) with a relatively higher treatment persistence of UST, probably serving as a proxy for effectiveness, suggesting that additional criteria, such as safety and patients´ profile, may play an important role in the selection of biologics.Read more P479 The prevalence and risk factors of hematologic malignancy in patients with intestinal Behçet’s diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The association of intestinal Behçet’s disease (BD) with the risk of hematologic malignancy is still unclear. We aimed to assess the prevalence and determine risk factors of hematologic malignancy in intestinal BD.

Methods

Using a cohort of patients with intestinal BD between 1997 and 2021, the prevalence and risk factors of hematologic malignancy were analysed by logistic regression analysis at inflammatory bowel disease centre of Severance Hospital, Seoul, Korea.

Results

Among 780 intestinal BD patients, 23 patients developed hematologic malignancy. Myelodysplastic syndrome (MDS) (n=12) was the most common hematologic malignancy, followed by aplastic anemia (AA) (n=7), leukemia (n=2), and lymphoma (n=2). Eight patients had developed hematologic malignancy before their intestinal BD diagnosis and 15 patients developed hematologic malignancy after their intestinal BD diagnosis. Of the 772 patients without previous hematologic malignancy, patients smoking history (p-value 0.019, odds ratio [OR] 49.513, 95% confidence interval [CI] 1.925-1273.4), history of at least one emergency room (ER) visit (p-value 0.025, OR 26.360, CI 1.501-462.92), and albumin lower than 3.3g/dL (p-value 0.046, OR 603.013, CI 0.108-328191.23) at diagnosis were positively associated with subsequent hematologic malignancy. Body mass index (BMI) (p-value 0.030, OR 0.569, CI 0.342-0.947) was negatively associated with hematologic malignancy.

Conclusion

The physicians who care for intestinal BD patients with risk factors should be aware and provide careful monitoring of the elevated risk of hematologic malignancy.Read more P793 Efficacy and safety of probiotics in inflammatory bowel disease: an umbrella review and updated meta-analysis of randomized controlled trialsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Probiotics hold potential in IBD, yet knowledge gaps persist. We aimed to perform an umbrella review of systematic reviews and updated metanalysis of all RCT assessing the effect of probiotics in on Crohn’s disease (CD) and ulcerative colitis (UC).

Methods

We searched MEDLINE, Web of Science, and Cochrane Central Register of Controlled Trials until September 2023 for systematic reviews and randomized controlled trials (RCT). Primary outcomes were clinical response and remission; secondary outcomes included endoscopic response, remission, and side effects. We calculated odds ratios using a random-effects model in R. Quality was assessed using the AMSTAR-2 (systematic reviews) and Jadad scale (RCTs), the Cochrane Collaboration tool was used to grade trials’ risk of bias.

Results

Out of 2613 search results, 67 studies (22 systematic reviews and 45 RCTs) met eligibility criteria. In the updated meta-analysis, the OR for clinical remission was 1.88 (95%CI 1.20-2.93, I²=60% - Figure 1). However, the positive effect was statistically significant only for UC (OR 2.00, 95% CI 1.28-3.11, I²=57%) but not for CD. Likewise, probiotics significantly decreased the odds of clinical recurrence in UC patients (OR 0.65, 95%CI 0.42-1.01, I²=52%) and in relapsing pouchitis (OR 0.03, 95%CI 0.00-0.25, I²=64%), but not in CD. The De Simone formulation consistently outperformed other probiotics in achieving remission and preventing recurrence in UC. On the other hand, the use of probiotics was not associated with better endoscopic outcomes. The occurrence of both mild and severe adverse events was comparable to control group.

Conclusion

Our results support the use of probiotics for patients with UC, both for the induction of clinical remission and for the prevention of relapse, as well for patients with previous diagnosis of pouchitis, and reinforces their good safety profile.Read more P508 Pre-operative exposure to tofacitinib is as safe as biologics in patients with ulcerative colitis undergoing colectomy: a multicentre observational studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Patients with ulcerative colitis (UC) receiving immunomodulators are at substantial risk of colectomy. Since robust evidence regarding the post-operative outcomes of patients treated with anti-JAKs in the pre-operative phase is lacking, we aimed to assess the risk of complications of tofacitinib exposure prior to colectomy in comparison with anti-TNFs, vedolizumab, and ustekinumab.

Methods

A multicentre, retrospective, observational study was conducted across 27 European Centres. Patients with active UC who underwent a total colectomy for medically refractory disease were included. Patients were considered exposed to tofacitinib when they had received the last dose within 4 weeks of surgery and exposed to biologics when they had received the last dose within 12 weeks of surgery. Primary outcome was the occurrence of any complications within 30 days (early) and 90 days (late) after surgery. Secondary outcomes were the occurrence of infections, sepsis, surgical site complications (SSC), venous thromboembolic events (VTE), hospital re-admissions and re-do surgery within the same timepoints.

Results

In total, 301 patients were recruited, whose baseline characteristics are reported in Table 1A. No significant differences were found in any outcome across the groups, except for a significantly higher rate of early VTE with anti-TNFs (P=0.047) and of late VTE with VDZ (P=0.03) (Table 1B). In the multivariate analysis, drug class was not associated with a significantly higher risk of any complications both at 30 and 90 days. However, urgent surgery provided a higher risk of any early complications (OR 3.04, 95%CI 1.33-6.96) and late complications (OR 4.57, 95%CI 1.31-15.91), early hospital re-admission (OR 9.90, 95%CI 2.23-43.95) and early re-do surgery (OR 6.86, 95%CI 1.40-33.47). A steroid dose higher than 20 mg of oral prednisone increased the risk of any early complications (OR 2.42, 95%CI 1.14-5.13), early SSC (OR 2.38, 95%CI 1.02-5.55), and early re-do surgery (OR 7.70, 95%CI 1.59-37.14). A higher Charlson comorbidity index increased the risk of any early complications (OR 1.40, 95%CI 1.06-1.84), early infections (OR 1.67, 95%CI 1.17-2.37), early sepsis (OR 2.67, 95%CI 1.46-4.90), and early SSC (OR 1.38, 95%CI 1.04-1.84).

Conclusion

Pre-operative tofacitinib treatment demonstrated a post-operative safety profile comparable to that of biologicals in patients with UC undergoing colectomy. No warning signals were found, with particular regard to VTE and infections. Due to its fast wash-out, tofacitinib could represent an appealing strategy in severe cases in which likelihood of urgent surgery is increased.Read more P794 Relationship between Ustekinumab Trough Concentrations and Clinical, Biochemical and Endoscopic Outcomes in Crohn’s Disease; A Multi-Center Nationwide Study (TARGET STUDY)Wed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Ustekinumab (UST) has been shown to be effective in inducing and maintain clinical and endoscopic remission in Crohn’s disease (CD). We aim to assess whether ustekinumab trough levels are associated with improved outcomes in CD in real life settings

Methods

We recruited patients with CD who were treated with ustekinumab for at least 6 months from January 2017 to June 2023. Patients received ustekinumab 6mg/kg intravenous induction followed by 90 mg every 4 or 8 weeks during maintenance were included. Clinical, biochemical, and endoscopic outcomes, trough concentrations of ustekinumab that was taken from week 42 to week 52 were included. Primary outcome was to assess if ustekinumab trough concentrations were associated with clinical remission, biochemical normalization, and endoscopic remission. Logistic regression was conducted to assess outcomes

Results

A total of 137 patients with CD. mean age of 34.1 years and 83 (60.6%) males. The mean serum levels of ustekinumab was 7.2 (SD 4.5). Using Spearman correlation analysis, a strong negative correlation was observed between ustekinumab drug levels and SES-CD score (r = -0.464, p < 0.001. Additionally, ustekinumab drug levels demonstrated substantial negative correlations with disease severity measured by HBI score (r = -0.582, p < 0.001), C-Reactive Protein(CRP) levels (r = -0.598, p < 0.001) and fecal calprotectin (FCAL) levels (r = -0.529, p < 0.001). A multivariate analysis adjusted for age, sex and BMI showed a significant association between ustekinumab serum drug levels and predefined outcomes. Ustekinumab serum drug level above 4.5 mcg/ml was associated with 24% increase in the likelihood of having an SES-CD score less than 3 (OR 1.24, CI 1.12-1.37, P<0.001), 44% more likely to achieve HBI score less than 5 (OR 1.44, CI 1.26-1.65, P<0.001), 52% higher likelihood of CRP less than 10 (OR 1.52, CI 1.31-1.77, p < 0.001), and 42% increased likelihood of FCAL less than 250 (OR 1.42, CI 1.24-1.62, p < 0.001).

Conclusion

Ustekinumab trough concentrations above 4.5 mcg/ml was associated with clinical, biochemical and endoscopic remission in Crohn’s disease. Prospective data is warranted to confirm these findingsRead more P509 Upadacitinib improves symptomatic responses in patients with moderately to severely active Crohn’s diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Upadacitinib (UPA), an oral Janus kinase inhibitor approved for the treatment of moderately to severely active Crohn’s disease (CD), has demonstrated the ability to provide rapid symptom relief within the first week of induction treatment in patients with CD.¹ As symptomatic remission is critical for patients, this phase 3 post hoc analysis evaluated the impact of UPA on patient-reported outcomes (PROs) of abdominal pain score (APS) and stool frequency (SF) over the full induction and maintenance time periods.

Methods

Data were pooled from the U-EXCEL (NCT03345849) and U-EXCEED (NCT03345836) induction studies evaluating patients with moderately to severely active CD with an average daily APS ≥ 2 and/or SF ≥ 4 and received UPA 45 mg (UPA45) once daily (QD) or PBO for 12 weeks. Patients who achieved clinical response to 12 weeks of UPA45 induction were re-randomised in a maintenance study (U-ENDURE, NCT03345823) to receive UPA 15 mg (UPA15) QD, UPA 30 mg (UPA30) QD, or PBO for 52 weeks. APS and SF were recorded in a daily diary and evaluated over time.

Results

The average daily APS (mean: PBO 1.9, UPA45 1.9) and SF (mean: PBO 5.6, UPA45 5.4), were similar between the treatment groups at induction baseline (BL). Of patients reporting BL APS ≥ 1 (PBO 91.6%, UPA45 92.4%) or BL SF ≥ 2.8 (PBO 85.6%, UPA45 85.2%), higher proportions of patients receiving UPA vs PBO achieved APS = 0 or SF ≤ 1, or complete resolution of symptoms (APS = 0 and SF ≤ 1) at week 12 of induction, as well as at week 52 of maintenance (all P ≤ .001; Figure 1A). During induction, the mean change from BL in APS and SF was improved with UPA45 vs PBO starting at week 2 through to week 12 (all P < .001; Figure 1B-C). Throughout the 52-week maintenance period, a higher proportion of patients receiving UPA15 or UPA30 achieved APS ≤ 1 or SF ≤2.8 vs PBO (Figure 1B-C). Patients treated with UPA30 demonstrated a numerically higher rate of symptomatic response vs UPA15. In patients who met the Crohn's Disease Activity Index (CDAI) criteria per US labeling (CDAI ≥ 220 at induction BL; clinical response [CR-100] at week 12 with UPA45),² comparable symptom improvements were observed over time compared to the overall study population.

Conclusion

Patients with moderately to severely active CD demonstrated improvements in APS and SF as early as 2 weeks after UPA induction treatment. A greater proportion of patients achieved PRO-defined remission within 12 weeks of UPA induction treatment compared with PBO, which were sustained through week 52 of UPA maintenance treatment.References:1. Colombel, J. F. et al. J. Crohn’s Colitis. 2023;17;i102–32. AbbVie Inc. RINVOQ® (upadacitinib) [Package Insert]. N. Chicago, Ill.: AbbVie Inc., 2023Read more P795 Efficacy and safety of etrasimod as a first-line advanced treatment following 5-aminosalicylic acid and/or thiopurines: Data from the ELEVATE UC 52 and ELEVATE UC 12 phase 3 clinical trialsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Etrasimod is an oral, once-daily, selective sphingosine 1-phosphate (S1P)_1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC). We present data from the ELEVATE UC 52 and ELEVATE UC 12 phase 3 clinical trials¹ assessing etrasimod efficacy and safety in patients (pts) who were biologic/Janus kinase inhibitor (JAKi)-naïve and previously took 5-aminosalicylic acid (5-ASA) and/or thiopurines.

Methods

In ELEVATE UC 52 (NCT03945188) and ELEVATE UC 12 (NCT03996369), eligible pts were randomised 2:1 to etrasimod 2 mg once daily or placebo (PBO). Pts in this post hoc analysis were naïve to prior biologic and/or JAKi treatments, and included regardless of prior/concomitant corticosteroids (CS). Pts in Cohort A were previously exposed to or currently taking 5-ASA, but naïve to prior thiopurines; pts in Cohort B were previously exposed to a thiopurine with/without prior/concomitant 5-ASA. Efficacy endpoints included clinical remission and endoscopic improvement (Weeks [Wks] 12 and 52), CS-free remission and sustained clinical remission (Wk 52) and symptomatic response (Wks 2, 4, 8 and 12). Data up to Wk 12 were pooled from both trials; Wk 52 data were from ELEVATE UC 52. Safety was assessed up to 52 wks.

Results

In Cohort A, 135 and 62 pts were randomised to etrasimod and PBO, respectively; more pts in the etrasimod vs PBO arm achieved clinical remission (Wks 12 and 52), endoscopic improvement (Wks 12 and 52), CS-free remission (Wk 52) and sustained clinical remission (Wk 52; all p<0.05; Figure 1A). In Cohort B, 69 and 35 pts were randomised to etrasimod and PBO, respectively; significantly more pts in the etrasimod vs PBO arm achieved clinical remission and endoscopic improvement (Wk 12) and sustained remission (Wk 52; all p<0.05; Figure 1B). In both cohorts, numerical differences in the etrasimod vs PBO arm in pts achieving symptomatic response were seen starting at Week 2. In both cohorts, safety findings were consistent with the overall population, with no increases in incidence rates of serious AEs or serious infections in the etrasimod vs PBO arm.

Conclusion

This post hoc analysis further characterises the efficacy and safety of etrasimod as a first-line advanced treatment after conventional 5-ASA and/or thiopurine therapy, and is consistent with previous results in the cohort of pts naïve to biologic/JAKi which showed greater treatment effects than in pts experienced with advanced treatments.² Limitations included post hoc analysis and small cohort sample sizes.References1. Sandborn WJ et al. Lancet 2023; 401: 1159–1171.2. Feagan B et al. United European Gastroenterol J 2022; 10: 388–389.Read more P452 Serum Amyloid A for Predicting Surgery and Disease Exacerbation in Patients with Newly Diagnosed Crohn’s DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Crohn's disease (CD) is characterized by relapsing-remitting course with highly heterogenous prognosis, ranging from quiescent disease to complicated course with stricturing, penetrating or need of abdominal surgery. Identifying biomarkers that determine their disease course can enable implementing more aggressive preventive strategies. Serum amyloid A (SAA) has been demonstrated to involve in the pathogenesis of Crohn’s disease (CD); however, its prognostic value is still uncertain. This study was determined to explore the prognostic value of SAA for CD-related surgery and disease exacerbation in newly diagnosed CD.

Methods

We conducted a retrospective cohort study and recruited newly-diagnosed CD patients at the First Affiliated Hospital of Sun Yat-sen University. Level of SAA was detected at diagnosis. The primary outcome was CD-related surgery. The secondary outcome was disease exacerbation, defining as newly developed structuring or penetrating lesions. Association between variables and outcome was evaluated through Kaplan–Meier method and Cox proportional hazard regression analysis. For continuous variables, the optimal cutoff values were determined by using the survminer R package in the analysis of primary outcome. The prognostic model was developed by cox proportional-hazards model. Concordance-index (c-index) was used to assess the predictive ability of the prognostic model.

Results

During 2187.6 person-years (median age, 28 years, 72.4% male), 87 surgery and 153 disease exacerbation events were documented. After adjustment, a 14% higher risk for surgery (adjusted hazard ratio, aHR [95% confidence interval]: 1.14 [1.05–1.23]; p=0.001) and a 12% higher risk for disease exacerbation (1.12 [1.05–1.19]; p<0.001) were observed with a 100-unit increase in SAA level. Patients with SAA levels ≥89.2 mg/L had aHRs of 2.08 [1.31–3.28] and 1.72 [1.22–2.41] for CD-related surgery and disease exacerbation, respectively. The association between SAA and outcomes was assessed as linear by the restricted cubic spline. Adding SAA into the model including known risk factors, including age at diagnosis ≥40 years, disease behavior, disease location, and initial biological treatment, led to significant improvement in its predictive ability for surgery (net reclassification index and integrated discrimination index, p<0.001) and disease exacerbation (net reclassification index and integrated discrimination index, p<0.001). Sensitivity analyses showed robust results.

Conclusion

Our study shows that higher serum SAA level at diagnosis was associated with poorer prognosis, including risk of surgery and disease exacerbation. And prognostic models based on SAA and known risk factors could better predict prognosis.Read more P624 Development and Validation of a Clinical Decision Support Tool to Predict Outcomes of ustekinumab Treatment in Patients with Crohn’s DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Ustekinumab (UST) has been demonstrated for the treatment of Crohn's disease (CD) with a high efficacy and safety profile. There is limited data concerning disease progression after UST treatment. This study aims to establish a clinical decision support tool (CDST) to identify Chinese patients with CD who are less likely to experience disease progression under UST treatment.

Methods

A multicentre, retrospective observational study was conducted among Chinese patients with CD initiating UST between 1 May 2020 and 20 October 2022. Disease progression (including CD-related surgery, hospitalization and complications) was evaluated at week 24 (±4w). Logistic regression analysis was performed to identify factors associated with disease progression. The CDST, established based on these factors, was both internally and externally validated. The performance of this tool was tested using receiver operating characteristic (ROC) area under the curve (AUC) analyses.

Results

A total of 519 patients were enrolled in this study. In the derivation analysis, four factors including prior biologics usage, prior immunosuppressant usage, baseline faecal calprotectin, and baseline haemoglobin were identified to correlate with progression. A good predictive ability of this model was confirmed by AUC as high as 0.76 for the internal validation cohort and 0.72 for the external validation cohort, respectively. The CDST stratified patients into low, intermediate, or high risk of progression with cut-off values of 6 and 16.

Conclusion

We developed and validated a scoring system to identify CD patients less likely to experience progression at week 24 with UST therapy. This CDST will facilitate therapy decision-making and precision medicine.Read more P453 Surveillance for colorectal dysplasia and neoplasia in Latin American patients with Ulcerative ColitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

colorectal cancer (CRC) in patients with inflammatory bowel disease (IBD) has worse prognostic features and a higher mortality rate compared to sporadic CRC. Screening colonoscopy is therefore an important tool to consider in this population. The aim of this study is to describe the findings of endoscopic surveillance of CRC in patients with IBD using the technology available in Latin American countries.

Methods

Descriptive, multicentre, cross-sectional, descriptive study conducted in multiple Latin American countries in patients with ulcerative colitis (UC) more than 8 years after diagnosis and ulcerative colitis with primary sclerosing cholangitis regardless of the time of diagnosis of colitis. Surveillance colonoscopies were performed according to the availability of technology in each country.

Results

78 subjects, 50% women, from 5 countries (Colombia, Costa Rica, Peru, Ecuador, and Dominican Republic), with mean age 47.9 (range 20.01-89.71; SD 151.4) years, mean age at disease diagnosis of 34.7 (range 8.52-80.9; SD 14.08) years, and mean time of disease of 12.8 (range 4.6-56.8; SD 8.9) years. 57.7% (45/78) with extensive colitis, 8.9% (7/78) with a family history of colorectal cancer. 52.6% (41/78) on biologic therapy. 24.4% (19/78) current use of Azathioprine. 9% (7/78) of corticosteroids. 70.5% (55/78) oral mesalazine. In 5.1% it was used white light, 1.3% high resolution white light, 76.9% digital chromoendoscopy and 16.7% chromoendoscopy with staining. In those with digital chromoendoscopy, NBI was used in 38.3% (28/73), 37% (27/73) LCI/BLI, and 24.6% (14/73) I-Scan. It was found pseudopolyps in 50% (39/78), and 11.5% (9/78) stenosis. 7.7% (6/78) had a history of previous dysplasia. Regarding the Paris classification modified by SCENIC consensus, 28.2% (22/78) found 0-I lesions, 16 subjects were 0-I s, and 6 subjects 0-Ip. 5 subjects had 0-II lesions, of which 4 subjects in 0-IIa, and 1 in 0-IIc. 1 subject had lesion type 0-III. 1 subject had mixed lesions (0-IIa+0-IIc), 6.4% (5/78) lesion with ulceration, 10.2% (8/78) with disruption of lesion borders, with KUDO classification, Kudo III, 5.1 (4/78) Kudo IV and 3.8% (3/78) Kudo V. Endoscopic resectability was possible in all lesions. Histological findings were: (11/78) low grade dysplasia, (1/78) high grade dysplasia and (3/78) adenocarcinoma. As for the presence of dysplasia not visible in white light in random biopsies, it was only detected in (2/78).

Conclusion

in this first Latin American study, endoscopic techniques with digital chromoendoscopy with targeted biopsies were preferred, most were endoscopically visible and resectable lesions suggesting that the yield of targeted biopsies is superior to random biopsies.Read more P635 Intravenous albumin infusion does not augment the response rate to a combination of exclusive enteral nutrition and intravenous steroids in Acute Severe Ulcerative Colitis: a randomized controlled trialWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

30-40% patients with acute severe ulcerative colitis (ASUC) fail intravenous (IV) steroids requiring medical rescue therapy/colectomy. Low baseline albumin predicts steroid non-response, and exclusive enteral nutrition (EEN) has been shown to improve steroid response and albumin levels. Albumin infusion due to its anti-inflammatory and anti-oxidant properties can further improve steroid response in ASUC, which was evaluated in present study.

Methods

In this open-label randomized controlled trial, patients with ASUC were randomized in 1:1 ratio to albumin + SOC + EEN vs. SOC + EEN (Jan2021 – Feb2023). Both arms received 5 days of EEN with 400 mg IV hydrocortisone/day. Patients in albumin arm were administered 5 days of 20% w/v intravenous albumin (100 ml). Primary outcome was steroid failure (need for rescue medical therapy or colectomy) and proportion of patients with adverse events.

Results

Sixty-one patients (albumin-30, SOC-31) (mean age-31.6 ± 10.4 years, male- 57.4%), were included. Baseline characteristics were comparable. There was no difference in steroid failure between albumin and SOC arm (10/30 (33.33 %) vs 13/31 (41.94 %), p=0.49). No adverse events were reported with albumin infusions. Colectomy rate (10 % vs 9.68 %, P=1), response to salvage medical therapy (88.89 % vs 76.92 %, P=0.62) and median duration of hospitalization (10.5 (7-16) vs 10 (7-20), P=0.43) were also comparable. Long-term composite outcome of colectomy and re-admission rates was numerically higher in the albumin than SOC arm (37.04 % vs 17.86 %), although it did not reach statistical significance.

Conclusion

There was no benefit of intravenous albumin infusion as an adjunct to IV steroids and EEN in patients with ASUC.Read more P480 Prevalence of Peripheral Joint Manifestations among Ulcerative Colitis Patients in the Middle East: A Systematic Review and Meta-AnalysisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Inflammatory bowel disease (IBD), specifically ulcerative colitis (UC), is a chronic gastrointestinal disorder often accompanied by various extraintestinal manifestations. Peripheral joint manifestations represent a common extraintestinal complication, contributing to patient morbidity. This study aimed to systematically analyse the prevalence of peripheral joint manifestations among UC patients in the Middle East, providing insights into regional variations and potential clinical implications.

Methods

A comprehensive search was conducted in electronic databases to identify relevant studies. Inclusion criteria were studies reporting the prevalence of peripheral joint manifestations in UC patients in Middle Eastern countries. Twelve studies were selected for quantitative synthesis, involving a total of 2086 UC patients. Random-effects meta-analysis was performed, and the prevalence of peripheral joint manifestations was calculated with a 95% confidence interval (CI).

Results

The overall prevalence of peripheral joint manifestations in Middle Eastern UC patients was 18.0% (95% CI: 12.0% to 24.0%). The individual study prevalence rates ranged from 3.2% to 52.3%. A symmetrical funnel plot indicated the absence of significant publication bias. Heterogeneity among the studies was substantial (I² = 95%). Regional variations among the individual studies findings were observed, with Saudi Arabian studies reporting relatively higher prevalence rates compared to studies from Kuwait and Turkey. Gender disparities were noted, but they were not consistent across all studies. No substantial publication bias was identified in the analysis.

Conclusion

This meta analysis reveals that peripheral joint manifestations are a common extraintestinal complication in Middle Eastern UC patients. Recognizing the regional differences and gender disparities is essential for healthcare providers in the region. Further research is needed to explore the underlying factors and to improve patient care. These findings contribute to a better understanding of the clinical burden of UC in the Middle East.Read more P646 Clinical decision support in the prevention of adverse effects associated with immunosuppressive drugs in patients with Inflammatory Bowel DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

With the goal of effective and early prevention and detection of medication-related adverse effects, an explosion of technological advances is taking place. However, none of these systems are currently intelligent enough to ensure safe prescribing of treatments on their own.

Purpose

To design and integrate clinical decision rules (CDR) to increase the safety of immunosuppressive treatments in patients with inflammatory bowel disease (IBD) into an electronic prescribing assistance software (HIGEA).

Methods

This is a descriptive study conducted in a tertiary university hospital in Madrid (Spain).1. We reviewed the technical product information sheet of the immunomodulatory drugs used in the treatment of patients with IBD and the current recommendations and clinical practice guidelines on the management of IBD.2. The CDR were developed within a multidisciplinary team of physicians and pharmacists by integrating data from pharmacogenetics, microbiology, biochemistry, immunology and haematology laboratories, the electronic medical record and the electronic prescribing programme.3. Integration was performed using a standard language (HL7).

Results

The technical product information sheet of 33 immunomodulatory drugs (19 biological therapies, 6 small molecules and 8 traditional disease-modifying drugs) and the clinical practice guidelines for the treatment of IBD of the European Crohn's and Colitis organisation (ECCO) and the Spanish working group on Crohn's disease and ulcerative colitis (GETECCU) were reviewed.A total of 169 CDR were developed: 2 related to pharmacogenetics laboratory values, 26 to microbiology, 38 to biochemistry, 24 to immunology, 42 to haematology, 28 to clinical history and 9 related to concomitant use of other drugs.Of the 169 CDR, 50 (29.58 %) were related to screening prior to initiation of immunosuppressive treatment, 10 (5.92%) to drug interactions and 109 (64.5%) related to clinical conditions requiring adjustment or discontinuation of immunosuppressive treatment.

Conclusion

The incorporation of personalised clinical rules into the medical prescription and pharmaceutical validation process will allow the selection of patients in whom there could be a safety problem with immunosuppressive treatment, increasing the percentage of early detected and avoided adverse events.Future steps will be to evaluate the impact of the implementation of the CDR tool on increasing safety, reducing healthcare costs and improving patient health outcomes.Read more P481 "I’ve been told to drop out of school because I need to focus on my health and that was just devastating to hear.": Experiences of Western Canadian young adults with inflammatory bowel disease transitioning from paediatric to adult careWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The incidence of patients diagnosed with inflammatory bowel disease (IBD) in childhood/adolescence is increasing worldwide; therefore, in the upcoming years, more patients will need to transition from paediatric to adult care. A smooth transition is essential to ensure continuity of care; however, transition is a difficult time for patients, when increasing responsibility for disease management needs to be balanced with full-time employment or schooling. This study explores the transition experience of young adults with IBD who have transitioned from paediatric to adult care.

Methods

We recruited young adults with IBD using purposive sampling from two IBD centres in Western Canada for participation in a semi-structured virtual interview. Eligibility required being transferred to adult care within the previous two years and being diagnosed with IBD at least one year before transferring. Interviews were audio recorded, transcribed verbatim, and then analysed with an inductive thematic analysis approach.

Results

We interviewed 16 young adults with IBD (Table 1). We grouped features of the transition experience described by participants into the following four major themes (Figure 1): 1) Anticipation and preparedness for adult care; 2) New and existing connections; 3) Skill development for disease management; 4) Comparison of adult care to paediatric care. In the first theme, participants described feeling unprepared for and nervous about adult care. In the second theme, participants described the structure of care and noted that adult care had less appointments and the adult care team took a less holistic approach to their IBD care. Subsequent themes focused on developing relationships with the new care team, the importance of existing social supports, and becoming responsible and independent in disease management.

Conclusion

The results outline four major themes that describe IBD patients’ transition experience. These themes provide insight into aspects of transition described by patients, which can be used to improve patient care. For example, participants characterized adult care as missing elements that were present in paediatric care, suggesting a potential need to prepare patients for care differences and support them through the care adjustments. Overall, this study provides valuable insights into patients’ transition experiences which can be used to inform the development of transition supports and improve patient-centred care.Read more P658 Safety and efficacy of MH002, an optimized live biotherapeutic product, for the treatment of mild to moderate ulcerative colitis: a first-in-disease, double-blind, randomized clinical trialWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Treatment options for patients with mild to moderate ulcerative colitis (UC) failing 5-ASA are limited. MH002 is an optimized consortium of 6 non-pathogenic, well-characterized commensal bacteria with immune modulating, wound healing and gut barrier protective effects. This study evaluated the safety, efficacy, and mechanistic effects of MH002 in mild to moderate UC.

Methods

In this 2:1-randomized, double-blind, placebo-controlled first-in-disease study (EudraCT 2020-001355-33), 45 patients with mild to moderate active UC (Modified Mayo Score [MMS] =4-8 but including Mayo Endoscopic Sub-score [MES] ≥2) received treatment with 400mg MH002 or placebo (PBO) once daily for 8 wks. Full colonoscopies with biopsies were performed at baseline and wk8, biopsies and endoscopy videos were scored by blinded central readers. The primary endpoint was the rate of treatment-emergent adverse events (TEAEs). Exploratory efficacy endpoints included clinical remission (MMS ≤2 with all sub-scores ≤1 and rectal bleeding sub-score =0), endoscopic improvement (MES ≤1), and UC-100 and biomarker normalisation (C-reactive protein [CRP] ≤5mg/L, faecal calprotectin [FCP] ≤250mg/kg). Changes from baseline (CFBL) in MES and stool consistency (Bristol Stool Form Scale) were also evaluated.

Results

MH002 was safe and well tolerated: a TEAE was reported in 11/31 (35%) patients with MH002 and in 8/14 (57%) with PBO. Most TEAEs were mild and unrelated to study treatment. Early discontinuations (7/45; 16%) occurred similarly in both groups. At wk8, patients achieved clinical remission, endoscopic improvement, and biomarker improvements at higher rates with MH002 vs PBO (Table 1). Clinical remission rates were 14% for MH002 vs 7% for PBO (Per-protocol Set [PPS]: 18% vs 0%). Significant differences in favour of MH002 over PBO were seen in the CFBL for MES at wk8 (P=0.05, 1-sided Wilcoxon) and for stool consistency at wk2 (P=0.0057, 1-sided Student t). In total, 14/45 (31%) and 36/42 (86%) patients had elevated CRP and FCP levels at baseline, resp. Of these, more patients treated with MH002 achieved normalisation at wk8 (CRP: 60% vs 25%; FCP: 36% vs 15%). Decreases in FCP and stool consistency with MH002 were observed as early as wk2 and were greater than with PBO through wk8 (Fig 1).

Conclusion

MH002 treatment was safe and well tolerated and resulted in clinically meaningful improvements in disease activity and inflammatory parameters. MH002 therefore represents a promising new treatment for mild to moderate UC patients insufficiently controlled with 5ASA. These results warrant further development in a phase 2/3 study.Read more P482 Diagnostic accuracy of contrast-enhanced ultrasound for fibrotic strictures of Crohn’s disease: a systematic review and meta-analysis of individual participant dataWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Crohn's disease (CD) often leads to the development of intestinal strictures, requiring effective differentiation between inflammatory and fibrotic for the optimal treatment strategies. Despite recent advances in drug development targeting fibrosis, current evaluation methods remain insufficient. Contrast-enhanced ultrasound (CEUS) is a promising modality for assessing vascularity and inflammation, yet its accuracy in fibrosis detection needs more validation.

Methods

A systematic review and meta-analysis were conducted using IPD to determine the diagnostic accuracy of CEUS in identifying intestinal fibrosis in CD. Our search included databases such as MEDLINE, EMBASE, and Web of Science up until March 23, 2023. Inclusion criteria required a confirmed diagnosis of CD and studies that evaluated the accuracy of CEUS parameters, including total area under the curve (AUC), wash-in AUC, wash-out AUC, peak enhancement, wash-in perfusion index, wash-in rate, wash-out rate, rise time, fall time, and mean transit time related to fibrosis in CD (Figure 1 (A)). The quality of included studies was assessed using the QUADAS-2 tool, with each study mandatorily using surgical specimen pathology as a reference standard in at least one instance.

Results

Our qualitative synthesis included eight studies encompassing 306 patients. These studies were generally assessed to have a high risk of bias. It is important to note that while peak enhancement and AUC were frequently examined across studies, neither parameter had established absolute cutoff values for the diagnosis of fibrosis. From the three studies where IPD was available, detailed data from 80 patients were included in the meta-analysis (colon n=11 and small bowel n= 69). Among them, 54 underwent surgical intervention with fibrosis being confirmed in 31. The highest diagnostic accuracy was observed for total AUC and wash-in AUC, with pooled sensitivity and specificity for predicting fibrosis at 0.86 (95% CI, 0.59–0.97) and 0.25 (95% CI, 0.03–0.76), respectively (Figure 1 (B)).

Conclusion

This meta-analysis with IPD pioneers the exclusive evaluation of CEUS for fibrotic strictures in CD. It reveals a significant risk of bias in the primary research and a notable absence of consensus on the CEUS parameters' threshold values for distinguishing fibrosis from inflammation. The observed low specificity highlights the need for innovative strategies in future research, such as integrating CEUS with techniques like elastography, to enhance the precision of fibrosis detection in CD. PROSPERO 2020 CRD42020214472. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020214472Read more P659 Prognostic markers in Treat-to-Target for Crohn’s Disease- an Asian institution’s experienceWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Endoscopic healing (EH) is a long-term treatment target in the Treat-to-Target approach for Crohn’s Disease (CD). However, not all patients with CD will achieve this treatment target due to a combination of factors. This study aims to evaluate the proportions of patients with CD who achieve EH at 24 months from diagnosis. Secondary aims include proportion of patients who achieve corticosteroid free clinical remission (CSFR), biomarker (BM) normalization and predictors of failure to achieve EH.

Methods

This is a retrospective study of all patients with Crohn’s disease seen at a tertiary hospital in Singapore from January 2010 to December 2021. Patients with a confirmed diagnosis of CD based on endoscopic, clinical and histological findings were identified from existing IBD registry. Those with a follow-up period of less than 12 months, no repeat endoscopy and missing data were excluded from analysis. We collected data on baseline demographics, disease characteristics and treatment received. Treatment targets were assessed in terms of CSFR, biomarkers normalization, EH and transmural healing (when available). We defined these targets as outlined in the selecting therapeutic Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) II initiative. Statistical analysis was performed in Python using statsmodels 0.14.0.

Results

We identified a total of 86 CD patients. After excluding 29 patients, 59 patients were included in the final analysis.Mean age at diagnosis was 33 years old, and 69.5% were males. Table 1 demonstrates the baseline demographics and disease characteristics of all patients. The median follow-up period was 101 months. Out of 59 patients, 88% (n=52) and 80% (n=47) achieved CSFR and biomarker normalization respectively at 12 months. At 24 months of follow up, EH was achieved in 54% (n =32) of all patients. Of those who achieved EH, 22 had repeat imaging and transmural healing was documented in 14 patients. On multivariate logistic regression, Montreal B3 (penetrating type) disease was predictive of failure to achieve EH (OR 9.8, p= 0.036). Use of biologics also showed a trend for failing to achieve EH though this was not statistically significant (OR 3.5, p = 0.075).

Conclusion

A vast majority of CD patients were able to achieve corticosteroid free clinical remission and biomarker normalization. Penetrating disease was predictive of failure to achieve EH at 24 months. This study provides additional evidence in determining treatment targets for CD patients based on their disease phenotypes. These findings could be further validated in larger cohort, prospective studies.Read more P483 Fatigue and brain morphology in active and remitted Crohn’s DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Extraintestinal symptoms like fatigue and psychosocial impairments are highly prevalent in IBD, especially during active phases of the disease. They not only significantly impair patients’ quality of life, but can also alter the disease course. Disturbances of brain-gut-interactions may contribute to these symptoms. The aim of this study was to examine associations between brain structure, inflammatory biomarkers and symptoms of fatigue, depression and anxiety in persons with Crohn’s Disease (CD) in different disease states.

Methods

We prospectively enrolled n=109 participants (n=67 persons with CD, n=42 healthy controls). All participants underwent cranial magnetic resonance imaging at 3Tesla, provided stool samples for analysis of faecal calprotectin and completed questionnaires to assess symptoms of fatigue, depression and anxiety. We analysed differences in grey matter volume (GMV) between patients and controls and associations between regional GMV alterations, neuropsychiatric symptoms and faecal calprotectin.

Results

Symptoms of fatigue, depression and anxiety were increased in patients with CD compared to controls, with the highest scores in active CD (Table 1). Patients exhibited regionally reduced GMV in cortical and subcortical sensorimotor regions, occipitotemporal and medial frontal areas. GMV in some of these regions showed a significant negative association with fatigue, but not with depression or anxiety (Fig. 1a). Subgroup analyses revealed symptom-GMV-associations for fatigue in remitted (Fig. 1b), but not in active CD (Fig. 1c), while fatigue was positively associated with fCal in active (Fig. 1c), but not remitted disease (Fig. 1b).Table 1HC (mean)SDrCD (mean)SDaCD (mean)SDStatistic (df)pSample size37-23-30---Age38.9713.6940.5214.4136.3312.680.66 (2)0.52Gender (m/f)12/25-7/16-16/14-3.97 (2)0.14Anxiety (HADS anxiety score)3.432.765.003.585.903.505.00 (2)0.009Depression (HADS depression score)1.912.643.333.474.403.205.32 (2)0.007Fatigue (WEIMuS total score)8.4911.8020.5215.8528.4313.9218.19 (2)< 0.001fCal--29,5137.83388.80313.9250.00< 0.001Figure 1

Conclusion

Our findings support disturbances of brain-gut-interactions in the development extraintestinal symptoms in CD, which may be particularly relevant for fatigue during remitted disease. Reduced GMV in the precentral gyrus and other sensorimotor areas could reflect key contributions to fatigue pathophysiology in CD. A sensorimotor model of fatigue in CD could also pave the way for novel treatment approaches, such as targeted noninvasive brain stimulation. Moreover, differences in gut-brain-disturbances between active and remitted disease with regard to fatigue may indicate the need for differential therapeutic approaches dependent on the disease state.Read more P675 Comparative efficacy of Infliximab, Adalimumab, and Ustekinumab in patients with biologics naive Crohn's disease：a retrospective observational single-center studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The number of biologics available for Crohn's disease (CD) has increased dramatically, but there is no established standard of selection and few direct comparisons of efficacy among the agents. In this study, we compared the efficacy of infliximab (IFX), adalimumab (ADA), and ustekinumab (UST) in biologics naive CD patients.

Methods

A retrospective analysis of clinical data from CD patients who received IFX, ADA, and UST as 1st biologics during the period 2014-2023 was performed.

Results

Of 137 CD patients, 8 patients who received IFX, 17 patients who received ADA, and 10 patients who received UST as 1st biologics were included. Patient background (IFX/ADA/UST group) was as follows: median age was 32/21/22 years, median disease duration was 1/2/2 years, median HBI was 5/6/6, median SES-CD was 9/6/9, median CRP was 1.59/0.49/1.03 mg/dl, median albumin was 3.7/4.3/4.2 g /dl. Prednisolone or budesonide was concomitantly administered at induction in 5 (62.5%)/4 (23.5%)/0 (0%) patients.The cumulative remission rate (IFX/ADA/UST group) was 62.5%/58.8%/85.7% at 52 weeks after biologics induction in all patients, with a higher rate in the UST group. The steroid-free remission rates at 52 weeks (IFX/ADA/UST group) were 50.0%/58.8%/90.0%, which were higher in the UST group. For patients with HBI≥5 at the biologics induction, the remission rate after 8/16 weeks was 83.3% (5/6)/66.7% (4/6) in the IFX group, 54.5% (6/11)/63.6% (7/11) in the ADA group and 75.0% (6/8)/100% (8/8) in the UST group. There were no significant differences among all groups. Regarding adverse events, one case of skin rash and one case of dizziness were observed in the IFX group, one case of skin rash was observed in the ADA group, and no adverse event was observed in the UST group. One case of intestinal obstruction occurred in the IFX group and two cases in the ADA group, but not in the UST group.

Conclusion

Induction of UST in biologics naive CD patients may be as effective as anti-TNFα antibodies.Read more P418 Lipopolysaccharide-Binding Protein (LBP) in Crohn's Disease (CD) Patients: A Promising Non-Invasive Biomarker Monitoring Disease ActivityWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Current biomarkers of inflammatory bowel disease (IBD) monitoring (serum C-reactive protein (CRP) and faecal calprotectin (FC)) have limitations in terms of specificity (SP) and sensitivity (SE), especially for Crohn’s disease (CD) patients. Lipopolysaccharide-binding protein (LBP) is a soluble acute-phase protein and is thought to partly reflect intestinal permeability by binding to bacterial lipopolysaccharides. The search for new biomarkers to monitor disease activity would improve the management of IBD patients.

Methods

This is a retrospective study including 69 IBD patients (43 CD and 26 ulcerative colitis (UC)) and 21 healthy controls (HC). Serum LBP levels were measured by enzyme-linked immunosorbent assay. Clinical, biological and endoscopic parameters were analysed for IBD patients. Statistical tests, including nonparametric tests and receiver operating characteristic (ROC) curve analysis, were used to evaluate the diagnostic accuracy of LBP.

Results

Demographics and baseline data of the overall cohort is presented in Table 1. IBD patients displayed a significantly higher LBP median (29.6 µg/mL [19.8-38.8] in CD and 22.8 [13.7-38.8] in UC) than HC (5.5 [4.4-6.5], P < 0.001) with no overlapping distributions, a finding supported by an AUC of 0.997 and 0.989, respectively for CD and UC patients (Figures 1A).In CD patients, LBP levels gradually increased with endoscopic severity, demonstrating a 1.7-fold rise in active patients compared to remitter patients (P=0.02) (Figure 1B). LBP levels were higher in Montreal B1 compared to B2 and B3 CD patients (P < 0.001) (Figure 1C). Overall, a robust correlation was observed between LBP and CRP (ρ=0.75, P < 0.001). The correlation increased upon the exclusion of cases with normal CRP levels but active endoscopic disease (ρ=0.79, P < 0.001). In those endoscopically active patients with normal CRP, LBP level was higher than in remitter patients (34.3 [29.4-37.6] vs 19.1 [10-24.7], P=0.01) with a discriminative cut-off of 25 µg/mL (SE of 100%, SP of 89%).Likewise, LBP level exhibited a positive correlation with FC (ρ=0.42, P < 0.01) which was further strengthened after excluding cases where FC measurements did not align with endoscopic activity (ρ=0.53, P < 0.01). The median LBP for those patients was 25.6 [18.5-31.5], reflecting again the interest of LBP measurement to evaluate CD activity when FC lacks sensibility.

Conclusion

Our study suggests that LBP might be a promising non-invasive biomarker for monitoring disease activity, especially in CD patients. Furthermore, in clinical situations where current biomarkers (CRP and FC) lack sensitivity for assessing disease activity, LBP could be discriminative and help filling the gap for reliable therapeutic decisions.Read more P676 Unveiling the impact on in utero exposure to biologic treatments for inflammatory bowel disease (IBD) on children's psychomotor development: Insights from the DUMBO registry of GETECCUWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Understanding the impact of in utero exposure to biologic medications in children is crucial to providing recommendations during pregnancy. The effect of biologics, particularly non-anti-TNF ones, on children's psychomotor development, has been inadequately studied.Our aim was to evaluate the impact of the exposure of biologics in utero on the psychomotor development of children during the first year of life.

Methods

Data from children born to IBD patients included in the DUMBO registry with complete Age and Stages Questionnaire (AQS-3) available up to 12 months of age were analysed. DUMBO is a prospective, observational, and multicentre registry endorsed by GETECCU, which enrols pregnant women with IBD throughout 5 years in 70 centres in Spain. Study protocol is summarized in figure 1a. Normal psychomotor development was defined by ASQ-3 scores above the lower limit of normality (referral zone) in all domains (communication, gross motor, fine motor, problem-solving, personal-social). Serious adverse events (SAE) were defined in accordance with the ICH Topic E 2 A Clinical Safety Data Management: Definitions and Standards for Expedited Reporting by European Medicines Agency. Variables associated with the risk of having impaired psychomotor development, including exposure to biologics in utero, were evaluated.

Results

352 children born to 343 mothers were included (9 pair of twins) (tables 1a, 1b and 1c). 134 children (38%) had been exposed to biologics in utero; from them, 50 (37%) had been exposed to adalimumab, 44 (32%) to infliximab, 3 (2.2%) to certolizumab, 1 (0.7%) to golimumab, 28 (20%) to ustekinumab, and 10 (7.5%) to vedolizumab. 8% of the mothers were smokers during pregnancy; no other toxic consumption (alcohol or drugs) was recorded. The ASQ-3 results across different domains are presented in figure 1b, and the impact of the different factors associated with the neurodevelopment in these children is summarised in table 1d. In the multivariate analysis, to have been born to a mother with CD (vs. UC) was associated with higher likelihood (OR=2, 95%CI=1.1-3.9), while to be premature was associated with lower likelihood (OR=0.3, 95%CI=0.1-0.6) of having ASQ-3 scores above the limit of normality in all domains at 12 months of age. Other variables, including the exposure to biologics in utero, had no impact on the AQS-3 scores at month 12.

Conclusion

In the multicenter, prospective DUMBO registry, the exposure to biologics for the treatment of IBD in utero (including anti-TNF and non-anti-TNF agents) did not impair the psychomotor development of the children. Our findings support the safety of these drugs and reinforce the recommendation to continue them during pregnancy.Read more P419 Proximal Crohn’s disease location is associated with a more benign course of perianal Crohn’s disease (the PERIAPROX study)Wed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Proximal Crohn’s disease (CD) location (L4 according to the Montreal Classification) is associated with a more severe course with higher risk of abdominal surgery. However, little is known about the relation with perianal disease. The aim of our study was to investigate the impact of L4 disease location on perianal disease incidence and clinical course.

Methods

A case-control study was conducted in the prospectively maintained ENEIDA database for all CD with and without L4 location between January 2005 and March 2023. Demographic data, disease characteristics, perianal disease diagnosis and evolution according to biologic therapy and surgery requirement were collected. Demographic data, CD characteristics, perianal disease diagnosis and course were analyzed. Cox proportional hazards and Kaplan-Meier methods were used for the analysis of perianal incidence, and biologic and surgery requirement.

Results

A cohort of 14022 CD patients were included in the analysis. The mean follow-up duration was 6.4 years (SD 4.9). L4 location showed a lower prevalence of perianal disease (18.0 vs 19.9%, p=0.018), with lower rate of fistulas (60.9 vs 66.1%, p=0.021) and perianal abscesses (33.5 vs 39.4%, p=0.013). Perianal disease and L4 were associated with male sex (OR 1.29, p<0.001), younger age (43 vs 44), and the structuring phenotype (OR 2.14, p<0.001). L4 location was associated with a lower incidence of perianal disease (HR 0.891, p=0.041), while proctitis was associated with a higher risk (HR=2.161, p<0.001). L4 location was also associated with a lower requirement for biologics (HR 0.712, p=0.023), along with advanced age (HR 0.988, p<0.001). Proctitis (HR 1.292) and a history of perianal surgery (3.373) were associated with a higher requirement for biologics. At univariate analysis, L4 location was associated with a lower requirement of surgery (HR 0.833), however at multivariate analysis this finding was not confirmed (p=0.525). Instead, a history of active smoking (HR 1.419), the use of biologics (HR 2.262), and CD penetrating pattern (HR 1.277) were associated with a higher requirement for perianal surgery.

Conclusion

L4 location is associated with a lower incidence of perianal disease and a more benign course with lower requirement for biologics and surgery.Read more P695 Untargeted proteomics analysis of baseline serum samples prior to biologic therapy initiationWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Biologic drugs such as anti-TNFα antibodies are predominantly used in a step-up setting and prescribed for Crohn’s disease (CD) patients who have failed, or are contraindicated for, first-line therapies. However, patient response to biologics is highly variable, with only a minority benefitting from a strong and sustained clinical response. Presently, there is no operationally effective means in clinical care to stratify patients on individual biologic drugs. Consequently, standard of care for those with CD remains inadequate and inefficient. To identify protein biomarkers associating with treatment outcomes, we performed an untargeted proteomics analysis of baseline serum samples from individuals with moderate to severe CD starting anti-TNFα treatment.

Methods

Biobanked serum samples from 47 (42 from Amsterdam, 5 from Oxford) moderate to severe CD patients starting anti-TNFα treatment (adalimumab, infliximab or their biosimilars) with documented 12 and 26-week treatment response were used for untargeted serum proteomic analysis using SomaLogic’s SomaScan® technology platform. Data was checked for outliers using robust principal component analysis. Supervised machine learning (ML) was used to predict treatment outcome.

Results

There were 29 responders and 18 non-responders to anti-TNFα treatment (week 26). Untargeted proteomics profiles passing SomaLogic’s quality controls were generated for all samples with 7,596 proteins detected in each sample. Robust principal component analysis for anomaly detection did not reveal any substantial outliers (see Figure 1). Five different ML algorithms independently generated mean AUCs and balanced accuracies from 5x 5-fold cross-validation ranging from 0.47 to 0.53 (see Table 1) indicating no reliable signal in the data. Notably, applying the ML algorithms to detect sample origin, samples from the 2 different clinical sites (Oxford or Amsterdam) could be confidently distinguished suggesting careful protocol alignment for serum collection is essential. Of 26 proteins previously reported to be associated with biologic treatment outcome, only PF4 was found to be significantly different between anti-TNFα responder and non-responders (P=0.0043). Overall, these metrics all fall well below what would be needed for a predictor to have value in the clinic.

Conclusion

ML analysis of serum proteomics profiles for 47 CD patients did not identify any strong and reliable biomarkers of biologic treatment response suitable for clinical applications. This small study suggests serum proteins are not suitable for anti-TNFα response prediction in this population. In addition, the serum proteomic profile is highly susceptible to differences in serum collection and storage methods.Read more P438 Histological scores are poor predictors of short-term response to therapy in acute severe ulcerative colitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Although all patients with acute severe ulcerative colitis (ASUC) undergo sigmoidoscopy and biopsy, the predictive value of various histological scores is unclear. We studied the association between histological scoring and the need for second-line rescue therapy and whether these scores predict the response to therapy in ASUC.

Methods

All consecutive patients of ASUC (as per Truelove and Witts criteria) admitted from 1st April 2019 to 31st January 2021 in North India were included. All patients, who underwent sigmoidoscopy and biopsy, underwent histological assessment by two independent pathologists [Simplified Geboes score (SGS), Robarts Histopathology Index (RHI) and Nancy histological index (NHI)]. The primary outcomes were to study the association between histological scores and the need for second-line rescue therapy in index admission and the accuracy of each score in predicting the need for second-line rescue therapy or colectomy at day 28. The secondary outcomes included an association between histological scores and endoscopic Mayo scores with response to corticosteroids on day three as per Oxford criteria.

Results

Eighty-two cases of ASUC (Mean age: 36 years, males 47.5%) were analyzed. Sixteen patients required second-line drug therapy and eight patients required colectomy in index admission. There was no significant association between the need for second-line therapy or colectomy and the baseline histological scores [NHI (p=0.61), SGS (p=0.116) and RHI (p=0.109)]. All three histopathological scores performed poorly to predict the need for second-line treatment or colectomy within 28 days of admission. No significant correlation was found between endoscopic Mayo score and histological scores. There was no significant association between the degree of inflammation on baseline histology and response to steroids (NHI (p=0.796), SGS (p=0.57) and RHI (p=0.941)]. There was a strong positive correlation among the three histological scores in patients of ASUC.

Conclusion

All three scores (SGS, RHI and NHI) performed poorly in predicting the need for second-line treatment or colectomy within 28 days of admission. There is a need for dedicated histopathology scores in the setting of acute severe ulcerative colitis.Read more P439 Mild Crohn’s disease is characterized by a unique serum metabolomic signatureWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Approximately 20-30% of patients with Crohn's disease (CD) experience a mild disease course following initial diagnosis. Balancing the effectiveness and safety of medical treatments is crucial in the management of mild CD. However, the main clinical challenge currently lies in identifying patients likely to maintain this mild disease course, underscoring the urgent need for biomarkers of mild CD. In this study, we therefore aimed to identify potential circulating biomarkers for patients with mild CD leveraging a metabolomics approach.

Methods

Patients with mild CD were retrospectively identified from participants of the Mount Sinai Crohn's and Colitis Registry (MSSCR). Baseline screenings in MSSCR included assessments of the use of biologicals and immunomodulators, history of IBD-related surgeries, and the presence of disease complications (including stricturing, penetrating, and perianal CD). Mild CD was defined as the absence of all these variables at baseline as well as after a 5-year follow-up period. Untargeted serum metabolomic profiling was performed to measure the circulating metabolome of these patients. Multivariable logistic regression analyses, adjusting for age, sex, measurement batch, and smoking behavior, were conducted to identify metabolites associated with mild CD.

Results

In total, 114 patients with CD were characterized in which 1,456 different metabolites were profiled, with 32 patients (28.1%) meeting the criteria for mild CD. The remaining 82 patients (71.9%) partially met criteria for mild CD; these were all biologic-naïve and did not undergo IBD-related surgeries. Multivariable logistic regression revealed 45 distinct metabolites that were significantly associated with the mild CD group (nominal P<0.05). Sphingomyelin compounds and ceramides exhibited the most prominent associations with mild CD (odds ratios [OR] all >2.0), while tryptophan, pantothenate, and salicylate metabolites were also linked to mild CD. Conversely, primary and secondary bile acid metabolites and amino acid derivatives from lysine-, tyrosine-, and proline metabolism were all inversely associated with mild CD.

Conclusion

Mild CD is associated with distinct alterations in metabolic pathways compared to patients with moderate-to-severe CD. Future research should focus on longitudinal assessments of these metabolites for disease monitoring and determining optimal therapeutic strategies for this clinical subgroup.Read more P696 Initiation of Vedolizumab did not provoke new-onset spondylarthritis in patients with inflammatory bowel disease: A Prospective Study Including Rheumatological and Blinded Imaging AssessmentsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Prior case series indicated a temporal relationship between use of vedolizumab and new-onset spondyloarthritis.

Methods

We aimed to evaluate the relationship between initiation of vedolizumab and development of new-onset spondyloarthritis in patients with inflammatory bowel disease, through serial clinical evaluation and magnetic resonance imaging. A single-centre prospective observational study of 24 patients with inflammatory bowel disease. Patients were eligible if they had active ulcerative colitis or Crohn’s disease and initiating vedolizumab, had no prior history of arthritis or spondyloarthritis and suitable for undergoing serial magnetic resonance imaging. Clinical evaluation was performed by a rheumatologist prior to first dose of vedolizumab and at weeks 8 and 24 weeks after administration. Axial magnetic resonance imaging was performed at baseline, weeks 8 and 24 and evaluated by a blinded central reader.

Results

Nine tumour necrosis factor inhibitor-naïve patients (4 male; mean age 53.2 yrs; 6 ulcerative colitis; 3 Crohn’s disease) and eight tumour necrosis factor inhibitor-experienced patients (7 male; mean age 48 yrs; 3 ulcerative colitis; 5 Crohn’s disease) completed all assessments. No patients developed new features of axial arthritis either on clinical or blinded radiological assessment at weeks 8 or 24, nor any features of peripheral spondyloarthritis including inflammatory oligoarthritis, enthesitis, dactylitis, or psoriasis (nail, body, or scalp). Both the tumour necrosis factor inhibitor-naive and tumour necrosis factor inhibitor-experienced patients demonstrated good intestinal response to vedolizumab.

Conclusion

Initiation of vedolizumab did not induce new features of axial or peripheral spondyloarthritis in tumour necrosis factor inhibitor-experienced or tumour necrosis factor inhibitor-naive patients with inflammatory bowel disease.Read more P721 Dutch Crohn’s disease patients’ (pediatric and adult) perspectives of CDED diet and Modulife programWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The Crohn’s Disease Exclusion Diet (CDED) with partial enteral nutrition can induce remission in patients with mild-to-moderate Crohn’s disease. As adherence is the key of (possibly) success of a medical therapy and CDED might be a complicated diet to perform, we aimed to investigate patients’ experience with CDED and the available tools (Modulife programme) to improve patientcare.

Methods

All mild-to-moderate active Crohn’s disease (CD) (adult and pediatric) patients treated with CDED as nutritional therapy as part of their medical treatment at Amsterdam UMC between 2019-2022 were approached for this retrospective qualitative study. A structured telephone interview was conducted by a dedicated dietician/doctor with the patients and/or parent/guardian in case of children. Questions about CDED-experience and Modulife program were either measured with the NET Promotor Score (NPS -100 - +100), as yes/no answer options or with 5-point likert scales (1=strongly agree/always to 5=strongly disagree/never). Lastly, patients were asked to evaluate the effectiveness of CDED on complaints and experience on a scale from 0-10.

Results

44 patients (33 pediatric/11 adults; 26 women) participated in the interviews. The majority (61%) of the pediatric patients started CDED at diagnosis. The remaining 39% started 1-11 years (median 3[IQR 2-5]) after diagnosis at an age of 7-17 years (median 15[IQR 12-16]). 91% of the adult patients started CDED 3-37 years (median 11[IQR 4-28]) after diagnosis and only 1 immediately after diagnosis at an median age of 48 [IQR 33-60] (range: 19-69). The majority of the pediatric participants would recommend CDED to others (77%) and consider to start the diet again (55%). All of the adults would recommend CDED to others and consider to start CDED again. The NPS scores on CDED experiences are shown in figure 1. The median score for the effect of the diet on complaints was 8[IQR 5-9] (range 0-10) and 7[IQR 6-7](range 2-8.5) for experience. The majority of the patients (75%) used the Modulife program always or often during therapy and did (strongly) agree that the Modulife program was helpful. A NPS of 31 was given for recommending the app to others. The recipes-feature was the most used and most esteemed part of the app and was assessed with a good NPS of 27 for recommendation to others.

Conclusion

The majority of the pediatric and all of the adult participants would recommend CDED to others and would reconsider starting the diet again. CDED is better assessed by adults (positive NPS) then children and/or their parents (negative NPS). Most of the patients, assess the Modulife programme very positively and the majority would rate this as helpful in performing the diet.Read more P458 Diagnostic accuracy of patency capsule and cross-sectional imaging for capsule endoscopy retention: A systematic review and meta-analysisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Although small bowel capsule endoscopy (SBCE) has been widely used to evaluate small bowel lesions including Crohn’s disease, there is a risk of capsule retention that can cause obstructive symptoms potentially necessitating surgical treatment. We conducted a systematic review and meta-analysis to evaluate the accuracy of patency capsule (PC) and cross-sectional imaging (CSI) for predicting capsule retention.

Methods

MEDLINE/PubMed, EMBASE, Web of science, and the Cochrane library databases were searched for articles that invested the diagnostic accuracy of PC or CSI for predicting capsule retention up to August 15, 2023. Pooled sensitivity and specificity were calculated using a bivariate random-effects model. Considering that SBCE was generally not performed when capsule retention was suspected on PC, the false-negative rates of PC and CSI were separately analyzed and compared using a single-proportion meta-analysis based on random-effects modeling. Quality assessment of the selected studies was performed using the revised Quality Assessment of Diagnostic Accuracy Studies-2 tool.

Results

A total of 22 peer-reviewed articles, including 17 articles for PC (covering 2,234 patients) and 7 articles for CSI (covering 302 patients) were included in this systematic review. The pooled sensitivity and specificity for predicting capsule retention with CSI were 64% [95% confidence interval (CI), 31%–87%] and 85% [95% CI, 62%–95%], respectively. The pooled sensitivity and specificity for predicting capsule retention with PC were 75% [95% CI, 43%–92%] and 94% [95% CI, 90%–96%], respectively (Figure 1, Table 1). Although there was no statistically significant difference in prediction accuracy between PC and CSI on the bivariate random-effects model (P=0.14), the pooled false-negative rate was significantly lower in the PC compared to CSI (2.5% [95% CI, 1.4%–4.7%] vs. 11.0% [95% CI, 5.2%–21.8%]; P=0.003) (Table 1).

Conclusion

Cross-sectional imaging showed good specificity, but showed moderate sensitivity in predicting capsule retention. In contrast, patency capsule showed good sensitivity and excellent specificity, with a significantly lower false-negative rate compared to cross-sectional imaging. Therefore, in patients with clinically suspicious small bowel stenosis, the patency capsule is a more reliable modality for predicting capsule retention.Read more P459 The prevalence and characteristics of inflammatory bowel disease-related ocular involvement in childrenWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Ocular manifestations (OM) in patients with inflammatory bowel disease (IBD) are uncommon, particularly in children. We aimed to explore the prevalence, characteristics and risk factors of IBD associated OM in a large epidemiologic cohort-based study.

Methods

A cross-sectional study was performed using the Maccabi Healthcare Services (MHS) database. The eligible population included all patients diagnosed with IBD as children (<18 years) between January 2005 and July 2023. An additional analysis was conducted on patients diagnosed with ocular disease during childhood (<18 years) and IBD during childhood or adulthood.

Results

Out of 2,567 children with IBD (males 55%, Crohn’s disease 64%), 78 (3%) were diagnosed with OM at any time during disease course. In 54 patients (69%), the OM occurred after IBD diagnosis with a median time of 2.6 (0.47-7) years between the two events, whereas in 24 patients (31%) OM preceded IBD diagnosis with a median time of 2.1 (0.6-5.7) years. OM was significantly associated with Crohn’s disease, compared with ulcerative colitis (78.2% vs. 63.6% in the entire cohort; p=0.03). The presence of OM was associated with increased usage of systemic corticosteroids (p<0.001), biologic agents (p=0.04) and longer duration since IBD diagnosis (p=0.04). There were 55 patients with OM during childhood who were ever diagnosed with IBD. In this population OM was also associated with increased usage of systemic corticosteroids (p<0.001) and increased hospitalization rate per year (p=0.048). The annual prevalence of OM increased gradually from 10/1000 patients in 2005 to 22/1000 patients in 2022 (p=0.55).

Conclusion

Ocular involvement in children with IBD is rare and more common in patients with Crohn’s disease with a stable prevalence rate. It is associated with a longer duration of disease, greater usage of systemic corticosteroids and biologic agents and with a higher rate of hospitalizations, potentially representing a more severe disease course.Read more P722 The steep ramp test is a valid practical test to assess cardiorespiratory fitness in patients with inflammatory bowel diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Comprehensive disease management of inflammatory bowel disease (IBD) requires a holistic approach that extends beyond achieving endoscopic healing. Monitoring health-related physical fitness (HRPF) parameters (i.e. body composition, cardiorespiratory fitness, muscular strength, muscular endurance, and flexibility) may lead to a more proactive approach to managing IBD, as IBD may affect HRPF due to e.g. chronic inflammation, malnutrition, corticosteroid use, and reduced physical activity. Yet, knowledge regarding HRPF in patients with IBD is limited. Assessment of cardiorespiratory fitness (CRF), a key component of HRPF in other chronic diseases, could offer valuable insights into physical capacity and overall health. However, the gold standard, measuring oxygen uptake at peak exercise (VO_2peak) achieved during cardiopulmonary exercise testing (CPET) is impractical for widespread implementation in clinical practice. The steep ramp test (SRT), a short-term maximal exercise test on a cycle ergometer, might serve as a less demanding assessment method to facilitate routine assessment of CRF in clinical practice and deliver more practical endpoints for intervention studies. This study aimed to examine the criterion validity of the SRT as compared with CPET in evaluating CRF in patients with IBD.

Methods

From August 2022 to October 2023, adult patients with IBD in remission or with mild-to-moderate clinical disease activity were consecutively enrolled. Each participant performed a SRT and a CPET within 14 days to examine CRF. The main outcome measures were the achieved work rate at peak exercise (WR_peak) for the SRT (SRT-WR_peak) and VO_2peak as well as WR_peak for CPET (CPET-VO_2peak and CPET-WR_peak). Validity of the SRT was evaluated with Pearson’s correlation coefficients between SRT-WR_peak and CPET-VO_2peak and SRT-WR_peak and CPET-WR_peak.

Results

A total of 50 participants, with a mean age of 42.9 years and 56% diagnosed with CD, were included (Table 1). One participant was excluded from the analysis due to the inability to achieve a maximal effort during CPET. Mean (±SD) WR_peak attained at the SRT was 4.32 (±1.06) W·kg^-1, and mean (±SD) VO_2peak and WR_peak achieved during CPET were 33.47 (±9.85) mL·kg^-1·min^-1 and 2.90 (±0.95) W·kg^-1, respectively. Figure 1 illustrates robust linear relationships with very strong correlations between SRT-WR_peak and CPET- VO_2peak (r=0.945, p<0.001) and SRT-WR_peak and CPET-WR_peak (r=0.960, p<0.001).

Conclusion

Results of this study suggest that the SRT is a valid alternative test for examining CRF in patients with IBD, indicating its potential application in both clinical practice and intervention studies. Further research should explore the criterion validity of practical tests for other components of HRPF.Read more P496 Interdisciplinary student-led screening clinics can identify undernutrition, sarcopenia and mental health risk in ambulatory patients with Inflammatory Bowel DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The changing landscape of allied health practice has led to the emergence of student-led clinics as a resource to enable workforce capacity. Undernutrition, sarcopenia, and poor mental health are common in inflammatory bowel disease (IBD) and affect quality of life. Despite high prevalence, these co-morbidities are under-recognised due to lack of service capacity. This study aimed to determine the frequency of undernutrition, reduced physical performance and mental health risk identified by a novel student-led interdisciplinary screening clinic in ambulatory patients with IBD.

Methods

Sixteen final year dietetic, physiotherapy or exercise physiology students conducted 5-10 weekly half day interdisciplinary outpatient clinics within a tertiary IBD service between July and October 2023. Following training, students completed all aspects of the interdisciplinary consult under direct dietetic supervision. Risk screening assessments comprised of anthropometrics, depression anxiety and stress scale-21 (DASS21), subjective global assessment (SGA), short physical performance battery (SPPB), handgrip strength (HGS) and inflammatory bowel disease-nutrition screening tool (IBD-NST). Consecutive patients attending a tertiary IBD outpatient service were contacted to participate in the clinic following their gastroenterology appointment. Descriptive statistics were completed, and prevalence is presented as number (n) and percentage.

Results

Screening assessments were completed for 88 patients in the 15-week period (Table1). Patient acceptance was high with 86% of patients approached consenting to participate. High hip to waist ratio was present in 68% (n=60/88) of patients suggestive of visceral adiposity (Figure 1a). The IBD-NST identified mild nutrition risk in 5% (n=4/88) of patients and generated a referral to dietetics with a moderate nutrition risk in 21% (n=19/88) of patients (Figure 1b). Malnutrition was detected in 10% (n=8/88) of the patient population (Figure 1c). Mental health risk was elevated in 63% (n=50/79) of patients screened (Figure 1e, f, g). Physical impairment was present in 52% (n=46/88) of patients (Figure 1h &1i). The screening clinic generated 48 referrals through to varied allied health disciplines for individualised therapy.

Conclusion

A student-led interdisciplinary screening clinic ensures timely identification of patient risk for undernutrition, sarcopenia and poor mental health, improving access to early intervention opportunities. Students can act as a valuable enabler for workforce capacity at a time when the health service providers are stretched.Read more P723 Upadacitinib in Crohn’s disease: Real world experience from an early access program in GreeceWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Upadacitinib is a novel selective Janus kinase 1 inhibitor, recently approved for the management of Crohn’s disease (CD) by Food and Drug Administration. In Greece, upadacitinib is available through an early access program for refractory patients who have exhausted their therapeutic options. Our goal was to describe our real practice experience.

Methods

This is a multicenter retrospective cohort study of adult patients with moderate to severe CD, who received upadacitinib. The primary endpoint was clinical response, defined by a reduction ≥3 in Harvey-Bradshaw index (HBI). Clinical remission was defined as HBI ≤4. Secondary endpoints included endoscopic and biochemical improvement based on physician’s assessment and CRP measurement, respectively. Outcomes were assessed at 12 weeks and at patient’s latest follow up. All patients received 45mg upadacitinib for 3 months and then 30mg for another 3 months, whereas the maintenance dose (30mg or 15mg) was based on the patient’s response. We also evaluated short -term safety.

Results

A total of 22 CD patients (12 female) received upadacitinib and were included in the analysis. Mean age 42.2 years (24-63). Five patients were active smokers. Mean treatment duration was 5.4 months (1-20). Two patients have not yet reached 12 weeks of treatment and were excluded from the efficacy analysis. Ten patients (45.4%) had ileocolonic Crohn’s, seven (31.8%) ileal disease and five (22.7%) Crohn’s colitis. Four patients had perianal disease and seven patients Crohn’s related surgery (5 ileocecal resection, 2 seton placement). Four patients had active extraintestinal manifestations: Three inflammatory arthritis and one atopic dermatitis. The majority of patients (15/20) had failed ≥ 3 biologics. All of them failed treatment with anti-TNF and 15 (75%) with ustekinumab. Six patients have just completed the induction period of 12 weeks, ten are on 30mg upadacitinib and four on 15mg. At 12 weeks, 18 patients achieved clinical response (90%). CRP was normal for 15/20 (75%) patients at 12 weeks. At last follow-up (mean 5.9 months, 3-20), all patients were in clinical remission. Endoscopy was available for six patients and improvement was documented for all of them. Adverse events occurred in 3 patients (15.7%): An episode of abdominal pain, a skin infection and a case of neutropenia. All adverse events resolved without discontinuing treatment.

Conclusion

In a small cohort of medically resistant Crohn’s patients, the short- term clinical efficacy of upadacitinib was high. No serious safety issues were recorded.Read more P497 Malnutrition in inflammatory bowel disease: a correlation between clinical and nutritional parametersWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

In recent years there has been a growing focus on malnutrition affecting patients with inflammatory bowel disease (IBD) due to its consequences, including increased risk of complications, reduced quality of life and response to treatment. Several screening tools are available to assess malnutrition, but none are specific to IBD. We assessed the accuracy of MUST and Saskatchewan IBD-Nutrition Risk tool (SaskIBD-NR) compared to malnutrition according to ESPEN criteria and the association between the mediterranean diet, clinical, biochemical, and anthropometric parameters and malnutrition.

Methods

This cross-sectional study was conducted at the tertiary IBD centres of Rho Hospital and Policlinico of Palermo between October 2022 and July 2023. Consecutive outpatients with an established diagnosis of IBD participated at the study. All patients completed the MUST and SaskIBD-NR tool. IBD type, age, smoking habit, disease features (location, behaviour,), steroid therapy, previous surgery, clinical and endoscopic disease activity and anthropometric data (BMI, waist and calf circumference, handgrip strength) were analysed. Mediterranean diet score was also administered to assess adherence to the Mediterranean diet.

Results

The study sample consisted of 158 IBD patients, 96/168 (60.7%) with Crohn’s disease and 62/168 (42.28%) with ulcerative colitis (UC) were enrolled. Median age was 46.5 (32-58). The handgrip strength mean values were 31.96±10.73 Kg and the calf circumference median values were 34 cm (32-37). The prevalence of malnutrition was 13.3 %; 16/96 (16.7%) were affected by CD and 5/62 (8.1%) by UC. A moderate correlation was found between the MUST and the SaskIBD-NR tool (P<0.0001, r:0.581, Spearman). MUST have good performance in detecting malnutrition in terms of sensitivity (89%) and specificity (90%) and large area under the ROC curve (AUC 0.924, p<0.001). SaskIBD-NR had lower accuracy (AUC 0.731;p=0.0002) and sensibility (695) but high NPV (94%). Calf circumferences had a strong accuracy in predicting malnutrition with AUC of 0.887 (p<0.0001) and sensibility of 84%. At the multivariate logistic regression, waist circumference (OR 0,69 95% CI: 0,54-0,89; p=0,004) and albumin (OR 0,03, 95% CI 0,01-0,85; p=0.04) were independently associated with malnutrition.

Conclusion

Malnutrition is frequent in IBD patients. SaskIBD NR tool is less sensitive than MUST but could be useful to exclude non-malnourished patients. Anthropometric parameters such as calf and waist circumference and bioumoral parameters such as albumin should be assessed because they can predict malnutrition. Further studies are needed to validate this finding.Read more P724 Long-term outcomes of exclusive enteral nutrition in the peri-operative period for Crohn’s disease: A seven year follow-up studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Exclusive enteral nutrition (EEN) is a recommended first-line treatment for Crohn’s disease flares in the paediatric population. Its use has yet to translate widely to the adult population. There is growing evidence for the use of EEN in the pre-operative setting to downstage the disease process and improve short term surgical outcomes. Little is known in this context regarding the long term effects of pre-operative EEN. Our study reports on follow up data for a cohort of patients who underwent surgery following pre-optimisation with EEN compared to those who did not. We assessed long term complications, disease recurrence and disease control as our key outcomes.

Methods

We carried out a seven year follow up study of the patients included in a retrospective, matched cohort trial conducted in a single, tertiary care, inflammatory bowel disease centre, in the UK. Patients pre- optimised with EEN prior to surgery were compared to a matched control cohort.

Results

Median follow up period was seven and six years for EEN and control groups respectively. Patients in the EEN group were more likely to be on maintenance medical therapy compared to control (73.47% vs 46.67%, p=0.005), however, admission rates and clinical recurrence rates were similar between groups (32.65% vs 24.66%, p=0.33 and 71.43% vs 65.58%, p=0.42). There was a moderate difference in complication rates beyond six months in favour of the EEN group (5.55% vs 17.80%, p=0.08). EEN patients were more likely to need further surgery however, this observation was not sustained when surgery for peri-anal disease was excluded (22.45% vs 13.69%, p=0.21)

Conclusion

Pre-optimising patients with EEN prior to Crohn’s disease surgery may improve short term surgical outcomes, it is unlikely to improve long term disease outcomes, based on results from this study.Read more P498 An expert Delphi consensus: Early identification of patients at risk of Crohn's disease in perianal fistulas and abscesses (PREFAB) and identification and management of isolated perianal Crohn's disease (ipCD) - Part B, ipCDWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

In clinical practice, some patients with ‘idiopathic’ perianal fistulae (iPAF) and no evidence of luminal IBD are labelled ‘isolated perianal Crohn’s disease’ (ipCD) and treated with IBD-directed therapies. However, there are no accepted criteria to guide which patients should be diagnosed as ipCD, or how they should be managed. This project aimed to provide a definition of ipCD, strategies for management, and a platform for building further understanding of this group.

Methods

An expert panel of IBD gastroenterologists, surgeons and radiologists took part in a Delphi consensus on ipCD. The first-round was an electronic survey, probing: 1) personal experience of ipCD; 2) how fistula histology may influence ipCD diagnosis; 3) patient and fistula features suggestive of ipCD; and 4) suggested management of patients with suspected-ipCD. Responses informed the creation of clinical criteria for ipCD, and statements on ipCD management, which were discussed, amended, and agreed-upon at a second-round virtual consensus meeting. Consensus was predefined as ≥70% ‘strongly agree’ or ‘agree with minor reservation’.

Results

>30 specialists participated. In round 1: 93% agreed ipCD is a separate Crohn’s phenotype; 83% reported having treated ipCD patients with IBD medical therapies; 73% agreed iPAF patients with fistula histology suggestive of ipCD could be labelled as histologically-confirmed ipCD; and 93% agreed histologically-confirmed ipCD with complex fistulation should be treated with IBD medical therapy (e.g., biologics). However, there was no consensus on the appropriateness of IBD medical therapy for simple fistulae. For iPAF patients without histological evidence of IBD, the panel agreed factors suggestive of ipCD. These included: family history of IBD, symptoms of IBD extraintestinal manifestations, co-existent/previous perianal lesions (fissures, anal stricture, tags), and certain fistula features. Factors were used to produce a criteria to diagnose ipCD and identify patients appropriate for a trial of medical therapy. If a trial of therapy is pursued, the panel agreed careful discussion of the risks of treatment, and known-unknowns, when treating ipCD. Optimised anti-TNF is preferred first-line (82% agreement) with a careful review of treatment response, and contemporaneous MRI, at 6-12 months (93% agree).

Conclusion

ipCD is a contentious label and standardisation of the diagnosis could help us better assess this group and their treatment outcomes. We present a suggested criteria for diagnosing this group, and a pragmatic approach to trialling biologic therapy. Key to managing this group is honest discussion regarding the known-unknowns of ipCD treatment, to manage patient expectations and support a joint decision-making approach.Read more P760 Post-marketing surveillance of tofacitinib in patients with ulcerative colitis in Japan: A final report of effectiveness and safety dataWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Tofacitinib is an oral Janus kinase inhibitor for the treatment of ulcerative colitis (UC). We present the final analysis of a 60-week post-marketing surveillance (PMS) study of tofacitinib in patients (pts) with UC in Japan.

Methods

A final analysis of safety and effectiveness data from a PMS study was conducted (final data as of 30 September 2022). All pts with UC in Japan receiving tofacitinib were registered. All adverse drug reactions (ADRs) during tofacitinib treatment were recorded. Data were excluded for 13 pts from 2 hospitals that did not obtain pt consent and were therefore not permitted for publication. In the risk-management plan, several ADRs were identified as clinically important events or as potential risks, for which all treatment-period data were used to calculate cumulative incidence rates (IRs; unique pts with events per 100 pt-years [PY] of exposure). Effectiveness was assessed by partial Mayo score as observed.

Results

In total, 2043 pts receiving tofacitinib were enrolled in the PMS study, of whom 1982 and 1969 were included in the final safety and effectiveness analyses, respectively. In total (safety analysis set), 60.5% of pts were male and mean age was 42.5 years, with 2706.4 PY of exposure. ADRs and serious ADRs were observed in 462 (23.3%) and 46 (2.3%) pts, respectively; one death occurred due to an intestinal abscess (not related to study drug per investigator’s assessment). Herpes zoster (HZ; non-serious/serious) was the most commonly reported infection (89 pts [4.5%]). The IRs of malignancy, cardiovascular events and venous thromboembolic events were all <0.5 per 100 PY of exposure (Table). At Week 60, 735 of 870 ongoing pts (84.5%) were in remission (Figure). Overall, 1038/1982 pts (52.4%) discontinued treatment, most commonly due to inadequate clinical response (508/1038 pts [48.9%]).

Conclusion

In this final analysis, the overall safety profile during the treatment period from PMS reports of tofacitinib in pts with UC in Japan was generally comparable with tofacitinib safety data previously reported in PMS reports from Japan and worldwide,1 and in the tofacitinib UC clinical programme.² However, rates of HZ were higher in this final analysis than in the tofacitinib UC clinical programme.² Tofacitinib was effective in Japanese pts with UC in a clinical practice setting. The majority of pts with evaluable partial Mayo scores achieved remission during the 60-week observation period, consistent with previously reported data from the tofacitinib UC clinical programme.²References:1. Rubin et al. Aliment Pharmacol Ther 2022;55:302–102. Sandborn et al. Aliment Pharmacol Ther 2022;55:464–78Study sponsored by Pfizer. Medical writing support provided by C Duncan, CMC Connect; funded by PfizerRead more P499 Anorectal Motility Disorders In Inflammatory Bowel Disease PatientsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

In spite of prolonged disease remission of IBD patients, induced by the new biological molecules, a significant number of them suffer from persistent debilitating symptoms with major impact on the quality of life. Frequently, these symptoms are due to post-inflammatory motility changes and misinterpreted as functional disorders. Our aim is to identify and characterize the anorectal motility dysfunction in IBD patients.

Methods

We are conducting an ongoing prospective study started in August 2019, which includes the IBD patients admitted in a Tertiary Gastroenterology Centre in Bucharest, with specific symptoms (anorectal pain, incontinence, difficult defecation). We perform high resolution anorectal manometry using Sandhill Scientific systems, the parameters being analysed using InSIGHT software. The manometric testing comprise measurements of anorectal pressure at rest, during squeeze, simulated evacuation, rectoanal inhibitory reflex (RAIR) and rectal sensory testing, in compliance with International Anorectal Physiology Working Group protocol

Results

We studied 30 patients (18 patients with Ulcerative Colitis and 12 patients with Crohn’s Disease, 18 females and 12 males, mean age 40 (±12.85) years. Only 33% (10 patients) had rectal active involvement. Symptoms were reported by 87% (26) patients: anal incontinence (85%), difficult evacuation (35%) and urgency (46%); rectal inflammation was not correlated with the presence of symptoms in our study group (p=0.28). Perianal surgical interventions didn’t represent a risk factor for fecal incontinence (p=0.18), or for dyssinergic defecation (p=0.1). Modified manometric parameters were found in 23 patients (79%). Low resting pressures were registered in 48% of patients; 55% of them presented low squeeze pressures; during push maneuvers, 34% of patients had insufficient rectal propulsive force, presenting low rectal pressures and 59% of them lacked anal canal relaxation. We performed sensibility testing on 18 patients: 9 patients presented criteria for hypersensitivity, hence reduced rectal compliance; 7 patients presented rectal hyposensitivity, while only 2 patients had normal rectal sensation. Recto-anal inhibitory reflex (RAIR) was present only in 28% of the patients, reflecting the dysfunction of the enteric neural system.

Conclusion

Patients with inflammatory bowel disease (IBD) have significantly higher rates of functional anorectal disease. Therefore, pelvic floor investigation is an essential tool in the investigation and management of IBD patients with ongoing symptoms not thought to be related to an IBD flare.Read more P528 Re-induction of intravenous ustekinumab to maintain drug persistence. A UK experienceWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

In this study we seek to add to the body of knowledge on the practical use of ustekinumab in patients with Crohns and Colitis. Patients commencing ustekinumab will mostly have failed, or are intolerant to, conventional biologic agents and therefore have a limited number of medical options available to manage their disease. Results from the IM-UNITI long-term extension study have shown that a proportion of patients will lose response to maintenance dose therapy, and a small number of studies have suggested that repeated induction doses of this therapy can prolong its effective use and allow patients a greater period of disease free remission.Shrewsbury and Telford hospital NHS trust is a multi-site UK hospital serving a large population in the west-midlands region which has established the routine use of usetkinumab therapy over 5 years ago and by reviewing data on our patient cohort we aimed to identify characteristics amongst patients who have required reinduction doses and how effective they have been in maintaining remission.

Methods

In this retrospective, interventional study two researchers gathered data including baseline characteristics, disease type and distribution, previous surgical and medical therapies and time from diagnosis on all patients who had received ustekinumab therapy over the past five years. We used biochemical and endoscopic data, as well as clinical records, to determine the efficacy of ustekinumab on the disease course. We identified the subgroup of patients requiring reinduction doses and noted whether this was a successful intervention and sought to describe similarities which could help identify patients at risk of failing maintenance therapy in future.

Results

Data from 213 patients was gathered (Crohns: 150, UC: 61, IBDU: 2) and of which 87 (Crohns: 63, UC: 24) received reinduction doses. Average time to reinduction from therapy commencement was 19.5 months (Crohns) and 16.3 months (UC) respectively. Of the reinduction group 63% showed improvement in their disease control and a variety of characteristics were noted amongst the successful patients for discussion including disease location, presence of perianal disease and time from diagnosis.

Conclusion

Ustekinumab reinduction is an important area for further research as it allows patients to prolong their successful therapy and delay the need for surgical intervention for difficult to manage disease. This study suggests characteristics which could inform further trials and establish protocols to aid clinicians when making decisions about switching biologic therapies.Read more P761 Clinical efficacy and durability of subcutaneous infliximab in patients with moderate-to-severe inflammatory bowel disease : a real-world data from a Korean multicentre prospective cohort studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Subcutaneous infliximab (IFX-SC) has shown comparable efficacy and safety with IV infliximab in ulcerative colitis (UC) or Crohn's disease (CD) since its launching in 2021. We aimed to investigate the one-year real-life efficacy and durability of IFX-SC in Korea.

Methods

From September 2021 to November 2023, patients with moderate-to-severe UC or CD, who are naive to any types of biologic agents or IFX were prospectively enrolled from 41 tertiary referral centers in Korea. After IV infliximab induction from Week (W) 0 to W2, patients received IFX-SC every 2 weeks from W6. Patients who administered IFX-SC less than W14 were excluded. Clinical remission (CREM), clinical response (CRES) at W26, W50, and one-year drug survival were assessed. In patients with CD, CREM was defined as Crohn’s disease activity index (CDAI) <150 points, and CRES was defined as a reduction in CDAI ≥70 points from baseline. In patients with UC, CREM was defined as partial Mayo score(pMS) of ≤1 points with no individual subscore of >1 point, and CRES was defined as a reduction from baseline in pMS of ≥2 points and ≥30% along with either a reduction in rectal bleeding subscore (RBS) of ≥1 point or an absolute RBS of ≤1 point19. Drug survival was evaluated based on the time of drug persistence from W0 to the last date of IFX-SC administration among drug-off cases.

Results

A total of 192 patients (UC with 53, and CD with 139) were enrolled, consisting of about 80% of biologic naïve cohort. Enrolled patients included young adults with a male predominance (Table 1). At W26, patients with UC showed 54.5% CREM and 88.6% CRES (Figure 1A). Among patients with CD, rates of CREM and CRES were 92.1% and 97.0%, respectively. Similarly, W50 CREM and CRES were also favorable with a rate of 57.1% and 89.3% among UC patients. In addition, among CD patients, favorable outcome was more obvious, showing 84.6% and 93.8% of CREM and CRES. Meanwhile, one-year drug survival was also investigated. As shown on the Figure 1B, one-year drug survival probability seemed favorable with a survival rate over 97% in both UC and CD patients (UC; 98.1% at W26 with 95% confidence interval [CI], 0.874–0.852, 96.1% at W50, 95% CI, 0.852–0.990, and CD; 97.8% at W26 with 95% CI, 0.933–0.993, 97.8% at W50 with 95% CI, 0.933–0.993). During the study, 3.1% (six patients) of serious adverse events were reported.

Conclusion

IFX-SC seems to be efficacious therapeutic option for patients with moderate-to-severe UC or CD patients in real-world settings. With a favorable drug survival and tolerable safety profile, it may facilitate individualized treatment with a good compliance.Read more P529 Assessing patient-perceived burden of disease in Crohn’s disease: a novel scoring approach in a real-world Australasian cohortWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The prevalence and burden of inflammatory bowel diseases (IBD) including Crohn’s disease (CD) are rising globally. We present a novel score to evaluate the patient-perceived burden of disease (PPBoD) in CD, and explored it in a large real-world Australasian cohort.

Methods

The Crohn’s Colitis Care (CCCare) Clinical Registry was interrogated in October 2023. Adults with CD across 17 IBD centres with an outpatient encounter in the last 14 months were included. A novel PPBoD score was designed for CD, which included patient-reported components from the Harvey-Bradshaw index (abdominal pain and patient-rated general wellbeing) as well as nocturnal bowel actions, defecation urgency and stool frequency. The PPBoD score was calculated as detailed in figure 1. A total score of 0 was defined as no PPBoD, 1-2 as mild, 3-4 as moderate and ≥ 5 as significant PPBoD. Correlations amongst PPBoD and demographics, disease and treatment factors were explored.

Results

A total of 3461 people with CD were assessed in the last 14 months and 3233 (93.4%) had adequate data to calculate PPBoD. Of these, 80.0% had either no or mild PPBoD (table 1). While gender varied significantly between PPBoD categories, age and BMI did not. People with lower PPBoD were more likely to be receiving advanced therapies and had lower rates of steroid use than those with higher PPBoD. There were no significant differences in the use of immunomodulators and/or aminosalicylates across PPBoD categories. The cohort was geographically dispersed across Australia (n = 2414, 74.7%) and New Zealand (n = 819, 25.3%). There was significantly higher PPBoD in New Zealand compared to Australia but notably people in New Zealand were less likely to be receiving advanced therapies (p < 0.001). In the subset of 1074 people (33.2%) with a recent faecal calprotectin, those with no PPBoD were more likely to have biochemical remission (faecal calprotectin < 100 μg/g). Data were available to assess endoscopic and radiological remission in 1049 people (32.4%); those with no PPBoD were more likely to be in remission. Less than 1% of people with no PPBoD had any days out of role due to CD, whereas those with higher PPBoD had more days out of role (Table 1).

Conclusion

We present a novel consumer-focused score to quantify PPBoD in CD. Within this geographically dispersed cohort, the majority had either no or mild PPBoD. Advanced therapy use appeared to be protective against high PPBoD. Further studies are required to validate this novel score to assess PPBoD in CD.Read more P837 Improving Vaccination Rates in Patients with Inflammatory Bowel Disease: A Single Centre Audit and Quality Improvement ProjectWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Patients with inflammatory bowel disease (IBD) are at an increased risk of infections. Vaccine preventable diseases in patients with IBD are associated with high rates of hospitalizations, costs, mortality and longer hospitalizations. Despite societal recommendations, the uptake of vaccinations is still suboptimal. We aimed to conduct an audit of vaccination status in patients with IBD followed by a quality improvement project (QIP) to improve the vaccination rates in the outpatient clinic setting.

Methods

This is a retrospective cohort study in a tertiary hospital in Singapore. Patients with a confirmed diagnosis of IBD aged >18 years’ old who attended outpatient clinics between June to September 2022 were identified, and their influenza (IFV) and pneumococcal (PCV) vaccination status was assessed. A QIP was instituted to increase the rate of IFV and PCV coverage in this ambulatory population. Interventions were directed at both the provider and the patient. All providers were educated on vaccination schedules and a standardized electronic template was implemented for clarity of documentation. Laminated posters of vaccination guidelines were placed in each consultation room. All patients were issued with a personalized vaccination card documenting their vaccination status and serving as a prompt for subsequent consultations. We analysed the rate of IFV and PCV coverage post implementation from November 2022 to June 2023.

Results

70 patients were identified in the pre-intervention cohort. 30 patients were either >65 years old or on immunosuppression, of which 6/30 (20%) received IFV and 11/30 (36.7%) already received PCV. In the post-intervention cohort, we assessed 187 consecutive patient clinic visits which comprised 115 unique patients. Baseline characteristics are detailed in Table 1. 73 patients were either aged > 65 years old or on immunosuppression, 65 patients had no IFV within 1 year, of which 20/65 (30.7%) obtained vaccination coverage for IFV in the post-intervention period (p=0.01). 63 patients were eligible for PCV and 12/63 (19%) received either pneumococcal conjugate vaccine 13 or pneumococcal polysaccharide vaccine 23 during this period (Fig. 1).

Conclusion

A structured QIP with an established protocol engaging patients and guiding providers significantly increased the rate of IFV but not PCV in our cohort. A major hurdle to timely PCV uptake was the erroneous perception of a wider window period by patients and providers given its 5-yearly interval, as compared to IFV. Overall adherence to societal guidelines and uptake of vaccinations is still suboptimal and more work needs to be done to educate providers and patients, increase vaccination uptake and reduce vaccine preventable diseases in patients with IBD.Read more P416 Turning Point: Declining surgery rates and predictors for surgery in a three-year prospective inception cohort of Crohn's Disease in ChinaWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Surgery in Crohn's disease is a critical management outcome. China currently faces a notable surge in CD incidence, making it an integral phase for improving diagnostic and therapeutic competencies. Analysing the rates of CD-related bowel surgeries in a prospective cohort offers significant insights for evaluating and optimizing disease management.

Methods

We conducted a single-centre, prospective inception cohort of CD patients since July 2019 at the Second Affiliated Hospital, Zhejiang University School of Medicine (ClinicalTrials.gov identifier NCT04135027). Annual follow-ups were performed. Survival analysis was used to identify predictors for bowel surgical outcomes. Bowel surgery encompassed gastrointestinal resections addressing complications such as obstruction, fistula, free perforation, and bleeding.

Results

A total of 438 newly diagnosed CD patients, predominantly male (73.5%), with a median age at diagnosis of 28.1 years were enrolled. Among them, 68 patients underwent surgery within three years. Surgery rates at one, two, and three years were 11.8%, 14.3%, and 15.4%, respectively. Specifically, patients enrolled in 2019-2020, 2020-2021, and 2021-2022 displayed surgery rates of 18.4%, 14.2%, and 5.3%, respectively during their first year in the study. Multivariate Cox regression demonstrated the enrolment timeframe (Hazard ratio 0.46, 95% Confidence Interval [CI] 0.22-0.96, P=0.039), smoke (Hazard ratio [HR] 3.98, 95% CI 2.02-7.87, P<0.001), and disease behaviour (stricturing, HR 29.75, 95% CI 10.34-85.56, P<0.001; penetrating, HR 39.13, 95% CI 13.18-116.17, P<0.001) and low albumin (HR 2.07, 95% CI 1.22-3.51, P=0.007) as significant predictors of surgery. Further analysis within the stricturing/penetrating subgroup maintained the enrolment timeframe (HR 0.45, 95% CI 0.21-0.95, P=0.035), smoke (HR 3.34, 95% CI 1.68-6.61, P<0.001), and low albumin (HR 2.03, 95% CI 1.19-3.48, P=0.01) as independent predictors. Propensity score matching confirmed smoke and low albumin as significant contributors to surgical risk.

Conclusion

A declining trend in the surgery rate among newly diagnosed patients was observed over the three years. Disease behaviour significantly stratified surgical outcomes. The enrolment timeframe, smoke, and low albumin emerged as independent predictors for surgeries in both the general cohort and the stricturing/penetrating subgroup.Read more P838 Determing factors that influence Vedolizumab Response in Inflammatory Bowel Diseases: A Prospective StudyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

In recent years, the development of biologic agents, including Vedolizumab, has offered new avenues for the treatment of IBD Understanding the factors that influence the response to Vedolizumab therapy is of paramount importance in optimizing patient care and treatment outcomes. However, for a drug like Vedolizumab, the exact concentration indicating the need for optimization and what influences it are still unknown.The aim of this research is to evaluate what parameter has influence on good response to Vedolizumab in patients with inflammatory bowel diseases.

Methods

160 patients with Crohn's disease and ulcerative colitis were included in this prospective study, who were treated with Vedolizumab biological therapy from October 2018 to February 2023 at a tertiary center for inflammatory bowel diseases. All patients were followed for a minimum of 14 weeks or until therapy discontinuation. Biochemical parameters (CRP, fecal calprotectin, hemoglobin, ferritin), clinical parameters (MTWS, HBI) were monitored in all patients before and during treatment. Vedolizumab concentration was measured in half of the patients during treatment with this drug. All data were processed using the statistical program SPSS 23.0 (Chicago, IL).

Results

Of the 160 patients, there was almost an equal distribution between male and female (males, 160/86 (53.7%)), with an average age of 51.5 years (± 16.51 SD). After one year of therapy, a statistically significant reduction in inflammation parameters was observed (FCP- p=0.007, Z= -2.694; CRP- p=0.008, Z= -2.646), as well as a statistically significant clinical response to therapy by reducing the disease activity index (p < 0.000, Z= -4.818). Using logistic regression duration of disease nor disease localization are predictive parameters for response to therapy (p = 0.330, Exp B 1.190) In a group of 80 patients, Vedolizumab concentration was measured in a cross-sectional analysis. Our cohort of patients had a median Vedolizumab concentration of 20.73 µg/ml. Patients who achieved remission had statistically similar Vedolizumab concentrations compared to patients with active endoscopic disease (Vedolizumab concentration UC 25.6541 vs 28.8152; p = 0.614; CD 20.0232 vs 18.3346 µg/ml; p = 0.729). Patients on Vedolizumab who had previously received anti-TNF therapy had a lower mean drug concentration compared to bio-naive patients (16.05 ug/ml / 20.34 ug/ml).

Conclusion

Previous anti-TNF therapy may have an impact on drug concentration and response to therapy, but it is necessary to determine other parameters that can also independently influence drug concentrationRead more P417 1 year follow-up of pediatric ulcerative colitis using intestinal ultrasoundWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Intestinal ultrasound (IUS) is an emerging tool that offers a non-invasive method for monitoring inflammatory bowel disease in pediatric patients, with increasing popularity worldwide. Assessment of IUS for monitoring pediatric Ulcerative Colitis (UC) has been limited to small samples of patients with no long-term follow up. Our aim is to utilize intestinal ultrasound assessments obtained at routine time points to determine changes in IUS parameters within 12 months of study enrollment in newly diagnosed children with UC, and their relationship to biochemical markers, clinical assessments, and endoscopic findings.

Methods

Pediatric patients with suspected ulcerative colitis were prospectively enrolled through the Edmonton Pediatric IBD Clinic. Participants underwent IUS, clinical assessments, bloodwork for biomarkers, and fecal calprotectin (FCP) testing at baseline, 1-, 3-, 6-, and 12-month visits, as well as endoscopy at baseline and 6-12 months. In each IUS assessment, the bowel wall thickness (BWT), presence of hyperemia, abnormal haustrations, and fat wrapping was determined in 4 bowel segments (right, transverse, descending, and sigmoid colon). The Pediatric Ulcerative Colitis Activity Index (PUCAI) scores and Ulcerative Colitis Intestinal Ultrasound Scores (UC-IUS) were calculated at each visit.

Results

42 patients (55% male) were included. Median UC-IUS total scores and BWT alone improved in all bowel segments over the study period. For the most affected bowel segment for all patients, median percent reduction of BWT was 39.6%, 34.2%, 33.7%, and 42.5%, at the 1-, 3-, 6-, and 12-month assessment respectively. The biggest decrease in UC-IUS scores and BWT occurred with the initiation of therapy between baseline and 1-month. UC-IUS scores significantly correlated with endoscopy at 12-months, clinical assessments at all time points, and biochemical markers of disease at all time points over the 12-month study period (p<0.05). BWT measurement alone also had significant correlation with endoscopy at 12 months; clinical assessment at 1-, 3-, and 6-months; and with biochemical markers at every time point (p<0.05). Patients with inflammatory bowel markers (indicated by elevated FCP (>250)) at 12-months were found to have significantly thicker BWT and UC-IUS scores at 3- and 6-months.

Conclusion

BWT and UC-IUS performed well in pediatric patients with newly-diagnosed UC, with UC-IUS scores and BWT measurements alone correlating significantly with endoscopic, clinical, and biochemical disease activity over the 12-month study period. BWT alone performed similarly to total UC-IUS scores. This data suggests that IUS can offer a non-invasive method to monitor long-term pediatric UC disease severity.Read more P839 Acute interstitial nephritis in patients with Inflammatory Bowel Disease treated with vedolizumab: a systematic reviewWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Acute interstitial nephritis (AIN) is a complication of drugs that may cause permanent kidney injury. AIN has been reported in inflammatory bowel disease (IBD) patients treated with the anti-integrin inbibitor vedolizumab. However, systematically collected data on cases of AIN associated with vedolizumab treatment is lacking. We therefore, through systematic review of existing literature, aimed to identify and describe reported cases of AIN.

Methods

We searched Medline, Embase, Cochrane, and Web of Science Core Collection between January 1, 2009 and April 25, 2023. The search yielded 1473 publications after deduplication, for which titles and abstracts were screened by two independent reviewers. Of these, 75 publications were reviewed in full-text. Demographics and clinical characteristics of AIN cases were extracted. Case causality assessment was performed according to the World Health Organization-Uppsala Monitoring Centre (WHO-UMC) system and the Naranjo Adverse Drug Reaction Probability Scale. Results were reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A prespecified protocol was registered in the PROSPERO database.

Results

Eight publications met the inclusion criteria and were included in descriptive analysis of AIN in patients with IBD treated with vedolizumab. A total of nine biopsy-confirmed cases of AIN were reported in six patients with ulcerative colitis and three with Crohn’s disease. The mean age at AIN onset was 36 years (range: 19-58). The majority of patients were females (n=6/9). Time from vedolizumab treatment initiation to AIN onset spanned from hours to 12 months. Common symptoms were fever, malaise, and myalgia. Creatinine levels were elevated in all patients (mean: 219 µmol/L; range; 133-410). Rechallenge after pause and treatment with corticosteroids were reported in three cases, where one attempt was successful. Five patients sustained permanent kidney injury. According to the WHO-UMC scale, six of nine cases were assessed as “possible” or “probable”, and the remaining three cases as “unlikely” or “unclassifiable”. Three patients were treated with concomitant mesalazine or proton pump inhibitors, which both are associated with an increased risk of AIN.

Conclusion

In systematic review of existing literature, we identified nine cases of biopsy-confirmed AIN in patients with IBD treated with vedolizumab. Our findings suggest that vedolizumab, although rarely, could potentially cause AIN in patients with IBD. Awareness of laboratory findings and symptoms consistent with AIN, along monitoring of the kidney function, could be warranted in patients with IBD treated with vedolizumab.Read more P436 The AI based Red Density score is correlated with the established and new histological indices for Ulcerative Colitis in an independent cohortWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Red Density (RD) is an automated endoscopic tool that is developed for the objective evaluation of disease activity in ulcerative colitis (UC). The initial development integrated histological disease activity based on Robarts histological index (RHI) in the machine learning algorithm. New histological scores for UC have been developed since.The aim of this study was to establish the correlation between RD and the Nancy histological index (NHI) and PICaSSO Histologic Remission Index (PHRI).

Methods

Patients included in 4 centers in the ongoing PROCEED-UC study (NCT04408703) had assessment with RD in the rectum and sigmoid at baseline, w52 or early termination visit. Biopsies were taken according to protocol. Biopsies were scored for the Geboes score (GBS), RHI, NHI, PHRI in a blinded way after initial scoring convention training. Correlation was tested on patient level between mean RD per segment and the different histological indices based on Spearman correlation.

Results

In total 96 patients from 4 centers were included representing 2634 RD images from 400 colonic segments with biopsies and corresponding RD score. Mean (± SEM) rectal RD score was 32.7 (± 4.54), 33.69 (± 5.25) and 64.86 (± 31.71) at baseline, w52 and ET respectively. Mean sigmoidal RD score was 38.13 (± 3.68), 42.82 (± 11.80) and 77.33 (± 24.65) at baseline, w52 and ET respectively. Analysis based on the segment with the highest mean RD score per patient showed significant correlation with NHI (r=0.60, p<0.0001), PHRI (r=0.62, p<0.0001). In the rectum the RD score at all time points correlated significant with NHI (r =0,53, p<0.0001) and PHRI (r=0.63, p<0.0001). Similar correlation was seen in the sigmoid for NHI (r=0.51, p<0.0001) and PHRI (r=0.22, p0.0108). A RD score of <57.5 (Likelihood Ratio (LR) 4.176; AUC 0.7820 (95CI 0.7047 - 0.8593), p<0.0001) was associated with histological remission based on NHI (<2) and a RD score of < 64.5 (LR 9.821; AUC 0.8133 (95%CI 0.7053 - 0.9212), p<0.0001) with histological remission based on PHRI (=0). The current dataset demonstrated to be stable in line with the previously established RD cut-off with GBS and RHI. ¹

Conclusion

In an independent cohort of patients with UC the correlation with the established and new histological indices for UC is confirmed. This underlines the value of RD as an objective endoscopic tool for the assessment of histological and endoscopic disease activity in UC.Ref1: Bossuyt P, Nakase H, Vermeire S, De G, Eelbode T, Ferrante M, et al. Automatic, computer-aided determination of endoscopic and histological inflammation in patients with mild to moderate ulcerative colitis based on red density. Gut. 2020;69:1778–86.Read more P840 Structural evaluation of Inflammatory Bowel Disease Comprehensive Care Units in BrazilWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

In Brazil there is no methodology for evaluating health services recognized as Comprehensive Care Units (CCU), making it difficult to assess the quality of care provided for IBD patients. Aims: Map the distribution of this units and identify strengths and weaknesses, considering local and regional characteristics with a view to proposing a ranking system for Brazilian centers.

Methods

The study was carried out in three phases. First, GEDIIB developed 22 questions to characterize CCU in Brazil. The questionary was constructed based on GETECCU criteria. All GEDIIB members were invited to respond to the survey with the 11 questions considered most relevant. In the last phase, an analysis of the results obtained in the CCU was carried out, using the IBM SPSS Statistics v 29.0.1.0 software. Descriptive statistics were used to characterize the unit´s profile. The chi-square test was used to compare categorical variables

Results

There were 109 responses, 53 from public centers. Of these, 11 were excluded. Most units were concentrated in the Southeastern region 22 (52.4%) and only one (2.4%) in the Northern region of Brazil. Thirty-nine centers (92.9%) perform endoscopic procedures, but only 9 (21.4%) have access to enteroscopy and/or capsule endoscopy. Thirty-three centers (78.6%) offer infusion therapy locally, 26 (61.9%) maintain IBD patient records, 13 (31.0%) reported having an IBD nurse, 34 (81.0%) have specific evidence-based protocols and only 7 (16.7%) have a patient satisfaction methodology. In the private scenario there were 56 responses, of which 10 were excluded. There is also a concentration in the Southeastern and Southern regions. Thirty-nine centers (84.8%) have access to endoscopic procedures and 19 perform enteroscopy and/or capsule endoscopy. Infusion therapy is available in 24 centers (52.2%). Thirty-nine (84.8%) maintain a specific database of IBD patients, 17 (37%) have an IBD nurse, 36 (78.3%) have specific evidence-based protocols, and 22 (47.8%) apply a patient satisfaction methodology. Multidisciplinary teams (p< 0.002) and infusion centers (p< 0.01) predominate in public centers as compared to private ones. Telemedicine (p< 0.027), capsule endoscopy (p< 0.001), exclusive registration of patients with IBD (p< 0.015) and patient satisfaction methodologies (p< 0.002) are predominant in private centers as compared to public centers.

Conclusion

IBD CCU in Brazil were mainly located in the southeastern and southern regions of the country. Most centers have dedicated multidisciplinary teams and specialists involved in IBD treatment. There is still a current need to improve the proportion of nurses' involvement in IBD care in Brazil.Read more P437 Feasibility study of a Point-of-Care assay for rapid determination of anti-TNFα biologics in capillary bloodWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Inflammatory bowel disease (IBD) patients benefit from therapeutic drug monitoring and personalized adjustment of anti-TNFα drugs such as adalimumab (ADL) and infliximab (IFX). Commercially available rapid assays allow the fast and easy measurement of ADL and IFX. Unfortunately, most ADL and IFX in-vitro diagnostic assays rely on serum as analyte matrix. This is a critical hurdle in point-of-care (POC) analysis, as it requires laboratory professionals, additional laboratory instruments and is time consuming. Therefore, two recently developed rapid tests for the determination of ADL and IFX that only require capillary blood (CB) or EDTA whole blood (WB) without further treatment are tested in a POC setup at three different study sites. The primary aim of this study is to demonstrate matrix equivalency of CB and EDTA WB compared to serum as reference.

Methods

This observational study was performed at three sites. Two sites in Switzerland, Clarunis Basel and Kantonsspital Baselland, and one site in France, Centre Hospitalier Universitaire de Saint-Étienne. Sample analysis was performed by healthcare professionals at the study sites with the established Quantum Blue® serum rapid tests and the newly developed capillary blood applications. Blood samples from patients under infliximab therapy were collected directly before infusion (trough level of drug). Samples from adalimumab-treated patients were collected irrespective of the injection schedule. In total, up to 100 IBD patients are anticipated in the study, 50 under infliximab therapy and 50 treated with adalimumab. This work evaluated the interim outcome after the analysis of 29 ADL and 18 IFX patients.

Results

Bland-Altmann analysis revealed a good agreement of CB and EDTA WB compared to serum for both IFX and ADL sample sets. The mean bias for the biologic’s trough level analysed in CB and compared to serum was 5.2% for IFX and -11.7% for ADL. Passing-Bablok analysis for CB versus serum resulted in a slope of 0.92 and an intercept at 0.08 for IFX and a slope of 0.86 and an intercept at -0.063 for ADL. A comparison of EDTA WB compared to serum revealed a mean bias of 7.8% for IFX and 7.4% for ADL. Passing-Bablok analysis for EDTA WB versus serum resulted in a slope of 1.00 and an intercept at 0.00 for IFX and a slope of 1.00 and an intercept at 0.30 for ADL.

Conclusion

The newly developed rapid Quantum Blue® assays for the determination of infliximab and adalimumab in capillary blood and EDTA whole blood are very well comparable to the analysis of either biologic in serum. This study furthermore demonstrated the assays are well suited to be used in a POC setting, such as infusion centres, rather than in a laboratory. Both assays are standardized to WHO reference material.Read more P621 Safety and effectiveness of vedolizumab and ustekinumab in inflammatory bowel disease patients after liver transplantation for primary sclerosing cholangitis: results from an ECCO-confer case seriesWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Primary sclerosing cholangitis (PSC) is a chronic progressive cholestatic liver disease often necessitating liver transplantation (LTX). Approximately 70% of PSC patients have a concomitant diagnosis of inflammatory bowel disease (IBD) and could need treatment with biological therapy on top of the immunosuppression to prevent transplant rejection. Vedolizumab (VDZ) and ustekinumab (UST), both agents with a favorable safety profile, are often used in this population despite lack of data concerning safety and effectiveness in the post-LTX setting.

Methods

A retrospective multicenter case series was performed as a part of the European Crohn's and Colitis Organisation [ECCO] Collaborative Network of Exceptionally Rare case reports [CONFER] project. Primary endpoints were clinical and endoscopic remission at week 52, occurrence of infectious complications, occurrence of malignancy, hospitalizations, and death after liver transplantation.

Results

In this retrospective study, 58 patients (male n= 34 (59%), median age 42 (interquartile range (IQR) 32-52) were included across 16 participating centers of which 24 (38%) were treated with UST and 40 (63%) with VDZ. Twelve patients (20%) were diagnosed with Crohn’s disease (CD), 44 (76%) with ulcerative colitis (UC), 2 (3%)- with unclassified IBD (IBD-U) and in 12 (20%) patients had an ileal pouch anal anastomosis (IPAA). Median disease duration was 16 years (IQR 13-26) and 33 (56%) had received biological therapy prior to LTX (33% anti-TNF, 11% VDZ, 5% UST). Median disease duration for PSC was 15.5 years (IQR 11-25) and median time since LTX was 6 years (IQR 4-10).Clinical remission, assessed according to physician global assessment, at week 52 was achieved in 44% of VDZ compared to 38% of UST treated patients (p=0.17), while endoscopic remission was seen in 17% of patients in the VDZ group versus 33% in the UST treated patients (p=0.87). Clinical effectiveness was similar across CD (respectively 33% and 20%), UC (33% and 37%) and IPAA patients (36% vs 60%). Infectious complications occurred in 21 patients (29%; 27% VDZ vs 33% UST) post LTX on biological therapy (p=0.66), malignancy occurred in 10 patients (14.1%, 12.8% VDZ vs 16.7% UST, p=0.66), hospitalizations in 32 (45%; 51% VDZ vs 34% UST, p=0.15), and death in 2 patients (3.4%; 2.1% VDZ vs 4.2% UST, p=0.66) (see table).

Conclusion

In IBD-PSC patients who underwent LTX both UST and VDZ show similar effectiveness with clinical remission rates of respectively 44% and 38% after 1 year. Safety profiles are similar although infectious complications and occurrence of malignancy remains an important concern in this patient group.Read more P456 Pragmatic trial design to compare real-world effectiveness of different treatments for inflammatory bowel diseases: the PRACTICE-IBD international consensusWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Pragmatic studies designed to test interventions in everyday clinical settings can successfully complement the evidence from registration and explanatory clinical trials. The international consensus project PRACTICE-IBD was developed to identify essential criteria and address key methodological issues needed to design valid comparative pragmatic studies in inflammatory bowel diseases (IBDs).

Methods

Statements were issued by a panel of 11 European experts in IBD management and trial methodology on four main topics: (I) study design; (II) eligibility, recruitment and organization, flexibility; (III) outcomes; (IV) analysis. The consensus process followed a modified Delphi approach, involving two rounds of assessment and rating of the level of agreement (1 to 9; cut-off ≥7 for approval) with the statements by 18 additional European experts in IBD (Fig.1)

Results

At the first voting round, 25 out of the 26 statements reached a mean score ≥7. Following the discussion that preceded the second round of voting, it was decided to eliminate two statements and to split one into two. At the second voting round, 25 final statements were approved: 7 for study design, 6 for eligibility, recruitment and organization, flexibility, 8 for outcomes, and 4 for analysis (Table 1).

Conclusion

Pragmatic randomized clinical trials can address important questions in IBD clinical practice, and may provide complementary high-level evidence, as long as they follow a methodologically rigorous approach. These 25 statements intend to offer practical guidance in the design of high-quality pragmatic clinical trials that can aid decision making in choosing a management strategy for IBDs.Read more P634 Durability of a second-line anti-TNFɑ agent compared to a different mechanism of action after first anti-TNFɑ failure in ulcerative colitis: CambiaCU StudyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

After first anti-TNFɑ (aTNF) failure in ulcerative colitis (UC), switching to a different mechanism of action (MoA) could decrease the rates of failure and discontinuation compared to a second aTNF and with a better safety profile.

Methods

We performed a multicenter and retrospective study (6 Andalusian sites) in which patients diagnosed of UC who had failed a first biological therapy with an aTNF and started a second-line biological therapy with another aTNF or a different MoA such as ustekinumab (UST), vedolizumab (VDZ), tofacitinib and filgobinib (JAK) were included. The aim of our study was to evaluate the long-term durability of a different MoA compared to a second aTNF after a first-line therapy failure with aTNF.

Results

185 patients with UC were included. There were no significant differences between both groups in term of age, sex, extension of disease, extraintestinal manifestations or IMIDs, smoking habit or HLA-DQA1*05. The only significant difference was disease duration (9 years MoA vs 12 years in second aTNF, p=0.02). 80 patients received a different MoA (37 VDZ, 24 UST, 7 JAK) and 105 a second aTNF (34 IFX, 60 ADA, 11 golimumab). Duration of first aTNF, although non-significant (p=0.06), tended to be shorter in the MoA group (7 months vs 12 months in aTNF group). The most frequent cause of suspension of first aTNF in the MoA group was primary failure (46% vs 31%, p= 0.02) and in the second aTNF group was secondary failure (51% vs 35%, p=0.02). The follow-up mean was 22.4 months in the group of a different MoA and 23.3 months in the second aTNF group. 60% of patients discontinued the second-line biological treatment, 64% with aTNF vs 35% with a different MoA. Durability of therapies in the group of different MoA was significatively longer compared with second aTNF (50% vs 31.4%, p=0.036) (figure 1). JAK showed the best durability (63.2%), followed by UST (66.7%), IFX (52.9%), VDZ (32.4%), ADA (21.7%) and golimumab (18.2%), with significant differences (p=0.03). Reasons for discontinuation were primary failure in 29.7% (63.6% second aTNF vs 36.4% different MoA), secondary failure in 25.9% (64.5% second aTNF vs 35.5% different MoA) and intolerance or adverse events in 6.4% (66.6% second aTNF vs 34.4% different MoA). Adverse events were reported in 12 patients, 8 with aTNF a 4 with other MoA (2 vs 0 infusion reactions, 1 vs 1 mild infections, 2 vs 1 respiratory adverse effects, 1 vs 1 cutaneous reactions, 1 vs 0 musculoskeletal effects, 1 vs 1 neoplasia).

Conclusion

Our study shows that after a first aTNF failure in UC, a switch to a biological therapy with a different MoA achieves longer survival compared to switching to a second aTNF, with less primary and secondary failure.Read more P457 Small bowel involvement proximal to the terminal ileum is a major risk factor for intestinal resection in patients with small bowel Crohn’s diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The current Montreal classification categorizes Crohn's disease (CD) with small bowel involvement into two groups: L1 and L3. The study aimed to investigate the significance of small bowel involvement proximal to the terminal ileum as a significant risk factor for intestinal resection.

Methods

We conducted a retrospective review of the medical records of Crohn's disease patients diagnosed between January 2001 and December 2020 at Seoul St. Mary's Hospital, St. Vincent Hospital, and Eunpyeong St. Mary's Hospital. The extent of small bowel involvement was independently assessed by two experienced gastrointestinal radiologists using conventional CT, CT enterography, or MR enterography at the time of diagnosis. The terminal ileum was defined as the distal ileal segment within 10 cm from the ileocecal valve and the jejunum was defined as the proximal 1/2 of the small intestine beyond the ligament of Treitz. Radiologic disease activity and fibrostenosis at the time of diagnosis were also scored as 0, 1, and 2 using Maglinte classification, respectively.

Results

Out of 617 CD patients, 346 were included in the study, while 271 were excluded due to radiologic noninvolvement of the small bowel, inadequate or missing radiologic data, initial diagnosis made at another institution, or diagnosis through surgery. Median age at diagnosis was 24 years (range 10-76) and 250 (72.3%) were male. The median follow-up duration was 53 months (4-201). During the follow-up period, 43 patients (12.4%) underwent intestinal resection. Small bowel involvement proximal to the terminal ileum was significantly associated with a higher cumulative risk of intestinal resection (15.4% vs. 3.5%, P=0.006). Neither jejunal involvement or colonic involvement (L3 vs. L1) showed a significant association with cumulative risk of intestinal resection (16.0% vs. 11.1%, P=0.222; 12.4% vs. 12.4%, P=0.773). Radiologic disease activity and fibrostenotic score at the time of diagnosis were significantly associated with the cumulative risk of intestinal resection, respectively (0% vs. 4.4% vs. 19.7%, P<0.001; 8.5% vs. 16.7% vs. 28.2%, P<0.001).

Conclusion

Small bowel involvement proximal to the terminal ileum was a major risk factor for requiring intestinal resection in patients with small bowel CD, while jejunal involvement was not. These findings suggest a need for subclassifying small bowel CD.Read more P643 Magnifying Endoscopy with Narrow Band Imaging for Graft Failure and Disease Recurrence in Patients with Crohn’s Disease after Intestinal TransplantationWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Crohn’s disease (CD) is one of the common causes of short bowel syndrome (SBS) and intestinal failure (IF). Intestinal transplantation (IT) is sometimes needed for patients with CD who develop IF after multiple intestinal resections due to CD-related complications, such as uncontrollable bleeding and penetrating diseases. However, there have been limited case reports concerning the endoscopic surveillance of CD patients after IT.

Methods

We retrospectively investigated two patients with CD who underwent IT because of SBS-IF after multiple intestinal resection. We administered post-transplantation immunosuppressants and conducted regular magnifying endoscopy with narrow-band imaging (ME-NBI) via ileostomy chimney for surveillance of grafte rejection. Endoscopic prediction of rejection were based on our previously published "VENCH" score which is composed of five parameters: "V" (villi appearance), "E" (erythema), "N" (capillary network), "C" (crypt widening), and "H" (heterogeneity). Endoscopic biopsy were taken for histologic confirmation of graft rejection severity.

Results

Case 1 was a 60-year-old male patient with CD who received three times of intestinal resection for small bowel stricture and perforation, followed by IT due to SBS-IF. He lived uneventful until seven years thereafter with bloody diarrhea presented. Endoscopic surveillance revealed normal VENCH score of background mucosa but deep longitudinal ulcers which was indicative of recurrence of CD rather than graft rejection. Anti-tumor necrosis factor alpha with adalimumab was prescribed and his diarrhea and graft ulcers improved. Case 2 was a 39-year-old male patient with CD who received extensive intestinal resection due to multiple perforations, followed by IT because of SBS-IF. Endoscopic surveillance revealed normal VENCH score without histologic graft rejection two years thereafter. Both enrolled cases demonstrated favorable outcomes after endoscopic surveillance of intestinal graft with ME-NBI and management accordingly.

Conclusion

The post IT follow-up of CD patients remains challenging. We highlight the usefulness of the ME-NBI using VENCH score for early detection of graft rejection and its value in monitoring CD patients after IT. Additionally, ulcerations without changes in morphology of surrounding villi should take into consideration the disease recurrence of underlying CD. Further research is needed in endoscopic follow-up and molecular genetics to better understand CD after IT.Read more P492 All intestinal ultrasound scores for ulcerative colitis (and IBUS-SAS) strongly correlate with endoscopic activity: a prospective studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Intestinal ultrasound (IUS) is gaining increasing acceptance as a reliable tool for tight monitoring of ulcerative colitis (UC). Although several IUS scores have been proposed, none has been formally implemented into official recommendations of international scientific societies. This study aims to compare the available IUS score for UC, in terms of correlation with endoscopic activity.

Methods

Patients with UC ≥ 18 years old undergoing partial or full colonoscopy between April and October 2023 were prospectively included. Endoscopic evaluation of at least the sigmoid colon was mandatory for inclusion, and patients with proctitis (Montreal E1) were excluded. Endoscopic activity was scored with both the Mayo Endoscopic Subscore (MES) and the Ulcerative Colitis Endoscopic Index of Severity (UCEIS), and defined by MES ≥ 1 and UCEIS ≥ 2. IUS was performed within 4 weeks of endoscopy. The Milan Ultrasound Criteria (MUC, Allocca et al.), the UC-IUS score (Bots et al.), the US Score from Parente et al., and the score from Hata et al. were included in the analysis. Applicability of the US Score from Civitelli et al, an IUS score developed for paediatric patients, and the IBUS-SAS, an IUS score validated for Crohn’s disease, was also evaluated. The Spearman’s rank coefficient (rho = ρ) was used to perform correlations, while receiver operating characteristic (ROC) curves were compared with the Hanley & McNeil method.

Results

Fifty-nine patients were included, of which 59.3% and 50.8% showed any endoscopic activity using the MES and the UCEIS, respectively. Detailed information about the population is reported in Table.All the evaluated IUS scores showed a significant positive correlation with endoscopic activity (p < 0.001), with the UC-IUS score and the US Score from Civitelli et al. outperforming the others both with MES (ρ = 0.745, ρ = 0.762) and UCEIS (ρ = 0.751, ρ = 0.769). The same scores showed the highest Areas Under the Curve (AUC) for detecting a MES ≥ 2 (UC-IUS: 0.841, 95%CI 0.722-0.923, p < 0.001; Civitelli et al.: 0.842, 95%CI 0.724-0.924, p < 0.001) [Figure].The optimal cut-offs for detecting a MES ≥ 2 with both the MUC and the Civitelli score were similar to that proposed by the Authors (> 5.04 vs > 6.20 and > 2 vs > 1, respectively).

Conclusion

All the included IUS scores showed good correlation with endoscopic activity. The UC-IUS and the US Score from Civitelli et al. performed better than the others in detecting a MES ≥ 2 and might be suggested to monitor disease activity of UC and intervene early during disease relapse.Read more P648 Dietary therapy using a short course of Exclusive Enteral Nutrition followed by the Crohn’s Disease Exclusion Diet in children with mild to severe Crohn’s Disease; maintenance update on the DIETOMICS trialWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Exclusive enteral nutrition (EEN) is the first-line treatment for active Crohn’s disease (CD) in children. CD Exclusion Diet (CDED) combined with Partial Enteral Nutrition (PEN) has demonstrated better tolerance with a comparable effect in inducing remission among children with mild to moderate CD. This study evaluated the effectiveness of 2 weeks of EEN followed by CDED+PEN for maintaining remission for up to 24 weeks in children with mild-severe disease.

Methods

We conducted an international, multicenter, randomized controlled trial comparing 2 weeks of EEN using Modulen®, followed by 3 phases of the CDED+PEN (hereafter CDED), to 8 weeks of EEN followed by PEN with a free diet (hereafter EEN), all extended up to week 24 with a follow up till week 52. Children aged 8-18 with luminal CD duration less than 3 years, mild-severe disease [pediatric CD activity index (PCDAI),15-47.5], and active inflammation [elevated C-reactive protein (CRP),or fecal calprotectin (FC)] were included. Remission was defined as PCDAI≤10. Stable immunomodulator (IM) treatment was allowed, and naïve patients could initiate IM from week 4.

Results

We randomized 56 patients into two groups: Group CDED (n=30) and Group EEN (n=26); mean age 12.7±2.4, 37% female. Intention-to-treat analysis revealed remission in 18/30(60%) patients with CDED compared to 11/26(42%) with EEN at week 24,p=0.18 and 27% in CDED and 23% in EEN at week 52,p=0.75. Per protocol analysis showed 18/20(90%) remission in CDED compared to 11/14(78%) in EEN at week 8, p=0.35. Among patients who achieved remission at week 8, 18/23(78%) with CDED and 9/14(64%) with EEN maintained remission up to week 24, p=0.15. In CDED,15/20(75%) and 100% of EEN used IM, p=0.04. All CDED patients without IM remained in remission. Reduction of >50% in FC from baseline was obtained in 55% in the CDED and 28% in EEN, p=0.12. PCDAI improved from 31.2[20-35.6] to 5[0-12.5] in CDED and from 22.5[20-29.3] to 5[0-15.6] at week 24 in EEN, p<0.001 to all. CRP and FC significantly improved in both groups. Z score BMI improved from -1.3 [-2.1-(-0.1)] to -0.2 [-0.9-0.4], p=0.003 in CDED and from 0.08[-1.1-0.4] to 0.2[-1.7-0.7] at week 24 in EEN,p=0.098. Remission at week 2 (p=0.006) and overall high compliance (p=0.009) were identified as predictors of response at week 24.

Conclusion

While 2 weeks of EEN followed by CDED+PEN was not superior to EEN at 14 weeks (as previously reported), extending CDED+PEN for 24 weeks successfully maintained remission for up to 52 weeks in children with mild-to-severe CD. Moreover, a subset of patients maintained sustained clinical remission following CDED monotherapy. The long-term implementation of dietary therapy using CDED+PEN resulted in a significant improvement in nutritional status.Read more P493 Do antiTNF or Ustekinumab trough levels correlate with joint extraintestinal manifestations activity in Inflammatory bowel disease patients?Wed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Inflammatory spondyloarthritis(SpA) are the most common extraintestinal manifestations (EIM) associated to inflammatory bowel disease (IBD), with a prevalence of 20-50% for axial SpA(axSpA) and 5-20% for peripheral(pSpA). AntiTNF is the optimal therapy in axSpA intolerant or refractory to NSAIDs, also effective in pSpA. An optimal trough level has not been yet established in this clinical setting. Aim, to evaluate the correlation between antiTNF and UST trough levels and joint EIM activity in IBD patients.

Methods

Prospective, multicenter,cohort study. IBD patients diagnosed with articular EIM under antiTNF or Ustekinumab(UST) for at least 6 months were included. Blood samples were obtained just before administering the drug(trough levels), and a simultaneous evaluation by a rheumatologist and a gastroenterologist, was performed. Definitions: inactive AxSp=ASDAS-CRP<1.3 and BASDAI<2, inactive pSp=arthritis, enthesitis and dactylitis=0, active AxSp=ASDAS-CRP >2.1 and BASDAI>4, active pSp= artritis, entesitis o dactilitis > 0. Aim, to evaluate the correlation between antiTNF and UST trough levels and joint EIM activity in IBD patients.

Results

A total of 135 patients were included: mean age 51 ± 15, 59 (43.7%)women), 80% CD. 60(44.4%) patients presented axSpA, 50(37%) pSpA and 25(18.5%) mixed. 12(8.9%) had active IBD. Table 1 summarizes the patients' main demographic and clinical characteristics distributed by SpA activity. Fifty-three(39%) were on infliximab (IFX), 61(45.2%), on adalimumab (ADA) and 22 (16.3%) on UST treatment. NSAIDs treatment(12.7% vs 3.1%, p<0.05), higher fecal calprotectin(FC)(486 ± 709 vs 228.2 ± 297, p<0.05), and the prior use of biologics(33.8% vs 17.6%, p<0.05) were more frequent among active vs inactive SpA patients. No differences between IFX(7.05 ± 4.16 vs 5.79± 4.05, p=ns), ADA(7.98 ± 4.20 vs 9.51 ± 6.15 p=ns) and UST levels(3.39 ± 3.47 vs 3.08 ±2.69, p=ns), were found between active and inactive SpA patients, even when were distributed by type of SpA(axSpA/mixed and pSpA). Body mass index(b:-0,29, p=0.01)FC(b:-0,28, p=0.01), and intensified therapy(b:-0,28, p=0.01) were associated to higher IFX levels in the whole SpA cohort.Patients with axSpA or mixed were articular active more frequently than pSpA patients(82% vs 18%, p <0.05). IBD activity was correlated to articular activity only among pSpA patients(2% active IBD in inactive pSpA vs 20% active IBD in active pSpA patients, p=0.03).

Conclusion

AntiTNF and UST trough levels are not correlated to joint activity in patients with IBD and SpA. In our study more than 80% of patients with active SpA were inactive regarding IBD. Only pSpA patients presented correlation between IBD and articular activities.Read more P494 Efficacy and safety of Upadacitinib in moderate to severe paediatric Crohn’s disease and ulcerative colitis in a tertiary Paediatric IBD (PIBD) centre – A case seriesWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Upadacitinib is a selective Janus kinase 1 inhibitor approved for the treatment of patients 18 years and older with the diagnosis of Crohn’s disease and ulcerative colitis. Although there is promising data for its use in adult inflammatory bowel disease (IBD), limited data are currently available on its use in paediatric IBD. We present our experience in this case series of patients ≤ 18 years on Upadacitinib.

Methods

We identified patients under the age of ≤ 18 years, started on Upadacitinib for the indication of IBD. Data on demographics, disease subtype, duration on Upadacitinib, number of biologic failures, tofacitinib use, concomitant biologic use, adverse events and clinical remission were gathered.

Results

12 patients with paediatric IBD (median age at Upadacitinib start 15.5 years, range 13.9 to 17.8 years, 8 (67%) males, were identified. 7 patients had Crohn’s disease, 3 patients had ulcerative colitis and 2 patients had IBD unclassified. 4 patients (33%) were diagnosed under the age of 6 years with early onset IBD (EOIBD), 1 was 3.5 years old, 1 was 4 years old and 2 were 5 years old. 11/12 (92%) patients had failed 3 or more biologics. Upadacitinib was used as monotherapy in all patients and previous biologic treatments were stopped. 1 patient with a partial response to tofacitinib was switched to Upadacitinib. All patients had active disease at commencement of Upadacitinib. All 12 (100%) patients were started on 45 mg of Upadacitinib. 8/12 (67%) patients have been followed up for at least 8 weeks. Out of the 8 patients, 5/8 (63%) patients were in clinical remission between 8-16 weeks of therapy, 2/8 (25%) had partial response and 1/8 (13%) has been refractory to treatment. Relapse of symptoms was noted in 1 patient after dose was dropped to 30 mg; this patient had achieved remission on 45 mg. No serious adverse events occurred; 2 patients noted to have increased triglycerides (max 5.75mmol/L; range 0.38-1.58mmol/L). 1 of them had previous exposure to tofacitinib and the triglycerides were already raised prior to starting Upadacitinib. 1 patient developed headaches, as a result, Upadacitinib dose was decreased. There were no incidences of shingles or other serious infections.

Abbreviations

CD, Crohn's disease; UC, ulcerative colitis; IBD-U; inflammatory bowel disease unclassified; Upa, upadacitinib; AEs; adverse events

Conclusion

The patients in this case series, started on Upadacitinib, are a heterogeneous group with refractory disease. In these paediatric and adolescent patients Upadacitinib seemed safe and efficacious with a low side effect profile. Further national and international collaborative studies are needed to confirm our findings.Table 1. Patient CharacteristicsRead more P649 Long-term follow-up of the PROTDILAT study; LONG-PROTDILAT Prospective multicenter randomized comparative study of endoscopic treatment of strictures in Crohn's disease (CD): self-expandable metal stent (SEMS) vs endoscopic balloon dilatation (EBD)Wed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The PROTDILAT study (Loras et al. Lancet Gastroenterol Hepatol.2022) at 1-year follow-up showed greater efficacy of EBD vs SEMS for the treatment of short strictures in CD.

Aims

To assess the long-term evolution of patients included in PROTDILAT study. 1)Percentage of patients free of surgery; 2)Factors related to surgery; 3)Need for endoscopic retreatments; 4)Effectiveness related to the type of initial endoscopic treatment (EBD vs SEMS); 5)Complications related to endoscopic or surgical treatment.

Methods

Retrospective study based on PROTDILAT trial database (patients with CD, obstructive symptoms, with stenosis <10cm). Data on medical, endoscopic and surgical treatment and smoking habits were collected. The effectiveness of endoscopic treatment is defined by the percentage of patients free of surgery and endoscopic retreatment at the end of follow-up.

Results

Information available on 80/80 patients (39 SEMS, 41 EBD), 39 women, age (median): 45y (IQR: 38-55); median stricture length 3.4cm (IQR: 2-5.5), 42.5% being anastomotic. Thirty percent (24/80) of patients required surgical resection [(median time to surgery 27.88 months (5.89-52.39)]. Factors associated to surgery: non- intensification of therapy (HR 0.23 (0.09-063)), treatment with EBD (HR 0.24 (0.09-0.7)) (with respect to treatment with EBD + SEMS) and number of stents (HR 2.88 (1.14-7.27)). Of the 56 patients free of surgery, during the entire follow-up (median 84 months (74.7-84.0)), a median of 2 endoscopic procedures (1-3) were performed: EBD in 45 cases (80.0%) and SEMS in 26 cases (46%). Thirty-eight-point seventy-five percent (31/80 patients) did not require neither surgery nor endoscopic retreatment during the follow-up. Out of 44/80 patients (16 SEMS vs 28 EBD) with primary treatment success in PROTDILAT study (1 year of follow-up) that not required surgery, the long-term effectiveness of endoscopic treatment was 56% for SEMS and 68% for EBD (p=0.4). The complications related to endoscopic or surgical treatment were 8.75% (7/80) versus 37.5% (9/24) respectively (p=0.002).

Conclusion

Endoscopic treatment (predominantly EBD) avoids surgery in most cases, requiring a low number of endoscopic treatments in the long-term. Patients at higher risk for surgery are those with a greater number of endoscopic treatments that include SEMS and EBD. On the contrary, protective factors are non-intensification of therapy and having been treated exclusively with EBD. Although there are no significant differences in the long effectiveness between SEMS and EBD, a trend for a better outcome is observed for EBD. To highlight a significant higher rate of complications observed in surgical treatment compared to endoscopic treatment.Read more P495 Comparative characteristics of joint damage and entheses of the upper and lower extremities in patients with inflammatory bowel diseasesWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The aim of study was to compare the incidence of joint damage and entheses of the upper and lower extremities in patients with inflammatory bowel diseases (IBD).

Methods

95 IBD pts were prospectively enrolled into the study: 55 pts with ulcerative colitis and 40 - with Crohn's disease. The average age of pts was 32 (26; 37) years. The average duration of the disease was 48 (12; 96) months. Using ultrasound, each pt was examined 14 joints and 68 enthesis of the upper and lower extremities. The vascularization was detected in the power Doppler mode. The presence of synovitis was established by detecting the proliferation of the synovial membrane and/or effusion in the joint cavity. Inflammatory (enthesis hypoechogenicity, enthesis thickening, presence of vascularity) changes in enthesis were also performed by ultrasound imaging.

Results

According to the results of ultrasound of the joints, synovites were detected in 41 pts (43%), including synovites with vascularization in 29 pts (31%). Synovites were most often detected in the ankle joints - in 28 pts (29%). Synovites with vascularization were most often detected in the elbow joints - in 11 pts (12%), in the wrist joints - in 11 pts (12%), in the knee joints - in 10 pts (11%). When comparing the incidence of lesions of the joints of the upper and lower extremities, it was found that synovites were more often observed in the joints of the lower extremities - in 42 pts (44%) than in the upper extremities - in 33 pts (35%). However, differences did not reach statistical significance (p=0.23).Enthesites were found in 72 pts (76%), including vascularized enthesites in 35 pts (37%). The most common enthesites were pes anserinus enthesitis in 42 pts (44%) and medial collateral ligament of the knee joint in 37 pts (39%). The most common enthesitis with vascularization was medial collateral ligament of the knee joint - in 24 pts (25%). Comparing the incidence of enthesis lesions of the upper and lower extremities, it was found that enthesites and enthesites with vascularization were significantly more often observed in the lower extremities (p=0.00, p=0.0001, respectively).

Conclusion

Pts with IBD had a higher incidence of lower extremity joint involvement, although the differences did not reach statistical significance. Entheses were significantly more often affected in the lower extremities.Read more P669 Efficacy of Ustekinumab-based integrated medicine therapy in patients with symptomatic stricturing Crohn's disease: a multicentre, prospective, observational cohort studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Strictures are the most common structural complication of Crohn's disease (CD). Surgery and endoscopic balloon dilation are the main treatments; however, there is no data about the efficacy of ustekinumab (UST) in patients with symptomatic stricturing CD.

Methods

In this multicentric study, we prospectively included adult CD patients treated with their first UST therapy for symptomatic strictures (confirmed on endoscopy or imaging). The primary endpoint was success at week 52, defined as UST continuation without prohibited treatment (corticosteroids, other biologics), endoscopic dilation, or bowel resection. The long-term endpoint was discontinuation of treatment for failure, bowel damage progression and time to surgery in the whole cohort. The effectiveness was determined by the relief of stenosis while the baseline factors independently associated with success were identified using a logistic regression model.

Results

Overall, 28 patients were included and analyzed for baseline [median age-34 (range 24-46) years; males-64.3%; median disease duration-10 (range 2–216) months; active smokers-10.7%]. The ileum was the most common site of stricture (67.9%), 21.4% of patients had colonic strictures, and 17.9% had multiple strictures. 35.7% of patients were steroid-dependent. Before enrollment, 10.7% of patients had got bowel surgery, 25.0% got perianal surgery, and 3.6% got endoscopic dilation treatment. 14.3% had received treatment of other biologics.The rate of success at 52 weeks was 71.4% while 8 patients quit due to stricture surgery, changed to anti-TNFs, or resumed exclusive enteral nutrition. In terms of stenosis remission, the SES-CD of strictures and DBE-CD decreased from 6.71±0.18 and 3.85±0.15 to 3.14±0.14 and 3.04±0.24, respectively. The Crohn’s disease obstructive score (CDOS) significantly decreased from 4.85±0.61 to 1.14±0.39 (p=0.025).In the assessment of disease activity, UST down-regulated the IBUS-SAS of ultrasound from 71.71±5.23 to 54.73±5.41 (p=0.036). HBI (p=0.14) had a downtrend during the follow-up period, and the concentrations of CRP (p=0.04) and FCP (p=0.025) also decreased respectively.The predictive factors of remission in patients who received ustekinumab were bowel wall thickness < 5 mm (p=0.031). No significant risk of surgery or failure has been observed yet (p=0.25).

Conclusion

Ustekinumab seems to be effective in controlling the progress of intestinal strictures in CD patients. Nevertheless, further cohort size expansion and data analysis are indispensable.Read more P536 Outcome of colorectal cancer surveillance in paediatric inflammatory bowel disease: Time for new guidelines?Wed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Paediatric inflammatory bowel disease (IBD) patients have an increased risk of colorectal cancer (CRC). Current guidelines advise to conduct CRC surveillance colonoscopy eight years following IBD diagnosis, or more often in case other risk factors for CRC are present, such as previous findings of colorectal dysplasia, or a concomitant primary sclerosing cholangitis (PSC) diagnosis. However, these guidelines are based on adult data and with no regard to the patient’s age, while frequent endoscopies impose a significant burden on children. In this study, we aimed to estimate the risk of dysplasia and CRC in paediatric IBD patients before the ages of 18 and 27 years.

Methods

Using the Dutch Nationwide Pathology Databank (PALGA), we examined the incidence and prevalence of dysplasia and CRC in patients up to 27 years in all Dutch paediatric IBD patients diagnosed between 1991 and 2023. Additionally, we assessed the influence of PSC diagnosis on CRC risk.

Results

Out of the 7,873 patients with biopsy-proven paediatric IBD, 24 developed dysplasia (0.34%) and two (0.025%) developed CRC before the age of 18 years. Out of the 3,425 patients from this cohort currently aged over 26 years, eleven (0.3%) developed CRC between 17 and 27 years. Overall, 120 patients (1.5%) were diagnosed with concomitant PSC, seven (5.8%) of which developed dysplasia and two (1.6%) of which developed CRC before the age of 27 years. The median time between IBD diagnosis and CRC diagnosis was 9.5 years in this cohort. Overall, CRC incidence before the age of 27 years decreased between 1991 and 2023. Additional clinical data on IBD localisation, severity of the disease, and concomitant diagnoses could not reliably be obtained from this database.

Conclusion

In this retrospective study, we found low prevalence of dysplasia and CRC in paediatric IBD patients, both before the age of 18 years and before the age of 27 years. PSC prevalence was low in this cohort, since only biopsy-proven PSC was included. However, we showed that PSC significantly increased the risk of CRC in paediatric IBD patients. Based on our findings it could be proposed to initiate CRC surveillance beyond the age of 18 years by experienced adult gastroenterologists, except in case of a concomitant PSC diagnosis.Read more P670 Intestinal Motility Changes in Patients Undergoing Removable Stent Treatment for Focal Crohn’s Disease StricturesWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Management and assessment of fibrostenotic Crohn’s disease(CD) is a research priority. Deep phenotyping is key for effective therapeutic development. In this study, we explore MRI assessed bowel motility before and after endoscopic stent treatment of focal fibrotic strictures in patients with CD.

Methods

Patients (n = 12, median age = 51 y) undergoing removable stent treatment were recruited as part of an approved study. Average CD diagnosis was 31y (range 16-57 y). All strictures were fibrotic in nature- three were de novo, while the remaining were anastomotic (ileocolonic). All patients had symptoms attributable to focal stricturing. Each patient had an MR – Enterography (MRE) scan (median 21 weeks) before and after (median 17 weeks) stent dilation. MR – Enterography (MRE) protocol included oral preparation, anatomical and cine ‘motility’ sequences across the abdomen in 20s breath hold (1 image/second). Motility sequences were processed with CE/FDA cleared GIQuant (Motilent, UK) to produce a quantitative map from which, objective data could be generated across the bowel. Stricture assessment was performed by a consultant radiologist.Non parametric statistics were used to investigate the following questions:1. Was the baseline regional motility (mean, range) at stricture, dilation and morphologically normal bowel different across patients (Kruskal-Wallis)?2. What were the changes in stricture motility pre and post stent placement (Wilcoxin Rank)?3. Was stricture motility associated with stricture morphology (Spearman’s Rho)?

Results

1. Motility at the stricture (126, range 62 to 139), pre-stenotic terminal ileum (252, range 80 to 478) and the global small bowel (269, range 166 to 339) was varied across the cohort (P < 0.001).2. All patients had improvement in symptom scores & reporting, without change in stricture motility (P = 0.94).3. A positive change in stricture motility was associated with reduced length of pre stricture dilatation (R = 0.64, P = 0.02)

Conclusion

Strictured intestine displayed reduced motility compared with adjacent bowel segments. While reduced, peristalsis was still present although paired analysis suggested no change pre and post stent stricture management. This implies that symptomatic relief was not related to altered peristalsis across the study. Finally, the length of dilation did appear to be associated with dynamic changes in stricture motility. In summary, as noted in stent-treated CD strictures, a dynamic physiological environment exists which can be captured with Cine MRI. These motility assessments, which have been studied as a proxy indicator of active CD, represent the first reported dynamic motility outcomes following stricture intervention.Read more P537 Analysis of immunological VAriables in ex vivo Tofacitinib-treated human biopsies from Active ulcerative colitis patients to predict clinical Response (the AVATAR study)Wed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Ulcerative colitis (UC) is characterized by chronically relapsing inflammation of the colonic mucosa. Tofacitinib (TOFA) is a paninhibitor of the JAK kinases, a family of intracellular kinases in volved in the signal transduction pathway of multiple inflammatory signals. Despite the efficacy shown by TOFA in inducing and maintaining remission in moderately-to-severely active UC, rates of primary non response remains high. We propose a new method to identify predictors of responsiveness to TOFA based on "ex-vivo" challenge of organ cultures from biopsies collected from candidate patients.

Methods

Baseline biopsies from inflamed areas of UC patients with active disease and candidate to receive TOFA 10mg b.i.d. for 8 weeks, were used for "ex-vivo" organ culture and stimulated with TOFA 20μM and 200nM or left untreated. After 24 hours, proteomic analysis was performed and quantitative expression of 92 inflammation-related human proteins (Olink® Human Inflammation panel) was correlated with week 8 clinical response defined by Modified Mayo Score (MMS). Intestinal biopsies were also collected at baseline and at 8 weeks for proteomic analysis. To decipher the nature of TOFA's effects, both unsupervised and supervised machine learning (ML) methods were employed (sklearn module, Python). The K-means method was used for unsupervised learning followed by a supervised ML approach to classify week 8 responders and non-responders. Data were transformed in into a second-order polynomial format and logistic regression was used for modelling.

Results

Between Jannuary 2022 and January 2023, 17 UC patients were enrolled (Table 1). At week 8, 13/17 (76.5%) patients treated with TOFA showed clinical response. Unsupervised ML, utilizing proteomic data from organ cultures stimulated with TOFA 200nM, achieved a 90% success rate in predicting a positive clinical response. This prediction was based on forming two distinct clusters, with significant contributions from key variables such as CASP-8, CCL19, CCL20, CD5, CXCL9, EN-RAGE, GDNF, HGF, IL-18R1, MCP-1, MCP-2, MCP-4, MMP-10, OPG, PD-L1, STAMBP, TNFRSF9, TRANCE, TWEAK, and VEGFA. In our supervised ML approach, logistic regression was employed with 30 shuffle splits to refine the predictive model. We discovered that transforming the dataset into a second-order polynomial format significantly enhanced the model's performance. The most effective logistic regression model achieved a mean precision score of 0.82 (Fig.1).

Conclusion

Our predictive model demonstrates a high level of precision in identifying positive treatment responses, emphasizing the potential of further dataset expansion and the use of advanced machine-learning to predict response in TOFA-treated UC patients.Read more P400 Experience with the use of intestinal ultrasound and application of the Milan Ultrasound Criteria in Colombian patients with ulcerative colitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Intestinal ultrasound (IUS) has been reported to be accurate in the diagnosis of ulcerative colitis (UC) and can also be applied to determine the extent of the disease, its severity and location of inflammation, also, is fast, effective, non-invasive, relatively inexpensive, and can be performed in health care centres of varying complexity. The aim of this study is to assess the validity and reproducibility of IUS in patients with UC, and evaluate the Milan Ultrasound Criteria (MUC) as a predictor of activity in UC.

Methods

analytical observational study in adults and paediatric patients with UC with different degrees of activity, and with a need for colonoscopy. Clinical, biochemical, endoscopic, and ultrasonographic variables were collected. Logistic regression analysis was performed. The presence of endoscopically active disease was the outcome (or dependent variable). All IUS parameters described were independent variables. Univariate analysis was used to identify candidate predictors. A significance level of 0.05 was used in all tests.

Results

Thirty-six subjects were included, predominantly male, 75% (27/36) were in endoscopic remission (Mayo score 0 -1), while 25% (9/36) had endoscopic activity (Mayo endoscopic score > 2). Median Colonic wall thickening (CWT) in patients in endoscopic remission (Mayo score 0-1) was 2.4 (IQR 2-2.8) mm compared to 3.1 (IQR 2.15-4.2) mm in patients with endoscopically active disease (Mayo score 2) with no statistically significant difference p=0.148. Colonic wall flow at power doppler (CWF) was present in 22.2 % (6/27) of patients in endoscopic remission compared to 44.4 % (4/9) of patients showing endoscopic activity (p=0.148). Endoscopic activity (p = 0.264). Loss of elasticity and peristalsis was present in 11.1% (3/27) patients in remission compared to 66.6% (6/9) in patients with activity (p=0.003). As for mesenteric fat hypertrophy, it was found in 44.4% (4/9) of patients with activity compared to 14.8% (4/27) in remission (p=0.098). Enlarged mesenteric nodes were found in 22.2% (2/9) patients with activity compared to 14.8% (4/27) in remission (p=0.615). Free fluid was present in 22.2% (2/9) of patients with activity compared to 7.4% (2/27) in remission (p=0.315). The mean value of the MUC score was 4.025 (observer 1 mean 3.85 with S: 77% and E: 70%, observer 2 mean 3.99, with S: 66% and E: 77%). The degree of interobserver agreement was 0.957.

Conclusion

IUS is a useful and effective tool in the evaluation of disease activity in patients with UC, with a MUC measurement of 4.025 suggesting an adequate diagnostic performance of this score, being the best cut-off point to discriminate between activity versus remission.Read more P623 Network meta-analysis to evaluate the comparative efficacy of advanced therapies as first line for maintenance treatment of adult patients with moderate-to-severe Crohn’s diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Subcutaneous (SC) CT-P13 provides patients and physicians with a new opportunity for maintenance treatment of Crohn’s disease (CD).¹ Given the rapidly expanding therapeutic armamentarium for CD and lack of direct comparative evidence,² an updated network meta-analysis (NMA) of data from Phase 3 randomised controlled trials (RCTs) was performed to evaluate the comparative efficacy of advanced CD therapies licensed in Europe or the US.

Methods

Eligible studies, identified by systematic literature review (PROSPERO no.: CRD42023413752), evaluated the efficacy of maintenance therapy using intravenous (IV) or SC infliximab, SC adalimumab, IV or SC vedolizumab, SC ustekinumab, SC risankizumab or oral upadacitinib, in patients with moderate-to-severe CD who responded to induction therapy. Head-to-head studies (including with treat-through designs) comparing licensed advanced therapies were also eligible. Studies were placebo- (PBO) or active-controlled and included 52–64 weeks of follow-up. Patients had not received prior tumour necrosis factor inhibitors, other biologics or Janus kinase inhibitors, thus each drug was received as first-line advanced therapy. Clinical remission and endoscopic response rates achieved with maintenance treatment were synthesised and analysed in a frequentist NMA random-effects model.

Results

There were 9 eligible RCTs (ACCENT I, LIBERTY-CD, CHARM, SEAVUE, GEMINI 2, VISIBLE 2, IM-UNITI, FORTIFY, U-ENDURE). Among 14 compared treatment arms, SC infliximab 120 mg every 2 weeks (Q2W) showed the highest risk difference (RD) versus PBO for achieving clinical remission during the maintenance phase (0.38 [95% confidence interval (CI): 0.23, 0.53]), followed by SC adalimumab 40 mg QW (0.32 [0.17, 0.48]) and oral upadacitinib 30 mg once daily (0.30 [0.08, 0.53]) (Figure A). Endoscopic response data were available from LIBERTY-CD, FORTIFY and U-ENDURE: among 5 treatment arms, SC infliximab 120 mg Q2W showed the highest RD (95% CI) versus PBO for achieving endoscopic response (0.39 [0.29, 0.49]), followed by SC risankizumab 180 mg Q8W (0.37 [0.17, 0.56]) and SC risankizumab 360 mg Q8W (0.27 [0.06, 0.48]) (Figure B).

Conclusion

In this updated NMA, SC infliximab 120 mg Q2W demonstrated a favourable efficacy profile in terms of achieving clinical remission and endoscopic response, when administered as a first-line advanced therapy for maintenance treatment of patients with moderate-to-severe CD.¹Remsima summary of product characteristics (https://www.ema.europa.eu/en/documents/product-information/remsima-epar-product-information_en.pdf). Accessed 1 November 2023.²Barberio B et al. Gut 2023;72:264–74.Read more P422 Prevalence of poor sleep quality assessed by wrist actigraphy and sleep questionnaire in Inflammatory Bowel Disease patients and its association with disease activity and quality of lifeWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

An association between active inflammatory bowel disease (IBD) and poor sleep quality has been proposed, however studies evaluating both subjective and objective assessment of disease activity and sleep quality are limited. Our study aimed to investigate the prevalence of poor sleep quality assessed by wrist actigraphy and sleep questionnaires in IBD patients and its association with disease activity and quality of life.

Methods

A prospective observational study was conducted in Siriraj Hospital, Mahidol University, Bangkok, Thailand from March 2021 to December 2022. Eligible IBD patients were categorized into remission, mild, and moderate-to-severe groups, based on standard clinical disease activity scores. Demographic data, inflammatory markers, inflammatory bowel disease questionnaire (IBDQ), sleep questionnaire (Pittsburgh Sleep Quality Index, PSQI), and seven-day sleep data from wrist actigraphy (Actiwatch^®, CamNtech, Cambridge, United Kingdom) were obtained. The prevalence of sleep disorder and group comparison were analyzed.

Results

Eighty-four participants (40 Crohn’s disease, 44 UC), consisting of 60 remission, 16 mild, and 8 moderate-to-severe disease activity, were enrolled. Baseline demographic data were comparable between each group. Lower hemoglobin and albumin levels, and higher serum C-reactive protein, and fecal calprotectin levels were found in the more clinically active groups (table1). Fifty patients (60%) had poor sleep defined by PSQI > 5 with a trend to be higher in the group with active symptoms (57% in remission, 63% in mild, and 75% in moderate-to-severe group, p=0.31). Using actigraphy, the group with moderate-to-severe symptoms tended to have longer sleep latency, more frequently awake after sleep, and poorer sleep efficiency than the other groups (Figure 1). Patients with more severe disease activity had poorer quality of life with a mean IBDQ of 190 in remission, 159 in mild, and 134 in moderate-to-severe group (p<0.001).

Conclusion

Poor sleep quality is common among IBD patients, even those with clinical remission. Those with more severe symptoms had poorer sleep quality and worse quality of life. Sleep assessment and treatment should be integrated into IBD standard clinical care.Read more P633 First-in-Human Pharmacokinetic and Safety Study of an Anti-TL1A Antibody, TEV-48574, in Healthy Volunteers and Asthma PatientsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

TEV-48574 is a human antibody that targets tumor necrosis factor (TNF)-like ligand 1A, also known as TNF superfamily member 15 (TNFSF15). TEV-48574 is in clinical development as a potential treatment for ulcerative colitis (UC) and Crohn’s disease (CD); and has been shown to reduce fibrosis, inflammation, and mortality in animal models of IBD and asthma.¹ The main objectives of this phase 1 study were to characterize the pharmacokinetics (PK) and safety of TEV-48574 in healthy subjects and mild asthmatic patients.

Methods

In the single ascending dose part of the study (SAD), healthy subjects were randomized 6:2 to active and placebo treatment; specifically participants were either administered TEV-48574 single dose (1, 4, 12, 36, 90, 200, 400, or 1000 mg) or placebo by subcutaneous route (SC). In the multiple ascending dose part of the study (MAD) patients with asthma were randomized 9:3 to active and placebo treatment in three cohorts. Cohort 1 received TEV-48574 200 mg Q2W or placebo (days 1, 15, and 29). Cohort 2 received a loading TEV-48574 dose of 800 mg on day 1 followed by 2 maintenance doses of 600 mg on days 15 and 29 (800/600 mg Q2W) or placebo. Cohort 3 received a loading TEV-48574 dose of 2300 mg on day 1 followed by 2 maintenance doses of 1600 mg on days 15 and 29 or placebo. Safety, tolerability, PK, and anti-drug antibody (ADA) levels were assessed at predetermined times. Measurement of total and free TL1A using ligand binding assays will be reported elsewhere.

Results

TEV-48574 was absorbed slowly with peak concentrations appearing at 72- 96 hours following SAD and MAD administration. It was eliminated gradually in a monophasic manner and the rate of elimination appeared similar across dose levels (Figure 1). Exposures as defined by maximum concentration (C_max) and area under the curve (AUC) of TEV-48574 increased in a dose-proportional manner with no accumulation. Mean t½ estimates ranged from 6.5 to 9.6 days (Table 1).Administration of TEV-48574 was generally well tolerated at doses up to 2300 mg. ADA-positive responses were observed at doses of 200 mg or lower in 23 of 48 TEV-48574-treated subjects in the SAD portion of the study and in 3 of 27 TEV-48574-treated patients in the MAD portion of the study and were not associated with safety signals.

Conclusion

TEV-48574 was well tolerated at all tested doses in healthy subjects and participants with asthma, with dose proportional increases in exposure and minimal accumulation after multiple dosing every two weeks. The data support further development of TEV-48574 in patients with IBD.1. Clarke A. et al. mAbs.2018;10:664-677.Read more P423 Incidence of Colorectal Cancer among Patients with Ulcerative Colitis in the Middle East: A Systematic Review and Meta-AnalysisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by mucosal inflammation of the colon. A well-documented long-term complication of UC is an increased risk of developing colorectal cancer (CRC). The Middle Eastern population, with its unique genetic and environmental factors, presents a distinctive context for the investigation of CRC risk in UC patients. This meta-analysis aims to systematically evaluate and synthesize the available data on the incidence of CRC among UC patients in the Middle East

Methods

A comprehensive literature search was conducted, identifying relevant studies from various databases and sources. A total of 12 studies met the inclusion criteria and were subjected to quantitative synthesis. The primary outcome measure was the incidence of CRC among UC patients in the Middle East. A random-effects model was used for data synthesis. Heterogeneity was assessed using the I^2 statistic.

Results

The meta-analysis included a total of 12 studies, comprising 13,881 UC patients in the Middle East. The overall estimated incidence of CRC in this population was 1.41% (95% confidence interval [CI]: 1.32% to 1.50%). Notably, there was substantial heterogeneity across the studies (I² = 100%).

Conclusion

This meta-analysis provides insights into the incidence of CRC among UC patients in the Middle East. The findings underscore the significance of recognizing and addressing the elevated risk of CRC in UC patients, particularly in the context of unique genetic and environmental factors in the Middle East. Further research is needed to refine risk assessment and optimize preventive strategies in this specific population. Ultimately, this study serves as a vital resource for clinicians and researchers seeking to combat the burden of CRC in Middle Eastern UC patients.Read more P444 Active perianal Crohn’s disease negatively impacts patients’ quality of life, psychosocial wellbeing and is associated with barriers related to social determinants of healthWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Perianal fistulizing Crohn’s Disease (PFCD) is associated with poor quality of life (QoL) and increased healthcare utilization. However, the effect of PFCD on patients’ lives remain incompletely understood. We conducted a survey-based study of patients with PFCD to examine the impact of perianal fistula disease activity on QOL, psychosocial wellbeing, and barriers related to SDOH.

Methods

Patients aged 18 years and above with a diagnosis of PFCD were included between July and November 2023 at Mount Sinai Hospital. Patient data, including demographics and clinical data, were obtained from patients and chart review. Perianal disease classifications were assessed through chart review. Crohn’s anal fistula quality of life (CAFQOL) scale, PROMIS scale for anxiety and depression, Internalised stigma for mental illness (ISMI), Everyday discrimination scale, health first screening tool for SDOH and the Cantril ladder of life scale were administered to patients. Patients with active PFCD, defined as perianal pain and/or drainage, were compared to patients with inactive PFCD, defined as lack of perianal pain or drainage. Descriptive statistical analysis was performed using SPSS

Results

A total of 50 patients were included in the study, of whom 39 had active disease and 11 inactive disease (Table 1). Annual household income was lower among patients with active PFCD (p=0.017). Disease characteristics such as Montreal classification, HBI and perianal disease classification, presence of proctitis, surgical history were similar across both groups. Overall, patients with active PFCD compared to inactive PFCD had higher CAFQOL scores (mean active:inactive;1.82:0.44, p<0.001). Patients with active PFCD also had higher rates of depression and anxiety (mean 2.06:1.23, p=0.020). Internalised stigma was higher among patients with active PFCD. There was no difference in discrimination faced as a consequence of PFCD. 20.5% and 12.8% patients with active PFCD reported facing social isolation and food insecurity respectively. By the Cantril ladder, patients with active PFCD had lower current life satisfaction compared to inactive PFCD (mean 6.03:7.60, p=0.024). However, there was no difference in their outlook on life satisfaction in 5 years.

Conclusion

In our cohort, perianal disease activity alone results in significantly worse quality of life and negatively impacts psychosocial wellbeing. Patients with active PFCD are at risk for barriers related to SDOH which are known to have implications on health equity.Read more P652 Transitioning Inflammatory Bowel Disease patients from an intravenous to a subcutaneous infliximab protocol: a single centre experience and patient satisfaction surveyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Infliximab is used for the treatment of Ulcerative colitis (UC) and Crohn's disease (CD). Subcutenanous (SC) infliximab (CT-P13) received regulatory approval from the European Medicines Agency for Inflammatory Bowel Disease (IBD) in July 2020. Our study aim was to assess the efficacy and safety of SC infliximab in our patient cohort at University Hospital Lewisham as well as gain patient feedback on their experience of subcutaneous infliximab compared to intravenous infliximab.

Methods

We retrospectively analysed the records of all patients receiving infliximab treatment from May 2022 to May 2023 for age, gender, diagnosis, clinical response, faecal calprotectin levels and side-effects. We designed a patient questionnaire for patients who were switched from IV to SC infliximab to assess patient preferences with regards to route of administration, satisfaction with treatment as well as reported side effects.

Results

60 patients (M:F ratio 1:1; average age 36.2y) were receiving infliximab during this time frame. 23 patients were switched to SC infliximab whilst 37 patients remained on IV infliximab. 37/60 (61.7%) had CD, 20/60 (33.3%) UC, and 3/60 (5.0%) IBD unclassified (IBD-U).Mean faecal calprotectin (FC) levels during treatment were comparable in both groups (Mean FC 117 in IV group; Mean FC 94 in SC group). No patient in either group required hospital admission or gastrointestinal surgery. 1/23 (4.3%) patients switched to an alternate biologic in SC group due to loss of response, whist 3/37 (8.1%) patients in IV group required a switch of biologic therapy over the same time frame.There were no major side effects reported in either the SC group or IV group. There were 5 minor side-effects recorded in the IV group - 4/37 (10.8%) rash; 1/37 (2.7%) mildly deranged liver function tests. There was 1 minor side effect reported in the SC infliximab group of mild injection site skin reaction 1/23 (4.3%)18/23 (78.2%) SC infliximab patients completed the patient satisfaction questionnaire. All respondents (18/18, 100%) found the drug more convenient to self-administer than attending the infusion unit for IV infliximab. 1 patient (4.3%) reported mild pain and skin reaction at the injection site. 22/23 (95.7%) of the SC group were satisfied with their treatment and preferred to continue on the SC regimen rather than receive IV infliximab. The one patient who preferred IV infusions reported fear of needles and self-injections as the reason for the IV preference.

Conclusion

Our study showed that SC infliximab was a safe, well tolerated and efficacious treatment compared to IV infliximab. Our patient satisfaction survey showed that a large majority of patients preferred the SC method of administration and were satisfied with their treatment.Read more P445 Wireless capsule endoscopy reading support for Crohn’s disease patients using deep neural networks with an active learning methodWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Artificial intelligence (AI) systems, in particular neural networks (NN), have been developed to detect lesions in wireless capsule endoscopy (WCE) in patients with Crohn’s disease (CD) in order to ease their reading. Despite acceptable performance on individual images, these tools do not analyze entire videos and require a large amount of labeled data. Active learning (AL) methods have already been used, proving their ability to limit labeling cost without reducing NN performance. The aim of this study was to evaluate several AL models in order to train an AI system able to differentiate normal and pathological entire videos with a limited labeled dataset.

Methods

Firstly, 76 WCEs of CD patients were used to automate the detection of the first and last image of the small bowel. They were identified by an expert and then used for training, validation and test of a NN. The model associated with the Viterbi algorithm predicted boundaries location and was compared with expert annotations.Secondly, 4286 images from the Crohn-IPI database¹ were used to train another NN to classify pathological or normal images. An image was considered pathological if it contained erythema, oedema, ulceration or stenosis. Four AL models with several selection criteria² were tested on a limited labeled dataset and their classification performance (normal/pathological image) was evaluated.Finally, 42 WCEs were used to assess performance of a pre-trained AL model to predict the normal or pathological nature of entire videos.

Results

Overall, the model detected the pylorus compared with experts with a median deviation (IQR) of 3 images (66.5) and the last ileal image with a median deviation of 98 images (336). A history of ileocolic resection non-significantly impaired the last ileal image location, with a median difference of 203 images (812, p=0.59).None of the four AL models showed superiority in classifying pathological or normal image, with a sensitivity of 60% and a specificity of 98%.Finally, the AL pre-trained NN assessed the pathological/normal status of entire videos with a sensitivity of 83% and a specificity of 50%.

Conclusion

Our study suggests the feasibility and efficiency of NN to identify the first and last image of the small bowel on CD patients WCE. Performances of the four AL models were similar but remained sufficient given the small amount of labeled data used. Prediction of the pathological/normal status of entire videos by AI systems seems feasible, but requires optimization to obtain acceptable results for current practice.1. De Maissin A et al. Multi-expert annotation of Crohn's disease(...) neural network, Endosc IntOpen(2021)2. Wang K et al. Cost-Effective Active Learning for Deep Image Classification, IEEE (...) Technology(2017)Read more P665 Statins use and the risk of colorectal cancer in patients with inflammatory bowel disease: A Systematic review and meta-analysisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Statin use has been linked to a reduced risk of advanced colorectal adenomas; however, its association with colitis-associated dysplasia and cancer is not well-defined. We aimed to perform a systematic review and meta-analysis to assess the pooled association of statin exposure with dysplasia and colorectal cancer in patients with inflammatory bowel disease (IBD).

Methods

We searched MEDLINE, EMBASE, and the COCHRANE library to identify full text articles analyzing the risk of CRC or dysplasia development based on statin use in patients with IBD. A meta-analysis was performed using a random-effects model to pool estimates and report hazard ratios [HRs] or odds ratios [ORs], following the data format specified in the individual studies.

Results

A total of 4 studies were identified as eligible for the meta-analysis. In the analysis of studies presented with time-to-event outcomes, statin use was associated with a statistically significant reduction in risk of colorectal cancer (HR 0.76, 95% confidence interval [CI] 0.61-0.95, P=0.016). Meanwhile, in the analysis of non-time-to-event study results, statin use was associated with a trend towards lower colorectal cancer risk (OR 0.28, 95% CI 0.07-1.10, P=0.068).

Conclusion

Statin use appears to be associated with a reduced risk of colorectal cancer in patients with inflammatory bowel disease. Statins may serve as potential chemopreventive agents for long-standing IBD patients, and further large-scale prospective studies will be needed to confirm its potential benefit.Read more P468 Relevance of anti-drug antibodies in context of supra-therapeutic anti-TNF concentrationsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The low serum concentration of anti-tumor necrosis factor-alpha (anti-TNFα) agents and the presence of anti-drug antibodies are related to poor therapeutic outcomes in inflammatory bowel disease (IBD). We aimed to evaluate the prognosis of patients having both antidrug antibodies and supratherapeutic drug concentrations.

Methods

IBD patients on maintenance infliximab (IFX) or adalimumab (ADA) therapy were prospectively recruited. Serum drug concentrations and antidrug antibodies were measured (Anser, Prometheus). The drug concentrations were classified as subtherapeutic (IFX: <3 µg/mL; ADA: <5 µg/mL), therapeutic (IFX: 3-8 µg/mL; ADA 5-10 µg/mL), and supratherapeutic (IFX > 8 µg/mL; ADA > 10 µg/mL) concentrations regardless of the timing of blood sample collection. We analysed the relationship between i) drug concentrations and ii) the presence and absence of anti-drug antibodies with use of systemic corticosteroids and anti-TNF discontinuation.

Results

Of 172 patients (122 CD [70.9%], 44 UC [25.6%], 3 IBD-U [1.7%], and 3 IBD-pouch [1.7%]), the median age was 32.3 years (range, 24.8-42.5), and the median duration of IBD was 9.7 years (range 5.3-15.6). IFX and ADA were used in 81 (47.1%) and 91 (52.9%) patients, respectively, and concurrent usage of immunomodulators and systemic corticosteroids was observed in 39 (22.7%) and 23 (13.4%) patients, respectively. Supratherapeutic, therapeutic, and subtherapeutic concentrations were observed in 74 (43.0%), 32 (18.6%), and 66 (38.4%), respectively. The patients with antidrug antibodies (n = 79, 45.9%) showed a higher frequency of having subtherapeutic drug concentrations (68.4% vs 12.9%, P < 0.001) compared to those without antibodies, and the presence of antibodies was an independent predictor of discontinuation of anti-TNFα agents (hazard ratio 3.50, 95% confidence interval 1.88-6.51, P < 0.001, Fig. 1A). In subgroup analysis, patients with antidrug antibodies and supratherapeutic drug concentration exhibited a tendency to have improved drug persistence compared to those with subtherapeutic drug concentration, albeit insignificantly (P = 0.099, Fig. 1B). However, the persistence in this group was still poorer than that observed in patients without antibodies (P = 0.003). Finally, neither anti-TNFα concentrations nor the presence of antidrug antibodies were associated with the need for additional systemic corticosteroid use within 6 months.

Conclusion

The presence of antidrug antibodies can predict the discontinuation of anti-TNFα agents despite supratherapeutic drug levels. While supratherapeutic drug concentration may improve the treatment persistence of anti-TNFα agents in patients with anti-drug antibodies, it does not last as long as in those without antibodies.Read more P666 Accuracy of information given by ChatGPT for patients with Inflammatory Bowel Disease in relation to ECCO guidelinesWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

As acceptance of AI platforms increases, more patients will consider these tools as sources of information. The ChatGPT architecture utilizes a neural network to process natural language, thus generating responses based on the context of input text. The accuracy and completeness of ChatGPT3.5 in the context of Inflammatory Bowel Disease (IBD) remains unclear.

Methods

In this prospective study, 38 questions worded by IBD patients were inputted into ChatGPT3.5. The following topics were covered: 1) Crohn’s Disease, Ulcerative Colitis, and malignancy, 2) maternal medicine 3) infection and vaccination 4) complementary medicine. Responses given by ChatGPT were assessed for accuracy (1 – completely incorrect to 5 – completely correct) and completeness (3-point Likert scale; range 1 – incomplete to 3 – complete) by 14 expert gastroenterologists, in comparison with relevant ECCO guidelines.

Results

In terms of accuracy, most replies (84.2%) had a median score of ≥4 (IQR:2) and a mean score of 3.87 (SD: +/- 0.6). For completeness, 34.2% of the replies had a median score of 3 and 55.3 % had a median score of between 2 and <3. Overall, the mean rating was 2.24 (SD: +/- 0.4, Median:2 IQR :1). Though group 3 and 4 had a higher mean for both accuracy and completeness, there was no significant scoring variation between the 4 question groups (Kruskal-Wallis test p:>0.05) (Table 1). However, statistical analysis for the different individual questions revealed a significant difference both for accuracy (p<0.001) and completeness (p<0.001). The questions which rated the highest for both accuracy and completeness were related to smoking, while the lowest rating was related to screening for malignancy and vaccinations especially in the context of immunosuppression and family planning.

Conclusion

This is the first study to demonstrate the capability of an AI-based system to provide accurate and comprehensive answers to real-world patient queries in IBD. AI systems may serve as a useful adjunct for patients, in addition to standard of care in clinic and validated patient information resources. However, responses in specialist areas may deviate from evidence-based guidance and the replies need to give more firm advice.Read more P469 Deep learning and minimally invasive endoscopy – panendoscopic detection of pleomorphic lesionsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Capsule endoscopy is a minimally invasive exam capable of performing a panendoscopic evaluation of the gastrointestinal tract. Nevertheless, capsule endoscopy is a time-consuming exam, revealing suboptimal diagnostic yield when considering the upper gastrointestinal tract. Convolutional neural network are models based on the human visual cortex architecture, suitable for image analysis. However, there is still an absence of studies about their role in capsule panendoscopy.

Methods

Our group developed a deep Learning model for panendoscopic automatic detection of pleomorphic lesions (namely vascular lesions, protuberant lesions, hematic residues, ulcers and erosions). In order to develop the convolutional neural network, 355 110 images (6 977 oesophageal, 12 918 gastric, 258 443 enteric, 76 772 colonic) from eight different capsule endoscopy and colon capsule endoscopy devices were divided in a training and validation dataset in a patient split design. The model’s output was compared to three CE experts’ classification. The model performance was evaluated by its sensitivity, specificity, accuracy, positive predictive value, negative predictive value, and area under the precision-recall curve.

Results

The panendoscopic convolutional neural network was composed by organ-specific neural networks. The binary oesophagus convolutional neural network had a diagnostic accuracy for pleomorphic lesions of 83.6%. The binary gastric network identified pleomorphic lesions with a 96.6% accuracy. The undenary small bowel convolutional neural network distinguished pleomorphic lesions with different potential with 97.6% accuracy. The trinary colonic model (detection and differentiation of normal mucosa, pleomorphic lesions and hematic residues) had 94.9% global accuracy.

Conclusion

Our group developed the first deep learning model for panendoscopic automatic detection of pleomorphic lesions in both small bowel and colon capsule endoscopy devices from multiple brands, solving a critical interoperability technological challenge. Deep learning-based tools may change the landscape of minimally invasive capsule panendoscopy.Read more P679 Anti-TNF de-escalation following a treat-to-target strategy with golimumab therapy intensification to reach continuous clinical response in ulcerative colitis: the In-Target GETAID trialWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Achieving deep and continuous remission with tight control could allow de-escalation in patients with UC. The in-TARGET study was a prospective two-phase trial in UC patients initiating golimumab (GLM), that aimed to determine the proportion of patients with continuous clinical response (CCR) and endoscopic remission (ER) after one year of treatment optimization strategy (phase 1); then to assess treatment de-escalation outcome in these patients (phase 2).

Methods

This was a multicentre prospective interventional study in GETAID centres. The study included adult patients with active UC (Mayo Score ≥6 with an endoscopic subscore ≥2), naive to biologics. In the first part of the study, patients received a conventional GLM regimen, depending on their weight (<80 kg; ≥80 kg). At week 10, primary responders continued with the standard maintenance regimen (50 mg or 100 mg/4 w) and non-primary responders had systematic treatment optimization (<80 kg, GLM 100mg/4 w; ≥80kg, introduction of an immunosuppressant) (Figure 1). In the second part of the study, patients in CCR and in ER (Mayo endoscopic score 0-1) at w 54, had treatment de-escalation: GLM discontinuation for patients receiving 50mg, and dose de-escalation to 50mg for those receiving 100mg.

Results

A total of 197 patients were included, mean duration of UC was 75.9 (± 95.3) months, the mean total Mayo score was 8.4 (± 1.7). At w 10, 14 patients had stopped treatment for failure, 83 (42.1%) had a primary response, and 100 (50.7%) non-primary responders had treatment optimization. At w 54, 95 (48.2%) patients were still on GLM; of these, 64 (32.5%) patients were in CCR and ER. At w 0 and 10, no factors were associated with CCR + ER at w54. Serum GLM levels after w10 were not associated with CCR and ER at w54. No patient developed anti-GLM antibodies between w0 and w54.Sixty patients participated in the second de-escalation phase of the study: in 18 GLM was discontinued, in 38 GLM dose was de-escalated from 100 to 50mg/4 w, and 4 patients refused dose de-escalation. At w 108, 34/56 (60.7%) patients were in CCR and ER, with no change in treatment. No factors were associated with w108 remission. At w108, 23 patients had relapsed: 4/18 (22.2%) among GLM discontinuations, 19/38 (50%) among patients de-escalated from 100 to 50 mg/4w.During follow-up, no colectomy was reported, and 14 severe non-UC related adverse events occurred (3 severe infections, 2 severe anaemias, and 1 rectal cancer).

Conclusion

One third of UC patients achieved a CCR with ER at one year with optimized GLM therapy. After de-escalation of GLM, 60% of remitters at one year maintained deep remission at two years. Anti-TNF de-escalation following a treat-to-target strategy could be considered in some UC patients.Read more P506 Prevalance of the osteoporosis/osteopenia and related factors in patients with inflammatory bowel disease : An observational single-center studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Inflammatory bowel disease is characterized by chronic progressive inflammation of the gastrointestinal tract which is mainly includes Crohn’s disease and ulcerative colitis. Patients with inflammatory bowel disease are at risk for osteopenia and osteoporosis. However,this topic is not well investigated and results of the studies are contradictory. The objective of this study was to investigate of the osteopenia/osteoporosis prevalance and related risk factors in patients with inflammatory bowel disease.

Methods

Patients with inflammatory bowel disease were consecutively recruited between September 2022 to September 2023 in our single-center, cross-sectional observational study. Bone mineral density was measured by dual energy X-ray absorption scans at the femur total, femur neck, femur ward’s and spine total. Relevant patients’ and disease-spesific parameters such as clinical (MAYO score or Harwey-Bradshaw index), biochemical, endoscopic and treatment history were recorded.

Results

A total of 177 inflammatory bowel disease patients, encompassing 60 with Crohn’s disease (33.9 %) and 117 (66.1%) ulcerative colitis, were enrolled. The median age was 42.3 years (range,18-75), the mean body mass index (BMI) was 23.87 kg/m² (range,12.4 - 42.24) and the mean disease duration was 6.9 years (range,1.8 - 32.4). Prevalance of the femoral osteoporosis and osteopenia were 7.9% (n=14) and 16.4 % (n=29) in our study population respectively. Lumbar osteoporosis and osteopenia were more prevalent in our study cohort, 16.9% and 28.2% respectively. According to our study results,female patients were significantly more effected from osteoporosis than male patients and BMI was negatively correlated with femoral osteoporosis in inflammatory bowel disease (p=0.019 and r= -0.210, respectively). The disease activity (total MAYO score) was significantly associated with femur total T score in patients with ulcerative colitis (p=0.007). Similar association was documented with high sensitivity C-reactive protein (hsCRP) and femur total T score, spine total T score (P=0.014 and p= 0.027, respectivey).

Conclusion

Based on our study results, inflammation is the most important risk factor for osteoporosis in patients with inflammatory bowel disease. Effective anti-inflammatory treatments may reduce prevalance of the osteoporosis in patients with inflammatory bowel disease.Read more P507 Can systematic upper gastrointestinal endoscopy benefit patients with Inflammatory Bowel Disease?Wed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

In the context of Inflammatory Bowel Disease (IBD), a comprehensive understanding of disease extent and related complications is essential for effective clinical care. While Crohn’s disease (CD) can affect the digestive tract from mouth to anus, ulcerative colitis (UC) is limited to the rectum and colon. This study investigates the potential utility of systemic gastroscopy in IBD management.

Methods

We conducted a retrospective cohort study using data from our gastroenterology department. Patients diagnosed with IBD who underwent systematic upper gastro-intestinal endoscopy (UGE) were included. Clinical, endoscopic, and histopathological data were gathered and analyzed.

Results

141 CD and 61 UC patients were included. The mean age was 40,7 years, and the female to male ratio was 1,33. 95.5% of these patients had no upper gastrointestinal symptoms prior to undergoing UGE. Among the symptomatic participants, the most frequent complaints were dyspepsia and pyrosis. In 73.9% of asymptomatic patients, UGE showed a normal mucosa, the abnormalities found in these patients were: non-specific gastro-duodenal erosions and ulcerations (8.5% of cases), mild esophagitis (4% of cases), aphthoid ulcerations (2% of cases) and duodenal stenosis (0.5% of cases). In symptomatic participants, UGE was normal in 4 cases, it showed atrophy of the fundus mucosa in 1 case, esophageal hernia in 2 cases, and esophageal aphthoid ulcerations in 1 case. Gastro-duodenal biopsies were consistently undertaken, among asymptomatic patients, histopathological abnormalities included: lymphoplasmacytic Infiltrate (47,7%) and helicobacter pylori (HP)(38,1 %), nonspecific duodenitis (44,7%), gastric metaplasia, focal gastritis, atrophic villi and crypt hyperplasia were objectified in 3,5%, 3%, 1,5% and 0,5% of cases. Granulomas were noted in only 1% of cases, and Cryptitis and crypt abscess in 0,5%. In symptomatic participants, histologic abnormalities included metaplasia in the fundus (0.5%), lymphoplasmacytic infiltrate (2.5%), HP (2,4%), atrophic villi in the duodenum (0.5%) and glandular atrophy (0.5%). Our analysis did not reveal any significant associations between endoscopic lesions and UC (p=0.36) or CD (p=0.09) nor the presence of symptoms (p=0.08), however, a significant association was identified between male gender and the presence of endoscopic lesions (p=0.033).

Conclusion

Although IBD patients might be asymptomatic, UGE and histopathological examination may reveal upper gastrointestinal abnormalities and aid to a better assessment and management of IBD patients.Read more P680 Comparative risk of serious infection with vedolizumab vs anti-TNF in Inflammatory Bowel Disease: Results from nationwide Swedish registersWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The real-world comparative safety of vedolizumab in inflammatory bowel disease (IBD) remains uncertain. We aimed to assess the risk of serious infection in IBD patients treated with vedolizumab, compared to (i) those treated with anti-tumour necrosis factor (TNF) treatment and (ii) the general population.

Methods

In this nationwide cohort study, treatment episodes were identified from Swedish health registers (from 1 May 2014 – 31 December 2020). Patients were considered exposed from initiation of treatment until 90 days after discontinuation of treatment. We used Cox regression with propensity score-matched cohorts to estimate hazard ratios (HRs) for incident serious infection, defined as infection requiring hospital admission.

Results

After propensity score matching, the cohorts were not materially different at baseline with regard to demographic, disease and treatment characteristics (Table 1). During 1376 treatment-episodes in patients with Crohn’s disease, there were 5.18 (95%CI: 3.98-6.63) serious infections per 100 person-years (PY) with vedolizumab vs 3.54 (95%CI: 2.50-4.85) per 100 PY with anti-TNF; HR 1.72 (95%CI: 1.12-2.65; Figure 1A). When examining site-specific infections in Crohn’s disease, vedolizumab was associated with an HR of 2.47 (95% CI: 0.96-6.39) for serious gastrointestinal infections. Compared to the rate of 0.75 (95%CI: 0.59-0.92) serious infections per 100 PY in the general population, vedolizumab demonstrated an increased HR of 7.00 (95%CI: 5.04-9.72).Across 1294 episodes among patients with ulcerative colitis there were 3.74 (95%CI: 2.66-5.11) serious infections per 100 PY with vedolizumab vs 3.42 (95%CI: 2.31-4.89) per 100 PY with anti-TNF, corresponding to HRs of 0.80 (95%CI: 0.47-1.36, Figure 1B) within the initial 1.1 years of treatment and 2.03 (95%CI: 0.65-6.32) after 1.1 years (follow-up truncated due to non-proportional hazards). In ulcerative colitis, there was no statistically significant association between vedolizumab treatment and any of the site-specific serious infections. Compared to the rate of 0.69 (95%CI: 0.53-0.87) serious infections per 100 PY in the general population, vedolizumab showed an increased HR of 5.45 (95%CI: 3.67-8.11).

Conclusion

Vedolizumab was associated with higher hazard ratios of serious infections compared to anti-TNF in Crohn’s disease, but not in ulcerative colitis. Nonetheless, in both IBD subtypes vedolizumab exhibited increased hazard ratios compared to the general population. These results underscore the importance of heightened clinical awareness of infections in vedolizumab-treated patients and may help clinicians understanding the optimal positioning of vedolizumab.Read more P625 Electronic patient-reported outcomes in Inflammatory Bowel Diseases on vedolizumab therapy: Interim analysis of the non-interventional German LISTEN II studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Integrating systematic monitoring of patient-reported outcomes (PROs) with clinical information may enhance disease management and improve patient outcomes. Vedolizumab (VDZ) is approved for treating patients with ulcerative colitis (UC) and Crohn’s disease (CD). The German, multicentre, prospective, non-interventional LISTEN II study evaluates patient characteristics and effectiveness of VDZ treatment in real-world clinical practice, focusing on PROs.

Methods

Adult UC or CD patients, who either initiate VDZ intravenously (IV) or switch from IV maintenance to subcutaneous (SC) formulation, are enrolled. Data on patient characteristics, modalities of VDZ use and disease activity are recorded quarterly over one year. PROs are recorded via weekly questionnaires in app (ePRO). Sustained ePRO use was defined as proportion of patients reporting at least one PRO for ≥80% of available questionnaires. Interim data up to 9 months follow-up are presented.

Results

Data of 299 UC and 174 CD patients (51% and 59% female, respectively) with a mean age of 40 years were analysed. VDZ treatment was newly initiated IV (start) in 259 UC and 151 CD patients and switched from IV to SC application (switch) by 40 UC and 23 CD patients at baseline. Total mean pMayo score decreased in UC start-patients from 5.0 to 1.7 and from 1.1 to 0.8 in switch-patients. In CD start-patients HBI score decreased from 5.5 to 2.5 and from 3.1 to 2.3 in switch-patients.The ePRO was initially utilized by 226 UC and 124 CD patients (51% and 61% female, 57% and 52% sustained ePRO users, respectively) with a mean age of 39 years; 86% were start- and 14% switch-patients. Disease activity at baseline was comparable to the overall population, showing a total mean pMayo score of 4.5 for UC and a HBI of 5.3 for CD patients. Most UC (82%) and CD patients (88%) used a patient support program for the first time. ePRO use declined to approx. 40% usage within the second quarter and to 30% during further follow-up.Overall, mean symptom scores reported via the ePRO declined during the 9-month follow-up period. The most notable improvements (baseline to month 9) were reported for the symptom impact on work productivity (from 3.9 to 1.7 points) in UC patients and for sick leave (from 1.3 to 0.4 points) in CD patients (Table). For most PROs reduction in symptom scores was apparent within the first week of ePRO-use (Figure).

Conclusion

LISTEN II real-world data confirm VDZ effectiveness in UC and CD patients, with reduction in disease activity in IV starters and maintained effectiveness in IV-to-SC switchers. Both UC and CD patients reported sustained symptom improvement under VDZ treatment, with scores indicating improvement within the first week of ePRO-use.Read more P406 A novel active learning-based digital pathology protocol annotation for histologic assessment in Ulcerative Colitis using PICaSSO Histologic Remission Index (PHRI)Wed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Histologic remission (HR) is a critical treatment target in Ulcerative Colitis (UC). Among several scoring systems, the PICaSSO Histologic Remission Index (PHRI) simplifies HR assessment by evaluating the presence of neutrophils in the bowel tissue. Our artificial intelligence (AI) system built upon PHRI showed remarkable accuracy in HR assessment. PHRI assess neutrophils in four different regions of interest, so segmentation of these compartments is crucial to predict PHRI automatically. However, creating labelled histopathological datasets to train fully-supervised segmentation models takes time and effort. Hence, this study explores the impact of an active learning (AL) algorithm on enhancing image segmentation to alleviate the burden of detailed pathologists’ annotation and to standardise protocol annotation.

Methods

Biopsy samples from an international real-life prospective UC study were digitised into whole slide images (WSI). Initial annotations of superficial epithelium, lumen and epithelium of crypts and lamina propria for 33 WSI were employed to train a U-Net segmentation model at baseline. An AL framework was employed to iteratively select and annotate 15 unannotated images while selecting those with the highest uncertainty. Uncertainty was calculated using Least confidence sampling, Margin Sampling, and Shannon Entropy. The most informative samples, based on the average of the three uncertainty measure, were selected in consecutive batches of 5 images, and pathologists were enlisted in a human-in-the-loop process to refine annotations. Subsequently, the segmentation model was retrained by incorporating the newly refined annotated samples, and its performance was assessed using a fully annotated test set of 19 WSI.

Results

Following the baseline model training, the model’s segmentation performance assessed by the Dice score and Intersection over Union (IoU) was 0.622 and 0.386, respectively (see Table 1). Applying the AL algorithm with newly annotated images notably improved model performance, especially with 10 images (Dice=0.651, IoU=0.415). However, training the model with an additional 5 newly annotated images, which exhibited lower uncertainty, did not yield further improvement (Dice = 0.651, IoU = 0.415). Thus, the 10 annotated WSI demonstrating more uncertainty resulted crucial for the AL framework.

Conclusion

This novel AL-based iterative framework exhibits promise in standardising digital tissue annotation by our PHRI-based AI model. It offers a novel approach for both clinical trial and clinical practice, aiming to alleviate the burden of WSI labelling and reduce the bias of annotation, thereby improving histological assessment in UC.Read more P632 Isolation of a novel metalloproteinases transcriptional signature with robust anti-TNF therapy predictive power in patients with Ulcerative ColitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Anti-TNF agents were the only biologic for Inflammatory Bowel Disease (IBD) patients. However, new drugs targeting α4β7 integrin, IL-12/IL-23, and janus kinases were added to the IBD therapeutic armamentarium. Anti-TNFs are first-line biological agents in our country, and for that reason, the discrimination of patients who will be refractory of those therapies before treatment is relevant to prevent IBD patients from the exposition to multiple therapeutic failures. Therefore, we wanted to isolate robust and reproducible transcriptional markers able to specifically predict the response to anti-TNF therapy, which will contribute to targeted prevention, improve individual outcomes and decrease therapy expenditures.

Methods

We analysed publicly available microarray and RNAseq datasets of colon biopsies (GSE12251, GSE16879 and GSE73661) and whole blood cells from different cohorts of patients with Ulcerative Colitis (UC) (GSE191328). R package was used to perform the differential expression analyses and calculation of receiver operating characteristic (ROC). Cytoscape software and Morpheus (broadinstitute.org) was used to perform network data integration and visualization. Also, we used our local cohort of UC patients to further validate our results by RT-qPCR (n=21).

Results

We isolated a transcriptional signature composed of eight metalloproteases (MMPs) with high association with disease activity. Most of the transcripts of that signature were significantly upregulated in colon biopsies of non-responder patients to anti-TNFs before treatment in three different microarray datasets, but not in vedolizumab-treated patients. ROC curves of the different MMPs showed variability in the correlation to anti-TNF response among the different datasets analysed. Only three out of eight MMPs were still showing robust predictive power with an area under the curve around of 80% when all dataset were combined. Interestingly, PBMCs isolated from our local cohort of IBD patients presented increased expression of those MMPs in refractory patients to anti-TNF therapy, confirming that these three MMPs have the highest predictive power both in colon tissue and in peripheral mononuclear cells.

Conclusion

Overall, our study revealed a novel and robust MMP-transcriptional signature associated with anti-TNF but not vedolizumab therapy response. Nevertheless, our results should be corroborated in independent cohorts of patients with UC to test their efficacy and sensitivity in the clinical setting. Our data definitively contribute to the change from a reactive approach to predictive, preventive and personalised medicine.Read more P407 Validation of a newly developed patient-reported experience measure for people with Inflammatory Bowel DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Patient‐Reported Experience Measures (PREMs) assess a patient’s healthcare experiences and are important to improve the quality of healthcare. A PREM specific to inflammatory bowel disease (IBD) was co-produced with service users. This study aimed to validate the PREM.

Methods

The IBD PREM contains 38-items and comprises three domains: ‘the care team’, ‘what matters to me’, and ‘living with Crohn’s or Colitis’. Scores can be calculated for each domain and summated to give a total score.Validation was completed on data collected from participants who completed the PREM every 3 months alongside the IBD-Control measure of disease activity at a single UK tertiary IBD service. The PREM was assessed for acceptability; reliability (internal consistency and repeatability); known groups validity; criterion validity and responsiveness. Face and content validity were completed before finalisation using ‘Think Aloud’ interviews.

Results

The dataset used for validation was extracted in September 2023 and contained responses from 287 participants (63% female, 89% White British, median age: 52) comprising 1,699 PREM responses between November 2021 and August 2023.Acceptability was demonstrated with very low rates of missing data (four items with >5% missing) and median submission duration of 4.8 minutes (IQR: 3.6 – 6.6). High Cronbach’s alpha scores (0.85, 0.97, 0.88 and 0.97 for each of the domains and total PREM score respectively) show internal consistency of the measure. However, the particularly high value on one domain and the total score suggest some overlapping items may remain. An intraclass corelation coefficient of 0.88 (95% CI: 0.85 to 0.91) suggests good repeat reliability over a two-week timeframe.Good comprehension of the measure by service users satisfied face and content validity. Known groups validity was supported with lower score on ‘living with Crohn’s or Colitis’ domain the for those with an IBD Control score of less than 13 by 0.38 (95% CI: 0.23 to 0.54), p<0.001). A low to moderate correlation of 0.37 (95% CI: 0.32 to 0.42) was found between the total PREM score and the IBD Control score, as expected.Ceiling and floor effects had a maximum of 6% demonstrating potential responsiveness of the PREM. The change over a year detected by those that stated that had experienced a change was 0.53 (95% CI: 0.41 to 0.66, n=38) on a five-point scale.ConclusionThe co-produced PREM is an acceptable, valid, reliable, and responsive tool to measure experience of IBD care for quality improvement. Further work should assess the potential for item reduction as well as correlation to other related measures.Read more P639 Tofacitinib induces clinical remission in patients with chronic pouchitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Up to 10% of ulcerative colitis patients and an ileal-pouch anal anastomosis will develop chronic or antibiotic refractory pouchitis. Several case reports and -series investigated the effect of tofacitinib for refractory pouchitis, but reported conflicting results(1-5). In this study, we aimed to prospectively evaluate the efficacy of tofacitinib in chronic or antibiotic refractory pouchitis using clinical and objective outcome measures.

Methods

We conducted a prospective single centre pilot study in which thirteen patients with chronic or antibiotic refractory pouchitis (Pouchitis Disease Activity Index (PDAI) ≥ 7, ≥2 episodes in the preceding year for which antibiotic therapy was started, or ≥4 weeks symptoms requiring maintenance therapy) were treated with tofacitinib 10mg BID for eight weeks. Clinical, biochemical, endoscopic and histologic disease activity was assessed at baseline and week 8. The primary endpoint was the proportion of patients reaching clinical remission, defined as a PDAI < 7 and a reduction of ≥ 3 points from baseline at week 8. Pouch endoscopy videos were scored by two gastroenterologists and pouch biopsies were assessed by an IBD pathologist, who were blinded to the time points and clinical outcomes. Medians and interquartile ranges were calculated, and Wilcoxon signed rank test was used to analyse changes from baseline.

Results

Thirteen patients (61% male, median age 34 years) were included(table 1). Three patients did not complete eight weeks of treatment due to adverse events (pyelonephritis, primo EBV infection, worsening of pouchitis), two of whom underwent an early termination endoscopy. In total, 31% achieved clinical remission (4/13) and 62% showed clinical response (8/13). Both the total PDAI score (11 (IQR 9 – 12.75) vs 8 (4.5 – 9.75), p = 0.033), and the clinical PDAI subscore (4 (3 – 4) vs 2 (0.25 – 3.75), p = 0.014) decreased significantly from baseline compared to week 8 or early withdrawal, respectively (figure 1). We did not observe a significant change in endoscopic PDAI subscore (4.5 (2 – 5.75) vs 3 (1 – 4.75), p = 0.120) or histologic subscore (3 (2 – 4) vs 2 (1 – 4), p = 0.214). Biochemical parameters did not decrease significantly compared to baseline (faecal calprotectin: 389 mg/kg (38 – 1222) vs 116 mg/kg (31 – 466), p = 0.530 (figure 2) and CRP: 1,2 mg/L (0.75 – 15.2) vs 0.95 mg/L (0.58 – 17.7), p = 0.307, (figure 3)).

Conclusion

In this pilot study, a clinical remission rate of 31% was achieved in patients with chronic pouchitis after eight weeks of treatment with tofacitinib. However, treatment duration of eight weeks is presumably too short to achieve biochemical, endoscopic or histologic response in these refractory patients.Read more P430 The influence of persistent organ damage on IFX pharmacokinetic modeling and disease progression assessment: findings from a prospective real-world study in inflammatory bowel disease patientsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Effective management of inflammatory bowel disease (IBD) relies on a comprehensive understanding of infliximab (IFX) pharmacokinetics (PK). This study's primary goal was to develop a robust PK model, identifying key covariates influencing IFX clearance (CL), while concurrently evaluating the risk of disease progression during the maintenance phase of IBD treatment.

Methods

The multicenter, prospective, real-world DIRECT study was conducted in several care centers, which included 369 IBD patients in the maintenance phase of IFX therapy. A two-compartment population PK model was used to determine IFX CL and covariates. Logistic and Cox regressions were applied to elucidate the associations between disease progression and covariates embedded in the PK model.

Results

The PK model included the contributions of weight, albumin, antidrug antibody (ADA), and fecal calprotectin (FC). On average, higher ADA, FC concentration and weight, and lower albumin concentration resulted in higher IFX CL. In the multivariate regression analyses, FC levels influenced the odds of disease progression in all its different definitions, when adjusted for several confounding factors (Fig. 1). Additionally, alongside FC, both IFX and C-reactive protein demonstrated a significant impact on the temporal aspect of disease progression.

Conclusion

In this 2-year prospective real-world study, readily available clinical covariates, notably FC, significantly impacted IFX availability in IBD patients. We demonstrated that persistent gut damage, as mirrored by FC, substantially influenced IFX clearance. Importantly, FC emerged as a pivotal determinant, not only of IFX pharmacokinetics but also of the progression of the underlying disease. These findings underscore the imperative need to integrate FC into forthcoming IFX pharmacokinetic models, amplifying its clinical significance.Read more P626 JNJ-77242113, an oral peptide selectively targeting the IL-23 receptor, demonstrates pharmacodynamic activity in rat and human colon tissue explants following oral dosingWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The interleukin (IL)-23 pathway is a pathogenic driver in psoriasis, psoriatic arthritis, and inflammatory bowel disease (IBD). There are currently no approved oral therapies selectively targeting the IL-23 pathway. JNJ-77242113 (JNJ-2113) is a targeted oral peptide that binds the IL-23 receptor with high affinity, and potently and selectively inhibits IL-23 proximal signaling and downstream cytokine production. Oral JNJ-2113 showed dose-dependent inhibition of IL-23–induced IL-17A production in rat blood and attenuated signs of disease in a rat colitis model. A Phase 1 study showed inhibition of IL-23–induced IFN-γ production in blood from participants dosed with JNJ-2113 (Fourie et al. ISID. 2023).

Methods

We evaluated IL-23–induced IL-22 expression in colon tissue after exposure to JNJ-2113 or JNJ-2100 (a tool molecule with similar affinity and potency). IL-22 mRNA was measured after IL-23 stimulation in rat colon biopsies treated with JNJ-2100 in vitro or in colon tissue from rats 6 h after oral JNJ-2100 dosing. Human colon explants from donors were treated in vitro with JNJ-2100 or JNJ-2113, stimulated with IL-23, and IL-22 mRNA was measured. Colon and rectum biopsies from healthy participants dosed for 10 days with oral JNJ-2113 or placebo in a Phase 1 study were obtained, stimulated with IL-23 ex vivo, and IL-22 mRNA was evaluated.

Results

Overall, inhibition of IL-23–induced IL-22 expression was observed in colon tissue exposed to JNJ-2100 or JNJ-2113. Dose-dependent inhibition of IL-22 expression was observed in rat colon biopsies exposed to JNJ-2100 in vitro. Colon explants from rats dosed with 0.3, 3, and 30 mg/kg oral JNJ-2100 showed dose-dependent inhibition of IL-22 expression (52%, 88% and 96%, respectively) compared with explants from rats treated with vehicle. Human colon explants exposed to JNJ-2100 or JNJ-2113 in vitro also showed dose-dependent inhibition of IL-23–induced IL-22 expression, with >90% inhibition at the highest doses. Importantly, in colon biopsies from Phase 1 participants dosed with oral JNJ-2113 versus placebo, significant inhibition of IL-23–induced IL-22 expression was seen (P<0.05), with an average of 65% and 66% inhibition observed in sigmoid colon and rectum biopsies, respectively.

Conclusion

These results demonstrate pharmacodynamic activity of JNJ-2100 in vitro and ex vivo in rat colon tissue, of JNJ-2100 and JNJ-2113 in vitro in human colon explants, and of JNJ-2113 in colon biopsies from healthy human volunteers. These data support development of JNJ-2113 for the treatment of IBD. Of note, a Phase 2b dose-ranging study has demonstrated clinical activity of JNJ-2113 in moderate-to-severe plaque psoriasis (NCT05223868).Read more P431 Assessing intestinal barrier healing by fusing ultra-high magnification endoscope and automated spatial multispectral imaging analysis in PSC-colitis patientsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

PSC colitis is associated with an increased risk of colorectal carcinoma. Endoscopic monitoring is crucial since endoscopic and histological activity can persist in PSC even during clinical remission. Recent evidence suggests that the presence of barrier dysfunction may predict relapse in quiescent patients. This study aims to assess mucosal and barrier healing in quiescent PSC colitis and evaluate the potential to predict outcomes by combining an ultra-high magnification endocytoscope (ECS) with intestinal barrier protein markers.

Methods

23 PSC-colitis patients in clinical remission requiring surveillance colonoscopy were prospectively enrolled. Ileal and colonic mucosa were assessed with high definition, virtual chromoendoscopy and ultra-high magnification ECS. Endoscopic remission was defined as MES ≤1, UCEIS≤1, PICaSSO≤3, while histological remission was defined as RHI≤3 without lamina propria or epithelial neutrophils, NHI ≤1 and PHRI=0. A novel ECS score was developed to assess ileal and colonic intestinal barrier (Table 1). The expression of tight junction proteins (Claudin-2, Occludin, and JAM-A) was evaluated through immunohistochemistry and multiplex immunofluorescence, and it was quantified as cell density and mean expression using the automated inForm® Akoya Biosciences digital multiplex platform. The occurrence of significant adverse outcomes (steroid use, flare-ups, hospitalization, colectomy) was evaluated over a 12-month follow-up period.

Results

Of 18 patients in endoscopic remission, 12 and 13 were in histological remission according to RHI and NHI, respectively. The ECS score correlated moderately with endoscopic score (r=0.57 for MES, r=0.44 for UCEIS and r=0.54 for PICaSSO) and strongly with histological scores (r=0.56 for RHI, r=0.61 for NHI and r=0.62 for PHRI), especially in the right colon. Only 5 patients experienced adverse outcomes. Notably, barrier healing, as indicated by an ECS score<3 in the ileum and <5 in the colon, was significantly associated with better outcomes. The three barrier proteins showed a distinct mucosal localisation in both ileum and colon, with higher cell density of Occludin and Claudin-2 in the epithelium, while higher JAM-A cell density in the lamina propria. The combined assessment of the intestinal barrier by ECS and Claudin-2 cell density significantly predicted outcomes in both colon and ileum (p=0.02 and p=0.04, respectively).

Conclusion

ECS combined with automated multispectral imaging analysis of intestinal barrier integrity is an innovative tool to assess barrier healing precisely and predicts significant adverse outcomes in PSC colitis patients in clinical, endoscopic, and histological remission.Read more P631 Effectiveness of Early Thiopurine Use in Korean Patients with Moderate-to-Severe Ulcerative Colitis: A Prospective Multicenter Cohort (MOSAIK) studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Thiopurines play an important role in the management of steroid-refractory steroid-dependent ulcerative colitis (UC). However, the effectiveness of the early use of thiopurines in UC remains controversial.

Methods

In this multicenter prospective cohort study, we divided patients with UC into those who underwent early (within 6 months of diagnosis) and late (6 months after diagnosis) thiopurine therapy to determine the effectiveness of early thiopurine treatment. The primary outcome was the cumulative rate of clinical relapse (Mayo score >2 points). Multivariate Cox proportional hazards regression was used to identify independent clinical factors associated with the outcomes.

Results

Overall, 333 patients with moderate-to-severe UC were included in the MOSAIK study. Of the 118 patients treated with thiopurines, 65 (55.1%) and 53 (44.9%) received thiopurine therapy within and after 6 months of diagnosis. The cumulative use rate of thiopurines was 38.96% at 3 years after diagnosis. The median initial dose of thiopurines was 0.7 mg/kg (0.3–2.0), and the median maintenance dose was 1.1 mg/kg (0.3–2.4). The cumulative rate of clinical relapse was not significantly different between patients who started thiopurine therapy within 6 months of diagnosis and those who started therapy 6 months after diagnosis during a 3–year period (p = 0.712). Multivariate analysis showed that the presence of extraintestinal manifestations (hazard ratio [HR]: 4.674, 95% CI: 1.210–18.061, p = 0.025) independently predicted an increased risk of clinical relapse.

Conclusion

Patients with UC who received early thiopurine therapy did not differ significantly in terms of clinical relapse compared with those who received late therapy.Read more P401 The diagnostic efficacy of the DETAIL questionnaire as a screening tool for spondyloarthritis in Korean patients with Inflammatory Bowel DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The DETection of Arthritis in Inflammatory boweL diseases (DETAIL) is a very simple questionnaire consisting of six items. Developed in Italy as a screening tool for spondyloarthritis (SpA) in patients with inflammatory bowel diseases (IBD), it has not been validated in Asian patients with IBD. This study aims to assess whether the DETAIL questionnaire demonstrates appropriate screening properties in Korean patients with IBD.

Methods

Adult patients with IBD experiencing musculoskeletal symptoms were prospectively enrolled. An IBD specialist assessed them using a Korean-translated version of the DETAIL questionnaire, and referred them to a rheumatologist. The diagnosis of SpA was made based on the Assessment of SpondyloArthritis international Society classification criteria. The performance of the DETAIL questionnaire was evaluated using a Bayesian analysis model, with results graphically represented using Fagan’s nomogram.

Results

Eighty-seven patients with IBD (58 with ulcerative colitis and 29 with Crohn’s disease) completed the DETAIL questionnaire. Male was 50.1%, and the mean age of the patients was 39.1±12.1 years. Among these patients, 30 (34.5%) were diagnosed with SpA (20 peripheral, 10 axial). In the DETAIL questionnaire, items 1 (exploring peripheral synovitis), 2 (exploring dactylitis), and 3 (exploring Achilles enthesitis), which assess peripheral SpA, demonstrated good performance, especially with the highest positive likelihood ratio (LR+) found in item 2 (LR+ 3.26). Meanwhile, questions about inflammatory low back pain (items 4, 5, and 6), exhibited poorer performance, with LR+ values near or below 1. In subgroup analysis, the DETAIL questionnaire exhibited superior performance in younger IBD patients (< 40 years old) across three items for peripheral SpA, compared to older IBD patients (≥ 40 years old). An affirmative response to at least two questions about peripheral arthritis yielded a posttest probability of SpA of 85% or more.

Conclusion

The DETAIL questionnaire demonstrates effective screening properties for detecting SpA in young Korean IBD patients.Read more P641 Faecal calprotectin determines non-response to corticosteroids in patients with immune checkpoint inhibitor colitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Immune checkpoint inhibitor (ICI) therapy has improved survival outcomes in patients with advanced malignancy. ICI colitis (ICI-C) is one of the most common adverse events which often leads to cessation of an otherwise effective therapy.^1,2 Corticosteroid therapy remains first-line treatment in patients with ICI-C. The aim of this study was to assess predictors of non-response to corticosteroid therapy to help guide early escalation to biologic therapy.

Methods

Multicentre retrospective analysis of adults hospitalized with ICI-C between July 2018 to March 2023. ICI-C was defined by patients who had current or prior immunotherapy who presented with diarrhoea with negative infective faeces PCR testing and admission diagnosis of ICI-C by their treating Physician. Baseline demographic, clinical, biochemical, and endoscopic data were collected. Grading of clinical severity on presentation and response to immunosuppression was defined by CTCAE diarrhoea grading with response defined as improvement to grade 1 or less.

Results

82 patients were analysed. 31 (38%) female, median age was 65.5 years (IQR 59-72)], 27 (33%) failed corticosteroid therapy and required biologic therapy. 34 (42%) had a faecal calprotectin on admission. On univariable analysis faecal calprotectin emerged as the sole predictor of corticosteroid non-response. ROC analysis identified an optimal faecal calprotectin cut-off of 620 mcg/g to identify corticosteroid non-responders [Sensitivity 75% (57.6-92.7), Specificity 77.8% (52.4-93.6), Accuracy 76.5%, PLR 3.37 (1.36-8.38), NLR 0.32 (0.13-0.78), AUROC 0.76 (0.616-0.911), OR 10.5 (2.24-49.3), PPV 75 (47.6-92.7), NPV 77.8 ( 52.4-93.6)].12/16 (75%) of patients with a faecal calprotectin ≥ 620 required biologic therapy.

Conclusion

Faecal calprotectin is a predictor of non-response to corticosteroid therapy in patients with immune checkpoint inhibitor colitis. This study identified a faecal calprotectin threshold of 620mcg/g as the optimal cut-off to identify corticosteroid non-response and need for second-line immunosuppression. These findings may help to reduce the need for endoscopic assessment and guide early escalation to biologic therapy.REFERENCES:1. Fujii T, Colen RR, Bilen MA, et al. Incidence of immune-related adverse events and its association with treatment outcomes: The MD Anderson Cancer Center experience. Invest New Drugs. 2018;36(4):638-646. doi:10.1007/s10637-017-0534-02. Wang Y, Abu-Sbeih H, Mao E, et al. Endoscopic and Histologic Features of Immune Checkpoint Inhibitor-Related Colitis. Inflamm Bowel Dis. 2018;24(8):1695-1705. doi:10.1093/ibd/izy104.Read more P611 Relation between AntiTNF levels during the induction and clinical and radiological outcomes in perianal Crohn´s diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Perianal Crohn's disease(PCD) significantly impacts quality of life with poor long-term prognosis. Anti-tumor necrosis factor(anti-TNF) therapy improves fistula closure rates. However, achieving permanent closure remains challenging. Our aim is to evaluate the relation between antiTNF(infliximab (IFX) and adalimumab(ADA) serum concentrations at induction(w2 and 6), and clinical and radiological outcomes at w24 and w52

Methods

We conducted a single tertiary center, retrospective, cohort study including patients with an established diagnosis of PCD treated with antiTNF because of perianal activity. Variables related to their PCD(phenotype, location, fistulas type) were collected. Regarding treatment, we collected serum levels at week 2,6,24 and 52, concomitant treatment and setons presence. We defined clinical response as the absence of drainage on physical examination and clinical remission as the absence of external fistula openings. Radiological response was defined as the absence of T2 hypersignal, gadolinium enhancement, abscess and proctitis in pelvic MRI

Results

65 patients were included, baseline characteristics are in Table1. None of the demographic characteristics collected were statistically significant related to clinical or radiological response although non smokers(p=0.01), ileal(p=0.02) and non-stricturing disease(p=0.01) had statistically significant higher drug levels. Taking into account the clinical response at w52, IFX mean levels at w2 were 25.8µg/mL(SD 4.1) in non responders and 30.9µg/mL(SD 14) in responders(p=0.39). At w6 they were 17.2µg/mL(SD 12.2) and 19.4µg/mL(SD 13.8) respectively(p=0.7). ADA mean levels at w2 were 13.3µg/mL(SD 7.7) in non responders and 14µg/mL(SD 6.3) in responders(p=0.87). At w6 they were 10.1µg/mL(SD 3.3) and 12µg/mL(SD 6.1) respectively(p= 0.59). For radiological response at w52 IFX mean levels at w2 were 27µg/mL(SD 15.3) in non responders and 32.7µg/mL(SD 14.5) in responders(p=0.45). At w6 the mean levels were 15.9µg/mL(SD 6.7) and 23.7µg/mL(SD 14.8) respectively(p=0.27). In ADA group the mean levels at w2 were 14.8µg/mL(SD 7.6) in responders and only one patient did not respond. At w6 ADA mean levels were 12.3µg/mL(SD 5.9) in non responders and 12.7µg/mL(SD 6.2) in responders(p=0.94). Early response at w24 was related with a long-term response at w52, 89.9% of the patients who responded at w52, had already responded at w24.

Conclusion

In our study we observed that almost 90% of the patients who had an early response also responded at w52, so trying to achieve an early response should be an aim in clinical practice. Despite the limited number of patients, our study shows a trend in the relationship between higher antiTNF levels and clinical and radiological response ratesRead more P612 Switching from intravenous to subcutaneous VEDOlizumab formulation in ulcerative colitis patients in clinical remission: the SVEDO Study, a multicenter IG-IBD studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The administration of biologic drugs in inflammatory bowel diseases (IBD) is increasingly moving from intravenous to subcutaneous formulations. Limited data is available on the effectiveness of subcutaneous vedolizumab in patients switching from long-term intravenous therapy. The aim of the study was to evaluate the efficacy and safety of vedolizumab subcutaneous administration after switching from intravenous administration in ulcerative colitis patients in corticosteroid-free clinical remission.

Methods

An observational, multicentre, prospective study was conducted by the Italian Group for the study of IBD in Italy (IG-IBD). Ulcerative colitis patients in clinical remission (pMAYO < 2) not receiving steroids for > 8 months before the switch, and with at least 6 months of follow-up were included. Switch from intravenous to subcutaneous vedolizumab was defined as successful in patients not experiencing a disease flare (pMAYO ≥ 2) or needing oral steroids or stopping vedolizumab during the 6 months of follow-up after the switch.

Results

One hundred sixty-eight patients were included. The switch was a complete success in 134 out of 168 patients (79.8%). In particular, vedolizumab retention rate was 88.7% at month six. No predictor of complete switch success was found at multivariate analysis. C-reactive protein and faecal calprotectin values did not significantly change after the switch (p = 0.07 and p = 0.28, respectively). Ten of the 19 patients who stopped subcutaneous formulation switched back to intravenous formulation, with a success in recapturing clinical remission in 80%. Twenty-two out of 168 patients (13.1%) experienced side effects while on subcutaneous formulation, including 4 cases of rheumatological side effects, 4 cases of injection site reactions, 3 allergic reactions, 3 cases of cancers.

Conclusion

Effectiveness of switching from intravenous to subcutaneous vedolizumab formulation in UC patients in steroid-free clinical remission is confirmed in a real-world setting.Read more P399 Impact of Body Mass Index on Clinical Outcomes in Intestinal Behçet’s diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The impact of underweight and obesity on clinical outcomes for intestinal Behçet’s disease (BD) is unknown. We aimed to identify the association between body mass index (BMI) and clinical outcomes in patients with intestinal BD.

Methods

We categorized 760 patients with intestinal BD according to the BMI at diagnosis into four groups (underweight, normal, overweight, obese) at Severance Hospital, Seoul, Korea between 1997 and 2021.We performed a Cox proportional hazard analysis to investigate the predictive capability of BMI for clinical outcomes such as biologics use, surgery, hospitalization and emergency room visit.

Results

Of the 760 patients, 130 patients were classified into underweight group (BMI<18.5), 384 patients into normal group (BMI 18.5~22.9), 152 patients into overweight group (BMI 23~24.9), and 94 patients into obese group (BMI≥25). Patients with a higher BMI group showed significantly lower cumulative rates of biologics use (p trend = 0.001), surgery (p trend = 0.008), hospitalization (p trend = 0.002), and emergency room visits (p trend = 0.003) than those with a lower BMI group.In a multivariate analysis, normal BMI group (HR: 0.667, 95% CI 0.483-0.992, p =0.014), overweight group (HR: 0.589, 95% CI 0.394-0.879,p=0.010), and obese group (HR: 0.515, 95% CI 0.321-0.828, p=0.006) were negatively associated with future hospitalization compared to underweight group. Overweight group (HR: 0.490, 95% CI 0.241-0.996, p =0.049) and obese group (HR: 0.312, 95% CI 0.116-0.840,p =0.021) were negatively associated with future biologics use compared to the underweight group.Normal BMI group (HR: 0.706, 95% CI 0.484- 1.029, p=0.070) and obese group (HR : 0.556, 95% CI 0.303-1.020,p=0.058) were negatively associated with future surgery compared to the underweight group. Normal BMI group (HR: 0.711, 95% CI 0.513-0.985, p=0.041) and obese group (HR: 0.602, 95% CI 0.376-0.963, p=0.034) were negatively associated with future emergency room visit compared to the underweight group.

Conclusion

Underweight could affect poor outcomes in intestinal Behçet’s disease. Physicians should pay attention to the patients with underweight and make an effort to improve nutritional status.Read more P473 Comparison of clinical performance of fecal calprotectin of laboratory methods with lateral flow based POC and home testsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

To confirm an IBD diagnosis and manage IBD patients, endoscopy is the gold standard to assess mucosal inflammation. Fecal calprotectin (fCAL) is a reliable biomarker of intestinal inflammation that highly correlates with endoscopic and histological findings. Fecal calprotectin testing is recommended in most IBD guidelines for diagnosis and disease course evaluation. Different assay technologies exist that need to measure fecal calprotectin comparably. These range from classic enzyme linked immunosorbent assays (ELISA), particle enhance turbidimetric immuno assays (PETIA), and rapid lateral flow assays (LFIA). LFIA[AL1] [RC2] s can be read by conventional tabletop readers or by everyday smartphone applications using the phone’s camera to acquire an image, detect the test cassette and calculate a quantitative result. As there is no international standard to date, fecal calprotectin assay manufacturers rely on their own internal calprotectin standardization. This study compared four different assays measuring the same clinical samples.

Methods

The 128 raw stool samples that were analyzed in this study were obtained from patients that presented with signs and symptoms suggesting intestinal inflammation and underwent endoscopic evaluation to establish or exclude an IBD diagnosis. Samples were extracted with the BÜHLMANN CALEX^® Cap stool extraction device. Each extract was then measured on the BÜHLMANN fCAL^® ELISA, fCAL^® turbo (PETIA), Quantum Blue^® fCAL extended lateral flow assay and smartphone based IBDoc^® fCAL home test. For the home test, two phones, iPhone 11 and Samsung Galaxy S7, were used to measure the lateral flow test cassettes. Each sample was measured one time on each assay and Receiver Operating Characteristic (ROC) curve analysis was performed and total agreement between each method was calculated.

Results

ROC curves were generated to assess the ability of each assay to differentiate between IBS and IBD with area under the curve (AUC) values ranging from 0.827 (Samsung Galaxy S7 to 0.835 (fCAL turbo). There was no significant difference between the methods. Commonly used cut-offs in the assessment of IBD patients are 100 and 250 µg/g, respectively. Positive and negative percent agreement (PPA/NPA) between the smartphone-based home test and the laboratory assays was calculated. The PPA was above 90% for all methods while the NPA was above 88% for all methods.

Conclusion

The results presented here show that the four BÜHLMANN assays measure fecal calprotectin extremely comparably and show an excellent clinical performance. This allows for the use of the methods interchangeably, depending on the needs of the patients and their care team.Read more P394 Unsuitability of the Oxidation-Reduction Potential measurement for the quantification of fecal redox status in Inflammatory Bowel DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Oxidative stress is a key pathophysiological process associated with the development and progression of inflammatory bowel disease (IBD). Biomarkers for oxidative stress, however, are scarce, as are diagnostic tools that can interrogate an individual’s gut redox status. Oxidation-Reduction Potential (ORP) measurements can provide insight into the redox (oxidation-reduction) status, which is relevant in understanding oxidative stress and associated pathophysiological processes. Until date, ORP analyses have not been explored in the context of IBD. This proof-of-concept study aimed to assess the potential utility of an ORP measurement probe in quantifying redox status in the fecal water of both IBD patients and healthy controls.

Methods

This proof-of-concept study recruited patients with Crohn's disease (CD), ulcerative colitis (UC), and healthy controls. Fecal samples were collected and analyzed for oxidation-reduction potential (ORP) using the PCE-228 redox probe at specific timepoints. Furthermore, the stability of ORP measurements was assessed across various test solutions with known ORPs by doing nine ORP measurements every 15 minutes.

Results

No significant differences in ORP measurement values were observed between patients with CD (n=5) (45 [30.0–62.0] mV), patients with UC (n=5) (48 [42.0–59.0] mV) and healthy controls (n=5) (25 [8.0–52.0] mV; p = 0.221) (Fig. 1A). Strikingly, ORP measurements exhibited high instability and rapidly fluctuated throughout time, presenting with values varying from +24 to +303 mV (Fig 1B). These fluctuations, potentially influenced by biological processes and limitations of the measuring equipment, precluded reliable measurements of ORP in fecal samples of patients with IBD.

Conclusion

ORP quantification may not be a reliable tool for assessing fecal redox status in patients with IBD or healthy controls. Our findings do not support further exploration of the specific ORP redox probe used in this study for determining fecal redox status. Future studies should focus on more sensitive methods to quantify fecal redox status and examine its biomarker potential in the context of IBD.

Funding

This study was supported by Janssen Research & Development LLC.Figure 1:(A): ORP measurement after 3 and 10 minutes in patients with IBD and healthy controls (B): Repeated ORP measurements across four different test solutions.Read more P410 Intraoperative Ultrasonography of the Small Bowel in the evaluation of resection margins during surgery for Crohn's DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Histological involvement of surgical resection margins in Crohn’s Disease (CD) is considered an important risk factor for disease recurrence after surgery. The extent of resection is currently left to preoperative investigations and surgeon's experience. Aim of the study is to evaluate usefulness of intra-operative ultrasonography (IOUS) of the small bowel to best identify the surgical site of resection and reduce the risk of histological involvement of resection margins.

Methods

Consecutive patients who underwent surgery for CD (ileocaecal or ileal resections for first or repeated surgery) from April 2022 to April 2023 were prospectively enrolled (IOUS group). All patients underwent to IOUS through a small mini-laparotomy with a linear wireless probe performed by an expert gastroenterologist and the location of the proximal ileal resection was decided considering the absence of intraoperative small bowel ultrasonographic signs of CD (wall thickness, mucosal, submucosal and muscular layer thickness, echogenicity of the wall stratification and mesenteric fat). A control group from the historical cohort of patients undergoing the same surgical procedures was included; for whom the site of the proximal ileal resection was decided only on the basis of the absence of macroscopic signs of disease as usually assessed.To minimize the selection bias, a propensity score analysis was performed identifying a subgroup of the historical cohort (non-IOUS group) matched for location of disease and repeated surgery.The primary endpoint was histological involvement of the resection margins, judged positive in case of granulomas or signs of active ulcerative inflammation.

Results

27 patients (59% male, mean age 39.3 y [SD 16.5], mean BMI 21.24 [SD 2.03]) were consecutively enrolled in the IOUS group. A 1:1 propensity score matching analysis was performed identifying 27 patients included in the non-IOUS group .The two groups were homogeneous in terms of gender, age, smoking, BMI, behavior of disease and surgical technique (laparoscopic or open technique).IOUS group presented a lower rate of histological positive margins compared to the non-IOUS group (18.5% vs 48.1% p = 0.021).No significant differences were found in terms of mean duration of surgery between the two groups (254.2 min vs 225 min [49.3-77.8]; p = 0.11) or in terms of mean length of surgical specimen (24.1 cm vs 34.1 cm [SD 13.5 -23.1]; p = 0.058)

Conclusion

IOUS of the small bowel appears to be a useful tool for IBD-surgeon in order to obtain a lower rate of histologically positive margins with a comparable duration of the surgery and no significant difference in length of the intestinal specimen.Read more P411 Is transmural healing better than mucosal healing in pediatric Crohn’s disease?Wed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

While the long-term benefit of achieving mucosal healing (MH) in Crohn’s disease (CD) has been demonstrated, data on transmural healing (TH), assessed by non-invasive imaging modalities (i.e. magnetic resonance enterography, MRE) are scarce, particularly in the pediatric setting. Nonetheless it has been deemed as an adjunctive target for CD by the STRIDEII consensus. We aimed to investigate the outcomes of pediatric CD patients with TH comparing them to those with MH and with “no healing”.

Methods

Prospective, single-center, observational study conducted at the Pediatric Gastroenterology and Liver Unit of the Umberto I Hospital, Sapienza University of Rome. Children with an established diagnosis of CD and under biological therapy undergoing an MRE and an ileocolonoscopy performed within a 3-month interval were consecutively enrolled. Transmural healing was defined as the complete healing of both the mucosa at endoscopy (absence of ulceration) and of the bowel layers at the MRE. In the presence of a normal colonoscopy but an active MRE children were deemed as MH. The group “no healing” (NH) included children with an active endoscopy, regardless of the MRE classification. At 6, 12, and 24 months, the following outcomes were evaluated and compared in the three groups: disease flares, CD-related hospitalization, CD-related surgery, need for step-up treatment, and occurrence of complications.

Results

93 children were included (30% female, mean age 11,2±3,8). Twenty-three (25%) were classified as TH, 27 (29%) as MH and 43 (46%) as NH. Overall, at the Kaplan Meier analysis, the risk of any unfavorable outcome was significantly lower in both TH and MH patients compared to NH (Log Rank p<0.0001 and p=0.002, respectively). Specifically, children with TH were at lower risk of hospitalization (p=0.02), and complications (p=0.007) compared to those with NH. No difference was found between MH and NH children for the same outcomes. Both TH and MH children were at lower risk of step-up treatment (p<0.0001 and p=0.0.0002, respectively) compared to NH. No difference was found between TH and MH patients for all the outcomes evaluated.

Conclusion

Achieving transmural healing in pediatric CD is associated with better long-term outcomes, although the additional benefit compared to reaching MH alone does not appear significant. However, the persistence of inflammation is associated with worse outcomes in all patients.Read more P424 Analysis of the intestinal microbiome using an Endoscopic Brush in Ulcerative colitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The precise pathogenesis of the Ulcerative colitis is still yet unknown, but one of its cause is known to be microbial dysbiosis.The mucosa-associated microbiota are more deeply involved in the pathogenesis of UC. However, the optimal sampling of mucosa-associated microbiome has yet to be investigated.In this study, we investigated the mucosa-associated microbiome in patients with ulcerative colitis, using endoscopic brush samples. We hypothesized that endoscopic brushing is precise and noninvasive method to get sample of mucosa-associated microbiome.

Methods

Patients with UC who visited the gastroenterology department of Korea University Anam hospital were screened for this study.Clinical data such as medical records, colonoscopy and fecal samples were reviewed.Using a stool and saliva sample collector kit respectively, the subjects provided stool and saliva samples. Brushing samples were collected during the sigmoidoscopy procedure with 3-4 brush strokes on the colon mucosa using the cytology brush.The samples were analyzed for microbiome in the Korea University Medical Center.

Results

From July 2022 to January 2023, we prospectively enrolled 19 patients with UC.Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria were the most common species in microbiota of brush, stool and saliva.(Fig.1-1)The microbiome between stool and brush was no significant difference in alpha and beta diversities.(Fig.1-2)However, Oral microbiome was different from stool and brush in beta diversities.(Fig.1-3) Patients were categorized into to analyze the oral microbiome. A trend was observed where increased disease severity was associated with an increase in Firmicutes.(Fig.1-4)

Conclusion

The microbiome of stool and brush was no significantly different. However, the novel sampling of mucosa-associated microbiome, endoscopic brush, is not inferior compared to currently used sampling of stool.Also the analysis of the oral microbiome suggested that Firmicutes could be considered a useful biomarker for assessing disease severity. Therefore, it is necessary to conduct followup research by increasing the number of subjects.Read more P425 Clinical Characteristics of Steroid-Dependent Ulcerative Colitis Patients after Acute Severe Ulcerative Colitis Treatment in East Asia and Australia/New Zealand: AOCC and ANZIBDC collaboration studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Intravenous steroid therapy (IVS) is the main initial treatment for acute severe ulcerative colitis (ASUC). The study aimed to assess corticosteroid dependency after treating ASUC and to explore potential differences between East Asian and Caucasian populations within the steroid-dependent group.

Methods

Patients from East Asia (China, Japan, South Korea, and Taiwan) and Australia/New Zealand diagnosed with ASUC based on the Trulove and Witts criteria from January 2015 to September 2022 were retrospectively included in the study. We specifically chose individuals responsive to intravenous corticosteroid treatment and divided them into two groups based on steroid dependency. "Steroid dependency" was defined as the inability to reduce steroid medication to a dosage below 10 mg/d (equivalent to prednisolone) within three months of initiating steroid treatment or experiencing a relapse within three months of discontinuing steroid therapy. Patients with a history of biologics or small molecules and those currently receiving them were excluded.

Results

Among 861 patients with ASUC (430 from East Asia and 431 from Australia/New Zealand), 626 received initial IVS, and 381 showed steroid response. Among these steroid responders, 102 patients (26.7%) were classified as steroid-dependent with no significant difference between East Asians and Caucasians (28.3% vs. 24.1%, p=0.44). For 1 year after ASUC, the colectomy rate (7.8% vs. 2.9%, p=0.04) and ASUC relapse rate (18.6% vs. 10.2%, p=0.03) were higher in the steroid-dependent than non-dependent group. For the management of steroid dependency, East Asians mainly repeated steroid treatment (60.9%), while Caucasians mostly switched to infliximab (57.1%). In the Cox regression analysis of 3-year follow-up data for the steroid-dependent group, Caucasians showed a significant increase in colectomy rates (adjusted hazard ratio [aHR] 1.59, 95% confidential interval [CI] 1.12-2.25, p<0.01) compared to East Asians. Additionally, relapse rates increased in Caucasians (aHR 1.37, 95% CI 1.13-1.65, p<0.01), while relapse rates decreased in thiopurine users (aHR 0.32, 95% CI 0.12-0.87, p=0.03).

Conclusion

Around one-fourth of patients with ASUC who initially responded to IVS became steroid-dependent. East Asians showed a more favorable prognosis compared with Caucasian in this steroid-dependent group.Read more P446 Influence of seasonal vitamin D deficit in clinical course of inflammatory bowel disease patientsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Vitamin D deficiency is common in healthy subjects and it is even more prevalent in inflammatory bowel disease (IBD). Vitamin D (VitD) may influence disease behavior. Whether a deficient vitamin D status facilitates flares or flares consume vitamin D is still a burning question. Data on seasonal variations of VitD levels in IBD are scarce. The aim of this study was to evaluate VitD deficit in IBD patients compared with general population and the influence of seasonal variation in their evolution.

Methods

A prospective two center study was performed. Patients with Crohn disease (CD) or ulcerative colitis (UC) and no comorbilities that may have influenced VitD were consecutively included from two IBD centers with geographical proximity (less than 100 kms) in order to have comparable solar radiation. Clinical and biochemical characteristics of patients were recorded. Patients were followed for two consecutive seasons, VitD was measured twice: during winter and during summer. VitD levels from general population were also available. Both hospitals share the same methodology for VitD testing. VitD levels were defined as normal (>30 ng/ml), insufficient (20-30 ng/ml), or deficient (<20 ng/ml). Data were analyzed and Mann-Whitney U test was applied using R to compare subsets of patients.

Results

199 patients with IBD were consecutively included (38.7% CD, 61.3% UC). 165 (83%) patients have consecutive determinations of VitD (both in summer and winter). Mean age was 47.1, being 54.8% males and 45.2% females. Median value of VitD in winter was 14 ng/ml, and 21 ng/ml in summer. Lab tests in our center for general population in winter presented a median value was 21.2 ng/ml in winter and 24 ng/ml in summer (Figure 1). According values of our laboratory in winter, just 31% of the general population presented VitD values > 30 ng/ml in summer and 26.7% do so in winter. For our cohort of patients with IBD, the results are more pronounced: only 3.8% presented normal values in winter and 23.2% in summer (Table 1). The average variation in VitD values has been 9.26 ng/ml between the two seasons. No statistically significant relationship was found between the factors analyzed (BMI, location, calprotectin levels or disease duration) and VitD levels, neither in summer nor in winter. Most patients remained in remission despite having low VitD levels (82,8% in winter and 80,3% in summer).

Conclusion

VitD deficit was frequent in summer and in winter in IBD and more prevalent than in general population. Despite frequent deficit only a small percentage of patients presented disease activity. No relationship was observed between VitD deficit and patients characteristics or calprotectin levels.Read more P447 Anti-αvβ6 integrin antibody as a novel serum biomarker for diagnosis of ulcerative colitis; a nation-wide multicenter validation study in JapanWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

There is no established diagnostic biomarker for ulcerative colitis (UC). Although we recently reported an anti-αvβ6 integrin antibody to diagnose UC, there is no large-scale validation study on this antibody to diagnose UC. This study aimed to validate the diagnostic value of anti-αvβ6 integrin antibody for UC in a nation-wide, multicenter cohort (UCV6-Dx Study).

Methods

We enrolled 1241 UC patients, 798 Crohn’s disease (CD) patients, and 207 other gastrointestinal disease patients from 28 Japanese high-volume referral centers. Anti-Integrin αvβ6 ELISA Kit (MEDICAL & BIOLOGICAL LABORATORIES CO., LTD., Tokyo, Japan) was used to measure the titer of anti-αvβ6 integrin antibody. The cut-off value was 1.64 U/mL (the mean +3SD of 83 serum samples from healthy volunteers determined by the manufacturer). The primary outcome was the diagnostic value of the anti-αvβ6 integrin antibody. Secondary outcomes were factors associated with false negative results in UC patients, factors associated with false positive results in non-UC patients, and the optimal cut-off values using receiver operating characteristic (ROC) analysis.

Results

The diagnostic sensitivity of the anti-αvβ6 integrin antibody in UC was 87.7% and the specificities were 82.0% in CD and 87.4% in other gastrointestinal diseases. Multivariate logistic regression analysis showed that false negative results in UC patients were associated with age at the time of sample collection [odds ratio (OR) 1.0242, p=0.034, 95% confidence interval (CI) 1.0018-1.0470], smoker (OR 2.5504, p=0.002, 95% CI 1.4216-4.5755), partial Mayo score (OR 0.8623, p=0.038, 95% CI 0.7495-0.9921), and advanced therapies (OR 0.5875, p=0.019, 95% CI 0.3765-0.9167) and false positive results in CD patients with disease location L2 (OR 2.6858, p=0.013, 95% CI 1.2323-5.8533). No factor was associated with false positive results in patients with other intestinal diseases. ROC analysis revealed that the optimal cut-off values estimated by the Youden method were 2.07 U/mL [area under the curve (AUC) 0.9003, sensitivity 85%, specificity 87%], and 1.78 U/mL (AUC 0.9206, sensitivity 87%, specificity 89%) for discriminating UC from CD and other gastrointestinal diseases, respectively.

Conclusion

The usefulness of anti-αvβ6 integrin antibody for diagnosing UC was validated in the Japanese large-scale, nation-wide multicenter study.Read more P472 A Real World Practice of Intestinal Ultrasound in the Monitoring of Disease Activity in Ulcerative ColitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Intestinal ultrasound (IUS) has emerged as an important monitoring tool in the clinical course of ulcerative colitis (UC). Previously known factors about UC have been considered in terms of the associations with IUS. However, a few studies reported about the associations between the findings of IUS and clinical factors.

Methods

We performed a multi-center, cross-sectional study of patients with UC who received IUS and clinical exams including endoscopy simultaneously. The primary endpoint was the association between endoscopic disease activity as Mayo endoscopic score (MES) and IUS finding as Milan ultrasound criteria (MUC). The secondary endpoint comprised the various clinical factors associated with MUC. Patients with MUC<6.2 were defined as low MUC group and others as high MUC group.

Results

A total of 35 patients were enrolled in this study. The numbers of Low- and high-MUC groups were 23 and 12, respectively. The median age in each group was 41 and 53 years old. The portion of male sex in each group was 57% and 75%. There were no significant differences in terms of body mass index, onset age, disease duration, current medication such as 5-aminosalicylic acid, steroid, immunomodulator, and biologics and small molecules between both groups.Compared with low and high MUC groups, endoscopic remission was more significantly associated with the low MUC group than the high MUC group (35% vs. 0, p = 0.032). In addition, the rate of disease activity ranged from remission to mild, as tolerable clinical activity, was also significantly higher in the low MUC group than the high MUC group (91% vs. 58%, p = 0.033). Other outcomes such as symptomatic remission, histologic remission, and biochemical response revealed similar rates between the two groups.

Conclusion

Low MUC of IUS in the patients with UC showed significant clinical association such as endoscopic remission and tolerable clinical activity. This study is now ongoing prospective research and further investigation into the relationship between IUS and clinical outcomes of UC will elicit robust results.Read more P387 Short and long-term outcomes of surgery for inflammatory (uncomplicated) ileocecal Crohn’s disease: multicentric retrospective analysis of 211 patientsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Surgical management for patients with inflammatory ileocecal Crohn’s disease (CD) could be a reasonable alternative to second-line medical treatment.

Methods

A retrospective analysis of patients intervened for primary ileocecal CD with uncomplicated (inflammatory) phenotype at four referral hospitals during 2012-2021 was performed. The objective was to assess short and long-term outcomes of patients operated on for inflammatory, ileocecal CD.Patients operated on due to inflammatory ileocecal CD (last 50 cm of the terminal ileum and cecum), were considered eligible to participate in this study. Operations performed during a 9-year period (2012-2021) were considered for the study. Patients who were operated for CD for advanced structural bowel damage (fibrotic strictures or penetrating phenotype), those who had had previous abdominal CD-related procedures, and patients who had disease activity in other anatomical regions at the time of surgery, were excluded from the study.

Results

211 patients were included. 43% of patients underwent surgery more than 5 years after diagnosis, and 49% had been exposed to at least one biologic agent preoperatively. 89% were operated by laparoscopy, with 1.6% conversion rate. The mean length of stay for patients was 5 days, with only 24 patients (11%) requiring a prolonged hospitalization. The complication rate was 23.7% (50 patients), but most complications were minor (Clavien-Dindo < IIIa), with only 11 patients (5%) presenting with major complications. Leak rate for patients who received a primary anastomosis was 2.9%. The median length of the resected bowel was 25 cm (7-92) and three patients (1.43%) received a stoma. Median follow-up was 36 (17-70) months. The endoscopic recurrence-free survival proportion at 24, 48, 72, 96, and 120 months was 56%, 52%, 45%, 38%, and 33%, respectively. The clinical recurrence-free survival proportion at 24, 48, 72, 96, and 120 months was 83%, 79%, 76%, 74%, and 74%, respectively. In multivariate analysis, previous biological treatment (HR=2.01; p=0.001) was associated with a higher risk of overall recurrence.

Conclusion

In this study, surgery in patients with primary inflammatory ileocecal CD is associated with good postoperative outcomes, low postoperative morbidity with reasonable recurrence rates. Further studies need to validate the present results.Read more P397 Distinct blood protein profiles associated with ileal and colonic ulcers in Crohn’s diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Ileal and colonic Crohn’s disease (CD) are nowadays considered as separate entities. Studies are needed to better characterise the biological specificities of these subphenotypes. In fine, this research should offer opportunities for the development of personalised medicine.

Methods

By combining different technologies (proximity extension assay, selected reaction monitoring and high-sensitivity turbidimetric immunoassay (hsCRP)), 207 serum proteins were measured in CD patients presenting no endoscopic lesions (endoscopic remission) (n=23), isolated ileal ulcers (n=17) or isolated colonic ulcers (n=16) (Table 1). To compare the endoscopic activity between the ileum and colon, and in order to obtain an assessment of the overall lesion burden, we used the Crohn’s disease endoscopic index (CDEIS) without dividing its total score (sum of each gut segment) by the number of inspected segments. The data analysis was conducted using Wilcoxon-Mann-Whitney test and area under the receiver operating characteristics curve (AUROC). The AUROC were compared using the bootstrap test (2000 replications).

Results

The median of the total CDEIS was higher in CD patients with isolated colonic ulcers than those with isolated ileal ulcers (23.1 vs 8.0) (Table 1). When compared to endoscopic remission, the presence of isolated ileal ulcers and isolated colonic ulcers were specifically associated with the level of 6 and 18 serum proteins, respectively: (high: JUN, CNTNAP2; low: FCRL6, LTA, CLEC4A, NTF4) (Figure 1A); (high: hsCRP, IL6, APCS, CFB, MBL2, IL7, IL17A, CCL19, CXCL10, CSF3, IL10, CLEC4G, MMP12, VEGFA; low: CLEC3B, GSN, TNFSF12, TPSAB1) (Figure 1B). No protein was associated with both isolated ileal ulcers and isolated colonic ulcers (Figure 1).All CD patients in endoscopic remission showed a normal level of hsCRP (<5 mg.L^-1). Compared to CD patients in endoscopic remission, CD patients with isolated colonic ulcers showed an increased median level of hsCRP (1.3 vs 5.9 mg.L^-1, p-value=0.0045) and this was not the case for CD patients presenting isolated ileal ulcers (1.3 vs 2.2 mg.L^-1, p-value=0.13). hsCRP detected ileal and colonic ulcers with an AUROC of 0.64 (p-value=0.07) and 0.77 (p-value=0.001), respectively. When compared to hsCRP (AUROC), the best marker pairs for detecting ileal or colonic ulcers were respectively CLEC4A×LTA (0.82 vs 0.64, p-value=0.06) or hsCRP×CSF3 (0.85 vs 0.77, p-value =0.02).

Conclusion

In CD patients, ileal and colonic ulcers were associated with distinct systemic responses. hsCRP showed a better capacity to detect patients with colonic than ileal ulcers. Some markers might help to detect ileal ulcers or to improve the ability of CRP for detecting colonic ulcers.Read more P414 Timing of biologics discontinuation is not associated with postoperative complications (POCs), infective complications, bleeding, or intra-abdominal septic complications (IASCs) after primary ileocecal resection for Crohn’s Disease: a retrospective analysis of 237 patients in a tertiary centreWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The role of biologics on postoperative complications in Crohn’s Disease (CD) is still debated. Recent studies showed that preoperative adalimumab, infliximab, ustekinumab, and vedolizumab were not associated with increased POCs and IASCs. While some studies defined a 12-week cut-off based on pharmacodynamics principles, the safest timing for biologics discontinuation remains unknown. We aimed to analyse different timing of biologics discontinuation and POCs, infective complications, bleeding and IASCs after primary ileocecal resection for CD.

Methods

This is a retrospective single-centre study including all consecutive patients undergoing primary ileocecal resection for CD between 2004-2022 and exposed preoperatively to biologics. Patients were divided into four groups according to the number of weeks between the last dose of biologics and surgery: Group 1 (≤6 weeks), Group 2 (>6 and ≤12 weeks), Group 3 (>12 and ≤30 weeks), Group 4 (>30 weeks). The primary aim was POCs. Secondary aims were postoperative Clavien-Dindo≥III complications, infective complications, bleeding and IASCs. Uni- and multivariable logistic regression analyses were performed.

Results

We included 237 patients who underwent primary ileocecal resection for CD with previous exposition to biologics. Group 1 (≤6w) included 42 patients, Group 2 (≤12w) 41, Group 3 (≤30w) 47, and Group 4 (>30w) 107. Patients received adalimumab (128 pts, 54%), infliximab (82 pts, 35%), ustekinumab (15 pts, 6%) or vedolizumab (11 pts, 5%). Ileocecal resection with primary anastomosis was performed in 233 patients (98%) and 31 patients (13%) had a stoma. Groups were different in age, BMI, smoking, preoperative antibiotics, Albumin, Haemoglobin, and laparoscopy with Group 1 having higher rates of major risk factors for POCs. However, POCs, postoperative Clavien-Dindo≥III complications, infective complications, bleeding and IASCs were not different among the groups. Other general characteristics and postoperative outcomes of the four groups were reported in Table 1. Logistic regression analyses comparing the study outcomes among the groups were not able to detect differences as shown in Table 2

Conclusion

The present study compared outcomes of different timing of biologics discontinuation for primary ileocecal resection for CD. No difference was found in POCs, postoperative Clavien-Dindo≥III complications, infective complications, bleeding and IASCs. Considering that patients treated with biologics ≤ 6 weeks before surgery had also a higher rate of risk factors for POCs and IASCs, biologics discontinuation seems not to have any impact on them. Large prospective multicentre studies are needed to confirm the safest period of preoperatory biologics discontinuation.Read more P415 The influence of bowel urgency on the quality of life in individuals with ulcerative colitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Ulcerative colitis (UC) is a persistent inflammatory condition marked by periods of relapse and remission, significantly impacting overall quality of life (QoL). Among the various symptoms influencing this quality, bowel urgency (BU) stands out as particularly distressing. BU manifests with profound negative implications on physical health, psychological well-being, and social aspects. Furthermore, bowel urgency (BU) is often omitted from the majority of disease activity scoring systems and is not consistently considered as a treatment outcome. Our objective was to explore the impact of BU on specific subgroups of QoL measures and its correlation with the partial Mayo score.

Methods

During this cross-sectional study, patients were categorized based on both BU and the concurrent partial Mayo score. The patients completed the Whoqol Bref questionnaire for assessing their QoL. Long-term outcomes, such as steroid use, hospitalization and colectomy, were evaluated at the 6-month follow-up.

Results

The study included 154 patients diagnosed with UC. When comparing BU with the partial Mayo score in terms of QoL, significant differences were found in the physical health domain (p<0.001), psychology domain (p<0.001), social relationship domain (p<0.014), and environmental domain (p<0.001). Among patients in remission according to the partial Mayo score (25/117, 21.3%), a notable proportion experienced bowel urgency (BU). BU was identified as a predictor for both steroid requirement (OR: 4.7; 95% CI [2.3-9.7], p<0.001) and hospitalization (OR: 4.7; 95% CI [2.3-9.7], p<0.001) during the six-month follow-up period. None of the patients required surgical intervention. Notably, even among patients in remission according to the partial Mayo score (25/117, 21.3%), bowel urgency (BU) persisted.

Conclusion

We noted that the existence of BU significantly impairs the quality of life for individuals with UC. Moreover, it is associated with an increased probability of future steroid use and hospitalization. Notably, some patients still experienced BU even while in remission. Further investigations are necessary to elucidate the mechanisms contributing to the persistence of these symptoms in these individuals.Read more P434 Incidence of chronic end-stage renal disease in patients with inflammatory bowel disease: a population-based cohort study from the French National Health Insurance DatabaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Renal disorders are among the extra-intestinal manifestations of inflammatory bowel disease (IBD), and treatments may also lead to renal failure. However, the incidence of end-stage renal disease (ESRD), defined as the need for renal replacement therapy (dialysis and/or renal transplantation(RT)), is poorly known. The primary objective of our study was to assess the incidence of ESRD in IBD patients, and to compare it with the non-IBD population.

Methods

We conducted a prognostic cohort study based on data from the French National Health Insurance Database(SNDS). Prevalent cases of IBD affiliated to the general health insurance scheme during the period 2011-2020 were identified on the basis of declarations long-term diseases ALD 24 or the presence of 2 hospital stays for IBD with ICD-10 codes or a single stay with reimbursement of specific treatments. Incident cases of ESRD were identified on the basis of a stay with a RT or a period with dialysis sessions for at least 45 days. Crude incidence rates of ESRD were calculated over the period for the IBD and the non-IBD population, with their 95% confidence intervals.

Results

A total of 280,283 IBD patients were included in the study over the period 2011-2020, 134,567 with ulcerative colitis(UC) and 145,716 with Crohn’s disease(CD). The mean age at study inclusion was 39.8 (± 17.1) years. The M/F sex ratio was 0.9. The mean age at incidence of ESRD in the non-IBD population was 65.0 (±17.0) years, the M/F sex ratio cases was 1.7. Among IBD patients, 534 patients began replacement therapy by dialysis or RT, they were younger than non-IBD patients (60.3(±16.7)years, P<0.001).The mean incidence rate of ESRD over the period was 26.4 per 100,000 person-years (IC95% 23.1-29.6), 480 (89.9%) patients entered ESRD by dialysis, and 54 (10.1%) by preemptive RT. In the non-IBD population the mean rate of ESRD was 15.9 per 100,000 person-years (IC95% 14.8- 17.1; P<0.0001 compared with IBD): 79,606 (94.5%) patients entered ESRD by dialysis, and 4,634 (5.5%) by RT (as compared with IBD,P<0.001). In subgroup analysis, the mean incidence rate of ESRD was 22.8 per 100,000 person-years (IC95% 18.9-26.7) in UC patients and 29.5 (IC95% 25.3-33.6) in CD patients. The rates of preemptive RT were 12.4% in UC patients (87.6% dialysis) and 8.6% in CD patients (91.4% dialysis). Over a median follow-up of 6.8 years, the survival rate after ESRD was 40.8% in ESRD-IBD patients VS 34.2% in ESRD non-IBD patients (P<0.001).

Conclusion

This study shows that the incidence of ESRD is significantly higher in IBD than in the non-IBD population, confirming the need for regular monitoring of renal function in our patients. The high incidence of RT confirms that access to transplantation is not restricted in this population.Read more P435 Plasma inflammation-related proteins as markers of anxiety and depression disorders in inflammatory bowel disease patientsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Up to 25%-35% of patients with inflammatory bowel disease (IBD) suffer from anxiety or depression. Inflammatory and immune response processes may play an important role in the co-occurrence of IBD and mood disorders. We aimed to investigate the plasma inflammation-related proteins that can characterize the anxiety and depression disorders in IBD patients.

Methods

Plasma was collected from 61 IBD patients, and the OLINK panel (Target 96 Inflammation) was used to quantify the expression levels of 92 inflammation-related proteins. The Hospital Anxiety and Depression Scale (HADS) was used to assess the anxiety and depression symptoms.

Results

Among the involved IBD patients (median age 37, 40.98% female), 26.23% had anxiety and 29.51% had depression. Compared with IBD patients without mental disorders, the plasma level of FGF-23 was significantly increased in IBD patients with anxiety or depression disorders (P=0.035). Besides, the levels of CCL20 (P=0.039) and CXCL1 (P=0.021) were up regulated in IBD patients with anxiety and depression, respectively (Figure 1). Correlation analysis showed that the plasma level of CXCL1 (r=0.254, P=0.047) and FGF-23 (r=0.318, P=0.012) were positively correlated with the total degree of anxiety and depression disorders, while DNER (r=-0.300, P=0.018) appeared a reverse correlation trend. On the other hand, the plasma level of FGF-23 (r=0.351, P<0.01) was positively correlated with anxiety degree in IBD patients. As for the depression disorder, we found a positive correlation in plasma CXCL1 (r=0.296, P=0.020) level, and negative correlations were found in levels of IL-8(r=-0.256, P=0.045), uPA (r=-0.264, P=0.038), IL-20 (r=-0.290, P=0.022) and DNER (r=-0.353, P<0.01) (Figure 2).

Conclusion

We found specific plasma inflammation-related proteins for anxiety and depression disorders in IBD patients. The high incidence of anxiety and depression in IBD patients may be attributed to the stimulation of high levels of inflammatory factors.Figure 1.Violin plots showing the differentially expressed proteins between groups. A.IBD patients without anxiety or depression VS with anxiety or depression; B.IBD patients without anxiety VS with anxiety; C.IBD patients without depression VS with depression.Figure 2.Pearson correlation heat map of plasma inflammatory protein level with HADS score. HADS, Hospital Anxiety and Depression Scale; HADS-A, HADS-Anxiety; HADS-D, HADS-Depression; *P<0.05, **P<0.01.Read more P454 Systemic free thiols associate with clinical and biochemical disease activity in Inflammatory Bowel Disease: a prospective diagnostic validation studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

In the pathophysiology of inflammatory bowel diseases (IBD), oxidative stress plays an important role. Lower levels of plasma free thiols (FT) reflect a higher oxidative stress burden and correlate with IBD disease activity. However, their clinical significance as biomarker for disease activity remains unclear. This study aimed to prospectively validate the utility of plasma FT levels as biomarker for clinical, biochemical, and endoscopic disease activity in patients with IBD.

Methods

In an ongoing prospective diagnostic trial aiming to include 100 IBD patients, we conducted an interim analysis of plasma FT levels in 52 patients with IBD (24 Crohn's disease [CD], 21 ulcerative colitis [UC], and 7 patients with undetermined IBD). Clinical disease activity was quantified by the Harvey-Bradshaw Index (HBI) for CD and Simple Clinical Colitis Activity Index (SCCAI) for UC. Biochemical disease activity was determined by measuring blood C-reactive protein [CRP] and faecal calprotectin [fCal]). Endoscopic disease activity was quantified with the Mayo endoscopic subscore for UC and the Simple Endoscopic Score (SES-CD) for CD. Plasma FT levels were assessed for correlations with disease activity parameters using linear and logistic regressions models. Discriminative capacity of biomarkers was evaluated through calculating receiver operating characteristics (ROC) statistics.

Results

Plasma FT levels were significantly negatively correlated in clinical parameters, like HBI (r = -0.53, p < 0.05) (Fig. 1A). Other inflammatory biomarkers, like CRP, were also negatively correlated with plasma FT levels and were reduced in patients with active IBD (r = -0.43, p < 0.05) (Fig. 1B). Plasma FT levels accurately discriminated between CD patients with clinically quiescent (HBI < 5) and active disease (HBI ≥ 5) (AUC = 0.80, p = 0.02, Fig. 1C), better than fCal (AUC = 0.55, p = 0.83). Plasma FT were not significantly different for biochemically quiescent (CRP < 5 mg/l) and active (CRP ≥ 5mg/l) disease (AUC = 0.69, p = 0.20, Fig. 1D). Both Mayo and SES-CD scores, after adjusting for confounders, also exhibited a trend towards negative association with plasma FT levels (Fig. 1E).Figure 1

Conclusion

Further completion of the trial will reveal whether systemic FT levels will reflect endoscopically observed disease activity, and this interim analysis shows strong correlations FT levels and parameters of clinically and biochemically active disease. Measuring systemic FTs in IBD may be a promising, minimally invasive strategy to monitor IBD disease activity.

Funding

NoneRead more P455 Deploying machine learning algorithms to stratify patients with inflammatory bowel disease using routinely collected electronic health recordsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Personalised medicine approaches are eagerly awaited to facilitate individualisation of medical care for patients with inflammatory bowel disease (IBD). Multiple approaches have already been explored in attempts to stratify patients into different prognostic trajectories. In this study we aimed to use machine learning algorithms to cluster patients based on their routinely collected electronic health records in an unsupervised approach.

Methods

We interrogated the rich electronic health records (EHR) of 619 patients with a diagnosis of IBD requiring an advanced therapy and attending the IBD service at King’s College Hospital (KCH), London, UK. Data for a seven year period (June 2016-May 2023) were included with variables that captured diagnosis, treatments, service utilisation and investigations. Ethical approval was provided following application to the KERRI committee (KCH committee for accessing anonymised HER). In a preliminary analysis, we employed a multi-step approach to analyse patient data, identify significant features through k-prototypes clustering and a combination of parametric and non-parametric statistical tests. We examined different cluster solutions up to six clusters.

Results

We included 38 quantitative and 32 qualitative variables for 350 patients with a diagnosis of CD and 269 with a diagnosis of UC. Missing data were addressed by imputation by k-NN, mode value and zero. In the context of the unsupervised learning approach, when k=3, key differentiating features included faecal calprotectin levels, body mass index, mean platelet volume, marital status, taking advanced therapy for less than 3 years, and service access (telephone or clinic appointments).

Conclusion

This first pass analysis suggests that patients who are relatively early in their journey with at least moderately active IBD take up more recourses of the IBD service. This associates also with their social circumstances. Further work will explore these interactions in more detail.Read more P488 Development and validation of a risk prediction tool for inflammatory bowel disease (IBD) diagnosis in patients presenting in primary care with abdominal symptoms, a UK based studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

There are no prediction models for a diagnosis of inflammatory bowel disease (IBD) in primary care. An IBD risk prediction tool has the potential to reduce the length of time patients have undiagnosed IBD symptoms and improve IBD clinical outcomes. Therefore, our aim was to develop and validate a risk prediction model for the diagnosis of IBD, ulcerative colitis (UC) and Crohn’s disease (CD) in men and women separately.

Methods

A population-based retrospective open cohort study using Clinical Practice Research Datalink (CPRD) Aurum database was undertaken between 1st January 2010 and 31st December 2019, including patients aged 18 years or older. Patients were followed from first presentation with lower gastrointestinal (GI) symptoms potentially related to IBD to the earliest of IBD diagnosis, loss to follow-up, death or study end. 2,054,530 patients were in the model derivation cohort and 673,320 patients in the validation cohort. Cox proportional hazards models were used to derive separate risk equations in men and women for IBD, UC and CD. Candidate predictors included demographic factors (age, sex, smoking, body mass index, Charlson comorbidity score, loperamide use), family history of IBD, co-existing conditions (anxiety, depression, irritable bowel syndrome (IBS), haemorrhoids), extraintestinal manifestations (EIM) (mouth ulcers, ophthalmic, primary sclerosing cholangitis, dermatological), investigations (hemoglobin, mean corpuscular volume, platelets, albumin, vitamin B12, ferritin, C-reactive protein, erythrocyte sedimentation rate, calprotectin level). Measures of calibration and discrimination (C-statistic and D-statistic, higher values indicate better discrimination) were determined in men and women separately in the validation cohort at 1,2,3 and 5 years after symptom presentation.

Results

In the derivation cohort, 15,105 (0.7%) patients had an IBD diagnosis (10.014 UC (66.3%) and 5,088 CD (33.7%)). The IBD prediction model included 41 and 40 predictors, and the UC model 37 and 36 predictors, in women and men respectively; the CD model included 37 predictors in both men and women. C-statistics and D-statistics in men were as follows: IBD model 0.77 and 1.74; UC model: 0.81 and 1.95; and CD model: 0.77 and 1.95, respectively. Similar values were observed in women.The measures of discrimination showed that the prediction models reliably differentiated patients with and without IBD, UC and CD in both sexes. Model calibration was good, tending to overestimate at higher risk thresholds in validation cohort.

Conclusion

A risk model of patient demographics, symptoms and investigations performs well for IBD, UC and CD and may help in prioritising suspected IBD referrals in symptomatic subjects in primary care.Read more P489 Systematic review and meta-analysis of the accuracy of computer-aided diagnosis in identifying endoscopic remission in Ulcerative ColitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Endoscopic remission (ER), the absence of active inflammation during endoscopy, is a key therapeutic target in Ulcerative Colitis (UC). ER is assessed during colonoscopy using standardised scoring systems. However, there remains significant inter-operator variability in assessing ER, for which the application of computer-aided diagnosis (CADx) could be a potential solution. A previous systematic review and meta-analysis on this topic was limited to literature up to June 2022 and did not assess the methodological quality of studies or heterogeneity amongst results. We aimed to update this review.

Methods

Searches were performed on six electronic databases and relevant reference lists up to May 2023. Data was extracted and screened independently by two reviewers. Methodological assessment was performed using the QUADAS-2 tool. An ‘image selection’ domain was added to the tool given the importance of endoscopic image quality in training and testing data on CADx’s accuracy. Meta-analysis was performed using a bivariate model. Heterogeneity was assessed through visual inspection of forest plots and receiver-operating characteristic curves, subgroup analyses and meta-regression. The overall quality of evidence was assessed using GRADE methodology.

Results

17 studies (16 full-text articles and one abstract) were identified. 15 studies adopted a cross-sectional design. All studies used expert endoscopists scoring of ER as the reference standard. The Mayo Endoscopic Score was the most commonly used scoring system (13/17). CADx assessed ER in real-time in one study, but was applied to images and videos obtained from previous endoscopic procedures in all other studies. Inception-v3 was the most common CADx system used (6/17). ‘Patient selection’ was the domain of greatest concern due to a considerable number of studies using images from the same public database and under-reporting participant characteristics. All studies had a low risk of bias (ROB) in the ‘image selection’ domain. One study was deemed overall high ROB, and two were deemed overall unclear ROB. Sensitivity analysis was performed by removing these studies and the abstract, and pooled estimates were obtained from the remaining 13 studies. CADx had a pooled sensitivity of 90.3% and specificity of 94.6% for diagnosing ER. The overall quality of evidence was moderate due to the failure of a significant proportion of studies to report sufficient participant characteristics.

Conclusion

There is moderate quality evidence that CADx has high sensitivity and specificity for diagnosing ER in pre-clinical studies. Further evaluation is required in randomised controlled trials to evaluate its efficacy in real-time and human-computer interactions.Read more P490 Prevalence and clinical features of chronic nonbacterial osteomyelitis in a nationwide cohort of children with inflammatory bowel diseasesWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Among musculoskeletal extraintestinal manifestations (EIM), the association between IBD and a rare autoinflammatory condition, chronic nonbacterial osteomyelitis (CNO), has been reported. The primary objective of our study was to report the clinical characteristics and the disease course of a cohort of patient with concurrent diagnosis of CNO and IBD. The secondary outcome was to define the prevalence of CNO in a nationwide cohort of patients with IBD.

Methods

This is a retrospective, multicenter study based on the Italian Society of Gastroenterology, Hepatology, and Pediatric Nutrition (SIGENP) IBD National Registry. The diagnosis of CNO was defined as the presence of uni- or multifocal bone inflammatory lesions with suggestive radiological or histopathological characteristics, having excluded infectious, oncological, or other inflammatory conditions. All patients under 18 years of age with a combined diagnosis of IBD and CNO identified in the registry were included.

Results

18 patients with a combined diagnosis of CNO and IBD out of 4229 patients with IBD were identified, with an overall prevalence of 0.4%. 15 (83.3%) patients were male. Median age at IBD diagnosis was 10.1 years (IQR: 6.16 years), whereas median age at CNO diagnosis was 11.7 years (IQR: 6.31 years). The most frequently reported IBD phenotype was CD (13 patients, 72.2%), followed by IBD-U (3 patients, 16.7%) and UC (2 patients, 11.1%). The diagnosis of concurrent CNO was more common in patients affected by CD than in those affected by either UC or IBD-U (13/1843, 0.7% vs 5/2886, 0.2%, p=0.01). Similarly, the occurrence of CNO was more frequent in male gender when compared to female one (15/2312, 0.6% vs 3/1917, 0.1%, p=0.01). All the patients had multifocal bone involvement; 2 (11.1%) developed subsequently dermatological manifestations consistent with SAPHO syndrome. In 8 patients (44.4%) IBD onset preceded CNO diagnosis, in 6 (33.3%) IBD onset followed CNO diagnosis, whereas in the remaining 4 patients (22.2%) the diagnosis of IBD and CNO was concomitant. Table 1. summarizes therapeutic approach to both conditions in each of the patient identified in our case series. At the end of follow-up, 14 (77.8%) patients had achieved IBD clinical and biochemical remission. Ten (55.6%) patients achieved clinical and radiological remission of bone lesions, 6 (32.3%) had achieved clinical remission but showed persistence of bone lesions at magnetic resonance imaging (MRI), 2 (11.1%) had persistence of both clinical and radiological activity.

Conclusion

Our findings support the hypothesis that CNO disease spectrum can be considered a rare extraintestinal manifestation of IBD, with a low but still non-negligible prevalence.Read more P491 Clinical application of ICCE criteria for suspected Crohn’s disease undergoing small bowel capsule endoscopyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Small-bowel capsule endoscopy (SBCE) is the primary diagnostic modality for exploring the small bowel (SB) in patients with suspected Crohn’s disease (CD) and inconclusive ileocolonoscopy findings, provided there are no obstructive symptoms or known bowel strictures. In 2005, the International Conference on Capsule Endoscopy (ICCE) established preselection criteria for these patients (Figure 1). SBCE is indicated if one criterion from group A is met, along with any other from the remaining groups (B/C/D). The aim of this study is to evaluate the diagnostic accuracy of ICCE criteria in unselected cases of suspected small bowel CD (SBCD) explored with SBCE.

Methods

An observational, single-center, retrospective study was conducted, including all SBCE performed in patients with suspected CD between January 2020 and August 2023. Demographic and clinical data, inflammatory markers, SBCE findings, confirmed CD diagnosis and indication to therapy were analyzed.

Results

A total of 46 patients were included (67.4% females, median age 43 years, IQR 32-60). SBCE identified lesions suggestive of CD based on Mow's criteria in 23.9% of patients (n=11). These findings led to a CD diagnosis in all cases, with subsequent initiation of immunomodulators or biologic therapy. In the study population, 35 (71.4%) patients had 2 ICCE criteria (A+B/C/D). The percentage of patients with ≥2 criteria did not differ significantly between those with and without CD (90.9% vs. 71.4%, p=0.18). However, overall ungrouped ICCE criteria showed a significant correlation with confirmed CD (OR 1.56, 95%CI 1.03-2.36). The creation of a model using 4 ungrouped ICCE criteria significantly improved CD prediction accuracy (area under the ROC curve 0.77, sensitivity 91%, specificity 51.4%). Patients with 4 ungrouped ICCE criteria had a higher likelihood of having confirmed CD (90 vs 48%, p=0.02).

Conclusion

In our patient cohort, the existing ICCE criteria seem insufficient for effectively identifying patients with a higher probability of SBCD. Our findings suggest that adopting a cut-off of 4 ungrouped ICCE criteria would increase the diagnostic accuracy of SBCE for SBCD.Read more P524 Etrasimod shows low risk of adverse events following concomitant use with opioids or antidepressants in patients with ulcerative colitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Etrasimod is an oral, once-daily (QD), selective sphingosine 1-phosphate (S1P)_1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC). Unlike the other S1P receptor modulator approved for UC, etrasimod and its metabolites do not have a molecular structure to inhibit monoamine oxidase (MAO).¹ Coadministration of drugs that inhibit MAO with opioids and antidepressants may increase the risk of adverse events (AEs), including hypertension.² This post hoc analysis evaluated the incidence of AEs potentially related to serotonin syndrome in patients taking etrasimod and concomitant opioids or antidepressants in the phase 3 ELEVATE UC 52 (NCT03945188) and ELEVATE UC 12 (NCT03996369) trials.

Methods

Safety data pooled from both trials were analysed in patients receiving etrasimod 2 mg QD (up to 52 weeks of exposure) with/without concomitant opioids or antidepressants. We report the proportions of patients who had ≥1 concurrent AE potentially related to serotonin syndrome, consisting of one standardised MedDRA Query, one query based on the Hunter Criteria and supplemental preferred terms (pyrexia, tachycardia and hypertension-related AEs).³

Results

Among 527 patients receiving etrasimod, 77 (14.6%) and 35 (6.6%) patients were taking concomitant opioids or antidepressants, respectively. Most patients on concomitant opioids or antidepressants were White (80.0–88.3%); male (50.6–51.4%); their median age was 35.0 (18.0–70.0) and 41.0 (19.0–74.0) years, respectively. More patients with vs without concomitant opioids or antidepressants, respectively, consumed alcohol (40.3% vs 24.7% and 48.6% vs 25.4%) and used tobacco (40.3% vs 20.9% and 34.3% vs 23.0%). The incidence of other AEs potentially related to serotonin syndrome was low and generally comparable in all subgroups; reported rates of pyrexia and tachycardia were similar in patients with/without concomitant opioids or antidepressants (Table). Hypertension-related AEs were infrequent and generally balanced. No AEs per the Hunter Criteria were reported in patients on concomitant opioids or antidepressants (Table). No reported AEs were serious or led to treatment discontinuation among patients taking these concomitant medications.

Conclusion

The incidence of AEs was low and comparable in patients receiving etrasimod with or without concomitant opioids or antidepressants. This analysis supports the low likelihood of clinically relevant drug–drug interactions between etrasimod and medications commonly prescribed to patients with UC, such as opioids or antidepressants.References1. Lee CA et al. Clin Pharmacol Drug Dev 2023; 12: 553–571.2. Sands BE et al. J Crohns Colitis 2023; online ahead of print.3. Dunkley EJC et al. QJM 2003; 96: 635–642.Read more P525 Utilisation of endoscopic ultrasonography for submucosal cushion measurement to determine eligibility for endoscopic submucosal dissection in ulcerative colitis-associated dysplasia: A case seriesWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Endoscopic submucosal dissection (ESD) has gained traction as an effective therapy for ulcerative colitis (UC)-associated dysplasia, yet identifying fitting ESD candidates is challenging by substantial submucosal (SM) fibrosis from chronic inflammation. We report our experience utilising endoscopic ultrasonography (EUS) to assess ESD eligibility by measuring SM cushion thickness.

Methods

Retrospective case-series includes nine patients who were diagnosed or referred to as UC-associated dysplasia in surveillance colonoscopies between August 2017 and October 2023. After scanning dysplastic lesions (Fig A-B), hyaluronic acid solution was injected into the SM layer (Fig C). EUS with a mini-probe quantified SM cushion beneath the dysplastic lesion (Fig D), and ESD was performed in cases with at least 2.0 mm of SM cushion thickness (Fig E-F).

Results

Among ten cases from nine patients, eight cases met the criteria and underwent ESD, while two cases (Patient 3, Patient 7) were regarded as unsuitable for ESD with SM cushion thickness less than 2.0 mm. Median disease duration was 19 years, and median age at diagnosis of UC-associated dysplasia was 50 years. Median SM cushion thickness ranged from 4.2 to 6.9 mm. Median procedure time was 50 minutes, and median size of resected specimens and lesions were 31.5 x 24.5 mm and 16.0 x 12.5 mm, respectively. en bloc resection was achieved in all cases, with an 87.5% R0 resection rate. No perforation occurred; only one required post-discharge endoscopic bleeding control after four days post-discharge.

Conclusion

EUS-measured SM cushion thickness may be a valid approach that provides an objective criterion for determining ESD eligibility in UC-associated dysplasia. This would help guide individualised treatment in UC-associated dysplasia, reducing unnecessary procedures or surgery.Read more P526 Handsewn versus Stapled Ileocolic Anastomosis for Crohn's: Comparable Outcomes Despite More Severe Disease Profile in the Handsewn GroupWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Stapled anastomosis is the most common anastomotic method after ileocolic resection for Crohn's disease, whereas handsewn end-to-end (HS-ETE) anastomosis is less frequently performed. The optimal technique for ileocolic anastomosis in Crohn's patients remains controversial. Some studies have suggested potential benefits of HS-ETE over SSTS, including lower recurrence rates, whereas others have found no difference. We aimed to compare short-term postoperative outcomes and long-term recurrence-free survival between the HS-ETE and SSTS groups at our center.

Methods

This retrospective study included consecutive patients who underwent ileocolic resection for Crohn's disease between 2012-2022 with either HS-ETE or SSTS anastomosis. The primary outcomes were perianastomotic recurrence and need for surgical/endoscopic intervention. Cox regression and Kaplan-Meier curves were used to compare recurrence-free survival.

Results

A total of 764 patients were included: 162 (21%) with HS-ETE and 602 (79%) with SSTS anastomosis. The median age of the HS-ETE and SSTS groups was 39 and 38 years, respectively. Males comprised 43% of the HS-ETE group and 51% of the SSTS group. The median BMI was 24 kg/m2 in both groups. The HS-ETE group had a longer median disease duration (10 vs. 7 years, p=0.02) and a higher rate of previous abdominal surgery (35% vs. 22%, p=0.01) than the SSTS group did. The ileocolonic location (78% vs. 66%, p=0.03) and perforating disease (45% vs. 35%, p=0.04) were also more common in the HS-ETE group. The median operative time (207 min vs. 147 min, p<0.001) and estimated blood loss (150 mL vs. 75 mL, p<0.001) were greater in the HS-ETE group. There were no differences in 30-day outcomes between the groups. Perianastomotic recurrence rates were similar between the HS-ETE and SSTS groups (29.6% vs. 28.9%, p=0.93). The 5-year recurrence-free survival rates were also comparable (HS-ETE, 56.4% vs. SSTS, 59%; p=0.94). Also, we found that the risk of requiring surgical or endoscopic intervention for recurrence between HS-ETE and SSTS was comparable (HS-ETE, 65.2% vs. SSTS, 74.2%; p=0.273)

Conclusion

Although the HS-ETE group had worse baseline disease characteristics, including longer disease duration, higher previous surgery rates, and more aggressive disease location and behavior, HETE and SSTS anastomosis after ileocolic resection for Crohn’s disease yielded comparable perioperative and long-term outcomes in our patient cohort.Read more P380 Integrated fecal metagenome and serum metabolome analysis revealed gut microbiome associated serum metabolites as diagnostic biomarkers for inflammatory bowel diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Gut microbiomes are altered among patients with IBD. Certain microbiome species were used as biomarkers for IBD diagnosis, yet with limited sensitivity and specificity, especially when used for the classification of UC and CD. Gut microbiome reprogramming was accompanied with metabolic shift. Previous studies discovered that gut microbiome-associated serum metabolites (GMSM) were disease-specific biomarkers with high sensitivity. The aim of this study is to explore how gut microbiome reprogramming is reflected in serum metabolome shift in IBD, and the potential of GMSM for IBD diagnosis and classification of UC and CD.

Methods

Shotgun metagenomic of stool and ultraperformance liquid chromatography-mass spectrometry based untargeted metabolomic profiling of serum samples from a discovery cohort of IBD and healthy individuals were performed. Spearman correlation analysis was used to identify GMSM that were differentially abundant among IBD and healthy individuals. Candidate GMSM for model construction were selected using LASSO and logistic regression. The selected GMSM panel was then transferred to multiple reaction monitoring based targeted detection. Diagnostic model for IBD and classification model for UC and CD were developed based on the GMSM panel using a training cohort, and then validated using an independent cohort consisting of patients with IBD, healthy individuals and patients with colorectal adenoma or non-adenoma polyps.

Results

Metagenome sequencing of fecal samples from 77 patients with IBD and 74 healthy individuals revealed significant shifts in gut microbiome, such as decrease in F. prausnitzii. Untargeted metabolomic profiling of serum from 76 patients with IBD and 28 healthy individuals revealed 724 differentially abundant metabolites, of which 151 metabolites were found to be significantly associated with gut microbiomes detected from the fecal samples (figure).Candidate GMSM for model construction were established using the method described and the ultimate panel consisted of 17 metabolites, including 10 GMSM for diagnostic model for IBD and 7 GMSM for classification model for UC and CD. Eventually, the diagnostic model for IBD achieved an area under curve (AUC) of 0.98 in the training cohort, and 0.92 in the validation cohort. The classification model for UC and CD achieved AUC of 0.94 in the training cohort, and 0.9 in the validation cohort. In addition, the diagnostic model for IBD also effectively distinguished IBD from patients with colorectal adenoma or non-adenoma polyps (table).

Conclusion

Based on GMSM, we developed diagnostic and classification models for IBD with high specificity and sensitivity, providing an accurate and non-invasive approach for IBD diagnosis and classification of UC and CD.Read more P390 Adiposity is negatively associated with a stenosing Crohn’s disease behaviour: a UK wide study in 8797 patients within the IBD BioresourceWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Obesity has been implicated in the pathogenesis of fibrosis. With the rising incidence of Crohn`s Disease (CD) alongside an obesity pandemic, we hypothesise that adiposity may be associated with stenosing CD.

Methods

Using NIHR IBD Bioresource data, we retrospectively assessed the relationship between body mass index (BMI) and stenosing CD by logistic regression. BMI was the primary variable of interest; CD behaviour the dependent variable; stenosing CD the primary outcome. Confounders were adjusted for in a multivariate model. Statistical analyses were performed using SPSS 28.0.1.1.

Results

8,797 patients diagnosed between 1942 and 2020 were included. Mean overall BMI was 26.3kg/m² (SD = 5.5). 52.7% had a BMI >25kg/m² (mean 30.2kg/m², SD 4.5). Majority had inflammatory CD (62.9%) followed by stenosing (25.1%) and penetrating CD (12%). Stenosing and penetrating CD were more common in the <25kg/m² BMI group (50.7%, 50.3% respectively) p<0.001. On univariate analysis, stenosing disease was positively associated with ileal disease location, disease duration, a surgical history, use of advanced therapies (infliximab, ustekinumab, vedolizumab, adalimumab) and azathioprine but negatively associated with BMI even after adjusting for confounders (OR 0.98, 95% CI [0.967-0.988]). On multivariate analyses, disease duration (OR 1.135, 95% CI [1.135-1.105-1.170]), ileal disease location (OR 3.69, 95% CI [3.22-4.24]), adalimumab (OR 1.47, 95% CI [1.30-1.66]) and ustekinumab (OR 1.512, 95% CI [1.14-2.01]) and azathioprine (OR 1.34, CI [1.189-1.529]) usage remained positively associated with stenosing CD (Table 1).

Conclusion

We observed a negative relationship between BMI and stenosing disease. This might reflect a change in eating behaviour due to persistent abdominal pain related to stenosing disease. Large longitudinal studies are needed to investigate this relationship further.Read more P404 Monocyte distribution width differentiates bacterial gastroenteritis from Acute Severe Ulcerative Colitis in patients presenting with diarrhoeaWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Monocyte distribution width (MDW) is a haematological parameter that can be generated by newer generation blood analysers on routine full blood examination. It reflects the variation in the size of monocytes and is elevated in the setting of infection, however its utility in inflammatory disorders in unknown.We aimed to assess whether MDW can help differentiate bacterial gastroenteritis from Acute Severe Ulcerative Colitis (ASUC) among patients presenting to the Emergency Department (ED) with diarrhoea. We further aimed to assess whether MDW correlated with disease activity and clinical outcomes in ASUC.

Methods

We conducted a retrospective cohort study comprising three patient groups: (1) ASUC, (2) bacterial gastroenteritis and (3) a control group of patients without active inflammation. The control group consisted of outpatients with chronic hepatitis B in immune control phase with normal liver transaminases and suppressed viral load < 2000 IU/mL. Clinical outcomes, routine biomarkers and MDW were recorded.

Results

A total of 176 patients were identified (53 ASUC, 70 bacterial gastroenteritis and 53 controls).At time of ED presentation, patients with bacterial gastroenteritis had the highest MDW (median 23.6, IQR 20.7-25.8) compared to ASUC (19.0, IQR 17.9-21.2) and controls (16.8, IQR 15.9-18.0; P<0.001). On receiver operator characteristic curve analysis, MDW discriminated bacterial gastroenteritis from ASUC with an area under the curve (AUC) of 0.78 (95% CI 0.70-0.87, P<0.001). Using Youden’s index, a MDW threshold > 22.3 had 64.3% sensitivity, 84.6% specificity, 63.8% negative predictive value and 84.9% positive predictive value for bacterial gastroenteritis.Of the 53 patients with ASUC, 25 responded to intravenous hydrocortisone while 28 were steroid non-responders and required infliximab (IFX). 24 patients responded to IFX rescue, while the 4 IFX non-responders received tofacitinib sequential therapy. In ASUC, MDW correlated positively with established markers of disease activity including CRP (Spearman rank correlation, rho=0.54, P<0.001), platelet count (rho=0.36, P=0.009) and faecal calprotectin (rho=0.35, P=0.02). A lower MDW on the day of IFX administration appeared to predict IFX response (AUC 0.80, 95% CI 0.61-1.00, P=0.002). At follow-up (median 85 days), MDW was predictive of biochemical remission with a faecal calprotectin < 100 µg/g (AUC 0.80, 95% CI 0.64-0.95, P<0.001).

Conclusion

MDW is a novel biomarker that may help distinguish ASUC from bacterial gastroenteritis at time of ED presentation in patients with diarrhoea. In ASUC, MDW correlates with existing markers of activity and may help predict IFX response.Read more P405 Intestinal ultrasound measures are highly correlated with small bowel Lewis score among patients with active Crohn’s diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Small-bowel assessment is of prime importance among patients with Crohn’s disease (CD). While small-bowel capsule endoscopy (SBCE) evaluates the extent of mucosal inflammation, intestinal ultrasound (IUS) provides a complementary information with regards to transmural disease involvement. We aimed to examine the correlation between SBCE and IUS, among patients with active CD, as well as sensitivity to therapeutic response during follow-up.

Methods

Patients with active small-bowel CD, who have been started on biologics, were included. Patients were prospectively followed with fecal calprotectin (FC), SBCE and IUS at baseline and after 14 and 52 weeks. Lewis score (LS), Limberg score (LI) and terminal ileum bowel-wall thickness (TIBWT) were documented for each patient. Response to treatment was defined as a 25%-reduction compared to the baseline measure of FC, LS, LI and TIBWT, while FC<150μg/mg, LS<135, LI<2 and TIBWT<3 mm, were defined as biochemical, endoscopic and ultrasonographic remission, respectively (week 0→week 14/ week 14 →week 52). Baseline correlations were obtained using the Spearman's correlation. Comparison between correlations were assessed using the Fisher's Z-transformation. Fisher's exact-test was performed to evaluate the correlation between the examined response/remission outcomes.

Results

Seventy-one patients were included (median age: 26 (22-43) years, male-49%). The median time between SBCE and IUS procedures was 3 (0-25) days. Baseline LS was well correlated with both TIBWT (r=0.6, p<0.001) and LI (r=0.6, p<0.001). Ultrasonographic remission was significantly correlated with both biochemical remission (FC and TIBWT [p=0.012], FC and LI [p=0.024]) and endoscopic remission (LS and TIBWT [p=0.035], LS and LI [0.013]), [Figure 1]. The baseline correlation between FC and LS (r=0.490, p<0.001) was numerically but not significantly higher than FC and BWT (r=0.386, p=0.002) or FC and LI (r=0.224, p=0.080) [p=0.500 and p=0.110, respectively]. No significant correlation was observed between FC and LS /TIBWT/LI response to treatment (p=0.347 p=0.261, p=0.864, respectively), while there was a trend regarding TIBWT and LS response to treatment correlation (p=0.052).

Conclusion

IUS measures are highly correlated with SBCE LS among patients with active CD, and provide an accurate and reliable assessment of disease activity during follow-up. Therefore, IUS may serve as a feasible and noninvasive tool in the monitoring and management of patients with CD.Read more P420 Natural history of intra-abdominal inflammatory masses (phlegmons) in Crohn’s diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Intra-abdominal inflammatory masses (phlegmons) are a feature of penetrating Crohn’s disease (CD). However, there are few data on the natural history and outcomes of inflammatory masses in CD. We aimed to describe clinical outcomes and predictors of surgery in individuals with CD and intra-abdominal inflammatory masses (IAIM).

Methods

We conducted a multi-center retrospective cohort study. Patients with a diagnosis of CD or inflammatory bowel disease unclassified (IBD-U) and a finding of phlegmon, phlegmonous change or inflammatory mass on cross-sectional imaging with IV contrast (MR or CT) at two tertiary care centers were included between July 2006 and April 2023. Data collected included demographics, clinical characteristics, Montreal CD classification, treatments at the time of and after IAIM diagnosis, and size and location of the IAIM. Primary outcome was surgery defined as any CD-related resection or surgical drainage. Bivariate comparisons between patients who did or did not undergo surgery were performed. Multivariable logistic regression was performed with backward selection of variables to identify those associated with surgery.

Results

A total of 100 patients were included, and comparison between those who did or did not undergo surgery is given in Table 1. Most were white (80%), 44% were women, and 12% were current smokers. A majority had ileocolonic disease location (77%) and 50% were on a biologic at time of diagnosis. Mean size of IAIM was 3.4 cm and the majority (72%) were located adjacent to small bowel. Radiologic evidence of intra-abdominal fistula was seen in 40%, and 30% of patients had a stricture adjacent to the IAIM.A large proportion required hospitalization (75%) and received intravenous antibiotics (64%); 13% progressed to an abscess, and the mean (SD) time to abscess was 108 (119.4) days. The majority (65%) underwent surgery, with a mean (SD) time to surgery of 59 (97.8) days. Seven patients developed sepsis, all of whom subsequently required surgery. On multivariable analysis, patients were more likely to require surgery if there was a concomitant stricture (aOR = 3.12, 95% CI 1.01 – 11.9) and less likely to require surgery if treated with steroids (aOR = 0.15, 95% CI 0.03 – 0.61). Antibiotic use was not associated with surgery (aOR 1.22, 95% CI 0.53 – 2.81) nor was IAIM size.

Conclusion

In this large retrospective cohort, most intra-abdominal inflammatory masses required surgery, particularly if there was a concomitant stricture. Patients treated with steroids were less likely to require surgery though this may be confounded by severity of disease.Read more P421 The faecal biomarker LDN-051 is a novel tool for monitoring disease activity and therapeutic response in Inflammatory Bowel DiseasesWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Crohn’s disease and ulcerative colitis, two forms of inflammatory bowel disease (IBD) require lifelong treatment and patient monitoring. Current predictors of relapse and therapeutic success have limitations, therefore there is high unmet need to identify novel biomarkers in IBD. Monitoring approaches for IBD are mostly invasive, time-consuming, and expensive. Therefore, a simple, rapid, and non-invasive test, with ability to differentiate IBD from other gastrointestinal conditions and to monitor disease activity, will have important clinical implications. Our previous mucosal cytokine profiling identified that Plasminogen activator inhibitor type 1 (PAI-1) is expressed in IBD patients with active disease, but not in control. Therefore, our aim was to assess the utility of PAI-1 in monitoring disease activity and therapeutic response of IBD patients in different biological samples.

Methods

Serum, biopsy and faecal samples were collected from 132 IBD patients and 30 controls without IBD. ELISA method was used to define the level of PAI-1 in the mucosa, serum, and faecal samples and the serum CRP levels were also determined. For the mucosal gene expression analysis qRT-PCR was used. The correlation and ROC analyses were applied to observe the relationship between the disease activity and PAI-1 level.

Results

The applied screening approach detected significant higher expression of PAI-1 in active IBD. We demonstrated that the serum, mucosal and faecal PAI-1 concentration was significantly elevated in IBD patients showing clinical and endoscopic activity. Additionally, in responder patients the initial PAI-1 level decreased significantly upon successful therapy, whereas it remained unchanged in non-responders. We also showed that faecal PAI-1 selectively increases in active IBD patients, but not in other organic gastrointestinal diseases. In addition, the stability analysis of faecal PAI-1 showed that the protein was detectable up to one week at room temperature and 4ºC. The serum, mucosal and faecal PAI-1 level showed positive correlation to the endoscopic activity. ROC curves demonstrated that faecal PAI-1 showed a relatively high power to distinguish between active and control patients. However, the serum CRP level no reflected to the therapeutic response.

Conclusion

Our results suggest that serum, mucosal and faecal PAI-1 expression reflects to the disease activity in IBD, which could be used to disease monitoring and possibly therapeutic response. The correlation between the faecal PAI-1 level and the endoscopic activity promotes that it could be used as a novel non-invasive disease specific faecal biomarker in the IBD diagnosis.Read more P440 Myenteric plexitis and active inflammation at surgical margins are high-risk predictors for postoperative clinical recurrence of Crohn’s diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Preventing postoperative recurrence is an important issue for clinical management of Crohn’s disease (CD). Identification of practical risk factors and an effective prophylactic treatment strategy has been desired for the prevention of postoperative recurrence. Although some of the clinical risk factors have been applied to select candidates for prophylactic treatments, these attempts have not fully prevented postoperative recurrence. In this study, we investigate the histological features at resected margins which predicted postoperative recurrence, and whether the initiation of prophylactic treatments could prevent postoperative recurrence in these cases.

Methods

We retrospectively reviewed the clinical recurrence rate in CD patients who underwent intestinal resection between January 2019 and December 2021. Clinical recurrence was defined by combination of serological, radiographic, and endoscopic findings or treatment escalation. To assess the histological risk factors for postoperative recurrence, resection margins of the surgical specimens were evaluated for the presence of myenteric plexitis, granulomas, and active inflammation. Each histological feature was evaluated from Grade 0 to 3. We also examined the ability of prophylactic treatments to prevent postoperative recurrence stratified with histological findings related to clinical recurrence rates.

Results

Of the 141 patients included in this study, 61.9% had plexitis (grade 3:Inflammatory cells at myenteric plexus, 10>HPF) at the proximal margin and 13.5% had active inflammation (grade 3: erosion or ulcer) at the distal margin. Log rank test identified the presence of plexitis (Grade3) (HR:1.84, 95%CI [1.05-3.22], p=0.029) at the proximal margin and active inflammation (Grade3) at the distal margin (HR:1.29, 95%CI [1.05-1.58], p=0.012) as possible risks of clinical recurrence (Figure). Multivariate analysis confirmed that the presence of plexitis (Grade3) at the proximal margin (HR 1.82, 95% CI 1.04-3.21, P=0.038) and active inflammation (Grade 3) at the distal margin (HR 2.31, 95% CI 1.18-4.46, P=0.013) were associated with postoperative clinical recurrence. Prophylactic use of immunomodulators (IM) and biologics did not show a significant reduction of clinical recurrence compared to treatment without IM and/or biologics in patient with histological risk factors (Table).

Conclusion

Our results indicate that the presence of plexitis in the proximal margin and active inflammation in the distal margin of the resected intestine are risk factors for postoperative recurrence. In these cases, initiation of prophylactic treatments with biologics and/or IM may not prevent the clinical recurrence.Read more P441 Optimization of deep learning architectures for differentiating cytomegalovirus infection in severe ulcerative colitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Cytomegalovirus (CMV) reactivation is common in patients with severe ulcerative colitis (UC). Patients with UC exacerbated by reactivated CMV experience worse prognoses than those without CMV reactivation. However, CMV is primarily diagnosed through biopsies, and it can take quite time to get results, making early diagnosis challenging. To address this, we have conducted research using deep learning to differentiate CMV from severe ulcerative colitis (UC), which has similar features, through endoscopic imaging, enabling early diagnosis of CMV.

Methods

This study leveraged endoscopic imaging to classify CMV and severe UC within a dataset comprising 86 cases from Ewha Womans University hospitals, deploying 7 convolutional neural networks. The training utilized a 4:1 ratio, enhanced by a 5-fold cross-validation, to counter the dataset's constraints. Networks underwent optimization for 10 epochs, a batch size of 10, sigmoid activation, and a learning rate of 1e-4. To improve the performance of the network, we employed augmentation techniques such as random rotations and flipping, and performed brightness standardization and resizing of resolution. Additionally, to distinguish lesions that are difficult to differentiate with RGB values, we converted the images to HSV values to separately process areas of reflected light and ulcerated regions.

Results

Among the total of 7 networks used in this study, Densenet121 showed the best performance with an accuracy of 0.8267 (Precision 0.7979). Densenet201 and MobileNetV2 also demonstrated the next best performances with accuracies of 0.7857 and 0.7143, respectively.The standardization and augmentation performed during the preprocessing process have been confirmed to improve the network's performance, and the network's robustness was verified through 5-fold cross-validation.

Conclusion

The research underscores the potential of deep learning models in differentiating CMV from severe UC through endoscopy images, indicating a promising direction for non-invasive diagnostics and timely treatment interventions.The results of the current study are based on data collected from two institutions, and thus, future research will involve multi-institutional studies to develop and test a more robust network with improved performance.Read more P460 The POCER index: application of a novel endoscopic score in a real-life cohort of patients with Crohn's disease after surgeryWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The Rutgeerts score (Rs) is the most widely used score that offers essential prognostic information in the field of postoperative management of patients (pts) with Crohn's disease (CD). A recent study has introduced the POCER postoperative index (Pi), which includes the circumferential extent and depth of anastomotic ulcers, which can be an additional tool to better define the prognosis of this category of pts

Methods

Our study aims to evaluate the Pi in a real-life cohort, its correlation with Rs, and its prognostic value. We conducted a single center retrospective study, evaluating different outcomes of pts with CD who underwent ileocolonic resection. All pts underwent the first endoscopic evaluation within 6-12 months to assess postoperative recurrence (POR). We applied both the Rs and the Pi. POR was defined as Rs≥2 or Pi≥2. A clinical and objective assessment was performed at 18-24 months. Clinical Recurrence (CR), evaluated in all pts, was defined with a Harvey-Bradshaw Index (HBI)≥5. Objective Recurrence (OR), evaluated in a subgroup, was defined by the presence of endoscopic activity and/or radiological activity (assessed by ultrasound (US) when a wall thickness≥4 mm was present)

Results

We included 103 pts who underwent ileocolonic resection, with a median age at surgery of 38 years old. The main indication for surgery was a stenotic disease. 63% of pts had ≥1 risk factor for POR. All pts underwent prophylactic biologic therapy. At 6 month, POR was observed in 50 (48.3%) and 17 (16.5%) pts, according to Rs and Pi, respectively. Mean Rs and Pi were 1.39 (± 1.31) and 0.70 (± 1.08); a moderate correlation (r=0.523) between the two was observed. We assessed the ability of Rs and Pi at 6-12 months to predict CR and OR at 18-24 months. A Rs≥2 predicted CR with an AUROC of 0.8345 (sensitivity 93.3% and specificity 59.3%). A Pi≥2 predicted CR with an AUROC of 0.693 (sensitivity 33.33% and specificity 84.88%). When evaluating the performance of the mean of the two scores, we observed that a mean score≥1.75 could predict CR with an AUROC of 0.807 (sensitivity 80.00% and specificity 68.6%). A mean score≥1.75 could also predict OR with an AUROC of 0.662 (sensitivity 45.45% and specificity 74.29%). We also evaluated the subgroup of pts with Rs 1-2 at 6 months and the significance of the addition of the Pi: although no statistical significance was observed, a Pi<1 had a specificity of 100% in predicting the absence of CR

Conclusion

Rs and Pi can be used to assess POR and predict CR and OR. The combination of the two might outperform each of them with a good compromise between sensitivity and specificity. The addition of the Pi in pts with Rs 1-2, might be helpful in clarifying the prognostic significance of this resultRead more P461 Deep learning model for endoscopic differential diagnosis between intestinal lymphoma and Crohn's disease: a multicenter studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Primary and secondary intestinal lymphoma (IL) are a relatively rare cancer, while easily misdiagnosed due to the unclear aetiology and unspecific clinical symptoms. Moreover, the endoscopic features of IL vary depending on pathological types, making it difficult to distinguish from Crohn's disease (CD). This study aims to develop deep learning models based on endoscopic images, facilitating the differential diagnosis of IL and CD.

Methods

We retrospectively recruited 271 patients with IL and 232 patients with CD from 6 tertiary centres in China. With out-of-focus or poor-bowel-prepared images excluded, we used 1739 IL and 1649 CD images for internal and external validation to build deep learning models. For internal validation, we used five-fold cross-validation with 1517 IL images and 1428 CD images from 5 centres randomly assigned without any patient overlap. 222 IL and 221 CD images from the 6th centre were used for independent external validation to measure the generalization ability of models. Further, we compared the performance of models with that of clinical physicians consisting of 2 junior physicians and 2 endoscopy specialists with more than ten years of clinical experience. We evaluated models using metrics such as accuracy, sensitivity, specificity, and the area under the receiver operating characteristic curve (AUC) and used the kappa statistic to measure the inter-rater reliability between models and clinical physicians.

Results

We developed multiple convolutional neural network models, including ResNet18, ResNet34, ResNet50, VGG16, VGG19, DenseNet121, Inception v3, and Xception. The top 3 models in the internal validation were Inception v3, Xception, and DenseNet121. Inception v3 showed the best performance (accuracy: 83.1%; AUC: 0.910), while Xception performed better on average (average accuracy: 76.8%; average AUC: 0.834). In the external validation, the top 3 models were Inception v3, DenseNet121, and VGG19. Inception v3 achieved the highest accuracy of 81.9%, while DenseNet121 had the best AUC of 0.903. Compared with clinical physicians, Inception v3 performed better than junior physicians (average accuracy: 67.2%) and showed good agreement with the best endoscopy specialist (kappa: 0.604, p<0.05).

Conclusion

Convolutional neural network models using endoscopic images were able to differentiate PIL from CD, with better-diagnosing performance than junior physicians, good agreement with specialists, and good generation ability, which were expected to assist clinical physicians lacking experience to differentiate PIL and CD more precisely under endoscope.Read more P462 The burden of mental health disease in people with inflammatory bowel disease - Crohn's Colitis Cure (CCC) Data Insights ProgramWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The impact of Inflammatory Bowel Disease (IBD) on individuals’ quality of life is well reported. Recent studies have shown that depression or anxiety affect almost 1 in 5 people with IBD and may be a predictor of active disease. We aimed to explore the burden of MHI in the Australasian IBD population and examine the real-world variation in screening and care across different sites and care settings

Methods

Crohn’s Colitis Care’s (CCCare) clinical quality registry (CQR) is created by deidentified data flowing across from routine care encounters. Data in the CQR for all individuals with a clinical encounter since August 2018 were interrogated in April 2023. Mental health data were collected from documentation during routine care or through patient consumer completion of embedded questionnaires, namely Depression Anxiety and Stress Scale 21 [DASS-21] and Kessler Psychological Distress Scale [K10]

Results

The CQR contained 6614 people with IBD with a mean age of 44.4 (SD +/- 22.09) and even gender distribution (50.9% female). 79.5% of people were from Australia and 20.5% from New Zealand. 57.1% of people had Crohn’s disease (CD), 40.4% ulcerative colitis (UC) and 2.5% IBDU with a mean disease duration of 13.3 years (SD +/-23.0). Anxiety was the 4^th most listed comorbidity affecting 17.8% of individuals, depression 7^th affecting 13.7% of people and both depression and anxiety 13^th affecting 9.1% of people with IBD. In total 40.8% or 2 in 5 people with IBD in Australasia had received a formal diagnosis of a MHI.2,928 consumers had been invited to complete the DASS-21 and 2,340 the K10 (44% & 35% respectively). Of the questionnaires sent, 32% of DASS-21s and 33% of K10s were completed. Rates of both invitation and completion varied significantly between centres. Invitation rates varied from 11% - 90% (p<0.001) while questionnaire completion rates varied from 26% to 46.8% (p<0.001).The mean DASS-21 score for all people with IBD was 8.1 for depression (7-10 indicating moderate disease), 6.6 for anxiety (6-7 suggests moderate disease) and 11.2 for stress (10-12 indicates moderate disease). Individuals with current fistulising CD (representing severe IBD phenotype) mean DASS-21 scores were higher than the wider IBD population, averaging 9.9 for depression (p<0.001), 7.4 for anxiety (p<0.001) & 12.9 for stress (p<0.001)

Conclusion

Individuals with IBD suffer from high rates of MHIs, with those suffering more severe disease phenotypes scoring worse on mental health assessment tools. Despite the availability of screening and monitoring tools, healthcare providers use these variably and insufficiently. This may result in unmet care needs. Standardisation of care addressing the psychosocial care needs of people with IBD is neededRead more P463 Infant neurocognitive screening with cerebral MRI and app-based assessment of generalised movements is feasible following exposure to maternal inflammatory bowel disease in-uteroWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Exposure to maternal inflammation in-utero is associated with an increased risk of neurocognitive developmental disorders in offspring, including cerebral palsy (CP). An increased risk of CP and neurological morbidity has been reported in infants of women with CD and UC in registry but not prospective cohort studies. Unsedated neonatal cerebral MRI (nMRI) allows for early assessment of brain microstructural integrity, with bipartietal diameter (BPD) predictive of cognitive and motor outcomes in preterm infants. Generalised movement assessments evaluate the character of infant’s spontaneous movements, can be undertaken remotely by parents with app-based technology (BabyMoves (BM) and are an early indicator of being high risk for cerebral palsy. nMRI & BM have not been used to screen for adverse neurocognitive outcomes in infants born to women with inflammatory disorders. We aimed to assess the feasibility of nMRI and BM in infants born to women with IBD and correlate abnormalities with maternal biochemical inflammation antenatally.

Methods

Pregnant women with IBD were assessed clinically and biochemically (faecal calprotectin (FC), CRP) in each trimester of pregnancy in this single centre prospective pilot study. Biochemically active disease was defined by FC >100ug/g or CRP >15mg/L. Infants underwent nMRI using a 1.5T MRI with T₁-weighted and T2/proton density-weighted sequences performed at 6-12 weeks post-corrected term. Parents filmed 2 BM videos at 12-14 & 14-16 weeks post-corrected term. nMRIs (Figure 1) and BMs were scored by blinded reviewers with validated scoring systems. Metric nMRI data were corrected for gestational age (cGA). Descriptive statistics and spearman correlation coefficients were performed.

Results

40 mother-baby pairs, 19 with CD & 20 exposed to a biologic drug, were recruited. Most patients were in biochemical remission throughout pregnancy with median FC <50ug/g and <13% having a CRP >15g/L in trimesters 1-3. At delivery 2/40 infants were premature, 4/40 low birth weight & 3/40 required neonatal intensive care. The median cGA at nMRI was 46 weeks 6 days (range 42 + 5-53 + 4). 2/39 MRI were of insufficient quality for scoring. 5/37 nMRI and 4/35 BM were abnormal, with 1/7 having a clinically significant adverse outcome (Table 1). Biparietal diameter did not correlate with maternal CRP or FC in any trimester of pregnancy.

Conclusion

nMRI & BM for infant neurocognitive disorder screening is feasible in the setting of maternal IBD. In this cohort of 40 infants, one clinically significant abnormality was identified in an infant of a mother with inactive IBD. Larger studies are required to stratify the risk of adverse neurocognitive outcomes in infants born to women with maternal inflammatory disorders.Read more P500 Systematic review of sexual function measurement instruments in the context of pelvic and perineal surgery for Inflammatory Bowel DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Sexual dysfunction after Inflammatory Bowel Disease (IBD), pelvic and perineal surgery is common but poorly discussed, investigated and treated in the peri-operative period. There remains no standardised measurement tool to assess sexual function in routine use for patients undergoing benign pelvic colorectal surgery.The necessity for open dialogue regarding sexual dysfunction was evidenced in a patient-led study conducted by Dames et al. Our primary objective was to undertake a systematic review of sexual function measurement instruments, to identify the need for a novel sexual function patient-reported outcome measure (sex-PROM) that may be used in the context of pelvic and perineal surgery for IBD e.g. fistula surgery, defunctioning ostomy formation, ileo-anal pouch formation and proctectomy.

Methods

We performed a systematic review according to Consensus-based Standards for the selection of health Measurement Instruments (COSMIN) criteria (Prospero registration: CRD42023403396). Embase, Medline and PubMed Databases were searched for previously validated patient-reported outcome measures that could be used in the assessment of sexual function. These instruments were evaluated for their psychometric properties, in addition to their overall quality, utility and suitability in the context of IBD and other benign surgery. A global rating was attained according to COSMIN criteria. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) checklist was applied to evaluate the quality of evidence. In addition, patient involvement in instrument development was assessed.

Results

Some 2331 articles were screened, 305 full-text studies were assessed for eligibility and 56 measurement instruments were identified and evaluated. All studies showed limited psychometric validation. The Female Sexual Function Index and the International Index of Erectile Function were among the highest-scoring instruments, however conveyed significant limitations, including an anatomical focus, limited exploration of quality of life and relationship satisfaction, and a lack of significant patient involvement in their development. All identified measurement instruments carried limited specific clinical utility for patients after IBD surgery.

Conclusion

Sexual dysfunction after pelvic surgery for inflammatory bowel pathology is multi-factorial. It can result from anatomical nerve damage but can also occur secondary to the psychological impact of altered body image, sexual self-esteem, and relationships and intimacy. We recommend the development of a novel patient-centred sexual function measurement instrument that may be used after benign pelvic/perineal colorectal surgery to be used in the clinical and research settings.Read more P501 Communicating Needs and Features of IBD Experiences (CONFIDE) Survey: Prevalence and patients’ experience of moderate-to-severe Crohn's disease symptoms in CanadaWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Bowel urgency is known to negatively affect a patient’s quality of life¹. The Communicating Needs and Features of IBD Experiences (CONFIDE) study explores patients’ experiences and the impact of moderate-to-severe Crohn's disease (CD) and ulcerative colitis symptoms on their lives in the United States, Europe, Japan, and Canada. The current analyses focus on Canadian patients with moderate-to-severe CD.

Methods

An online, quantitative, cross-sectional survey was conducted between February and April 2023 in patients with CD. Moderate-to-severe CD was self-reported and defined based on previous treatment, steroid use, and/or hospitalisation. Data on patients' experiences and the impact of CD were descriptively summarised.

Results

A total of 107 Canadian patients with CD completed the survey (71% male, mean age 45.1 (14.8) years, mean disease duration 10 (10.2) years), of which 79% were receiving advanced therapies at the time of the survey. The top three symptoms currently (in the past month) experienced by patients were diarrhoea (49%), bowel urgency (44%), and loud stomach gurgling/rumbling (40%). Of the patients who had ever experienced bowel urgency (67%), 61% reported experiencing it at least once a week in the past 3 months. Of the patients who had ever experienced bowel urgency-related accidents (48%), 33% reported doing so at least once a week in the past 3 months. Overall, 35% of patients reported wearing diaper/pad/protection at least once a week in the past 3 months due to fear of bowel urgency-related accidents (Table). Bowel urgency (32%), fear of faecal seepage/unnoticed leakage of stool, and increased stool frequency (27% each) were the leading causes for declined participation in work/school (Fig. 1 A). Over one-third of patients declined participation in social events due to bowel urgency (36%) and fear of BU-related accidents (32%; Fig. 1 B). Overall, 37% and 29% of patients declined participation in physical exercise due to bowel urgency and fear of passive incontinence, respectively (Fig. 1 C).

Conclusion

Bowel urgency was the second-most common symptom among patients with moderate-to-severe CD and the most reported symptom leading to patients declining participation in work/school, social events, and physical exercise. Despite receiving treatment for CD, including advanced therapies, many patients with moderate-to-severe CD continue to report bowel urgency, bowel urgency-related accidents, and the use of diaper/pad/protection. These results underscore the immediate need for a holistic approach to CD management in Canada, focusing on symptom control.Reference:1. Panaccione, R., et. al., (2023), American Journal of Gastroenterology. 118, S912-S912.Read more P502 Multimodal profiling of peripheral blood identifies proliferating circulating effector CD4 T cells as predictors for response to integrin alpha4 beta7-blocking therapy in patients with Inflammatory Bowel DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Despite the success of biological therapies in inflammatory bowel disease (IBD), patient management remains challenging due to a lack of therapy response predictors.

Methods

Here we prospectively sampled two cohorts of IBD patient cohorts receiving the anti-integrin α4β7 antibody vedolizumab. Samples were subjected to mass cytometry, single-cell RNA sequencing, single-cell V(D)J sequencing, serum proteomics, and multidimensional flow cytometry to comprehensively assess vedolizumab-induced immunological changes in the peripheral blood and their potential associations with treatment response.

Results

Vedolizumab induced changes in the abundance of both circulating innate and adaptive immune cell compartments and modified the T cell receptor diversity of circulating gut-homing CD4⁺ memory T cells. Through integration of multimodal parameters and machine learning, we identify that pretreatment activated proliferating CD4⁺ memory T cell abundance is associated with treatment failure, independent of clinical variables, thereby providing a reliable predictive classifier with significant implications for the personalized management of IBD patients.

Conclusion

Our study provides a comprehensive framework for assessing therapy response and understanding the mechanisms underlying resistance in chronic immune-mediated inflammatory diseases such as IBD. Identifying personalized treatment strategies based on individual patient characteristics, as exemplified by our "stratify to target" approach, can significantly improve IBD management.Read more P503 Differentiation of patients with IBD at increased risk of CRC using UR-CARE: A Single Centre ExperienceWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The United Registries for Clinical Assessment and Research (UR-CARE) platform aims to facilitate and improve the daily clinical care of patients with Inflammatory Bowel Disease (IBD). The possibility of updating the medical data in UR-CARE at each patient visit allows for strict follow-up and enables the doctor to draw relevant recommendations. The study is aimed at identifying registered IBD patients at increased risk of colorectal cancer (CRC) via UR-CARE.

Methods

Outpatients and inpatients with a confirmed IBD diagnosis, who had signed informed consent, were entered with their clinical data in UR-CARE to the centre UMHAT “Tsaritsa Yoanna-ISUL”. Only the statistical and filter opportunities of the digital platform were used. The study was conducted with our own data from our centre database.

Results

274 IBD patients (120 with ulcerative colitis [UC], 144 with Crohn’s disease [CD] and 10 with IBD unclassified [IBD-U]) were entered in UR-CARE. Among all registered patients, colorectal dysplasia was entered for 19 (6.93%) persons (15 males; 14 with UC). The column for “Dysplasia” in the drop-down menu could be left empty. These 19 patients with colorectal dysplasia make up 7.98% of all 238 patients with filled in one of the three options for dysplasia. 7 (2.55%) IBD patients (5 males; 5 with UC) had primary sclerosing cholangitis, and for two of them with UC, colorectal dysplasia was entered. Among all registered IBD patients, four had undergone surgery for CRC, and one patient was operated on for familial adenomatous polyposis. UR-CARE filtered 73 patients with extensive and left-sided UC with a duration of UC ≥ 8 years who should undergo screening colonoscopy for dysplasia.

Conclusion

UR-CARE can quickly and effectively differentiate patients with IBD and at an increased risk of developing CRC. It enables the provision of graphic data and provides access to the files of patients at high risk of CRC, allowing for their individual follow-up.Read more P540 Non-serious adverse events in patients with ulcerative colitis receiving etrasimod: An analysis of the phase 2 OASIS and phase 3 ELEVATE UC 52 and ELEVATE UC 12 clinical trialsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Etrasimod is an oral, once-daily, selective sphingosine 1-phosphate (S1P)_1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC). Adverse events (AEs) pertaining to tolerability, laboratory and serious AEs are described elsewhere^1,2; we present a post hoc analysis of the incidence, onset and duration of the most commonly occurring non-serious AEs in the etrasimod UC clinical programme.

Methods

Data from the pooled Placebo-controlled UC cohort, derived from the phase 2 OASIS (NCT02447302) and phase 3 ELEVATE UC 52 (NCT03945188) and ELEVATE UC 12 (NCT03996369) double-blind clinical trials, were included. Cohorts comprised OASIS and ELEVATE UC 12 12-week induction periods alongside the ELEVATE UC 52 12-week induction and 40-week maintenance periods utilising a "treat-through" design. Patients (pts) with moderately to severely active UC were eligible for the etrasimod UC clinical programme. Pts were randomised to etrasimod 1 mg once daily (QD; OASIS only), etrasimod 2 mg QD or placebo. Proportions and incidence rates (IRs) of non-serious AEs (MedDRA v24.1 Preferred Terms of headache, pyrexia, nausea, fatigue and dizziness) were analysed in the Placebo-controlled UC cohort.

Results

Among 943 pts (any dose of etrasimod, N=629 [288.1 pt years (PY)]; placebo, N=314 [115.1 PY]), there were 77, 36, 30, 15 and 23 headache, pyrexia, nausea, fatigue and dizziness AEs, respectively. All were non-serious and did not lead to treatment discontinuation, apart from one case of pyrexia in which early termination visits were incomplete. Proportions and IRs (per 100 PY) for headache and dizziness AEs were higher with etrasimod (any dose) vs placebo (IRs: 13.45 vs 8.63 and 6.52 vs 1.69, respectively); IRs for other non-serious AEs were similar in etrasimod (any dose) and placebo groups (Table). Onset of AEs varied over time and most AEs were short in duration (Figure shows onset and duration for headache and dizziness AEs). Most AEs were deemed not related to study treatment by the site investigator. Pts with dizziness on Days 1–3 had similar changes in heart rate vs those with dizziness after Day 3. No consistent trend in heart rate was observed in pts receiving etrasimod with early dizziness.

Conclusion

Among pts in the etrasimod UC clinical programme, all headache, pyrexia, nausea, fatigue and dizziness events were non-serious. IRs were similar for most non-serious AEs across treatment groups, excluding headache and dizziness. Most non-serious AEs were short in duration and judged as not related to study treatment, suggesting they may not impact on the overall tolerability of etrasimod.References1. Sandborn WJ et al. Gastroenterology 2020; 158: 550–61.2. Sandborn WJ et al. Lancet 2023; 401: 1159–71.Read more P541 Long-term follow-up results of darvadstrocel for complex perianal fistulas in patients with Crohn's disease: 3-year outcomes from a Japanese phase 3 studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Darvadstrocel (DVS), a suspension of expanded human allogeneic mesenchymal stem cells extracted from adipose tissue, is for the treatment of complex perianal fistulas in patients with Crohn's disease (CD). In Japan, DVS was approved in 2021 based on the Japanese phase 3 study Week 52 data combined with the pivotal study ADMIRE-CD data. Patients who participated in the Japanese study were monitored for 3 years, and we report the results at Week (W) 156.

Methods

This was an open-label, uncontrolled, phase 3 study (converted to a post-marketing clinical study after approval) conducted from March 2019 to February 2023 in Japan. Subjects had complex Crohn’s perianal fistulas (CPF) refractory to conventional treatments with a maximum of 2 internal openings (IO) and 3 external openings (EO). The fistula tract was curetted approximately 2-3 weeks before DVS administration, and a drainage seton was placed. On the day of administration, seton was removed, fistula tracts were curetted again, and IO was sutured. A total of 24 mL of DVS (including 120x10⁶ cells) was administered around the IO and into the wall of fistula tracts. During the 2-year follow-up period after W52, medical and surgical treatment for CD and CPF was given as needed, and subjects were assessed every 6 months.

Results

22 Japanese patients were enrolled from 9 sites. The mean (SD) age was 36.4 (10.4) years, 63.6% were male, and the mean (SD) duration of CD was 11.3 (6.6) years. By W156, most frequently reported adverse events (AE) were anal fistula (7/22), proctalgia (7/22), and nasopharyngitis (6/22). New serious AE occurred after W52 were found in 9 subjects: COVID-19 (4), CD (2), perianal fistula, small bowel obstruction, premature labour (1 each). None of these were considered DVS-related. At W156, the combined remission rate (clinical and MRI assessment) was 15/22 (68.2%, 95% CI [48.7%, 87.6%]), clinical remission rate (clinical assessment) was 15/22 (68.2%, 95% CI [48.7%, 87.6%]), response rate (no drainage from ≥50% of treated EOs) was 20/22 (90.9%, 95% CI [78.9%, 100.0%]), and relapse rate (at least 1 relapse by W156 after achieving remission at W52) was 3/15 (20.0%, 95% CI [0.0%, 40.2%]). Mean Perianal Disease Activity Index (PDAI) total score (SD) was 4.8 (2.2) at baseline, which was decreased to 2.1 (2.1) at W52, and 1.7 (2.0) at W156. Mean Crohn's Disease Activity Index (CDAI) total score (SD) was 94.3 (60.1) on the day of administration, which was decreased to 73.7 (73.6) at W52, and 71.4 (51.2) at W156.

Conclusion

This is the first prospectively observed clinical outcomes in CPF for 3 years after DVS administration. There were no new safety findings, and fistula remission observed at W52 was maintained until W156.Read more P542 Clinical decision support tool guided selective intensive induction strategy of ustekinumab in patients with Crohn’s disease: real-world evidenceWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Clinical decision support tool (CDST) of ustekinumab (UST) can predict the possibility of drug response¹. However, the potential benefits of initial intensification induction therapy (IIT) to improve clinical outcomes for different responders has not been explored². We aimed to evaluate the effectiveness and safety of the strategy of initial IIT for Crohn’s disease patients who exhibit varying responses based on UST-CDST.

Methods

This is a multicenter retrospective study included active Crohn’s disease patients who were low, intermediate and high probability responders according to UST-CDST (Figure 1). IIT was defined as intensive induction by 2 or 3 initial doses of a weight-based intravenous UST. The patients treated with standard therapy (ST) were identified as controls. The primary endpoint was corticosteroid-free clinical remission (CFCR) at week 24. The secondary endpoint was clinical remission, clinical response, endoscopic remission, endoscopic response, and CRP normalization at week 24. Propensity-matched analyses were applied to ensure comparability.

Results

A total of 296 patients were included, with 69 patients receiving IIT and 227 patients receiving ST. At week 24, in low-intermediate probability responders, IIT group was associated with higher rates of CFCR (72.3% vs 43.0%, OR 3.47 [95%CI 2.15-5.68], clinical remission (77.3% vs 47.1%, OR 3.82 [95%CI 2.33-6.37]), clinical response (78.1% vs 60.1%, OR 2.37 [95%CI 1.43-3.97]), endoscopic remission (50.6% vs 22.4%, OR 3.55 [95%CI 1.65-7.92]) and endoscopic response (83.1% vs 44.1%, OR 6.23 [95%CI 2.75-15.26]). CRP normalization were comparable. In high probability responders, all end points did not demonstrate statistically significant differences (Table 1). The cut-off UST trough concentration for predicting corticosteroid-free clinical remission was determined to be 1.43µg/mL, with an area under the curve (AUC) of 0.612, a sensitivity of 55.0%, and a specificity of 70.0%. No serious adverse events occurred.

Conclusion

Initial dose intensification induction in low-intermediate responders based on UST-CDST was superior to the ST in both clinical and endoscopic remission at week 24, which provide a novel strategy for stratifying patients at baseline.1. Park J, Chun J, Yoon H, Cheon JH. Feasibility of a Clinical Decision Support Tool for Ustekinumab to Predict Clinical Remission and Relapse in Patients With Crohn's Disease: A Multicenter Observational Study. Inflamm Bowel Dis. 2023;29(4):548-554.2. Ren H, Kang J, Wang J, et al. Efficacy of Ustekinumab Optimization by 2 Initial Intravenous Doses in Adult Patients With Severe Crohn's Disease [published online ahead of print, 2023 Aug 24]. Inflamm Bowel Dis. 2023; izad184.Read more P543 Patients in trials of moderate-to-severe UC who are exposed to placebo are more likely to suffer harm than those receiving active treatment: The lack of clinical equipoise in traditional study designsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Ulcerative Colitis (UC) is a relapsing-remitting inflammatory disease of the colon and rectum. There are many challenges to the recruitment of eligible individuals into clinical trials for IBD, including the availability of multiple standard-of-care treatment options and patient refusal to participate in randomized placebo (PBO)-controlled trials due to fear of receiving PBO. Patient harm across clinical trials for moderate-to-severe UC has not been adequately examined. We sought to quantify the potential harm to patients recruited to PBO.

Methods

We reviewed phase 3 clinical trials of therapies for moderate-to-severe UC including anti-TNF-alpha (infliximab, adalimumab, golimumab), anti-integrin (vedolizumab), anti-interleukin (IL) 12/23 (ustekinumab), anti-IL23 (mirikizumab, guselkumab), Janus kinase inhibitors (tofacitinib, upadacitinib), and sphingosine-1 phosphate receptor modulators (ozanimod, etrazimod). We analyzed the proportions (# of pts. with events/cohort size) of adverse events (AEs), serious adverse events (SAEs), disease exacerbation AEs (DEAEs), and disease exacerbation SAEs (DESAEs). We calculated Number Needed to Harm (NNH = 1/Incidence rate in cohort) for PBO (NNH_PBO) and experimental therapy (NNH_Rx) in each trial. Maintenance phase NNHs were categorized as treat-through (TT) or re-randomized (RR).

Results

We identified an increased probability of AEs in the PBO arm of 7/11 induction (NNH_PBO= 2.18-11.06; NNH_Rx=2.47-16.52), 1/8 TT maintenance, and 5/11 RR maintenance (NNH_TTPBO = 1.2-3.1; NNH_TTRx =1.1-16.4; NNH_RRPBO = 1.3-10.8). We identified an increased probability of SAEs for 8/11 induction (NNH_PBO=14.5-58.0; NNH_Rx=22.13-101.0), 4/8 TT, and 5/11 RR (NNH_TTPBO = 3.9-23.3; NNH_TTRx =4.2-29.9; NNH_RRPBO = 8.8-35.0). Patients were at increased probability of DEAEs in the PBO arm of 8/11 induction (NNH_PBO=7.38-43.20; NNH_Rx=12.50-106.33), 7/8 TT, and 7/10 RR (NNH_TTPBO = 3.0-11.1; NNH_TTRx =4.3-15.0; NNH_RRPBO = 2.7-25.2). DESAEs were at increased probability of harm in the PBO arm of 8/9 induction (NNH_PBO=29.00-116.00; NNH_Rx=47.43-119.75), 3/5 TT, and 7/10 RR (NNH_TTPBO = 14.4-52.0; NNH_TTRx =13.2-230.0; NNH_RRPBO = 11.2-25.2).

Conclusion

In PBO-controlled clinical trials of therapies for moderate-to-severe UC, there are increased AEs and SAEs for patients who receive PBO, especially for DEAEs and DESAEs. Induction treatment responders re-randomized for maintenance to PBO experienced greater harms (i.e. lower NNH) than TT PBO patients. These findings raise concern about clinical equipoise in moderate-to-severe UC clinical trials and support ongoing efforts to design trials with active comparator arms and adaptive or platform methodologies.Read more P588 Evolution and management of inflammatory joint pathology with non-anti-TNF therapies in inflammatory bowel diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The role of ustekinumab (UST) and vedolizumab (VDZ) in articular extra-intestinal manifestations of IBD remains unclear and most existing studies are retrospective. The aim of this study is to analyze the incidence of new onset or worsening of a preexisting IBD-associated arthropathy in patients treated with UST and VDZ.

Methods

An observational prospective study in a tertiary care University hospital was conducted. IBD patients undergoing treatment with VDZ or UST with previous spondyloarthritis (SpA) or new onset arthropathy were included. Articular manifestations were evaluated by a rheumathologist within 72 hours. IBD and rheumatological related variables were assessed at baseline and after 6 months, including demographics, clinical, biochemical, endoscopic and ultrasound data.

Results

201 patients were on treatment with UST and VDZ. Of these, 80 were referred to rheumatology for previous SpA or symptoms onset. 56 (70%) with VDZ and 24 (30%) with UST. 24 (30%) of them were classified as SpA: 22 (92%) had a previous diagnosis and 2 (8%) debuted during treatment with VDZ or UST. The remaining 56 (70%) were diagnosed with other rheumatological pathologies. Type of arthritis was: peripheral arthritis, 11 (46.4%); axial, 7 (29%) and mixed, 6 (25%).Most patients had received 1 or 2 biological therapies (73%), 90% of them were anti-TNF experienced. 48% of patients received UST or VDZ in monotherapy, without disease-modifying antirheumatic drugs (DMARDs).The most frequent type of arthritis in patients with previous SpA was peripheral (50% peripheral only and 18% mixed). Joint activity remained stable or even improved in these patients. Only 2 (9%) had axial disease flare-up, one with UST and one with VDZ. Both patients had moderate intestinal activity (C-reactive protein; CRP > 2.5 mg/dl and faecal calprotectin; FC > 600 ug/g). Treatment was not discontinued in any case.SpA debuted in 2 patients with mixed arthritis on treatment with VDZ. Both patients also had poor IBD control (CRP > 3.5 mg/dl and CF > 600 ug/g). A change of biologic therapy was performed in addition to adjusting treatment with concomitant DMARDs.

Conclusion

In our experience, treatment with UST and VDZ did not worsen joint pathology in patients with SpA. Most of them remained stable or improved. Patients with joint flare-ups also had poor control of bowel activity, which could be the main cause of worsening SpA.Read more P589 Real-world data on upadacitinib in the treatment of inflammatory bowel disease: safe and highly effective with extremely positive patient feedbackWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Upadacitinib is a selective Janus kinase inhibitor that has recently been approved in England for the treatment of ulcerative colitis (UC) and Crohn’s disease (CD) though real-world data is lacking. Furthermore, there is very limited information available on patient reported experiences of treatment with a small molecule compared with biological therapies. The object of this study was to provide real-world data on the efficacy of upadacitinib in the treatment of IBD in conjugation with collecting specific patient-reported feedback on acceptability and experience of treatment with upadacitinib.

Methods

We prospectively collected data on all IBD patients treated with upadacitinib between November 2022 and November 2023 in a large NHS Trust serving approximately 1% of the population of England. The primary objective was to assess patient response to induction at 8 weeks (UC) and 12 weeks (CD). Demographic details, biochemical markers (faecal calprotectin and CRP) and disease activity scores were recorded. We also undertook a bespoke anonymised electronic survey to assess the patient experience and views on treatment with upadacitinib in comparison to previous treatments.

Results

Forty-two patients were included in the study (34 UC/8 CD). The average age was 41 (range 18-76) and 27 (64%) were male. 11/34 UC patients were biologic naïve. All CD patients were biologic experienced with the majority exposed to an anti-TNF, vedolizumab and ustekinumab. Overall, 34/40 (85%) patients responded to induction treatment based on disease activity scores (27 UC, 7CD), with 68% (22 UC, 5 CD) in remission. Data was missing for two patients. Response rates were similar between biologic naïve and biologic exposed patients (82% and 86% respectively). In the UC cohort, mean calprotectin at baseline improved from 1718ug/g (range 8-6000ug/g) to 311ug/g (4-3014ug/g). In the CD cohort, mean calprotectin improved from 1719ug/g (115-5874ug/g) to 314ug/g (4-917ug/g). 3/42 (7%) of patients discontinued upadacitinib due to disease progression with the remaining 93% continuing treatment. Our patient survey results revealed very high satisfaction with treatment (85%), with the vast majority preferring treatment with upadacitinib to their previous biological therapy.

Conclusion

In this real-world study, induction therapy with upadacitinib was well tolerated and demonstrated good efficacy with excellent response and remission rates in a mixed patient cohort that included many with highly refractory disease. No unexpected safety signals were seen. The patient experience was overwhelmingly positive. If this data is replicated in larger studies there is an increasingly strong rationale for introducing upadacitinib earlier in the sequencing of advanced therapies.Read more P590 Use of upadacitinib in Refractory Paediatric Inflammatory Bowel Diseasein: A Single-Center Cohort StudyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Upadacitinib (UPA) is a novel selective JAK-1 inhibitor that has demonstrated efficacy in the treatment of ulcerative colitis (UC) and Crohn's disease (CD) and has received regulatory approval in adults only. Current data on the efficacy of this drug in children are limited. We report our experience in the treatment of pediatric patients with UC and CD with failure of immunosuppressive and biologic therapies. The aim of this study was to evaluate short-term effectiveness and safety UPA therapy in children with IBD.

Methods

Disease activity was monitored using clinical PUCAI/PCDAI scores, faecal calprotectin (FC), C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), platelet. Hemoglobin (Hb), leukocyte, total cholesterol, prothrombin time, INR - international normalized ratio, fibrinogen, activated partial thromboplastin time, thrombin time were evaluated to assess side effects. At baseline biochemical and previous therapies were recorded.

Results

We performed a prospective analysis of clinical outcomes from January to October 2023 during UPA therapy 11 children aged 12 to 16 years (4 boys, 7 girls) 3 with UС and 8 with CD. All 11 children had received immunosuppressive and biological therapies prior to UPA prescription without success. UPA induction was administered in UC for 8 weeks and CD for 12 weeks at a dose of 45 mg once a day, then 15 mg once a day as maintenance. At the beginning 2 (18%) of 11 children had high PUCAI/PCDAI disease activity and remain 9 (82%) had mild disease activity. Elevated white blood cells was determined in 3 (27%) out of 11 children, platelet increase in 9 (82%) children, and Hb less than 110 g/L in 6 (54%) children, elevation of ESR and CRP was observed in 7 (63%) subjects. FC was elevated in 5 (62.5%) out of 8 children. Total cholesterol was normal in all patients, coagulation tests showed increased fibrinogen in 3 out of 11 children. After induction 3 (27%) of 11 children achieved remission and 8 (73%) had clinical response according to the PUCAI/PCDAI score. Elevated white blood cells was detected in 2 (18%) and decrease Hb persisted in 3 (27%) out of 11 children, elevation of ESR persisted in 5 (45%) and CRP in 6 (54%) of 11 children. FC was elevated in 6 (75%) out 8 patients. Total cholesterol and the coagulation tests remained within normal range. Side effects were not observed and UPA maintenance treatment was continued in all children.

Conclusion

In this real-world experience in drug-resistant pediatric patients with UC and CD we verified the efficacy and safety of UPA, but longer follow-up is needed.Read more P591 Treatment of microscopic colitis: retrospective analysis of consecutive single centre patientsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Microscopic colitis (MC) is a chronic autoimmune inflammatory condition of the colon that causes watery diarrhoea along with other symptoms like bowel incontinence. MC is a benign condition with no increase in cancer risk or impact on survival but it usually requires treatment due to significantly impaired quality of life. Even though MC therapy is symptom oriented, recent studies have shown that almost half the patients require long-term medical treatment.

Methods

A retrospective analysis of consecutive MC patients treated in Lithuanian University of Health Sciences Hospital Kauno Klinikos over the last 6 years was performed. Patient characteristics and clinical information was obtained from electronic records.

Results

94 MC patients were treated in our centre since 2017, 46 (49 %) with collagenous colitis (CC), 39 (41.5 %) with lymphocytic colitis (LC), 2 (2.1 %) with incomplete CC and 7 (7.4 %) with incomplete LC. 77 patients were female (82 %). Median age was 59 years [44.8-70.3]. There was a tendency for men to be younger (median 42 [37-68]) than women (median 60 [50-70.5]) but not significantly (p>0.05).During the 6-year period 67 patients (71.3 %) were treated with budesonide, 33 (35.1 %) received only one course and went into clinical remission while 34 (36.2 %) needed either multiple courses or continuous treatment for relapsing or chronic active disease respectively. Primary non-response to budesonide wasn’t documented in any patient. 8 patients (8.5 %) were treated with azathioprine due to budesonide dependency or intolerance but it was discontinued in all but 1 patient due to lack of response or adverse events. 3 patients (3.2 %) were treated with biological therapy. 1 patient was treated with adalimumab which was discontinued due to adverse events, 1 was treated with infliximab which was switched to vedolizumab due to loss of response, and 1 was treated with vedolizumab which was switched to adalimumab due to primary non-response. At the time of analysis 61 patients (64.9 %) were receiving no active treatment, 21 (22.3 %) were receiving intermittent courses of budesonide, 6 (6.4 %) had been prescribed budesonide on demand, 3 (3.2 %) were taking budesonide continuously, 1 (1.1 %) was taking azathioprine and 2 (2.1 %) were on biological therapy. There was no difference between CC and LC patients.ConclusionA little less than half of the patients needed long-term medical treatment. While budesonide was widely used and usually effective, we observed a need for advanced therapies as well.Read more P592 Higher predictive power of epigenetic signatures for response to vedolizumab and ustekinumab in anti-TNF naïve patients with active Crohn’s diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Despite the significant progress in IBD care with biological therapies, the current 'trial-and-error' method remains suboptimal. Previous results from our EPIC-CD study demonstrated that two distinct epigenetic panels of 25 and 68 DNA methylation markers, respectively, were associated with (non-)response to vedolizumab (VDZ) and ustekinumab (USTE) in active Crohn’s disease (CD)¹. Data from clinical trials have demonstrated that response rates in patients naïve to biological treatment are higher. We therefore aimed to evaluate the performance of our models in bionaive and anti-TNF exposed subpopulations.

Methods

We prospectively measured peripheral blood DNA methylation profiles from 184 adult CD patients prior to treatment with VDZ or USTE in a discovery (n=126) and independent validation (n=58) cohort using the Illumina EPIC BeadChip array. Between 26 and 52 weeks, patients were categorized as responders or non-responders based on a combination of endoscopic response (≥50% reduction in SES-CD score), steroid-free clinical response (≥3-point drop in Harvey-Bradshaw Index (HBI) or HBI ≤4 AND no systemic steroids), and/or biochemical response (≥50% reduction in C-reactive protein (CRP) and fecal calprotectin or a CRP ≤5 g/mL and fecal calprotectin ≤250 µg/g). Epigenetic biomarker identification and classification analyses were conducted through stability selection gradient boosting on the discovery cohort. Subsequently, the performance of the identified epigenetic biomarkers was assessed independently on the validation cohort, with patients stratified by prior anti-TNF exposure.

Results

Out of the 58 patients in the validation cohort, 25 received treatment with VDZ, and 33 with USTE, with 52% (n=13) and 36% (n=12) respectively naïve to anti-TNF treatment. Baseline characteristics between anti-TNF naive and anti-TNF exposed patients showed no significant differences, despite a slight significant age difference in the vedolizumab group, where anti-TNF exposed patients were significantly younger (table 1).In the overall independent validation cohort, the prediction models demonstrated an AUC of 0.75 for both VDZ and USTE. However, after stratification by prior anti-TNF exposure, we observed increased performance of our models among anti-TNF naive patients for both VDZ (AUC_non-exposed=0.85 versus AUC_exposed=0.66) and USTE (AUC_non-exposed=0.97 versus AUC_exposed=0.63 (figure 1).

Conclusion

Our findings demonstrate that prior anti-TNF exposure leads to somewhat reduced predictive power of our epigenetic models for Vedolizumab and Ustekinumab response. The predictive models may therefore find its optimal application in bio-naive patients, although they remain significant in anti-TNF exposed patients.Read more P593 Efficacy of Risankizumab in Patients With Moderately to Severely Active Ulcerative Colitis by Prior Advanced Therapy Failure and Mechanism of Action: Post Hoc Analysis of the INSPIRE and COMMAND Phase 3 StudiesWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Risankizumab (RZB), a monoclonal antibody targeting interleukin-23 p19, demonstrated superior efficacy compared with placebo (PBO) in the induction and maintenance of patients with moderately to severely active ulcerative colitis (UC) in the INSPIRE and COMMAND studies. Here, we evaluated whether RZB was an effective induction and maintenance therapy based on the number (0, 1, ≥ 2) and types of prior advanced therapies (ATs).

Methods

Eligible patients with an Adapted Mayo Score of 5-9 points and endoscopic subscore of 2-3 (confirmed by central reading) were randomised 2:1 (intravenous [IV] RZB 1200 mg [RZB1200] or PBO) for 12 weeks (wks) in the phase 3 induction substudy of INSPIRE. Clinical responders (per Adapted Mayo Score) to RZB IV treatment in phase 2b and phase 3 induction were randomised 1:1:1 (subcutaneous [SC] RZB 180 mg (RZB180), SC RZB 360 mg (RZB360), or withdrawn to PBO [withdrawal, WD]) for 52 wks in COMMAND. Efficacy and safety outcomes were assessed at induction wk 12 and maintenance wk 52 in patients who were non-advanced therapy-inadequate responders (non-AT-IR), had 1 or ≥ 2 AT failures, and among patients previously treated with tumor necrosis factor inhibitors, vedolizumab, or Janus kinase inhibitors.

Results

Proportions of AT-IR patients were similar across treatment groups for the induction (RZB1200 51.2% [333/650]; PBO 52.3% [170/325]) and maintenance studies (RZB180: 74.9% [134/179]; RZB360: 74.7% [139/186]; PBO [WD] 75.4% [138/183]). Significantly greater proportions of patients receiving RZB achieved the primary endpoint of clinical remission per Adapted Mayo Score at wk 12 vs PBO in the non-AT-IR and AT-IR subgroups (RZB1200: 29.7%, 11.4% vs PBO: 8.4%, 4.3%, respectively); consistent results were observed at wk 52 in patients treated with either RZB maintenance dose vs PBO (RZB180: 50.9%, 36.6%; RZB360: 61.7%, 29.5%; vs PBO [WD] 31.1%, 23.2%, respectively) (P ≤ .05, Fig. 1-2). Regardless of the number of prior AT failures or class of prior therapy, numerically higher proportions of patients treated with RZB achieved clinical remission, clinical response, endoscopic improvement, and histologic endoscopic mucosal improvement at wk 12 of induction and wk 52 of maintenance. Rates of treatment-emergent adverse events were similar among subgroups in induction and maintenance.

Conclusion

RZB induction and maintenance therapy was effective and well-tolerated in patients with moderately to severely active UC regardless of a patient’s prior experience with advanced therapies. Numerically higher efficacy was observed in non-AT-IR compared to AT-IR subgroups.Read more P594 One-year success rates of targeted therapy in Ulcerative Colitis patients revisitedWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Multiple new treatment options have been introduced in Ulcerative Colitis (UC) in recent years, leading peers to recommend a treat-to-target treatment approach, including mucosal or even histopathological healing. Patient-reported outcomes, and explicitly those validated on subjective patient-based values, are most commonly neglected in evaluating long-term treatment outcome while being of great importance in defining treatment success.We re-examined registration and prospective trials with at least one year follow-up to estimate chance of beneficial outcome for patients using the most modern, though surely most expensive, medication. We compared endoscopic improvement and improvement on patient-reported outcomes in the long-term follow-up of new drug therapies in biological naïve patients as a marker for treatment success.

Methods

We assessed long-term endoscopic outcome measures and patient-reported outcomes measures in major registration trials of new biologicals and advanced small molecules in the period 2000-2023 by examination of PubMed. In these trials almost all UC patients had to be 5ASA-, corticosteroid- and/or immune suppressive refractory before inclusion in study.

Results

In figure 1, an overview is shown of long-term endoscopic and PROM improvement endpoints in major registration trials.When focusing on endoscopic improvement or mucosal healing achieved by biologicals or advanced small-molecules in 5ASA-, corticosteroid- and/or immune suppressive refractory UC patients, most patients did not reach the pre-defined endpoint. In addition, although some registration trials report PROM data, improvement based on PROM’s is not consistently reported.

Conclusion

Reaching endoscopic improvement as definition of treatment success is unsuccessful in more than 60% of patients when accounted for placebo in all modern-era therapies for ulcerative colitis. As a consequence, when endoscopic treat-to-target treatment goals are strictly applied, surgery is warranted in more than 60% of UC patients within one year. Furthermore, lack of reporting of PROMs in registration trials complicate direct comparisons of alternative important endpoints.Read more P595 Assessment of mucosal healing after exclusive elemental diet using small bowel capsule endoscopy in paediatric Crohn’s diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Exclusive elemental nutrition (EEN) is an effective treatment for induction of remission and is recommended as first-line induction therapy in children with active luminal Crohn’s disease (CD). Evaluating treatment response is important because endoscopic or mucosal healing is associated with long-term outcomes, but it is difficult to perform repeated colonoscopies in children. Small bowel capsule endoscopy (SBCE) is used to diagnose small bowel lesions and is more convenient than colonoscopy. This study aimed to evaluate the improvement of small bowel mucosal lesions using SBCE in paediatric CD patients treated with EEN as induction therapy.

Methods

We retrospectively reviewed data from patients under 18 years of age who were newly diagnosed with CD and commenced EEN as induction therapy between May 2018 and April 2023. Among these patients, we included those who completed EEN for more than 6 weeks and underwent SBCE at both the time of diagnosis and within 2 weeks of completion of EEN. We analysed the proportion (%) of patients who achieved mucosal healing (defined as the Lewis score < 135) and patients exhibiting improvement in ulcers on the follow-up SBCE after EEN. We also compared the Lewis score, laboratory tests, and BMI z-score before and after EEN using the paired t-test.

Results

A total of 71 patients (57 males, 14 females) were included with a mean age of 13.3 ± 2.27 years (range 7-17 years). After 6 to 8 weeks of EEN, 64 patients (90.1%) showed improvement in ulcers on follow-up SBCE, including 35 patients (49.3%) with complete disappearance of ulcers and 29 patients (40.8%) with partial disappearance of ulcers. Seven patients (9.9%) showed no improvement. The Lewis score was significantly decreased (p < 0.001). In addition, mucosal healing, defined as the Lewis score < 135, was achieved in 28 patients (38%). When comparing laboratory tests before and after EEN, haemoglobin and albumin increased (p < 0.001), and ESR, CRP, and fecal calprotectin decreased significantly (p < 0.001). However, BMI z-score was not improved after EEN (p = 0.46).

Conclusion

Most patients showed improvement in ulceration on SBCE after EEN. Additionally, improvements in blood test and fecal calprotectin levels were noted following EEN. It is suggested that SBCE is a useful tool to evaluate mucosal healing after EEN in paediatric Crohn's disease.Read more P375 Histological activity predicts the risk of colectomy after biological treatment in biological-naive patients with Ulcerative ColitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Treatment failure with biological agents is common in patients with ulcerative colitis (UC), but the impact of baseline histological disease activity is unknown. We aimed to investigate the predictive role of histopathological findings for biological treatment failure in UC patients.

Methods

This is a sub-study of the Danish IBD Biobank Project. Adult bio-naïve patients with UC (n=129) were followed prospectively while undergoing biological treatment. Histological activity was assessed using the Nancy Index and the Geboes score in intestinal biopsies sampled before treatment. Endoscopic activity was assessed using the Mayo Endoscopic Subscore, and clinical activity was measured using the Simple Clinical Colitis Activity Index (SCCAI). Associations between histological activity and treatment outcomes were assessed in multivariable models which incorporated the following fixed covariates: age, gender, disease duration, body mass index >30, disease extent, the SCCAI, and the Mayo Endoscopic Subscore. Correlations between histological, endoscopic, clinical, and biochemical activity were assessed using Spearman’s rank correlation.

Results

Colectomy was needed in 17.1% (n=22) of UC patients during follow-up (Table 1). Histological activity at baseline measured using the Nancy Index was the only significant predictor of the risk of colectomy during follow-up (Nancy 2 vs. 4: HR 0.14, 95% CI 0.02-0.84, p=0.03; Nancy 3 vs. 4: HR 0.11, 95% CI 0.02-0.53, p=0.01) beside baseline haemoglobin concentration (HR 0.32, 95% CI 0.16-0.64, p<0.01. Figure 1). The risk of colectomy was also significantly predicted by a Geboes grade above 5.0 at baseline (HR 2.72, 95% CI 1.14-6.50, p=0.02). In contrast, endoscopic and clinical activity did not predict the risk of colectomy. At baseline, the Nancy Index and the Geboes score were moderately correlated to endoscopic activity, and weakly, but significantly correlated to biochemical markers haemoglobin, albumin, and C-reactive protein. Meanwhile, poor correlations were found between histological activity and clinical activity.

Conclusion

The risk of colectomy during biological treatment in bio-naïve UC patients was significantly predicted by histological disease activity, but not endoscopic or clinical disease activity. Our study suggests that histological assessment before initiating biological treatment should be encouraged in UC patients.

Funding

This study is funded by a restricted grant from Takeda A/S, Louis-Hansen Fonden, and a public fund hosted by Hvidovre Hospital.Read more P389 Comparative Evaluation of ChatGPT and Human Specialists in the Application of ECCO Guidelines for the Management of Inflammatory Bowel Diseases and Malignancies: A Proof-of-Concept StudyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Societal guidelines on colorectal dysplasia screening, surveillance and endoscopic management in inflammatory bowel diseases (IBD) are rather complex, and physician adherence to them is suboptimal.We aimed to evaluate the use of ChatGPT, a large language model, in generating accurate guideline-based recommendations for colorectal dysplasia screening, surveillance and endoscopic management in IBD in line with European Crohn’s and Colitis Organization (ECCO) guidelines.

Methods

Thirty clinical scenarios in the form of free text regarding colorectal dysplasia in IBD were prepared and presented to ChatGPT and four gastroenterologists, two of them specializing in IBD and two with non-IBD specialties. Two additional IBD specialists subsequently assessed all responses provided by ChatGPT and the four gastroenterologists, judging their accuracy according to ECCO guidelines.

Results

ChatGPT provided accurate recommendations in 90% of cases (27/30), while among the four gastroenterologists the correct response rates were 28/30 (93%), 23/30 (77%), 26/30 (87%), and 25/30 (83%). The latter two represent the correct response rates of the IBD experts.No statistically significant differences were observed between the accuracy of ChatGPT versus all gastroenterologists (p=0.44), or between the accuracy of ChatGPT versus the IBD experts and non-IBD expert gastroenterologists (p=0.71).

Conclusion

This study highlights the potential of language models in enhancing guideline adherence regarding colorectal dysplasia in IBD. Further investigation of additional resources and prospective evaluation in real-world settings are warranted.Read more P396 Bowel ultrasound training in European and Mediterranean Countries: results of a surveyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Bowel ultrasound (US) is a cost-effective, non-invasive, accurate, and readily available tool for the diagnosis and monitoring of patients with inflammatory bowel disease (IBD). Moreover, it can be an accurate tool in the hands of gastroenterologists for the initial assessment of patients with chronic and acute intestinal disorders -such as abdominal pain and diarrhoea- to rule in and out organic causes.Currently, it is not known how many European residents in gastroenterology or internal medicine who care for IBD patients have the opportunity to have a bowel US training. Tha aims of our study were to investigate the bowel US training in Europe and the perception of utility of this diagnostic technique.

Methods

The participants of the survey were residents from different Countries who voluntarily chose to take part in one of the two first editions of the bowel US course, one of the optional courses held during the UEG Summer School in Prague (2022 and 2023).Participants answered an initial test in a digital anonymous questionnaire.

Results

Among the 135 participants in the course, 104 (77%) answered all the questions. Respondents were from 28 European and Mediterranean area Countries.The majority of respondents (60.6%) were residents in their 3rd and 4th year of specialization (men 58.7%). Among the respondents, 61 (58.7%) stated they had a general abdominal US training period during their residency (62.5% of them reporting <100 exams performed). (Figure 1) It was not offered any bowel US training to 76% of residents. (Figure 2) Among the respondents, the Italian residents showed the highest probability to have a bowel US training (7/13, 53,8%). At a Likert scale, 96.2% stated that bowel US is important for their future profession (Figure 3) and 93.3% stated it is important for treatment decision in gastroenterology. (Figure 4)

Conclusion

Our survey reveals, despite the possible limits given by the response and selection bias, that in Europe bowel US training is deficient and heterogeneous.Only one every four participants received a bowel US training during their residency, despite bowel US knowledge is considered a necessary skill by approximately 95% of young gastroenterologists who participated in the course. Since less than 2/3 have a US period during their residency (often insufficient), it is likely that most residents interested in bowel US are forced to acquire this skill attending other specific courses during or after their residency.Solutions may be represented by the implementation of specific courses or with the institution of minimum bowel US training level during the residency.Read more P412 Faecal Calprotectin as a predictor of endoscopic and histologic remission in patients with Ulcerative ColitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Faecal calprotectin (FCP) is a reliable surrogate marker for disease activity in ulcerative colitis (UC). However, there are no consensus cut-off values for histoendoscopic remission. The aim of the study is to correlate FCP with Mayo Endoscopic Score (MES) and histological disease activity (Geboes score) of UC patients in clinical remission.

Methods

We performed a prospective study including adult UC patients at the McGill IBD Center between 2013 and 2017. Patients in clinical remission (partial Mayo score ≤2) or disease relapse, undergoing endoscopy for disease activity or dysplasia surveillance, were enrolled. Before bowel preparation, FCP was collected. MES was documented during colonoscopy. Biopsies were taken throughout the colon and histological activity was assessed using Geboes score (GS) by a blinded expert gastrointestinal pathologist.

Results

The study included 253 patients, of which 117 (46%) were male with a mean age of 38.2 years (standard deviation [SD] ± 24.8). 46% of the patients had pancolitis at the time of colonoscopy. 5-aminosalicylate were used by 68.4% of patients while 20.9% were on immunomodulators, 19% on biologics and 0.4% on small molecules as treatment. Regarding endoscopic correlation, it showed that an FCP ≥ 200 μg/g predicts MES > 1 despite clinical remission, yielding sensitivity of 59% and specificity of 74%. A FCP ≥ 123 predicts MES > 0 despite clinical remission (58% sensitivity and 70% specificity), also aiding to differentiate MES 0 from MES 1 (61% sensitivity and 70% specificity). As to histologic correlation, a FCP ≥ 80 μg/g identified histological disease activity using Geboes criteria (GS score > 3.1) in patients with clinical remission, yielding 64.7% sensitivity, 58.7% specificity and 77% positive predictive value (Figure 1). When using a GS score threshold of > 2, a cut-off value of FCP ≥ 50 μg/g, appears to be the most clinically relevant to identify patients in clinical remission who continue to have active histologic inflammation, with an 49.6% sensitivity, 41.6% specificity and 40% positive predict value. Results are summarized in Table 1.

Conclusion

FCP correlates very well with endoscopic and histologic disease activity and can be used as a surrogate marker for disease activity. Our study prospectively demonstrated the optimal cut-off values helping to discriminate endoscopic healing and histologic remission.Read more P413 Bowel Urgency in patients with Ulcerative Colitis: prevalence and association with clinical, endoscopic data and disabilityWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Bowel urgency (BU), identified as the sudden need for bowel movements, is increasingly being recognized as an impactful symptom in patients with ulcerative colitis (UC), distinct from stool frequency (SF) and rectal bleeding (RB). We aimed to assess the association of BU with patient-reported outcomes (PRO), including SF and RB, as well as clinical and endoscopic activity and disability in a real-world setting, using data from the IBD-Disk:Italian translation and validation study.

Methods

We conducted a cross-sectional multicentre study, consecutively including ≥ 18yo UC patients between February 2023 and October 2023. Demographic, clinical and endoscopic data were collected. Clinical remission was defined as partial Mayo score ≤ 1 and endoscopic activity as MES ≥ 1. All patients completed the following questionnaire for disability IBD-Disk and IBD Questionnaire-32 (IBDQ-32) for quality of life. BU was assessed using the question about regulating defecation in the past 7 days using a 10-point NRS ranging from 0 (absolutely disagree) to 10 (totally agree) from the IBD-DISK. RB was measured from question 22 of IBDQ and SF from question 1 of IBDQ-32, both using a 7-point NRS ranging from 0 (always) to 7 (never).

Results

209 UC patients with a median age of 37(IQR 28-52) were enrolled, 111(53.1%) being female. Overall, 31 (14.8%) had proctitis, 91(45.5%) had left colitis and 87(41.6%) had extended/pancolitis. The median pMAYO score was 4(IQR=2-6), while the median MES was 2(IQR=1-2). 75% patients (35.9%) reporting BU were more likely to have moderate clinical (pMAYO=5; IQR=3-6) and endoscopic activity of disease (median MES=2; IQR=1-2) compared to those without urgency (p< .0001). Additionally, BU was associated with a higher median rate of hospitalizations in the previous 12 months (Δ=1; p<0.001).Patients with BU reported a higher degree of RB(33.3%) and SF(50,7%) than patients without BU (p< .0001).Noteworthy, individuals with BU had higher median IBD-DISK total score (29; IQR=9-52) and lower scores for IBDQ-32 (168;IQR=138-196) compared to patients without BU [median IBD-DISK=17(IQR=5-39); median IBDQ-32=181,IQR=158-202), p<0.001]. In the univariate analysis, BU was associated with a higher IBD-DISK total score (OR=1.04,CI=1.02-1.06; p<0.001) and SF (OR=0.59,CI=0.45-0.78; p=0.001), without being associated with RB (p=0.57) and IBD-Q32 total score (p=0.84).

Conclusion

BU can be a surrogate marker for UC clinical and endoscopic activity. Our findings suggest that it is an independent factor from RB and it is associated with disability. Hence, it can be considered as an additional key PRO in UC. However, a systematic standardized approach for BU definition and assessment is strongly awaited to incorporate it as treat-to-target measureRead more P432 Real-time automated assessment of histological disease activity in patients with ulcerative colitis using single wavelength endoscopy technologyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Assessment of mucosal healing as a key denominator in the treat-to-target strategy for managing ulcerative colitis remains challenging. To address this, objective evaluation of histological disease activity holds promise. Recent offline research shows encouraging results using a new deep-learning convolutional neural network based on single wavelength endoscopy technology (SWE-CAD) (Fujifilm Co, Japan). We aimed to validate the real-time performance of a new bedside prototype SWE-CAD model during standard colonoscopy.

Methods

A bedside module for real-time use was integrated in the endoscopy room to evaluate histological disease activity in patients with ulcerative colitis with Mayo Endoscopic Scoring (MES) ranging between 0 and 3. Imaging was performed in rectum and sigmoid following a standardized protocol based on white light and SWE (i.e. monochromatic light of 410nm). Biopsies were taken as reference at the center of the imaged region and were scored for the Geboes score (GBS). The SWE-CAD output was displayed on the separate monitor of the bedside module as a blue or red-colored indication, corresponding to histological remission or non-remission, respectively. Each region (2 in rectum and 2 in sigmoid) was simultaneously scored for MES by the endoscopist.

Results

In a total of 36 patients histological disease activity was automatically scored using the SWE-CAD. On a section level this CAD-system showed an accuracy of 96.4%, corresponding sensitivity was 99.3% and specificity was 85.5%.When differentiating for disease activity as mild, moderate and severe, accuracy was 97.7%, 62.8% and 95.0%, respectively. On a per-patient level, overall diagnostic accuracy remained high with 94.4%, with only 2/36 underestimations when compared to GBS.

Conclusion

In this pilot trial, we successfully tested a novel CAD-system, utilizing SWE technology, for real-time assessment of histological disease activity in patients with UC. The system demonstrated exceptional clinical accuracy at 94.4% per-patient level, potentially aiding physicians in interpreting subtle endoscopic abnormalities, leading to cost-effective and individualized patient management.Read more P433 Short-term outcomes of surgical treatment in primary ileocecal Crohn’s disease patients. Results of Crohn’s(urg) study, multicenter, retrospective, comparative analysis between indications for luminal and complicated phenotypeWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Recent evidence challenges the current standard of offering surgery to patients with ileocecal Crohn’s disease only when they present complications of the disease.

Methods

A retrospective, multicenter comparative analysis was performed including patients operated for primary ileocecal CD at 12 referral centers. Patients were divided in 2 groups, according to indication of surgery for inflammatory (ICD) or complicated (CCD) phenotype. Short-term results were compared. Patients operated on for primary isolated ileocaecal CD (last 50 cm of the terminal ileum and cecum), either for predominantly inflammatory phenotype or for complications of the disease (stricturing or fistulizing pattern), between January 2012 - December 2021 were considered eligible to participate in this study. Patients with previous abdominal procedures for CD, and patients who had activity of the disease in other intestinal segments other than the ileocaecal region at the time of surgery, were excluded from the study.

Results

2013 patients were included, 291 (14.5%) in the ICD group. No differences were found between groups in time from diagnosis to surgery or in the levels of exposure to biologic drugs before indication of surgery. CCD patients had higher rates of low BMI, anemia (40.9 vs. 27%, p: < 0.001), and low albumin (11.3 vs. 2.6%, p: < 0.001). CCD patients had longer operations, lower rates of laparoscopic approach (84.3 vs. 93.1%, p: 0.001), and higher conversion rates (9.3 vs. 1.9%, p: < 0.001). CCD had longer hospital stay and higher postoperative complication rates (26.1 vs. 21.3%, p: 0.083). Anastomotic leakage and reoperations were also more frequent in this group. More patients in the CCD group required an extended bowel resection (14.1 vs. 8.3%, p: 0.017). In multivariate analysis, CCD was associated with prolonged surgeries (OR: 3.44, p: 0.001) and requirements of multiple intraoperative procedures (OR: 8.39, p: 0.030).

Conclusion

Indication of surgery in patients who present an inflammatory phenotype of CD was associated with better outcomes when compared to patients operated on for complications of the disease, without a difference between groups in time from diagnosis to surgery.Read more P450 Influence of radon levels at home in the clinical course of inflammatory bowel disease incident patientsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Inflammatory Bowel Diseases (IBD) are a group of pathologies of unknown etiology associated with some environmental factors, only partially identified. The role of indoor radon, a radioactive gas, has not been formally studied and it might play a role on the evolution of the disease. The aim of this study is to analyze if residential radon exposure is associated with the evolution and development of flares or hospitalizations of IBD new diagnosed patients in a radon-prone area.

Methods

An observational prospective study was developed between June 2020 and September 2023, including incident cases with IBD that had been living at least 5 years in the same dwelling, those with a change of address in the last 5 years prior to diagnosis were excluded. All patients were followed-up through one year to assess the evolution of the disease. Hospitalizations related with the disease during the period, and number and severity of flares (measured by Partial Mayo Score and Harvey- Bradshaw) were collected. Radon levels were measured over three months in the participants’ home. Each individual was provided with a residential radon meter (a RSKS trace detector), given and read by the Galician Radon Laboratory, a certified radon laboratory. Radon concentrations were categorized into three groups, 0-99 Bq/m³, 100-299 Bq/m³ and >299 Bq/m³. Results are expressed as Odds Ratios with their 95%CI obtained through logistic regression.

Results

136 patients with IBD (78 ulcerative colitis, 52 Crohn’s disease and 6 unclassified colitis) were included and prospectively followed, with a median age of 52 years old (IQR 40 – 59). 50% were females. There were no statistically significant differences in radon levels, taking levels of 0-99 Bq/m³ as reference, between patients hospitalized compared with non-hospitalized (OR 0.8 95%CI 0.3-2.1 for 100-299 Bq/m³, OR 1.7 95%CI 0.6-5.0 for >299 Bq/m³) nor in patients with a flare compared with patients without flares during the follow-up year (OR 0.4 95%CI 0.0-4.5 for 100-299 Bq/m³, OR 5.4 95%CI 0.8-34.3 for >299 Bq/m³). Radon levels were not associated with the number of flares either (OR 0.6 95%CI 0.3-1.7 for 100-299 Bq/m³, OR 1.5 95%CI 0.5-4.5 for >299 Bq/m³). Results are shown in table 1. Stratifying by type of IBD, results do not vary. For Crohn’s disease, OR for flare are 2.5 (95%CI 0.4-16.1) and 4.1 (95%CI 0.6-27.9), and for hospitalization 1 and 6.5 (OR95% (0.2-205-2). For ulcerative colitis, OR for flare are 0.6 (95%CI 0.2-1.8) and 1.8 (95%CI 0.4-7.8) and for hospitalization 0.9 (95%CI 0.1-17.1) and 9.3 (95%CI 0.6-134.0).

Conclusion

Indoor radon concentration seems to be not associated with an initial worst evolution of IBD patients in terms of hospitalizations or flares.Read more P451 Specific Oral Manifestations in Patients with Crohn's DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Extra-intestinal manifestations of Crohn's disease (CD), including arthropathic, mucocutaneous, ophthalmic and hepatobiliary disorders, have a prevalence ranging from 16.7% to 40%. Oral manifestations of CD are classified into specific manifestations directly related to intestinal inflammation and non-specific manifestations. The aim of this study was to determine the frequency and characteristics of specific oral manifestations in patients with CD.

Methods

We retrospectively evaluated 676 patients with CD who were followed up for at least 6 months between June 2013 and February 2023 at our tertiary care center. Specific oral lesions were clinically defined as cobblestoning, orofacial granulomatosis, lip/cheek swelling with fissuring, and pyostomatitis vegetans. Confirmation of specific lesions was made by experienced dentists for each case.

Results

Of the 676 CD patients (58.9% male, median age 38 years) followed for 6.83 years (IQR 3.45-11.76 years), 96 (14.2%) had oral lesions. Specific oral lesions were found in 8 patients (1.2%), while 88 (13.1%) had non-specific lesions. The specific lesions included cobblestoning (n=2), orofacial granulomatosis (n=3), glossitis with fissuring (n=2), and lip swelling with fissuring (n=2). Patients with specific lesions were predominantly male (75%) with a median age of 46.5 years (range 23-68 years). Disease location was ileal (25%), colonic (25%), and ileocolonic (50%), with perianal disease in 50%. Disease behavior was inflammatory in 7 and penetrating in 1 patient. Three patients were active smokers. Three patients had prior major abdominal surgery. Concurrent extraintestinal manifestations included peripheral arthritis/arthralgia (n=7), sacroiliitis (n=1), and uveitis (n=2). Immunomodulators were used in 7 patients and biologics in 5 patients. All specific lesions were associated with active disease (median CRP 35.5 mg/L, range 6-151 mg/L; median CDAI 313, range 227-480) and improved with immunomodulator or biologic therapy.

Conclusion

In this large cohort of CD patients, the frequency of specific oral manifestations was 1.2%. These lesions were associated with active disease and improved with immunosuppressive treatment, highlighting the need for close collaboration between gastroenterologists and dentists for early recognition and optimal management.Read more P484 Intestinal Ultrasound Can Detect Active Inflammation In Inflammatory Bowel Disease Patients Despite Combined Clinical And Biomarker RemissionWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Intestinal ultrasound (IUS) has only recently been implemented in the USA for inflammatory bowel disease (IBD) monitoring. Colonoscopy is considered the gold standard for evaluation of inflammation but may not be feasible for every assessment due to cost, time, and accessibility. Clinical activity scores and biomarkers are used instead as adjunct measures of disease. Since IUS incurs low cost and time with easy accessibility, our study aimed to demonstrate the utility of incorporating IUS into IBD practice by evaluating the sensitivity and specificity of these adjunct measures of inflammation and the impact of decisions made based on IUS.

Methods

This retrospective cohort analysis evaluated patients with IBD at our institution who underwent IUS from July 2020 to May 2021. The patients were reviewed for repeat IUS visits until July 2022. Patients received IUS regardless of clinical or biomarker remission, and/or if they were able to receive a colonoscopy. Clinical remission was defined as UCAI ≤ 5 and partial Mayo ≤ 2 or HBI ≤ 5. Biomarker remission was defined as ESR ≤ 40 mm/hour; CRP ≤ 8 mg/L; FCP ≤ 125 mg/mg; and fecal lactoferrin ≤ 30 mcg/mL. Combined remission was defined as both clinical and biomarker remission. The sensitivity and specificity of these groups was evaluated based on IUS. Treatment plans were decided based on IUS findings. Patients with normal IUS maintained therapy while those with positive findings required a change/escalation of therapy. These patients had repeat IUS to ensure the changes resulted in reduction of inflammation.

Results

In 148 total patients receiving IUS, 62% (N=92) had active disease. Clinical remission (figure 1) was 41% sensitive and 75% specific while biomarker remission was 49% sensitive and 58% specific to IUS findings. When combined (clinical + biomarker remission), sensitivity increased to 62% and specificity decreased to 52% (figure 2). There was a total of 39 repeat ultrasounds. Inflammation was improved at repeat IUS, measured by a decrease in overall bowel wall thickness in 77% (30/39) patients for a mean of 0.121 cm. Vascular flow improved in 79% (15/19) of patients with abnormal Doppler at initial IUS by a mean of 0.65, and mural stratification improved in 80% (20/25) of patients with mural disruption at initial IUS.

Conclusion

Our study showed that even when combining biomarker results and clinical scores, the sensitivity for detecting inflammation was 62%. Additionally, as demonstrated by the improvement in inflammation at IUS follow up, clinical decisions based on IUS results effectively reduced inflammation in IBD patients. As such, IUS is necessary in the management of IBD to effectively identify and treat patients with masked inflammation.Read more P485 Do intestinal ultrasound scores have a role in the diagnosis of post-operative recurrence?Wed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Ileocolonoscopy and Rutgeerts endoscopic score remains the gold standard to evaluate post-operative recurrence (POR) in Crohn's disease (CD) patients. Intestinal ultrasound (IUS) is proposed as a non-invasive alternative to ileocolonoscopy for the diagnosis of POR, with a sensitivity of 94% and specificity of 84%. There are several IUS scores that evaluate CD disease activity such as SUS-CD (validated), IBUS-SAS and Simple US Score, which have not yet been studied in the diagnosis of POR. The aim of this study is to assess whether IUS parameters and ultrasound scores correlate with endoscopy in the diagnosis of POR.

Methods

A unicentric retrospective study was performed. There were included patients with CD with both an ileocolonoscopy and intestinal ultrasound performed for the detection of POR, the time between tests was less than 6 months and there was no therapeutic change between tests. Endoscopic POR was evaluated with Rutgeers score (RS), considering POR RS ≥i2b. In IUS, were used: Simple US Score, SUS-CD and IBUS-SAS.

Results

103 patients were included, baseline characteristics are in Table 1. 30 patients (29.1%) had no endoscopic POR, 22 (21.4%) had RS i2a, 12 (11.6%) RS i2b and 39 (37.9%) had severe POR (RS i3-i4). The mean wall thickness measured by IUS in patients without endoscopic POR was 2.7 mm (SD +/- 1.3) versus 5.0 (SD +/- 1.7) in patients with RS ≥i2b (p 0.001). Hyperemia (Limberg >1) was present in 60 patients (82.2%) with RS ≥i2a vs in 4 patients (13.3%) without endoscopic POR (p 0.001). Both hyperemia and wall thickness had a sensitivity of 89.0% and specificity of 76.7% in the diagnosis of POR.The mean values for IUS scores were: Simple US Score 5.5 (SD +/- 3.1), SUS-CD 2.1 (SD +/- 1.8) and IBUS-SAS 32.9 (SD +/- 26.3). There were positive correlation for IUS scores (Simple US Score r 0.68, SUS-CD r 0.68 and IBUS-SAS r 0.67) with RS (p <0.0001). For the Simple US Score an area under the ROC curve (AUC) of 84.13% (95% CI 76.81 – 91.45) was obtained, with a score ≥3, the sensitivity (S) was 82.19% and specificity (E) 80.0%. IBUS-SAS presented an AUC of 84.93% (95% CI 77.98 - 91.87), a result ≥15 granted a S 82.19% and E 80.0%. The SUS-CD index had an AUC of 83.38% (95% CI 75.55 - 91.20), a result ≥1 presented S 82.19% and E 80.0%.

Conclusion

In our experience, IUS scores (IBUS-SAS, SUS-CD and Simple US Score) show a high sensitivity and specificity in the diagnosis of POR. The three scores had AUC greater than 80%, IBUS-SAS showed slightly higher AUC results.Read more P486 Chronic kidney disease in inflammatory bowel disease: systematic review and meta-analysisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Chronic kidney disease (CKD) is defined by a reduction in kidney function (estimated glomerular filtration rate < 60 mL/min/1.73m²) and/or damage markers that are present for at least three months, regardless of the underlying aetiology. Case reports and cohort studies suggest that inflammatory bowel disease (IBD) is associated with CKD. The extent and magnitude of a potential association between IBD and CKD is currently unknown.

Methods

A comprehensive search was conducted in EMBASE, MEDLINE, Web of Science, the Cochrane database, and SCOPUS. Two separate reviewers were involved in the process of article selection and evaluation. In studies where a comparison between an IBD population and a non-IBD control population was available, odds ratios were calculated to quantify the association. To derive an overall estimate of the effect, the Mantel–Haenszel test was employed, utilising a random effect model. This systematic review was registered with PROSPERO (ID RD42023381927).

Results

Fifty-four articles were included in the review [Table].Eight articles compared an IBD population with a healthy control population (102.230 total patients with IBD and 762.432 total non-IBD controls) and were included in the meta-analysis, although with high heterogeneity (I² 88%). An increased risk of CKD in the IBD population was observed, with an overall odds ratio of 1.59 (95% CI 1.31-1.93) [Figure].Importantly, this effect was independent of 5-aminosalicylic acid use. Data on other therapies was sparse, except for known nephrotoxic medication like tacrolimus and cyclosporine. Interestingly, several studies reported a decreasing relative risk with increasing age, potentially reflecting an increased baseline risk in this ageing population.

Conclusion

The existing evidence on CKD in IBD was systematically reviewed, including all human epidemiological studies. An increased CKD prevalence in IBD was found, independent of medication. Hence, we suggest regular measurements of kidney function by determination of baseline serum creatinine for all patients with IBD, irrespective of the therapeutic regimen. For patients having a normal baseline function, we would recommend annual follow-up. A more systematic research approach regarding CKD and IBD is warranted.Read more P487 Automated Scoring of Patient Endoscopy Videos Using Deep Learning Techniques: A Promising Approach for Clinical Trials in Inflammatory Bowel DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Accurate assessment of patient endoscopy videos is crucial for various clinical trials, including those related to inflammatory bowel diseases (IBD). However, manual scoring by trained local and central readers can lead to discrepancies, inconsistencies, and logistical challenges. To address these issues, we devised a novel approach utilizing deep learning techniques to automate the analysis, parsing, and scoring of patient endoscopy videos. Our objectives were to reduce human error/variability, accelerate endoscopic scoring by enhancing read accuracy, and lower clinical trial cost.

Methods

We developed and trained deep learning models using a large dataset of labeled patient endoscopy images. The models were designed to predict the Mayo endoscopic score (MES), which serves as a standardized measure of disease severity in IBD. Our approach developed convolutional neural networks (CNNs) to extract features from raw video data and processed them into meaningful patterns. The models were optimized using transfer learning and validated on external endoscopy video datasets through rigorous testing protocols.

Results

Using an iterative process, we developed two sets (total 4) of proof-of-concept (POC) Artificial Intelligence (AI) models using frame level datasets from endoscopy videos. First, quality was assessed by the blur detection model, currently performing at > 90% accuracy, and the bowel preparation model, performing at > 95% accuracy compared to the labels provided by human annotators. Second, MES sub-score prediction currently performs with >75% accuracy for 4-level Mayo sub-score prediction and >90% accuracy in predicting advanced MES scores (2 or higher compared with consensus score derived from 3 annotators).

Conclusion

The presented study highlights the potential of deep learning techniques in revolutionizing the assessment of patient endoscopy videos in clinical trials for IBD. Automating the endoscopic scoring process enables faster, more accurate, and cost-efficient evaluations, ultimately leading to better detection of patient outcomes. Future research directions involve further refining the models to enhance their performance and expand their application to other gastrointestinal diseases.Read more P544 Ustekinumab safety and effectiveness in ulcerative colitis patients: results from a large real-life studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Ustekinumab (UST) is an interleukin-12/interleukin-23 receptor antagonist recently approved for treating ulcerative colitis (UC), but with limited real-world data. We assessed therefore the effectiveness and safety of UST in UC patients in a real-world setting

Methods

This is a multicentre, retrospective, observational cohort study. The primary endpoint was the clinical remission rate (partial Mayo score, PMS, ≤1). Other endpoints were corticosteroid-free remission (CSFR) rate, clinical response rate (PMS reduction of at least 2 points), and faecal calprotectin (FC) reduction at week 24.

Results

We included 256 consecutive UC patients (M/F 139/117, median age 52). The clinical remission and clinical response rates at 8 weeks were 18.7% (44/235) and 53.2% (125/235), respectively, and 27.6% (42/152) and 61.8% (94/152) at 24 weeks, respectively. At 24 weeks, CSFR was 20.3% (31/152), and FC significantly dropped at week 12 (p=0.0004) and 24 (p=0.038). At 8 weeks, patients naïve or with one previous biologic treatment, showed higher remission (p=0.002) and clinical response rates (p=0.018) than patients previously treated with ≥2 biologics (finding not confirmed at week 24). Adverse events occurred in six patients (2.3%), whereas four patients (1.6%) underwent colectomy.

Conclusion

This large real-world study shows that UST effectively and safely treats UC patients.Read more P545 Long-term efficacy of ozanimod up to 3 years in patient response subgroups identified using group-based trajectory modellingWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Ozanimod is approved in multiple countries for the treatment of adults with moderately to severely active ulcerative colitis (UC). A previous post hoc analysis of individual outcomes in the phase 3 True North trial (NCT02435992) identified 5 groups of patient-response trajectories to ozanimod using group-based trajectory modeling (GBTM) and found that populations with fast response had higher rates of disease control, including patient-reported intestinal symptoms and objective measures of disease activity. This analysis of the True North open-label extension study (OLE; NCT02531126) evaluated the durability of ozanimod in the 5 groups for up to 3 years in the OLE (Week [W] 142).

Methods

In patients who entered the OLE from the 5 patient groups (Group 1 [super-response], Group 2 [sustained improvement], Group 3 [partial improvement], Group 4 [fast rebound], and Group 5 [slow rebound]), symptomatic endpoints were evaluated throughout the OLE until W142. Clinical and mucosal endpoints were evaluated at OLE W46, W94 and W142. Efficacy endpoints were evaluated using nonresponder imputation analysis.

Results

The percentage of patients who continued into the OLE was similar among the 5 trajectory groups, but higher proportions of patients in Groups 1–3 completed W52 before entering the OLE (Group 1 [84.2%], Group 2 [85.9%], Group 3 [86.7%], Group 4 [32.0%], and Group 5 [28.6%]). Notably, more patients from Groups 1 (60.6%), 2 (62.3%), and 3 (60.0%) completed OLE W142 than those in Groups 4 (20.0%) and 5 (26.3%). More patients in Groups 1–3, with the highest rates in Group 1, retained symptomatic response and remission through OLE W142 with continuous ozanimod treatment compared with those in Groups 4 and 5 (Figure). Higher proportions of patients in Groups 1–3 achieved and sustained response in all clinical and mucosal outcomes at OLE W46, W94, and W142 compared with Groups 4 and 5 (Table).

Conclusion

This analysis showed that personalized patient trajectory response-based modeling distinguished patients in terms of long-term outcomes. Specifically, patients with more robust patterns of response (Groups 1–3, especially Group 1) had higher sustained rates of symptomatic, clinical, and mucosal efficacy for up to 3 years of ozanimod treatment in the OLE than patients with less robust response patterns (Groups 4 and 5).Read more P546 Endoscopic findings related to the long-term response to anti-TNF-α antibody treatment in patients with Crohn's diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Anti-TNF-α antibody treatment in Crohn's disease patients has been established, but loss of treatment response has become a problem in recent years. No studies have investigated the endoscopic findings related to loss of response particularly in the long-term treatment. In this study, we investigated the endoscopic findings associated with diminished efficacy of anti-TNF-α antibodies in Crohn's disease patients treated over a long period of time.

Methods

A total of 79 patients with Crohn's disease who were observed for at least 1 year after the anti-TNF-α antibody treatment was initiated at our hospital were included in this study. These patients were stratified into cases with and without loss of response to the anti-TNF-α antibody treatment, and the endoscopic findings were compared between the two groups. A case with loss of response was defined as one in which the dose was increased or the duration of treatment was shortened during the anti-TNF-α antibody treatment or the anti-TNF-α antibody preparation was changed to another due to lack of response to the initial preparation. The findings examined were aphtha, erosion, cobblestone-like mucosa, fistula, multiple ulcer, longitudinal ulcer, and anal lesion. Mann-Whitney's U test, χ² test, and logistic regression analysis were used for statistical analysis, and differences with p < 0.05 were considered significant.

Results

The mean observation period for all patients was 85.5 months, and the longest period was 188 months. Of the 79 patients included, 29 met the criteria with loss of response, and 50 did not (loss of response rate 37%). Comparisons between the loss of response group and the no loss of response group by univariate analysis showed that anal lesions (66% vs 42%, p = 0.028), stenosis (75% vs 48%, p = 0.021), and multiple ulcers (82% vs 53%, p = 0.011) were significantly more frequent in the loss of response group. The multivariate analysis on these items identified anal lesions (OR: 3.06, 95% CI 1.04-9.04, p = 0.042) and multiple ulcers (OR: 5.33, 95% CI 1.59-17.9, p = 0.0068) as independent risk factors for loss of response.

Conclusion

In this study, Crohn's disease patients with endoscopic findings of anal lesions and multiple ulcers were prone to loss of response to the anti-TNF-alpha antibody treatment after long-term administration. This result is considered to be very useful for developing a treatment strategy for patients requiring long-term anti-TNF-α antibody treatment.Read more P379 PD-1-positive cells contribute to the diagnosis of Inflammatory Bowel Disease and can aid in predicting response to vedolizumabWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Differentiating inflammatory bowel disease (IBD) from other inflammatory diseases is often challenging. Programmed cell death protein-1 (PD-1) is expressed in T cells and is an indicator of their exhaustion. The role of PD-1 expression in diagnosing IBD and predicting the response of biologic agents remains inconclusive.

Methods

In this study, endoscopic biopsy samples of 19 patients diagnosed with IBD and other inflammatory diseases were analysed using multiplexed immunohistochemistry . Other inflammatory diseases comprised five patients with intestinal tuberculosis, and five with intestinal Behçet’s disease. Additionally, a separate prospectively maintained "vedolizumab (VDZ) cohort", established in 12 ulcerative colitis(UC) patients who underwent endoscopic biopsy before VDZ administration was analysed to predict response to VDZ.

Results

In the immunohistochemistry analysis, the cell density of T cell subsets, including helper T cell (Th), cytotoxic T cell (Tc), regulatory T cell (Treg), PD-1+ cell, PD-1+ Th, PD-1+ Tc, and PD-1+ Treg was investigated and compared between IBD and other inflammatory disease. Cell densities of PD-1+ cells (p=0.028), PD-1+ Th (p=0.008), and PD-1+ Treg (p=0.024) were higher in IBD compared with other inflammatory disease.(Figure 1) In addition, the proportion of PD-1+ cells in Th and Treg was higher in the IBD group than in the other inflammatory disease group (median 7% vs. 3%, p=0.008; median 6% vs. 2%, p=0.004, respectively). Comparing within IBD, the cell density of Treg was higher in Crohn’s disease(CD) than in UC (p=0.042), whilst the cell density of Tc was higher in CD than in UC with marginal statistical significance (p=0.066). In the VDZ cohort, patients with a 14-week steroid-free clinical response had higher levels of PD-1+ cells (p=0.026), PD-1+ Th (p=0.026), and PD-1+ Treg (p=0.041) than the no response group.(Table 1)

Conclusion

We explored the relationship between PD-1 expression and IBD using multiplexed immunohistochemistry. We compared IBD and other inflammatory disease in their expression of various immune cells including PD-1+ cells, and found IBD had higher PD-1 expression, as well as higher PD-1+ Th and PD-1+ Treg compared with other inflammatory diseases. In addition, VDZ-responsive patients had higher PD-1 expression. Our study confirmed the difference in PD-1 expression in IBD and other inflammatory diseases and revealed that PD-1 expression could be a predictive marker for VDZ responsiveness.Read more P388 Eliakim score performance among patients with active Crohn’s diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Pan-enteric capsule endoscopy [PEC] (PillCam Crohn’s, Medtronic, USA) is a useful tool for disease assessment and monitoring in Crohn’s disease (CD). We have previously demonstrated the reliability and accuracy of Eliakim score (ES) in the assessment of CD-activity among patients with quiescent disease. We aimed to examine the performance of ES among patients who experienced clinical flare, as well as its responsiveness and sensitivity to change during follow-up (≤52weeks).

Methods

Patients with CD who have been started on biologics were included. They were prospectively followed with clinical visits, biomarkers and PEC at baseline, and after 14 and 52 weeks. At each time-point Crohn’s disease activity index (CDAI), C-reactive protein (CRP) and fecal-calprotectin (FC) levels were collected, and Lewis score (LS) and ES were calculated (independently reviewed by two experienced readers). Inter-class classification (ICC) was used to asses for agreement between readers. Baseline correlations were obtained using the Spearman's correlation. Repeated-measures correlation (RMC) was calculated using the rmcorr package in R (version 3.3-1). William's test was used to assess difference between correlations.

Results

Seventy-four patients were included (median age of 31.0 [22.5-46.5] years, male–50%). 142 PEC procedures were performed (Baseline– 62, week 14– 58, week 52– 22). Inter-rater agreement between both readers was high for both the LS and ES (ICC of 0.872 [p<0.001] and 0.925 [<0.001], respectively). At baseline, the correlations between FC and ES (r=0.509 [p<0.001]) and FC and LS (r=0.467 [p<0.001]) were comparable (p=0.68). RMC between biomarkers and ES were higher than between biomarkers and LS (CRP: r=0.376 [p=0.005] vs. r=0.204 [p=0.138], FC: r=0.549 [p<0.001] vs. r=0.412 [p=0.003], for ES and LS, [p=0.034/0.021], respectively), while no difference was observed (p=0.77) with regard to CDAI score (r=0.381 [p=0.007] vs. r=0.346 [p=0.015]). Performing sub-group analysis restricted to procedures which were confined to the small bowel (n=88), RMC was numerically higher (p=0.12) between FC and ES (r=0.590 [p=0.001]) than between FC and LS (r=0.470 [p=0.010]).

Conclusion

ES is a reliable and accurate scoring system in assessing mucosal inflammation in patients with active CD, and might have a higher sensitivity to clinical/inflammatory biomarker changes over time compared to LS.Read more P398 The Burden of Psychiatric Manifestations in Inflammatory Bowel Diseases: A Systematic Review with Meta-analysisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Psychiatric manifestation in individuals with inflammatory bowel disease (IBD) has been the subject of extensive research, but uncertainties remain regarding its precise magnitude, its impact on intestinal disease, and the whole burden of psychiatric manifestations.This systematic review aims to synthesize available evidence on the prevalence and impact of psychiatric disorders in patients with IBD.

Methods

A systematic search of PubMed/MEDLINE, EMBASE, and SCOPUS databases was performed to identify relevant studies published between January 2010 and January 2023. Cross-sectional, case-control, cohort, registry, and population studies that addressed the prevalence of depression, anxiety, bipolar disorder, and schizophrenia in patients with IBDs and that met the specific inclusion criteria were selected. A meta-analysis to assess the strength of association between IBD and selected psychiatric disorders was also performed. Data extraction and quality assessment were performed.

Results

The search yielded a total of 3209 articles. 193 met the inclusion criteria, but only 26 studies provided the complete data for the analysis (Table 1).Overall, the prevalence of psychiatric comorbidities was found to be significantly higher in IBD compared with the general population. The analysis revealed a moderate but significant association between IBD and depression, with a pooled odds ratio (OR) of 1.42 (95%CI 1.33-1.52). (Fig.1)Also, anxiety emerged as a prevalent comorbidity in IBD with a pooled OR of 1.3 (95%CI =1.22-1.44). Evidence on the relationship between bipolar disorders and IBD was limited and mixed, with a pooled OR of 1.64 (95%CI=1.20-2.24), despite a substantial heterogeneity (I²=94.01%). Only three studies examined the association between schizophrenia and IBD, providing widely heterogeneous results, with an inconclusive OR (p= 0,73), estimated at 0.93 (95%CI=0.62-1.39).

Conclusion

This systematic review with meta-analysis highlights that patients with IBD, both CD and UC, frequently experience psychiatric comorbidities such as depression, anxiety, bipolar disorders, and, to a lesser extent, schizophrenia. These disorders are more prevalent in IBD patients than in the general population. Depression and anxiety are particularly prevalent. Bipolar disorder is still an underexplored area in the context of IBD. Data on the relationship between schizophrenia and IBD is sparse and inconclusive and requires further research. Given the high prevalence of psychiatric comorbidities in IBD patients, the results of this systematic review underscore the need for a deeper understanding of these associations and early identification and tailored interventions for mental health in patients with IBD to improve their quality of life.Read more P532 The enhanced recovery after surgery protocol take its place in inflammatory bowel disease surgeryWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The enhanced recovery after surgery (ERAS) protocol is an evidence-based standardised multimodal programme formulated to reduce surgical stress and optimise recovery after surgery. The ERAS represents the best care practice for patients undergoing colorectal surgery. To ensure high compliance with active ERAS elements, patients must be educated to actively participate in the perioperative care pathway. ERAS protocols were originally designed to treat patients with colorectal cancer (CRC), only few studies have assessed this protocol in IBD patients. The aim of this study was to investigate the adherence to ERAS in IBD patients.

Methods

This retrospective study enrolled adult patients who underwent elective colorectal surgery and the ERAS protocol at our institute between May 2020 and December 2022. The patients were divided into IBD and non-IBD group. Data on medical history were collected from electronic health records. Preoperative, intraoperative, and postoperative data were collected for each patient using a self-reported mobile application (iColon). Adherence was calculated for at least 75% of active ERAS items. Chi-square test was used to compare categorical variables.

Results

619 patients, 492 non-IBD and 127 IBD, were enrolled. The overall adherence to ERAS protocol items was similar between the two groups (84% vs 82%, p 0.2). Adherence was evaluated during the three ERAS phases in the groups: preoperative (92% vs 90%, p 0.11), hospitalization (63% vs 62%, p 0.8), post-discharge period (96% vs 93%, p 0.2). Moreover, focusing on the preoperative ERAS items adherence, there were significant difference between non-IBD and IBD group in nutritional optimization (84% vs 67%, p <0.001) but no difference were reported in the patient’s pre-habilitation adherence (74 % vs 71%, p 0.4).

Conclusion

The feasibility of ERAS protocol was good in colorectal surgery as well as in IBD surgery. We need to focus on a tailored nutritional optimization in order to improve adherence and compliance among IBD patient.Read more P533 Photo Biomodulation treatment in patients with Ulcerative ColitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Current UC treatment options still fall short in both effectiveness and safety. Rectal inflammation may be particularly difficult to treat. Photo-biomodulation (PBM) involves the irradiation of specific non-ionizing, non-thermal light exerting an anti-inflammatory effect. PBM has demonstrated efficacy in various dermatologic and mucosal inflammatory conditions. These observations combined with ex-vivo mucosal healing studies suggest a potential efficacy of this therapy in inflammatory bowel diseases. Therefore, we aimed to assess the safety and efficacy of PBM treatment in UC patients with significant rectal inflammation.

Methods

The PhotoPill-ProctCare system comprises a rectal tube that delivers therapeutic 850nm, illumination to the rectal mucosa, at ~1 J/cm². UC patients with clinical and endoscopic evidence of rectal inflammation were enrolled to the study. The rectal device was inserted and activated for 4 minutes. The study included two parts. Part 1 involved 6 treatment sessions over 14 days. Part 2 included up to 6 additional treatments over 6 weeks. Primary endpoint was treatment safety. Secondary endpoints were clinical, biochemical, endoscopic, histologic, and microbiome composition parameters during and following the intervention.

Results

Five patients were recruited for the part 1 of the study and 6 to part 2. All patients tolerated the treatment well. Two patients reported adverse events related to intervention; these were mild in severity and spontaneously resolved (mild abdominal discomfort up to 2 hours post-treatment). Two unrelated events included COVID infection and URTI. In part 2, two patients dropped out after 6 sessions due to lack of efficacy.Overall, 4/11 patients (36%) achieved clinical remission. Response was observed in 7/11 patients (63%). Mayo score decreased from 7.82±1.4 at baseline, to 4.91±1.93 post treatment (p<0.01). Rectal bleeding sub-score decreased from 1.91±0.61 to 1.09±0.67 (p=0.03), and stool frequency sub-score decreased from 2.09±1 to 1±0.74 (p<0.01) respectively. Mean Ulcerative Colitis Endoscopic Index of Severity decreased from 6.75±1.33 to 5.9±1.5 (p=0.02). The number of host (human genome) reads within microbiome samples (likely indicative of shedding of epithelial cells) decreased post-treatment significantly in 4 patients and did not increase significantly in any of the patients. Moreover, several gut bacteria species (e.g. Bacteroides species) and bacterial pathways that are known to be associated with IBD activity, decreased significantly post-treatment.

Conclusion

This pilot study demonstrated the safety and efficacy of rectal Photo-Biomodulation for induction of response and remission in UC patients. Further studies are needed to confirm these preliminary results.Read more P377 Proportion of IBD patients with suboptimal control in daily clinical practice – real-world evidence from the IBD Podcast studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Crohn’s disease (CD) and ulcerative Colitis (UC) are inflammatory bowel diseases (IBD) characterized by chronic inflammation of the digestive tract. Increasing evidence highlights the unmet need, the burden of disease, the progressive nature of the disease and subsequent intestinal damage, limited efficacy of current treatments and suboptimal disease management^1-3. The IBD-PODCAST study aimed to estimate the proportion of patients with Crohn’s disease (CD) and ulcerative colitis (UC) with suboptimal disease control based on STRIDE-II⁴ criteria in a real-world setting across 10 countries.

Methods

A non-interventional, cross-sectional (with a limited retrospective component), multi-center, multi-country study was conducted in 2185 patients across 103 sites in Austria (n=111), Belgium (n=132), Canada (n=163), Germany (n=438), Greece (n=157), Italy (n=220), Portugal (n=130), Spain (n=396) Turkey (n=240) and UK (n=198). Criteria for suboptimal control were largely based on STRIDE-II⁴ and modified by an expert panel (Table 1) in order to evaluate disease control in this cross-sectional study.

Results

2185 patients (CD: n=1108, UC n=1077) with a mean age (SD) of 44.0 (14.8) years and mean disease duration (SD) of 12.4 (9.2) years were included (52.2% male). Ileal CD was present in 39.1% of patients and 35.3% of UC patients had extensive colitis. Among patients with CD and UC, 77.3% and 65.3% respectively, were on targeted immunomodulators (biologics or small molecule drugs) and, according to STRIDE-II⁴ -based therapeutic windows, 85.6% of CD and 85.4% of UC patients were assigned to the long-term (LT) treatment phase. At index point, suboptimal control at index was detected in 52.2% of patients with CD and 44.3% of patients with UC with relative consistency across countries. Impaired quality of life (QoL), clinically-significant EIMs, steroid overuse and signs of active inflammation in UC and CD, and fistulas in CD contributed most to the identification of suboptimal disease control in LT patients. More than one criterion indicating suboptimal control was seen in 37% of patients. Treatment optimization opportunities were observed in 49% of CD and 61% of UC patients on advanced therapy.

Conclusion

This study presents a high percentage of suboptimally-controlled IBD patients in a large multinational real-world cohort suggesting a large disease burden in IBD patients, a high unmet medical need and continuous requirements to improve standard of care in IBD. Future analysis should focus on monitoring and response to suboptimal control, and specific analysis of QoL in these patients.Read more P374 Real-life effectiveness and safety of ustekinumab treatment in patients with ulcerative colitis: An Asan-Crohn’s and Colitis Association in Daegu-Gyeongbuk (CCAiD) multicenter cohort studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The real-life data on ustekinumab (UST) for Asian patients with ulcerative colitis (UC) are limited. We aimed to assess effectiveness and safety of UST for Korean patients with UC.

Methods

This was a multicenter retrospective study on patients with UC who received UST at 4 academic centers in Korea between January 2021 and April 2023. The primary endpoint was clinical remission defined as partial Mayo score (PMS) ≤2 and no subscore >1 at week (W) 8 of therapy. Secondary endpoints included clinical remission (W16–20 and W52–56), corticosteroid-free clinical remission (W8, W16–20 and W52–56), clinical response defined as reduction of PMS ≥3 and at least 30% from baseline with either a decrease in rectal bleeding subscore ≥1 or an absolute rectal bleeding subscore ≤1 (W8, W16–20 and W52–56), endoscopic remission defined as Mayo endoscopic subscore 0–1 (W16–20 and W52–56), durability of UST at W52–56 and adverse events.

Results

A total of 55 patients were included and 54 were analyzed excluding one in clinical remission at baseline (Male, 66.7%; Median age at UST initiation, 44.5 years; Disease duration at UST initiation, 7.5 years; Previous exposure to biologics/small molecules, 70.4%; Extensive colitis, 64.8%; Median baseline Mayo score, 8; Concomitant use of systemic corticosteroids, 48.1%; Concomitant use of immunomodulators, 38.9%). Out of 54 patients, 27 patients (50%) reached to W52–56 or stopped UST, while remained 27 patients still under maintenance UST therapy, not reaching W52–56. At W8, W16–20, and W52–56, 53.7% (29/54), 63% (34/54), and 44.4% (12/27) achieved clinical remission and 68.5% (37/54), 70.4% (38/54), and 51.9% (14/27) showed clinical response, respectively (Figure 1). Endoscopic remission rates at W16–20 and W52–56 were 57.4% (31/54) and 37% (10/27), respectively (Figure 1). The durability of UST at W52–56 was 74.1% (20/27). Multivariable analysis revealed that previous exposure to biologics/small molecules was negatively associated with clinical remission at W8 (OR: 0.10; 95% confidence interval [CI] 0.02–0.57; p=0.01) and W16–20 (OR: 0.18; 95% CI 0.04–0.91; p=0.04), whereas the concomitant use of immunomodulators showed a positive association with clinical remission at W8 (OR: 4.19; 95% CI 1.11–15.77; p=0.03). Adverse events occurred in 23 patients (42.6%) and serious adverse event in one patient (1.9%) (Table 1).

Conclusion

UST was effective with an acceptable safety profile for Korean patients with UC. Previous exposure to biologics/small molecules was negatively associated with clinical remission at both W8 and W16–20.

Financial Support

This work was supported by the National Research Foundation of Korea(NRF) grant funded by the Korea government(MSIT) (NRF-2021R1A2C2095096).Read more P386 Persistence of bowel urgency despite clinical remission after induction therapy is associated with unfavorable long-term outcomes in patients with ulcerative colitis: results from the multicenter UC-RGENCY studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

STRIDE 2 recommendations define clinical remission as no rectal bleeding and normalization of stool frequency in patients with ulcerative colitis (UC), without including bowel urgency (BU) despite its negative impact on quality of life.In this large multicenter cohort, we aimed to assess whether the persistence of BU after induction therapy is independently associated with poor long-term outcomes in patients with UC.

Methods

From a multicenter retrospective study, we included consecutive UC adult patients previously exposed to at least one anti-TNF agent, with partial Mayo score (pMS) > 2, who started biologics or small molecules between Jan2019 and June2022. BU was defined as a binary criterion based on the SCCAI definition.The primary endpoint was the time to drug discontinuation due to active UC. Secondary endpoints were time to relapse, time to colectomy as well as steroid-free clinical remission (pMS ≤ 2) (CFREM), endoscopic remission (CFREM + Mayo endoscopic score (MES) ≤ 1), and mucosal healing (CFREM + MES ≤ 1 + histological remission i.e. Nancy index ≤ 1) at last follow-up.

Results

Among 473 patients with UC, 270 were assessed for BU after induction therapy (week 16) (mean age 43.0±17.0 years-old, median UC duration 6 [3-11] years, female gender=54.0%, pancolitis=45.9%). The median follow-up was 14 [8-22] months.The rate of CFREM after induction therapy was 54.4% (147/270) while 21.5% (58/270) had remaining bowel urgencies after induction therapy. Among the 147 patients achieving remission after induction therapy, 12 had persistent BU (8.2%), while 62.6% (77/123) of patients with no CFREM after induction therapy did not have any BU.The agreements between BU and rectal bleeding (75.2%, κ-coefficient = 0.33±0.06) or normalization of stools frequency (67.9%,κ-coefficient = 0.35±0.05) were mild. Among the patients with persistent BU after induction therapy, only 3.7% had no endoscopic activity (MES = 0).In multivariable analyses including CFREM at week 16, persistence of BU after induction therapy was independently associated with the time to drug discontinuation (HR=2.0[1.1-3.5], p=0.016) and colectomy (HR=4.4[2.3-8.4], p<0.001), and absence of mucosal healing (OR = 5.0[1.1-24.8], p=0.046) at last follow-up. A trend was also observed regarding the association between remaining BU after induction therapy and no CFREM (OR=6.1[0.8-48.0], p=0.085) or absence of endoscopic remission (OR=2.4[0.9-6.1], p=0.077) at last follow-up.

Conclusion

Persistence of BU despite clinical remission is associated with higher risk of drug discontinuation due to active UC, colectomy and lower likelihood of mucosal healing.Bowel urgency should be implemented into international guidelines to define clinical remission in patients with UC.Read more P393 The frequency of COVID-19 infection and the impact of vaccination on the disease morbidity in Polish pediatric patients with Inflammatory Bowel DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Little is known about morbidity of Covid-19 infection in pediatric patients with inflammatory bowel diseases (IBD). The aim of this study was to evaluate the frequency of SARS-CoV-2 infection in children with IBD.

Methods

A prospective, observational cohort study to evaluate morbidity of coronavirus disease 2019 (COVID-19) among pediatric patients with IBD. The questionnaire included information concerning numbers of vaccine doses, patients’ medication and disease activity. Disease flare was defined by worsening IBD symptoms and change in IBD medications.

Results

A total of 320 children with IBD, 169 with Crohn’s disease (CD)-52,8%, 150 with ulcerative colitis (UC) - 46,9%, 1 unclassified -0,3%, responded to the questionnaire concerning COVI-19 vaccination. Among the participants 114 (35,6%) patients have suffered from COVID19 (62 CD- 54,4%, 51 UC- 44,7%, 1 unclassified - 0,9%). In 79 cases (69,3%) COVID-19 course was mild, in 31 (27,2%) it was moderate, and 3 (2,6%) children had severe disease. There was no statistically significant difference in morbidity among patients with CD and UC. A total of 127 (39,7%) patients received at least 1 COVID-19 vaccine, and among them 22 (17,3%) children got COVID-19 infection after vaccination. 91 (47.2%) of unvaccinated patients got COVID 19 infection. Following SARS-CoV-2 disease, 22 (19.3%) patients reported exacerbation of IBD during or after COVID 19. In 82 (71.9%) patients COVID-19 infection had no effect on the course of their IBD. Among patients with exacerbation during/after SARS-CoV-2 disease, 3 (13.6%) were vaccinated and 19 (86.4%) of them were not vaccinated.

Conclusion

Based on the outcomes from our questionnaire concerning COVID-19 vaccination state on the large cohort of pediatric patients with IBD, we conclude that unvaccinated patients get sick more often than vaccinated ones, and there is no difference in the frequency of SARS-CoV-2 infection between children with CD and UC. Also, there is no statistically significant difference in the severity of COVID-19 infection between vaccinated and unvaccinated patients. Vaccination against COVID-19 has no effect on the exacerbation of IBD during/after infection.Read more P605 Intravenous Ustekinumab maintenance treatment is effective in patients with Crohn’s DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

With the usual subcutaneous (SC) doses (90 mg every 8-12 weeks) of Ustekinumab some patients will only partially respond or experience secondary loss of response. Intravenous (IV) dose of Ustekinumab is more affordable than the subcutaneous does in China. However, the evidence of intravenous administration maintenance when shortening subcutaneous dose is not effective enough is limited.

Methods

We conducted a retrospective study to evaluate the effectiveness and safety of IV Ustekinumab in patients with Crohn´s disease (CD). Patients received Ustekinumab with insufficient efficacy or loss of response to 90 mg SC treatment could escalate to IV maintenance at regular intervals through every clinic visit and could deescalate back to SC maintenance when the efficacy is satisfied. We obtained data from 247 patients.

Results

Follow-up data beyond 24 weeks (24w) were available for 229 patients and data beyond 52 weeks (52w) were available for 144. Baseline characteristics of the included patients are shown in Table 1. Complicated forms (B2-B3; 55.6%) predominated and perianal disease was present in 45.3% of patients. 136(58.12%) patients were naïve to biological treatments, 41.8% had received at one and 8.97% more than 2. Steroid-free clinical remission were observed in 88.1%(185/210) patients at 24 weeks.35/104(33.65%) had a normal level of fecal calprotectin(FCP) and 56/115(48.70%) achieved endoscopic remission at 52 weeks. Serious adverse events were reported in 0.81% of patients. Logistic regression demonstrated that 24w C-reactive protein, baseline FCP and frequency of IV treatment were associated with endoscopic remission at 52w (Figure 1).

Conclusion

Patients who lose response to the intensified dose of Ustekinumab SC could benefit from intravenous administration as maintenance treatment.Read more P606 A Retrospective Observational Study of Patterns of Biologic Drug Change in Inflammatory Bowel DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The treatment of inflammatory bowel disease (IBD) has evolved over the past two decades. Due to the recent introduction of multiple new biologics, it is crucial to understand the temporal patterns of drug change. This study aimed to examine the patterns of biological drug change over time and identify predictors of change in a cohort of patients with IBD.

Methods

We performed a retrospective study of patients diagnosed with IBD who were initiated on biologics and followed up at King Abdulaziz University (KAU) hospital, Jeddah, Saudi Arabia between June 2017, and October 2022. The KAUH inflammatory bowel disease information system (IBDIS) database was used to identify eligible patients. The study's primary objective was to describe biologics drug change patterns. Secondary outcomes included identifying predictors of drug change and time to discontinue biologics. Uni- and multi-variable odds ratios (ORs) were used to determine the predictors of drug change.

Results

A total of 910 patients who were registered in the IBDIS database were screened; 475 patients fulfilled the study criteria. 67% had CD, and 53.3% were males. The mean age at diagnosis was 22.6 (11.0) years. The most selected first and second choice of biologic was adalimumab (58.2% and 39.1%, p<0.001) and infliximab (37.6% and 48.9%, p=0.004) for both CD and UC, respectively. Ustekinumab was the primary third choice for CD (65.4%), while vedolizumab was the third choice for UC (83.3%). The proportions of patients who switched from first- and second-line adalimumab, infliximab, and vedolizumab were 52.3% and 20.9%, 37.6% and 39.9%, and 10.1% and 18.3%, respectively. On multiple regression analysis, a history of venous thromboembolism (VTE) (OR=3.60, 95% CI=1.20-11.71, p=0.025) and active smoking (OR=0.34, 95% CI=0.12-0.82, p=0.026) were associated with drug change for all patients. When stratified by disease subtype, drug change was associated with a diagnosis made between age 17 and 40 years (OR=0.46, 95% CI=0.23-0.90, p=0.024) and EIMs (OR=2.07, 95% CI=1.16-3.76, p=0.015) in CD while selecting vedolizumab as first biologic (OR=0.30, 95% CI=0.09-0.92, p=0.041), male gender (OR=2.40, 95% CI=1.04-5.73, p=0.043), and history of VTE (OR=7.32, 95% CI=0.23-49.97, p=0.031) were associated with drug change in UC.

Conclusion

Despite introducing several new biologics, anti-TNF therapies remain the preferred first and second choice of biologics for patients with IBD. The use of adalimumab is associated with the highest risk of switch. Multiple predictors of drug change over time exist for both diseases. The selection of vedolizumab as the first biologic for UC is associated with a lower risk of drug change.Read more P607 Increased rates of fractures and malignancy in elderly onset IBD in SingaporeWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Elderly onset inflammatory bowel disease (EOIBD) has variable characteristics in the published literature. We performed this study to report the disease characteristics, treatment exposure, and clinical outcomes of EOIBD compared to adult onset IBD (AOIBD) in Singapore.

Methods

This is a retrospective study involving IBD patients seen at two tertiary hospitals in Singapore from January 2020 to September 2023. Patients were identified from the Singapore National IBD registry. Those with missing data on age of IBD diagnosis were excluded. Data on baseline demographics, disease characteristics, treatment and disease-related complications were collected. EOIBD is defined as age of diagnosis ≥ 60 years old and AOIBD as those diagnosed from age 18 to 59 years old. The characteristics was compared between these two groups. Data was analysed using SPSS version 27.0.

Results

1116 patients were included in the final analysis, 10.6% (n =118) were EOIBD as shown in Figure 1. 50% were male with a mean age of diagnosis at 68 years old. The comparison between EOIBD and AOIBD are shown in Figure 1 and Table 1. There is a higher proportion of Crohn’s disease (CD) (45.7% vs 37.4%) in EOIBD. In terms of treatment, there is significantly lower use of thiopurines amongst EOIBD (34.5% vs 46.8%, p = 0.012). There was a trend of higher use of methotrexate among EIOBD (19.6% vs 10.6%, p = 0.067) although this was not statistically significant and this is similarly observed in the use of biologics (32.8% in EOIBD vs 27.1% in AOIBD, p = 0.205). There were no significant differences in corticosteroids (CS) exposure, CS dependence and mean number of CS courses used. There was a lower proportion of IBD-related surgery in EOIBD (12.1 vs 18.5%, p = 0.094) with EOID having a significantly lower mean number of IBD-related surgery (1.1 vs 1.6, p <0.001). Among EOIBD, there were significantly higher rates of malignancy (17% vs 6%, p <0.001) and fractures (18.1% vs 9.2%, p = 0.02); the latter despite a statistically higher mean level of vitamin D (20.9 ng/ml vs 18.3 ng/ml, p = 0.026). There were no differences in IBD-related hospitalization.

Conclusion

EOIBD is associated with increased rates of fractures and malignancy compared to AOIBD. Therefore, bone health and malignancy screening should be regularly performed in this group of patients to clinical outcomes.Read more P608 Steroid use in a high proportion of IBD patients – first results from the Spanish cohort of the IBD-DICE studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Corticosteroids (CS) have been an important therapeutic resource for treating inflammatory bowel disease(IBD) for the last 70 years. Guidelines still recommend CS in several clinical scenarios. Inadequate use of CS poses the patient at significant risks for irreversible side effects. However, the proportion of IBD patients with CS excess use in a real world setting, particularly in Spain, remains unclear. We aim to evaluate the proportion of Spanish IBD patients experiencing CS use/dependency as well as risk-associated factors.

Methods

IBD-DICE was a multicentre, international study to evaluate determinants and consequences of CS excess in IBD patients. In Spain, a total of 253 IBD patients (51% CD, 47% UC, 2% IBD-U) with quiescent or active disease were consecutively enrolled at 4 IBD-experienced sites from May to November 2021. Data on CS use (orally administered prednisone and/or budesonide) were captured by a web-based steroid assessment tool (SAT). CS dependency was defined as 1 or more CS courses within the last 12 months and/or no reduction of CS within the last 3 months without recurrent disease activity. SAT data were available for 253 IBD patients (56% were treated with ASA5, 29% with anti-TNF, 7,5% with IL-12/23 inhibitor).

Results

The majority of the 253 patients presented quiescent (64.43%,n=163/253) or mild (21.74%,n=55/253) disease activity rather than moderate (11.5%,n=29/253) or severe disease activity (2.37%,n=6/253). Of all patients, 17.8% (n=45/253) received at least 1 cycle of oral CS over the past 12 months (51.1% [n= 23/45] had moderate to severe disease). In fact, 65.7% [n =23/35] of the total patients with moderate to severe activity need CS. Of those 45 patients, 18 (45%) were treated for more than 3 consecutive months, one of them up to 13 months.CS use was similar between UC patients (16.81%, n= 20/119) and CD patients (18.6%, n=24/129; p=0.75, Chi-square test). A third (31.1%, n=14/45) of all patients on CS had received 1 or more courses of CS and/or could not taper CS within 3 months after CS initiation. These patients were considered steroid-dependent of whom the majority (85.7%, n=12/14) had moderate to severe disease (table 1). Of the remaining 31 patients who tapered oral CS, 7 relapsed during the following 3 months.

Conclusion

We found that 17,8% of IBD Spanish patients are receiving CS, mostly in moderate to severe flares. CS-dependency was found in 31.1% of the patients, because of prolonged use (>3 months) of the drugs. Long-term CS use is still common in practice, which could result in avoidable side-effects. Measuring CS dependency or excess in routine clinical practice is feasible and could form part of on-going quality improvement programs.Table 1. Steroid use over the past 12 monthsRead more P609 Artificial intelligence in the image recognition of pouchoscopies in patients who have undergone restorative proctocolectomy with ileal pouch anal-anastomosis (IPAA)Wed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Restorative proctocolectomy with ileal pouch anastomosis (IPAA) has become the gold standard in the surgical treatment of ulcerative colitis, with pouchitis being the most common late complication of IPAA. Pouchoscopy is the diagnostic tool of choice to examine the pouch in cases of pouchitis. Artificial intelligence (AI)-based image recognition programmes can assist the examiner in making a diagnosis, support in the education of physicians in training and potentially improve patient outcomes. The use of artificial intelligence has not yet been demonstrated in patients with IBD. The aim of this study is the development of an image recognition algorithm based on Convolutional Neural Networks (CNN) that reliably detects the endoscopic findings of pouchitis analogue to the PDAI score in endoscopic images.

Methods

The dataset consisted of 10 pouchoscopy videos, which were split into individual frames and assessed using a specially developed labelling tool. In the training process, the labelled images were divided into training, validation and test datasets (ratio 60:20:20). Pre-trained networks and hyperparameters were selected by cross-validation. The defined networks were then fine-tuned through tenfold cross-validation and evaluated for accuracy, specificity, precision F1 score and AUC.

Results

Our dataset consisted of 7130 images, with 1961 images in the „Inflammation“ group, 2326 images in the „Not assessable“ group and 2843 images in the „Healthy“ group. The final model has been cross-validated 10 times and has been shown to be able to correctly assess the endoscopic features of pouchitis to a certain extent. However, its performance is not yet sufficient for clinical use.

Conclusion

The work has shown that it is possible to develop an image recognition programme using artificial intelligence that is capable of detecting endoscopic features of pouchitis to a certain extent. Our model is not yet able to make a reliable classification, so it is not yet ready for practical use. However, it should be noted that this project was a feasibility study with a small number of cases and a limited patient population. Further research and more data are needed to sufficiently train the model. Once this is done, the model could be further developed to make reliable classifications and be used in clinical practice.Read more P610 Ustekinumab demonstrates superior treatment persistence over anti-TNF in Crohn’s disease patients previously treated with vedolizumabWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

With the rise in biologic therapies to manage moderate to severe inflammatory bowel disease (IBD), determining the optimal treatment sequence has become crucial. This aids in the selection of the next biologic agent after prior exposure or unresponsiveness to a previous regimen. Vedolizumab (VDZ) is a gut-specific α4β7-integrin inhibitor recognized for its efficacy in treating moderate to severe IBD. Yet, only a few studies have assessed the comparative effectiveness of alternative biologics, such as ustekinumab (UST) and antitumor necrosis factor agents (anti-TNF), following VDZ exposure.

Methods

In our retrospective study conducted at Chang Gung Memorial Hospital at Linkou, a leading 3700-bed medical facility in Taiwan, we examined 110 IBD patients who underwent treatment with UST or anti-TNF agents (including adalimumab and infliximab) from May 2019 to September 2023. UST's standard maintenance dosing in Taiwan is every 12 weeks. We utilized Kaplan-Meier analysis and Cox proportional hazards models to evaluate the 52-week treatment retention of UST versus anti-TNF.

Results

Of the 110 participants, 40 were diagnosed with ulcerative colitis (UC), and 70 with Crohn’s disease. The demographics between the anti-TNF and UST groups regarding age, gender, and body mass index were comparable. The primary reason for vedolizumab discontinuation in both groups was secondary non-response (Table 1). UST exhibited a notably higher 52-week retention in overall IBD (HR: 5.36, 95% CI: 1.84-15.62, P = 0.002, Figure 1a) and in Crohn’s disease patients (HR: 10.75, 95% CI: 1.34-86, P = 0.025, Figure 1b) compared to anti-TNF. While UST also showed superior persistence at 52 weeks in UC patients, the difference was not statistically significant (HR: 2.25, 95% CI: 0.63-8, P = 0.211, Figure 1c). At the 52-week mark, 73.5% of the anti-TNF group and 81% of the UST group were not on steroids. Secondary non-response was the predominant cause for discontinuation of the current biologic. Notably, UST required more frequent dose adjustments than anti-TNF. The safety profile of both treatments was comparable.

Conclusion

UST showed superior treatment persistence, compared to anti-TNF in Crohn's disease patients who had previously been exposed to vedolizumab. However, UST required more frequent dosing adjustments compared to anti-TNF.Read more P376 A prospective multi-model study on diagnostic performance of 18F-FAPI PET/CT in comparison with 18F-FDG PET/CT or magnetization transfer MR imaging to detect intestinal fibrosis in Crohn’s diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Accurate and early detection of Crohn's disease (CD) induced intestinal fibrosis is crucial for effective clinical management, yet it remains an unmet requirement. The magnetization transfer MR Imaging (MTI) was reported to offer high accurancy for detection of intestinal fibrosis. Recently, the utilization of fibroblast activating protein inhibitor (FAPI) PET/CT has emerged as a promising tool for assessing fibrosis. The diagnostic efficacy of ¹⁸F-FAPI PET/CT in detecting intestinal fibrosis was compared with that of ¹⁸F-FDG PET/CT and MTI.

Methods

Twenty-two rats were treated with TNBS for 2-4 weeks to simulate fibrosis development, and multi-model quantitative imaging was performed during a week. The mean and maximum standardized uptake values (SUV_mean and SUV_max) were calculated on ¹⁸F-FAPI and ¹⁸F-FDG PET/CT, as well as the normalized magnetization transfer ratio on MTI (normalized MTR). Pathological evaluation of intestinal fibrosis was performed, and MTI was used as the imaging standard for fibrotic analysis. Imaging and pathological criteria were used to compare the diagnostic effects of fibrosis imaging parameters. Ten patients with 34 cases of intestinal stenosis were prospectively recruited to validate their diagnostic performance using the same imaging protocol.

Results

In patients, the accuracy of MTI (AUCs=0.90-0.91, P≤0.05) was comparable to FAPI uptake (AUCs=0.80-0.87, both P≤0.01) but higher than that of FDG uptake in distinguishing between non-to-mild and moderate-to-severe fibrosis (AUCs=0.53-0.82, P=0.01-0.36). In rats, FAPI uptake showed a rapid response to intestinal fibrosis at an early disease phase (week 0-2) and demonstrated a significant increasing trend with prolonged treatment duration (week 0-4;). In contrast, normalized MTR and FDG uptake presented only a minimal response at week 2 and did not correlate so clearly with treatment duration. Consistently, in early disease phase (rats treated till week 2), the correlations of FAPI uptake (SUV_mean: R=0.69) with fibrotic scores were stronger than those of FDG uptake (SUV_mean: R=0.17) and normalized MTR (R=0.52). In late disease phase (rats treated till week 3 or 4), normalized MTR (R=0.93) showed stronger correlations with fibrotic scores than FAPI uptake (SUV_mean: R=0.55) or FDG uptake (SUV_mean: R=0.19).

Conclusion

In accurately identifying early-stage intestinal fibrosis, ¹⁸F-FAPI PET/CT demonstrates vast potential and outperforms the performance of the other two imaging modalities, warranting further research. However, ¹⁸F-FAPI PET/CT offer an equal performance for characterization of intestinal fibrosis with MTI and has significant advantages compared to ¹⁸F-FDG PET/CT in the whole disease course from Crohn's disease.Read more P385 Epithelial neutrophil localization and Claudin-2 immunohistochemical "leaky gut" expression are innovative predictors of outcomes in Ulcerative Colitis patients in endoscopic remissionWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Patients with Ulcerative Colitis (UC) in clinical and endoscopic remission (ER) may still experience disease relapse, emphasizing the need to identify reliable predictors of outcome in clinical practice. Recently, neutrophil-based histological scores have highlighted the pivotal role of neutrophils in predicting disease outcome. Furthermore, the impairment of the intestinal barrier has been proposed as a crucial element in forecasting disease outcomes. Hence, this study aims to assess the predictive role of epithelial versus lamina propria neutrophil localization and barrier proteins expression in UC patients in ER.

Methods

UC patients in clinical remission who underwent colonoscopy between January 2020 and June 2022 at two tertiary referral centres were retrospectively enrolled. Patients in ER, defined by Mayo Endoscopic Score (MES) ≤1 and UC Endoscopic Index of Severity (UCEIS) ≤1 were included. Histological activity was assessed with Robarts Histopathology Index (RHI), Nancy Histological Index (NHI) and PICaSSO Histological Remission Index (PHRI). Neutrophil localization in the epithelium and lamina propria was accurately evaluated. Additionally, immunohistochemical expression of epithelial barrier proteins, namely Claudin-2 and JAM-A, was assessed to evaluate the integrity of intestinal barrier. Two pathologists experienced in IBD independently analysed all histological slides to ensure reliability. Kaplan-Meier were plotted to analyse survival free from adverse events such as flare-up, change/optimization of medication or hospitalization over a 12-month follow-up period.

Results

Out of 60 UC patients in ER (58.3% males, mean age 44.2±13.6 years), 36.7%, 38.3% and 36.7% were in histological remission according to RHI, NHI and PHRI, respectively. 25% of patients developed an adverse outcome within 12 months. Neutrophils in the epithelium significantly correlated with adverse outcomes compared with lamina propria localization (p=0.03) or their absence altogether (p<0.01). Claudin-2 showed significantly higher expression according to endoscopic and histological activity (Table 1), while no significant difference was found for JAM-A. Notably, strong and diffuse claudin-2 expression was associated with a higher rate of adverse outcomes (p<0.01), as well as the simultaneous presence of epithelial neutrophils and Claudin-2 (p=0.04). Substantial agreement between pathologists was found (K=0.67).

Conclusion

This multicentre retrospective study highlights the potential role of epithelial neutrophils localization and claudin-2 ‘leaky gut’ protein expression as practical clinical tools to predict outcomes in UC patients. These findings hold promise in guiding patient-tailored therapy in IBD.Read more P516 Subcutaneous infliximab cut-off points in a large cohort of Spanish patients with inflammatory bowel disease and factors associated with long-term outcomesWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Evidence suggests that subcutaneous formulation of biosimilar infliximab (CT-P13) (SC-IFX) is capable to maintain clinical remission safely and to increase drug levels with a good acceptance in patients with Crohn’s disease (CD) and ulcerative colitis (UC) patients. The aims of this study were to evaluate which are the adequate drug concentration thresholds to maintain remission, and the factors involved in the long-term outcomes.

Methods

Multicentre, descriptive, and observational study including CD and UC patients who were going to be switched from IV-IFX to SC-IFX on the ENEIDA registry (a large, prospectively maintained database of the Spanish Working Group in IBD–GETECCU). All patients were on clinical remission at least 24 weeks before changing. Clinical activity, C reactive protein (CRP) and fecal calprotectin (FC), as well as trough levels were collected at baseline, at 12, 24 and 56 weeks.

Results

Two hundred and twenty patients were included 74 UC (34%) and 146 (66%) CD. IV-IFX was mainly administered due to active disease (73%) and perianal disease (12%) and for 52.5 months [range 25-89]. Pre-switch, 106 (49%) were with intensified IV-IFX dose and 97 (44%) were on concomitant immunomodulatory therapy (IMM). Many patients (172, 78%) remained with standard dose. While that SC-IFX levels significantly increased following the switch from IV to SC-IFX, clinical indices, CRP levels and FC remained unchanged during the 52 weeks of follow-up (figure).SC-IFX levels were significantly higher between patients receiving the standard IV-IFX dose than those receiving the intensified IV-IFX dose, but CRP and CF were significantly lower at all observed points. IMM at baseline and perianal disease had no effect on IFX trough levels. However, the higher body mass index was associated with a decrease in IFX trough levels. Low levels before switching and high levels at week 24 were associated with better outcomes. SC-IFX levels of 16.6 μg/dl (11.4-21.6) at week 12 were significantly associated with deep remission (CRP<5 mg/L and FC <250 μg/g) (p=0.017). The suggested optimal SC-IFX cut-off concentration in all patients and in both UC and CD is shown in the table.During 1 year of follow-up, 29 (13%) patients discontinued IMM, 19 (8.6%) had adverse events, 5 (2.3%) were hospitalised, 12 (23.2%) required surgery and 14 (6%) withdrawn SC-IFX. Global drug persistence was high (92% at week 52), but outcomes were worse in CD than in UC.

Conclusion

Switching from IV IFX to SC IFX has been shown to safely maintain long-term remission in patients with CD and UC. Our cut-off point for deep remission was 12.22 μg/g at week 12 and 13.23 μg/g at week 56.Read more P371 Calprotectin Testing: A Methods Comparison StudyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

In conventional laboratory-based Enzyme Linked Immunosorbant Assays (ELISA) for calprotectin measurement, raw stool is returned to and manually processed by testing laboratories. The OCS-Pledia calprotectin test uses the same stool collection device as the OCS-Pledia FIT test used in the UK Bowel cancer screening programme. In brief, individuals sample their stool with a picker and transfer to a preprepared buffered diluent, which is then returned to the laboratory for fully automated analysis.We have previously shown that a stool concentration of >100ug/g measured using the IDK calprotectin ELISA was the optimal cut-off to distinguish IBS from IBD (sensitivity 86%, specificity 90%, positive predictive value 39%, negative predictive value 99%).We undertook a methods comparison study to report the stability, linearity and potential bias of the OCS-Pledia calprotectin assay compared with IDK ELISA.

Methods

32 stool samples were collected from people with GI pathology, and homogenised. Samples were prepared for calprotectin testing using IDK and OCS-Pledia less than 4 hours from excretion (mean2.6 [SD]1.3 hrs). Samples were left at room temperature and further extracts taken at 6, 24, 48, 72, and 168 hours. Pairwise analysis of samples across the reporting range was undertaken and linearity and bias assayed by Pearson’s correlation and Bland-Altmann analysis, respectively.

Results

Calprotectin was stable over one week in both the OCS-Pledia buffered and the IDK ELISA unbuffered stool samples. However, OCS-Pledia results showed lower variance than that of the IDK ELISA, especially at later time points. There was a linear relationship between calprotectin measured with the OCS-Pledia and IDK-ELISA assays (R2=0.85; p<0.0001). The OCS-Pledia calprotectin assay has a positive bias across the reporting range. This led to 40 samples reading elevated calprotectin levels on OCS-Pledia but within normal range on IDK-ELISA. All 40 had colonic inflammation and therefore were false negative IDK-ELISA. Calprotectin concentrations of 600ug/g and 400ug/g measured using the OCS-Pledia assay were equivalent to concentrations of about 250ug/g and 100ug/g measured using the IDK ELISA.

Conclusion

OCS- Pledia assays for the measurement of calprotectin are likely to superseded conventional ELISAs because they are cheaper, easier to automate and do not involve laboratory staff pre-processing stool samples. Like conventional ELISA assays calprotectin is stable for at least one week. Clinicians will need to be aware, however, of the positive bias across the reporting range of calprotectin and adjust their positivity thresholds.Read more P384 Serum biomarkers of proteolytic type III and type IV collagen remodeling differentiate patients with Inflammatory Bowel Disease according to infliximab treatment response or non-responseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Characterized by chronic inflammation, patients with Inflammatory Bowel Disease experience detrimental remodeling of their intestinal extracellular matrix (ECM). Treatment with anti-inflammatory drugs can reduce the inflammation, leading to remission and tissue healing. However, adequate monitoring of patients is critical to ensure and maintain treatment response. As potential surrogate markers of ECM remodeling, we investigated blood-based neoepitope biomarkers of type III and type IV collagen in patients with IBD. We aimed to determine the value of the biomarkers for monitoring and predicting response to infliximab (IFX).

Methods

A total of 160 IBD patients initiating IFX treatment at visit 1 were included, having blood drawn at visits 1, 2, and 3, with treatment response evaluated at visit 3 using the Physicians Global Assessment (PGA) score. The response was defined as a PGA of 0 at Visit 3. Measuring the biomarkers C3M (MMP-9 degraded type III collagen) and C4A3-HNE (neutrophil elastase degraded type IV collagen α-3 chain) in the blood, we evaluated their ability to differentiate responders and non-responders to IFX induction therapy. The serum biomarker levels at each visit between responders and non-responders were statistically assessed using a mixed-effects model correction applying Bonferroni’s multiple comparison test and receiver operating characteristics (ROC).

Results

At all three visits, patients not responding to IFX treatment had significantly elevated C3M levels (p<0.001, <0.01, and <0.01) (Figure 1A). Quantifying serum C4A3-HNE demonstrated an elevation in responders at visits 1, 2, and 3, with a significant biomarker increase at visit 2 compared to non-responders (p<0.05) (Figure 1B). Determining the serum C3M levels at Visit 3 resulted in identifying non-responders with an area under the curve of 0.695 (sensitivity: 74.4% and specificity: 60.0%, p=0.009).

Conclusion

Quantifying the MMP-9 degraded C3M biomarker in the serum of IBD patients could differentiate responders and non-responders at visit 1 upon initiating IFX treatment. Serum C3M remained elevated in non-responders throughout the study period and applying ROC analysis quantifying C3M at Visit 3 could assist in identifying non-responders to IFX treatment. The C4A3-HNE biomarker was elevated in responders at all three visits, being statistically elevated at visit 2, indicating potential as a surrogate marker of IFX treatment response. Our data suggest differences in the proteolytic remodeling of type III and IV collagen quantified by neoepitope biomarkers between responders and non-responders to IFX treatment. The differences were quantifiable already at treatment initiation (visit 1).Read more P395 The frequency of SARS-CoV-2 infection and the impact of vaccination on the disease morbidity in Polish pediatric patients with Inflammatory Bowel Disease treated with biologic therapiesWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Little is known about morbidity of Covid-19 infection in pediatric patients with inflammatory bowel diseases (IBD) treated with biologic medications. The aim of this study was to evaluate the frequency of SARS-CoV-2 infection in children with IBD who received biologic therapies.

Methods

A prospective, observational cohort study to evaluate coronavirus disease 2019 (COVID-19) vaccination state, and its effect on the disease course among pediatric patients with IBD. The questionnaire included information concerning numbers of vaccine doses, patients’ medication and disease activity. Disease flare was defined by worsening IBD symptoms and change in IBD medications. Outcomes were stratified by vaccine type and IBD medication classes.

Results

A total of 320 children with IBD, 169 with Crohn’s disease (CD)-52,8%, 150 with ulcerative colitis (UC) - 46,9%, 1 unclassified -0,3%, responded to the questionnaire concerning COVI-19 vaccination. In our cohort 141 (49,7%) patients received biologic therapy: 13 patients (9,2%) adalimumab (ADA), 54 (38,3%) infliximab (IFX), 27 (19,1%) vedolizumasb (vedo), 29 (20,6%) ustekinumab (ust), 6 - vedo + ADA (4,3%), 1 - IFX + vedo (0,7%), 11 - ust + ADA (7,8%). 32 (22,7%) patients had COVID-19 infection during biological therapy (ust 6- 4,3%, vedo 7- 5,0%, ada 2-1,4%, ifx 12- 8,5%, ust + ada 2- 1,4%, vedo + ada 3- 2,1%). Among the patients on biologic treatment suffering from COVID-19, 25 (78,1%) children had mild course of the infection, 4 moderate (12,5%), 2 severe (6,3%), and 1 unknown (3,1%). A total of 127 (39,7%) patients received at least 1 COVID-19 vaccine, and among them 8 (6,3%) patients who received 1 dose of COVID-19 vaccine got the infection during biologic therapy. In our group, 193 (60,3%) patients have not been vaccinated against COVI-19, and 24 (12,4%) suffered from the disease during biologic therapy.

Conclusion

Based on the outcomes from our questionnaire concerning COVID-19 vaccination state on the large cohort of pediatric patients with IBD, we conclude that unvaccinated patients get sick more often than vaccinated ones, and that the use of biological treatment has no impact the frequency of covid infections or their course.Read more P408 Complete endoscopic healing, the future therapeutic target in Crohn's disease? Results of a prospective multicenter studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The STRIDE II guidelines recognize endoscopic healing (EH), defined by an SES-CD score ≤2 or a CDEIS score <3, as one of the main therapeutic targets in Crohn's disease (CD). Nevertheless, complete endoscopic healing could reduce the risk of long-term complications in CD. The aim of this study was to assess the risk of long-term complications in CD according to the degree of endoscopic healing achieved.

Methods

We conducted a prospective multicenter study that included all patients with CD undergoing colonoscopy for EH assessment or dysplasia screening between September 2019 and September 2022 in one university hospital, one general hospital and one private center. Two groups were compared: patients with complete EH (CDEIS = 0) and those with partial EH (CDEIS <4). The primary endpoint was CD relapse, defined as the need for drug intensification and/or initiation of corticosteroid and/or CD-related hospitalization and/or development of a fistula (luminal or perianal) or abscess, and/or the need for bowel resection. Patients were followed up every 6 months for two years. Based on previously published data, 138 patients were expected to demonstrate a 13% difference with a two-sided alpha risk of 5% and a power of 80%.

Results

A total of 133 patients were included. The majority of patients were female (55%), non-smokers (63%), with a median disease duration of 10 (IQR, 4-19) years. Fifty-seven (43%) patients had ileocolonic location and 81 (61%) an inflammatory (B1) behavior. Patients had been on treatment for a median of 18.0 months (IQR 8.6-52) prior to colonoscopy, with no difference between the two groups. There was no significant difference between the two groups apart from BMI. Eighty-four (63%) patients had complete EH. After adjustment for BMI, the risk of relapse was significantly higher in the CDEIS>0 group (23% vs. 41%, HR = 2.05; IC95% = [1.09 - 3.87]; p=0.027). After a median follow-up of 23.3 months, the number of drug intensification, hospitalizations, use of corticosteroids, occurrence of abscess, fistula, or bowel resection in the CDEIS 0 and CDEIS > 0 and <4 groups were 20% and 35% (p=0.065), 2.4 and 16% (p=0.005), 2.4% and 10% (p=0.10), 3.6% and 18% (p=0.009), 7.1% and 18% (p=0.048), 7.1% and 18% (p=0.048) respectively.

Conclusion

This prospective multicenter study confirms that complete endoscopic healing is associated with better long-term outcomes than partial endoscopic healing in patients with CD, as well as fewer surgeries and hospitalizations and an overall decreased risk of treatment failure.Read more P409 Optimal endoscopic healing thresholds defined by MM-SES-CD < 22.5 and SES-CD < 4 are associated with low risk of disease progression in Crohn’s diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

After initiation of therapy in Crohn's disease (CD), it remains unclear what the optimal endoscopic healing (EH) threshold to target is using the SES-CD and the MM-SES-CD (Modified Multiplier Simple Endoscopic Score for Crohn’s disease). We assessed MM-SES-CD and SES-CD thresholds that are best associated with low likelihood of long-term disease progression.

Methods

Week 48 endoscopy videos from patients with CD who participated in the CALM long-term extension LTE study were obtained and re-read by central readers to obtain a SES-CD and MM-SES-CD score, which was used for the derivation cohort. A real-world validation was performed with data from 99 patients that had clinical response using a mixed cohort of biologic therapies from the McMaster IBD database. The primary outcome was disease progression, defined as a new internal fistula/abscess, stricture, perianal fistula or abscess, CD-related hospitalization or surgery since the end of the CALM trial for the derivation cohort, and over the observed period of follow-up for the validation cohort. The maximum Youden index was calculated to determine the optimal MM-SES-CD and SES-CD thresholds. Receiver operating characteristic curve analyses compared threshold scores of various remission definitions on disease progression. Kaplan-Meier survival curve analyses were performed to compare the time to disease progression from the end of study endoscopy in the derivation cohort.

Results

In the derivation cohort, the optimal thresholds associated with a low likelihood of disease progression were MM-SES-CD <22.5 and SES-CD <4. A significantly greater proportion of patients with a MM-SES-CD ≥22.5 had disease progression as compared to patients with MM-SES-CD <22.5 [10/17 (58.8%) vs. 3/44 (6.8%), p<0.001]. Similarly, a significantly greater number of patients with a SES-CD ≥ 4 had disease progression compared to those with a SES-CD <4 [11/25 (44.0%) vs. 2/36 (5.6%), p<0.001]. Compared to other clinical or endoscopic remission definitions, obtaining a MM-SES-CD <22.5 at the end of the CALM study performed the best for predicting disease progression [AUC: 0.81 (95% CI: 0.68-0.94), p<0.001](sensitivity 76.9% (95% CI: 46.2-95.0), specificity 85.4% (95% CI: 72.2-93.9)). Compared to those with lower scores, patients with MM-SES-CD ≥ 22.5 (log-rank p<0.0001) and SES-CD ≥ 4 (log-rank p=0.0002) had a significantly greater probability of disease progression (Figure 1A/B). These findings were confirmed in the validation cohort (Figure 1C/D).

Conclusion

Achievement of MM-SES-CD <22.5 and SES-CD <4 was associated with low risk of CD progression and may be a suitable target for EH in clinical trials and practice. Our findings support that targeting EH may modify the natural course of CD.Read more P428 Nutritional, Muscular status and micronutrient deficiencies in patients with Inflammatory Bowel DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Malnutrition and micronutrient deficiencies are common in inflammatory bowel disease (IBD). Nutrient deficiencies increase the morbidity and complications of IBD. The aim of this study was to evaluate the nutritional and muscular status and identify micronutrient deficiencies of patients with IBD receiving treatment.

Methods

A total of 105 patients with IBD were enrolled prospectively in the department of gastroenterology and pediatrics from June 2019 to October 2021. To obtain objective data, iron, ferritin, phosphate, folate, Mg, 25-OH vitamin D, vitamin B12, and Zinc were measured in the patient's serum. In addition, body composition analysis was performed using bioelectrical impedance analysis to gain information regarding muscular status.

Results

There were 51 patients with ulcerative colitis (UC), 54 with Crohn's disease (CD), and the gender ratio (M:F) was 54:51. The average age was 37±18 years, which was significantly lower in patients with CD than UC (28.6±15.9 vs. 45.3±16.3, p<0.001). The mean body mass index (BMI) was 22.0 ± 3.7 kg/m², lower in patients with CD than UC (21.2 ± 3.8 kg/m², vs. 22.0 ± 3.3 kg/m², p=0.030). The disease activity of the patients was 64.8% in remission, with 17.1% mild, 15.2% moderate, and 2.9% severe. In the UC and CD patient groups, skeletal muscle index(SMI) and adjusted skeletal muscle mass were lower in patients with CD compared to UC.(SMI : 35.8±5.5 vs. 32.8±4.7 %, p<0.004, adjusted skeletal muscle : 8.2±1.9 vs. 7.0±1.5 kg/m², p<0.001) However, there was no difference of SMI and adjusted skeletal muscle according to disease activity in both UC and CD patients (Table 1). Iron was lower in patients with CD compared to UC (63.3 ± 42.5 vs. 82.8 ± 44.0 ug/dL, p=0.024). Ferritin, phosphorus, folic acid, vitamin B12, and zinc were also within normal limits. Magnesium was lower in patients with CD compared to UC (2.08 ± 0.15 vs. 2.15 ± 0.19, p=0.036 mg/dL). Vitamin D levels showed insufficient vitamin D in patients with UC and vitamin D deficiency (below 20 ng/mL) in patients with CD (20.1 ± 10.6 vs. 19.0 ± 9.9 ng/mL, p = 0.567) (Table 2).

Conclusion

Nutritional status of patients with IBD is favorable, and the lack of trace elements, specifically iron, magnesium, and vitamin D, and reduced skeletal muscle mass were observed to be prominent in patients with CD compared to UC.Read more P429 Explainable AI identified metabolome and diet interactions in the blood and faceal samplesWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Background: Inflammatory Bowel Disease (IBD) represents a multifaceted condition that can be characterised by the interplay of four primary elements: immunity, genetics, microbiome and environmental factors. Among these, the relationship between nutrition and the metabolome is pivotal and a number of machine learning based approaches have been developed in an effort to gain a better understanding of this relationship. Nevertheless, to date, these approaches suffer from interpretability, thereby restricting their practical applicability within clinical settings.Hence, in this study, we leverage two publicly available datasets, the UK Biobank (UKB) and the Human Microbiome Project Phase II IBD Multi’Omics Database (HMP2), to perform metabolomics-based IBD disease predictions. We apply explainable an AI (XAI) based framework to understand these predictions and explore the diet-metabolite relationships in IBD and non-IBD individuals.

Methods

4,137 plasma samples (2,099 IBD, 2,038 non-IBD) from UKB and 546 fecal samples (411 IBD, 135 non-IBD) from HMP2 with complete dietary data were used in the analysis. Random forest classification, optimized by grid search and estimator retraining was then trained to predict disease with Shapley Additive exPlanations (SHAP) included downstream to generate further insight on the model’s predictions. Finally, diet-metabolite associations were examined using Spearman-based correlations.

Results

From the plasma dataset, inflammatory markers, HDL and LDL cholesterols and omega 3 fatty acids were identified in relationship with IBD diagnosis. Within the feces samples, the discriminatory metabolites identified included B vitamins, phospholipids, urobilin, and taurine, and these latter provided a better predictive power than the plasma derived biomarkers (AUC: fecal 0.90.(95% CI: 0.84-0.96), plasma 0.66 (95% CI: 0.61-0.71). Regarding diet contribution, fish, fruit, vegetables, and processed foods exhibited a strong correlation with metabolites in both datasets, with correlations in fecal samples exhibiting a stong difference between IBD and non-IBD patients.

Conclusion

While this study has certain limitations, these results suggest that, compared to healthy individuals, IBD patients are characterised by a distinct gut profile primarily influenced by diet. It also suggests that disease, or health, influences how the gut responds to food intake. Future studies should confirm these findings using XAI and analysing both gut and blood matrices in same individuals along with their dietary intake for personalized IBD therapy development.Read more P448 The role of SARS-CoV2 infection in the clinical outcomes of patients with Inflammatory Bowel DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Immunosuppression has been identified as one of the main risk factors for complications and clinical outcomes in SARS-CoV2 infection, this takes special interest in patients with Inflammatory Bowel Disease (IBD), where there are a significant proportion of patients under immunosuppressant treatment such as biologics and steroids. On the other hand, SARS-CoV2 infection has been associated with recurrence or new onset of immune-mediated diseases like IBD.

Methods

This is a transversal, descriptive and observational study that included patients with IBD and history of SARS-CoV2 infection detected by laboratory tests and accepted to answer the questionary. Analyzed variables: sex, type of IBD (phenotype and localization), COVID-19 symptoms, treatment and severity, exacerbations, and its symptoms. Statics: we used SPSS software version 25 for the descriptive analysis and frequencies.

Results

We interviewed 186 patients, 105 women (56.5%) and 81 men (43.5%); 146 (78.5%) had Ulcerative Colitis (UC) and 40 (21.5%) Crohn´s disease (CD). Of the total of interviewed patients 82 (44.3%) had history of SARS-CoV2 infection, 16 (19.3%) were asymptomatic, 59 (71.1%) had a mild course of the infection, 8 (9.6%) moderate and no one had severe disease. The most common clinical manifestations were asthenia/adynamia (61.2%), cough (50.7%) headache (44.8%), rhinorrhea (44.8%) and fever (43.3%). Gastrointestinal manifestations were presented in less than 10%. For the infection treatment 69.1% patients used acetaminophen, 13.2% nonesteroideal anti inflammatory drugs (NSAIDs), 1.5% steroids and 4.4% antiviral therapy. Of the 82 patients who presented the infection, 24 (29.3%) had at least one clinical manifestation of disease flare. The most common one was diarrhea in 15 patients (62.5%),10 (41.6%) had abdominal pain, 7 (20.1%) patients had arthralgia and one patient (4.1%) required hospitalization due to disease flare. Of the 24 patients that had disease flare, only 10 (41.6%) received treatment optimization.

Conclusion

SARS-CoV2 infection prevalence in patients with IBD were 44.2% in this study. The most common clinical course of the infection was mild and moderate disease, no severe cases were reported. The infection caused mild to moderate exacerbation in 28% patients and one patient had severe exacerbation that required hospitalization.Read more P449 Beyond a patient's control: assessing non-modifiable factors of transition readiness in IBD patients who have transferred to adult careWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The transition from paediatric to adult care is an important time for a patient diagnosed with inflammatory bowel disease (IBD) in childhood/adolescence. A systematic review by Johnson et al., identified non-modifiable and modifiable factors that impact transition readiness. This review summarized positive associations with non-modifiable factors, such as females had higher self-management scores than males, patients with Crohn’s disease or a family IBD history associated with higher self-efficacy scores. Older age at diagnosis was associated with lower self-management scores in one study. Lack of or conflicting associations were found with respect to medication type and age at diagnosis. We aim to assess the prevalence of these non-modifiable factors in our patient population at time of transfer to adult care.

Methods

We conducted a medical chart review of patients with IBD who had their first adult care appointment between 2015 and 2022 at an academic IBD clinic in Alberta, Canada. We recorded information on non-modifiable factors, including gender, diagnosis, age at diagnosis, family history of IBD, and IBD medication type at time of first adult appointment. We used descriptive statistics to summarize the non-modifiable factors in our patient population.

Results

We reviewed the medical charts of 198 patients. The median age of IBD diagnosis was 14.4 years old (IQR: 13.0-15.9) with 2.5% of patients were diagnosed between 0-4; 6.1% between 5-9; 51.0% between 10-14; 40.4% between 15-17. At time of first appointment in adult care, 29.5% were on biologic monotherapy; 28.3% were on biologic combination therapy; 33.3% were on either 5-ASA or an immunosuppressant; the remaining 9.1% were either not on any IBD medications or medications were not documented. 43% of patients were female gender; while 60.0% of patients had Crohn’s disease; 6.6% had IBD-U, and 33.3% had ulcerative colitis. Further, 13.6% of patients had a first degree relative with IBD.

Conclusion

This study reports the prevalence of non-modifiable factors associated with transition readiness. By identifying these factors, we can direct more resources towards supporting specific populations in achieving transition readiness. For example, our study found that only 13.6% had a first degree relative with IBD – a factor positively associated with self-efficacy. This represents a large population without a relative with IBD that could benefit from resources designed to improve self-efficacy. Overall, this study supports future research aimed at designing interventions to improve readiness tailored to patients who may benefit the most.Read more P464 Could Chat Generative Pre-Trained Transformer (ChatGPT) be an AI-provided friend of the patients for frequently asked questions concerning their IBD management? An evidence- and guidelines-controlled textual analysis of AI-provided outputsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Artificial intelligence (AI) is gradually and potentially entering the everyday lives of patients with Inflammatory Bowel Disease (IBD). Systems such as Chat Generative Pre-Trained Transformer (ChatGPT), based on large language models (LLM), are now within reach. It is necessary to weigh whether these LLM systems can be real generators of medical information and whether the latter is generated based on credible databases and evidence. This study evaluated and analysed whether the outputs of ChatGPT to common questions from IBD patients can provide credible and scientifically reliable outputs.

Methods

IBD-expert physicians retrieved a list of ten IBD frequently asked questions in their clinical practice. The ten with the highest frequency (Q1-10) were collected from the total number of questions and then input on ChatGPT (see Table) on three different days (18^th, 19^th, and 20^th August 2023), and each output generated by the chatbot was categorised as O1, O2, and O3. The same research team evaluated the AI-generated responses by ChatGPT for each question by objectively comparing them with the available evidence (provided by meta-analyses, systematic reviews and ECCO guidelines).

Results

Q1 O1-3 were reliable, with a correct definition of the absence of definitive therapy for IBD. In Q2 O1-3, ChatGPT failed to clarify the lack of solid evidence for nutritional therapy in IBD. Q3 O1-3 provided corrected guidance on repeat endoscopic examinations for IBD. Q4 O1-3 did not provide reliable answers on removing topical therapy in ulcerative colitis. In Q5 O1-3 good advice was given to the IBD patient on how to plan a pregnancy. Q6 O1-3 brought out the lack of ChatGPT update (stopped in September 2021), limiting the range of new oral small molecule therapies available for the IBD patient. In Q7 O1-3 ChatGPT correctly outlined the need for individual risk stratification for endoscopic surveillance of colorectal cancer. In Q8 and Q9 O1-3 ChatGPT correctly weighed the risk of infection/cancer during biologic therapy and how heritability is only one piece of the pathogenetic puzzle of IBD. Finally, in Q10 he correctly elucidated the possibility of biological therapy preventing post-operative recurrence of Crohn's disease.

Conclusion

ChatGPT is a potentially useful complementary tool for communicating with IBD patients. It is necessary to improve the degree to which it is updated and sources on appropriate databases (e.g., Scopus, Web of Science, and MEDLINE). Ultimately, there are still significant limitations. Much of the latest findings, in fact, are excluded from ChatGPT evaluation. A portion of the outputs provided are partially incorrect or not fully detailed and not yet ready to be released to the patient without a physician filter.Read more P465 Upadacitinib is effective and safe for the treatment of ulcerative colitis and Crohn’s disease: 1-year prospective real-world experienceWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Upadacitinib (UPA) is a novel selective Janus kinase 1 inhibitor that has shown efficacy and received approval for the treatment of moderate-to-severe ulcerative colitis (UC) and Crohn's disease (CD). We previously reported a large real-world experience of UPA induction in UC and CD (Friedberg, CGH. 2023). Here we report our 1-year real-world experience.

Methods

This is a prospectively collected study of clinical outcomes of UPA treatment in patients with UC and CD using predetermined intervals at weeks 0, 2, 4, 8, then every 3 months until week 52 as part of a formalized treatment protocol at our institution. We used the Simple Clinical Colitis Activity Index and the Harvey-Bradshaw index, as well as C-reactive protein and faecal calprotectin to assess efficacy, and also recorded treatment-related adverse events and serious adverse events.

Results

110 patients were initiated on UPA and followed for a one-year period (CD=57, UC=44, IBDU=5, pouchitis=4). 109/110 (99%) were biologic exposed and 31/110 (28.2 %) were tofacitinib exposed. 99/110 (90%) were initiated on UPA for luminal disease (Table 1). 54 patients remained on UPA therapy at 1 year. In UC: week 8 clinical response and remission was 24/47 (51.1%), 39/47 (83%), respectively; week 26 clinical response and remission was 20/34 (58.8%), 24/34 (70.6%), respectively; 52 week clinical response and remission was 17/30 (56.7%), 29/30 (96.7%), respectively. In CD: week 8 clinical response and remission was 14/32 (43.8%), 25/32 (78.1%%), respectively; week 26 clinical response and remission was 9/22 (40.9%), 15/22 (68.2%), respectively; 52 week clinical response and remission was 10/17 (58.8%), 13/17 (76.5%), respectively. 56 patients discontinued UPA prior to the 1 year follow-up, 13 were due to adverse events[DR1] . The most commonly experienced AEs leading to discontinuation was dermatological side effects (CD=2, UC=2). One instance of shingles occurred leading to discontinuation. No other serious infections or serious adverse events including VTE, MACE, or malignancies occurred.

Conclusion

In this large 1-year real-world experience in medically resistant patients with UC or CD, we report that UPA is both effective and safe, including in those who had prior exposure to tofacitinib.Read more P372 Barriers and facilitators of the transition from paediatric to adult care in inflammatory bowel disease: A Western Canadian perspectiveWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Patients diagnosed with inflammatory bowel disease (IBD) in childhood/adolescence face additional challenges compared to those diagnosed in adulthood, including more extensive disease and higher risk of complications. The need to undergo transition from paediatric to adult care is associated with an increase in health care utilization and a decrease in adherence to medical appointments and medications. An effective transition may reduce these negative impacts, but there remains a need to engage the stakeholders involved in transition to identify ways to improve the transition process. This study aims to describe the perspectives of key stakeholders - patients, parents, and health care providers - on barriers and facilitators of a successful transition from paediatric to adult care.

Methods

We conducted a qualitative description study informed by naturalistic inquiry. Patients, parents, and providers from Western Canada were recruited using purposive and snowball sampling for a virtual semi-structured interview. Interviews were recorded, transcribed, and then analyzed by latent content analysis.

Results

We interviewed 17 patients, 13 parents, and 15 providers. Preparedness as a facilitator was the only theme to emerge across all groups. Groups described preparedness as knowing disease history (patients & providers), expectations of adult care (providers), and having a peer support program (parents). A supportive adult care team was identified as a facilitator by patients (n=10) and parents (n=4) who described an adult care team as one with open lines of communication, and one that is welcoming and caring. Additional facilitator themes included patient characteristics (i.e., patients who were mature, organized, and independent), and supportive parents and home environment, where a patient’s self-confidence and ability to advocate for themselves was encouraged. A barrier theme of patient factors was characterized by providers (n=8) and parents (n=4) as patients in denial of their IBD or who had mental health comorbidities. In the theme of hovering parents and family factors, providers (n=12) described parents who were reluctant to transfer disease responsibility to their child, and families with economic and/or personal challenges. Additional barrier themes included the need to navigate a new health care system and travel to clinic.

Conclusion

The results suggest a uniform agreement is necessary amongst stakeholders to ensure the development of resources aimed at preparing patients. Our study found differences in how stakeholder groups characterize the barriers and facilitators of transition. Future research should engage multiple stakeholder groups in designing transition interventions and supports for patients with IBD.Read more P383 Chronic Recurrent Multifocal Osteomyelitis associated with Paediatric Inflammatory Bowel disease: A Multi-Center Retrospective Study from the Paediatric IBD Porto Group of ESPGHANWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Chronic Recurrent Multifocal Osteomyelitis (CRMO) is a rare, autoinflammatory bone disorder. CRMO was linked with inflammatory bowel disease (IBD), either as an extra intestinal manifestation or as a paradoxical effect of anti-TNFa therapy. Our goal was to define the clinical features and natural history of patients carrying a dual diagnosis of CRMO and IBD

Methods

Medical records of pediatric patients with a dual diagnosis of IBD and CRMO were reviewed in nineteen centers from the Paediatric IBD Porto Group of ESPGHAN. Collected data included demographic characteristics, disease features, laboratory studies, bone imaging findings and outcomes of each disease

Results

Forty five patients (21 [47%] females) with a diagnosis of CRMO and IBD (32 [71%] with Crohn’s disease) were included. Median age at the time of dual diagnosis was was 10.2 (IQR 12-13.5) years. Patients were divided into 3 groups, based on whether CRMO developed before, during or after IBD diagnosis. In 15 patients (33%), CRMO was diagnosed ±3 months from the time of IBD diagnosis, with 8 (53%) and 2 (13%) exhibiting mild and moderate-severe IBD activity, respectively. In 20 children (44%) IBD preceded CRMO diagnosis by >3 months with a median time of 238 (85-344) weeks. At the time of dual diagnosis, 12 (60%) patients were in IBD remission and 5 (25%) exhibited moderate-severe disease activity; however, CRP and ESR were elevated (1.5 [0.4-3.4] mg/dL and 35 [21-55] mm/h, respectively) while median fecal calprotectin was 567 (68-1800) mcg/gr, including 4 patients <100 mcg/gr. 17 patients (85%) were on anti-TNFa medication at the time CRMO developed. In 10 (22%) patients CRMO preceded the diagnosis of IBD (>3 months before IBD evolution) with a median time 46 (25-248) weeks. At time of IBD presentation, CRMO was in remission in 5 patients (50%). 4 patients were diagnosed with IBD, despite the lack of any abnormal gastro-intestinal symptoms. In patients in which CRMO was diagnosed after or during IBD diagnosis, different therapeutic regimens were used, including anti-TNFa agents, methotrexate, ustekinumab, NSAID’s and corticosteroids. Two patients also received bisphosphonates. In patients in which CRMO was diagnosed after or during IBD diagnosis, CRMO remission, defined as lack of bone pain, was achieved in 22.2 (15-51.8) weeks. CRMO complications occurred in 4 patients and included vertebral collapse, length discrepancy, bone fracture and bone deformity

Conclusion

In the largest cohort to date, CRMO presentation was not necessarily related to clinically active intestinal inflammation and could present before, during or after IBD diagnosis. CRMO remission was achieved in all patients; Nevertheless, a small number of patients developed significant bone complicationsRead more P391 A not so innocent bystander: The prevalence and burden of anaemia at IBD onsetWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Anaemia is the most common systemic complication of Inflammatory Bowel Disease (IBD). Contemporary studies linking its prevalence with symptom burden at disease onset are limited. We present the prevalence and disability associated with anaemia in a large new onset adult IBD cohort.

Methods

Demographic, clinical and biochemical indices were collected prospectively in patients referred with suspected IBD between January 2021 - April 2023. Anaemia was defined as haemoglobin (Hb) of <115g/L in women and <130g/L in men. Iron deficiency was defined as Ferritin <30ug/L (<100ug/L if active inflammation – CRP >5mg/L, Faecal Calprotectin [FCP] >200ug/g) or Iron saturations <15%. IBD disk scores were collected in a subgroup of patients. For two groups, non-parametric Mann-Whitney U tests were utilised, with a pairwise Dunn test and holm corrected p values for more than two.

Results

Hb results were available for 586 patients (182 CD, 170 UC, 234 non-IBD). Of these, an IBD disk score was available for 245 (84 CD, 71 UC, 90 non-IBD). Hb levels were significantly lower in CD than non-IBD (Table 1).Overall, a significantly larger proportion of patients with CD were anaemic than UC (X² 10.2 p=0.001, odds ratio 2.4 [95% CI 1.39-4.16]). Whilst most anaemic patients in both groups were iron deficient, many without anaemia also had demonstrable iron deficiency (Figure 1).In CD, Hb levels were significantly lower in ileocolonic disease than either isolated ileal (median Hb 125vs135.5g/L, p=0.002) or isolated colonic (125vs139g/L, p=0.002). Across IBD, Hb significantly correlated with Harvey Bradshaw Index (n=142, Spearman’s Rho [SR] -0.23 p=0.007), Partial Mayo (n=143, SR -0.23 p=0.006), Simple endoscopic score for CD (n=130, SR -0.29 p<0.001) and FCP (n=314, SR -0.23 p<0.001).Regarding overall disease burden, Hb correlated with overall disability as determined by the IBD disk (n=155, -0.23 p=0.004). Anaemic patients had higher overall disability (total disk score 62.5vs49 p=0.007). Using individual disk domains, those with anaemia had higher fatigue (median 9vs8, p=0.012), disruption of education or work (7vs4, p<0.001), impairment of body image (7vs4, p=0.019) and reduced sexual function (5.5vs1, p=0.004). When compared in a linear regression alongside age, body mass index, ethnicity, IBD type and baseline FCP, Hb was the second strongest predictor of overall disk score (Model fit R=0.515, BMI t=3.05 p=0.003, Hb t=-2.41 p=0.019).

Conclusion

Anaemia is frequently present at IBD onset, particularly in CD. Nearly half of those without anaemia have demonstrable iron deficiency. Severity of anaemia is associated with overall disease activity but influences symptom burden and disability beyond that which is attributable to mucosal inflammation alone.Read more P402 Early diagnosis of Crohn’s disease with perianal lesions as first clinical symptom: Development and validation of a new MR imaging-based model diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Early diagnosis is crucial for the treatment and prognosis of Crohn's disease. Perianal fistulae or abscesses may present as the initial manifestation of Crohn's disease (CD) in patients. Despite magnetic resonance imaging (MRI) is the gold standard for the clinical assessment of perianal fistulae, there is shortage of MRI properties for clinical use in early perianal fistula diagnosis in CD.

Methods

Data from patients with a definitive diagnosis of PFCD and cryptoglandular disease (CGD) between September 2013 and December 2020 were examined retrospectively. The data was splited into training and test sets at a 7:3 ratio. The MRI characteristics were reviewed by two gastroenterology radiologists in consensus. The characteristics were then used to train a random forest classification model to predict a diagnosis of PFCD. The validity of the model was assessed using the area under the receiver operating characteristic curve (AUROC) and confusion matrix. Predictor importance was determined using the Shapley additive explanation (SHAP) framework.

Results

A total of 144 patients diagnosed with PFCD and 406 patients diagnosed with CGD were included. Utilizing the Boruta algorithm, 12 significant features which confirmed important for the diagnosis of PFCD, and a random forest classification model was developed. The model demonstrated an area under the receiver operating characteristic curve (AUROC) of 0.9294 (95% CI: 0.8706-0.9882), an accuracy of 0.9515 (95% CI: 0.9067-0.9788) and a kappa of 0.8779. SHAP values was utilized to estimate the variable importance, and the top five features were ulceration in rectal wall, thickened rectal wall, T2 hyperintensity, submucosal fistula and age. The model for predicting PFCD diagnosis based on MRI was dynamically visualised using a web display approach (https://doctoryang1971.shinyapps.io/forceplot/).

Conclusion

We have developed a multi-modal visual dynamic prediction model that can be effectively used to guide the early diagnosis of patients with Crohn's disease who present with perianal fistula at their first clinical visit. PFCD is likely to originate as transmural ulcers leading to submucosal inflammation or fistulae before penetrating the anal sphincter and developing into complex perianal fistulae.Read more P403 A new criterion, combining bowel wall thickness and submucosal index (SMI), is useful for estimating endoscopic improvement in Ulcerative ColitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Endoscopic improvement (EI), Mayo endoscopic subscore of 0 or 1, is considered a therapeutic target in ulcerative colitis (UC) treatment. The potential to estimate EI non-invasively is an advantage of intestinal ultrasound (IUS). In a former study, we developed a new ultrasound parameter, the submucosal index (SMI), calculated as the ratio of the thickness of the submucosa to the thickness of the bowel wall (BWT), and reported that combining BWT and SMI could be a practical criterion for estimating EI without the assessment of bowel wall vascularity using color Doppler evaluation. In the present study, we validated the EI estimation ability of our B-mode-based UC criterion, Kyorin Ultrasound Criterion for UC (KUC-UC; BWT<3.8mm and SMI<50%), using an external cohort.

Methods

Patients who underwent IUS and CS at Kyorin University Hospital were included. The inclusion criteria were (1) both IUS and endoscopy (sigmoidoscopy or CS) for UC were performed between July 2021 and June 2022, (2) the interval between IUS and endoscopy was within 15 days, and (3) no change or addition of therapeutic agents between the two examinations. IUS findings including BWT, SMI, and modified Limberg score were evaluated. In the modified Limberg score, the threshold of normal BWT was less than 3 mm, while the original Limberg score employed less than 4 mm.

Results

The KUC-UC criterion defined as BWT < 3.8 mm and SMI < 50.0% is practical because it uses only B-mode findings and does not require complex calculations. We tested the ability of this criterion to estimate EI in UC. A total of 122 colon segments were evaluated by transabdominal IUS and CS. The criteria showed a sensitivity of 67.3%, specificity of 97.1%, PPV of 94.6%, and NPV of 80.0%. In the previous development cohort, the PPV and NPV of KUC-UC were 95.5% and 82.7%, respectively. Based on the above, this validation cohort is considered equivalent to the development cohort. BWT < 3 mm and MUC have been reported as useful criteria for EI estimation. In the present cohort, BWT <3mm showed a sensitivity of 67.3%, specificity of 91.4%, PPV of 85.4%, and NPV of 79.0%, and MUC demonstrated a sensitivity of 75.0%, specificity of 88.6%, PPV of 83.0%, and NPV of 82.0%. These results indicate that KUC-UC has a considerable potential to estimate EI as BWT < 3 mm or MUC.

Conclusion

External validation showed that KUC-UC, using only B-mode findings without complicated calculations, is feasible, accurate sonographic criteria to estimate the EI of UC. The KUC-UC criterion could be one of the options for estimating EI in UC.Read more P426 Hematological Composite Scores in Patients with Inflammatory Bowel DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Ulcerative colitis (CU) and Crohn’s disease (CD) are described as inflammatory bowel diseases (IBD). Emerging as potential blood-based inflammatory biomarkers in various chronic diseases are the neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammatory index (SIRI, calculated as neutrophils × monocytes/lymphocytes). In this work we aim to analyze if these hematological composite scores differ between IBD patients and healthy controls, and whether they are related to disease activity.

Methods

A total of 197 IBD patients, 130 with CD and 67 with CU, and 208 age- and sex-matched healthy controls were recruited. NLR, MLR, PLR, and SIRI were calculated. Multivariable linear regression analysis was performed to study whether these scores differ between patients and controls and how they related to IBD activity scores.

Results

After multivariable analysis adjustment, NLR and PLR, but not SIRI and MLR, were significantly higher in IBD patients compared to controls (table 1). C-reactive protein and SIRI and NLR correlated in patients with IBD. Nevertheless, fecal calprotectin was not related to none of these blood scores. Besides, disease activity parameters were not associated with any of the composite blood-based scores in both patients with CD and CU.

Conclusion

NLR and PLR, independently, are heightened in IBD patients in contrast to controls. However, SIRI and MLR do not share this distinction. Surprisingly, none of the four hematological scores displayed correlations with disease activity in either CD or UC patients.Table 1. Multivariable analysis of the differences between patients and controls in hematological count cells and scoresRead more P427 Inflammatory bowel disease after liver transplantation: a retrospective cohort study from Latin AmericaWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The management of inflammatory bowel disease (IBD) in the setting of liver transplantation (LT) is a significant challenge. Previous data have described conflicting results on the incidence of relapses, risk of colectomy and post-transplant prognosis. In addition, there is no guidelines to recommend specific immunosuppressive regimens in this scenario. Our aim is to describe the IBD course in a cohort of liver transplanted patients in Latin America.

Methods

Medical records from two quaternary centers were reviewed using informatics tools to identify patients with Crohn’s Disease (CD) and Ulcerative Colitis (UC), associated with LT, from January 2010 and July 2023. Data on demographics, IBD phenotype, immunosuppressive therapy and infections were extracted.

Results

Among 1,683 patients that underwent LT, 45 had concomitant IBD diagnosis. Most for them (55%) were diagnosed with IBD prior to the LT. The median age at IBD diagnosis was 45 years and 57% were male. The majority had UC (80%). The causes of LT were primary sclerosing cholangitis in 24 (53.3%) patients, overlapping with autoimmune hepatitis (AIH) in 15 (33.3%), isolated AIH in 9 (20%), AIH with or without primary biliary cholangitis (PBC) in 4 (8.8%), viral hepatitis in 3 (6,6%) and other causes in 2 (4.4%) patients. Regarding immunosuppression, 19 (42.2%) patients were treated with tacrolimus, 10 (22.2%) with tacrolimus and mycophenolate mofetil, 8 (17.7%) with tacrolimus and azathioprine, 3 (6.6%) tacrolimus and everolimus, 3 (6.6%) with mycophenolate mofetil and cyclosporine, 2 (4.4%) patients with cyclosporine monotherapy. Before LT, 13 (28.8%) patients were treated with aminosalicylates and/or thiopurines, while 2 (4.4%) of them were on biologics. After LT, 20 (44.4%) patients required biological therapy, 11 (24.4%) were treated with anti-TNF (infliximab and adalimumab), 5 (11.1%) with vedolizumab, 3 (6.6%) with ustekinumab and 1 with tofacitinib. Seven (15.5%) patients required total colectomy for refractory disease, 75% after LT. Sixteen (35.5%) patients developed serious infections and the most frequent were cholangitis and cytomegalovirus (68.7%). Two patients developed adverse events, such as infliximab-induced autoimmune hepatitis and thrombocytopenic purpura related to the tacrolimus. Eight (17.7%) patients had malignancies, 3 of them related to the baseline conditions such as hepatocellular, gallbladder carcinoma, colorectal cancer, while 4 patients died during the follow-up.

Conclusion

In our experience, IBD patients undergoing LT exhibited an aggressive disease course and required concomitant biological therapy, despite the ongoing immunosuppressive regimens.Read more P442 Renal lithogenic risk in patients with Inflammatory Bowel Diseases correlates with microbiota composition, urinary profile and dietary intakeWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Nephrolithiasis (NL) is a common extra-intestinal complication of inflammatory bowel diseases (IBD), often related to enteric hyperoxaluria. Growing evidence highlights the association between NL and gut microbiota, but no data are available on the urinary microbiota in IBD patients. Our study aims to analyse the relationship between diet, urinary lithogenic profile, and gut and urinary microbiota in patients with IBD.

Methods

We prospectively enrolled consecutive adult patients with IBD. All patients underwent abdominal ultrasound, blood tests and 24h-urine collection for lithogenic profile analysis. Moreover, a nutritional evaluation was performed, and all patients underwent bioimpedance measurement. Urinary and gut microbiota were analysed through 16S rRNA sequencing.

Results

60 patients were enrolled: 32 with Crohn’s disease (CD) and 28 with ulcerative colitis (UC). NL was more frequent in CD than in UC (28% vs 14%). In patients with NL, gut microbiota analysis showed a lower relative abundance of Agathobacter (p<0.05) and a reduction in alpha diversity (p<0.05) [figure 1]. No statistically significant difference was found in urinary microbiota composition comparing patients with the presence or absence of NL. Protein (g/die) and phosphorus (mg/die) dietary intake were significantly associated with oxaluria (mg/L) (p=0.032 and p=0.007, respectively). At the same time, protein and calcium (mg/day) intake were significantly associated with NL (p= 0.018 and p= 0.023, respectively). Oxaluria and calcium oxalate relative saturation ratio (RSRCaOx) were significantly higher in CD compared to UC [Table 1].

Conclusion

Patients with IBD and NL have distinctive gut microbiota features. CD patients showed a higher prevalence of NL and oxaluria levels than UC. In addition, NL occurrence and oxaluria correlated with some nutritional parameters. Further studies are needed to identify patients with IBD at greater risk of NL by connecting the parameters of the gut microbiota, urinary profile and dietary intake to act on modifiable factors aiming to reduce this risk.Read more P443 Transmural Remission Associates with a Lower Risk of Phenotype Progression in Crohn’s DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Patients with Crohn’s disease (CD) are at risk of progressing from inflammatory to stricturing and penetrating phenotypes. The influence of the type of remission on phenotype progression has not been adequately evaluated.

Methods

Retrospective cohort study including surgically naïve CD patients with inflammatory or stricturing phenotype evaluated concomitantly by magnetic resonance enterography and colonoscopy. The degree of remission was correlated with the risk of progressing to stricturing and penetrating phenotypes.

Results

381 CD patients were included, 21.8% with transmural remission, 21.3% with isolated endoscopic remission, 10.5% with isolated radiologic remission, and 46.5% without remission. Patients with transmural remission presented the lowest rates of phenotype progression (1.2%), with a significant difference compared to isolated endoscopic remission (18.3%, P≤ 0.001), isolated radiologic remission (17.5%, P=0.002), and no remission (36.9%, P≤0.001). In multivariate regression analysis, transmural remission (OR 0.023 95%CI 0.003-0.171, P<0.001), isolated radiologic remission (OR 0.342 95%CI 0.141-0.826, P=0.017), and isolated endoscopic remission (OR 0.441 95%CI 0.220-0.881, P=0.020) resulted in lower rates of phenotype progression compared to no remission.

Conclusion

The degree of intestinal remission correlates with the risk of phenotype progression. Patients with transmural remission are at the lowest risk of progressing to stricturing and penetrating phenotypes.Figure 1 presents the Kaplan-Meier estimates of remaining free of penetrating complication (upper curve) and free of stricturing and/or penetrating complication (lower curve) after the baseline assessment in patients with no remission (A), isolated endoscopic remission (B), isolated radiologic remission (C), and transmural remission (D). B1, non-stricturing non-penetrating phenotype; B2, stricturing phenotype; B3, penetrating phenotype.Read more P373 Primary sclerosing cholangitis associated with inflammatory bowel disease: clinical characteristics of patients from reference centers in BrazilWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Inflammatory bowel disease (IBD) and primary sclerosing cholangitis (PSC) are closely associated pathological entities that, when present in combination, create a phenotypically different disease, referred to as PSC-IBD. The occurrence of PSC complicating IBD seems to vary depending on the studied population. The aim of this study was to describe the clinical profile of patients with PSC-IBD in reference centers in Brazil.

Methods

Descriptive cross-sectional study in 7 tertiary centers. Patients with PSC and IBD were identified. Data were collected from patients' charts. The following variables were studied: age, age at diagnosis of IBD and PSC, type of IBD, Montreal classification, medications used, occurrence of colorectal cancer and dysplasia, colectomy and liver complications. The study was approved by the ethics and research committee.

Results

Ninety-three patients were included. The mean age of the patients was 43,8 years (range 17 to 73). 63 patients were male (67.7%). UC was more frequent 74.2% (N=69). The mean age at diagnosis of IBD and PSC was 31.4 years (range 6 to 67) and 35.6 years (range 8 to 72), respectively. The diagnosis of PSC preceded that of IBD in only 15 (16.1%) cases. Among patients with UC, the majority (61/69) had extensive colitis (88.4%), and 47.8% (33/69) had already used at least one biological therapy. Only 9 (13%) patients with UC required colectomy. Regarding CD, colon involvement occurred in 21 (87.5%) patients and 20 (83.3%) needed to use at least one biologic. Just 3 CD patients (12.5%) had isolated disease in the small intestine. In our study, liver cirrhosis occurred in 20 (21,5%) cases of the studied population, and 13 (14%) patients required liver transplantation. Fourteen (15,1%) IBD patients had dysplasia or colorectal cancer (CRC). Use of biological therapy was more frequent in patients with CD than in those with UC (83.3% vs 47.8%; p=0.002). There was a trend towards a higher occurrence of CRC in the UC population (p=0.08).

Conclusion

In our studied PSC-IBD population, UC was more common than CD. Furthermore, we observed that in this subgroup of IBD with PSC, UC presented a more severe phenotype, with a superior occurrence of extensive colitis and need for biological therapy. In CD, most patients have colonic involvement. Interestingly, we observed a greater need to use at least one biologic in CD patients (p=0.002), as well as the need to use multiple biologics compared to UC patients (p=0.009). Additionally, there was a trend towards greater occurrence of CRC in UC patients. The rates of occurrence of dysplasia and liver cirrhosis in our casuistic emphasize the demand for more intensive follow-up in patients with IBD and PSC.Read more P382 The burden of anxiety, depression and perceived stress in patients with inflammatory bowel disease: a cohort study from north IndiaWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Patients with Inflammatory bowel disease (IBD) are susceptible to psychiatric co-morbidities. We aimed to ascertain the burden of anxiety, depression, and perceived stress in patients with IBD from north India.

Methods

Consenting adult patients with an established diagnosis of IBD were enrolled. The enrolled patients filled the Hospital Anxiety and Depression Scale (HADS) and Perceived Stress Scale (PSS) questionnaires. The patient and disease characteristics were analyzed to determine the correlations and predictors of psychiatric comorbidities. Spearman’s rho (ρ) was used for assessment of correlation between disease attributes and psychological disorders.

Results

A total of 318 patients (255 UC, 63 CD; mean age 40.13±12.06 years, 168 [52.8%] males; mean partial Mayo score 2.10±2.35; and mean HBI 2.77±2.13) were enrolled. The prevalence of anxiety, depression and moderate to high perceived stress was 14.15%, 12.57%, and 41% respectively. Females had higher mean perceived stress, anxiety and depression scores compared to males. The partial Mayo score (PMS) correlated poorly with anxiety (ρ=0.083, p=0.187), depression (ρ=0.123, p=0.49) and perceived stress (ρ=0.169; p=0.007). The Harvey Bradshaw index (HBI) correlated fairly with anxiety (ρ=0.336, p=0.007) and poorly with depression (ρ= 0.287, p=0.022) and perceived stress (ρ=0.20; p=0.117). Younger age (OR 0.93, 95% CI 0.90-0.97; p=0.001) and hand grip strength (OR 4.63, 95% CI 1.88-11.42; p=0.001) predicted anxiety in patients with UC while rural area of residence (OR 4.75, 95% CI 1.03-21.98; p=0.046) and HBI (OR 1.60, 95% CI 1.12-2.29; p=0.009) were significant predictors of anxiety in patients with CD.

Conclusion

Psychiatric comorbidities are common in patients with IBD, with higher prevalence in females. Young adults with UC and sarcopenia; and individuals with active CD living in rural areas are at an increased risk of anxiety.Read more P466 Ultrasound muscle assessment for sarcopenia screening in patients with Inflammatory Bowel Disease: A prospective study (SarcUS-IBD)Wed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Sarcopenia is prevalent among patients with Inflammatory Bowel Disease (IBD) and impacts IBD patient’s surgical and therapeutic outcomes, thus necessitating effective diagnostic tools to assess muscle mass and function in this population.

Methods

A total of 153 consecutive patients were enrolled, 100 in the "training cohort" and 53 in the "study cohort". Three superficial muscles (Rectus Femoris (RF), Rectus Abdominis (RA) and Biceps Brachii (BB)) were chosen for sarcopenia detection with muscle ultrasound (US). The "training cohort" served for feasibility and interobserver variability assessment of US measurement. In the "study cohort", muscle ultrasound (US), bioelectrical impedance analysis (BIA), and magnetic resonance imaging (MRI) were employed to measure muscle parameters. BIA served as the reference standard for comparison. Accuracy of a self-reported questionnaire for sarcopenia screening was assessed.

Results

The prevalence of sarcopenia in IBD patients was 50%. Muscle US demonstrated good diagnostic accuracy in detecting sarcopenia compared to BIA, with Area Under the Receiver Operating Characteristic Curve (AUROC) values of 80% and 85% for RA and BB thickness, respectively. Moreover, an Ultrasound Muscle Index (USMI) was defined by the sum of RA, BB, and RF thickness measurements divided by the square of the patient's height, resulting in an AUROC of 81%. Several muscle cutoffs for sarcopenia were recognized, with those of RA and USMI being correlated with the highest positive (84.3%) and negative (99%) predictive values, respectively. Excellent inter-rater and intra-rater reliability (ICC > 0.95) were observed for US measurements. Additionally, the agreement between the US and magnetic resonance measurements of rectus abdominis was excellent (ICC 0.96).

Conclusion

The findings of this study emphasize the potential of muscle US as a reliable diagnostic tool for assessing sarcopenia in IBD patients. The study provides cutoff values for US measurements, aiding clinicians in accurate diagnosis. Self-reported questionnaires showed limitations in identifying sarcopenia, underlining the importance of objective measures like US or BIA. Muscle loss in IBD patients appears to be associated with disease activity rather than systemic inflammatory markers. This research has significant implications for disease management in IBD patients and underscores the need for further investigations with larger cohorts and long-term follow-ups to validate these findings.Read more P467 Towards AI-Augmented Clinical Decision Making: An Examination of ChatGPT's Utility in Acute Ulcerative Colitis PresentationsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

ChatGPT is a large language model based chatbot created by OpenAI. Since its release, ChatGPT has gained widespread attention among the healthcare community regarding its potential utility as a medical practice tool. In addition, ChatGPT can be adapted to serve as a clinical-decision support tool. In this study we explored the potential of ChatGPT as a decision support tool for acute Ulcerative Colitis (UC) presentations in the setting of the emergency department (ED).

Methods

Our investigation centered around 20 distinct acute UC presentations to the ED, accumulated over two years. Case summaries - embodying crucial data points such as symptoms, vital signs, and laboratory results - were processed by ChatGPT. For each case, we asked ChatGPT to assess disease severity based on the TrueLove and Witts classification, substituting erythrocyte sedimentation rate ≥30 with C-Reactive protein ≥12. Furthermore, it was to recommend hospitalization or outpatient care for each case based on the disease severity. The answers were compared with assessments made by our department's gastroenterologists and the actual decision made by the physician in the ED.

Results

Overall, ChatGPT categorized 12, 7 and 1 patient with severe, moderate and mild disease, respectively. For each case, ChatGPT supplied a detailed answer depicting severity of every variable of the criteria and an overall severity classification (table 1). Compared to our gastroenterologists’ assessments, ChatGPT graded 16/20 (80%) of the patients with the same severity. A high degree of reliability was found between the two assessments as the average measure intra-class correlation coefficient of absolute agreement was 0.839 (95% confidence interval 0.588-0.937, F= 5.95, p<0.001). Inconsistencies in four cases stemmed primarily from inaccurate cut-off values for systemic variables. Following severity assessment, ChatGPT leaned towards hospitalization for 16 out of 18 (88.9%) patients. For two moderate UC cases, however, it could not provide a decisive recommendation. Comparatively, only 12 out of the 20 patients were hospitalized in actual clinical practice.

Conclusion

In this unique study, findings suggest that Chat-GPT, has potential as a clinical decision-support tool in assessing UC severity and recommending suitable settings for further treatment. While this concept warrants further investigation and validation, its ability to evaluate a clinical scenario based on established criteria could greatly benefit the field of Inflammatory bowel disease and gastroenterology.Read more P504 Prevalence of gastrointestinal infections in ulcerative colitis patients assessed with QIASTAT-DX® GASTROINTESTINAL PANEL 2Wed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

In inflammatory bowel disease (IBD), an acute clinical flare may be due to either disease exacerbation or an enteric infection. Thus, it is recommended to exclude infections before escalating IBD therapy. In this setting, conventional tests identify only a minimal proportion of infections (i.e. 10%). Whether nucleic acid multiplex tests can expand the range of detected pathogens and increase the overall prevalence is still a matter of debate.

Methods

We performed a single-center transversal prospective study at Fondazione IRCCS Policlinico Ca’ Granda. Stool samples from consecutive ulcerative colitis (UC) patients experiencing a disease flare and a group of patients in clinical remission were enrolled between February and October 2023 and tested with QIAstat-Dx Gastrointestinal Panel 2 (Qiagen GmbH, Hilden, Germany) for simultaneous qualitative detection and identification of nucleic acids from multiple viruses, bacteria, and parasites. Clinically active disease was defined as a Partial Mayo Score (PMS) of ≥2.

Results

Overall, 85 UC patients were enrolled. Demographics and clinical features are displayed in Table 1. Median age was 42 (18-79), 52% were males. The two most common treatment regimens were mesalamine (54%) and biologic/small molecule treatment (35%). 66 (78%) patients were clinically active, while 19 (22%) were in remission. In the active group, median bowel movements were 5 (3-15), 58 (88%) patients had loose stool, 32 (49%) reported abdominal pain, 40 (61%) urgency, 10 (15%) overnight symptoms, 6 (9%) fever. Median PMS was 5 (2-8). Median hemoglobin was 13.8 (8.2-16.4) g/dL, fecal calprotectin 508 (<5-4980) ug/g. Prevalence of gastrointestinal infections with QIAstat-Dx was 30 vs. 10% (p=0.13) in active vs. remission group, respectively. The most common infections were: C.Difficile infection (CDI) (4 cases), Cytomegalovirus (CMV) (4 cases) and enteropathogenic E.Coli (EPEC) (4 cases). Regarding viral and E. Coli infections, clinical remission (PMS <2) occurred spontaneously. As for CMV, Campylobacter spp., and CDI, all patients except one achieved remission following specific antimicrobial treatment. In one patient CMV infection led to hospital admission (circulating CMV DNA 35,395 IU/mL). The remaining patient did not receive specific antiviral therapy since sigmoidoscopy only detected isolated CMV+ cells, and remission was achieved with UC treatment escalation.

Conclusion

In UC patients experiencing a clinical flare, prevalence of gastrointestinal infections with QIAstat-Dx® Gastrointestinal Panel 2 is numerically higher than patients in remission. Further studies are needed to investigate whether increased detection could influence the clinical outcomes of IBD patients and time and costs for the healthcare system.Read more P505 Accelerating Crohn's Disease clinical trials using generative artificial intelligenceWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

At Unlearn.AI, we expedite decision making and address challenges of lengthy and costly Crohn’s Disease (CD) trial enrollment by introducing deep learning models that create digital twins of trial participants, which are comprehensive forecasts of health outcomes. These generative predictions are incorporated into standard linear and logistic regression analyses, in addition to more advanced methods, in clinical trials. Our TwinRCT technology, which aligns with regulatory guidance, augments standard RCTs for easy integration into clinical programs. We demonstrate the expected benefit of these solutions in a subset of IBD Plexus data that were not previously involved in the training of the generative model, showcasing its potential to transform future CD trials.

Methods

We developed a generative deep learning model using data from approximately 4,500 Inflammatory Bowel Disorder (IBD) participants in observational studies and randomized controlled trial (RCT) control arms from the IBD Plexus program of the Crohn’s & Colitis Foundation. The trained model was used to forecast, entirely from each participant’s baseline data, the control outcomes of participants in a held out set of 300 participants. The resultant forecasts, or digital twins, represent comprehensive longitudinal trajectories across a range of outcomes, laboratory measures, and vital signs. We evaluated the expected benefits of incorporating the digital twins in linear and logistic regression models, analyzing the change from baseline to follow-up (Weeks 12 through 52) on sCDAI total score, change in daily bowel movement count, change in abdominal pain score and proportion of patients achieving clinical remission (sCDAI < 150; sCDAI is very closely related to CDAI).

Results

Digital twins provided substantial attainable benefit across outcomes and time points, enabling up to 21% overall sample size reduction or 34% reduction in the control arm only.

Conclusion

TwinRCTs offer a strategic enhancement to traditional RCTs by minimizing the required sample size needed to identify significant treatment effects. Aligning with existing FDA and EMA guidelines, TwinRCTs can be effectively utilized in Phase 2 and Phase 3 CD studies for faster decision making, as well as reduced timelines and costs, without increasing regulatory risk over standard approaches.Read more P378 The link between periodontitis and disease activity in inflammatory bowel diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Periodontitis and inflammatory bowel disease (IBD) share similarities in their aetiopathogenesis and patients with IBD are reported to have more often severe periodontitis. Conversely, recent studies have suggested that periodontitis also impacts IBD activity. In this study we used two distinct IBD-populations to assess whether the presence of periodontitis is associated with increased IBD activity, disability, and severity.

Methods

Identical questionnaire-based surveys were conducted in Sweden and Denmark, distributed by the respective patient-organisations. The survey included self-reported oral health as well as IBD-related characteristics. Oral health was assessed by the Periodontal Screening Score (PESS), which is a validated instrument to screen for severe periodontitis (indicated by a score ≥5), and by the number of remaining teeth, as tooth loss is the ultimate outcome of untreated periodontitis. Disease activity in patients with ulcerative colitis (UC) was assessed by the Simple Clinical Colitis Index (SCCAI), and in Crohn’s disease (CD) by the Harvey & Bradshaw’s Activity Index (HBI). Disease related disability was assessed by the Inflammatory bowel disease disability index (IBD-DI).

Results

In total, 1,879 IBD patients, encompassing 898 patients (47.8%) with UC and 981 patients with CD (52.2%), completed the questionnaire. In both UC and CD, severe periodontitis was significantly associated with a higher level of current disease activity [OR 1.51 (1.18;1.93); p=0.001] based on SCCAI/HBI, increased IBD disability score [Coef. 3.62 (1.46;5.79); p=0.001], and increased disease activity in the last 12 months (defined as number of episodes of disease activity in the last 12 months) [OR 1.50 (1.20;1.87); p=<0.001]. Tooth loss (<20 remaining teeth) was associated with both an increased disease activity in the last 12 months [OR 1.36 (1.05;1.76); p=0.018] as well as IBD disability score [Coef. 4.15 (1.66; 6.65); p=0.001]. Tooth loss also showed a tendency to be associated with current disease activity (SCCAI/HBI), although this was not significant [OR 1.31 (0.99;1.75); p=0.062]. IBD severity (a composite parameter of history of IBD-related surgery and/or treatment with biological therapy) was neither associated with severe periodontitis [OR 1.17 (0.90;1.54); p=0.241], nor tooth loss [OR 1.30 (0.95;1.78); p=0.100].

Conclusion

In this questionnaire-based study with responses from 1,879 IBD patients from two countries, we found the presence of periodontitis and tooth loss to be closely associated with both increased disease activity and disability in IBD patients. These findings emphasize the need for an increased focus on the oral health of patients with IBD.Read more P381 Intestinal ultrasound in newly diagnosed Ulcerative Colitis predicts the need for colectomyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Upon diagnosis of ulcerative colitis (UC), it remains challenging to predict who will have a severe disease course, ultimately necessitating colectomy. Predictive tools capable of risk-stratifying patients and individualize treatment are warranted. The aim of this study was to assess whether Intestinal ultrasound (IUS), performed at the onset of UC, could help predict the need for colectomy within the first year of diagnosis.

Methods

In a Danish prospective inception cohort, all new-onset adult patients with UC (including unclassified IBD) with left-sided or extensive colitis underwent IUS near the diagnostic endoscopy. The assessment included the International Bowel Ultrasound Segmental Activity Score (IBUS-SAS) and the bowel wall thickness (BWT) of the most inflamed segment. Besides IUS, we recorded age, gender, smoking, BMI, the Mayo endoscopic score (MES), the Simple Clinical Colitis Activity Index (SCCAI), and biomarkers hemoglobin (hgb), C-reactive protein (CRP), albumin and fecal calprotectin.

Results

During inclusion (May 2021 – April 2023), we included 193 UC patients with Montreal classification E2 or E3. In total, 12/193 (6%) underwent colectomy within the first year or during follow-up (min. 6 months). Baseline characteristics are presented in Table 1.Univariable analyses identified high MES, CRP, SCCAI, IBUS-SAS, and BWT, along with low Hgb and albumin, as significantly associated with an increased colectomy risk. Multivariable analysis with stepwise reduction identified only SCCAI (OR: 2.0, CI 1.2–3.3, p<0.005) and BWT (OR: 1.6, CI 1.1–2.3, p=0.01) as independent predictors. Through ROC analysis, BWT presented the highest accuracy (AUC: 0.89), and the optimal cut-off by Youden Index for colectomy prediction was > 6.1 mm. Combining all the significant non-IUS predictors, CRP, MES, SCCAI, hgb, and albumin yielded an AUC of 0.88. The highest accuracy was found by combining SCCAI and BWT, with an AUC of 0.94. Kaplan-Meier curve for colectomy-free survival is presented in Figure 1.Among patients with BWT>6.1mm, 18/21 (86%) started systemic steroids within the first week, compared to 43/125 (34%) of patients with BWT ≤ 6.1, p=0.007. Among patients with BWT > 6.1mm, 11/21 (52%) started biologics within the first 31 days, compared to 5/125 (4%) of patients with BWT≤6.1mm, p<0.001.Despite more aggressive treatment, 8/21 (38%) with BWT>6.1mm had a colectomy compared to 2/125 (2%) with BWT≤6.1mm.ConclusionIUS at UC onset, specifically BWT, is a robust predictor of colectomy risk within the first year of diagnosis. Combining clinical symptom scores with IUS enhances predictive accuracy. It can accurately identify patients at an increased risk of colectomy, guiding early treatment decisions for improved patient outcomes.Read more P392 Behaviour of Childhood-onset Inflammatory Bowel Disease through AdulthoodWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The incidence of childhood-onset inflammatory bowel disease (IBD) is rising but the data on the behaviour of the disease during the adulthood are scarce. Therefore, the aim of our study was to determine whether the long-term prognosis of childhood-onset IBD differs from adult onset IBD.

Methods

All IBD patients referred to a terciary IBD centre between April and October 2023 were identified. Previous surgical interventions, biologic use and disease course after transition to adult care were retrieved from medical records. Upper gastrointestinal tract localisation, multiple bowel segments involvement, perianal Crohn`s disease, stenosing and/or penetrating disease behaviour were considered as risk factors for complicated disease course. Differences between childhood- and adult-onset IBD in surgery rates, biologic use, time to surgery and time to biologic were analysed statistically.

Results

In total, 331 IBD patients were included. Childhood-onset IBD patients represented 21% of the cohort (70 out of 331). There were no differences between the two groups concerning the presence of complicated disease course risk factors (for both groups present in 67% of patients).The proportion of operated patients was significantly higher in the childhood-onset group (63% vs. 45% in childhood- vs. adult-onset group, respectively; p=0,0087). The time to first surgery was significantly longer in the childhood- compared with adult-onset group (8,5 years vs. 4,4 years, respectively; p<0,0001); mean age of first surgery in childhood-onset group was 23 years (range 9 to 39) with the majority (88%) of childhood-onset patients having been operated in their adult years.Concerning biologics, there was significantly higher proportion of patients on biologics among childhood-onset patients (80% vs. 66% childhood- vs. adult-onset group, respectively; p=0.0205), which was also the case for multiple biologics use (51% vs. 26% childhood- vs. adult-onset group, respectively; p=0.0205). The time to the use of the first biologic was significantly longer among childhood-onset patients (7,5 years vs. 4,9 childhood- vs. adult-onset group, respectively; p=0.0113).The majority of childhood-onset patients (70%) had ongoing disease activity in adulthood as defined by admission, corticoisteroid use, need for change of biologic or need for surgery.

Conclusion

Despite the similar risk for complicated disease course at diagnosis, there is higher rate of surgery and biologic use among childhood-onset inflammatory bowel disease patients as compared with adult-onset patients. In the majority of childhood-onset patients, first surgery and biologic use is delayed compared to adult-onset population which may contribute to the complicated disease course in their adult years.Read more P360 Prevalence and risk factors for fatigue in patients with inflammatory bowel disease and endoscopic healingWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Fatigue is a frequent symptom among patients with inflammatory bowel disease (IBD). While the recent STRIDE II international guidelines consider disability-free and normal quality of life as therapeutic targets, the degree of endoscopic healing required to limit fatigue is unknown. The aim of this study was to investigate the prevalence of fatigue and its determinants in a cohort of IBD patients with endoscopic healing.

Methods

We conducted a single-center cross-sectional study between January 2019 and June 2023. All consecutive IBD patients with endoscopic healing Crohn's disease (CD, CDEIS <4) and ulcerative colitis (UC, Mayo ≤ 1) were assessed for disability (IBD-disk) the day of the colonoscopy. Fatigue and severe fatigue were defined by an IBD-Disk energy subscore >5 and >7, respectively.

Results

166 patients were included, of whom 64% (107/166) had CD. The majority of patients were treated with anti-TNF (91/166, 55%), half of them in combination therapy (44/166). The prevalence of fatigue and severe fatigue were 39% (65/166) and 23.5% (39/166) respectively, with no significant difference between CD and UC (p=0.59). The prevalence of fatigue in patient with partial endoscopic healing (Mayo 1 and CDEIS>0 and <4)) and with complete healing (Mayo 0, CDEIS 0) was 44.4% (24/54) and 36.6% (41/112) p =0.424.In multivariate analysis, factors associated with fatigue were female gender (OR=4.2, [1.1; 16.5], p= 0.040), presence of joint pain (OR=4.36, [1.0; 18.2], p= 0.04), sleep disturbance (OR =26.2, [5.5; 124.4], p <0.0001). Younger age (OR=0.95, [0.9; 0.99], p= 0.023) was associated with a significantly lower risk of fatigue. In multivariate analysis, severe fatigue was associated with female gender (OR=3.2, [1.1; 9.2], p= 0.026), the presence of joint pain (OR=2.9, [1.1; 8.1], p= 0.037) or sleep disorders (OR =11.3, [3.6; 35.9], p <0.0001).

Conclusion

One third of IBD patients with endoscopic healing suffer from fatigue. Female gender, arthralgia and especially sleep disorders are risk factors for fatigue. These results argue in favor of a holistic management of IBD patients.Read more P327 Profiling serum metabolome and lipidome to differentiate primary sclerosing cholangitis from Inflammatory Bowel Disease and healthy controlsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Currently, the diagnosis of primary sclerosing cholangitis (PSC) is challenging due to a lack of specific biomarkers. Identification of a distinct metabolome and lipidome profile of PSC patients is crucial to facilitate diagnosis and contribute to a more accurate risk stratification. Therefore, our study aimed to assess the alterations in metabolites and lipoproteins in the serum of patients with PSC compared to patients with inflammatory bowel disease (IBD) and other extraintestinal manifestations (EIM) and healthy controls (HC).

Methods

Nuclear magnetic resonance (NMR) spectroscopy of serum samples from 33 patients with PSC (24 patients with IBD and 9 patients without IBD) was performed and compared with 64 patients with IBD and other EIM as well as with 40 sex-, age-, and BMI-matched HC. Univariate and multivariate analysis methods were used for data analysis.

Results

PSC patients exhibit a disease-specific amino acid and lipid profile in comparison to IBD and other EIM, as well as to HC. Intermediate density lipoproteins (IDL) and IDL apolipoprotein (Apo) B levels and free cholesterol content of very low density lipoprotein subfraction 4 were increased in PSC compared to the control groups. Several low density lipoprotein subfractions of PSC patients showed an increase in ApoB, cholesterol, free cholesterol, triglycerides, and phospholipids in comparison to IBD and other EIM. In addition, concentrations of the amino acids glycine, histidine, phenylalanine, and tyrosine were higher in PSC patients compared to IBD and other EIM.

Conclusion

NMR spectroscopy identified a specific metabolome and lipidome profile in PSC patients compared to IBD and other EIM, as well as to HC. Thus, in addition to the established image morphology, using NMR profiling can improve diagnosis of PSC and a differentiation of patients with PSC from HC and those with IBD and other EIM.Read more P287 Clinical aspects of late-age Onset Inflammatory Bowel DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Inflammatory bowel disease (IBD) is a clinical condition affecting mainly young and middle-aged adults. However, a significant proportion of new IBD cases is diagnosed in older individuals, as the incidence of IBD and our population mean age are increasing. Older patients with IBD comprise two groups: those with a new diagnosis of IBD (Late-age onset IBD) and patients with juvenile or adult-onset IBD who have reached an advanced age. Patients with late-age onset IBD represent a significant challenge due to the inherent characteristics of this population, such as polypharmacy, comorbidities, and fragility, as well as the scarcity of specific IBD studies in this age range. We aimed to evaluate clinical aspects and epidemiology of late-age onset IBD patients (>60 years) as compared to patients with IBD diagnosed at earlier ages (<60 years).

Methods

Retrospective analysis of data from 63 patients with late-age onset IBD and 128 younger patients followed in an IBD referral center. Groups of patients including both Crohn’s disease (CD) and ulcerative colitis (UC) were randomized in a 1:2 ratio based on sex, disease location and phenotype, and year of diagnosis, from January 2001 to December 2021. Medical records data comprised disease severity, medical treatments, clinical and endoscopy remission, surgical treatment, comorbidities, and deaths.

Results

A total of 63 old-age onset IBD (57.1% female, 90.5% Caucasians, mean age: 72.00 ± 6.44 years; 52.4% UC) were included. Significantly lower utilization of immunomodulator [CD (36.7% vs. 70.0%; p=0.0020) UC (15.2% vs. 45.6%; p =0.003] and biological agents [CD (50.0% vs. 75.0%; p=0.020) UC (12.1% vs. 33.8%; p =0.003] was observed in old-age onset IBD patients. Higher disease severity was observed in patients with CD diagnosed at younger ages (90.0% vs. 66.7%; p=0.006). Higher frequency of comorbidities (92.06% vs. 31.25%; p<0.0001) and deaths (7.9 % vs. 0.7%; p=0.0015) were observed in old-age onset IBD patients. No significant differences were observed concerning clinical and endoscopy remission, use of corticosteroids and aminosalicylates and surgery (p>0.05).

Conclusion

Despite lower IBD severity and lower utilization of immunomodulators and biologic agents, late-onset patients have substantial comorbidities and higher mortality. Further studies in this specific population are needed.Read more P288 Fecal leukocyte esterase level can predict endoscopic activity for Inflammatory Bowel Disease patientsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The urine leukocyte esterase (LE) strip is widely employed to detect leukocyte presence in human body fluids due to its simplicity, speed, and cost-effectiveness. Our previous study demonstrated that fecal LE (FLE) correlated with fecal calprotectin (FC) which serves as a surrogate marker reflecting disease activity in inflammatory bowel disease (IBD) patients. This study aims to assess the correlation between FLE and endoscopy severity.

Methods

This prospective study included IBD patients at National Taiwan University Hospital from December 2021 to November 2023. FLE and FC in the same stool sample, which was collected within one month of endoscopy, were analyzed. The correlation between FLC, FC, and endoscopic severity scores was assessed using the Pearson method. Active disease in ulcerative colitis (UC) and Crohn's disease (CD) patients was defined as Mayo endoscopic score (MES) ≥ 2 and simple Endoscopic Score for Crohn's Disease (SESCD) ≥ 8, respectively. Sensitivity, specificity, positive and negative predictive values (PPV and NPV, respectively), and the Area Under the Receiver Operating Characteristic curve (AUROC) were analyzed by using SPSS.

Results

A total of 177 IBD patients (93 with UC, 84 with CD) were included. The correlation between FLE and FC levels was moderately positive (r=0.305, p<0.001). The correlation between FLE and endoscopic severity in UC and CD patients was 0.442 (p<0.001) and 0.293 (p=0.007), respectively. Among UC patients, the area under the receiver operating characteristic curve (AUROC) for predicting MES ≥ 2 by FLE and FC was 0.717 and 0.787 (p=0.241), with an optimal cutoff of 2+ for FLE and 42.5 mg/kg for FC, respectively. At this cutoff point, FLE demonstrated a sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for predicting MES ≥ 2 as 52.3%, 81.6%, 71.8%, and 65.6%, respectively. For CD patients, the AUROC for predicting SESCD ≥ 8 by FLE and FC was 0.761 and 0.869 (p=0.203), with an optimal cutoff of 2+ for FLE and 225 mg/kg for FC, respectively. FLE exhibited a sensitivity, specificity, PPV, and NPV of 81.8%, 64.4%, 74.3%, and 95.9% for predicting SESCD ≥8 respectively, at this cutoff.

Conclusion

Our results demonstrated that FLE can predict endoscopic activity, which is a cheaper and widely available monitoring tool, might be an alternative choice to FC for IBD monitoring.Read more P289 Bowel Stiffness Assessed by Shear-wave Ultrasound Elastography Predicts Disease Behavior Progression in Patients with Crohn’s DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

There is a lack of reliable predictors of disease behavior progression in patients with Crohn’s disease (CD). Real-time shear-wave elastography (SWE), a novel method for evaluating tissue stiffness, is reportedly helpful in determining the prognosis of liver cirrhosis or breast cancer. However, its value for assessing CD has not yet been investigated. We aimed to explore the value of SWE and other ultrasound parameters at diagnosis in predicting CD behavior progression.

Methods

We retrospectively collected data from CD patients with the non-stenotic non-penetrating disease (B1 phenotype based on the Montreal classification). All patients underwent intestinal ultrasound with SWE measurement at baseline and were followed up. The endpoint was defined as disease behavior progression to stricturing (B2) or penetrating (B3) disease. A multivariate Cox regression model was used to explore the association between baseline SWE and subsequent outcome. We also established a multivariate nomogram to predict the risk of disease behavior progression and evaluated its performance with receiver operating characteristic curve and decision curve analysis.

Results

A total of 130 CD patients with B1 phenotype were enrolled. Twenty-seven patients (20.8%) developed B2 or B3 disease, with a median follow-up of 33 months. Multivariate analysis identified that SWE ≥12.75 kPa was the only independent predictor of disease behavior progression (HR 1.08, 95% CI 1.03-1.12, P=0.001, Fig 1A). A restricted cubic spline with multiple covariates adjusted showed an approximately linear positive correlation between SWE and the risk of disease behavior progression, with a cut-off of 12.75 kPa (Fig 1B).We further established a multivariate nomogram incorporating SWE and other clinical characteristics to predict the risk of disease behavior progression quantitatively (Fig 1C). Compared to the model composed solely of SWE, the multivariate nomogram showed a higher but less significant performance (0.738 vs. 0.792, p=0.169, Fig 1D). However, the decision curve analysis showed that the model outperformed the single indicator of SWE in predicting endpoint events, especially those occured after 12 months of baseline (Fig 1E).

Conclusion

Intestinal stiffness assessed using SWE is an independent predictor of disease behavior progression in patients with CD. CD patients with SWE ≥12.75 kPa at diagnosis are prone to progress toward stricturing or penetrating diseases, which warrants timely intervention.Read more P290 Evaluation of response to chronic and acute stress in patients with Crohn’s diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Impaired response to stress in patients with chronic inflammatory disease, such as rheumatoid arthritis, is associated with decreased cortisol secretion. The aim of this study was the evaluation of response to chronic and acute stress in patients with Crohn’s Disease (CD).

Methods

Data was collected from patients who underwent surgery due to complications of Crohn’s (n=26)(CD group) or due to other indications (n=31) (control group). Patients on corticosteroid treatment during last 3 months and other immunological comorbidities were excluded. Cortisol concentration of the hair (proximal 3cm to the sculp) was measured as an indicative marker of stress taking place the last 3 months (chronic stress). Cortisol concentration in the saliva was measured at day 2 post surgery in a daily fluctuation manner (6 measurements in 24h), as an indicative marker of response to acute stress. The chemiluminescence method was used for cortisol measurements. Cortisol concentrations were correlated with DASS 21 questionnaire (validated Greek version),consisting of 21 questions which correspond to separate measurment scales for stress, anxiety or depression. SPSS was used for statistical analysis.

Results

Hair samples were measured from 17 CD patients and 20 controls. CD patients had significant lower concentrations of hair cortisol (median = 6.375 pgF/mg, IQR = 4.821 - 9.949) compared to control group (median = 9.643 pgF/mg, IQR = 6.602-14.637) (Mann-Whitney U-test P = 0.034). Saliva samples were measured from 21 CD patients and 27 controls. In regards to the post surgical cortisol fluctuation (acute stress), there was no significant difference between the two groups. No significant difference was observed between cortisol concentrations, and questionnaires results.

Conclusion

In CD, as in other immunological diseases, hypothalamic-pituitary–adrenal axis appears to be affected, leading in decreased response to chronic stress. This observation may have important implications for the pathophysiology, prognosis and treatment of CD.Read more P291 Longitudinal assessment of Illness Identity in patients with Inflammatory Bowel DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The concept of Illness Identity (IID) describes the way a patient integrates a chronic illness into the self-concept and has been examined in several chronic diseases. We distinguish four IID dimensions: acceptance, enrichment, engulfment and rejection. In patients with Inflammatory Bowel Diseases (IBD) IID engulfment has been shown to be associated with quality of life (QoL) and important psychosocial factors like anxiety and depression.As IBD often show a relapsing course with varying disease activity and symptom burden, it is unclear whether IID is a stable concept or whether it changes over the disease course.

Methods

In 2018 we started to recruit patients with active Crohn´s Disease or Ulcerative Colitis before the beginning of a new therapy with biologics (t1) and did follow-up examinations 6- 12 months (t2) and 2-3 years (t3) after the baseline examination. Until now we were able to reassess 71 of 83 at t2 and 16 of 83 patients at t3We assessed IID with the Illness Identity Questionnaire (Oris et al.). Anxiety and depression were assessed with the Hospital Anxiety and Depression Scale and QoL was assessed with the IBDQ.We analysed correlations between these factors at t1, t2 and t3 and calculated linear mixed-effects models to analyse the stability of IID over time. Pearson correlation between changes in IID and changes in disease activity were also examined.

Results

IID engulfment is associated with poorer QoL (r= -0.696, p= 0.003) at t3. Higher anxiety scores are linked to poorer QoL (r= -0.630, p=0.009) and higher depression scores are linked to poorer QoL (r= -0.502, p= 0.048) at t3.In the linear mixed-effects models of IID dimensions we found no significant changes in IID over time (IID enrichment : mean difference of 1.03, p= 0.297; IID acceptance : mean difference of -0.19, p= 0.824; IID rejection : mean difference of 0.69, p= 0.259; IID engulfment : mean difference of -0.22, p= 0.771. Changes in IID engulfment correlated positively with changes in disease activity (r= 0.626; p = .0095), whereas no significant correlations were found for the other IID dimensions (Fig 1.))

Conclusion

Our preliminary results suggest stability of IID in patients with IBD over a period of up to 3 years. These results confirm our previous findings, demonstrating that especially IID engulfment is linked with a poorer QoL and changes in IID engulfment correlate with changes in disease activity.Read more P292 Endoscopic findings in ileocolic anastomoses: Crohn's disease vs oncologic surgeryWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Endoscopic lesions of ileocolic anastomoses (ICA) are frequent findings in postoperative Crohn's Disease (CD) patients, associating with the risk of future recurrence by the modified Rutgeerts score (mRS). However, erosions and ulcers, mostly idiopathic, have also been described in colorectal cancer surgery anatomoses.

Methods

Primary aim: to evaluate the incidence of ICA lesions in CD and their impact on therapeutic choices. Secondary aim: to compare the endoscopic findings of ICAs in CD with those of patients operated for right colon adenocarcinoma (ICA-CRC). We performed a single-center retrospective study where we included all patients with CD submitted to ileocolic anastomoses and endoscopic reassessment up to 2 years after surgery (2010 to 2023). We randomly selected ICA-CRC patients with surveillance colonoscopy within the same interval.

Results

23 patients with CD; 48% male; age at date of surgery 18-65 years (median 41). Prior therapy: corticotherapy 14%; thiopurines 26%; anti-TNF 44%. Surgery: ileo-cecal resection 65%; right hemicolectomy 26%; previous anastomosis resection: 9%. Clavien Dindo ≥1: 9%. Surveillance colonoscopy: 4-24 months after surgery (mean 11); ICA assessed in 83%; Lesions in ICA-CD 60%: ulcers 46%; erosions 43%; stenosis 4%; mRS ≥2a: 30%; Therapeutic change: 60%. 66 with ICA-CRC; mean age 67years; adjuvant therapy 26%; cardiovascular risk factors 22%; Clavien Dindo ≥1: 22%; Surveillance colonoscopy (mean): 12 months after surgery; ICA lesions 4% (erosions). No patient with erosions had symptoms and no therapy was introduced. Comparing the two groups: CD patients were younger (p <0.001), had fewer postoperative complications (p 0.01) and more often had ICA lesions (p <0.001).

Conclusion

ICA lesions in CD, compared to ICA-CRC, were more frequent, despite the younger age of the patients and fewer postoperative complications, which favors CD recurrence. Erosions in ICA-CRC appear to have no clinical relevance.Read more P293 Safety and diagnostic yield of wireless video capsule endoscopy in early onset inflammatory bowel disease (EOIBD) in children under the age of 6 years in a tertiary paediatric IBD centreWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Wireless video capsule endoscopy (VCE) is a well-established diagnostic tool used in the evaluation of small bowel disease in paediatric IBD. Patients usually swallow the capsule. Young children are rarely able to swallow the capsule and these therefore need to be placed with the help of an OGD and an ACORN device. 2 capsule systems were used: PillCam and MiroCam. The aim of this study was to look at the safety of capsule insertion in children less than 6 years of age and to also look at the diagnostic yield.

Methods

We conducted a retrospective review of our VCE data base over a 7 year period from April 2016 to August 2023.

Results

We conducted a retrospective review of our VCE data base over a 7 year period from April 2016 to August 2023. 22 patients (14 male) and 27 capsule episodes were included into the study with a an age range at point of capsule insertion between 2 years and 5 months and 5 years and 8 months (median 5 years). All capsules were inserted with an ACORN device. All patients had a histologically proven diagnosis of EOIBD; during this period 4 patients had 2 VCEs and 1 patient 3 VCEs placed. All patient had genetic tests performed, only 1/24 patients had a monogenic mutation confirmed. 15/27 (56%) of all capsules were normal, 8/27 (30%) showed small bowel ulcerations only, 2/27 (7%) showed both small bowel and colonic ulcerations and 5/27 (19%) showed colitis only. We were able to insert the capsule in all 27 capsule episodes without any complications. All studies were complete with the capsule entering the colon and no capsule got stuck.

Conclusion

Wireless video capsule endoscopy in early onset inflammatory bowel disease in children under the age of 6 years is safe with a diagnostic yield of around 50%. This modality should be used in the diagnostic pathway of EOIBD.Read more P294 ArgesUCEIS: A high-performance, generalizable AI models for scoring Ulcerative Colitis Endoscopic Index of Severity (UCEIS) component scores in endoscopy videosWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Ulcerative Colitis (UC) endoscopic disease severity assessment is crucial in drug development and impacts clinical outcomes. We developed ArgesUCEIS, a set of three AI algorithms, to estimate UCEIS component scores that quantify the degree of bleeding, ulceration/erosion, and vascular obliteration in endoscopy videos. Our goal is to validate the locked algorithms that automate UCEIS component scoring using prospective UC clinical trial data.

Methods

We trained three distinct AI algorithms (ArgesUCEIS) to estimate degree of bleeding, ulceration/erosion, and vascular obliteration, respectively, based on human readings using endoscopy videos from a UC clinical trial (UNIFI: NCT02407236, Phase 3, 965 subjects, 3128 videos) where 20% of the total data was kept as a holdout set. The AI-model training had two steps: 1) training a feature extraction module using self-supervised learning (SSL); 2) training a supervised small transformer network with attention-based classifier using SSL features to estimate corresponding UCEIS component scores, with the attention layer potentially identifying representative frames. We validated the locked AI-models for UCEIS component scores using an independent UC trial (QUASAR: NCT04033445, Phase 2b induction study, 313 subjects, 615 videos), scoring baseline and week 12 endoscopic visits. AI model scores were compared to human read UCEIS component scores using AUC, Accuracy, and F1 score. Additionally, a Spearman correlation analysis assessed the relationship between UCEIS component model scores and human-read Mayo endoscopic subscores (MES) at both visit weeks.

Results

The locked AI models were evaluated on independent QUASAR data for all three component models, showing moderate to high performance with AUC, Accuracy, and F1 score, comparable to the UNIFI holdout set results (Table 1), indicating their generalizability. Figure 1 shows representative frames ("high attention") for each model, providing insights into the frame-level features used by ArgesUCEIS to estimate disease severity. Spearman correlation analysis indicated small to moderate correlations of bleeding, ulceration/erosion, and vascular AI models with human-read MES at baseline (0.22, 0.48, 0.37) and week 12 (0.50, 0.66, 0.61) visits, respectively, all with p-values below 0.05.

Conclusion

ArgesUCEIS, a set of three AI models for estimating UCEIS component scores, were validated using prospective UC clinical trial data and holdout data. They showed good performance with moderate to high AUC and accuracy, automating endoscopic disease severity assessments. They can be used alongside or independently of MES. They have potential to improve quality, efficiency, and enhance our understanding of drug's endoscopic impact in UC clinical trials.Read more P286 Variation of outcomes in inflammatory bowel disease at ten Australasian centres - Crohn's Colitis Cure (CCC) Data Insights ProgramWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Inflammatory bowel disease (IBD) is a global health issue with Australia having amongst the highest prevalence rates worldwide. Our study examined the quality, safety and equity of care amongst ten Australasian centres using Crohn’s Colitis Care electronic management record. The aim was to describe current care delivery at each centre for a range of performance indicators to provide a baseline from which to engage in a regional care quality benchmarking initiative

Methods

Deidentified data prospectively entered by clinicians during routine clinical practice throughout 2022 were retrospectively analysed. Only centres with >100 eligible people with IBD and an assessment during the trial period were included. Sites from Australia and New Zealand were a mixture of public and private IBD referral centres

Results

The cohort included 7172 people with IBD from 10 centres; 58.6% with Crohn’s disease (CD), 39.1% ulcerative colitis (UC) and 2.3% IBD-unclassified (IBDU). Mean age was 44.3 (SD +/- 18.0) with an even gender balance (50.7% female). The number of people with IBD per centre ranged from 201 to 2151 (median 566).In the total cohort, 38.3% were currently on advanced IBD therapy (biologics or new small molecules), with centre variation from 30.8% to 43.5% (p<0.001). Of those on advanced therapy, 42% were on dose escalated therapy which varied between centres substantially from 18% to 64%. Current steroid use ranged from 0.3% to 6.1% (median 1.6%; p<0.001). Documented IBD surgical rates varied from 0.1% to 7.2% (median 2.0; p<0.001). IBD admission rates ranged from 0.1% to 13.6% (median 1.2; p<0.001) while current smokers comprised 1.7% to 12.5% (p<0.001) of the cohort with a mean of 6.0% across all ten centres. A total of 3,379 faecal calprotectin’s (FCP) with an overall remission rate (< 250μg/g) of 71% varying from 63.4% to 83.1% (median 69.1; p=0.001); 2,616 lower endoscopies were performed with an observed remission rate of 56%; this varied between sites from 0% to 69%.Recorded Influenza vaccination rates varied from 6.3% to 54.4% (median 19.8) and Covid vaccination rates from 14% to 78.5% (median 43.4). Skin care check completion rates ranged from 16.3% to 32.3% (median 22.9). The centre with the highest documented healthcare maintenance completion rate across all three domains was private.

Conclusion

Despite advances in treatment and much literature addressing care guidelines and targets, significant disparity in care documentation and outcomes remains for people with IBD in routine care. CCCare as an IBD-specific EMR supports easy, serial examination of these measures at scale and is therefore a useful tool to measure and drive efforts to improve these deficiencies and reduce unwarranted care variationRead more P298 Adherence to diagnostic and treatment recommendations for the management of acute severe ulcerative colitis: a prospective and multinational studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Acute severe ulcerative colitis (ASUC) is a serious, potentially life-threatening condition. Hospital admission and prompt medical therapy with intravenous steroids is crucial, but rescue medical therapy is frequently needed, and surgery is often required. Our aim was to assess the adherence to main diagnostic and management recommendations within the MASC multinational study.

Methods

MASC was a prospective, multinational cohort study, including all consecutive patients hospitalized for ASUC between February 2019-January 2020. The primary outcome was surgery during the first 90 days after admission. We used descriptive statistics to determine the proportion of patients fulfilling each diagnostic and treatment recommendation according to ECCO and AGA.

Results

A total of 823 patients from 123 centers in 32 countries in five continents were included (median age 39 years [IQR, 28-54], 56% male, 64% non-smokers; Table 1). Most cases (74%) had a previous diagnosis of ulcerative colitis, and around half (48%) with prior ASUC episodes. Upon admission, they were under 5-ASA therapy (60%), thiopurines (14%), or biologics (21%). They were mostly admitted to the Gastroenterology ward (74%). During the initial assessment, 112 patients (15%) did not have stool culture or C. difficile testing, and CMV was evaluated in 50% of cases. Endoscopic assessment was performed in 66% of patients, mainly by flexible rectosigmoidoscopy (74%).Regarding treatment, 3.4% of patients received exclusive parenteral nutrition, 70% low molecular weight heparin, and 42% prophylactic antibiotics (Table 2). Steroids were started after a median of 0 days (IQR, 0-1), mostly with methylprednisolone or hydrocortisone (64%), 26% with other steroids, and 7% were managed without steroids. Infliximab was started in 159 patients (19%) after a median of 6 days (IQR, 4-8) after starting steroids, with 27% after >7 days. Most of the patients (93%) had some type of tuberculosis screening done prior to infliximab. Twenty-eight patients (3.4%) started cyclosporine. Thirty-two patients (4%) received other rescue therapy different from infliximab or cyclosporin. Colectomy was performed in 25 patients (3%).

Conclusion

The diagnostic and medical management of ASUC remains heterogeneous and different from current recommendations. This context demands more evidence and consensus on the best management of ASUC.Read more P272 Healing of Perineal Wounds after Proctectomy for Crohn's Disease: A Systematic Review and Meta-AnalysisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Non-healing perineal wounds are common in patients undergoing proctectomy for Crohn’s disease. We systematically reviewed the literature and performed a meta-analysis to estimate the pooled proportion of perineal wound healing after proctectomy for Crohn’s disease.

Methods

A comprehensive literature search was conducted in PubMed, Embase, and Scopus databases to identify relevant studies reporting perineal wound healing after proctectomy in patients with Crohn’s disease from 2010 to 2023. Articles were screened and those reporting perineal wound healing rates after proctectomy were included. Data on the study characteristics and proportion of healed wounds were extracted. Random effects meta-analysis was performed to estimate the pooled proportion and 95% confidence intervals using the ‘meta’ package in R. Heterogeneity was assessed using the I2 statistic.

Results

The literature search yielded 501 articles, of which 252 articles remained after removing duplicates. After screening the titles and abstracts, four retrospective cohort studies involving 332 patients with Crohn’s who underwent proctectomy were included in the meta-analysis. Across the four studies, the pooled proportion of completely healed perineal wounds at 6 months was 65% (95% CI 52%-80%) and at 12 months was 70% (95% CI 60%-83%). Significant heterogeneity was found between studies (I²=86% at 6 months). Only one study examined the predictors of impaired healing after proctectomy. Factors such as age, sex, BMI, smoking, steroid use, presence of high fistula-in-ano, and surgical technique were not significantly associated with impaired healing in univariate and multivariate analyses in this study. However, preoperative perineal sepsis was independently associated with impaired healing in the univariate and multivariate analyses in this study (p = 0.001). Study 4 included both Crohn's disease (n=54) and ulcerative colitis (n=20) patients who underwent proctectomy and reported fewer overall perineal complications in patients with UC than in those with Crohn’s disease (15% vs. 46.3%, p=0.01).

Conclusion

This meta-analysis revealed complete perineal healing in 70% of patients with Crohn's 12 months after proctectomy. Significant heterogeneity was observed between the studies. This review highlights the gaps in the best practices for optimizing perineal wound healing after proctectomy. These findings suggest the need to study techniques, such as vacuum-assisted closure and flap reconstruction. Further research is needed to identify modifiable factors to increase healing rates and develop evidence-based protocols for surgical approach, wound closure, and postoperative care in Crohn's disease patients.Read more P273 Defining the prognosis of children with Crohn Disease with the support of magnetic resonance enterography: a multi-center multi-reader studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Ileocolonoscopic assessment is the most accurate method for detecting intestinal inflammation in Crohn disease (CD), but it allows the assessment only of a limited tract of the small intestine and does not provide data on inflammation beyond the mucosa. The auxiliary use of magnetic resonance enterography (MRE) can overcome these limitations and allow to predict the course of CD. Paediatric Inflammatory Crohn's MRE Index (PICMI) is a multi-point index of intestinal inflammation (mucosal and transmural) in children with CD created on the basis of MRI. The aim of the present study is to assess whether this completely non-invasive index at diagnosis could predict the course of CD in children and to test the inter-reader agreement as surrogate of index reproducibility.

Methods

All children diagnosed with CD in two tertiary referral centres with a 1-year minimum follow-up were enrolled in the study. MRE at diagnosis was blindly evaluated by 3 expert radiologists and PICMI was calculated for all patients. Children’s disease was stratified according to PICMI at diagnosis into remission (<10), mild (11-55), moderate (56-120) and severe (>120). Inter-observer agreement among radiologist was calculated. Data at follow-up were collected at 6-8 weeks, 1 year, 3 years and 5 years after CD diagnosis. Association between PICMI at diagnosis and CD prognosis was evaluated.

Results

A total of 71 children (52 males) with proven CD were enrolled in the study and PICMI was calculated for 68. PICMI at diagnosis was stratified into remission 6 (8.8%), mild 29 (42.6%), moderate 24 (35.3%), severe 9 (13.2%). Inter-observer agreement was calculated with an intraclass correlation coefficient of 0.65 which indicates moderate reliability between the 3 raters. PICMI score at diagnosis significantly correlated with PCDAI (Paediatric Crohn's Disease Activity Index) at diagnosis (p: 0.036). Steroid-free remission at 1, 3 and 5 years was comparable between PICMI groups: remission + mild vs moderate + severe (p: 0.606). CRP and calprotectin negative steroid free remission at 1,3,5 was also comparable (p: 0.578). PICMI at diagnosis was associated with the probability of biologic introduction at 1 year: incidence rate ratio IRR: 2.17 (1.09-4.42); p=0.019, 3-year IRR: 2.12 (1.15-3.96); p=0.011, and 5 years: 2.21 (1.20-4.08); p=0.007 (figure 1).

Conclusion

PICMI score is a reliable and reproducible index to determine activity in children with Crohn’s disease. Children with more active disease at diagnosis according to PICMI have shown an increased need to progression to biologic treatment in order to gain a comparable rate of steroid free remission and inflammatory marker negativity if compared with children with lower PICMI scores.Read more P274 Renal failure in children with inflammatory bowel diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Renal manifestations may occur in children with inflammatory bowel disease (IBD). The cause of renal manifestations is often unclear, but may occur as an extra-intestinal manifestation or due to IBD treatment. Renal complications can lead to acute renal failure, a severe complication and associated with a risk of developing chronic kidney disease (CKD). Current paediatric ECCO/ESPGHAN guidelines recommended to regular monitor renal function with calcineurin inhibitors. However, these recommendations are based on limited knowledge of renal manifestations in paediatric IBD. The aim of this study was to investigate the diagnosis and underlying causes of renal failure in children with IBD.

Methods

Cases of renal failure in children <19 years with IBD were collected from the international, prospective PIBDSETQuality Safety Registry¹. A monthly survey was sent to participating paediatric gastroenterologists throughout the world asking to report cases of renal failure within their clinical practice. Renal failure was defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m² based on the Schwartz formula. Upon reporting a case of renal failure, a follow-up form was automatically sent to obtain more information about renal failure, IBD characteristics and outcomes (including CKD, defined as an eGFR <60 for >3 months).

Results

From November 2016 until August 2023, 220 gastroenterologists from 36 countries participated in the Safety Registry and 38 cases of renal failure were included. Characteristics at time of renal failure are reported in Table 1. Reported causes and diagnoses of renal failure are represented in Figure 1. Most frequently reported causes were IBD medication (n=12) and IBD itself (n=10). IBD medication included 5-ASA (n=5), tacrolimus (n=2) and one case of azathioprine or ibuprofen, vedolizumab, adalimumab, cyclosporine A and ciprofloxacin. Of the cases most likely caused by IBD itself, disease activity was remission (n=4), mild (n=2), moderate (n=3) or severe (n=1). In the majority of cases (n=26, 68%) creatinine was measured during routine follow-up, and not due to kidney-related symptoms. In 13/37 patients creatinine remained elevated after a median follow-up of 82 weeks [41-136 weeks]. Nine patients developed CKD, two patients required renal replacement therapy.

Conclusion

This is the first prospective study to report cases of renal failure in children with IBD. Renal failure can occur without symptoms, and may lead to CKD. Timely identification of cases of renal failure is important to adequately treat and monitor patients. We recommend to monitor creatinine in all children with IBD, independent of drug use, every 6 months.

References

1. Aardoom et al. BMJ Open. 2020Read more P224 JAK-STAT-Driven Tryptophan Degradation Fuels Mucosal Inflammation through QPRT Suppression-Induced Quinolinic Acid OverflowWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Inflammatory bowel disease is characterized by disturbed metabolism, including disrupted tryptophan (TRP) metabolism along the kynurenine pathway (KP). However, the molecular mechanism how this fuels inflammation is not understood. Here, we unravel rewiring of TRP metabolism in IBD by combining murine DSS colitis with multi-omics of longitudinal IBD cohorts.

Methods

Serum metabolites were associated with CRP, e/pMayo, SESCD and CDAI (n=83 UC, n=51 CD). Mucosal IDO1 and QPRT expression (both KP enzymes; indoleamine2,3-dioxygenase1, quinolinate phosphoribosyltransferase; n=273 UC) was correlated with Nancy index and eMayo. Murine enterocytes were treated with Qprt siRNA, LPS or IFNγ and cytokines measured by RT-qPCR. Tissue and serum of DSS colitis (C57BL/6, 2.5%, 5 days) and human PBMC or colon organoids (hOG) treated with IFNγ or Tofacitinib (Tofa) were analysed by LC-MS. Blood and biopsies for metabolomics and transcriptomics were obtained over 14 weeks from IBD patients (n=62) first introduced to biologics. Mucosal IDO1/QPRT expression was assessed at week 0, 8 and 16 in Tofa-treated UC (n=15).

Results

In longitudinal IBD therapy intervention cohorts, restoration of serum TRP metabolism was associated with 12-month disease control. Quinolinic acid (QUIN) levels relative to other TRP derivatives positively correlated with several disease activity metrics. Increased mucosal IDO1 and decreased QPRT expression upon proceeding disease severity suggested unbalanced QUIN levels as a joint result of augmented TRP turnover by IDO1 and blocked QUIN conversion by QPRT in active disease. In-vitro, QUIN overflow exaggerated pro-inflammatory cytokine responses. Accumulation of colonic QUIN was reproduced in DSS colitis and resulted in NAD+ (nicotinamide adenine dinucleotide) exhaustion, suggesting a local KP roadblock due to QPRT suppression. Integrated metabolomics and transcriptomics of IBD blood and biopsies confirmed TRP hyper-degradation at the inflammation site and revealed common JAK/STAT pathway upregulation in blood and mucosa. As IDO1 exerts the KP via JAK/STAT, IFNγ-induced KP-activation was rescued by JAK inhibition (JAKi) in human PBMC and hOG. Ultimately, we found mucosal QPRT and IDO1 expression to be significantly associated with therapy response to Tofa in UC, suggesting their baseline expression as an a priori predictor of JAKi therapy response.

Conclusion

TRP wasting in IBD appears to fuel mucosal inflammation due to QPRT suppression and subsequent QUIN overflow. Whether this mechanism is unique to IBD remains to be shown. Obvious future applications may include diagnostic patient classification and targeting therapeutic interventions in the TRP pathway.Read more P225 Mucosal transcriptomic profiles associated with clinical response in patients with Ulcerative Colitis receiving filgotinibWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Filgotinib (FIL) is an oral, once-daily, JAK1 preferential inhibitor approved for the treatment of Ulcerative Colitis (UC). In the phase 2b/3 SELECTION trial (NCT02914522), FIL had a high level of efficacy in inducing and maintaining histological remission and endoscopic response, relative to placebo (PBO). Here, we described the changes in the mucosal transcriptomic profiles associated with histologic and endoscopic responses following FIL or PBO treatment.

Methods

Patients with moderately to severely active UC were enrolled into one of two cohorts (biologic-naive or biologic-experienced) and randomized 2:2:1 to receive FIL 200 mg (FIL200), FIL 100 mg (FIL100) or PBO from baseline to week 10. RNA was extracted from colon biopsies collected at baseline and week 10, and RNA sequencing (RNA-seq) was performed according to standard protocols. Clinical responses of interest included histological remission (assessed by categorical Geboes score) and endoscopic response (both defined in Figure legend) at week 10.To assess transcriptional variability, RNA-Seq data were analyzed by a spectral map separately for baseline and week 10. Differentially expressed gene (DEG) analysis was used to explore differences in transcriptional expression for multiple comparators: from baseline to week 10 between patients with or without clinical response, separately, by treatment arm and cohort.

Results

RNA-Seq data were available for 1086 patients across treatment arms at baseline and/or week 10. Spectral map analysis showed no visual association between baseline transcriptional variability (principal component [PC]1: 26%) and achieving either histological remission or endoscopic response at week 10, nor with the treatment arm. At week 10, the main source of transcriptional variability (PC1: 32%) was visually associated with achieving histological remission or endoscopic response, but not with the treatment arm. From the DEG analysis, more significant genes were associated with histological remission in the FIL200 arm compared with either the FIL100 or PBO arms, especially for biologic-naive compared with biologic-experienced patients (Figure A). Furthermore, more significant genes were associated with endoscopic response in the FIL arms compared with PBO (Figure B).

Conclusion

The overall transcriptional response associated with histological remission or endoscopic response was greater in FIL treatment arms than the PBO arm. This transcriptional response differed between biologic-naive and experienced patients, suggesting that transcriptional changes associated with clinical response were influenced by both FIL treatment and previous biologic use. Preliminary data suggests these transcriptional changes occur in pathways related to UC pathogenesis.Read more P226 Disability in Crohn’s Disease Patients at diagnosis: Findings from the CROCO (Crohn´s Disease Cohort) studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Crohn’s disease (CD) can lead to progressive bowel damage and disability. Disability has been proposed by the SPIRIT-IOIBD consensus as an endpoint in disease-modification trials. Despite this, there is scarce data on disability at CD diagnosis.

Methods

The Crohn´s Disease Cohort (CROCO) is an ongoing prospective cohort study with newly diagnosed CD patients (within 12 months of diagnosis) aiming to assess the evolution of bowel damage and disability over time. Disability evaluation was conducted via the validated IBD-Disability Index (IBD-DI), which encompasses 14 questions ranging from 0-100 intended to measure overall health, sleep and energy, affect, body image, pain, defecation, interpersonal activities, and work and education.¹ This study explored disability scores (DS) and their association with disease features and activity at diagnosis in patients with newly diagnosed CD. The IBD-DI was categorized as previously reported in no disability (scores 0-20), mild disability (scores 21-35), and moderate-severe disability (scores 36-100).²

Results

From a cohort of 261 patients [58% male, median age at diagnosis of 35yo (IQR 25-49)], 224 completed the IBD-DI at inclusion. Median time from inclusion to baseline visit was 4 months (IQR 1.7-7.8). Most patients presented with ileal or ileocolonic disease location (87%) and an inflammatory phenotype (69%); 16% had perianal disease and 27% had extraintestinal manifestations. At inclusion, 21% had been hospitalised, and 10% had a CD-related surgery. Treatments included steroids (56%), immunosuppressants (34%), and anti-TNF therapy (40%). The median DS at inclusion was 22.2 (IQR 10.4-37.9), with 48% exhibiting no disability and 30% displaying moderate-severe disability (Figure 1). Moderate-severe disability at baseline visit was associated with female gender (OR 3.65, 95%CI 2.01-6.62, p<0.001), stricturing behaviour (OR 2.34, 95%CI 1.1-4.98), Harvey-Bradshaw Index (OR 1.36, 95%CI 1.23-1.5, p<0.001), extraintestinal manifestations (OR 2.61, 95%CI 1.41-4.84, p<0.002), and steroid use (OR 1.89, 95%CI 1.04-3.45, p=0.034). No significant associations were found with age, smoking, or biomarkers (Table 1).

Conclusion

One-third of newly diagnosed CD patients have moderate-severe disability. Disability was associated with female gender, disease phenotype, clinical severity, extraintestinal manifestations, and steroid usage. Disability is an important feature of newly diagnosed CD and may characterize a unique group of patients at diagnosis.

References

1 - PMID: 266469342 - PMID: 27516406Read more P227 The learning curve for using intestinal ultrasonographyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The use of intestinal ultrasonography (IUS) is recommended for suspected or known inflammatory bowel disease (IBD), but the technique is challenging to learn. This prospective study examined how the accuracy of IUS increases with operator experience (“learning curve”) and if prior abdominal ultrasound experience facilitates the learning process.

Methods

The study included five gastroenterologists: four trainees and one expert sonographer. Two trainees had limited abdominal ultrasound experience (< 50 exams) and two had extensive experience (> 500 exams); none had IUS experience. The trainees received an eight-hour course on IUS and one week of hands-on training with the expert sonographer on approximately 50 IUS exams. Thereafter, over a four-week period, each trainee performed 99 examinations and reported four IUS findings. The expert sonographer repeated the exam, and concordance (k) between the expert and trainees was assessed in three consecutive testing periods of 33 exams each.

Results

A progressive improvement in concordance was observed for all IUS findings from Period 1 to Period 3, overall and for both groups of trainees, although those with experience in abdominal ultrasound had faster learning curves. The minimum number of examinations required to achieve concordance with the expert operator (after the initial 50 exams) for detecting increased bowel wall thickness was 34 and detecting bowel dilatation was 29. However, a minimum of 47 examinations was necessary to achieve concordance for detecting intra-abdominal complications, considered an advanced IUS competence. The number of examinations required to achieve concordance was higher for trainees without than with abdominal ultrasound experience.

Conclusion

Basic competence in IUS can be acquired with relatively few examinations, while advanced competence requires more extensive training, particularly for gastroenterologists without abdominal ultrasound experience. These findings have implications for the development of training programs and the establishment of proficiency levels in IUS.Read more P228 Predictors of steroid therapy refractoriness in admitted Acute Severe Ulcerative Colitis patientsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

One third of acute severe ulcerative colitis (ASUC) patients are steroid refractory and require colectomy or rescue therapy. Risk stratifying ASUC patients who are steroid non responders to facilitate early initiation of rescue therapy or consideration of colectomy remains an unmet needs in the management of ASUC.

Methods

Records of admitted patients with ASUC over a 5-year period were included. Clinical (diagnosis history, previous medications, disease extent) laboratory (FBC, CRP and albumin at admission and day 3, CRP/albumin ratio) and endoscopic scores (Mayo and UCEIS) at admission were recorded. The primary outcome was response to IV steroids. Secondary outcomes were the proportion of patients requiring re admission or initiation of advanced therapy (biologics or small molecules) within 1 year.

Results

Our study included 103 ASUC patients (44/103 male, median age: 41 years(Min:18, Max:84, range:66, IQR:27). 53 patients were steroid responders, 50 patients were non responders. Among non responders 48 had rescue therapy and 5 had colectomy at index admission (3 after rescue therapy and 2 without rescue therapy). There was no statistical significant difference between both groups in age, gender, disease extent and duration, haemoglobin level, platelets, CRP level, Mayo score of sigmoid, UCEIS score of rectum and sigmoid. There was statistically significant difference between both groups in being on oral steroids at entry, duration of hospital stay, albumin at admission, day 3 albumin, CRP/Albumin ratio at day 3 and Mayo score of rectum.On univariate analysis, albumin at admission and at day 3, CRP/Albumin ratio at day 3 and being on oral steroids at entry predicted non response to steroids while on multivariate analysis, being on steroids at admission was the only factor independently associated with steroid non-response(OR= 4.695, 95% CI: 1.79-12.34, P=0.002).Among steroid responders, 13(24.5%) required readmission within 1 year while only 3(6.7%) of the steroid non responders who received rescue therapy required readmission.Twenty five(47.2%) of steroid responders required initiation of advanced therapies within 1 year of index admission while 28 didn’t. Patients who required initiation of advanced therapy have statistically significant lower hemoglobin and higher platelets than who didn’t. Hemoglobin was the only factor to predict initiation of advanced therapy in multivariate regression analysis(-0.043, P=0.029)

Conclusion

Being on oral steroids at admission for ASUC can predict non response to IV steroids with majority may benefit from upfront advanced therapies at Day 1 of admission. Nearly half of the admitted ASUC patients who respond to steroids require treatment escalation to advanced therapies at 1 year.Read more P229 Comparison of Different Histological Scoring Systems for Ulcerative Colitis [Nancy Histological Index, Robarts Histopathology Index and IBD-DCA (Inflammatory Bowel Disease-Distribution, Chronicity, Activity Score)] Among Specialists in GI Pathology and General Pathologists Pre- & Post WorkshopWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Histopathology is an emerging treatment target and an important parameter in predicting clinical outcomes of patients with ulcerative colitis (UC). Histological scoring indices Nancy Histological Index (NHI) and Robarts Histopathology Index (RHI) have been developed and validated for UC. We aim to compare the inter-observer reliability of NHI, RHI and the recently described Inflammatory Bowel Disease-Distribution, Chronicity, Activity (IBD-DCA) Score among gastrointestinal (GI) pathologists versus general pathologists pre- and post-workshop to determine the scoring system with the best reproducibility.

Methods

Digital whole slide images of 20 H&E-stained biopsies of ulcerative colitis (UC) cases are scored independently by 6 GI pathologists and 44 general pathologists that attended the Singhealth GI Pathology Course 2023 using NHI, RHI and IBD-DCA on the digital Pathpresenter platform. The 44 course participants performed the scoring before the course and again after attending a 3-hour IBD workshop on the assessment of histological remission using these 3 scoring systems. Data tabulation using “Free Online Surveys” platform is collated and intraclass correlation coefficient (ICC) of each component of the scoring indices is calculated. The ICC values of <0.5, 0.5–0.75, 0.75–0.9, and >0.9, indicate ‘poor’, ‘moderate’, ‘good’, and ‘excellent’ agreement, respectively.

Results

There is good inter-observer reliability for IBD-DCA ‘Activity’ component (ICC 0.85) and NHI (ICC 0.83) among GI pathologists while lBD-DCA ‘Distribution’ component (ICC 0.395) has the poorest agreement. Poor to moderate inter-observer reliability for all 3 scoring systems (ICC 0.4 – 0.6) is seen among the 44 participants pre-workshop with an observed post-workshop improvement, achieving best agreement for the NHI, ‘lamina propria neutrophils’ component of RHI and IBD-DCA ‘activity’ component (ICC 0.7).

Conclusion

GI pathologists are generally consistent in assessing disease activity in UC with good inter-observer reliability for NHI (a scoring system with an emphasis on activity grade) and only the ‘activity’ component of the IBD-DCA. Our study confirms NHI as a reliable scoring system for UC with the best reproducibility and favour its application to assess histological response in routine clinical practice to help gastroenterologists better manage patients with UC. We have also demonstrated that improvement in NHI scoring reproducibility can be achieved after training workshop for pathologists less familiar with the application of IBD histological scoring.Read more P328 Ischemic Ulcers Do Not Significantly Impact The Endoscopic Recurrence Score In Crohn’s Disease: A Multicenter Comparative Study After Right-Side Resections For Crohn’s Disease And Colorectal CancerWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Post-operative recurrence (POR) is common in patients with Crohn’s disease (CD) who have undergone surgery. Endoscopy, mainly based on Rutgeerts’ score, is crucial for the diagnosis of POR, showing also high prognostic value. More recently, several studies have suggested that the current endoscopic score system could be affected by the ischemic (not inflammatory) nature of some anastomotic ulcers, particularly at the level of the mucosal inverted stapled line, so overestimating the prevalence of the "real" anastomotic POR. However, these studies, based on the comparison between CD patients and subjects undergone right-side resection for colorectal cancer (CRC), included a very small population. Starting from these considerations, we performed a retrospective study aimed to directly compare the prevalence of anastomotic POR in CD with that of patients undergone right-side resection for CRC in a wide population.

Methods

A retrospective study was conducted at four Italian Institutions (2 with a high volume of IBD admissions; 2 with a high volume of CRC admissions). All patients performed endoscopy within 8 months from surgery. We selected all consecutive CD and CRC patients undergone a surgical resection with an anisoperistaltic stapled L-L anastomosis. The diagnosis of POR of CD was made in accordance with the modified Rutgeerts’ score (i0, i1, i2A, i2B, 3, 4). The global prevalence of POR (Rutgeerts’s score ≥2) was recorded. Furthermore, we directly compared the prevalence of the isolated anastomotic ulcers of CD (Rutgeerts i2A) to that detected in CRC patients.

Results

At the end of the study, we enrolled 221 CD patients and 72 CRC subjects. POR was recorded in 127 CD patients (57%). According to the endoscopic grade system, POR was scored as i0: 56 pts (25%), i1: 38 pts (17%); i2A: 42 pts (19%), i2B: 26 pts (12%), i3: 20 pts (9%), i4: 39 pts (18%). In the CRC group, endoscopy detected anastomotic ulcers in 2 out of 72 patients (3%); 1 case (1.4%) of CRC early recurrence was observed. When comparing the prevalence of isolated anastomotic ulcerations in CD (i2A) vs those in CRC patients, the prevalence of ulcerations was significantly higher in CD patients (19% vs 3%; p<0.01; OR=6.3).

Conclusion

Our study confirms the high prevalence of early recurrence in CD patients, highlighting the role of early (within 6-8 months) post-operative endoscopy in CD setting. The prevalence of anastomotic (ischemic) ulcers in CRC patients is very low and, as a consequence, this issue should not represent a real diagnostic matter if shifted into the POR setting of CD. Prospective, multicentre and directly comparative studies are needed to confirm our results.Read more P329 Sarcopenia is a risk factor of post-operative recurrence of Crohn’s diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Sarcopenia is defined as reduction in skeletal muscle mass and muscle strength; it was found in up to 50% of patients with Crohn's disease (CD) in several studies.In CD patients sarcopenia is a risk factor for surgery, post-operative complications and worse surgical outcomes; furthermore, it is a negative prognostic factor for endoscopic remission in patients treated with biologics.The aim of our study was to evaluate the impact of sarcopenia on endoscopic recurrence at 6-12 months follow-up in CD patients after ileo-colic resection.

Methods

CD patients undergoing primary elective ileo-colic resection surgery between 2013 and 2023 were enrolled. Patients with previous intestinal surgery, pre-operative complications (abscess, perforation) and immunosuppressive or biologic therapy after surgery were excluded. Sarcopenia was defined as the sex- and height-adjusted Total Psoas Area Index (TPAI) lower than 5.4 cm²/m² (men) and 3.56 cm²/m² (women), calculated at the level of the third lumbar vertebra on MRI scans performed within 3 months before surgery. Already known risk factors for post-surgical disease recurrence were considered. Uni- and multi-variate analyses were performed to evaluate if sarcopenia before surgery could influence endoscopic recurrence (Rutgeers score ≥ i2) of disease 6-12 months after surgery.

Results

Seventy-two CD patients were included. Endoscopic recurrence (at 6-12 months follow-up colonscopy) was found in 22% of patients and it was associated with the presence of pre-operative sarcopenia (1.4% vs 15.3%;p<0.001) and surgical complications (2.78% vs 6.94%;p=0.024), while it was not associated with comorbidies, familiarity, smoke, extension of resection or pre-operative therapy, PCR and albumin. Sarcopenia was identify as predictor of endoscopic recurrence (OR=25;p=0.005) as well as surgical complications after resection (OR=99.7;p=0.032). Neither medical or surgical complications showed statistically significant correlation with the presence of pre-operative sarcopenia (p=0.819).

Conclusion

Sarcopenia in CD patients before surgery seems to be an independent prognostic factor for endoscopic recurrence. Perioperative interventions to improve sarcopenia may have positive impact on surgical outcomes and disease recurrence.Read more P330 Rate of disability at diagnosis in patients with inflammatory bowel diseases: Results from a prospective population-based inception cohort, IBD Prognosis StudyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Inflammatory bowel diseases (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), are chronic, progressive diseases associated with a high level of disability over time. In the current study, we aimed to investigate the occurrence of disability at the time of IBD diagnosis and determine its association with the initial disease presentation.

Methods

Incident adult patients (≥18 years old) with newly diagnosed UC or CD according to the Copenhagen IBD Criteria were included in the IBD Prognosis Study, a prospective, population-based, inception cohort covering a catchment areas of approximately 20% (1.1 million) of the Danish population. Disability was assessed using the validated IBD-Disability Index version 2.¹ We defined no, moderate, and severe disability scores as 0-20, 36-50, and 51-100 points.² A severe disease presentation was defined by the need for glucocorticoids, immunomodulators, biologics, or surgery within three months of disease. Multivariable logistical regression analyses were conducted by adjusting for gender, age, and IBD phenotype.

Results

Out of the original cohort, 208 (67.5%) and 128 (63.1%) patients with incident UC and CD, respectively, responded to the questionnaires. In comparison to non-responders, the former differed only in a higher proportion of female patients and never-smokers with UC, while a higher proportion of current smokers among patients with CD responded.The mean IBD Disability scores differed significantly between UC (24.2, standard deviation (SD) 18.1) and CD (28.8, SD 18.6, p=0.01), with every fourth and third patient, respectively, experiencing moderate or severe disability (moderate: UC: 9.9%, CD: 22.4%, p=0.002); severe: UC: 12.3%, CD: 11.2%, p=0.77).Independent factors associated with disability were extensive UC as well as female gender and extra-intestinal manifestations in both UC and CD (Table 1).In multivariable logistical regression analyses adjusting for age at disease onset, gender, and disease phenotype, severe disability was significantly associated with a severe initial presentation of IBD, including IBD-related hospitalization and initiation of biological therapies (Figure 1).

Conclusion

In this prospective population-based inception cohort of unselected patients with newly diagnosed IBD, we found every third and every fourth patient with UC and CD to experience moderate-to-severe disability at the time of diagnosis, which was independently associated with a severe disease presentation. These findings have implications for patient management and surveillance strategies.

References

1 Peyrin-Biroulet L, et al. Gut. 2012. doi: 10.1136/gutjnl-2011-300049.2 Gower-Rousseau C et al. Gut. 2017. doi: 10.1136/gutjnl-2015-310151.Read more P331 Photoplethysmography waveform analysis detects inflammatory status in patients with inflammatory bowel diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Early detection of inflammatory flares and corresponding treatment adjustment were shown to improve inflammatory bowel disease (IBD) patient care. Current episodic inflammatory biomarker testing allows limited monitoring and is associated with suboptimal compliance. We aimed to test the feasibility of monitoring patient inflammatory status by non-invasive photoplethysmography (PPG) waveform analysis.

Methods

Patients hospitalized due to IBD flares and flaring outpatients treated with IV biologics were continuously monitored using a finger-based PPG device. Flares were defined as Harvey Bradshaw index>5, or partial Mayo score> 3, or fecal calprotectin >250mcg/gr, or C-reactive protein (CRP)>1.5X the upper normal limit. We extracted and analyzed features from the raw PPG waveform to predict levels of CRP, erythrocyte sedimentation rate (ESR), and platelet counts during hospitalization. Ambulatory patients were assessed at each scheduled infusion. Models were developed using support vector machines (SVMs). The dataset was partitioned into a training set, comprising 75% of the data, and a validation set, comprising the remaining 25%. Principal component analysis (PCA) on the PPG waveform features was conducted to assess potential distinctions correlating with levels of inflammatory markers.

Results

Monitoring results were available from twenty-six patients (14 Crohn's disease, 12 ulcerative colitis). Analysis of all pooled PPG measurements revealed that the PPG waveform analysis enabled prediction of ESR results with R² 0.91, and root mean square error (RMSE) 5.6; of platelet count with R² 0.87 RMSE 59.1; and CRP with R² 0.69 RMSE 1.55. Analysis of individual patient data demonstrated that PPG features reflected different ESR values along the treatment course as depicted in a representative example in Figure 1. Dynamics of PPG measurements were demonstrated in all monitored patients as compared to partial detection of inflammatory dynamics by conventional biomarkers.

Conclusion

Analysis of PPG waveform features allowed continuous passive monitoring of the inflammatory status in patients with IBD and was sensitive to daily dynamics in a heterogenous patient population. This technology may allow feasible, sensitive and continuous patient inflammatory state monitoring and support optimized IBD patient care.Figure legend:PPG signal features reflect the changes in ESR values across treatment daysEach dot represents a single measurement. Colors represent different days. Dot diameter is proportional to ESR values.Read more P223 Early prediction and objective criteria to define failure of rescue medical therapy in acute severe ulcerative colitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Medical rescue therapy (MRT) is effective in intravenous corticosteroid refractory acute severe ulcerative colitis (ASUC). We recently described the ADMIT-ASC score to identify patients on admission at high risk of steroid failure. In this setting, our primary objective in this analysis is now to identify parameters at admission which could identify non-response to MRT, following corticosteroid failure. Co-primary objective is to develop and validate a model to identify non-responders to MRT.

Methods

Two cohorts were studied, for discovery and validation. Retrospective analysis of 66 adult ASUC admissions receiving MRT between 2015-19 at Gold Coast University Hospital and Logan Hospital was first performed. Clinical, endoscopic and laboratory data were collected. Non-response was defined as undergoing colectomy during the index admission. Univariable and multivariable logistic regression were employed to identify predictors of non-response. A predictive model was developed based on thresholds obtained from ROC curves. The predictive model was validated in 99 patients admitted to Gold Coast University Hospital and Sunshine Coast University Hospital between 2020-23.

Results

In the 2015-19 cohort, out of 66 episodes who received MRT, 11 episodes (16.7%) underwent colectomy during the same admission. UCEIS at admission was the strongest predictor of non-response to MRT [OR 3.03 (95%CI 1.47-6.22), p 0.033), AUROC 0.7552 (95%CI 0.6271 – 0.8832]. UCEIS score ≥6 had sensitivity 100%, specificity 41.7%, PPV 26.3%, NPV 100%, to predict non-response to MRT. CRP on day 3 after commencing rescue therapy (CRP Day R+3) was also a predictor for non-response to MRT (OR 1.02 (95%CI 1.00-1.05), p 0.015). A score comprising 2 points involving UCEIS ≥ 6 and CRP value of ≥ 22 mg/L on day R +3 was developed (1 point each). Score of 2 points had accuracy 79.6%, specificity 75%, sensitivity 100%, PPV 47.4%, NPV 100%, AUROC 0.8750 (95%CI 0.8070-0.9429) for non-response to MRT. In the validation cohort, 6 (6.1%) patients underwent colectomy during the same admission after failing MRT. On implementing the score, a score of 2 points had accuracy 86.7%, specificity 88.1%, sensitivity 66.7%, PPV 28.6%, NPV 97.4%, AUROC 0.8095 (95%CI 0.6423-0.9768) for predicting non-response to MRT.

Conclusion

UCEIS score at admission and CRP on day 3 after commencing MRT are predictors of non-response to MRT. We have developed and validated a model to identify non-response to medical rescue therapy, and objective criteria to mandate surgical intervention.Read more P231 Impact of the depth of mucosal healing on the burden of ulcerative colitis : a cross-sectional studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Ulcerative colitis (UC) is a major cause of disability, affecting physical, emotional and social well-being. The recent STRIDE II international guidelines consider disability-free and normal quality of life as therapeutic targets. Today, the degree of mucosal healing required to reduce disability, incontinence and bowel urgencies is poorly known.

Methods

We conducted a single-center cross-sectional study between January 2021 and June 2023. All consecutive patients with UC and endoscopic healing (Mayo ≤ 1) underwent IBD-disk disability assessment the day of the colonoscopy. Histological healing was defined as Nancy score 0 or 1 (2 biopsies per segment from rectum to right colon). Moderate to severe disability was defined as an overall score ≥ 40. Incontinence was defined by a Wexner score >5 and bowel urgency by an NRS urgency score > 1).

Results

A total of 57 patients were included, with 34 (59.6%) women. Median age and disease duration were 47.4 (interquartile range [IQR] [43.5; 51.2]) and 13.0 years (IQR, 13.1-18.4), respectively. 37/57 (65%) patients had complete endoscopic healing Mayo 0 and 43/54 (80%) histological healing. The median overall IBD-Disk score was 29 [25.5; 37.5] and 27 (47%) had moderate to severe disability. There were no differences in terms of age, gender, body mass index, smoking status, disease extension and treatment for the 3 groups Mayo 1, Mayo 0 and histological healing. The rate of moderate to severe disability was not different among patients with Mayo 0 (7/20, 35%) vs. Mayo 1 (20/37, 54%) patients (p=0.26), or in patients with (22/43, 51%) or without histological healing (4/11,36%) (p =0.51). Of the 35 patients assessed, bowel urgency were reported in 11 (31.4%), with no difference between the two definitions of endoscopic healing (p=0.72) or histological healing (p=0.37). Among the 35 patients with a Wexner score evaluation, incontinence was observed in 19% (4/21) and 14% (2/14) of Mayo 0 and Mayo 1 patients respectively (p=0.99), and 24% (6/25) vs. 0% (0/7) of patients with or without histological healing (p=0.3).

Conclusion

Half of patients with UC who achieved endoscopic healing reported a moderate to severe disability. Mayo 0 (vs. 1) endoscopic healing and histological healing do not appear to provide any short-term benefit in terms of disability, fecal incontinence or bowel urgency.Read more P232 Common variable immunodeficiency-associated enteropathy in consecutive patients from a tertiary hospitalWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Common variable immunodeficiency (CVID) patients may develop intestinal inflammatory involvement in 9-20% of cases, although its diagnosis, management and prognosis are not well established.

Methods

We performed a transversal study with retrospective data collection. We reviewed all clinical records from consecutive adult CVID patients followed in Gregorio Marañón Hospital (Spain) from January 1st 1990 to January 1st 2023. A diagnosis of CVID-associated enteropathy (CVID-E) was established if patchy intestinal inflammation (Crohn-like pattern) or colonic inflammation (ulcerative colitis-like pattern) was demonstrated, or villous atrophy was observed in duodenal biopsies (celiac-like pattern) or inflammatory infiltrate was observed in colonic biopsies (microscopic colitis-like pattern). Differences between CVID-E patients and the rest of the CVID cohort were evaluated using chi-square and T student methods, when appropriate.

Results

89 patients with confirmed CVID following ESID criteria were included. Patients’ characteristics are summarised in Table 1. All patients were receiving intravenous or subcutaneous Igs and reached an Ig G trough level >1000 mg/dL. CVID-E was diagnosed in 26 patients (29,2%), at a median of 6,4 years after CVID diagnosis. Surprisingly, 10 patients (38,5%) were diagnosed with CVID-E before or at the same time of CVID diagnosis. 5 patients were dead (19,2%), and the causes of death were gastric cancer (1 patient), liver complications (1), infectious complications (1), enteropathy (1) and unknown cause (1). 73,1% suffered from GI infections (Giardia lamblia, Campylobacter jejuni and Clostridioides difficile were the most frequent agents). The most frequent pattern of the disease was Crohn-like disease (Figure 1). Although exclusive celiac-like pattern was found in only 3 patients, 5 Crohn-like, 4 UC-like and 2 microscopic colitis-like pattern patients also presented duodenal atrophy. Unexpectedly, 46,2% of CVID-E patients suffered from concomitant liver involvement. Eight patients received corticosteroids, 2 azathioprine and 1 patient received infliximab and subsequent ustekinumab. One patient needed subtotal colectomy, another ileal resection and another patient received a terminal colostomy due to severe perianal disease. CVID-E patients presented statistically more frequent liver involvement, more GI infections, and a tendency towards more GI cancer.

Conclusion

CVID-E is frequent among CVID patients. These patients suffer from more GI infections, liver involvement and probably more GI cancer. Screening of levels of Igs at diagnosis of IBD and celiac disease is advisable as CVID diagnosis can occur at the same time or even after enteropathy diagnosis.Read more P365 Incidental terminal ileitis in asymptomatic patients. Is it Crohn’s disease?Wed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Inflammation of the terminal ileum is a common finding during colonoscopy, even in patients without symptoms as an accidental finding. Nevertheless, there are no guidelines or wide consensus about the indications for treatment or follow-up, since the clinical importance and natural history of this entity has not yet been fully investigated.

Methods

This was a retrospective cohort study, where the electronic database of the Gastroenterology Department of University Hospital of Heraklion, Greece was searched through using the term "inflammation of terminal ileum" and "ulcers of terminal ileum", through the years 2012-2023. All cases with terminal ileitis as an accidental finding in asymptomatic patients, where colonoscopies performed for miscellaneous reasons (e.g. screening colonoscopy, follow-up colonoscopy after polypectomy) were identified. Patients with symptoms, or known Crohn’s Disease (CD) were excluded. Patients’ demographics, endoscopic and clinical follow-up data, as well as treatment and final diagnosis of CD were registered. Possible risk factors for terminal ileitis [smoking, use non-steroidal anti-inflammatory drugs (NSAIDs)] were also recorded. Univariate and multivariate analysis of the data was performed with SpSS v22 software.

Results

In a total of 465 cases with terminal ileitis 205 had known CD, 153 underwent colonoscopy for symptoms whereas 107 patients (62 females) underwent colonoscopy with no associated symptoms and constituted the study population. Among these 107 patients [median age 50, interquartile range (IQR) 39-64years, median BMI 25kg/m², IQR 23.2-27.1kg/m², median follow-up 4years) 27 (25%) patients were current smokers, 32 (30%) ex-smokers and 22 (20%) reported recent use of NSAIDS (Table 1).During follow-up, 88 (82%) patients had a new colonoscopy with persistence of terminal ileitis in 66 (62%) of them, 68 (64%) developed symptoms, 37 (35%) were diagnosed with CD,39 (36%) received treatment, and 18 (17%) required hospitalization.In the group of the patients that required treatment, only 8 (7.4% of the study population) eventually required systemic immunosuppression (corticosteroids, thiopurines, biologic agents.In multivariate analysis, there was no statistically significant correlation between the persistent terminal ileitis on follow-up colonoscopy and BMI, the use of NSAIDs, or ex-smoking. Nevertheless, there was a significant correlation between active smoking and the persistence of terminal ileitis (p=.005).

Conclusion

Most of the patients with incidental, asymptomatic terminal ileitis remain asymptomatic and don’t require treatment. Close monitoring is required since diagnosis of Crohn’s disease is established in one third of them.Read more P366 Risk factors and outcomes of chronic antibiotic-refractory pouchitis in Korean ulcerative colitis patients: a single center retrospective studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Chronic inflammation of the pouch after total proctocolectomy with ileal pouch-anal anastomosis (IPAA) remains a morbid complication in ulcerative colitis (UC). The goal of this study was to investigate risk factors and clinical outcomes of chronic antibiotic-refractory pouchitis (CARP) in Korean patients with UC.

Methods

This was a single center retrospective study on patients with UC who underwent total proctocolectomy with IPAA at Asan Medical Center in Korea between January 1987 and December 2022. CARP was defined as failure to respond to a 4-week course of a single antibiotic, needing more than 4 weeks of therapy with 5-aminosalicylates, steroids, immunomodulators or biologics/small molecules, while chronic antibiotic-dependent pouchitis (CADP) was defined as more than 3 episodes of pouchitis per year or persistent symptoms requiring long-term antibiotics to maintain disease remission. Primary outcomes were endoscopic remission defined as complete mucosal healing of chronic pouchitis and pouch failure defined as the requirement of diverting loop ileostomy or pouch excision. Univariable and multivariable logistic regression analysis were used to identify risk factors of CARP.

Results

A total of 251 patients were included and 232 were analyzed (Male, 57.3%; Current smoker, 13.4%; Median age at surgery, 44 years; Disease duration at surgery, 4 years; Previous exposure to biologics/small molecules, 23.7%; Extra-intestinal manifestations, 8.2%; Preoperative cytomegalovirus infection, 19.4%). The most common cause of surgery was steroid refractoriness (50.9%), followed by dysplasia/colorectal cancer (26.7%). The median time from surgery to chronic pouchitis was 48 months (interquartile range 23.5–100.0). Among 74 patients (31.9%) with chronic pouchitis, 31 patients (13.4%) were CARP and 43 patients (18.5%) were CADP. The most frequent endoscopic phenotype according to Chicago classification was focal inflammation of the pouch in all groups (chronic pouchitis, 47.3%; CARP, 35.5%; CADP, 55.8%). Patients with CARP were less likely to have concomitant probiotics compared with CADP (29.0% vs 72.1%; p<0.01). Endoscopic remission rate in chronic pouchitis, CARP, and CADP were 14.9% (11/74), 9.7% (3/31), and 18.6% (8/43), respectively (Table 1). Pouch failure rate in chronic pouchitis, CARP, and CADP were 13.5% (10/74), 16.1% (5/31), and 11.6% (5/43), respectively (Table 1). In a multivariable analysis, current smoking status was positively associated with CARP development (OR: 3.56; 95% confidence interval 1.33–9.52; p=0.01).

Conclusion

Current smoker with UC who underwent IPAA had a higher risk of CARP. Concomitant use of probiotics was less likely to be associated with developing CARP.Read more P367 Are patients with Inflammatory Bowel Disease and two or more associated Immune-Mediated Inflammatory Diseases different from those with no or one associated disease?Wed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

It is well known that immune-mediated inflammatory diseases (IMIDs) are frequently diagnosed in patients with inflammatory bowel disease (IBD). However, few studies have taken into account whether the number of associated IMIDs influences IBD. Our aim was to evaluate the clinical, demographic, and drug needs of patients with IBD based on the number of other IMIDs they present.

Methods

Cross-sectional study that included patients treated at the IBD Unit of the Central University Hospital of Asturias (Spain) between August 2020 and December 2021. Demographic data and disease characteristics were collected and IMID diagnosis was confirmed in the medical records of each patient. Patients were split into three groups: non-IMID, 1-IMID, and two or more associated IMIDs. Hospitalizations, drugs and surgery requirement were analyzed. The comparison between groups was carried out using the Kruskal-Wallis test, and Pearson's Chi-square test or Fisher's exact test. When there was a significant difference between any of the groups, a post-hoc test was performed with p-value correction following the Benjamini and Hochberg method.

Results

A total of 1,620 patients were included in the analysis. 1,067 (66%) had no IMID, 394 (24%) had one IMID, and 159 (9.8%) had two or more IMIDs. Overall, the most frequent IMIDs were spondylarthritis (14%), psoriasis (7.5%), erythema nodosum (4.3%), intrinsic asthma (2.8%), and uveitis (2.5%). The presence of an IMID was associated with older age, longer duration of IBD, female sex, and Crohn's disease (Table 1). The use of steroids, immunomodulators, and biologics, as well as the need for hospitalizations, was higher in patients with several IMIDs. When we analyzed the groups of patients with one and with two or more IMIDs, the only significant differences were a longer duration of disease, a greater prevalence of Crohn's disease, and a higher use of steroids, immunomodulators, and biologics among patients with two or more IMIDs. The percentage of patients with joint (spondylarthritis, psoriasic arthritis, juvenile idiopathic arthritis), cutaneous (psoriasis, hidradenitis suppurative, erythema nodosum, pyoderma gangrenosum) and ocular (uveitis and episcleritis) IMIDs and intrinsic asthma was higher in the group with two or more IMIDs than in the group with one IMID.

Conclusion

10% of patients with IBD have two or more associated IMIDs. The duration of IBD and the need to use steroids, immunomodulators and biologics is greater than in patients with one IMID.Read more P368 Correlation between patient-reported outcome measures in inflammatory bowel disease and other measures of disease activity: a systematic reviewWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The clinical activity of inflammatory bowel disease (IBD) has traditionally been evaluated by healthcare professionals. To allow direct reporting of symptoms by patients, several patient-reported outcome measures (PROMs) have been developed. We evaluated the correlation between IBD-specific PROMs and measures of endoscopic activity.

Methods

A systematic review of the literature was performed up to June 2022. Searches were conducted in three databases (PubMed, Scopus and Web of Science). The search protocol was registered in PROSPERO (CRD42022383899). Studies reporting the correlation between self-administered, IBD-specific PROMs and endoscopic scores were included. A descriptive analysis was performed by assessing the correlation between PROMs and IBD endoscopic activity. PROMs used in Crohn’s disease (CD) and ulcerative colitis (UC) were considered separately.

Results

Seventeen PROMs were identified encompassing a series of IBD signs and symptoms, mainly abdominal pain (n=10), stool frequency (n=6) and rectal bleeding (n=4). Twenty-two studies assessed correlations of PROMs with existing clinical measures of disease activity and/or their accuracy in predicting remission. The mainly used endoscopic indices were Simple Endoscopic Score for CD (SES-CD) and Mayo endoscopic subscore (MES) (n=11), and clinical indices were Harvey–Bradshaw Index for CD (n=7) and SCCAI for UC (n=7). Most studies used more than one comparator as standard for validation. A marked heterogeneity in the study design and statistical methods was observed. In CD, five studies analysed correlations between PROMs and SES-CD. They generally found weak correlations with PROMs (PRO2, n=2; mobile Health Index [mHI]-CD, n=1) (Figure), except for one which found a negative moderate correlation between PRO2 and SES-CD. The strongest correlation was with the stool frequency item of the Monitor IBD at home (MIAH) questionnaire. In UC, four studies assessed the correlation between PROMs and MES. Positive weak-to-moderate correlations were found with PRO2, MIAH rectal bleeding item and mHI-UC MES in four studies.

Conclusion

In CD, PROMs poorly correlate with endoscopic activity. However, in UC, rectal bleeding reasonably correlates with endoscopic status. It is well known that IBD symptoms overlap with those of other digestive diseases as functional disorders, especially in CD. In line with this, our data suggest that PROMs cannot substitute endoscopic data to monitor disease activity in IBD, especially in CD patients. Nonetheless, they represent a valuable complementary instrument to comprehensively describe disease control by capturing patient perspective. More studies are needed to better evaluate correlations between PROMs and clinical disease activity measures.Read more P119 Single-cell RNA sequencing in Inflammatory Bowel Disease in patients with Primary Sclerosing Cholangitis: a distinct form of colitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Primary sclerosing cholangitis (PSC) is an inflammatory disorder of the bile ducts, in which Inflammatory bowel disease (IBD) concomitantly occurs (PSC-IBD). Substantial differences in clinical presentation are observed between PSC-IBD and ulcerative colitis (UC). In this study we aim to find distinct pathomechanisms for PSC-IBD using single-cell RNA sequencing.

Methods

Forty-seven colonic samples of PSC-IBD (n=24), UC (n=18) and non-IBD subjects (n=5) were collected. Whole biopsies were dissociated into single cells using collagenase digestion. Library preparation was done with 10x Genomics and sequencing was performed on an MGI2000 sequencer. Then, differential abundance, differential expression, and cell-cell interaction analyses were performed. Stainings for DUOX2 and HLA-DR were performed on paraffin embedded colon mucosal slides.

Results

In total, 71,798 high quality cells identified 54 distinct cell types, including a new type of epithelial cells: DUOX2+ enterocytes. DUOX2+ enterocytes are almost exclusively present in diseased inflamed colon and can act as antigen presenting cells through the expression of MHC2 on its surface. A general shift in cell type composition upon inflammation was observed, comparable between PSC and UC samples. However, an increased abundance was seen for stem cells in non-inflamed (NI) PSC, and not in UC-NI, compared to healthy controls. Additionally, we found distinct gene expression patterns between PSC and UC inflammation: while activation of inflammatory monocytes was observed in PSC inflammation, several types of fibroblasts were activated upon UC inflammation.

Conclusion

We describe DUOX2+ enterocytes, which may play a role in both PSC and UC colitis through antigen presentation. Furthermore, we show that intestinal inflammation in PSC-IBD, as compared to UC, is characterized by distinct mucosal cell composition and cell-specific gene expression patterns. PSC colitis, and not UC colitis, is driven by activation of inflammatory monocytes, with antigen presentation through HLA-DRB1, and activation of CD4+ T cells. Additionally, an increased abundance of stem cells in PSC-NI could be related with the increased colorectal cancer risk in PSC-IBD.Read more P120 A novel population of classical monocytes is expanded in CD and defined by an upregulation of genes relating to mononuclear cell differentiation and response to microbesWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

In Crohn's disease (CD), differentiation of classical blood monocytes to intestinal macrophages in the mucosa generates inflammatory rather than regulatory cells. Microbial products and cytokines can systemically reprogramme monocytes via effects on myelopoiesis. We hypothesised that in CD transcriptional changes occur in monocytes prior to their recruitment to the intestine which predispose to pro-inflammatory signatures in the mucosa. Here, we used single cell RNAsequencing (scRNAseq) to explore monocyte heterogeneity and identify CD-associated changes in gene expression profiles.

Methods

PBMCs were isolated from newly diagnosed CD patients (n=10) and matched healthy controls (HC, n=10). scRNAseq was performed using the 10x Genomics Chromium 3’ assay at a target capture rate of 10,000 cells/sample and sequencing at ~50,000 reads/cell. A dataset was generated using Cell Ranger and following unsupervised clustering (using Seurat) the CD14+ and CD16+ monocyte populations were selected. Data were further analysed using Seurat, DeSEQ2, g:Profiler, GSEA and Cytoscape.

Results

In addition to non-classical and intermediate monocytes, five transcriptionally distinct clusters of classical monocytes were identified in both CD patients and controls. One cluster (‘cluster 3’) was significantly increased in abundance in CD; other clusters were present at similar frequency in health and CD. Cluster 3 was defined by gene ontology (GO) pathways related to response to bacteria, cell migration, lymphocyte proliferation and response to oxidative stress. In CD compared with health, the most upregulated genes included those encoding EGR (early growth response) proteins 1-3 that play a key role in the functional plasticity of monocytes, and the key inflammatory cytokine IL-1β, as well as cytokines and regulators of their signalling (e.g. CXCL2/3, SOCS3). Overall, in Cluster 3, GO pathways positively enriched in CD related to microbial response signalling, canonical WNT signalling and mononuclear cell differentiation.

Conclusion

Classical monocytes are heterogeneous and include a novel subset that is expanded in CD. In this population, the expression of genes and pathways related to functional plasticity, response to microbes and inflammatory activity are enhanced in CD. These data support a systemic reprogramming of monocytes in CD that predisposes to inflammatory activity upon recruitment to the intestine.Read more P198 Systematic review to highlight practices and programmes for transition for adolescents with Inflammatory bowel diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Adolescents with inflammatory bowel disease (IBD) will eventually transition from the family-centric paediatric healthcare team to the adult service. This process happens at an appropriate age or level of development and depends on a number of factors such as transition readiness, disease specific factors, and local policies and practice. This transition period is challenging for patients, families and healthcare providers. The use of structured transition programmes is increasingly incorporated into standards of care, yet the optimal format is not yet fully delineated, and practices vary considerably. The aim of this study was to carry out a systematic review of structured transition programmes and their components to assess impact on disease-specific and transition-related outcomes.

Methods

A literature review was carried out in four main databases (PubMed, CINAHL, CENTRAL, EMBASE) and relevant publications from the year range 1970-2023 reviewed. Inclusion criteria: reporting on adolescent IBD patients and investigating structured transition programmes/interventions. Exclusion criteria: not reporting outcomes relating to transition readiness/skills or disease related outcomes. Two investigators reviewed the articles, extracted data, and two assessed bias.

Results

There were 3432 articles identified from initial searches, and 38 included in the final review. Twenty-six studies reported the use of structured transition programmes, and 12 investigated discrete interventions. The key outcomes studies included knowledge, self-efficacy, adherence, clinic attendance and transition readiness. These outcomes consistently improved with the use of structured transition programmes. Those adolescents with IBD transitioning with no structured programme experienced a 3.5-fold increase in IBD related surgical rates, and 2-fold increase in hospital admission rates. Structured transition programmes were shown to significantly improve transition readiness assessment scores. Transitional care programmes consistently improved the following outcomes; relapse/admission rates, corticosteroid use, quality of life, and surgery. The bias assessment showed between-study heterogeneity, low quality of evidence, and high risk of bias.

Conclusion

Transition outcomes for adolescents with IBD were consistently improved with the use of structured transition programmes. This literature review highlights the considerable variation in delivery of transition care, and the need for optimization of strategies. There is no current standardized model for adolescent IBD patients in Australasia, and this review will guide development of regional IBD transitional care consensus statements.Read more P199 External validation of Intestinal Ultrasound score: IBUS-SAS with clinical (CDAI), biomarkers and endoscopic scoring system (SES-CD)Wed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Intestinal ultrasound (IUS) is a non-invasive tool for assessing disease activity in patients with Inflammatory bowel disease. International Bowel Ultrasound Segmental Activity Score (IBUS-SAS) is a comprehensive score proposed by an expert consensus with good reliability. We aim to assess the correlation of the IBUS-SAS with clinical and endoscopic scores and biomarkers in patients with Crohn’s disease (CD) in a point-of-care setting.

Methods

This retrospective study was conducted from October 2021 to September 2023. All patients with CD who underwent colonoscopy at initial presentation or assessing disease activity on follow-up were included. At the clinic visit, Crohn’s disease activity index (CDAI), C-reactive protein levels (CRP), Faecal calprotectin (FC) were documented. IUS was performed in the clinic and IBUS-SAS was documented. A colonoscopy was done within 1 week of the clinic visit. Endoscopic disease activity was documented using Simple Endoscopic Score in Crohn’s disease (SES-CD).

Statistical Analysis

Pearson’s correlation was performed between IBUS-SAS and the clinical and endoscopic scores and the biomarkers. ROC analysis was done to assess the threshold value of IBUS-SAS to predict the presence of endoscopic disease activity.

Results

181 patients were included in the study.In patients with clinical remission, the median IBUS-SAS was 8 (± 23.5). The median IBUS-SAS was 62 (± 21.47), 70 (± 15.47) & 64 (± 0.58) in patients with mild, moderate to severe & severe CDAI respectively. The Pearson correlation coefficient between IBUS-SAS & CDAI was 0.7 (95% CI 0.62-0.77; p < 0.001).The IBUS-SAS in patients with normal CRP levels (< 5mg/L) was 8 (± 19.54) & in patients with elevated CRP was 64 (± 18.99). The IBUS-SAS in patients with normal FC was 8 (± 19.65) & elevated FC (>250mcg/g) was 64.5 (± 22.66). The Pearson correlation coefficient between IBUS-SAS & CRP was 0.49(95% CI 0.37-0.60; p < 0.001) and with FC was 0.58 (95% CI 0.46-0.68; p < 0.001).The IBUS-SAS correlated well with SES-CD score with IBUS SAS scores of 8 (± 12.92), 53.5 (± 16.35), 65 (± 20.83) & 65 (± 8.62) in patients with inactive, mild, moderate, & severe SES-CD respectively. The Pearson correlation coefficient between IBUS-SAS & SES-CD was 0.77 (95% CI 0.7-0.82; p < 0.001).The IBUS-SAS score of > 37.5 revealed an area under the curve of 0.96 (95% CI 0.92 – 0.99) with a sensitivity of 94% & specificity of 91% to predict endoscopic disease activity (SES-CD > 3).

Conclusion

The IBUS-SAS score correlated very well with clinical and endoscopic disease activity as well as biomarkers. A score > 37.5 had a sensitivity of 94% and specificity of 91% to predict the presence of endoscopic disease activity.Read more P200 Oral Mannitol for bowel preparation in IBD patients: a post-hoc analysis of a multicentre, controlled, randomized clinical trialWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Bowel preparation is the most burdensome part of the whole colonoscopy procedure according to patients. A diagnosis of Inflammatory Bowel Disease (IBD) implies the need for lifelong repeated colonoscopies, therefore amplifying the problem. Bowel preparation with oral Mannitol, a sugar alcohol with a sweet taste, could significantly improve the patients’ tolerance as it has a quick onset, is single dose and has a low volume.^1-3

Methods

This is a post-hoc analysis of IBD patients included in the SATISFACTION study, a third phase multicentre, international, randomized, endoscopists-blinded controlled trial⁴. Patients were randomized (1:1) to 750mL of oral mannitol (OM, 100 g in 750 mL water) to be drunk in a single dose 4 hours before colonoscopy versus a standard split preparation with 2L PEG-ASC (PEG). An intention to treat analysis was performed on patients who underwent colonoscopy and who took bowel preparation even partially. Biological important parameters summarising the rate of bowel cleansing and patients’ satisfaction were collected.

Results

A total of 55 IBD patients (M = 24, P = 31, Crohn’s = 12, Ulcerative Colitis = 40, Microscopic colitis =3) from 7 centres were ruled in for this post-hoc analysis. The two population were comparable in terms of age and sex and diseases (Table 1). A statistically significant preference of OMl over PEG was found in terms of taste (numerical rating scale – NRS, p < 0.001), willingness to reuse the preparation (p = 0.03), and of time of first evacuation (M 56.6 minutes, P 90.7, p = 0.01). No differences were found in terms of adequate bowel cleansing as assessed by the Boston bowel preparation scale (96% OM, 97% PEG), adherence to bowel preparation (complete in 100% OM, 94% PEG) and easy of use (88% OM, 71% PEG). Minor and expected adverse events of special interest such as nausea and abdominal pain were comparable in the two courts (12% OM, 3% PEG).

Conclusion

Bowel preparation with a very low volume of oral mannitol in a single dose 4 h before colonoscopy provides better satisfaction among IBD patients and showed an excellent efficacy and safety profile as compared to the standard split preparation with 2L PEG-ASC. Same day bowel preparation with oral mannitol is a reliable option for colonoscopy in IBD and an effective strategy to improve the patients’ acceptance.

Funding/Acknowledgment

The Satisfaction study was funded by NTC, Milan, Italy.

References

1. Spada C et al. Eur J Clin Pharmacol. 2022 Dec;78(12):1991-2002.2. Fiori G et al. Clin Transl Sci. 2022 Oct;15(10):2448-2457.3. Carnovali M et al. Clin Transl Sci. 2023 May;16(5):759-769.4. Tontini G.E. et al. Endoscopy 2023; 55; s64Read more P201 Deep learning and minimally invasive inflammatory activity assessment: development and score correlation of a pan endoscopy convolutional networkWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Capsule endoscopy (CE) is a valuable tool for assessing inflammation in patients with Crohn's disease (CD). The current standard for evaluating inflammation are validated scores like (and clinical laboratory values) like Lewis score (LS), Capsule Endoscopy Crohn's Disease Activity Index (CECDAl) and ELIAKIM. Recent advances in artificial intelligence (Al) have made it possible to automatically select the most relevant frames in capsule endoscopy. In this study, our objective was to develop an automated scoring system using CE images to objectively grade inflammation.

Methods

Pan-enteric CE videos (PillCam Crohn's) performed in CD patients between 09/2020 and 01/2023 were retrospectively reviewed and LS, CECDAl and ELIAKIM scores calculated. We developed a convolutional neural network based automated score consisting in the percentage of positive frames selected by the algorithm (for small bowel and colon separately). We correlated clinical data and the validated scores with the artificial intelligence generated score (AIS).

Results

A total of 61 patients were included. The median LS was 225 [0-6006], CECDAI was 6 [0-33], ELIAKIM was 4 [0-38] and SB_AIS was 0.5659 [0-29.45]. We found a strong correlation between SB_AIS and LS, CECDAl and ELIAKIM scores (Pearson's r= 0.751, r= 0.707, r= 0.655, p =0.001). We found a strong correlation between LS and ELIAKIM (r= 0.768, p = 0.001) and very strong correlation between CECDAl and LS (r= 0.854, p = 0.001) and CECDAl and ELIAKIM scores (r= 0.827, p = 0.001).

Conclusion

Our study showed that the Al-generated score had a strong correlation with validated scores indicating that it could serve as an objective and efficient method for evaluating inflammation in CD patients. As a preliminary study, our findings provide a promising basis for future refining a CE score that can accurately correlate with prognostic factors and aid in the management and treatment of CD patients.Read more P202 Streamlining primary and secondary care pathways reduces the time-to-specialist IBD care: the emergence of FIT and the relative decline of calprotectin testing in primary careWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Streamlining primary and secondary care pathways reduces the time-to-specialist IBD care. Prior to the COVID-19 pandemic, using an algorithm that screens endoscopy reports for probable IBD, we halved the time to IBD specialist review and treatment. Previous studies report that faecal immunochemical testing (FIT) could be used like calprotectin to test for suspected IBD.We sought to define the changing use of calprotectin and FIT prior to the diagnosis of IBD, and to determine whether their use influenced the time to secondary care treatment.

Methods

We conducted a retrospective observational cohort study of the time from endoscopic diagnosis of IBD to initiation of treatment. Demographics, stool testing, referral route, disease type, clinical review and treatment data were recorded from our electronic patient record.We sought factors associated with a delay in treatment defined as the upper quartile of time-to-treatment using logistic regression.

Results

Between 01/07/16 and 01/09/23 there were 805 new diagnoses of IBD (503 UC, 225 Crohn’s disease and 77 IBD-U). Monthly diagnosis rates were stable across the pandemic, except for March 2020 due to endoscopy unit closure. The median time from endoscopy to specialist review was 19.0 days (IQR7.0-44.0) and time to outpatient treatment 5.0 days (IQR 0.0-29.0 days).Overall, the use of pre-IBD diagnosis stool biomarkers has increased over time, but since 2020 there has been a progressive rise in FIT, and a decrease in calprotectin, testing (Fig 1). By 2023, people with a new diagnosis of IBD were more likely to have FIT than calprotectin testing. Whilst stool biomarker testing did not influence the time-to-IBD treatment, FIT testing was associated with a reduced delay from primary referral to endoscopy (OR 0.17 p=0.023).Factors associated with a delay in treatment were a diagnosis of Crohn’s disease versus UC/IBDU, having your index endoscopy undertake by a colorectal surgeon and being managed on a non-emergency pathway. IBD nurse contact prior to medical clinic review was associated with a significant reduction in delay to treatment (OR 0.55 p=0.003)

Conclusion

In the Southwest of the UK, pre-IBD diagnosis FIT, is now more common than pre-IBD diagnosis calprotectin testing. Factors linked to a delay in treatment were being diagnosed with Crohn’s disease versus UC/IBDU, having your index endoscopy undertaken by a colorectal surgeon and not specialist nurse or gastroenterologist and being managed on a non-emergency pathway. Further studies are needed to understand the influence of FIT versus calprotectin testing in the primary care diagnosis of IBD.Read more P203 Surveying outcomes of service user experience on the effects of emotional well-being and schooling in paediatric IBD (PIBD) patients in a tertiary PIBD centreWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

We conducted a prospective survey with our PIBD patients and parents seeking outcomes in accordance with our ICN- Improve Care Now participation goals to ‘Improve and optimize the care of children and teens with IBD in underserved and underrepresented populations by addressing healthcare disparities’.

Methods

We sent out a survey to our PIBD patients focusing on their overall satisfaction with the service we deliver in relation to their emotional wellbeing and schooling. We prospectively sent this to our patient cohort of 280 PIBD patients, collecting both quantitative and qualitative data.

Results

76/280 patients and parents (27%) responded, of whom 60/76 (79%) completed the entire survey. Of those responders 45 (75%) were mothers speaking on the behalf of their children aged 5-12 years (n=20 patients). 4 (7%) patients completed the survey themselves, of whom 3 (75%) were aged between 12-18 years. 39 (65%) parents and patients were overall satisfied that the IBD team spoke about getting the right help and support for the child at school. Although 39 (65%) of the patients strongly agreed that we provided information and materials on IBD and support, 21 (35%) of the patients felt that we did not provide the necessary information and education to schools to support them whilst at school.30 (50%) of the overall responders to the survey did not feel that the team had discussed with them the effect IBD has on their feelings and emotions.

Conclusion

Our survey has highlighted the need to provide more education at diagnosis and throughout patient care. This can be achieved by providing physical education packs for schools to be given to every child at diagnosis along with our already established welcome pack. We currently ask patients and families if they would like us to contact their school with information about IBD. This is something we can potentially change, by giving all patients a letter for school at diagnosis for them to give to schools. Caring for the patient’s emotional wellbeing is essential as part of delivering a holistic approach in the care we provide. Although we do offer referral to psychology at diagnosis, this should be followed up regularly and should be included as a standard when patients seen in clinics.Read more P204 Utility of Rotational Thrombo-Elastometry as an Objective Measure of Hypercoagulability in Patients with Ulcerative Colitis-A Prospective Case Control StudyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Inflammatory bowel disease (IBD) has an increased risk of venous thromboembolism (VTE) with factors like hospitalization and surgery increasing this risk. Although few recent guidelines recommend anticoagulation thromboprophylaxis for hospitalised IBD patients, there is wide variation in reported practices for VTE prophylaxis. This study was aimed to evaluate Rotational Thrombo-Elastometry (ROTEM) for assessing blood coagulation status in ulcerative colitis (UC) and to evaluate the relationship between ROTEM, disease severity and response to treatment.

Methods

This was a prospective age- and sex-matched study with 60 patients each in UC and irritable bowel syndrome (IBS) groups, latter being controls. Clinical details, blood investigations including ROTEM and D-dimer were collected and analysed after taking informed consent. Hypercoagulable state was defined using Kaufmann’s classification. ROTEM parameters [clotting time (CT), clot formation time (CFT), alpha angle (AA), maximum clot firmness (MCF), maximum lysis (ML)] and D-dimer levels were compared between the two groups.

Results

Of the 60 UC patients (age: 38.6±11.64 years, 44 males); 15(25%) were in remission, 18(30%), 17(28.3%) and 10(16.7%) had mild, moderate, and severe disease respectively. The UC group had significantly more hypercoagulable ROTEM than the control group (66.7% vs. 36.7%, p=0.001). Hypercoagulable ROTEM was found in 9(60%), 8(44.4%), 14(82.3%) and 9(90%) of those in remission, with mild, moderate and severe UC respectively.Compared to controls; CT [292.36±70.45 vs 337.56±77.89, p=0.001], CFT [103.15±30.31 vs 128.61±40.18, p=0.0001], AA [69.88±5.19 vs 65.36±6.4, p=0.00004], MCF [65.75±5.64 vs 63.25±4.43, p=0.008] and D-dimer levels [329(63-2358) vs 145.5(54-1304), p=0.00001) were significantly abnormal in UC group. Among UC patients with mild, moderate and severe disease; only CFT, AA and D-dimer were significantly different between the groups. There was no significant difference in ROTEM values and D-dimer level in patients with severe UC after one week of treatment.On univariate analysis; partial Mayo score [OR: 1.49, 95% CI: 1.04-2.12, p=0.028], serum albumin [OR: 0.32, 95% CI: 0.10-0.98, p=0.04], hemoglobin [OR: 0.59, 95% CI: 0.40-0.86, p=0.007], and platelets [OR: 1, 95% CI: 1.01-1.02, p=0.035], were predictors of hypercoagulable state in active UC. On multivariate analysis; only haemoglobin [OR: 0.61, 95% CI: 0.38-0.98, p=0.04] was found to be significant independent predictor.

Conclusion

UC patients had hypercoagulable ROTEM regardless of activity of inflammatory process. The degree of hypercoagulability increased with disease activity. Low haemoglobin was found to predictive of hypercoagulable state in active UC patients.Read more P205 Histologic image-based ensemble model to identify myenteric plexitis and predict endoscopic postoperative recurrence in Crohn’s disease: a multicentre, retrospective studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Myenteric plexitis is correlated with postoperative recurrence of Crohn’s disease (CD) when relying on traditional statistical methods. However, comprehensive assessment of the myenteric plexus remains challenging. This study aimed to develop and validate a deep learning system to predict postoperative recurrence through automatic screening and identification of features of the muscular layer and myenteric plexus.

Methods

In this study, we retrospectively reviewed 205 CD patients who underwent bowel resection surgery from 2 hospitals. Patients were divided into a training cohort (n=108), an internal validation cohort (n=47) and an external validation cohort (n=50). A total of 190960 patches from 278 whole-slide images of surgical specimens were analysed using ResNet50, and 6144 features were extracted after transfer learning. Spearman correlation analysis, LASSO logistic regression and the interclass correlation coefficient test were utilized for feature selection. We used five robust algorithms to construct classification models. The performances of the models were evaluated by the area under the receiver operating characteristic curve (AUC) in three cohorts.

Results

The stacking model achieved satisfactory accuracy in predicting postoperative recurrence of CD in the training cohort (AUC: 0.980; 95% CI 0.960-0.999), internal validation cohort (AUC: 0.908; 95% CI 0.823-0.992), and external validation cohort (AUC: 0.868; 95% CI 0.761-0.975). The accuracy for identifying the severity of myenteric plexitis was 0.833, 0.745, and 0.694 in the training cohort, internal validation cohort and external validation cohort, respectively.

Conclusion

Our work initially established an interpretable stacking model based on muscular layer and myenteric plexus features extracted from histologic images to identify the severity of myenteric plexitis and predict postoperative recurrence of CD.Read more P279 Excessive accumulation of neutrophils in the epithelium, but not lamina propria, predicts resistance to ustekinumab in ulcerative colitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Many patients experience primary treatment resistance when treated with ustekinumab for ulcerative colitis (UC). Predictive clinical parameters would allow such individuals to be identified pre-treatment so alternative strategies could be initiated. We explored the utility of the different histological features present in baseline samples to predict ustekinumab resistance.

Methods

We assessed the total Geboes score (TG) (0–22, least to most severe), and the epithelial and lamina propria neutrophil subscores (EpiN and LpN, respectively) (both 0–3) in a subset of patients with moderate-to-severely active UC (n = 448) enrolled in the phase 3 UNIFI study that evaluated the efficacy of ustekinumab therapy. We explored the relationships between histological parameters and clinical indices of activity, including faecal calprotectin (FCP), CRP, Mayo score, and treatment outcomes (clinical remission, endoscopic healing and mucosal healing at week 8, and disease clearance, which combines these all) using Spearman rank correlation. Area under the receiver operating characteristic curve (AUC) analyses were performed (presented with 95% confidence interval, CI). Analyses were performed using R 4.2.3 (Vienna, Austria) and GraphPad Prism (v 9.5.1).

Results

TG correlated highly with EpiN (ρ = 0.804, p < 0.0001) but did not correlate with LpN (ρ = 0.082, p = 0.07). Neither EpiN (ρ = 0.081, p = 0.09) nor LpN (ρ = -0.011, P = 0.82) correlated with FCP, though EpiN correlated weakly with log₁₀FCP (ρ = 0.113, p = 0.017). Full Mayo score correlated with EpiN (ρ = 0.23, p < 0.0001) and TG (ρ = 0.23, < 0.0001).Of the patients with pre-treatment EpiN of 0, 23.1%, 26.9%, 23.1% and 19.2% experienced clinical remission, endoscopic healing, mucosal healing and disease clearance, respectively. Response rates incrementally reduced as EpiN increased, such that 4.2%, 12.5%, 8.3% and 4.2% of patients with EpiN of 3 achieved these outcomes, respectively. Similar trends were seen with tertiles of TG, though not with LpN. EpiN and TG predict mucosal healing with AUC 0.59 (CI: 0.50 - 0.68; p = 0.044) and 0.61 (CI: 0.52 - 0.70; p = 0.016), respectively. The addition of other clinical variables did not improve performance of the models.

Conclusion

There is weak or insignificant correlation between Geboes score parameters and other clinical indices of UC activity. EpiN and TG, but not LpN, stratify patients’ response to ustekinumab, with almost 6-fold difference in clinical remission between high and low EpiN. TG and EpiN predict resistance to ustekinumab, suggesting that the epithelial inflammatory milieu may be key to driving resistance to ustekinumab and possibly other therapies. This supports recent evidence highlighting the role of neutrophils in resistant UC.Read more P280 Comparative responsiveness of disease activity indices in moderately-to-severely active Ulcerative Colitis: a post-hoc analysis of the UNIFI trialWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Clinical, endoscopic, histological, and composite instruments are used to measure disease activity in ulcerative colitis (UC). We compared responsiveness of the Mayo Clinic Score (MCS), modified Mayo Clinic Score (mMS), partial Mayo Clinic Score (pMS), Robarts Histopathology Index (RHI), and UC-100 score after treatment with ustekinumab in patients with moderately-to-severely active UC.

Methods

Publicly available data from the phase 3 UNIFI induction trial (NCT02407236) comparing the efficacy and safety of ustekinumab versus placebo in patients with moderate-to-severe UC were obtained from Vivli (Vivli ID #7549) and Yale University Open Data Access Project (#2021-4848). Post-hoc analyses were performed on patient level data to ascertain outcomes of interest. Treatment assignment was the criterion for change in evaluation of responsiveness, which was quantified using the probability of a treated patient having a larger change than a placebo patient (win probability [WinP]) and estimated using nonparametric methods. Extent of responsiveness was interpreted according to Cohen’s benchmarks as very small (WinP<0.56); small (0.56≤ WinP<0.64); medium (0.64≤ WinP<0.71); and large (WinP≥0.71).

Results

Data from 961 patients with moderately-to-severely active UC randomised in UNIFI were included. At baseline, 319 patients received placebo and 624 patients received ustekinumab. A total of 912 (94.9%) patients completed the induction trial. Overall mean baseline index scores were: MCS 8.9 (±1.6), mMS 6.6 (±1.3), pMS 6.2 (±1.4), RHI 16.6 (±8.1), and UC-100 score 71.4 (±16.5) (Table). The UC-100 demonstrated a large degree of responsiveness (WinP 0.72 [95% CI: 0.66, 0.78]). The MCS (0.68 [0.62, 0.73]), mMS (0.69 [0.63, 0.75]), and pMS (0.65 [0.59, 0.71]) demonstrated similar, medium effect sizes (all comparisons p>0.05) (Figure). The RHI alone had a relatively small effect size (WinP 0.63 [0.56-0.70]). Among individual UC-100 components (Mayo Clinic stool frequency subscore, Mayo Clinic endoscopic subscore, and RHI), the endoscopic score was most responsive (WinP 0.59 [0.36-0.82]). The combination of endoscopy and RHI was associated with a medium degree of responsiveness (WinP 0.69 ([0.34, 1.00]).

Conclusion

UC disease activity indices are similarly responsive to change. Depending on trial design and measurement feasibility, different instruments can be considered optimal for evaluation of efficacy. The mMS is similarly responsive to the MCS without including the physician global assessment and may be more appropriate for determining trial eligibility and defining primary endpoint, whereas the UC-100 may be more appropriate for measuring treatment effect when an objective continuous measure is needed.Read more P281 The role of transabdominal ultrasound in evaluating Ulcerative Colitis disease activity and predicting treatment responseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

As a non-invasive, accurate, and feasible examination, transabdominal ultrasound（TAUS） is of great value in disease monitoring of ulcerative colitis. The cut-off for disease activity of 3.0 or 4.0 mm is often debated， and studies lacked assessment of treatment response. This study aimed to assess the diagnostic accuracy of TAUS in detecting disease activity in adult patients with UC using endoscopy as the reference standard and evaluate TAUS for treatment response in a longitudinal cohort.

Methods

This study prospectively consecutive adult patients with an established diagnosis of UC in the First Affiliated Hospital of Zhengzhou University between June 2022 and September 2023. The patients with moderate-to-severe disease activity at baseline should have follow-up endoscopic assessment after induction, with available corresponding TAUS. The primary outcome of this study was the difference in BWT in the descending colon(DC) or sigmoid colon(SC) for patients with and without segmental endoscopic response after treatment. Endoscopic remission was defined as MES=0-1 or UCEIS=0-1, and Endoscopic response as a decrease of MES ≥1 or a reduction of UCEIS ≥2.

Results

A total of 315 colon segments in 80 patients were included. 171 (54.3%) colorectal segments had endoscopic remission and 144(45.7%) were in endoscopic activity. The TAUS parameters correlated with the Mayo endoscopic sub-score with significant differences between patients in endoscopic remission and patients in endoscopic activity. And we found 3.45mm(AUROC 0.833;95%CI 0.789-0.878， P＜0.001) to be the cutoff for endoscopic remission with 78% sensitivity and 75% specificity. The multivariable analysis identified BWT， the Colour Doppler Signal(CDS), and the wall layer stratification as independent predictors for endoscopic activity（ P＜0.001、=0.004、=0.001）. BWT in the DC or SC was significantly lower in patients with endoscopic response than those without after treatment. A 28% decrease in BWT from baseline predicted endoscopic response [AUROC 0.743;95%CI 0.589-0.896， P=0.015] with 58% sensitivity and 93% specificity. Multivariable analysis among all the ultrasound parameters considered normal wall layer stratification at baseline as the only independent predictor of endoscopic response at reassessment (odds ratio [OR]23.334, 95% CI 2.257-241.219; p = 0.008).

Conclusion

TAUS, importantly BWT, CDS, and wall layer stratification as the crucial parameters, is highly accurate in detecting disease activity and treatment response when evaluated against endoscopic outcomes. Normal intestinal wall stratification at baseline predicts long-term endoscopic response.Read more P282 High Correlation Between Fecal Immunochemical Test and Fecal Calprotectin for the Evaluation of Activity in Inflammatory Bowel DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Fecal calprotectin (FC) is one of the most widely used biomarkers in IBD. The evidence suggest it has a good correlation with clinical disease activity, endoscopic and histological indices, thereby it can be used as treatment target. However, the availability and cost of the FC, makes it unattainable in some regions. We aimed to assess the correlation of noninvasive Fecal Immunochemical Test (FIT) and FC for activity prediction in IBD.

Methods

Consecutive outpatients with Crohn’s disease or ulcerative colitis were clinically evaluated and stool samples for FIT and FC were collected. The Mayo endoscopic sub-score and SES-CD were used to define endoscopic activity. Spearman’s rank correlations were used to evaluate the association between FIT and FCP. Receiver operator characteristic (ROC) curves were constructed to calculate the accuracy of FIT and calprotectin in discriminating patients with endoscopic inflammation.

Results

Two hundred and six patients (148 ulcerative colitis and 58 Crohn’s disease) were enrolled. There was a good correlation between FIT and FC (Spearman rank correlation coefficient r_s = 0.71, P < 0.01). For calprotectin, a cutoff value of 250 mg/g predicted endoscopic inflammation with 75% sensitivity, 90% specificity, 97% positive predictive value, 50% negative predictive value, and an area under the curve of 0.861. For FIT, a cutoff value of 20 mg/g indicated endoscopic inflammation with 62.5% sensitivity, 90% specificity, 96% positive predictive value, 60% negative predictive value, and an area under the curve of 0.82.

Conclusion

Fecal Immunochemical Test has a good correlation with fecal calprotectin and can identify patients with IBD with endoscopic activity with a predictive accuracy similar to fecal calprotectin.Read more P283 Efficacy and safety of etrasimod in patients with moderately to severely active UC in Japan: Integrated analysis of the phase 3 ELEVATE UC 12 and ELEVATE UC 40 JAPAN trialsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Etrasimod is an oral, once-daily (QD), selective sphingosine 1-phosphate (S1P)_1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC). We evaluated efficacy and safety among Japanese patients with moderately to severely active UC with contextualisation to the global population.

Methods

ELEVATE UC 40 JAPAN (NCT04706793) was a multicentre, double-blind, 40-week trial of patients from Japan who completed the 12-week phase 3 ELEVATE UC 12 induction trial (NCT03996369; study design described elsewhere¹), resulting in a combined 52-week treatment period. Eligible patients were aged 16–80 years with documented history of inadequate/loss of response or intolerance to ≥1 approved UC therapies. Patients (hereafter the ‘Japan cohort’) continued baseline-assigned treatments from ELEVATE UC 12 (etrasimod 2 mg QD or placebo QD). Efficacy was assessed at Weeks 12 and 52 in patients with a Modified Mayo score (MMS) 5–9; the primary endpoint was clinical remission at Weeks 12 and 52. Pooled treatment-emergent adverse events (TEAEs) from ELEVATE UC 12 and ELEVATE UC 40 JAPAN were assessed up to Week 52.

Results

The Japan cohort comprised 32 and 16 patients receiving etrasimod and placebo, respectively; 28 and 14 patients with an MMS of 5–9, respectively, were included in the analysis. Baseline demographics were similar between treatment groups. A numerically higher proportion of patients receiving etrasimod vs placebo achieved the primary efficacy endpoint (Figure). Similar patterns were observed for all key secondary endpoints (Table). TEAEs occurred in 84.4% (27/32) and 62.5% (10/16) of patients receiving etrasimod vs placebo, respectively. The safety of etrasimod was similar between Japanese and global UC populations.

Conclusion

In this Japanese population, numerically higher proportions of patients achieved all efficacy endpoints with etrasimod vs placebo. Efficacy and safety findings were consistent with the global ELEVATE UC population.¹

Reference

1. Sandborn WJ et al. Lancet 2023; 401: 1159–1171.Read more P284 Sex-specific aspects in IBD: a multidimensional viewWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Inflammatory bowel diseases (IBD), including Ulcerative colitis (UC) and Crohn's disease (CD), are chronic intestinal disorders characterised by varied intestinal symptoms and a negative impact on the patients` quality of life. Increasing evidence demonstrates sex differences regarding the prevalence, pathophysiology, clinical presentation and treatment outcome of IBD. While for some factors evidence is rather good, for others data are conflicting – thus a deeper understanding of sex related differences in IBD courses is still needed.

Methods

In this monocentric, cross-sectional study 221 IBD patients were stratified into 2 groups according to gender/biological sex (male [n=106]; female [n=113]). We evaluated patients personal and medical data including disease-specific quality of life (IBDQ) as well as clinical (HBI, PMS) and biochemical (CRP, fecal calprotectin) parameters of disease activity. Furthermore, we isolated and stimulated PBMCs with various pathogens to test ex vivo cytokine responses of this heterogeneous IBD cohort.

Results

Binary logistic regression analysis suggested an independent association of diagnostic delay (p= 0.039), IBD entity (p= 0.001), IBDQ (p= 0.001), and vitamin D3-25-OH serum level (p= 0.035) with disease activity for female IBD patients, while for male IBD patients an independent association was only suggested for IBD entity (p= 0.004) and IBDQ (p= 0.001) (figure 1). Next, we tested the association between the number of ADT (Advanced Therapies) taken during the overall course of the disease with both disease activity and diagnostic delay. We found a significant association between ADT and disease activity in both sexes (male-p = 0.015, female-p=0.037), but ADT was only significantly associated with diagnostic delay in female IBD patients (p=0.044) (figure 2). Regarding the frequency of therapies used in both sexes, we found that male patients are more frequently subscribed prednisolone (Mann-Whitney-U, p= 0.009) as well as 5-ASA (p= 0.004) (figure 3). Cytokine responses upon PBMC stimulations with various pathogens showed a significant trend in Interferon gamma levels in male CD patients (p< 0.05) (figure 5A). A significant negative correlation between Interferon gamma levels and CD activity has only been found in male CD patients, but not in female CD patients (figure 5B).

Conclusion

In this analysis of a cross-sectional study, we are able to illustrate sex-specific aspects of not only clinical courses in IBD patients but also within specific immunological responses – highlighting the importance to closely take the IBD patients sex into consideration in the upcoming era of personalized medicine.Read more P285 Communicating Needs and Features of IBD Experiences (CONFIDE) Survey: European and US Patient and Health Care Professional Perspectives on the Broad Impact of Bowel Urgency in Ulcerative colitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Bowel urgency (BU) affects quality of life and psychosocial function of patients with moderate-to-severe ulcerative colitis (UC). This study used data from the Communicating Needs and Features of IBD Experiences (CONFIDE) survey to explore the patient and health care professional (HCP) perceptions on the broad impact of BU on patients’ emotions and daily lives.

Methods

Online, quantitative, cross-sectional surveys were conducted among patients with moderate-to-severe UC and HCPs in Europe (France, Germany, Italy, Spain, UK), the United States (US) and Japan. Data from Europe and US are presented here. A 7-point scale was used to rate the emotional impact of BU (Patients: 1=does not make me feel like this at all, 7=makes me feel like this a great deal; HCPs: 1=patients do not experience at all, 7=patients experience a great deal) and interference of BU with 12 different aspects of patients’ daily lives (Patients: 1=does not interfere, 7=interferes a great deal; HCPs: 1=no impact on patients and 7=impacts patients a great deal).

Results

Surveys were completed by 556 patients and 503 HCPs in Europe and 200 patients and 200 HCPs in the US. Among patients experiencing BU in the past month (Europe:30%, US:47%), most reported emotional impacts due to BU (mean rating [MR]≥4.1), as did the HCPs (MR≥5.2). In Europe, patients felt embarrassed when having to run to the bathroom due to BU (MR=5.0); HCPs reported that patients felt anxious/nervous due to BU as well as panic and embarrassment when having to run to bathroom due to BU (MR=5.8 each; Figure). In the US, similar to patients (MR=4.8), HCPs (MR=5.8) perceived their patients felt anxious/nervous due to BU.Impacts of BU on daily life were reported by patients (MR≥4.2) and HCPs (MR≥4.6). In Europe, patients reported a high impact on spontaneous activities (MR=5.1); HCPs reported a high impact on patients’ ability to travel (MR=5.8; Table). In the US, patients reported a high impact of BU on the choice (variety) and quantity of food/drinks (MR=5.2 each); HCPs perceived a high impact on patients’ spontaneous activities and ability to travel (MR=5.7 each). While most HCPs (Europe:58%, US:54%) ranked BU among top five most impactful symptoms, it was not among the top three most impactful symptoms on treatment decisions.

Conclusion

In both Europe and US, BU affected patients emotionally and limited their ability to travel and make spontaneous plans. Despite the broad impact of BU from both HCP and patient perspectives, with HCPs perceiving (numerically) a higher impact than patients, it was not among the top three most impactful symptoms on HCPs’ treatment decisions. Increased awareness of BU among HCPs is needed when making treatment decisions for patients with UC.Read more P105 Mendelian Randomization screening for JAK inhibitor related potential serious adverse eventsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

JAK inhibitors (JAKi) suppress the JAK/STAT signalling pathway through inhibition of the four Janus kinase proteins JAK1, JAK2, JAK3 and TYK2. JAKi are licensed for the treatment of a wide range of immune mediated inflammatory diseases (IMIDs) including inflammatory bowel disease. Concerns have been raised for the potential of this class of medication to associate with serious adverse events, particularly in those older than 65 years of age or with previous cardiovascular comorbidities. Mendelian randomization (MR) uses genetic variants as instrumental variables (IVs) to examine the causal effects of an exposure (e.g. inhibition of a drug target) on an outcome (e.g. the risk of developing a disease and/or potential adverse effects due to alteration of gene activity). We carried out a comprehensive MR evaluation to explore the therapeutic potential of JAKi for a range of IMIDs, and to study the unintended drug effects that might be caused by this therapeutic strategy.

Methods

The basis of MR relies on the use of genetic variants as IVs that are reliably related to the risk factor and that are not susceptible of reverse causation and confounding. We used genetic variants (SNPs) associated with protein levels and gene expression (pQTLs and eQTLs, respectively) as IVs to study the effects of inhibiting the genes in the JAK/STAT signalling pathway. The underlying assumption is that these IVs serve as proxies of the effects of JAKi. As a source of the effect estimates on the selected outcomes, we used summary statistics from a compiled list of genome-wide association studies.

Results

We used the MR approach to chart the range of possible outcomes associated with JAKi treatment. First, we explored the therapeutic potential of JAKi for IMIDs. Second, we evaluated a range of potential adverse events associated with JAKi, focusing particularly on cardiovascular, infectious and cancer-related malignancies. Our MR results confirm a general tendency towards JAK/STAT signalling pathway involvement in IMIDs risk, implying the suitability of JAKi for IMIDs. Regarding potential adverse outcomes, we carried out stratification-based analyses to evaluate whether potential adverse events are enhanced in individuals at particular high risk. The MR analyses highlighted potential risk of JAKi for non-IMIDs traits, particularly when targeting JAK2. This includes already known associations with cardiovascular disease and specific cancer types.

Conclusion

We performed an outcome-wide exploration based on MR to characterize the therapeutic potential and range of adverse effects expected for JAKi. We recapitulate the known potential of these drugs to treat IMIDs, while uncovering specific severe adverse effects associated with this therapeutic target.Read more P106 Single-cell transcriptomic analysis reveals insights into the mechanism of action of Granulocyte-monocyte apheresisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Granulocyte-monocyte apheresis (GMA) is a non-pharmacological treatment approved for the management of ulcerative colitis (UC), particularly steroid-dependent cases. The exact mechanism of action and immunological changes associated with GMA remain undescribed. Gene expression analysis at the single-cell level (through scRNA-Seq) has emerged as a key tool of choice to characterize drug response at the molecular level. We used scRNA-Seq to characterize the transcriptomic effects and immune cell population alterations in GMA.

Methods

We generated scRNA-Seq from peripheral blood mononuclear cells (PBMC) of two ulcerative colitis (UC) patients undergoing GMA treatment. We compared the gene expression profile before and after 5 sessions of GMA treatment. The analytical pipeline included quality control and classical filtering steps, cell-type annotation, differential gene expression analysis and pathway enrichment profiling.

Results

We report three main results. First, we observed significant reductions of cell types directly affected by GMA treatment in UC patients. This includes classical CD14+ monocytes and Natural killers, which are central components of the innate system. Of note, we observed a remarkable increase in Double-negative T cells (dnT) after 5 sessions of GMA treatment, suggesting potential expansion of protective populations involved in decreased inflammation. Second, we observe a variety of genes and regulatory pathways altered by GMA treatment. In total, we detect 86 differentially expressed genes (DEGs), which overall are biased towards downregulation (63%). Of note, we detected dnT-s exhibiting upregulation of NEFL that is associated with the MAPK cascade and downregulation of genes related to immune response and signaling pathways. Finally, the effects of GMA treatment extend beyond the above mentioned populations, with particular alterations in CD4+ T cell populations such as CD4+ central memory and CD4+ Naive (7 and 13 DEGs, respectively).

Conclusion

For the first time, we generated single-cell transcriptomic profiles to characterize the effects of GMA treatment in peripheral blood of UC patients. Our preliminary analysis detects important alterations in the gene regulation and cell type composition in samples obtained after 5 sessions of GMA. Through expansion of this dataset to include more time points and profiles for more individuals, we will discuss the longitudinal changes and molecular mechanisms involved in response to GMA treatment.Read more P107 Comparing the Colonic Tissue Proteome of Active and Inactive Ulcerative ColitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Ulcerative colitis (UC) is an inflammatory bowel disease that begins at the rectum and can advance proximally and continuously throughout the colon. In this pilot study, we aim to differentiate the protein expression between active and inactive patients, comparing the same tissue region of the colon pairwise between active and inactive UC. Additionally, we are looking to build on previous work to determine which proteins are differentially proteolyzed in active UC and postulate whether this alternative post-translational processing significantly correlates to disease activity. Here, we aim to use a multi -omics approach to spatially profile the entire large intestine.

Methods

We used an N-terminomics proteomic approach to determine whether proteins are differentially expressed and proteolytically processed in all colon segments of patients with active and inactive UC. Colon tissues were retrieved from patients and classified according to disease activity. Five active and five inactive UC patients were compared from each of the colonic regions (rectum, sigmoid, transverse, ascending colon). Samples were quantified by liquid chromatography and tandem mass spectrometry (LC-MS/MS). Peptides were identified and matched at a 5% false discovery rate (FDR). Boxplot analysis was used to determine the upper and lower threshold for protein fold changes between conditions, and various bioinformatic software (MetaScape, StringDB, TopFINDer) were used to analyze the data.

Results

Primary analysis discovered a combined 36 statistically changing proteins in patients with active disease, including several that have previously been published and others that are direct interactors with known biomarkers for active UC, including calmodulin and S100A9. Interestingly, S100A9 was translated significantly more in the transverse colon of patients with active UC but was not in other colonic regions. Protease activity was noticeably different in active and inactive UC, in addition to having unique activity dependent on the region of the colon from which the samples were acquired. For example, delta-catenin was processed more in active UC in the rectum and transverse colon, whereas it’s processing was enriched in inactive UC in the sigmoid colon.

Conclusion

While this pilot study is incomplete, the promising initial results exhibit the power of a proteomics and N-terminomics approach to elucidate the mechanisms that contribute to UC pathogenesis. There appears to be a pattern in how proteins and their altered proteolysis leads to an increased likelihood of active UC.Read more P108 Response to vedolizumab in ulcerative colitis is associated with reduced neutrophil extracellular traps formation and IL-1β production: insights from NEUTROVED studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Vedolizumab (VDZ) is a humanized mAb against integrin α4β7. VDZ inhibits gut inflammation by impeding intestinal T-cell homing, however, recent data suggest that effects of α4β7 blocking extend beyond T-cells to alterations in innate immunity. Neutrophils are key components of innate immune response and inflammation in ulcerative colitis (UC). Studies have provided evidence linking neutrophils with UC pathogenesis, through autophagy induction and production of IL-1β-enriched neutrophil extracellular traps (NETs). NEUTROVED aimed to investigate the effects of VDZ treatment on neutrophils that may be associated with clinical and endoscopic response.

Methods

Patients with moderate-to-severe UC who received VDZ in standard medical care were evaluated in two timepoints, 24 hours before treatment initiation (T1) and at week 14 of treatment (T2). Clinical/endoscopic scores and common laboratory indexes were evaluated. In parallel, RNA-sequencing in peripheral neutrophils was performed, and markers of NETs in plasma and intestinal biopsies were assessed.

Results

In total 5 patients completed the study until today (Table 1). In T2, 4 patients demonstrated complete remission, and one patient had mild disease. No adverse events were recorded. RNA-sequencing analysis of paired samples revealed 248 significantly downregulated and 109 upregulated genes in peripheral neutrophils after VDZ treatment. Bioinformatics analysis using the GeneCodis4 web-based tool revealed that downregulated DEGs clustered mainly in immune-related pathways, including neutrophil degranulation, Toll-like receptor cascades, signaling by interleukins, NETs formation, and HIF-1 signaling pathway, while upregulated DEGs were involved in RNA metabolism-related processes, and the ribosome biogenesis pathway. A comparative analysis between these differentially expressed genes (DEGs) and our previous RNA-sequencing data of peripheral neutrophils isolated from active UC patients (n=24) highlighted a set of 168 DEGs as restored targets after VDZ therapy. Of note, several unique genes implicated in neutrophil activation, including IL-1 signaling components, were found significantly downregulated after VDZ therapy. In line with the abovementioned transcriptome alterations, markers of NETs and IL1β-bearing NETs in plasma and colonic tissue were significantly reduced, recapitalizing clinical and endoscopic response to VDZ.

Conclusion

Response to VDZ treatment in UC is related to anti-inflammatory actions on neutrophils characterized by reduced NETosis and IL-1β production through NETs. Further mechanistic studies investigating the possible effects of VDZ on innate immunity and neutrophil-mediated responses are warranted.Read more P222 Inflammatory Bowel Disease and cardiac function: a systematic review of literature with meta-analysisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Morphological and functional cardiac involvement is rarely seen in inflammatory bowel disease (IBD) patients but there is evidence that IBD patients have an increased risk of cardiovascular events despite the lower prevalence of traditional cardiovascular (CV) risk factors when compared to the general population. Our systematic review and meta-analysis examined the relationship between IBD and cardiac function, namely incidence of heart failure (HF) and clinical and subclinical echocardiographic changes.

Methods

Two medical databases, PubMed and Scopus, were systematically searched up to September 2022 to identify all studies reporting heart failure and/or echocardiographic changes in IBD patients.

Results

We identified 1287 original papers and included 18 in our qualitative analysis. Through analysis of echocardiographic data, we found subtle systolic and diastolic changes in IBD patients. We also found higher vascular dysfunction with increased aortic stiffness, coronary microvascular dysfunction resulting in worse cardiovascular outcomes. This group had an increased risk for HF hospitalizations compared with general population. We have also performed a meta-analysis with 9 studies which included echocardiographic data. In the IBD population we found reduced E/A ratio (Std. MD -0.51, 95% CI: -1.00 to -0.02, p = 0.04, I² = 87%, p<0.0001), higher values of E/E’ ratio (Std. MD 1.46, 95% CI: 0.86 to 2.07, p<0.00001, I² = 80%, p=0.02). We evaluated left ventricular function using longitudinal global strain which was decreased in IBD patients (Std. MD 0.66, 95% CI: 0.48 to 0.84, p<0.00001, I² = 0%, p= 0.55). Overall IBD patients had increased LA diameter (Std. MD 0.06, 95% CI: 0.12 to 0.24, p = 0.50, I² = 20%), and an increased LA area (Std. MD 0.03, 95% CI: 0.24 to 0.29, p = 0.85, I² = 0%), but no statistical significance was not reached. A significant increase in inter-atrial and right intra-atrial conduction delay was observed in IBD patients (Std. MD 0.88, 95% CI: 0.45 to 1.31, p<0.0001, I² = 42%; Std. MD 0.9, 95% CI: 0.57 to 1.22, p < 0.00001, I² = 0%, respectively). We found no significant bias in our analysis using CASP checklist.

Conclusion

There is significant evidence to conclude that the IBD population has increased risk for LV and atrial dysfunction, vascular changes, arrhythmias, and heart failure hospitalization. Screening with sensitive imaging like speckle tracking echocardiography could identify early subclinical changes. IBD is in fact a cardiovascular risk factor and tight inflammation control may reduce the risk.Read more P243 Multi-modality intestinal ultrasound is accurate and reproducible to distinguish inflammatory from chronic fibrotic strictures in Crohn’s disease – results from the STRICTURE studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

In 30%-50% of patients with Crohn’s disease (CD) stenotic complications occur¹. There is currently no imaging modality to identify stricture composition, which would allow early targeted (anti-inflammatory vs surgical) treatment. Intestinal ultrasound (IUS) and advanced modalities (contrast-enhanced ultrasound (CEUS) and shear-wave elastography (SWE)) have the potential for transmural disease evaluation. The STRICTURE study investigated whether (advanced) IUS techniques could distinguish between inflammatory- (IP) and non-inflammatory phenotypes (non-IP) of stricturing CD.

Methods

In this prospective, cross-sectional study consecutive patients with small bowel CD undergoing surgery were included. Patients were eligible if they had a non-passable stricture during endoscopy in the small bowel and/or a stricture at cross-sectional imaging (IUS or MRE)². Prior to surgery, IUS, CEUS and SWE were performed. Two blinded sonographers scored the cine-loops for IUS and CEUS. After surgery, histological slides were retrieved and location matched with IUS. Two blinded pathologists scored for inflammation, adipocytes and fibrosis. Subsequently the predominant phenotype was determined as: [1] inflammatory (IP; Nancy score 4 with no marked fibrosis/adipocytes), [2] fibrotic (FP; structural changes due to marked fibrosis/adipocytes³) or [3] mixed phenotype (MP; inflammatory and fibrotic aspects but no predominant phenotype). FP and MP were both classified as non-IP.

Results

A total of 36 patients (age: 42±18 years) with a mean BWT of 6.7±1.7 mm were included. Median time between IUS and surgery was 14 [3-50] days. A total of 7 patients had an IP, 18 a FP and 11 a MP. For the conventional IUS parameters, loss of wall layer stratification (WLS) was more frequently found in IP strictures(OR: 7.87 [1.24-50.00], p=0.029). For CEUS, most parameters were significantly higher in IP versus non-IP (Table 1) and at multi-variable logistic regression Wash-in area under the curve remained the only accurate parameter to distinguish IP from non-IP (OR:1.55 [1.03-2.34], p=0.035) [Figure 1]. SWE inversely correlated with CEUS (Table 1, Figure 1) but did not differentiate between IP and non-IP (33.30 kPa vs 43.49 kPa, p=0.48). The agreement for BWT and loss of WLS was good (ICC: 0.77, p<0.001) and moderate (κ: 0.56, p<0.001), respectively. For CEUS, the most accurate parameters had good to excellent agreement [Table 1].

Conclusion

Loss of WLS and CEUS are accurate to distinguish an IP from a non-IP stricture in CD and CEUS inversely correlates with SWE. In addition to accuracy, reproducibility was high and multi-modality IUS could be of additional value in this specific population to select patients most suitable for anti-inflammatory treatment.Table 1Figure 1Read more P244 The first step to IBD prevention exploring rate of pre-clinical inflammation in subset of asymptomatic subjects at risk of IBD: screening stage of the PIONIR trialWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

With the increasing prevalence of inflammatory bowel diseases (IBD) globally, it is necessary to start focusing efforts on prevention of the diseases. The Genetic, Environmental, Microbial (GEM) study identified biological signatures predictive of developing IBD in first degree relatives (FDR) of patients with Crohn’s disease (CD). The ongoing PIONIR (Preventing IBD ONset in Individuals at Risk) study is a randomized controlled trial aimed to explore whether the Tasty & Healthy diet can change the CD-risk associated biomarkers of healthy FDRs who are particularly high risk of developing CD, originally followed in the GEM cohort. We report here the rate of IBD and pre-IBD inflammation in a subset cohort.

Methods

Subjects, 6-35 years of age from the GEM cohort who were identified by a combination of predictors at recruitment to GEM to have an increased risk for persistently elevated fecal calprotectin (FC) (i.e. Microbiome Risk Score (MRS), increased gut permeability and/or multiplex family of CD) were approached to perform a new FC test. Subjects who had FC>70µg/g, confirmed by a second sample, were offered a panenteric video capsule endoscopy (VCE), but some elected to proceed to ileocolonoscopy instead.

Results

For the PIONIR recruitment, a total of 450 subjects were approached from 7 sites in Israel and Canada, of whom 183 consented and provided a stool sample for FC (Figure). FC was elevated in 57 (31%) subjects, confirmed by re-testing in 36 (20%); 25/36 underwent VCE/ileocolonoscopy (Figure). In total, 8 (4.4% of the screened cohort) had normal-appearing mucosa, in 10 (5.5%) there were non-specific mucosal changes (e.g. several erosions or erythema), 6 (3.3%) had ulcers compatible with CD and 1 (0.6%) was inconclusive. The median FC of those eventually diagnosed with CD (816 [IQR 361-1123) was higher than the remaining 30 without IBD with elevated FC (175 [111-281], p=0.003). FC>275µg/g was highly predictive of CD in the entire cohort (AUROC 0.97 (95%CI 0.93-0.99); sensitivity 83%, specificity 94%).

Conclusion

Preclinical mucosal inflammation in VCE/ileocolonoscopy was found in 18 of 183 (9.8%) screened subjects (i.e. elevated FC with either normal or nonspecific mucosal findings), 134 (73%) had normal FC and 11 (6%) with elevated FC had missing VCE/ileocolonoscopy data. Six had CD (3.3%, or 17% of the 36 with elevated FC). Detecting subjects at risk at their preclinical stages, possibly with FC>275µg/g, is the first necessary step in developing preventive strategies for IBD.Read more P245 Biologics Sequencing in Clinical Units (BISCUITS): Comparing outcomes in Crohn’s disease patients on second-line biologicsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Optimal drug sequencing for patients with Crohn’s disease (CD) who fail first line therapy with TNF-α inhibitors (TNFi) remains unclear. BISCUITS uses validated real world data from the UK IBD Registry (IBDR) to compare outcomes in CD patients who failed first line therapy with TNFi and underwent either a within-class switch (WCS) to an alternative TNFi or an out-of-class switch (OCS) to a different mechanism of action.

Methods

A feasibility study of 86,000 IBDR patient records identified a potential cohort of 2,678 CD patients who switched from a TNFi to a second biologic. Patients with no other prior IBD diagnosis who switched between 26/08/2015 and 31/03/2021 were included. The primary outcome was time to treatment failure after WCS or OCS, defined as days between initiation of second line (index) biologic and cessation, analysed using unadjusted Kaplan-Meier survival curves & Cox proportional-hazards models. Secondary outcomes included corticosteroid- and surgery- free drug persistence at one year (no drug stop, no steroid treatment or IBD related surgery within 365 days of index), analysed using binary logistic regression adjusting for age at index, early or later treatment with first line TNFi, primary non-response (PNR) or secondary loss of response (SLOR) to first-line TNFi, and immunomodulation therapy at index.

Results

An initial cohort of seven UK sites contacted, consented, and validated data for 180 patients; demographics and significant differences in case mix are shown in Table 1. Preliminary unadjusted findings suggest that OCS were less likely to discontinue index treatment compared to WCS (hazard ratio (HR): 0.64, 95% Confidence Interval (CI): 0.42 – 0.96, p = 0.03). Subgroup analysis in patients who experienced PNR to their initial TNFi indicated OCS were less likely to discontinue index treatment compared to WCS (HR: 0.25, 95% CI: 0.12 – 0.51, p < 0.001). Conversely, no significant difference in drug persistence was seen in the SLOR group (HR = 0.81, 95% CI: 0.49 – 1.36, p = 0.4), as shown in Figure 1. Binary logistic regression indicated OCS were more likely to show steroid-free drug survival at one year (adjusted odds ratio (aOR): 2.10, 95% CI: 1.10 -– 4.10, p = 0.026), surgery-free drug survival at one year (aOR = 3.31, 95% CI: 1.70 – 6.65, p < 0.001), and steroid- & surgery- free drug survival at one year (aOR = 2.14, 95% CI: 1.13 – 4.10, p = 0.02).

Conclusion

Real world data from this study shows overall higher drug persistence rates in OCS patients and higher steroid- and surgery- free drug survival at one year. OCS was similarly associated with significantly higher rates of drug survival in patients with PNR, but no significant difference was seen in patients with SLOR.Read more P246 Histologic remission is an important therapeutic target in patients who achieve endoscopic remission of ulcerative colitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Histologic activity has been established as a crucial prognostic determinant in individuals diagnosed with ulcerative colitis(UC), while achieving histologic remission is increasingly recognized as a significant long-term therapeutic goal. However, the available literature still lacks adequate evidence concerning the selection of an optimal histological index and its utility in predicting prognosis

Methods

This retrospective study involved the analysis of medical records and endoscopic results from patients diagnosed with UC between January 2015 and December 2022. Endoscopic remission was defined as a Mayo endoscopic sub-score of ≤1. Histological assessment utilized the Nancy index, with a score of ≤1 indicating histological remission. Among patients with UC who achieved endoscopic remission, the study assessed the maintenance of remission and the occurrence of recurrence based on histological remission

Results

A total of 114 patients with UC who achieved mucosal healing were enrolled for histological evaluation. Among them, 16.7% (19/114) experienced flare-ups, and a statistically significant inverse correlation was observed with histologic remission (see Table). Multivariate analysis further identified non-histologic remission (Nancy index >2) as an independent risk factor for recurrence (Hazard ratio: 3.513, CI: 1.334-9.257, P=0.011). Particularly noteworthy was the significantly lower recurrence rate when histologic remission is achieved, especially in patients with MES 1 (see Figure)

Conclusion

Our study demonstrated a robust correlation between histologic remission assessed by the Nancy index and sustained clinical remission. The Nancy index, reflecting relatively straightforward histological activity, is considered a valuable metric that can aid in establishing treatment goalsRead more P136 Blood-based biomarkers of type III collagen remodeling as surrogate markers of endoscopic disease activity in patients with Ulcerative ColitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The chronic inflammation of Ulcerative Colitis (UC) causes excessive extracellular matrix (ECM) remodeling, resulting in clinical complications. Currently, endoscopic evaluation remains the gold standard method for determining disease activity. However, due to its invasiveness and accompanying patient discomfort, novel methods are wanted. Focusing on type III collagen, a major component of the intestinal ECM, we sought to investigate three blood-based neoepitope biomarkers of type III collagen formation, degradation, and fibrosis resolution as surrogate markers of disease activity.

Methods

Fifty-one patients with UC were scored endoscopically at weeks 0 (W0) and 24 (W24), according to the total Mayo score (TMS) and the UC Endoscopic Index of Severity (UCEIS). Three biomarkers of type III collagen remodeling, PRO-C3 (formation), C3M (MMP-9 degradation), and CTX-III (fibrosis resolution), were measured in the sera of patients and evaluated against the disease activity scores. Patients were grouped based on their disease activity score, and the biomarkers were evaluated by one-way ANOVA, correcting for multiple comparisons using Tukey (parametric data) or Dunn’s test (nonparametric).

Results

Grouping patients according to the TMS at W0, patients with severe disease had elevated serum C3M compared to patients with mild or moderate disease (p<0.05 and <0.01) (Figure 1A). Based on the UCEIS, patients with a severe disease presented with reduced CTX-III than moderate disease activity (p<0.05) (Figure 1C). While not statistically significant, a numerical trend of elevated C3M levels with increasing endoscopic disease activity was observed at W24 (Figure 1B). No statistically significant results were achieved evaluating C3M according to the UCEIS score, CTX-III according to the TMS or PRO-C3 according to the TMS and UCEIS score (Data not shown).

Conclusion

The serum levels of C3M were elevated in patients with UC at W0 when scoring their endoscopic disease activity using the TMS. At W24, a similar trend of elevated C3M with increasing disease activity could be observed. Using the UCEIS score, the CTX-III biomarker reflecting type III collagen resolution was reduced in patients with severe endoscopic disease. The data suggest an elevation of MMP-9 catalyzed type III collagen degradation with disease severity and reduced type III collagen resolution. The PRO-C3 biomarker provided no statistical value in the current study.Read more P137 Salivary calprotectin: a potential biomarker in inflammatory bowel disease?Wed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Background: Biomarkers are used frequently for evaluation and monitoring of IBD. Fecal calprotectin (FCP) is an already established biomarker in IBD, nevertheless patients often do not feel comfortable with stool manipulation. A saliva sample collection is particularly interesting due to its noninvasiveness and readiness of collection. We aimed to assess if salivary calprotectin (SCP) could be used as a new biomarker to assess disease activity.

Methods

In this observational cohort study, saliva was collected through the passive drool technique from adult IBD patients. All patients were submitted to a previous oral examination performed by a dentist. Recent history of antibiotic treatment (within the preceding month), proton pump inhibitors or non-steroidal anti-inflammatory drugs were exclusion criteria. Determination of FCP and SCP levels was accomplished using Elia Stool Extraction Kit and Elia Calprotectin 2 test. Intestinal disease activity was assessed with fecal calprotectin levels and the Harvey-Bradshaw Index (HBI) or Partial Mayo score (PMS). Ethical approval was obtained.

Results

92 patients (56 with CD and 36 with UC) were included. Clinical characteristics are presented in Table 1. Patients had a median FCP of 45 mg/Kg and a median SCP of 206.5 mg/Kg. No significant correlations between SCP and FCP, CRP (C-reactive protein), ferritin and ESR (erythrocyte sedimentation rate) were found. However, there was a significant correlation between fecal calprotectin and CRP (p<0.001) and ESR (p=0.011). Disease activity scores did not correlate significantly with SCP, although there was a significant correlation between FCP and PMS (p=0.006).IBD patients were stratified based on a composite criterion for inactive disease HBI score <5 for CD or a PMS ≤ 2 for UC, and FCP cutoff value of 150 mg/Kg), with no significant difference in SCP between the two groups, despite the significant difference in FCP (p<0.001). No significant differences between different treatments groups or no treatment in salivary calprotectin concentration were found using Kruskal–Wallis H tests (CD (χ2(4) = 6.211, p = 0.184; UC group (χ2(3) = 1.201, p = 0.753)). 77% of patients with IBD do not have periodontal health. Nonetheless, there was no significant difference in the median SCP value between patients with or without periodontal health. Although the median SCP value was higher in patients with UC without periodontal health, the difference was not statistically significant (0.484).

Conclusion

SCP does not correlate with FCP and do not represent a reliable biomarker to distinguish disease activity in patients with IBD patients. Moreover, according to our results, it cannot be used as a marker of lack of oral health, namely periodontitis.Read more P174 Treg Cell and Human Intestinal Myofibroblast-Derived Amphiregulin induced by TGF-β Promotes Colitis-Associated Intestinal FibrosisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Intestinal fibrosis is one of the most threatening complications of Crohn’s disease (CD). Intestinal fibrosis is usually the result of chronic inflammation, and T cell response is the main driver of intestinal inflammation. At present, there are few researches on the mechanism of Treg cells in intestinal fibrosis, and the role of Treg-derived Areg in intestinal fibrosis has not been studied.

Methods

AREG and TGF-β expression was assessed in patients with CD with or without intestinal fibrosis by quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR). In this study, dextran sulfate sodium (DSS)-induced chronic colitis model in wild-type (WT) and Areg^-/- mice and T-cell transfer model with WT and Areg^-/- Treg cells were used. CD4⁺ T cell expression of AREG induced by Treg cell differentiation-related cytokines and self-secreted cytokines was determined by Western blotting. Human intestinal myofibroblasts expression of AREG induced by different cytokines was determined by qRT-PCR. The effect of AREG on proliferation/migration in human intestinal myofibroblasts was determined.

Results

AREG and TGF-β expression was increased in fibrotic sites compared with nonfibrotic sites from patients with CD. Although DSS-induced more severe colitis in Areg^-/- mice, which developed less severe intestinal fibrosis compared with WT mice on DSS insults. Transfer of Areg^-/- Treg cells induced less severe fibrosis in Rag^-/- mice compared with WT Treg cells. TGF-β promoted AREG expression in Treg cells by activating Smad3. In addition, TGF-β promoted the AREG expression in Treg cells in a time and dose dependent manner. TGF-β also promoted the AREG expression in human intestinal myofibroblastss from CD patients with fibrosis. AREG promoted human intestinal myofibroblast proliferation and motility.

Conclusion

These findings revealed that Treg and human intestinal myofibroblast-derived AREG induced by TGF-β promotes intestinal fibrotic responses in experimental colitis and human patients with CD.Read more P175 HucMSC-Exo ameliorate experimental colitis via modulating gut microbiota and metabolitesWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Gut microbiota and metabolites have been shown to influence the development of inflammatory bowel disease (IBD). Exosomes derived from human umbilical cord mesenchymal stem cells (HucMSC-Exo) have been identified as a promising biological therapy for the treatment of IBD. Previous studies have described that HucMSC-Exo could modulate gut microbiota. However, the mechanism remains unclear. Here, we explored the role of gut microbiota and metabolites in HucMSC-Exo-mediated amelioration of experimental colitis.

Methods

Dextran sulfate sodium (DSS) was used to induce colitis. The role of HucMSC-Exo were assessed in colitis mice. Fecal microbiota transplantation (FMT) and sterile fecal filtrate gavage were employed to evaluate the effect of gut microbiota and metabolites. Gut microbiota and metabolites were analyzed through 16S rRNA sequencing and metabolomic profiling. The proportion of CD4+ T cells were phenotyped by multicolour flow cytometry.

Results

HucMSC-Exo treatment alleviated colon inflammation by regulating flora composition, significantly up-regulated the levels of bacteria such as Bacteroides, Parabacteroides distasonis, and Tannerellaceae. Meanwhile, HucMSC-Exo transformed metabolite short-chain fatty acid (SCFA) profiles, particularly increased butyrate level. Additionally, HucMSC-Exo selectively up-regulated the frequencies of regulatory T (Treg) cells as well as down-regulated the ratio of T helper type 17 (Th17) cells in colonic lamina propria to maintain intestinal immune homeostasis and repaired the colonic mucus barrier. FMT and sterile fecal filtrate gavage were conducted to confirm the above mechanism. Microbiota from HucMSC-Exo-treated mice alleviated the colitis over microbiota from DSS-treated mice. Sterile fecal filtrate from HucMSC-Exo-treated mice and butyrate induced similar beneficial outcomes, such as improved the Th17/Treg balance and repaired the colonic mucus barrier. Collectively, HucMSC-Exo ameliorate colitis by directly modulating gut microbiota and metabolites.

Conclusion

HucMSC-Exo ameliorated experimental colitis via directly modulating gut microbiota and metabolite butyrate, which could regulate CD4+T cells homeostasis and repair colonic mucus barrier. The findings demonstrated the HucMSC-Exo as a potential gut microbiota and metabolites modulator to treat IBD.Read more P176 TYK2 inhibition attenuates the stimulation of sensory neurons with hyper-IL-6Wed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Abdominal pain and diarrhoea are a cause of significant morbidity for people with colitis. Recent single cell RNA sequencing of sensory neurons innervating the gut highlights a likely role for sensory nerves in the pathophysiology of these symptoms based on the marked expression of cytokine receptors from the IL-6 receptor family in gut projecting sensory neurons. In keeping with the reported downstream signalling pathway for these receptors marked co-expression of TYK2 transcripts were also found along with IL-6 signal transducer (GP130) in colonic nociceptors characterised by expression of the capsaicin receptor TRPV1. These observations suggest that TYK2 inhibitors may ameliorate symptoms of pain and diarrhoea in people with colitis by preventing neurogenically mediated gut contractility and nociceptor activation.

Methods

TYK2 mediated sensory neuron activation: changes in the intracellular [Ca²⁺]_i within thoracolumbar (T12-L5 spinal segments) dorsal root ganglia sensory neurons were examined in cells cultured overnight and loaded with Fluo-4-AM (30min) prior to imaging. Responses were measured to the hyper-IL-6 fusion protein of the soluble IL-6 receptor and IL-6, which transactivates the GP130 receptor subunit to mimic IL-6 family receptor signalling following pre-treatment with vehicle, the TYK2 inhibitor Deucravacitinib (100nM) or the pan-JAK inhibitor Pyridone-6 (2 μM). Afterwards cells were exposed to capsaicin (1 µM) followed by 50 mM KCl, to confirm the presence of nociceptors and neurons respectively by positive response.All experiments were performed using tissue from male C57/B6 mice euthanised by rising concentration of CO₂followed by exsanguination in accordance with Schedule 1 of the UK Animals Scientific Procedures act (1986).

Results

Application of hyper-IL-6 produced a robust increase in [Ca²⁺]_i levels in DRG sensory neurons which was significantly attenuated by pre-treatment with the TYK2 specific inhibitor Deucravacitinib (p<0.01) or the pan JAK inhibitor Pyridone-6 (p = <0.05).

Conclusion

Findings demonstrate that inhibition of TYK2 inhibitor prevents sensory neuron activation in response to IL-6 trans-signalling. This data suggests that TYK2 inhibitors may have utility for the treatment of abdominal pain in people with colitis.Read more P177 Beta-CGRP in inflammatory bowel disease: a protective neuropeptide of the gutWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Experimental models indicate that beta calcitonin gene-related peptide (beta CGRP), libertated by enteric neurons, has a potential role on gastrointestinal mucosa homeostasis, but its real role is not well profiled. We measured beta-CGRP circulating levels in a cohort of subjects with a recent diagnosis of inflammatory bowel disease (IBD), to assess the potential role of this neuropeptide in its pathogenesis.

Methods

Morning serum beta-CGRP levels were measured by ELISA (CUSABIO, China) in 96 consecutive patients recently diagnosed of IBD patients (< 1 year) and compared with those belonging to 50 matched healthy controls (HC) and 50 chronic migraine (CM) patients matched by age and sex. We only allowed treatment with either steroids or mesalazine, and registered cardiovascular comorbidities, autoimmune concomitant diseases or extraintestinal manifestations. Statistical analysis was made using SPSS®.

Results

Beta CGRP concentrations were lower in IBD patients (3.1±1.9 pg/mL; 2.9 [2.4-3.4] pg/mL) when comparted to HC (4.7±2.6; 4.9 [4.0-5.8] pg/mL; p<0.001) and CM patients (4.6±2.6; 4.7 [3.3-6.2] pg/mL; p<0.001). Respecting IBD subtypes, beta-CGRP levels were lower in ulcerative colitis patients (3.0±1.9pg/mL; 2.5 [2.1-3.4] pg/mL) as well as Crohn’s disease patients (3.3±2.0 pg/mL; 3.2 [2.4-3.9] pg/mL) to those of HC (p<0.01 and p<0.05, respectively) and CM (p<0.01 and p<0.05, respectively). Beta-CGRP levels in CM did not differ to those with HC (p=0.92).There were no significant differences when patients were classified by presence/absence of cardiovascular risk factors (yes: 3.1±1.7 pg/mL; no: 3.2±2.1 pg/mL; p=0.93); autoimmune comorbidities (yes: 3.4±1.4 pg/mL; no: 3.1±2.0 pg/mL; p=0.24); mesalazine treatment (yes: 3.1±1.9 pg/mL; no: 3.2±1.9 pg/mL; p=0.91); or steroid treatment (yes: 3.0±1.9 pg/mL; 3.2±1.9 pg/mL; p=0.52). Main characteristics and main results are exposed in table 1 and figure 1.

Conclusion

The reduction in serum beta-CGRP concentrations y patients with recent diagnosis of IBD, compared to two control groups, strongly supports a role for this neuropeptide in the pathophysiology of the disease since its early stages. This decrease was found in both IBD subtypes. Our data indicate a protective role of beta-CGRP in the homeostasis of the gastrointestinal tract.This study has been co-funded by Instituto de Salud Carlos III (ISCIII) through the project PI20/01358 and by Fondos Europeos de Desarrollo Regional (FEDER), "Una manera de hacer Europa".Read more P178 Changes in composition and structure of ileal mucus in Crohn’s disease patients compared to healthy controlsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Crohn’s disease (CD) is a chronic transmural disease that can affect any part of the gastrointestinal tract. Typically, the terminal ileum is impacted. The pathogenesis of this disease results from a complicated interaction of multiple factors, with the intestinal barrier playing a critical role. The intestinal barrier in the ileum is comprised of epithelial cells that are coated with a mucus layer. This barrier is permeable to nutrient absorption and microbiota. Detailed analyses of human ileal mucus are currently absent. Our study aimed to comprehend the function of mucus and the biophysical and biochemical stimuli that exist in the mucus layer during ileal inflammation, in contrast to the healthy state.

Methods

We enrolled 28 patients diagnosed with Crohn’s disease (CD) and 27 healthy individuals as part of our study. Mucus and biopsies from the terminal ileum were collected during a colonoscopy. The extent of clinical, endoscopic and histologic inflammation in the terminal ileum at the time of collection was evaluated using the Harvey-Bradshaw Index, Simple Endoscopic Score, and modified Naini and Cortina score. The disease trajectory and dietary behaviors of all patients and healthy controls were documented. Samples were processed following protocols for various analyses, including rheology, proteomics and scanning electron microscopy (SEM).

Results

Our study presents the first data on the rheology and viscoelastic properties, of human ileal mucus. Interestingly, we discovered notable variations in the viscoelastic properties of mucus in CD patients compared to healthy individuals. Furthermore, the mucus mesh size and structure differed in CD patients in comparison to healthy controls. The SEM pictures also displayed these quantitative changes. We further assessed clinical characteristics, encompassing duration of disease, and observed certain variations, although their significance is not yet statistically established.A distinct profile was detected in CD patients compared to healthy controls using proteomic analysis. The ileal mucus of CD patients demonstrated elevated levels of ITGB2 and S100 proteins, which are involved in inflammatory pathways. Moreover, a correlation was found with histologic inflammation at the time of the collection.

Conclusion

In our study, significant changes in mucus composition and structure were found in the terminal ileum of CD patients, compared to healthy controls. This preliminary analysis provides a basis for further investigations to establish correlations between mucus composition and viscoelastic properties, and the subsequent effects on the underlying epithelial barrier.Read more P179 Decrease in Butyric Acid in fecal matter in patients with Inflammatory Bowel Disease is associated with the levels of secretory Immunoglobulin A and fecal calprotectinWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Accumulating evidence shows that the development of IBD is always accompanied by dysbiosis of the intestinal microbiota. Short-chain fatty acids (SCFAs) are produced by prebiotic intestinal bacteria, with mportant anti-inflammatory functions, delaying the clinical progression of IBD. The aim of this study is to compare SCFA levels in fecal matter in patients with IBD versus patients with Spondyloarthritis (SpA) and healthy controls.

Methods

24 patients were evaluated for the presence of gastrointestinal symptoms, demographic data and inflammatory markers: fecal calprotectin, C-reactive protein (CRP), secretory IgA (SIgA) and erythrocyte sedimentation rate (ESR). The quantification of SCFAs (acetic-AC, propionic-AP, butyric-AB and total SCFAs-ACCC-T) from fecal matter was analyzed by ultra-high pressure liquid chromatography coupled to mass spectrometry (UHPLC-Q/ TOFMS).

Results

33.3% of patients with IBD were men, with body mass index >25 in 16.7%; 83.3% presented more than 2 gastrointestinal symptoms at the time of sample collection, 33.3% had high levels of fecal calprotectin, 50% had CRP levels higher than 3mg/L and high ESR in 33.3% and a mean SIgA. of 27.73±5.03 g/mL. Very decreased levels of butyric acid (BA)ug/mL and T-SCFA were observed in IBD (9.45±4.89 and 121.73±65.94, respectively), compared to CS (BA 20.84±8.83 and total SCFA.12±122.09)., SpA SG (AB 13.35±10.44 and total AGCC 150.73±128.52) and SpA without OS (AB 21.13±5.68 and AGCC-T 219.51±229.65). Significant differences were found in fecal BA levels between the study groups (p=0.027). Interestingly, this metabolite in the CS group and the SpA group without OS did not show differences between them, but compared to the IBD group p=0.015 and 0.009 respectively, with a decrease in IBD. And interestingly, no differences were evident between fecal SCFA levels between the IBD group and the SpA group with OS even without a diagnosis of IBD. A principal component analysis was performed for the IBD group where two components were identified that group where COMP.1 was defined by a high correlation between the levels of each of the ACCC (AB CCF= 0.994, AA CCF= 0.935, AP= 0.610 and AGCC-TCCF= 0.910) that had an inverse relationship with COMP.2 which was made up of SIgA (CCF=0.988) and fecal calprotectin (CCF= 0.988).

Conclusion

SCFAs play a key role in maintaining immune homeostasis both locally and systemically. BA levels were significantly lower in patients with IBD compared to CS and those with SpA. This evidence clearly supports the hypothesis that relates the lack of BA with an exacerbated inflammatory response that could give rise to a dysfunctional intestinal epithelial barrier by regulating the production of mucosal antibodies such as SIgA.Read more P180 Novel biomarkers associated with inflammatory bowel diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Inflammatory bowel disease (IBD) is a chronic multi-factorial disease characterized by inflammation of the gastrointestinal tract. Currently, the mechanisms underlying the disease are far from being elucidated. Thus, the study of proteins involved in its pathogenesis would allow further insights into the molecular mechanisms underlying IBD.

Methods

The serum and intestinal mucosa (ileum and left colon) proteomic profiles of patients with Crohn´s disease (CD) and ulcerative colitis (UC) and healthy controls (HC) were analyzed using a label-free quantitative proteomics approach (Table 1). Data mining and pattern recognition techniques were performed to identify hidden relationships that are not detectable using classical linear classifiers, and thus identify potential markers able to discriminate between the different study groups. Six candidate biomarkers were selected for further validation using enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry (IHC) in serum and intestinal tissue samples, respectively (Table 2).

Results

Comparison of serum proteins between UC patients and HC revealed statistically lower levels of protein 1 and 2 and higher levels of protein 3. The comparison of potential biomarkers between CD and HC group showed lower levels of protein 1 and higher levels of protein 3. In addition, protein 4 was differentially upregulated in CD patients compared to UC (Figure 1A). Regarding the intestinal biopsies, protein 5 showed higher intensity in the IHC staining of ileum from CD patients compared to HC, whereas protein 6 was significantly decreased in left colon and ileum from CD and UC patients compared to HC (Figure 1B). These proteins are involved in thyroxine transport, regulation of chemotactic chemokine activity, inflammatory processes, triglyceride homeostasis, oxidative stress and regulation of NF-kappa-B activation in the cytosol.

Conclusion

In this study, we have identified a panel of six potential biomarkers that could help to elucidate mechanisms involved in IBD pathogenesis. Their roles in the pathophysiology need to be clarified in further experiments.Read more P181 Combination of EPIC-CD epigenetic signatures accurately identifies non-response to multiple biologics in patients with active Crohn’s diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

While the introduction of biologicals has revolutionized Crohn’s disease (CD) care, the current trial-and-error approach to treatment selection is insufficient, emphasizing the unmet need for predictive biomarkers. We previously developed 2 distinct panels of 25- and 68 epigenetic markers that were accurately associated with (non-)response to vedolizumab (VDZ) or ustekinumab (USTE) in both anti-TNF naïve and experienced patients. In this analysis of the EPIC-CD study, we examined how both models performed in detecting Crohn’s disease patients unresponsive to treatment with multiple biological agents.

Methods

We measured peripheral blood DNA methylation profiles in an independent cohort of adult CD patients that were sequentially treated with anti-TNF (infliximab, adalimumab), VDZ and/or USTE using the Illumina EPIC BeadChip array. Treatment failure was determined using objective outcome measures including endoscopy, MRI or the need for resection combined with clinical- and biochemical parameters (CRP and/or fecal calprotectin (FCP)). Using raw methylation data and our previously developed VDZ and USTE models, predictions were generated, and the percentages of true and false negatives were subsequently calculated.

Results

We included 34 CD patients (53% females, median age 36, median disease duration 13 years). Of these, 27 patients had a history of VDZ failure, 26 had experienced USTE failure, and 19 had failed both VDZ and USTE determined with endoscopy (82%), MRI (6%), or surgical resection (12%) and supplemented by CRP (35%) and/or FCP (47%) and clinical outcome assessment (94%). Notably, we observed a substantial proportion of patients with extensive disease location (67.6%), perianal disease (52.9%), and/or a history of IBD-related surgery (70.6%), underscoring the therapy-refractory nature of this cohort. Both VDZ- and USTE-response prediction models demonstrated accurate prediction of non-response, with a true negative rate of 89% (24 out of 27) for VDZ and 92% (24 out of 26) for USTE. When specifically targeting patients who failed both VDZ and USTE, the models correctly identified 16 out of 19 (84%) as non-responders. Twelve of these 19 patients (75%) had previously failed anti-TNF treatment.

Conclusion

We demonstrate the predictive power of the EPIC-CD epigenetic signatures to effectively identify patients that failed both VDZ and USTE treatment. Our results hold considerable clinical significance, as accurately pinpointing non-response to a combination of multiple biological agents enables clinicians to directly consider alternative modes-of-action, such as JAK inhibitors.Read more P239 Characteristics and outcomes of portal vein thrombosis in patients with Inflammatory Bowel Disease in KoreaWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Portal vein thrombosis (PVT) is known to occur frequently in patients with inflammatory bowel disease (IBD), particularly when compounded by factors such as abdominal infection, IBD flares, or intra-abdominal surgery. However, PVT can lead to diverse complications, causing acute issues like intestinal ischemia or necrosis and long-term problems such as portal hypertension, varices, and ascites. Nevertheless, there is a significant shortage of research regarding the characteristics and prognosis of PVT in the context of IBD. Particularly, with the rising prevalence of IBD patients in Asia, the authors conducted an evaluation of clinical presentation and prognosis of PVT in IBD patients at a large tertiary hospital in South Korea.

Methods

This study is a retrospective study conducted at a single tertiary center in South Korea. It examined patients aged 18 and above diagnosed with inflammatory bowel disease (IBD) who had confirmed portal vein thrombosis (PVT) between June 1, 1989, and December 15, 2021. The study focused on investigating patient characteristics, PVT characteristics, treatment methods, and outcomes. The diagnosis and resolution of PVT were confirmed using enhanced CT imaging.

Results

A total of 78 patients met the inclusion criteria for this study. Only 21% (16/78) received oral anticoagulants, yet nearly all patients (96%; 75/78) achieved Complete Radiologic Resolution (CRR). When comparing baseline characteristics between the anticoagulation use group and the non-use group, a trend was observed with a higher utilization of anticoagulants in cases where the main portal vein was involved rather than only the left or right portal vein (p-value 0.006). However, when conducting multivariable analysis, no factors significantly influenced CRR, especially anticoagulant use and surgery status.

Conclusion

PVT concomitant with IBD demonstrated favorable outcomes regardless of anticoagulation use.Read more P240 The impact of environmental factors in the onset, activity and severity of inflammatory bowel diseases in a population-based Danish setting – findings from IBD Prognosis StudyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The role of environmental exposures in inflammatory bowel diseases (IBD) remains elusive despite their implicated significance. The aim of the current study was to investigate pre-diagnostic environmental factors affecting incident patients with onset of ulcerative colitis (UC) and Crohn’s disease (CD) and their impact on the disease activity at diagnosis.

Methods

Incident adult patients (≥18 years) with newly diagnosed UC or CD according to the Copenhagen IBD Criteria were included in the IBD Prognosis Study, a population-based inception cohort representing approximately 20% of the Danish population (1.1 million). Environmental factors were systematically assessed using the International Organization of Inflammatory Bowel Disease environmental factors scheme.¹A severe disease presentation was defined by the need for glucocorticoids, immunomodulators, biologics, or surgery within three months of disease, while severe disease activity was defined endoscopically (Mayo Endoscopic Score=3; Simple Endoscopic Score-Crohn’s Disease (SES-CD) >16) or as a composite of both high clinical disease activity (Simple Clinical Colitis Activity Index >10 or Harvey-Bradshaw Index>7) and biochemical inflammation (C-reactive protein >10 mg/L or fecal calprotectin >1800 μg/g. Univariate and multivariate logistic regression analyses adjusting for age, gender, and disease phenotype were conducted to examine the association between specific environmental factors and disease activity and severity of UC and CD.

Results

Out of the original cohort, 208 (67.5%) and 128 (63.1%) patients with incident UC and CD, respectively, responded to the questionnaires, with no discernible differences between respondents and non-respondents.Patients with UC and CD exhibited disparities in the frequency of the following pre-diagnostic environmental factors: first-degree relatives with IBD (UC: 11.5%, CD: 24.2%, p=0.009), previous appendectomy (UC: 2.9%, CD: 10.2%, p=0.005), active smoking (UC: 14.4%, CD: 25.8%, p=0.01), soft drinks daily (UC: 18.3%, CD: 34.4%, p=0.003), and access to mains drainage (UC: 93.3%, CD: 85.2%, p=0.02).Further, several environmental factors were independently associated with intensive treatment needs, including biologics or surgery, a severe initial presentation of IBD (table 1) as well as heightened disease activity (Figure 1).

Conclusion

This population-based cohort study identified several modifiable and non-modifiable environmental factors associated with the onset, disease activity, and initial presentation of UC and CD. emphasizing the need for heightened awareness and potential intervention strategies.

References

1. Halfvarson J et al., Inflamm Bowel Dis. 2006. doi: 10.1097/01.mib.0000228998.29466.ac.Read more P241 Systemic redox status associates with disease activity and clinical phenotypes in Inflammatory Bowel DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Oxidative stress is a key pathophysiological mechanism in inflammatory bowel diseases (IBD). Systemic levels of oxidative stress are reflected by reduced levels of free thiols (FT) in circulating proteins, especially those in albumin, which associates with disease activity in IBD. Yet, clinal value of circulating FT level as biomarkers of disease and therapy response remains largely unexplored. Here we investigated the association between plasma FT levels and clinical parameters, the plasma inflammatory proteome and medication use.

Methods

Plasma samples from 1,028 patients with IBD (567 Crohn's disease [CD] and 461 ulcerative colitis [UC]), and 500 healthy controls (HCs) participating in the 1000IBD and LifeLines projects were profiled for free thiols (FT), uric acid, bilirubin and 92 inflammation-related proteins (Olink Inflammation panel^Ò). All biomarkers were associated with clinical phenotypes using general linear models adjusting for age, sex, body mass index, smoking and medication use.

Results

Plasma FT levels were significantly lower in IBD compared to HCs (p<0.05) (Figure 1A), with patients with UC showing even lower levels than patients with CD (p<0.05). Patients with UC on induction therapy had lower FT levels compared to patients on maintenance therapy (p<0.05). Furthermore, FT levels of patients with IBD were strongly associated with systemic inflammation (C-reactive protein [CRP], p<0.05) (Figure 1B). In both patients withCD and UC, reduced FT levels were associated with elevated levels of inflammation-, apoptosis-, and growth factor-related proteins, including C-X-C motif chemokine 9 (CXCL9) (Figure 1C-D), CUB domain-containing protein 1 (CDCP1) and caspase-8 (CASP8), proteins previous associated with preclinical IBD^1-3. Furthermore, specifically for patients with UC, reduced FT levels were associated with elevated eotaxin-1 (CCL11) (Figure 1C), monocyte chemotactic protein-1 (MCP-1), and several cytokine biomarkers like Interleukine-6 (IL6) and Interleukin-17A (IL17A).

Conclusion

Systemic FT levels associate with inflammatory disease activity and clinical therapy and may offer potential utility in clinical assessments. This study highlights the intricate involvement of oxidative stress in various inflammatory pathways and components, particularly in innate/adaptive immune balance, cell damage, and apoptosis. These findings contribute to a deeper understanding of the interplay between oxidative stress, inflammation, and IBD.Funding: This study was supported by Janssen Research & Development LLC.References:1. Leibovitzh H, et al. Gut. 20232. Chen J, et al. JCC. 20233. Bergemalm D, et al. Gastroenterology, 2021Figure 1Read more P242 Immune-cell specific biomarker of early intestinal inflammation: Neutrophil elastase degraded fragment of type III collagen is elevated in patients with Inflammatory Bowel DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Inflammatory Bowel Disease (IBD) is characterized by epithelial barrier injury of the gastrointestinal (GI) tract. The disease course encompasses abnormal immune responses and excessive secretion of proteases from immune cells. Neutrophils are the first to migrate into the inflamed interstitial matrix, where type III collagen is significantly deposited. Detection of mucosal inflammation in early stages is crucial to prevent cumulative clinical damage, as a delayed diagnosis can hinder effective treatment. Thus, we aimed to develop a biomarker that reflects early intestinal inflammation prior to it becoming medically evident; allowing us to distinguish patients that would respond to an anti-inflammatory treatment.

Methods

A competitive enzyme-linked immunosorbent assay targeting a human neutrophil elastase derived fragment of type III collagen was developed (C3-HNE). The validation was conducted by assessing its dilution recovery, matrix spiking, interference, and inter- and intra-assay variation. The biological relevance was evaluated in commercial samples, one preclinical, and two clinical studies. In the preclinical study, C3-HNE was measured in serum samples from a dextran sodium sulfate (DSS)-induced colitis rat model. In the commercial samples and clinical cohorts, C3-HNE was measured in serum from patients with IBD and healthy donors (HD). To compare the biomarker levels between groups, two-way ANOVA with a Fisher's LSD, and Mann-Whitney U-tests or Kruskal-Wallis (Dunn’s corrected) were conducted.

Results

The novel biomarker C3-HNE was successfully validated, resulting in a technically robust assay with acceptable technical parameters (Table 1). In the preclinical study, the analysis revealed significant difference in the C3-HNE levels between the control and DSS groups on day 4 (p=0.01) (Figure 1A). Additionally, C3-HNE was released earlier (day 1) in the timeline than the elevation of the current disease activity (DAI) score (day 7) (Figure 1A-B). In both clinical cohorts and commercial samples, C3-HNE levels were significantly higher in patients with Crohn's disease (CD), ulcerative colitis (UC) and IBD than in HD (p<0.01, p<0.05 and p<0.05) (Figure 1C-E). Based on the ROC analysis, the biomarker can significantly discriminate between HD and CD, UC or IBD (Table 1).

Conclusion

C3-HNE is elevated in patients with CD, UC and IBD compared with HD. Furthermore, C3-HNE reflects early stages of clinically apparent mucosal damage during experimental colitis. This biomarker holds the potential to identify early mucosal damage or acute inflammation in the GI tract; nevertheless, additional studies are needed to evaluate its clinical validity.Read more P344 Achieving Crohn's Disease treatment targets following the STRIDE-II recommendations in clinical practiceWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) initiative proposes therapeutic targets for inflammatory bowel disease (IBD) to be used for a treat-to-target clinical management strategy. However, there is lack of information regarding how many patients actually achieve defined treatment targets as outlined in STRIDE-II after initiation of new therapies. The objective of this study was to investigate the treatment response of Crohn’s disease (CD) patients according to the STRIDE-II recommendations in the first year after starting a new pharmacological therapy in clinical practice.

Methods

CD patients included in a remote monitoring care-path using myIBDcoach, starting a new therapy between January 1^st 2020 and December 31^st 2021 were eligible for inclusion. The short-term (2-4 months) treatment target was defined as clinical response based on at least 50% decrease in the Monitor IBD at home (MIAH) questionnaire, a patient-reported outcome measure validated to predict endoscopic disease activity. Intermediate (5-9 months) targets were clinical remission (MIAH ≤3.6) and normalization of inflammatory parameters, i.e. faecal calprotectin (<150 ug/g) and C-reactive protein ([CRP] <10 mg/L). Long-term (10-12 months) targets were absence of disability (IBD-control questionnaire ≥13), and a combination of MIAH score ≤3.6 and calprotectin <150 ug/g as surrogate markers for endoscopic remission.

Results

39 CD patients were included in the current analysis, of which two started treatment with thiopurines and 37 with a biological. At baseline, median MIAH score was 3.0 (IQR 3.1) and median IBD-control score was 8.5 (IQR 9.0). After three months of therapy, 26% of patients showed clinical response and 64% of patients were in clinical remission (median MIAH 2.2 [IQR 1.8]). As for intermediate targets, clinical remission was seen in 62% (median MIAH 2.0 [IQR 2.3]), and CRP and calprotectin normalization in 79% and 59% of patients, respectively. At the end of follow-up, 41% had low surrogate marker scores indicative for endoscopic remission (median MIAH 1.9 [IQR 1.6] and median calprotectin 109.0 [IQR 241.0]). Resolution of disability was achieved in 65% (median IBD-control score 14.0 [IQR 6.0]). Three patients (9%) achieved all treatment targets within a year of follow-up (Table 1).

Conclusion

This study used an incident user real-world cohort to evaluate the STRIDE-II recommendations. While all patients achieved at least one treatment target, only 9% achieved all treatment targets according to the STRIDE-II recommendations. Using these recommendations provides good guidance in clinical settings. However, treatment approaches need to be improved to reach the optimal outcomes in daily clinical practice.Read more DOP83 Intestinal epithelium-specific deletion of the Aryl hydrocarbon Receptor (AhR) reduces intestinal Tight Junction permeability thereby hindering homeostatic antigen sampling and tolerogenic immune responsesWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The Aryl Hydrocarbon Receptor (AhR) plays important functions in intestinal stem cell differentiation, intestinal homeostasis, and immune regulation, however, its role in regulating intestinal tight junction (TJ) barrier and immune tolerance remains poorly understood. In this study, we assessed the role of intestinal epithelium-specific AhR deletion on the intestinal paracellular TJ barrier and its role in homeostatic intestinal antigen sampling and immune tolerance.

Methods

Ahr^fl/fl, and Ahr^Vil-Cre mice were maintained in a specific pathogen-free area until injected with tamoxifen (i.p) to delete the Ahr gene, and then moved to the normal housing. The AhR deletion was maintained by weekly tamoxifen injections for 3 weeks. We performed physiological assessments of the gut epithelial barrier and used flow cytometry, confocal immunofluorescence imaging, and qRT-PCR analysis were also employed to assess the effects of epithelial AhR deletion.

Results

Conditional gut epithelium-specific knockout of AhR (Ahr^ΔIEC) significantly increased the colonic transepithelial resistance (TER) and reduced the paracellular flux of urea and inulin. Assessment of transcript levels in the mouse colonic tissues, after 3 weeks of AhR deletion, showed that Ahr^ΔIEC colonic tissues had higher transcript abundance of barrier-forming proteins like Claudin-3, -4, and occludin with reduced abundance of the pore-forming claudin-2. Ultrastructural investigation of intestinal TJs of Ahr^ΔIEC mice showed diffused, laterally extended, and collapsed TJ architecture. Ahr^ΔIEC did not alter the baseline levels of TNF-α, IFN-γ, and IL-4 however, the transcript levels of IL-6, IL-1β, and IL-17A showed marked elevation. The Ahr^ΔIEC colonic tissues also showed increased infiltration by CD45⁺ immune cells under baseline conditions with a high abundance of inflammatory dendritic cells (DCs), macrophages (MΦs), and Th17 cells with a corresponding reduction in their tolerogenic counterparts and T_reg cells. The Ahr^ΔIEC also showed reduced colonic transcript levels of IL-10, a key anti-inflammatory cytokine, and Programmed death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA4), the two key proteins, involved in limiting the pro-inflammatory responses in the gut mucosa. In-vitro, AHR^-/- in Caco-2 cells also reduced paracellular TJ permeability, and co-culture assays with human dendritic cells showed reduced basal to apical paracellular podia formation and antigen sampling by DCs.

Conclusion

Our data show that deletion of the AhR gene in the gut epithelial cells reduces the epithelial paracellular TJ permeability in-vitro and in-vivo and also highlights the role of homeostatic paracellular TJ permeability in the development of intestinal immune homeostasis.Read more DOP84 Colonic CD4+ T cell senescence is implicated in the progression of experimental colitis in aged miceWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Evidence from recent epidemiological data suggests that the burden of IBD in the elderly is increasing globally. However, the mechanisms underlying the age-related IBD susceptibility remain elusive. Aging leads to a progressive functional decline of the immune system, rendering the elderly increasingly susceptible to autoimmune disease. Herein, we sought to determine the role of immunosenescence in age-dependent colitis and to explore the underlying mechanisms.

Methods

Young (2-3 months), middle-aged (10-12 months), and aged (20-24 months) mice were established models of colitis by 2% dextran sulfate sodium salt (DSS) treatment. Weight loss, colon length, disease activity indexes (DAI) and histological scores were evaluated to assess the severity of colitis. Using a second-generation fluorogenic substrate for β-galactosidase and multi-parameter flow cytometry, we detected the senescence-associated β-galactosidase (SA-βGal) activity in lymphocytes isolated from colon, including CD4⁺ T cells, CD8⁺ T cells, B cells, natural killer cells, microphages, neutrophils and dendritic cells. Based on the immunocytes that exhibit greatest age-related increases in SA-βGal activity, inflammatory cytokines such as TNF-α、IFN-γ、IL-17 were evaluated in senescent immunocytes through flow cytometry. Single-cell and bulk RNA-seq of colonic immune cells in mice with different ages were performed to further investigate the precise molecular mechanisms.

Results

Ageing increased the severity of DSS-induced colitis wherein aged mice exhibited worsened weight loss, shortened colon length, higher DAI and histological scores compared to young mice. The greatest age-associated increases of SA-βGal activity were observed in colonic CD4⁺ T cell populations. Additionally, aging resulted in systemic activation of CD4⁺ T cells, exhibiting an expansion of CD4⁺ effector memory T (T_EM) cells in colon, as well as in spleen. Aged colonic CD4⁺ T cells generate higher levels of IFN-γ and IL-17 comparing to young colonic CD4⁺ T cells, especially in status of colitis. Moreover, the accumulated CD4⁺ T_EM cells in the aged colon were the main source of IL-17 production. Single-cell analysis revealed that aging increased colonic CD4⁺ T_EM cells, which were associated with T cell-mediated cytotoxicity and cytokine-mediated signaling pathway. Splenic CD4⁺ T_EM cells isolated from aged colitis mice were confirmed to involve in cellular senescence, Th17 differentiation and inflammatory signaling pathway through bulk RNA-seq.

Conclusion

These results provide a significant insight into the contribution of senescent CD4+ T cells to age-dependent colitis and provide an attractive possibility that targeting T cell specifically might be a potential strategy to treat elderly IBD patients.Read more P044 Evaluation of the CO2 Footprint of Laparoscopic Ileocecal Resection for Terminal Ileitis in Crohn's DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Each year, huge amounts of carbon dioxide (CO2/equivalents) are generated and healthcare systems play a major role in the production of those so called greenhouse gases (GHG). The aim of this study is to assess the environmental impact, in particular the CO2 footprint, of laparoscopic ileocecal resection (ICR) for terminal ileitis in Crohn’s disease (CD) patients.

Methods

This is a prospective, multicentre evaluation of the carbon dioxide (CO2) emission caused by the care of CD patients undergoing laparoscopic ICR for terminal ileitis. All processes and products used during laparoscopic ICR for terminal ileitis in adult CD patients (≥16 years) between March and May 2023 were collected by one monitor. A Life Cycle Assessment (LCA) was conducted, including midpoint and endpoint analysis, to evaluate and compare the environmental impact, mainly focussing on CO2 (-equivalents), of all products and processes.

Results

The total CO2 footprint of a laparoscopic ICR for terminal ileitis in one CD patient (including transport of staff and patients) was 139 kg CO2eq, which equals a one way trip by car from Amsterdam to Berlin. Major contributors to CO2 emissions (“hotspots”) were transport of employees, transport of patients, medication, laparoscopic tools, electricity in theatre and a combination of standard surgery items. In addition to the carbon footprint, a significant impact on ozone formation, human carcinogenic and ecotoxicity, water consumption and mineral resource scarcity was found. The amount of disability-adjusted life years (DALY’s) as a result of the environmental impact of one laparoscopic ICR are equal to approximately 2.5 hours of health damage per laparoscopic ICR.

Conclusion

The “5 R principle” (refuse, reduce, reuse, repurpose, recycle) is an import aspect in reduction of the CO2 footprint and in current medical guidelines, which should be taken into account by all employees (e.g. consider traveling by train/carpooling). The total CO2 footprint of a laparoscopic ICR for terminal ileitis in one CD patient is 139 kg CO2eq. In addition to quality of life (QoL) and overall costs, the carbon footprint and overall the environmental impact of all medical procedures, should be taken into consideration and should be optimized if possible in the multimodal treatment of patients with CD terminal ileitis. Therefore, further research into the environmental impact of (medical/surgical) treatment of CD patients is warranted and more process data should become available.Read more P045 MMP12 stimulates colonic afferents, and nociceptors through the activation of PAR1Wed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Abdominal pain is a cause of significant morbidity for people with colitis. We have previously shown that biopsy samples from people with Crohn’s disease (CD) are pro-nociceptive suggesting that peripheral nociceptor activation is a cause of pain in colitis. Furthermore, these effects were correlated with biopsy expression of macrophage metalloproteinase (MMP12), which was shown to stimulate mouse and human colonic nociceptors highlighting the potential utility of MMP12 inhibitors to act as visceral analgesics. Following on from this work we sought to determine the contribution of proteinase-activated receptor 1 (PAR1) to MMP12 mediated nociceptor activation.

Methods

MMP12 mediated sensory neuron activation: changes in the intracellular [Ca²⁺]_i within thoracolumbar (T12-L5 spinal segments) dorsal root ganglia sensory neurons were examined in cells cultured overnight and loaded with Fluo-4-AM (30min) prior to imaging. Responses were measured to MMP12 or the PAR1 receptor agonists TRAP6 following pre-treatment with vehicle, the MMP12 inhibitor MMP408 or the PAR1 antagonist SCH79797. Afterwards cells were exposed to capsaicin (1 µM) followed by 50 mM KCl, to confirm the presence of nociceptors and neurons respectively by positive response.MMP12 mediated colonic nociceptor activation: electrophysiological recordings were made of lumbar splanchnic nerve activity and of the isolated colorectum (ex-vivo) perfused with carbogenated Krebs solution, and responses determined following application with MMP12 alone or in the presence of respective MMP12 or PAR1 inhibitors.All experiments were performed using tissue from male C57/B6 mice euthanised by rising concentration of CO₂followed by exsanguination in accordance with Schedule 1 of the UK Animals Scientific Procedures act (1986).

Results

Application of MMP12 or TRAP6 produced a robust increase in [Ca²⁺]_i levels in DRG sensory neurons classified as nociceptors by their co-sensitivity to capsaicin. These effects were significantly attenuated by pre-treatment with respective MMP12 or PAR1 inhibitors, with the response to MMP12 also being inhibited by PAR1 antagonist pre-treatment. Consistent with this pattern of nociceptor stimulation, the application of MMP12 also a robust activation of colonic afferents that was abolished by inhibition of MMP12 or PAR1 activity.

Conclusion

Findings demonstrate that MMP12 stimulates colonic afferents, and nociceptors through the activation of PAR1.Read more P046 Real-world data on the treatment with Mirikizumab in a mostly biological-experienced Ulcerative colitis cohortWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Mirikizumab was approved for treating Ulcerative colitis (UC) in May 2023. However, real-world data, especially in biological-experienced patients, is scarce. We aimed to determine the treatment efficacy and persistence of Mirikizumab in mostly treatment-experienced UC patients.

Methods

All patients treated for UC in the Inflammatory Bowel Disease (IBD) outpatient clinic of the University Hospital Frankfurt from 07/23-11/23 were analyzed retrospectively. Data on clinical (Simple Clinical Colitis Activity Index (SCCAI)) and biochemical disease activity (fecal calprotectin (FC)), as well as patient history, were collected. Patients were followed up for at least 12 weeks.

Results

Seventeen patients with UC were included. Sixteen patients had already received at least one biological agent before starting Mirikizumab. Twelve patients were exposed to ≥ 2 biological agents, and four patients to ≥ 4 biological agents before starting Mirikizumab. One patient received Mirikizumab as a first-line treatment. 4 patients were treated with Ustekinumab before the therapy with Mirikizumab. Nine patients received oral steroids as a concomitant treatment. The median SCCAI at the time of the first infusion/start of induction was 7. We report a reduction in clinical disease activity from 7 to 5 based on the preliminary data of the SCCAI. Biochemical disease activity was assessed with FC levels. The median FC level at the start of the induction was 557.5. At week 8, the median FC level was 513 based on 7 out of 17 patients reached week eight until November 2023. Intravenous induction therapy was extended in 2 of 17 patients.There was no report of adverse events.

Conclusion

We report preliminary real-world data on the evidence and efficacy of Mirikizumab. In our interim analysis, Mirikizumab is an effective and safe treatment in biological-experienced UC patients.Read more P047 Deconditioning in quiescent Crohn’s Disease patients with heightened fatigue perceptionWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Heightened fatigue perception and premature exercise fatigue are common in inflammatory bowel disease (IBD). Physical deconditioning is greater in patients with increased fatigue perception relative to patients with a lower perception of fatigue, implicating deconditioning as an aetiological factor.This study used physiology and multiparametric Magnetic Resonance Imaging and Spectroscopy (MRI/MRS) during exercise to comprehensively phenotype quiescent IBD fatigue.

Methods

Participant body mass and regional body composition was assessed by DEXA, and tknee extensor strength and fatiguability using isokinetic dynamometry (Cybex, USA). A supine CPET was performed using an MR-compatible Ergometer (Cardiostepper, Ergospect) to standardize relative exercise intensity for in-bore ¹H MRI measures. ¹H MRI data were collected on a Philips 3T Ingenia wide bore scanner using a Philips Head/Neck coil and in-built posterior coil. Across rest, steady-state exercise (50% VO₂ peak) and recovery, Phase Contrast-MRI was used to compute cardiac output and cerebral blood flow (CBF), and T₂ Relaxation under spin tagging (TRUST-MRI) to measure brain oxygen extraction fraction (OEF).³¹P MRS data was collected on a 3T Philips Achieva using a 14cm 31P coil over the medial gastrocnemius. Ischaemic plantar flexion exercise was performed at 50% maximum voluntary contraction (MVC) using an MR-compatible ergometer (Trispect, Ergospect) during non-localized pulse-acquire 31P-MRS. 31P spectra were analysed using the AMARES function in jMRUI Beta 6.0. In vivo muscle mitochondrial flux during post-exercise PCr recovery (VPCr = kPCr * ΔPCr) where ΔPCr is PCrendrecovery –PCrendex) was quantified after reinstating limb blood flow and fitting PCr recovery to a mono-exponential function in GraphPad prism (PCr(t) = PCrinitial+(PCrend – PCrinitial)(1-exp(-k.t) where t is time from start of non-ischaemic recovery).

Results

16 quiescent CD patients and 12 age and BMI matched HV’s completed the study. General fatigue score was greater in CD relative to HV (P = 0.001, Table 1). Body composition, isometric strength, fatigue development were not different between groups (Table 1). CBF response to steady-state exercise was less in CD (P = 0.003) alongside the maintenance of cardiac output and brain OEF in HV (Figure 1). V_PCr following ischemic plantar flexion exercise was less in CD than HV (P = 0.02, Figure 1) (Figure 1).

Conclusion

Greater fatigue perception in CD was accompanied by lower CBF on exercise and blunted post-exercise PCr resynthesis, but no differences in body composition, strength and fatiguability relative to HV. These finding point to greater deconditioning in CD, corroborated by their lower daily step count relative to HV.Read more P121 Characterisation of the miRNAome in Crohn’s Disease patients reveals transcriptomic changes associated with tissue composition and drug treatmentWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Gene regulation plays a major role in Crohn's Disease (CD) susceptibility and drug response. MicroRNA (miRNA)-mediated mechanisms tune gene expression at the post-transcriptional level. MiRNAs are 20-to-25-nt long non-coding RNAs that repress protein expression by direct inhibition or cleavage of the targets. Evaluating the miRNAome is emerging as a promising tool to clarify pathogenesis and identify promising biomarkers. We characterised the regulatory miRNAome across disease subtypes, gut tissue locations and infliximab treatment in CD.

Methods

We generated 120 transcriptomic profiles from terminal ileum and left colon biopsies from Hospital Universitario de la Princesa (Madrid). This cohort is composed of 10 patients with active endoscopy, 10 quiescent CD cases, and 10 controls (30 in total). In a balanced setting, half of the samples were incubated with infliximab for 18 hours at 37ºC and the rest with basal medium (Table 1).We carried out an exploratory analysis to gain insights into the determinants of miRNAome variability, including variance partition analyses and linear mixed modelling to detect significantly altered miRNAs. We also harnessed results from several publications including GSE16879 dataset to perform a comparative study with infliximab response signatures.

Results

Tissue location is the primary determinant of miRNA expression variability. The Variance Partition model identified 30 top miRNAs whose variability is maximised across regions. However, patient-specific effects also play a relevant role. We also identified 96 differentially expressed miRNAs between terminal ileum and left colon, with an overrepresentation of molecules involved in stress and developmental pathways (Fig.1). Among these, we find miR200s and miR429, that are associated with suppression of epithelial-mesenchymal transition and are up-regulated in colon more than in ileum. Down-regulation of miR196 is also shown in terminal ileum.Regarding the effects of infliximab treatment, we detected nine deregulated miRNAs which are associated with cellular response pathways. These include miR200s and miR192, which targets NOD2 and down-regulates NF-κB. Our results show an up-regulation of miR192 upon infliximab incubation (log2FC=2.37), which is associated with a reduction in TNFα expression and, consequently, with induced overexpression of miR192. We conclude that this miRNA is a potential target for therapy development.

Conclusion

In short, tissue location, and to a lesser extent disease subtype, are the main determinants of miRNAome in CD. A few treatment-responsive miRNAs like miR192 and miR200s are identified, in spite of detection challenges, emphasizing the need to improve our comprehension of the miRNA dynamics associated with drug response.Read more DOP53 Long-term Efficacy and Safety of Risankizumab in Patients With Moderate to Severe Crohn's Disease up to 3 Years of Treatment: Results From the FORTIFY Open-Label Long-term ExtensionWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The ongoing FORTIFY maintenance open-label extension (OLE) substudy evaluates the long-term efficacy and safety of risankizumab (RZB), a p19 interleukin-23 inhibitor, for treatment of moderate to severe Crohn’s disease (CD). Here, we report 2-year results of FORTIFY OLE.

Methods

The FORTIFY (NCT03105102) OLE enrolled patients (pts) who completed 52-wks maintenance dosing in the FORTIFY substudies or RZB phase 2 OLE.^1,2 All pts received 180 mg subcutaneous (SC) RZB every 8 wks (Q8w), starting at wk56, except for pts who had prior rescue therapy (single 1200mg intravenous [IV] RZB dose then 360mg SC Q8w) who continued 360mg SC Q8w in the OLE. Pts with inadequate response (increased symptoms plus objective marker of inflammation) during the OLE could receive rescue therapy as described above. Pooled data from both treatment groups (RZB 180 mg & 360 mg SC) were assessed. Clinical outcomes were evaluated every 24 wks (endpoint definitions in Figure footnote). Endoscopy was performed every 96 wks. Results are reported as observed. Efficacy data for pts receiving rescue therapy in the OLE were included up to rescue initiation. Safety was assessed through the cutoff date of 05MAR2023. As this trial is ongoing, most patients have not reached the wk152 study visit. Any treatment-emergent adverse events (TEAEs) reported on or after the first dose in the OLE were analysed.

Results

As of the cutoff date, 1147 pts entered the OLE, of which 203 (17.6%) pts received rescue therapy during the OLE. Clinical response and remission rates were generally maintained with RZB from wks 56 to 152 (CD activity index [CDAI] clinical response, 85.8% to 86.5%, respectively; enhanced clinical response, 88.6% to 89.2%; CDAI clinical remission, 68.5% to 77.6%; stool frequency/abdominal pain score clinical remission, 64.4% to 71.0%) (Figure). At wks 56 and 152, respectively, rates of endoscopic response were 53.4% and 74.2%, endoscopic remission were 37.5%, and 58.9%, and ulcer-free endoscopy were 31.0% and 50.0%. There were no new trends for exposure-adjusted rates of TEAEs, and rates of adjudicated major cardiovascular adverse events, malignancies, serious infections and hepatic events remained stable with no new safety risks identified. There were no events of active tuberculosis, serious hypersensitivity, or adjudicated anaphylactic reaction. Three deaths occurred during the OLE (see Table footnote), all assessed by investigators as unrelated to study drug.

Conclusion

Pts receiving long-term RZB maintenance therapy in FORTIFY demonstrated sustained clinical and endoscopic efficacy with at least 3 years of treatment. The safety profile is consistent and supports long-term RZB treatment.¹doi: 10.1093/ecco-jcc/jjab093²doi: 10.1016/S0140-6736(22)00466-4.Read more DOP54 Guselkumab and golimumab combination induction therapy in Ulcerative Colitis results in early local tissue healing that is sustained through guselkumab maintenance therapyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Combination induction therapy with guselkumab (GUS), an interleukin (IL)-23p19 subunit antagonist, and golimumab (GOL), a tumor necrosis factor (TNFα) antagonist, induced higher rates of clinical remission, endoscopic, and histologic outcomes than either monotherapy at Week (WK)12 in patients (pts) with ulcerative colitis (VEGA NCT03662542). Data through WK38 suggested the continued benefit of combination induction even after a transition to GUS monotherapy at WK12. We explored early molecular changes in colon tissue in a subset of pts at WK4 to define mechanistic contributions of each monotherapy and combination; these parameters were evaluated again at WK38 to assess potential carry-over of efficacy.

Methods

Colon biopsies were obtained at baseline (n=195), WK4 (n=42 substudy), and WK38 (n=172). Transcriptional profiles were generated with RNA sequencing (RNAseq). Gene correlation network analysis was applied in conjunction with publicly available single cell RNAseq data to define biologically relevant bulk and cell type-specific transcriptional modules associated with molecular features of disease. Gene set variation analysis (GSVA) was used to quantitatively assess changes in biologic modules with treatment.

Results

At WK4, combination induction (n=10) showed significant (p<0.05) decreases in molecular features compared to GUS (n=19) and GOL (n=13), including transcriptomic modules representing the IL-23 pathway, interferon response, and inflammatory epithelial and myeloid transcriptional states associated with endoscopic improvement at WK4 (Mayo endoscopy subscore of 0 or 1) (combination 5/11, GOL 1/13; GUS 2/19). Reduction (p<0.05) in inflammatory modules persisted through WK38 with combination vs monotherapy induction. Module changes between treatments at WK4 indicated a stronger correlation between GUS and combination (R=0.8; p=2.2e-16) than GOL and combination (R=0.52; p=4.1e-12), with processes associated with epithelial and stromal biology, and mucosal inflammation. In contrast, the combination effect on specific neutrophil/myeloid biology at WK4 was more similar to GOL than GUS, supporting the early role of GOL in targeting innate inflammation.

Conclusion

Combination induction with GUS and GOL showed significant reductions in major inflammatory features of disease as early as WK4 which persisted through WK38 with GUS maintenance. Correlative analysis supports the role of GUS as the primary driver of tissue healing, with GOL further contributing to innate inflammatory activity, which demonstrate differential and complementary mechanisms of action of TNFα and IL-23p19 subunit blockade.Read more DOP55 High diagnostic accuracy of 4-probe methylation biomarkers in paediatric Inflammatory Bowel Disease by epigenome-wide analysisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The application of -omics technology offers important opportunities for biomarker discovery to personalise management of patients with inflammatory bowel disease (IBD). In previous work, we reported a characteristic profile of genome-wide DNA methylation in peripheral blood leucocytes from children with paediatric IBD (pIBD) at diagnosis defining the IBD methylome. This characteristic pattern of genome-wide alterations was replicated in inception cohorts of adult patients in UK and Scandinavia.

Methods

Whole blood DNA methylation profiling was performed using the Illumina EPIC array on 86 pIBD patients and 30 non-IBD controls. Patients had a median age of 12 y and were prospectively recruited from gastroenterology clinics in Oxford and Cambridge, UK. In modelling, we utilised the paediatric BISCUIT and PICTS study cohorts from Scotland as our training data. Publicly available data from the RISK paediatric CD cohort from North America was accessed (GSE11261) to further assess accuracy of the model. The model was then subjected to further testing in an Oxford-based paediatric coeliac cohort and adult cohorts with IBD, and rheumatoid arthritis (RA)(Table 1).

Results

Genome-wide methylation changes in the Oxford/Cambridge cohort were highly consistent with the index BISCUIT and PICTS cohorts. Four single methylation sites were selected to make up a diagnostic model involving the genes, RPS6KA2, VMP1, CF1 and ARHGEF3 (Figure 1) in the index cohort and validated in the Oxford/Cambridge cohort. Following receiver operating characteristic (ROC) area under the curve (AUC) analyses the model demonstrated an AUC of 0.912 (95% CI: 0.86-0.96) (Table 1). To further validate our model, we compared pIBD who were CRP-positive (>5 mg/l) and CRP-negative (<5 mg/l) at presentation against non-IBD children. In the CRP-positive group, we found an AUC of 0.99 (95% CI: 0.99-1). Within the CRP-negative group an AUC of 0.90 was observed against controls (95% CI: 0.83-0.96). The model was further validated using methylation data at the baseline timepoint in the RISK cohort, with an AUC of 0.93 (95% CI: 0.90-0.96). In further analyses, we demonstrated specificity for IBD compared with paediatric coeliac disease; and accuracy higher in childhood-onset AUC than adult-onset disease AUC; the model is not accurate in diagnosis of RA.

Conclusion

We confirm a characteristic pattern of DNA methylation changes in childhood-onset IBD; and derive and validate a 4-probe model for diagnosis with high accuracy in both Europe and North America. The model is specific for pIBD compared with symptomatic children with no demonstrable pathology; and children with coeliac disease; and may provide an alternative to current markers in blood and stool, including calprotectin.Read more P019 Development of hydrogel systems for targeted rectal delivery of intestinal cells to injured mucosa in inflammatory bowel diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Crohn’s Disease (CD) and Ulcerative Colitis (UC) are Inflammatory Bowel Diseases (IBD) affecting over 6.8 million people worldwide. CD and UC are chronic and progressive diseases, characterised by destructive inflammation of the intestinal tract. IBD management consists of drugs such as steroids, aminosalicylates, immunosuppressants, and biologics that aim to induce disease maintenance and remission. However, frequent, and systemic drug administration leads to limited local effects, severe side effects, and low patient compliance. Ultimately, about 20% of UC and up to 80% of CD patients require surgical colon removal. Thus, new approaches to locally restore the inflamed mucosa and initiate colonic wound repair are required.Human intestinal organoids (HIOs) are 3D cell aggregates derived from primary tissue or stem cells grown in vitro. They demonstrate a similar composition architecture to the primary intestinal tissue. Studies showed that HIOs can engraft into injured colonic mucosa resulting in wound repair. Thus, delivery of HIOs to damaged intestinal epithelium represents a promising therapeutic option in IBD treatment.The project aims to develop hydrogel systems with embedded HIOs and obtain human-relevant information on their efficacy in the restitution of injured colonic mucosa using an improved and human-relevant organ-on-a-chip technology.

Methods

A series of thermoresponsive hydrogels were fabricated (based on methylcellulose/hyaluronic acid polymers) and characterised. Following the embedment of HIOs into hydrogels, the morphology and viability of HIOs were determined using microscopy and MTT assays. Inflammation was induced through the administration of LPS to the basolateral side of the gut chip. Hydrogel/HIO systems were applied to the apical chip compartment via flow for 24 hours. Subsequently, hydrogel/HIO systems were removed from the chip, and HIO engraftment into injured mucosa was determined utilising permeability (4 kDa dextran) and cytokine release assays (ELISA IL-8).

Results

Our findings show that the gels were liquid at 25 °C and solidified at 37 °C and demonstrated low cytotoxicity. Additionally, our results suggest that the hydrogel systems had a restorative and possibly protective effect on the villi structures in the gut chip. Microscopy results clearly demonstrated the presence of fully differentiated villi structures in the chips that were treated with the hydrogel/cell systems (Figure 1B). These villi structures were absent in the not-treated chips (Figure 1A).

Conclusion

This study suggests that development of organoid-based hydrogels that can serve as a safe, effective, and inexpensive therapy (compared to surgery) and significantly improve the treatment of IBD.Read more P020 Effects of Anti-TNF Treatment on Browning of Mesenteric Adipose Tissue with Crohn's DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Crohn's disease (CD) is characterized by the expansion of mesenteric fat, known as creeping fat (CrF), to the inflamed segments of the intestine. Our group observed that CrF showed a conversion to beige tissue, a phenomenon known as "Browning", characterized by an elevated gene expression of thermogenin (UCP-1), the gene characteristic of browning¹. A recent study also showed that when browning was induced in mice in a TNBS colitis model, mesenteric hypertrophy improved and inflammation in adipose tissue was reduced². The aim of this study is to assess whether the administration of anti-TNF biologic treatment (infliximab) in patients with CD is related to the increase in adipose beige tissue in the CrF.

Methods

Immunohistochemistry staining of UCP-1 was conducted on CrF samples from CD patients receiving anti-TNF treatment (≥6 months) and anti-TNF-naïve patients. Additionally, we analysed the gene expression of beige adipose markers in CrF from CD patients treated with anti-TNF drugs, comparing them to those untreated. UCP-1 gene expression was also studied in adipose-stem cells isolated from CrF. Ongoing experiments involve treating adipose stem cells with infliximab (10ug/ml) for 24 hours to assess the potential conversion of white to beige adipose tissue.

Results

The study revealed a significant increase in UCP-1 staining in CrF samples among patients receiving anti-TNF treatment compared to anti-TNF-naïve CD patients (Fig 1.A). This trend was consistently observed in mesenteric CrF tissue. Beige markers TMEM26 and CPTB1 exhibited significant increases in anti-TNF-treated CrF, and other beige tissue markers showed a notable trend (Fig 1.B). Adipose stem cells displayed a significant increase in UCP-1 gene expression in anti-TNF-treated CrF compared to untreated patients (Fig 1.C). Exciting preliminary data suggest that infliximab treatment increases UCP-1 and the anti-inflammatory cytokine IL-4 gene expression in adipose-stem cells from active CD patients (Fig 1.D). This novel data implies a direct relationship between anti-TNF treatment and heightened browning in white adipose tissue of CD patients.

Conclusion

This study reveals a notable increase in UCP-1 gene expression in adipose tissue CrF of CD patients undergoing anti-TNF treatment. The findings suggest that anti-TNF therapy may trigger the transformation of white adipose tissue into the "beige" type, potentially mitigating inflammation. Browning CrF presents a promising therapeutic avenue for CD management, warranting further investigation.Ref:1. D. Monfort-Ferré et al. J Crohn Colitis., 2022;16(10):1571–83, 2. Zuo L et al. J Crohn Colitis. 2023 21;17(8):1179-1192.Read more P021 Higher TNFα and IL-6 mucosal levels in ulcerative colitis patients with more severe endoscopic activityWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterised by colonic mucosa inflammation. Its clinical course is marked by alternating periods of relapse and remission that impair patients' quality of life. In the last decades, novel therapies have shown to be effective for UC resulting in lower rates of colectomy. However, there is still a significant proportion of non-responding patients that change from one treatment to another, being exposed to its potential adverse events. Thus, predictive factors of response to available drugs are needed to tailor the best treatment strategy for each patient. The aim of our study was to measure TNFα and IL-6 levels in colonic biopsies from patients with UC with moderate to severe endoscopic activity.

Methods

A prospective, observational single-centre study was designed and it is currently on going. Adult UC patients with moderate to severe endoscopic activity (Mayo Endoscopic Score (MES) > 1) in a routine colonoscopy were included. Biopsies from inflamed (MES>1) and non-inflamed (MES=0) colon of each patient were homogenised and processed by using RIPA buffer and ultrasounds to obtain cell lysates. Human Luminex Discovery Assay (2 plex) was used for the simultaneous detection and quantitation of IL-6 and TNFα. Data are shown as percentage, median, interquartile range (IQR) and mean ± standard deviation (SD) as appropriate.

Results

So far, 21 patients were consecutively included (mean age 53.8 years (SD 17.0), 52.4% female). About 43% of patients had left-sided UC, 28.5% extensive UC and 28.5% proctitis. Regarding endoscopic activity, 61.9% of patients showed MES=2 and 38.1% were MES=3. Fourteen patients (66.6%) were bio-naïve and 7 (33.3%) had been exposed to anti-TNFα. IL-6 was detected in biopsies from colon with MES ≥ 2 of 18 (85.7%) patients, of which 10 (55.6%) patients also TNFα was found. Neither IL-6 nor TNFα were detected in biopsies from non-inflamed colon (p=0.00). Median IL-6 in inflamed colonic samples from patients with MES-2 was 25.6pg/ml (IQR 0.2-74.3) and 92.2pg/ml (IQR 16.9-314.3) in those with MES-3 (p=0.09). Median TNFα in inflamed colonic biopsies from patients with MES-2 was 0.0pg/ml (IQR 0.0-20.0) and 22.2pg/ml (IQR 0.0-34.3) in patients with MES-3 (p=0.12) (Figure 1). No differences were found in TNFα levels between anti-TNFα naïve patients and those patients previously exposed to anti-TNFα (p=0.96).

Conclusion

IL-6 and TNFα are elevated in inflamed colonic mucosa, particularly in those patients with more severe endoscopic activity, while they are not found in non-inflamed colonic mucosa. The correlation between cytokine levels and endoscopic severity suggests their potential as biomarkers for treatment response.Read more P022 Development of a novel experimental model for studying creeping fat in Crohn's DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

A characteristic feature of Crohn's disease (CD) is the transformation of mesenteric adipose tissue into creeping fat (CrF), which becomes inflamed and surrounds the transmural lesion. The occurrence of this condition has been associated with the severity of inflammation and post-surgical recurrence. In this study, we present a promising model of CD induced by 2,4,6-trinitro-benzene sulfonic acid (TNBS) that exhibits experimental CrF. This model provides an innovative tool for the development of surgical techniques as well as the implementation of new therapeutic strategies, as it more accurately depicts the nature of the pathology.

Methods

Acute colitis was induced by intrarectal instillation of TNBS under conventional conditions. Five days after the administration, acute colitis developed (Fig. A). The variation in the percentage of weight compared to the initial weight was analyzed. Clinical activity was assessed through colonoscopy on the third and fifth days based on parameters such as hyperemia, the extension of ulcers, and presence of stenosis. Further, the weight-to-length ratio of the colon, as well as the area of the lesions, was also collected. All obtained data were analyzed in order to identify any possible differences between the sexes or between the groups that presented CrF or not.

Results

The frequency of CrF occurrence was approximately 50% in both sexes. Even though, females had smaller volume of CrF and a greater presence of fistulas. As compared to controls, the weight of the animals with CrF decreased (Fig. B) and their clinical activity index increased (Fig. C). Moreover, the area of the lesion was significantly increased in the group with CrF as compared with the group without CrF (Fig. D). The CrF group also demonstrated a significant increase in the weight-to-length ratio of the colon. There were no significant differences between the sexes in the aspects mentioned above.

Conclusion

The group presenting CrF showed a significant increase in all parameters of disease severity analyzed. We would like to emphasize that animals exhibiting severe symptoms by the fifth day were precisely those that manifested the development of CrF. Importantly, it is noteworthy that monitoring the disease through colonoscopy avoids the necessity for the sacrifice of animals, thereby facilitating a reduction in sample size.Read more P088 Single-cell transcriptomic analysis identifies early immune disturbances in preclinical Crohn's diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Despite the increasing incidence of Crohn’s disease (CD), its early immune disturbances have not been described yet. The preclinical period provides an opportunity to gain insight into the initial processes involved in the pathogenesis of the disease. The main aim of our study was to describe how the subclinical inflammatory process is modifying the individual’s immunologic environment while the patient is still on preclinical period.

Methods

We analysed scRNASeq data from peripheral blood mononuclear cells (PBMC) of patients with incidentally-diagnosed CD according to ECCO criteria during the colorectal cancer screening programme, after histologic confirmation. Their gene expression profile was compared to healthy individuals acquired from publicly available datasets. The analytical pipeline included merging of the datasets followed by batch correction concerning integration from different studies, quality control and filtering, and finally cell-type annotation and differential gene expression analysis.

Results

Two patients with CD (mean age 53,5 years) and 2 healthy controls were included. We observed distinct transcriptomic profile in preclinical patients compared to controls, with small intragroup differences. The cell-type annotation identified B cells (B), CD4+ and CD8+ T-cells (CD4T, CD8T), dendritic cells (DC), monocytes (Mono) and natural killer cells (NK). The analytical pipeline included 17,021 cells (B:3,274, CD4T:5,798, CD8T:3,476, DC:315, 2, Mono:928, NK:3,230) and 3000 quantified genes. Considering each cell type individually, we identified 49 differentially expressed genes (DEG) between CD patients and controls (B:39, CD4T:37, CD8T:41, DC:42, Mono:37, NK:37), from which 30 were DEGs in all cell types.Building on the list of 49 detected DEGs, we report three insights into the preclinical period of the disease. First, pathway analysis revealed significant enrichment of the pathway that is related to immunoregulatory interactions between lymphoid and non-lymphoid cells, and functional annotation analysis identified gene products that are related to immunological defense. Second, we identified significant transcriptomic alterations in genes that have previously been related to the symptomatic phase of IBD, or reported as potential biomarkers. Third, after performing principal component analysis we observed greater separation between the patients groups in the CD8T cells compared to the other cell-types.

Conclusion

This study reveals the initial transcriptomic profiles and the main pathways that precede the onset of symptomatic inflammatory bowel disease. Our findings may help in identifying potential targets for early disease intervention.Read more P089 Development and preliminary evaluation of a suicidal risk assessment protocol in a research trial using the Patient Health Questionnaire (PHQ-9)Wed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

People with Inflammatory Bowel Disease (IBD) have an increased risk of depression and self-harm. Participants in IBD research trials often disclose severe depression symptoms, including thoughts of self-harm and suicidal ideation, in validated self-administered questionnaires such as the Patient Health Questionnaire-9 (PHQ-9). However, there is no standard protocol for responding to such disclosure in research trials and the opportunity to support people at risk is potentially missed. We developed and evaluated a risk assessment protocol for the IBD-BOOST randomised controlled trial (ISRCTN71618461).

Methods

Participants completed the PHQ-9 scale at baseline, six-month and 12-month follow-up. Responding to item 9: ‘Thoughts that you would be better off dead or of hurting yourself in some way’, if a participant indicated ‘More than half the days’ or ‘Nearly every day’, the trial database automatically alerted the research team to risk assess the participant. Trial risk assessors, trained in the protocol, contacted participants by telephone, completed the risk assessment protocol (Figure 1) and signposted participants to appropriate professional services. Risk assessments were completed at the first occurrence of a PHQ-9 item 9 response. Risk assessments were reviewed by the Chief Investigator and summarised to trial governing committees.

Results

780 participants were randomised. Overall, there were 58 PHQ-9 risk alerts during the trial (baseline, six- or 12-month follow-up), 41 of which were new alerts and required risk assessment. One participant declined assessment so 40 risk assessments were completed. 24 participants were assessed as low-risk and 16 participants as medium-risk, with 12 declaring previous suicide attempts. No participants were rated as high-risk. The mean time for the risk assessment phone call was 14 minutes (range 5-36 minutes) and total time spent on calls was approximately nine hours. Trial participants who received a risk assessment expressed appreciation for being contacted and all except two wished to receive information about professional support services. In a focus group, trial risk assessors reported positive experiences of conducting the risk assessment with suggestions for improvement, which resulted in minor modifications to the protocol.

Conclusion

Our evaluation demonstrated that it was viable for a research trial team to successfully conduct a risk-assessment protocol for trial participants reporting thoughts of self-harm, with training and support from senior colleagues. Resources are required for training and delivery, but it is not unduly onerous. Trial participants appeared to find completing the assessment acceptable. The revised protocol will be made available for researchers to use.Read more P090 Prevotella copri promotes colitis in mice by reducing expression of ATF4 and disturbing the gut microbiotaWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Colitis is a disease that carries a significant global disease burden, with a growing prevalence. Studies in humans and mice have explored the role of the intestinal microbiota that contribute to inflammatory bowel disease (IBD). Prevotella copri is a common human gut microbe that has been linked to inflammatory disorders.

Methods

C57BL/6 mice were divided into four groups: normal control group, P. copri group, DSS model group, DSS model+ P. copri group. Mice were gavaged with P. copri or PBS for 14 consecutive days, starting from the first day. Experimental colitis was induced by 2% DSS treatment from day 8. Mouse colon tissues were analyzed by quantitative real-time polymerase chain reaction, immunoblots, immunohistochemistry, and transcriptome. Serum and intestinal epithelial cell (IEC) amino acids were measured by high-performance liquid chromatography-tandem mass spectrometry. The analysis of the microbiome was done through the 16S ribosomal DNA sequencing.

Results

In the present study, our experiment confirmed that P. copri was significantly associated with the exacerbation of DSS-induced colitis by reducing expression of ATF4 and altering the gut microbiota composition. Leucine concentration of serum and IEC were increased in P. copri-gavaged mice, which clearly suppresses ATF4 expression. The dysbiosis of the intestinal microbiota and impaired α-defensin production by Paneth cells are also the leading causes of why P. copri-gavaged mice are more susceptible to DSS-induced colitis.

Conclusion

Taken together, the results proposed that P. copri aggravated the severity of colitis in the mice with DSS-induced colitis. This was done by reducing the expression of ATF4 and disturbing the gut microbiota. Thus, targeting P. copri may be an effective strategy in the treatment of IBD.Read more P091 Single-cell metabolic phenotyping of monocytes and macrophages in Crohn’s diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Crohn’s disease (CD) is a chronic inflammatory disease, which can affect any part of the gastrointestinal tract. It is characterized by alterations in the innate and adaptive immune systems. Changes in both monocyte and macrophage (MΦ) populations have been reported in CD patients. However, the precise contribution of these cells to disease pathogenesis and progression remains unclear. Our hypothesis is that in CD, the local environment affects the metabolism of monocytes and MΦ. Furthermore, we believe that the cell’s metabolism is essential for the phenotypic and functional identity of these cells. The aim of this study is to analyze and compare the metabolic signatures of peripheral blood monocyte subsets and tissue MΦ in CD patients with ileitis (iCD), deep remission (rCD) and healthy controls (HC).

Methods

A total of 28 adults from the IBDome⁵ cohort were analyzed, consisting of 10 individuals with iCD, 8 with rCD and 10 HC. Suspension mass cytometry was utilized to analyze peripheral blood mononuclear cells (PBMCs) using a 34-marker panel targeting key proteins and rate-limiting enzymes across multiple metabolic pathways. In addition, we conducted further analysis on intestinal tissue obtained during ileocolonoscopy using imaging mass cytometry. This allowed for the application of a similar marker panel to compare the metabolic states of tissue-resident MΦ (ongoing analysis) with the identified signatures found in peripheral blood.

Results

Peripheral blood samples of CD patients and HC were analyzed. FlowSOM clustering of CD45⁺ events discriminated 11 major clusters of PBMCs. Reclustering based on CD14 and CD16 allowed the identification of 4 monocyte clusters, including classical monocytes. Classical monocytes exhibited unique metabolic signatures that distinguished them from other monocyte populations. Ongoing investigations targeting metabolic signatures in the monocyte-MΦ compartment will determine whether disease states differ significantly between the single disease entities.

Conclusion

Single-cell phenotyping using suspension and imaging mass cytometry can assess metabolic states of the monocyte-MΦ compartment in CD and HC. Such insights may provide novel markers for monitoring disease activity and reveal potential therapeutic targets.Read more P146 Latent activation of the extrinsic coagulation pathway in patients with ulcerative colitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Ulcerative colitis (UC) is associated with an increased risk of venous thromboembolism. We investigated the correlation of UC severity with latent activation of the extrinsic coagulation pathway and colonic stromal tissue factor (TF) expression.

Methods

Plasma exosomes, microparticles (EM), TF protein, activities of EM-bound TF (EM-TF) and FVIIa, as well as TF mRNA (F3) in primary colonic stromal cells in culture were measured.Disease extent by Montreal classification, medications, UC clinical activity by partial Mayo score (PMS), endoscopic severity by the MS endoscopic component (eMS; loss of response defines as ≥2), quality of life by the short IBD questionnaire- SIBDQ, complete blood count, CRP, ESR and albumin were retrieved. Statistical significance (p) was assessed with the following tests: Student’s t for 2 groups with normally distributed values, Mann-Whitney U if not, Wilcoxon test for paired data. Correlation of continuous against scale variables was assessed with Pearson’s or Spearman’s r and corresponding p values for linear or logarithmic continuous variables, respectively.

Results

Plasma was obtained from 38 UC patients (31 males, disease duration 151±25 months, 14 with extensive colitis, 5 current smokers) and 28 healthy blood donors (HBD; 20 males) who served as controls. TF mRNA (F3) was measured in primary colonic stromal cells in culture from 12 UC patients (11 males, disease duration 169±53 months, 8 with extensive colitis, 1 current smoker) and from 7 controls undergoing screening colonoscopy.UC patients had 4- and 3.7- times more exosomes and microparticles than controls, respectively (A). TF protein correlated with PMS (r 0.443), albumin (-0.362), ESR (0.353), PLT (0.575) and endoscopic UC severity (0.468; B). EM-TF activity was 1.6-times higher (C) and correlated to disease extent (E3: 1.9 x E2), albumin (-0.624), endoscopic severity (0.422; D) and SIBDQ (-0.64). Downstream, FVIIa activity was 2.2-times higher. Refractory-to-treatment patients had 5.8-, 1.5-, 2.1- times higher TF protein (E), MP-TF, FVIIa activity, respectively. Within responders, the need for steroids or biologics correlated with 2.2-times higher MP-TF activity. Colonic stromal cells from patients with UC maintained a 2.2-times higher F3 (F), which correlated to PMS (0.56), albumin (Spearman’s r -0.543), endoscopic severity (M3: 8.3 x M2). All the aforementioned were statistically significant with a < 0.05.

Conclusion

The extent of spontaneous activation of the extrinsic coagulation pathway is associated with clinical and endoscopic UC activity and response to treatment. TF in colonic stromal cells mirrors its systemic activity and indicates the possible contribution of such cells to increased TF plasma bioactivity.Read more P147 IBD relevant pathways are upregulated in Paneth cells in a murine model of dietary induced intestinal inflammationWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Dietary constituents are believed to play a role in the development of Crohn’s disease (CD) (1). Recently we were able to demonstrate, that polyunsaturated fatty acids (PUFA), induce a CD like enteritis phenotype in genetically susceptible mice (2,3). Furthermore, we could show, that PUFA intake correlated negatively with disease course in CD patients (3). In this project we tried to untangle the role of Paneth cells (PC) in the development of PUFA induced enteritis.

Methods

scRNA sequencing was performed on cells isolated from mice lacking one allele of Gpx4 (GPX4^+/-IEC) in their intestinal epithelial cells (IEC) after feeding them a PUFA enriched western style diet (PUFA-WD). Furthermore, mice lacking both alleles of Gpx4 in their PC (GPX4^ΔPC) where fed a PUFA-WD for four weeks and enteritis was assessed based on a histological enteritis score and immunhistochemical stainings.

Results

scRNAseq of murine intestinal cells revealed an upregulation of IBD relevant pathways (such as JAK or TNFα) in Gpx4 deficient IECs and PC. GPX4^ΔPC mice developed a CD like enteritis phenotype, characterized by a mucosal and submucosal infiltration of neutrophils, macrophages and other leucocytes, after only four weeks of PUFA enriched diet, indicating that GPX4 dependent intestinal inflammation is controlled by PC.

Conclusion

The upregulation of IBD relevant pathways in our model of dietary induced intestinal inflammation renders this model a valuable tool to investigate mechanistical understanding in the role of dietary components in IBD. Our results further link PC metabolism to the development of intestinal inflammation.

References

1. Adolph TE, Meyer M, et al Nat Rev Gastroenterol Hepatol 20222. Mayr L, Grabherr F, et al Nat Com 20203. Schwaerzler J, Mayr L, et al Gastroenterology 2022Read more P148 Longitudinal single-cell data informs deterministic modelling of inflammatory bowel diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Crucial contributions to our understanding of the inflammatory process in inflammatory bowel disease (IBD) have been made using single cell level approaches. Extracting mechanistic details of cell and gene dynamics would be critical to understanding the mechanisms mediating mucosal healing and predicting response to specific therapies. However, this remains challenging. Therefore, our aim was to use ordinary differential equations (ODEs) for mathematical modelling of cell abundance and prediction of biological processes in IBD.

Methods

We used mathematical modelling of published longitudinal single-cell mRNA sequencing (scRNA-seq) data from DSS colitis in mice to simulate cellular dynamics during IBD. We validated our predictions using pseudo-bulk gene expression analysis and flow cytometry. We also analysed a published microarray dataset from colonic biopsies of 51 IBD patients prior to infliximab treatment.

Results

Based on the scRNA-seq data, we used our mathematical model to predict the immune dynamics of a different mouse colitis protocol. We validated these predictions experimentally using flow cytometry and found good agreement between model simulation and experimental data (predicted vs. observed, Pearson's rho=0.92). We found that the estimated turnover rates predicted the protein level of the proliferation marker KI-67 (rho=0.88) in DSS colitis. Finally, we wanted to investigate whether our mathematical model reflected processes in human IBD. We reasoned that genes correlated with epithelial cell dynamics might be indicative of mucosal healing after DSS retrieval. We found more highly correlated genes when using simulated epithelial abundance compared to experimentally measured epithelial abundance. Many genes associated with tight junctions (Cldn8, Cftr, Crb3, Jam2) were among the highly positively correlated genes and genes associated with inflammation (Il1b, Jak2, Il10ra) were among the negatively correlated genes with epithelial cell abundance. We then looked for differentially expressed (DE) genes in pre-treatment colon biopsies between responders and non-responders to infliximab. We found a significant overlap of 25 positively correlated genes with upregulated DE genes in responders, i.e. associated with tight junctions, and 73 negatively correlated genes with upregulated genes in non-responders, i.e. associated with inflammatory pathways.

Conclusion

We demonstrate that mathematical modelling of colonic cell dynamics provides insight into IBD progression and treatment response. Furthermore, our results suggest that pre-treatment barrier integrity may predict and influence response to infliximab treatment.Read more P149 Bacteroides uniformis ameliorates pro-inflammatory diet-exacerbated colitis by targeting endoplasmic reticulum stress-mediated ferroptosisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Pro-inflammatory diet is positively associated with the risk and progression of inflammatory bowel diseases. Recently, ferroptosis was observed in patients with dietary pattern-associated colitis. However, the mechanisms underlying the effects of a pro-inflammatory diet and whether it mediates ferroptosis are unknown. This study aimed to clarify the mechanisms of pro-inflammatory diet in colitis.

Methods

Mice were fed a dietary inflammatory index-based pro-inflammatory diet for 12 weeks. Subsequently, colitis was chemically induced using 2.5% dextran sulfate sodium with or without a ferroptosis inhibitor (ferrostatin-1). Body weight, histological scores, immune response, and mucosal barrier function were evaluated to assess intestinal inflammation.Colon tissue transcriptomics, fecal microbiome, and serum metabolomics were applied to identify diet-microbe-host interactions. Dietary inflammatory index of 36 patients with Crohn’s disease were evaluated. Their intestinal specimens were also collected. The biological functions of Bacteroides uniformis were observed in vitro and in vivo.

Results

Pro-inflammatory diet induced low-grade intestinal inflammation and exacerbated colitis by activating glutathione peroxidase 4-associated ferroptosis in the endoplasmic reticulum stress-mediated pathway; ferrostatin-1 treatment reversed this pro-inflammatory potential. Additionally, the pro-inflammatory diet triggered colitis by modulating the gut microbiota and metabolites. Notably, supplementation with B. uniformis improved the pro-inflammatory diet-aggravated colitis by inhibiting endoplasmic reticulum stress-mediated ferroptosis. Co-culturing B. uniformis with intestinal epithelial cells revealed it is non-enterotoxigenic and non-enteroinvasive.

Conclusion

Pro-inflammatory diet drives colitis by targeting endoplasmic reticulum stress-mediated ferroptosis, possibly in a gut microbiota-dependent manner. Pro-inflammatory diet restriction and microbial-based therapies may be effective strategies for preventing and treating inflammatory bowel disease.Read more P150 Ulcerative Colitis Patients’ Luminal Zinc Induces Clostridioides difficile Virulence and Exacerbates Inflammatory ResponsesWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The refractory acute severe UC patients are often complicated by C. difficile infection (CDI), resulting in higher surgery and mortality rates. However, few studies have observed C. difficile’s pathogenicity in real UC patients’ gastrointestinal microenvironments, and the actual role of C. difficile in UC development remains unknown. We found zinc concentrations among UC patients’ feces were significantly higher than those among Crohn’s disease patients and healthy subjects. Additionally, we previously reported that excessive zinc would promote the growth and virulence of C. difficile. Therefore, we hypothesized that the increased UC patients’ luminal zinc may up-regulate C. difficile virulence and promote intestinal inflammatory responses, leading to an exacerbated UC progression.

Methods

UC patients’ stool samples (n=40) were collected and analyzed by qPCR and ICP-MS to determine the presence of C. difficile and the fecal zinc concentrations. C. difficile was cultured in BHIs with or without zinc (ZnSO₄) in an anaerobic chamber. Expression of virulence genes was analyzed using RT-qPCR, transcriptome sequencing, and western blot. Human colonic organoids and Caco-2 cells were co-cultured with C. difficile or zinc-treated C. difficile, and cytotoxicity, permeability, and inflammatory cytokine release were assessed. TLR5 knock-out Caco-2 cells were constructed using sgRNA-guided Cas9 nuclease and co-cultured with C. difficile or zinc-treated C. difficile to verify whether zinc-induced C. difficile’s pathogenicity was mainly through flagellar formation.

Results

C. difficile was detected in ~35% of UC patients’ fecal samples. Luminal zinc concentrations (~915μM, p<0.01) were significantly higher among UC patients than CD patients or healthy subjects. The UC patients’ luminal concentration of zinc promoted C. difficile growth, suppressed its exotoxins release, and induced higher expression of its flagella-related genes, resulting in higher cytotoxicity and inflammatory responses in human colonic organoids and Caco-2 cells. However, zinc-treated C. difficile did not induce higher inflammation and pathogenicity in TLR5 knock-out Caco-2 cells.

Conclusion

The association between C. difficile and UC aggravation may partially stem from UC patients’ excess luminal zinc promoting C. difficile flagellin expression, inducing inflammatory responses, and worsening UC progression.Read more P151 Characterization of platelet activation profile in Inflammatory Bowel DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Platelet-related markers associated with a procoagulant state have been described for Immune-mediated Inflammatory Diseases (IMIDs), but a broader profiling of these abnormalities in Inflammatory Bowel Disease (IBD) is lacking.

Methods

Cross-sectional study to describe and compare platelet biomarkers of IBD outpatients, both Crohn’s Disease (CD) and Ulcerative Colitis (UC), vs healthy controls (HC).Patients over 18 years old with a diagnosis of CD or UC according to the European Crohn’s and Colitis Organization (ECCO) criteria were included. Fecal calproctectin (Fcal) >=150ug/g was used as a cutoff level for active disease. Exclusion criteria for IBD patients are listed under Table 1.Fibrinogen (FBG) receptor on platelet’s surface was determined with anti-CD41 and anti-CD61 monoclonal antibodies (mAbs); and von Willebrand factor receptor with anti-CD42a and anti-CD42b mAbs.Platelet activation markers [TRAP and ADP-induced activation of fibrinogen (FBG) receptor, and P-selectin (Psel) and CD63 exposure] were determined, respectively, through binding of PAC1, anti-P-selectin and anti-CD63 (mAbs).All variables were determined by flow cytometry.

Results

55 patients (27 CD, 28 UC) and 75 HC have been included. 43 IBD patients had active disease (21 CD, 22 UC). Complete baseline characteristics of the IBD population are described in Table 1.Basal Psel (% of positive cells) was increased in CD vs UC (median [IQR]: 5.64 [4,4-10,4] vs 2,9 [1,8-6,8], p=0,02) and vs HC (3,5 [1,4-6,8], p=0,008). ADP-induced Psel was increased in CD vs HC (mean, SD: 49.92, SD 12.75 vs 41.943, SD13.15, p=0,007). Basal CD63 (% of positive cells) was significantly higher in active IBD vs HC (W = 1143, p = 0.02) and inactive IBD vs HC (W = 528, p= 0.006). CD42a (% of positive cells) was decreased in IBD vs HC (W = 1128.00, p=0.007) and CD vs HC (W = 777.00, p =0.04). CD42b (% of positive cells) was also decreased in IBD vs HC (mean, SD: 106.9 SD, 17.32 vs 115.7, SD 28.42, p=0,01) and CD vs HC (104.06 SD 14.49, p=0,03). No differences in basal or TRAP/ADP induced PAC binding, and in CD41 or CD61 expression were observed among groups. Multiple linear regression showed association of Fcal with basal Psel in IBD patients (p=0,02); and Spearman’s correlation showed negative moderate correlation between Fcal and basal Psel (r=0,3; p=0,003)

Conclusion

Features of platelets in IBD suggest increased platelet degranulation and reduced vWF receptor with regards to healthy controls, specially in CD, but no differences in FBG-related receptors. Inverse moderate correlation between Fcal and Psel in IBD patients suggests depletion of intra-platelet granules at higher levels of gut inflammation.Read more P152 Longitudinal immune profiling of peripheral blood in patients with Ulcerative ColitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Recent literature has established the communication and mutual influence between the gut and the brain, referred to as the gut-brain axis. While inflammatory bowel disease (IBD) poses a risk for neuroinflammation and brain dysfunction, the molecular mechanisms are not fully understood. This study aims to investigate longitudinal changes during Ulcerative Colitis (UC), focusing first on the characterization of peripheral immune cell subsets, circulating cytokines, and extracellular vesicles (EVs).

Methods

In our study, we examined 19 UC patients in both active (mean age in years: 45,63) and remission phases (mean age in years: 46,16). A gastroenterologist at the Gastroenterology Department from the Otto-von-Guericke University in Magdeburg, Germany assessed all participants, categorizing them into stages using Mayo scoring and calprotectin levels. We analysed peripheral whole blood and plasma samples using different flow cytometry-based approaches.

Results

Our findings indicate an upregulation of the neutrophil (CD16⁺, CD15⁺) numbers during the active stage followed by a significant reduction during remission, indicating an increase in innate inflammation as a first line of defence and a balanced state during remission. Classical (CD14⁺, CD16^-) monocytes were decreased, along with similar results in the intermediate (CD14⁺, CD16⁺) subset. Nonclassical monocytes (CD14⁺, CD16⁺⁺) increased from the active to the remission stage. Surface expression of activation marker CCR2 was downregulated for all monocyte subsets, whereas CX3CR1 was upregulated specifically in intermediate monocytes during remission. Compared to the active stage peripheral dendritic cell (CD14^-, CD16^-) numbers increase during remission suggesting less colonic infiltration. Peripheral regulatory T cells (Tregs) (CD127 ^low/-, CD25⁺), which are important for the reestablishment of homeostasis are upregulated during remission. Characterization of cytokine levels in plasma revealed an upregulation of the proinflammatory milieu during the active stage, especially with elevated IL-18 and TGF- β1 levels. Finally, those changes were accompanied by alterations of the surface markers expressed by isolated circulating EVs.

Conclusion

Our initial results indicate the feasibility of evaluating the gut-brain axis through liquid biopsy. We unravel the composition of the peripheral inflammatory milieu during the active phase. Currently we are focusing on the assessment of the CNS-derived metabolites and their bidirectional communication with the gastrointestinal system.Read more P153 Artificial Intelligence to predict interleukin-23 signalling activity from H&E stained whole slide images of Inflammatory Bowel DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Interleukin23 (IL-23) is a cytokine that plays a crucial role in the pathogenesis of inflammatory bowel disease (IBD), making it a highly validated therapeutic target. Understanding the role of IL-23 in IBD at the histopathological level is crucial for determining effective treatment strategies, providing insights into IBD patients who fail to respond to targeted therapies, or predicting those who are likely to lose response. In this context, there is a surge in utilizing artificial intelligence (AI) for histopathological data in IBD and other disease indications. Here, we present an automated computer vision approach to predict IL-23 signalling activity directly from routinely stained Hematoxylin and Eosin (H&E) images

Methods

A total of 1502 samples with matched clinical data and H&E biopsy images were included from 991 Crohn’s disease (CD) and 511 ulcerative colitis (UC) samples. IL-23 signalling activity was calculated using gene set variation analysis on RNA-seq data collected from the same tissue biopsies. The data were obtained from the IBD Plexus program of the Crohn’s & Colitis Foundation. The proposed approach is based on vision transformers (ViTs) which is a type of deep learning model. ViTs divide the input image into fixed-size patches, transform it into linear embedding, and analyze it with the self-attention mechanism. This enables ViTs to incorporate relationships between different patches of the input image to identify regions predictive of IL-23. Our approach was trained in a weakly supervised manner to automatically identify tissue regions that correlate with IL-23 signaling activity. The model produces interpretable heatmaps to interrogate model predictions and allow clinicians to visualize and interpret the significance of different tissue regions predictive of IL-23

Results

We performed 5-fold cross-validation on the splits obtained at the patient level, retaining the data distribution of IL-23 signaling activity, biopsy location, and diagnosis. We separately validated the performance of the proposed model on both disease categories, including CD and UC. The proposed approach achieved an area under the curve (AUC) of 0.82 ± 0.04 on unseen data from CD and an AUC of 0.80 ± 0.02 for UC. The 5-fold results for both disease categories are shown below

Conclusion

The presented results highlight the significance of computational pathology algorithms to identify IL-23 signalling activity from H&E images. Pathological interpretation from the heatmaps may help understand disease pathomechanism and optimize the treatment options for IBD patients by timely identification of IL-23 status. We are further validating the clinical utility of such heatmaps and expanding the use of H&E to predict other patient-centric endpointsRead more P271 Impact of Biologics on Surgical Trends in Inflammatory Bowel Disease: Insights from a Lower-endemic RegionWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Biologics have revolutionized inflammatory bowel disease (IBD) treatment, yet their impact on surgery rates remains variable in real-world studies. This nationwide cohort study in Taiwan aims to investigate the influence of biologics on surgery trends and identify associated risk factors in a region with lower IBD endemicity.

Methods

A retrospective population-based cohort study was conducted using data from Taiwan's National Health Insurance Database, spanning from January 1, 2003, to December 31, 2018. The cohort included 2676 eligible IBD patients, 725 Crohn's Disease (CD) and 1951 ulcerative Colitis (UC). Patient characteristics, surgery outcomes, and the related risk factors were analyzed.

Results

During the study period, 292 CD and 186 UC patients underwent surgery, with 245 in the pre-biologic era and 233 in the post-biologic era. Cumulative probabilities of intestinal surgery (IS) for CD patients were 20%, 35%, and 44% at 1^st, 5^th, and 10^th years, while anal surgery (AS) rates were 3%, 5%, and 7%, respectively (Figure 1). UC patients exhibited lower surgery rates. Cox model analysis revealed age at diagnosis > 60 years as a significant risk factor for IS, but not AS, in both CD and UC groups. Gender and biologics era showed no association (Table 1). After the first IS, CD and UC patients had high 2^nd IS rates of 31% and 24%, respectively.

Conclusion

This nationwide study in a lower endemic area provides insights into IBD surgery trends. The first 7 years of the biologics era did not alter surgery rates, but age at diagnosis > 60 years was associated with a higher IS rate. After the initial operation, IBD patients demonstrated a higher rate of subsequent surgeries.Read more DOP72 Pregnancy for IBD-patients with an enterostomy is feasible but is associated with complicationsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

As inflammatory bowel disease (IBD) is frequently diagnosed in young adults, the disease often coincides with pregnancy. There are several indications for enterostomies in the treatment of IBD. Literature on enterostomy complications during pregnancy and pregnancy-outcomes remains scarce. Gaining insight in the incidence of complications and the course of these pregnancies serves as a first step in developing guidelines for the difficult question of how, when and by whom complications during pregnancy should be monitored and treated. The aim of this study was to assess enterostomy related complications and pregnancy-outcomes in female IBD patient with an enterostomy during pregnancy.

Methods

For this multicenter cohort and survey study, all patients who have been pregnant while having an enterostomy and who gave birth between 2016 and 2023 in three Dutch university medical centers were included. Complications of the enterostomy and pregnancy-outcomes were collected retrospectively from electronic patient files. In collaboration with gastroenterologists, surgeons, gynaecologists and IBD-patients, a survey was designed. Through this digital questionnaire, all participants were asked about their experience during pregnancy and any long-term enterostomy related complaints.

Results

Data was collected on 37 patients (mean age at conception 32.6 years; 64.9% Crohn’s disease (CD), 32.4% ulcerative colitis (UC), 2.7% IBD undetermined (IBD-U)), comprising 48 pregnancies of which four ended in a miscarriage. Enterostomy related complications occurred in thirty of the full-term pregnancies (68.2%), with decreased stoma-output (43.2%), small-bowel obstruction (29.6%) and leakage (25%) being the most prevalent. In a quarter of the pregnancies, surgical revision of the stoma was needed due to obstruction (27.3%), prolapse (27.3) and peristomal herniation (45.6%). A full overview of documented complications can be found in table 1. Of the fourteen women who completed the questionnaire, six reported non-resolved complications at least six months after delivery (42.9%). Eighteen pregnancies ended in a caesarean section (40.9%). There were 45 infants (one gemelli pregnancy), of whom eight (17.8 %) were born prematurely,eight (17.8 %) had low birth weight (17.8%) and eight (17.8 %) were small for their gestational age.

Conclusion

Being pregnant and giving birth with an enterostomy is feasible, but is in two third of pregnancies associated with complications. A reduced stoma output and leakage can be prevented by early counseling. Proper guidance before, during pregnancy and postpartum is therefore crucial for IBD-patients with an enterostomy.Read more DOP73 Early biological use in a Belgian, prospective inception cohort of patients with Inflammatory Bowel Disease: the PANTHER cohortWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The growing number of advanced therapies has revolutionized the management of inflammatory bowel disease (IBD). Although early use of biological therapies is associated with better long-term outcomes, no data exist for the Belgian population. To this end, we evaluated treatment patterns in biological use and persistence in a Belgian inception cohort.

Methods

The PANTHER (Prognostic biobANk of paTients witH Early cRohn’s or colitis) cohort consists of adult IBD patients recruited in 3 Belgian IBD referral centres. Patients are included within 3 months after diagnosis and are naïve for immunosuppressives and biologicals, and without previous IBD-related surgery. Treatment use and outcomes are prospectively collected, and time trends for biological use were analysed using log-rank tests and Cox regression (R 4.3.2).

Results

Between 2015 and 2023, a total of 473 newly-diagnosed IBD patients were recruited (270 Crohn’s disease (CD) [57%]; 199 ulcerative colitis (UC) [42%]; 4 [1%] IBD type unclassified) (Table 1). During a median (IQR) follow-up of 2.6 (1.3-4.3) years, 64 patients (14%) required surgery (n=10 colectomy; n=54 ileocecal/small bowel resection); and 250 patients (53%) received biological therapy within the 1st year after diagnosis. Most patients were treated with anti-TNF (CD 67%; UC 55%) as first-line biological, followed by anti-integrins (CD 24%; UC 43%) and anti-IL12/23 (CD 9%; UC 2%). Time series analysis showed a significant increase in biological use within the 1st year after diagnosis when comparing patients diagnosed between 2015-2017 (44%) to those between 2018-2020 (57%), and to 2021-2023 (66%) (p=0.03) (Fig. 1A). Factors associated to this early biological use were younger age (HR=0.99 [95%CI: 0.98-0.99]), a diagnosis of CD (HR=2.2 [95%CI: 1.6-2.8]); and perianal disease in CD (HR=2.8 [95%CI: 1.8-12.8]). Within this early biological exposure group, 26 patients (10%) needed a resection later on. Therapy persistence over time was higher with early exposure rates in patients diagnosed in 2021-2023 (82%) and 2018-2021 (71%), as compared to 2015-2017 (63%) (p=0.08) (Fig.1B). The mode-of-action of first-line biological did not show any association with persistence (HR=1.0 [95%CI: 0.4-3.0]). Overall, only 26% of patients had to switch to a second-line, with a switch [anti-TNF >anti-IL12/23] being the most frequent in CD (50%); and from [anti-TNF >anti-integrins] (46%) or vice versa (40%) in UC.

Conclusion

In this Belgian inception cohort, two thirds of patients are currently initiated with biological therapy within the first year after diagnosis. This increased biological use is associated with high therapy persistence rates of >80% after a median follow-up of 1.5 years, and with low rates of surgical resections.Read more DOP62 A core molecular resistome characterised by extracellular matrix dysregulation and neutrophil degranulation predicts resistance to multiple therapies in Ulcerative ColitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Several transcript signatures have been published that predict anti-TNF resistance in ulcerative colitis (UC). However, clinical translation is hampered by suboptimal validation performance, partly because of insufficient emphasis on potential pathophysiology. Moreover, predictors of ustekinumab response are lacking. We interrogated transcriptomic datasets and anti-TNF predictive signatures to investigate resistance mechanisms and applicability to ustekinumab.

Methods

Transcript profiles of colonic biopsies taken before treatment for moderate-to-severe UC were analysed from Gene Expression Omnibus. Patients were then treated with infliximab (n = 24 and n = 22), golimumab (n = 84) or ustekinumab (n = 358). Molecular pathways from the Reactome database that were differentially enriched between mucosal healing responders and non-responders post-induction were found, along with shared pathways between cohorts. The largest cohort was used to calculate enrichment of published resistance signatures in actively inflamed mucosa using Spearman correlation. Hierarchical clustering was undertaken for non-responders. Analyses were performed using R 4.2.2 (Vienna, Austria).

Results

Many biological pathways were associated with resistance across the cohorts (1079 pathways, adjusted p value<0.01). Sixty pathways were shared between 3 or 4 datasets. Those relating to extracellular matrix (ECM) activity, neutrophil degranulation and interleukin signalling were most prominent. Network analyses revealed that proteins forming these pathways interact in vivo, forming a discrete functional module. The enrichment of published transcript signatures correlated highly. For instance, correlation between enrichment of UC1 (Czarnewski et al, 2019) and M5 (Friedrich et al 2021) was 0.96. Over-representation analyses showed that these signatures represent processes such as interleukin signalling and neutrophil activity. Hierarchical clustering of non-responders revealed two distinct groups, including those with high (NRhi) and low (NRlo) signature enrichment (Figure 1). Cellular deconvolution analyses showed that neutrophils are more prevalent in NRhi compared to NRlo and that eosinophils may be more frequent in NRlo than NRhi.

Conclusion

ECM dysregulation and neutrophil activity may underlie a core ‘resistome’ that heralds poor treatment outcomes to anti-TNFs and ustekinumab. Supporting this, the enrichment scores of published transcript signatures in inflamed tissue correlate highly, suggesting that many of these represent shared, or similar, molecular mechanisms of resistance. However, there is a separate resistant cohort with different molecular drivers. These findings have implications for precision medicine approaches in UC.Read more DOP63 Mortality in Pediatric-onset Immune-Mediated Inflammatory Disease – A Nationwide StudyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Patients with pediatric-onset immune-mediated inflammatory diseases (pIMID) show more aggressive phenotypes compared to patients diagnosed as adults. Despite this, data on mortality is extrapolated from patients diagnosed in adulthood, which might underestimate the actual risk. We aim to estimate the effect of pIMID compared to reference individuals from the general population on the long-term risk of all-cause mortality.

Methods

A population-based cohort study using the nationwide Danish health care registers. We included all patients diagnosed with pIMID in Denmark from 1980 to 2018 and matched them to up to ten reference individuals from the general population (with no recorded IMID) based on sex, age at diagnosis, and area of residence. Exposure was pIMID, defined as ICD codes indicative of autoimmune hepatitis, primary sclerosing cholangitis, Crohn’s disease, ulcerative colitis, juvenile idiopathic arthritis, system lupus erythematosus, or vasculitis registered before age 18.The primary outcome was all-cause mortality. The secondary outcome was cause-specific mortality. Cox survival analysis was used to estimate hazard ratios (HR) and Aalen survival analysis to estimate rate differences with corresponding 95% confidence intervals (CI) adjusted for the year of diagnosis and family income.Denmark has universal free health care, and health care data can be accessed through the nationwide health registers, continuously updated since 1980.

Results

We included 11,581 individuals diagnosed with pIMID, and 99,665 matched reference individuals, accounting for 1,371,994 person-years of follow-up. Median age at pIMID diagnosis was 12.6 years (IQR: 7.9 – 15.9). During follow-up, 152 pIMID patients and 316 reference individuals died, resulting in an all-cause mortality adjusted HR (aHR) of 3.8 (95% confidence interval [CI]: 3.1-4.7) compared to reference individuals without pIMID. This corresponded to 7.8 (95%CI: 6.1-9.5) additional deaths per 10,000 person-years. The strongest associations were found for gastrointestinal disorders (aHR 22.8 [95%CI: 9.6-64.1]), gastrointestinal cancers (aHR 19.2 [95%CI: 5.0-74.2]), and lymphoproliferative diseases (aHR 6.8 [95%CI: 2.8-16.8]). The aHR of suicide was 2.9 (95%CI: 1.6-5.0).

Conclusion

Patients diagnosed with pIMID have a four-fold increased risk of mortality when followed into adulthood. This underlines the severe disease course of pIMID and highlights the need for lifelong multidisciplinary care.Read more DOP85 An anti-fibrotic role for eosinophils in a DSS colitis RAG-/- and an in vitro co-culture modelWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

In several disease areas, such as in the liver and lungs, a pro-fibrotic role for eosinophils has been suggested. However, information about the role of eosinophils in the development of intestinal fibrosis is scarce. We therefore aimed to assess the functional and mechanistic role of eosinophils in intestinal fibrosis and fibroblast activation.

Methods

Chronic DSS colitis (3 DSS cycles of 1 week DSS administration followed by 2 weeks of recovery (1.75% - 2.25% - 2.25%)) was introduced in 6-8-week-old C57BL/6 RAG^-/- mice to induce intestinal fibrosis (Figure 1A). Mice were injected intraperitoneally with anti-CCR3 to deplete eosinophils (n=8) or with an isotype control (n=8). Intestinal fibrosis was assessed based on collagen deposition (hydroxyproline assay, Martius Scarlet Blue staining (MSB) and second harmonics generation (SHG)), while COL1A1 expression was assessed via RT-qPCR. Gene expression was performed using RT-qPCR and protein expression via the MSD platform. Secondly, circulating eosinophils were isolated from non-IBD controls (n=3) and co-cultured with fibroblasts, isolated from resection specimens obtained from the terminal ileum of Crohn’s disease patients undergoing right hemicolectomy (n=3). The effect of eosinophils on fibroblast activation was assessed through the expression of α-SMA via flow cytometry and immunocytochemistry. Lastly, fibroblasts were stimulated with 10ng/mL eosinophil cationic protein (ECP), a protein exclusively produced by eosinophils (n=3), in order to study whether this mediator could affect fibroblast activation.

Results

Anti-CCR3 mediated eosinophil depletion in the chronic DSS model resulted in increased fibrosis based on the hydroxyproline assay (p=0.06) (Figure 1B), MSB (p=0.0009) (Figure 1C) and COL1A1 expression (p=0.03) (Figure 1D). Similarly, we identified an increased collagen deposition in the eosinophil-depleted group based on the SHG (Figure 1E). Furthermore, an increase in the pro-fibrotic IL-1β and TGF-β3 on protein (p=0.03 and p=0.06) and gene level (p=0.04 and p=0.005) could be found in the eosinophil depleted mice. Co-culturing eosinophils with fibroblasts resulted in decreased α-SMA expression, indicative of a decrease in active fibroblasts. This could be observed via both flow cytometry (p=0.001) (Figure 1F) and immunocytochemistry (Figure 1G). Similarly, when fibroblasts were stimulated with ECP, a decrease in α-SMA was observed (p=0.04) (Figure 1H).

Conclusion

Depletion of eosinophils in a chronic DSS RAG-/- model resulted in more intestinal fibrosis. Similarly, in an in vitro setting, eosinophils, as well as ECP, decreased α-SMA expression in fibroblasts, suggesting that eosinophils may inactivate fibroblasts.Read more DOP86 FOod Additives on the Mucosal barrier study (FOAM): Effect of five emulsifiers on inflammation, intestinal permeability, and the microbiome: preliminary resultsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Common emulsifiers are associated with intestinal inflammation and are therefore excluded in new dietary therapeutic strategies in inflammatory bowel disease. Human data are scarce and involve a limited number of emulsifiers. We aimed to investigate the effect of five different emulsifiers on systemic and intestinal inflammation, intestinal permeability, and the gut microbiome.

Methods

We recruited 60 healthy volunteers to a 7-week double-blind placebo controlled randomized trial. After 1 week of recording their habitual diet (baseline), participants followed an emulsifier-free diet (EFD) for 6 weeks, starting at baseline. After 2 weeks, participants combined the EFD with 3 daily brownies that contained either 2.75 g carboxymethyl cellulose, 1.350 mg polysorbate-80, 380 mg carrageenan, 3.55 g soy lecithin, or 8.72 g native rice starch, or no additives (placebo) for a period of 4 weeks. Anthropometric measurements and bio samples were taken at baseline, week 2 and week 6. Blood samples were collected for routine tests, LPS-binding ELISAs, and serum proteomics using the Olink Target 96 Inflammation and Cardiometabolic panels. Stool samples were collected for analysis of the microbiota (16S rRNA sequencing), short chain fatty acids (Gas Chromatography – Mass Spectrometry (GC-MS)), and faecal calprotectin (FC) analysis. Urine samples were collected following the 2-hour lactulose mannitol ratio protocol to measure intestinal permeability (using GC-MS).

Results

Of the 60 healthy volunteers, 2 were excluded due to NSAID use. Median (IQR) age was 25.5 years (23.0-33.0), median BMI was 22.7 kg/m² (21.2-25.6) and 19.0% were male. There was a median weight loss of 0.1 kg (p=7.6*10^-4, paired Wilcoxon, unadjusted p-value). At week 6 and week 2, FC decreased significantly compared to baseline (p= 4.69*10^-4, and p=2.81*10^-4 respectively, paired Wilcoxon, unadjusted p-value, Table 1 and Figure 1A). No significant increase in FC was noted after consumption of any emulsifier during the trial. In the placebo arm, faecal acetic acid concentration was increased at week 2 (p=0.04). Compared to baseline, there was an increase in both acetic acid and propionic acid concentration (p=0.006 and p=0.04 respectively, paired Wilcoxon, unadjusted p-value, Figure 1B) in the same arm at week 6.

Conclusion

In this double-blind placebo controlled randomized trial faecal acetic and propionic acid increased in the placebo arm, but did not after consumption of any of the emulsifiers. FC did not increase after consumption of any emulsifier. Pending analysis will shed light on the effect of an EFD and distinct emulsifiers on the serum proteome, intestinal permeability and gut microbial changes.Read more DOP74 Short and long-term effectiveness and safety of ustekinumab in Ulcerative Colitis in real life: the ULISES studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Primary aim: To assess the durability of ustekinumab treatment in patients with ulcerative colitis (UC). Secondary aims: To assess the short-term effectiveness, the durability of response, and the tolerability of ustekinumab in clinical practice.

Methods

Retrospective, multicenter study including UC patients who had received the 1^st ustekinumab dose at least 16 weeks before inclusion. Patients were followed-up from the 1^st ustekinumab dose to treatment discontinuation or last visit. Only patients with active disease [Partial Mayo Score (PMS)>2] at ustekinumab start were considered in the effectiveness analysis. Clinical effectiveness was based on PMS. Patients who stopped ustekinumab before their last visit were considered not in remission at subsequent time points (negative imputation).

Results

620 patients were included (table 1). 78% of patients who started ustekinumab maintenance treatment, did it with 90 mg every-8-weeks dose. 155 patients (25%) withdrew ustekinumab during follow-up [median=12 months (m)]. Incidence rate of ustekinumab discontinuation was 20% per patient-year of follow-up. The probability of maintaining ustekinumab is shown in figure 1A. Among patients who withdrew ustekinumab, the main reasons were primary non-response (39%) and loss of response (35%). Anaemia at baseline (HR=1.5, 95%CI=1.1-2.1), steroids at baseline (HR=1.5; 95%CI=1.06-2.08), and more severe clinical activity at baseline (HR=1.5; 95%CI=1.09-2.06) were associated with higher risk of ustekinumab discontinuation. Short and long-term effectiveness of ustekinumab is shown on figure 1B. Moderate-severe vs. mild disease activity at baseline (OR=0.3, 95%CI=0.2-0.5), male sex (OR=0.5; 95%CI=0.4-0.8), and increased number of previous biologics (OR=0.6, 95%CI=0.6-0.8) were associated with lower likelihood of steroid-free remission at week 16. A total of 57 (25%) patients among those with active disease at baseline and with steroid-free remission at week 16, lost response during a median follow-up of 8 m (IQR=3-16 m) (figure 1C). The dose was escalated in 72% of patients with loss of response, and 80% improved (67% remission); an intravenous reinduction was given in 3 patients, and none of them improved. A total of 176 patients (28%) had at least one adverse event, with infections being the most frequent (11%). No negative impact on extraintestinal manifestations and/or immunomediated diseases was seen.

Conclusion

Ustekinumab was effective in inducing remission even in highly refractory UC patients. A proportion of patients discontinue the treatment, mostly due to primary failure and loss of response. Dose escalation may be effective to regain response after loss of effectiveness. The safety profile was similar to previously reported.Read more DOP75 Frequency and effectiveness of dose escalation of biologic therapy in Inflammatory Bowel Disease: The RAINBOW-IBD study of ENEIDAWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Despite their effectiveness in inflammatory bowel disease (IBD), biologic drugs often require dose escalation. Primary aim: To describe the frequency and effectiveness of dose escalation of biologics: infliximab (IFX), adalimumab (ADA), golimumab (GOL), vedolizumab (VED), and ustekinumab (UST). Secondary: To study the reasons for and the durability of escalation, and to identify predictive factors for relapse and for therapy discontinuation after it.

Methods

Adult patients from ENEIDA registry who received biologics were included. Dose escalations were specifically analysed. Survival curves assessing the impact of several variables on the durability and on clinical relapse were compared using the log-rank test. Predictive factors associated with therapy discontinuation and the risk of relapse after dose escalation were assessed by Cox-regression.

Results

Out of the 19,720 patients with biologics included in ENEIDA, 5,096 (26%) had their dose escalated, which were analysed. The frequency of escalation per patient-year of follow-up was: 5% (95% confidence interval [CI]=4.3-5.6%), 7% (6.3-7.7%), 7% (6.9-7.1%), 10% (9.9-10.1%), and 12% (11.9-12.1%) in patients receiving IFX, ADA, GOL, VED and UST, respectively (Figure 1).The main reason for dose escalation was loss of response (60%). Remission and clinical response were recaptured after dose escalation, respectively, in: 49% and 89% (IFX), 41% and 86% (ADA), 46% and 85% (GOL), 32% and 87% (VED), and 47% and 92% (UST). The probability of maintaining the dose escalated at 12 and 24 months was: 88% and 78% (IFX); 82% and 71% (ADA); 82% and 66% (GOL); 84% and 75% (VED); and 93% and 88% (UST), respectively (Figure 2).Predictive factors of relapse after re-achieving remission with dose escalation were: 1) IFX: previous biologic exposure (Hazard ratio [HR]=1.2, 95%CI=1.1-1.4), and IBD duration (HR=0.97, 95%CI=0.96-0.99); 2) ADA: ADA monotherapy (HR=1.2, 95%CI=1.01-1.35); 3) VED: Crohn’s disease (HR=1.56, 95%CI=1.1-2.2), and IBD duration (HR=0.9, 95%CI=0.8-0.99); and 4) UST: ulcerative colitis (HR=2.4, 95%CI=1.5-3.9). Predictive factors of therapy discontinuation after dose escalation were: 1) IFX: previous biologic exposure (HR=1.2, 95%CI=1.1-1.4), and disease duration (HR=0.98, 95%CI=0.97-0.99); 2) ADA: ADA monotherapy (HR=1.2, 95%CI=1.1-1.25); and 3) UST: ulcerative colitis (HR=1.4, 95%CI=1.1-1.9).

Conclusion

A proportion of IBD patients dose escalate biologics in the long-term. Dose escalation is an effective strategy to recapture response and remission. The durability of escalation seems to be relatively high over time. Prior biologic experience, IBD type, and a short evolution of IBD were identified as predictive factors of relapse and therapy discontinuation after dose escalation.Read more P109 Organic Cation Transporter (OCTN)-1 variants shape innate immunity and predict individual response to vedolizumab In ulcerative colitis patientsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Limited evidence is available about predictors of response to specific medications for ulcerative colitis (UC). OCTN1, an organic cation transporter, with its variants, could modulate the inflammatory response and potentially modify drug response to immune-modulatory therapy (anti-TNFα and vedolizumab), perhaps predicting individual response.

Methods

We first confirmed the ability of OCTN1 to differentially modulate IL1β secretion under different stimuli in a human leukemia monocytic cell line (THP-1) and in human peripheral blood mononuclear cells. We therefore prospectively enrolled a cohort of UC patients starting either anti-TNFα or vedolizumab, determined their OCTN1 genotype and evaluated their clinical features at baseline and clinical response to therapy or disease remission (according to clinical Mayo score) after six weeks (T1) and six months (T2). We finally enrolled a cohort of UC patients in clinical and endoscopic remission (according to full Mayo score) under immune-modulatory therapy (anti-TNFα or vedolizumab) for at least two years.

Results

OCTN1-deficient THP1 cells showed reduced IL-1β secretion in response to peptidoglycan (PGN) and Fusobacterium nucleatum (Fn), whilst primary monocytes bearing OCTN1 503F variant displayed an increased production of IL-1β in response to PGN and live bacteria. We therefore enrolled 90 patients, 50 starting anti-TNFα and 40 vedolizumab. Patients with 503F genotype showed higher rates of pancolitis as compared to 503L genotype. Among patients with 503L genotype, vedolizumab results highly associated with long-term response (OR 8.92, 95%CI 0.50-11.0; p=0.019), whilst conversely co-presence of 503F genotype and vedolizumab therapy disclosed an opposite role on the long-term response rate (OR 0.02, 95%CI 0.00-0.81; p=0.038).The population of UC patients in clinical and endoscopic remission was composed by 92 patients, 63 under anti-TNFα and 29 under vedolizumab. Of note, similar trends of disease extension were observed across genotypes: higher rates of pancolitis were observed in the 503F population as compared to 503L (62.5% vs 44%). Furthermore, among patients in remission with 503F genotype, the percentage of subjects receiving vedolizumab was sensibly lower than among patients with 503L genotype (87.5% anti-TNFα vs12.5% vedolizumab among 503F genotype; 56% anti-TNFα vs 44% vedolizumab among 503L genotype).

Conclusion

Mutated OCTN1 genotype (503F) favors an increased IL1β secretion from human stimulated leukocytes, thus suggesting a worse disease course with higher rate of pancolitis and lower response to vedolizumab as compared to 503L.Read more P110 Heterogeneous response of colonoid-derived monolayers to TNFα and IFNγ exposure: functional and morphological characterizationWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Despite the progress made in the diagnosis and treatment of inflammatory bowel diseases (IBD), incidence and prevalence are still growing. Considering the lack of human preclinical studies, reliable models that mimic the inflamed intestinal epithelium are increasingly explored. Patient-derived colonoids are a powerful tool that recapitulate, in vitro,many physiological features of the human colon. The present work aims to characterize, functionally and morphologically, colonoid-derived monolayers (CDMs) and the changes induced by TNFα and IFNγ, comparing their effects with Caco-2 monolayers.

Methods

Colonic crypts, isolated from biopsies of 5 healthy volunteers undergoing colonoscopy for reasons other than IBD, were embedded in 70% (v/v) Matrigel^® and grown for 5-7 days. IntestiCult^TM OGM was used to generate cystic-like colonoids, further expanded in suspension cultures. After dissociation, cells were seeded at 7.5x10⁵ cells/cm² onto 24-well inserts coated with Matrigel^® (1:50). The integrity of the epithelial barriers was monitored by TEER. When monolayers reached confluence (TEER≥100 Ω·cm²), IntestiCult^TM OGM was switched to ODM. Differentiated CDMs were exposed for 24h to 25ng/mL TNFα and 25ng/mL IFNγ. Changes in cell morphology and viability, IL8 and NF-kB p65 levels, and FITC-D4 apparent permeability (P_app) were determined. Caco-2 cells, seeded at 5x10⁴ cells/cm², were exposed after 21 days to the same cytokine cocktail for 24h: TEER was monitored and IL8 release was quantified.

Results

CDMs developed into robust epithelial barriers, with TEER values increasing over time, indicating that tight junctions were formed. Immunocytochemistry (ICC) staining for villin and MUC2 revealed that cells were polarized and differentiated. Exposure to TNFα and IFNγ impaired significantly, although heterogeneously, the barrier integrity of CDMs and increased the release of IL8. When the barrier damage was more severe, FITC-D4 P_app and NF-kB p65 levels also raised, while cell viability was reduced. ICC images showed a large number of apoptotic cells near the basal side, and a decrease in the expression of villin and MUC2, suggesting that cell polarity and differentiation were impaired. In Caco-2 monolayers, cytokine exposure induced a mild damage on the barrier integrity and a significantly lower release of IL8, when compared to CDMs.

Conclusion

CDMs from different patients formed functional barriers that showed heterogenous sensitivity to TNFα and IFNγ exposure. In essence, all CDMs showed compromised epithelial barriers, altered cell morphology, and increased IL-8 levels. Differences between the IL8 released by Caco-2 and CDMs highlight the variation in the inflammatory response of the two models.Read more P111 Dietary emulsifier κ-carrageenan does not directly affect intestinal permeability in organoid-derived epithelial monolayers from patients with Crohn’s diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The dietary emulsifier carrageenan (CGN) is widely used to optimise the texture of processed foods such as ice cream, plant-based milk and processed meat products. However, CGN is suggested to play a role in IBD development by exerting pro-inflammatory effects and increasing intestinal permeability, as shown in immortalized cell lines and murine models. Specifically kappa-carrageenan (κ-CGN) has been shown to disrupt barrier function of intestinal epithelial cells. In this study, we investigated if κ-CGN can directly increase intestinal permeability in organoid-derived epithelial monolayers from patients with Crohn’s disease (CD).

Methods

Organoid cultures were derived from colonic biopsies of 5 patients with CD (Table 1) and seeded on Transwell® inserts to obtain epithelial monolayers. Two independent experiments were performed per patient (n = 10). Once a confluent monolayer was formed, non-inflamed and inflamed conditions were established by adding regular culture medium or inflammatory stimuli (100 ng/mL TNF-α, 20 ng/mL IL-1β, 1 µg/mL flagellin) to the basolateral side, respectively. The next day, both inflamed and non-inflamed monolayers were stimulated with 100 µg/mL κ-CGN on the apical side, or with regular culture medium as control. The basolateral side was also renewed with either the inflammatory stimuli or regular culture medium. Transepithelial electrical resistance (TEER) was measured after 24 and 48 hours of κ-CGN exposure to study permeability of the epithelium. Relative TEER (% change compared to baseline) was compared between controls and κ-CGN stimulated conditions (repeated measures ANOVA, Šídák's multiple comparisons correction).

Results

As expected, exposure to inflammatory stimuli on the basolateral side resulted in a significant reduction of TEER of the monolayers after 48 hours (+ 24 hours pre-stimulation), compared to the non-inflamed conditions (-22.54 ± 4.557 %, p<0.0001, paired t-test) (Figure 1A). After 24 hours of stimulation with κ-CGN, TEER did not significantly change in both the non-inflamed (p=0.90) and inflamed conditions (p=0.80), compared to the control conditions. Also after 48 hours, exposure to κ-CGN did not significantly affect the TEER in both non-inflamed (p=0.94) and inflamed (p=0.74) conditions (Figure 1B). RNA analysis of the organoid-derived monolayers is ongoing to explore the inflammatory potential of κ-CGN and possible effects on mucus production.

Conclusion

The dietary emulsifier κ-CGN does not directly alter the permeability of the intestinal epithelium of CD patients. Further analysis of gene expression of inflammatory markers and mucus production is ongoing. Possible indirect effects, through alterations of the microbiota or immune cells, should still be explored.Read more P112 Lymphocytic colitis can be transcriptionally divided into channelopathic and inflammatory lymphocytic colitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The pathobiology of the non-destructive inflammatory bowel disease (IBD) lymphocytic colitis (LC) is poorly understood. We aimed to define an LC-specific mucosal transcriptome to gain insight into LC pathology, identify unique genomic signatures, and uncover potentially druggable disease pathways.

Methods

We performed bulk RNA-sequencing of LC and collagenous colitis (CC) colonic mucosa from patients with active disease, and healthy controls (n=4-10 per cohort). Differential gene expression was analyzed by gene-set enrichment and deconvolution analyses to identify pathologically relevant pathways and cells, respectively, altered in LC. Key findings were validated using reverse transcription quantitative PCR and/or immunohistochemistry. Finally, we compared our data to a previous cohort of ulcerative colitis and Crohn’s disease patients (n=4 per group) to distinguish non-destructive from classic IBD.

Results

LC can be subdivided into channelopathic LC, which is governed by organic acid and ion transport dysregulation; and inflammatory LC, which is driven by microbial immune responses. Inflammatory LC displays an innate and adaptive immunity that is limited compared to CC and classic IBD (Fig. 1). Conversely, we noted a distinct induction of regulatory non-coding RNA species in inflammatory LC samples. Moreover, compared to CC, water channel and cell adhesion molecule gene expression decreased in channelopathic LC, whereas it was accentuated in inflammatory LC and associated with reduced intestinal epithelial cell proliferation.

Conclusion

We conclude that LC can be subdivided into channelopathic LC and inflammatory LC that could be pathomechanistically distinct subtypes despite their shared clinical presentation. Inflammatory LC exhibits a dampened immune response compared to CC and classic IBDs. Our results point to regulatory micro-RNAs as a potential disease-specific feature that may be amenable to therapeutic intervention.Read more P162 The Biosimilar Switch: IBD nurse's experience in Our Lady of Lourdes HospitalWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

A biological medication contains an active substance that is produced from a biological source such as living cells, hormones or enzymes. The active substance in a biological medicine is what makes the medicine work. Biological medicines are also called biologics. A biosimilar medicine is a biological medicine that is developed to be highly similar to an existing biologic but they are not identical and so cannot be considered to be generics. Biosimilars were introduced in Ireland in 2014. In 2018, Our Lady of Lourdes Hospital commenced a procurement programme to decide which Infliximab biosimilar to switch our patients to. This process would allow for a huge cost-saving to the hospital budget and also allowed for the allocation of a whole-time clinical nurse specialist to add the IBD nursing team. The infliximab biological switch was then carried out starting in October 2019.All patients received a letter explaining the switch and a booklet to explain the meaning of biosimilars. The patients were then either phoned or spoken to in person by either the IBD nurse or a GI pharmacist, and any questions or concerns addressed.

Methods

A patient satisfaction survey was sent to each patient 6 months after the switch. Each questionnaire was sent with a prepaid return envelope. The questionnaire consisted of 7 questions with tick box answers.1. Gender?2. Age?3. Did you receive a letter and information booklet in the post prior to the day of your infusion switch.4. Did you get the opportunity to talk to someone on the phone prior to your infusion?5. Did you get the opportunity to speak to a nurse or pharmacist on the day of your infusion? If so who?6. Were you given a named person to contact if you had any issues after our first infusion?7. Were you happy with the overall experience of the infliximab biosimilar switch?

Results

86 patients were switched from the originator to the biosimilar Flixabi. 22 responses were received.1. 11 male; 11 female2. Age 16-19 - 2; 20-29 - 1; 30-39 - 4; 40-49 - 4; 50-59 - 9; 70-79 - 1; preferred not to answer - 1.3. 20 received the letter and booklet; 2 did not.4. 15 spoke to someone on the phone; 6 did not and 1 could not remember.5. 22 - spoke to a nurse; 0 - pharmacist.6. 20 - yes; 2 - no.7. 21 - yes; 1 - unsure.

Conclusion

Of the 86 patients who were switched 22 responded to the questionnaire. 21 patients were happy with their overall experience with how the switch was conducted.Read more P163 PI(4,5)P2 alleviates colitis by inhibiting intestinal epithelial cell pyroptosis through NNMT-mediated RBP4 m6A modificationWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Lipid metabolism disorder is a critical feature of Crohn’s disease (CD). We previously reported that phosphatidylinositol (PI), and its derivative phosphatidylinositol bisphosphate (PIP2) were significantly associated with CD activity. The underlying mechanisms remained unknown. We aimed to explore the function of phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2], the major PI derivative, in modulating CD pathogenesis.

Methods

Lipidomics was used to analyse the relationship between CD activity and PI or PIP2. The mucosal expression of PI(4,5)P2 in patients with CD was measured by immunofluorescence. Dextran sodium sulfate (DSS)-induced colitis mice and lipopolysaccharide (LPS)-induced Caco-2 cell model were established to explore the function and mechanism of PI(4,5)P2. MeRIP and mRNA sequencing were applied to further reveal the mechanism of PI(4,5)P2.

Results

Lipid PIP2 was substantially negatively associated with disease activity and high-sensitivity C-reactive protein. PI(4,5)P2 expression was downregulated in the inflamed mucosa of patients with CD. PI(4,5)P2 alleviated mice colitis, with improvements in survival rate, colon length, body weight, and disease activity index. PI(4,5)P2 also alleviated DSS-induced tissue damage, tight junction loss, and intestinal epithelial cell (IEC) pyroptosis. In the in vitro LPS-induced cell model, PI(4,5)P2 inhibited pyroptosis, NLRP3, and caspase-1 expression, and reduced IL-18, IL-1β, and lactate dehydrogenase (LDH) secretion. PI(4,5)P2 mediated NNMT upregulation in mice and Caco-2 cells. NNMT knockdown restricted the inhibitory effect of PI(4,5)P2 on IEC pyroptosis. NNMT inhibited the stability of RBP4 mRNA via the m6A modification to prevent pyroptosis upon PI(4,5)P2 treatment.

Conclusion

PI(4,5)P2 inhibited IEC pyroptosis through NNMT-mediated RBP4 m6A modification, which ameliorating colitis. PI(4,5)P2 may be a therapeutic target for CD.Read more P164 MRT-6160, a VAV1-directed molecular glue degrader, inhibits disease progression and inflammation in a T-cell transfer model of ColitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

VAV1 is an immune-restricted guanine nucleotide exchange factor critical for T-cell receptor (TCR) and B-cell receptor (BCR) signalling. The role of VAV1 in T-cells has been demonstrated in knockout mice, which exhibit decreased effector functions and resistance to autoimmune disease models, and in CRISPR-based screens, where VAV1 has been highlighted as a top hit among positive regulators of T-cell function. Until now, VAV1 has remained undruggable by conventional small molecules. MRT-6160 is a first-in-class molecular glue degrader that specifically targets VAV1 for proteasomal degradation. Given the role of VAV1 in TCR and BCR signalling, MRT-6160-mediated degradation could be an effective therapeutic approach to treating autoimmune disease.

Methods

We first tested the impact of MRT-6160-mediated human (h)VAV1 degradation on primary human cells using in vitro stimulation-based assays. Oral bioavailability of MRT-6160 and in vivo degradation of murine (m)VAV1 was then examined in mice. We tested the efficacy of MRT-6160 using a T-cell adoptive transfer model of colitis treating recipients of pathogenic CD45RB^high CD4+ T-cells (8 per group) with anti-TNF (25 mg/kg, Q3D) or MRT-6160 (1 mg/kg, QD) for 41 days following cell transfer. Disease activity index (DAI), comprising stool consistency and weight loss, was assessed every 3 days. At study termination, mesenteric lymph nodes (mLN) were profiled by flow cytometry and colon tissues were assessed for cytokine expression and histopathology.

Results

Degradation of hVAV1 by MRT-6160 inhibited T-cell activation, proliferation, and cytokine production in a dose-dependent manner. Orally administered MRT-6160 degraded mVAV1 and inhibited colitis disease progression by 85%, reducing average end point DAI scores more than a standard of care control (vehicle, p<0.0001; anti-TNF, p=0.0107). Compared to vehicle treated groups, MRT-6160 treated mice had fewer IL-17A+ (12.6 and 5.3% respectively) and TNF+ (37.6 and 17% respectively) CD4+ T cells in mLN tissue. Colon weight:length ratio was significantly reduced in MRT-6160-treated mice (42.5 mg/cm) compared to vehicle (70.3 mg/cm) and anti-TNF (61.2 mg/cm). Finally, pro-inflammatory cytokine expression in the colon mucosa was reduced in MRT-6160-treated mice compared to vehicle (IL-6: 1305.8 and 682.3 fg/mg; TNF: 175.5 and 66.9 ng/mg; respectively), as well as histopathological evidence of disease.

Conclusion

MRT-6160 demonstrates strong activity in a preclinical model of colitis reducing DAI, effector cytokine production, and colon tissue damage. These data suggest that MRT-6160-mediated degradation of VAV1 may have therapeutic benefit in IBD patients and warrants further clinical development.Read more P165 Guselkumab binding to CD64+ IL-23–producing myeloid cells enhances potency for neutralizing IL-23 signalingWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

IL-23 is implicated in the pathogenesis of inflammatory bowel disease (IBD) and myeloid cells that express FcγRI (CD64) have been identified as the primary cellular source of IL-23 in inflamed IBD gut tissue. Guselkumab (GUS) and risankizumab (RZB) are monoclonal antibodies (mAbs) specifically directed against the IL-23p19 subunit. GUS is a fully human IgG1 mAb with a native Fc region while RZB is a humanized IgG1 mAb with a mutated Fc region. Here, we evaluated CD64 and IL-23 expression in IBD patient gut biopsies, binding of GUS and RZB to CD64, and the functional consequences of CD64 binding by IL-23p19 subunit mAbs, in in vitro assays.

Methods

IL23A and FCGR1A (CD64) expression was analyzed from bulk and single-cell RNAseq datasets. Binding of mAbs to IFNγ-primed human monocytes, as well as binding to IL-23–secreting inflammatory monocytes and capture of endogenously secreted IL-23, were assessed by flow cytometry. Internalization of IL-23, GUS, and RZB within CD64⁺ macrophages was evaluated using live cell confocal imaging. Potency of GUS and RZB for inhibiting IL-23 signaling was determined in a co-culture of THP-1 (a CD64⁺ monocyte cell line activated to produce IL-23) and an IL-23 reporter cell line (measuring biologically active IL-23).

Results

Analysis of RNAseq datasets showed that FCGR1A, IL23A, and IL12B were significantly increased in inflamed versus non-inflamed IBD gut biopsies and that IL23A was predominantly expressed by FCGR1A-expressing myeloid cells. In in vitro assays GUS, but not RZB, showed Fc-mediated binding to CD64 on IFNγ-primed monocytes. CD64-bound GUS simultaneously captured IL-23 secreted from the same cells. GUS, but not RZB, bound to the surface of CD64⁺ macrophages and mediated internalization of IL-23 to low pH intracellular compartments. GUS and RZB demonstrated similar potency for inhibiting signaling by IL-23 present in THP-1–conditioned media. However, in a co-culture of IL-23–producing THP-1 cells with an IL-23–responsive reporter cell line, GUS demonstrated enhanced potency compared to RZB for inhibition of IL-23 signaling.

Conclusion

Our transcriptomic analysis supported previous observations of CD64⁺ myeloid cells as a key source of IL-23 production in inflamed IBD gut tissue. GUS binding to CD64 on IL-23–producing cells likely contributed to the enhanced functional potency of GUS compared to RZB for inhibition of IL-23 signaling in the co-culture assay. These in vitro data support a hypothesis for optimal enrichment of GUS in inflamed tissues where CD64⁺ IL-23–producing myeloid cells are increased and in proximity to IL-23–responsive lymphoid cells, enabling GUS to more potently neutralize IL-23 by targeting IL-23 at its source of production.Read more P190 Identification of clinical risk factors for postoperative endoscopic recurrence in Crohn’s disease: a prospective, multicenter cohort studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Further refinement of clinical risk stratification for postoperative endoscopic recurrence in patients with Crohn’s disease is required to identify patients who will benefit from prophylactic therapy. Therefore, we aimed to assess risk factors for endoscopic recurrence in a large prospective, multicenter cohort study.

Methods

CD patients (≥16 years) scheduled for ileocolic (re-)resection (ICR) and those who underwent an ileocolonoscopy at 6 months following ICR were included. Primary outcome of the study was endoscopic recurrence (modified Rutgeerts’ score ≥ i2b at 6 months). Multivariable logistic regression was performed to identify clinical risk factors. The model included a random effect for the study center to correct for potential correlation between treating center and the outcome.

Results

In total, 298 patients underwent ICR (79.2% primary ICR, 20.8% re-resection) after a median disease duration of 5.3 years (IQR 1.0 – 12.4). 60.4% of patients were female with a median age at surgery of 34.1 years (IQR 25.7 – 50.5). 67.8% of the patients were exposed to ≥1 biological prior to surgery. Postoperative prophylactic medication (<12 weeks to ICR) was initiated in 85/298 (28.5%) patients; 24.7% immunomodulator, 29.4% anti-TNF, 27.1% combination therapy [immunomodulator with anti-TNF agent], 4.7% vedolizumab, 14.1% ustekinumab. Mean time to postoperative ileocolonoscopy was 6.2 months (SD 1.3). Endoscopic recurrence was diagnosed in 37.9% of the patients. Multivariable logistic regression identified active smoking (adjusted OR [aOR] 3.12; 95% CI 1.63 – 5.98) and penetrating disease behaviour (aOR 1.92; 95% CI 1.04 – 3.57) as risk factors for endoscopic recurrence, whilst ileocolic disease (versus ileal disease; aOR 0.27; 95% CI 0.15 – 0.49) and postoperative prophylactic medication (aOR 0.24; 95% CI 0.12 – 0.47) were identified as protective factors for endoscopic recurrence (Table 1).

Conclusion

Active smoking and penetrating disease behaviour at time of surgery were identified as risk factors for early postoperative recurrence in Crohn’s disease. Reversely, ileocolic disease at time of surgery and initiation of postoperative prophylactic medication were identified as protective factors for early endoscopic recurrence. Young age at surgery, perianal disease and a prior intestinal resection, included as risk factors in the current international guidelines, were not associated with early endoscopic postoperative recurrence in this large prospective cohort study.Read more P191 Inflammatory bowel disease type unclassified in paediatric-onset IBD: A nationwide cohort study in Scotland with up to 20 years follow-up shows reclassification in the majority and mild course in those remaining as IBDUWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Inflammatory bowel disease type unclassified (IBDU) is the least common subtype of IBD accounting for around 10% of incident cases in children. There are a lack of long-term longitudinal data to fully elucidate both disease course and reclassification rate in IBDU. Our aim is to clarify disease course and reclassification rate by presenting nationwide data of an IBDU cohort with long-term (9-20 years) follow-up.

Methods

In a nationwide study, we analysed our prospectively identified 11 year cohort of IBDU patients diagnosed 01/01/03-31/12/13 via all Scottish paediatric IBD centres (Aberdeen, Edinburgh, Glasgow) and followed-up into adult services until 01/01/23. All had a diagnosis of IBDU based on the Porto diagnostic criteria and Paris PIBD phenotypic classification using a combination of clinical, endoscopic, histological and radiological findings. Follow-up data were obtained retrospectively from electronic medical records (demographics, diagnostic plus all repeat endoscopic and radiological assessments, longitudinal disease severity based on defined global clinician assessment, medical treatment and surgical outcomes) at fixed time points (5 and 10 years post-diagnosis) and at the last follow-up.

Results

A total of 116 patients were initially identified as IBDU, with 14 patients excluded as they emigrated out of the area before the first time point. 102 patients were included in the analysis (57/102 (56%) male, median (IQR) age at diagnosis 11.5 (9.1-13.2) years) with a median (IQR) length of follow-up of 10.5 (8.6-14.0) years. A change of diagnosis was made in 61/102 (60%) patients with 30/102 (29%) reclassified as Crohn’s disease (CD) and 31/102 (30%) as ulcerative colitis (UC) after a median (IQR) disease duration of 5.0 (2.0-8.2) and 4.7 (1.8 – 7.7) years respectively. Patients who remained as IBDU had a milder disease course compared to those reclassified as CD/UC with higher 1-5 year remission rates (30/39 (77%) in IBDU vs 16/57 (28%) in CD/UC-reclassified, p<0.05), lower rates of moderate-to-severe disease (3/39 (8%) in IBDU vs 31/57 (54%) in CD/UC-reclassified, p<0.05), less need for biologics across all time points (all p<0.05) and a higher proportion managed on aminosalicylates or no medication (all p<0.05). Higher rates of surgical resections were observed by last documented FU in CD/UC-reclassified patients (IBDU 1/41 (2%) vs CD/UC-reclassified 11/61 (18%), p=0.02).

Conclusion

In our nationwide paediatric IBDU cohort the majority (60%) of patients were reclassified as either UC or CD over the longest published median follow-up (10.5 years); those who remained with an IBDU classification had a milder disease course and decreased need of biologic escalation.Read more DOP56 Fibrosis-related transcriptome unveils a distinctive matrix remodelling pattern in penetrating but not in stricturing ileal Crohn's DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Fibrosis underlies most of CD complications requiring surgery, such as intestinal strictures and penetrating events. We previously demonstrated there were no histopathological differences on transmural fibrosis and fibromuscular changesbetween penetrating and stricturing ileal CD. This study aimed to investigate and compare the fibrosis-related transcriptomic profiles of penetrating and stricturing ileal CD.

Methods

Using Nanostring technology and comparative bioinformatics, we analysed the expression of 787 genes covering the core pathways and processes involved in fibrosis, in 34 ileal surgical specimens, 11 B2 and 23 B3, the latter encompassing 12 with associated stricture(s) (B3s) and 11 without (B3o). Each patients’ tissue was retrieved from three FFPE 20mm-sections. Quality control of extracted RNA was performed according to Nanostring parameters and principal component analysis (PCA) graph for the distribution analysis. For the selection of the differentially expressed genes (DEGs) we adopted a P-adjusted <0.05 and a Fold Change ≤-1.5 or ≥ 1.5. Statistical analysis adopted level of significance at 5%.

Results

We included 34 patients, in a well-balanced sample for age (at diagnosis and at surgery), gender, CD localization, perianal disease and therapy. Inflammation and fibrosis histopathological scoring were similar (median of 3 and 1, respectively), in the three groups. No DEGs differentiated B3s and B3o subgroups, which were grouped as B3. The B2 and B3 groups showed a very good clustering on the gene heatmap, which uncovered 30 DEGs between the 2 groups, all being upregulated in B3 and, conversely, downregulated in B2 patients – Figure. More than half of the upregulated genes have been established or partially involved in CD fibrogenesis (yellow-box and line, respectively), while 8 DEGs have been implicated in fibrosis in other organs (brown-line box) and 3 others having an anti-fibrotic role in other tissues (green-line box). Importantly, the vast majority of the most significantly active biologic processes and pathways in the B3 group were related to response to TGF b and matrix organization, production and degradation, unveiling a continuous process of tissue healing and destruction distinctive of this aggressive phenotype.

Conclusion

Despite the histopathological similarities of fibrosis between stricturing and penetrating ileal CD, their fibrosis-related transcriptomic profiles are distinct. Penetrating CD was remarkable for the activation of all the unveiled DEGs and of biologic pathways concerning permanent matrix production and degradation. Hence, although fibrosis underlies both penetrating and stricturing CD, therapeutic targets may differ even in end-of-stage disease.Read more DOP57 Cystic fibrosis risk variants confer a protective effect against Inflammatory Bowel Disease in large-scale exome sequencing analysisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Genetic mutations that produce defective Cystic fibrosis transmembrane regulator (CFTR) proteins are known to cause cystic fibrosis (CF), a lethal autosomal recessive Mendelian disorder. Existing studies have debated the roles of CFTR mutations in Inflammatory Bowel Disease (IBD), with inconclusive evidence supporting both risk and protective effects.

Methods

We generated the largest IBD exome sequencing callset with 38,744 cases and 69,570 controls of European ancestries from the International Inflammatory Bowel Disease Genetics Consortium. After rigorous quality control analyses, we performed association testing using a logistic mixed-model implemented in REGENIE v.2.2.4. A set of LD-pruned high-confidence variants (MAF > 1% and call rate > 99%) was used for polygenic effect parameter estimation, which was included as covariates. To control for residual population structure and sequencing heterogeneity, we included as covariates a binary variable representing the sample sequencing platform and the top five principal components calculated from LD-prune well-genotyped common SNPs. Sex as a biological variable was also included as a covariate. Firth correction was applied to association tests with P < 0.05 to control for case-control imbalance.

Results

Here, we report two lines of evidence establishing a protective role of CF-causing variants against IBD. First, we found delF508, the known CF-causing variant that accounts for 70% of all CFTR mutations observed in CF patients, is significantly associated with IBD (P=1.7E-10) with a protective effect (BETA=-0.30, SE=0.048). The conclusion remained unchanged if we excluded individuals carrying two copies of delF508. Second, we conducted an unweighted gene burden test of CFTR restricted to all variants (excluding delF508) annotated as CF-causing in the Clinical and Functional Translation of CFTR (CFTR2) database. This burden test indicates a significant association between CF-causing variants and IBD (P=1.1E-6) with a slightly smaller protective effect (BETA=-0.23, SE=0.047). As a negative control, another burden test was performed on CFTR using all rare (MAF<0.001) nonsynonymous non-CF-causing variants. This test showed no significant association (P=0.42).

Conclusion

Leveraging a large-scale IBD exome sequencing dataset, we report two lines of evidence that convincingly suggest CF-causing variants confer a protective effect against IBD. Follow-up experimental studies are warranted to investigate the cellular pathways that CF-causing mutations disrupt to exert such an anti-inflammatory effect, which may provide insights for novel therapeutic interventions for IBD.Read more DOP58 Human Leukocyte Antigen drives methylation signatures in primary sclerosing cholangitis but not in IgG4-related sclerosing cholangitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Primary sclerosing cholangitis (PSC) and IgG4-related sclerosing cholangitis (IgG4-SC) are fibro-inflammatory hepatobiliary conditions, with genetic, environmental, and immunologic risk factors, in which epigenetic alterations may provide insights into pathophysiology and novel biomarkers.

Methods

Whole blood DNA methylation profiling and genotyping was performed in 70 PSC (57 with PSC and ulcerative colitis (PSC-UC)), 56 IgG4-SC, 66 UC, and 88 healthy controls (HC), with MethylationEPIC and Global Screening arrays (Illumina). UC patients were selected to match the clinical characteristics of UC in the PSC-UC cohort. Methylation data was processed with Minfi and limma, genotyping analysed with Plink, and meQTLs with linear models.

Results

There were 31, 13 and 8 Holm-significant methylation differences between PSC and controls, IgG4-SC and controls, and UC and controls respectively (8 probes shared). Inflammatory genes (including CEP97, IFNAR1, TXK, and SMAD2) and methylation loci associated with mitochondrial DNA copy number (C5orf36, PYY, and MTRNR2L1) were predominant. Sub-analyses of PSC-UC and PSC without IBD detected 25 and 4 differences with HC respectively (p<0.05). DNA methylation age acceleration was observed in IgG4-SC, but not on PSC, PSC-IBD or UC. MeQTL analyses to identify genetic determinants of methylation revealed a strong HLA signal in PSC but not IgG4-SC, with 19/40 significant findings in 5 clusters (HLA-DRB1, HLA-DPB1, BTNL2, CSNK2B, and SFTA2). There was no overlap with the 36 meQTLs found in IgG4-SC. Using multivariate adaptive shrinkage for meQTLs in PSC, IgG4-SC, and UC yielded 5505 meQTLs with local false discovery rate <0.05 in at least one condition, with 1230 unique to PSC, and 1043 to IgG4-SC.

Conclusion

We identify characteristic epigenetic alterations in PSC and IgG4-related disease, providing insights into disease pathogenesis; and highlight the potential interaction with germ-line variation.Read more DOP59 Integration of in silico analysis and in vitro functional analysis reveals Tissue Factor Pathway Inhibitor 2 (TFPI2) as a master transcriptional regulator and potential target to impede Infliximab resistance in adult UC patientsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Standard biological therapy for moderate-severe cases of UC consists in the use of Infliximab (IFX), an anti-tumour necrosis factor α (anti-TNF-α) targeting agent. However, approximately 40% of the patients do not respond to IFX. While transcriptional alterations have been widely associated with non-response to IFX, the precise factors that regulates this altered gene expression remains poorly understood. The aim of this study was perform a robust in silico analysis to identify master transcriptional regulators (MTRs) which regulate gene expression changes in IFX non-responsive UC patients, followed by perturbation in vitro to establish their functional role in UC pathogenesis.

Methods

Differentially expressed genes (DEGs) identified from four independent public datasets were applied to the GeneXplain platform to identify transcription factors (TFs) enriched for the DEG’s. This was followed by an upstream analysis to identify MTR’s which regulate expression of these genes through the TFs. We next explored the role of these MTRs in driving UC-associated phenotype, using siRNA-mediated knock-down in a novel IBD-like in vitro system comprising of normal rectal epithelial cells treated with TNFa.

Results

Over 200 TFs were identified in both upregulated and downregulated genes in IFX non-responders across all data sets. RELA, NANOG, FOSJUN were the top 3 TF’ enriched for upregulated genes in three out of the four datasets. Using the TF data, the upstream analysis identified CXCL8, SELE, PTGS2, FCGR3, TFPI2 as the top five MTRs. Next, we showed that of the 5 MTRs, only TFPI2 (tissue factor pathway inhibitor 2) were significantly upregulated in an IBD-like in vitro model (normal rectal epithelial cell line: CRL1831 +TNFa). siRNA-mediated knock-down of TFPI2 in this model resulted in a significant decrease in genes including TNFAIP6, TNFAIP3, FCGR3B, BIRC3 and CXCL5, all of which were predicted in silico to be upregulated by TFPI2 during the upstream analysis. Intriguingly, we showed that downregulation of TFPI2 resulted in significant amelioration of pro-inflammatory cytokines including IL1β, IFNγ, IL10, IL13, IL6 and IL8.

Conclusion

Our study for the first time identifies key MTRs such TFPI2 which acts as a master regulator of genes whose upregulation drives poor response to IFX. Therefore, these results warrant further in vitro/ex vivo investigation to rationalise their role of TFPI2 as a potential therapeutic target, whose perturbation in UC patient would likely result in improved response to IFX.Read more P011 Altered Expression and Enzymatic Activity of Xanthine Oxidase in Inflammatory Bowel DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Xanthine oxidase (XO) is involved in the last steps of purine metabolism; indeed, it catalyzes the oxidation of hypoxanthine to xanthine and xanthine to uric acid (UA) with the production of superoxide anion. The accumulation of UA has been shown to initiate the inflammatory process through NLRP3 inflammasome and the production of reactive oxygen species (ROS) contributes to inflammation-related tissue damage. In murine models of colitis, XO inhibitors, allopurinol or febuxostat, reduced the expression of proinflammatory cytokines supporting the involvement of XO in the intestinal inflammatory process. This study aims to conduct a thorough investigation of the role XO plays in IBD pathogenesis and to explore the potential of XO inhibition as a therapeutic strategy.

Methods

Biopsies from the colon of patients with ulcerative colitis (UC) and Crohn’s disease (CD) were collected at University Hospital of Cagliari. Disease activity was assessed using Mayo and SES-CD scores. XO expression levels were evaluated using Real-Time PCR, validated by GEO database (GSE11223, GSE117993). XO enzymatic activity was quantified spectrophotometrically in protein extracts from the biopsies. XO and NLRP3 inflammasome activation pathway, including NLRP3, ASC, and CASPASE1, was investigated using immunohistochemistry (IHC). In vitro, Caco2, HT29, SW480 cells were treated with xanthine, XO inhibitors (allopurinol, febuxostat) to assess XO inhibition on NLRP3 activation, analyzed by immunocytochemistry (ICC).

Results

Biopsies from the sigmoid colon of 15 HC, 20 UC, and 15 CD patients, as well as from the ileum of 10 HC and 10 CD, were analyzed. Increased XO expression was found in UC and CD sigmoid mucosa (Relative Quantification [RQ]: 1.93 vs. 0.99, p=0.004), and CD ileum (RQ: 2.72 vs. 1.26, p=0.004), confirmed by GEO data. XO activity was higher in UC and CD sigmoid (3.86 nmol UA/min/mg in UC, 4.82 in CD vs. 1.03 in HC, p<0.001) and CD ileum (8.41 vs. 1.83 in HC, p<0.001). IHC confirmed that XO and the NLRP3 inflammasome pathway are more highly expressed in IBD patients than HC, predominantly within epithelial cells. In vitro studies on Caco2, HT29, and SW480 cells demonstrated that suppressing XO activity with XO inhibitors leads to the inhibition of the NLRP3 pathway.

Conclusion

XO expression was higher in IBD pts than in HC individuals. Alongside this increase in XO activity, there was a concurrent hyperactivation of the NLRP3 inflammasome. The inhibition of XO activity in cell lines resulted in reduced activation of the NLRP3 inflammasome pathway. These findings support the hypothesis that XO plays a critical role in the pathogenesis of IBD and highlight its potential as a therapeutic target.Read more P012 Intestinal epithelial cells as targets of thiopurines in Inflammatory Bowel Disease paediatric patients-derived organoidsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Thiopurines, azathioprine (AZA) and mercaptopurine (MP), are immunomodulators used to maintain remission in patients with inflammatory bowel disease (IBD). Intestinal epithelial cells play a key role in the pathogenesis of IBD, however, their role as target cells for thiopurines has not been elucidated. The aim of the project is to establish an in vitro IBD model using organoids starting from intestinal biopsies of IBD paediatric patients to investigate thiopurine effects on intestinal epithelium.

Methods

Forty-four IBD patients (mean age 14.4 years, 21 males) were enrolled. Intestinal biopsies were used to isolate crypts and generate adult stem cell-derived organoids. The cytotoxicity of thiopurines (0.2-200 µM for 72 hours) was evaluated by CellTiter-Glo 3D assay. Gene expression was evaluated using TaqMan assays. Thiopurine metabolites were quantified by LC-MS/MS analysis. Proteomic profiles were analyzed by Q-Exactive Plus mass spectrometer, western blot and REACTOME pathway software. Statistical analysis was performed using GraphPad and R software.

Results

IBD patients-derived organoids were sensitive to thiopurine treatment in a dose-dependent manner with a high interpatient variability (Two-way ANOVA p-value<0.0001; IC50 2.24 µM for AZA (95% CI: 1.28–5.53 µM) and 2.65 µM for MP (95% CI: 1.43–8.27 µM)).A significant negative correlation was observed between the viability after thiopurine exposure and mRNA expression of candidate genes involved in thiopurine pharmacokinetics (ITPA, TPMT, PACSIN2 and NUDT15). The most abundant thiopurine metabolite measured on organoids treated with IC50 of MP was MeTIMP, with a concentration correlated with cell viability after MP exposure (p=0.0056, ρ=-0.99). Proteomic analysis on organoids treated with IC20 of thiopurines (0.2 μM) showed 45 differentially expressed proteins in common between AZA and MP (p<0.05). REACTOME enrichment analysis revealed as the most altered pathways: vesicular traffic, autophagy, protein ubiquitination and interferon signalling, while no proteins related to apoptosis were induced. Among these proteins, TRIM32, a ubiquitin ligase involved in STING activity, a key regulator of both interferon I expression and NF-kB activation, resulted downregulated by the treatment (t-test AZA: p=0.0006; MP: p=0.014) and its basal levels negatively correlated with viability rates after thiopurine exposure (AZA: p=0.006, ρ=-0.85; MP: p=0.002, ρ=-0.88). Organoid exposure to thiopurines also decreased p-STING/STING ratio, particularly after MP treatment (t-test p=0.025), and increased autophagy, assessed as LC3-II levels (t-test AZA: p=0.0006; MP: p=0.014).

Conclusion

Organoid cultures provide new insights on the mechanism of action of thiopurines in the intestinal epithelium.Read more P013 Magnetic Resonance Imaging-Based Average T2 Signal as A Non-Invasive Measure of Fibrosis In Enteric Crohn’s DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

In Crohn’s Disease (CD), 10% of patients present with fibrostenosis with a further 10% progressing from inflammatory to a fibrostenotic disease behaviour over 7 years. 40% of fibrostenotic CD patients need surgery at 5 years compared to ~10% with inflammatory disease. Present non-invasive fibrosis biomarkers lack the required accuracy needed to be used routinely for clinical decision making. T1, T2, diffusion weighted imaging, motility and bowel volumes have shown promise in the non-invasive measure of fibrosis.

Methods

The primary objective of this study is to undertake biological validation of MRI measures as independent imaging biomarkers of histological fibrosis with the primary outcome being the correlation between MRI measures and histological fibrosis measures. GI-Seg (Motilent, London, UK) is an image analysis tool used to segment the gastrointestinal tract on T2W MRI scans.Patients with CD histological diagnosis and in need of surgical resection for stenosis attended a one-hour 3T MRI scanning session within 12 weeks prior to their intestinal resection surgery. Histological samples were scored by a specialized gastrointestinal pathologist for inflammation, fibrosis, and muscular hypertrophy. An expert radiologist with the help of the histopathologist located the strictures on DWI, quantitative T2&T2 scans, and T2 weighted clinical MRI scans. GI-Seg was used to generate a 3D model of the stricture on T2W scans measuring bowel wall volume and average signal intensity of each stricture. Pearson correlation coefficient was used to quantify the correlation between the variables.

Results

A total of 10 CD patients, encompassing 20 strictures, were included in the study. The analysis revealed that the average T2 signal has a significant correlation with global fibrosis scores (r(20) = .563, p = .010) (Figure) and total inflammation scores (r(20) = .451, p = .046). Additionally, stricture volume showed a fair correlation with chronic inflammation component scores (r(20) = .453, p = .045). Notably, quantitative T1 values correlated with total inflammation scores (r(17) = .493, p = .045).

Conclusion

The study reveals fair correlations between the T2 signal average and both global fibrosis and global inflammation scores, as well as between stricture volume and chronic inflammation in CD strictures. While these findings indicate that the GI-seg tool's measurements of bowel wall volume and signal intensity have potential utility as imaging biomarkers for fibrosis and inflammation, the results also underscore the necessity for additional markers that are specifically correlated with fibrosis. Such markers are essential to distinctly identify fibrotic changes, independent of inflammatory processes.Read more P014 First-time-in-human visualisation of CCR9 expression in the gut by positron emission tomographyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

CCR9/CCL25 is the key axis for recruiting lymphocytes to the small intestine and represents a potential treatment target in Crohn’s disease (CD). AZD7798 is a first-in-class monoclonal antibody for CD that depletes CCR9+ lymphocytes. Monitoring CCR9+ cell depletion and repletion in the blood is straightforward, but difficult in the primary tissues of interest (small bowel, mesenteric lymph nodes) which require invasive procedures to access. For AZD7798, an understanding of pharmacodynamics in gut is crucial to guide further clinical development. To address this need, we have developed a CCR9-specific PET tracer based on the small molecule CCR9 antagonist vercirnon.

Methods

Specific binding of [³H]vercirnon was assessed in-vitro using autoradiography. Specific binding and dosimetry of [¹¹C]vercirnon was assessed in-vivo in cynomolgus monkeys.Subsequently, a first-time-in-human study (NCT05818514) was performed in healthy volunteers to assess the biodistribution, binding to CCR9 in abdominal regions of interest, and safety of [¹¹C]vercirnon, administered intravenously at microdoses (<10μg). Two PET-CT examinations were performed 14 days apart to assess reproducibility.

Results

In-vitro specific binding of [³H]vercirnon to CCR9 was confirmed in human thymus sections and CCR9-expressing cell pellets.In-vivo specific binding of [¹¹C]vercirnon to CCR9 was putatively demonstrated in the gut of non-human primates (NHPs) in pre-treatment/displacement studies with excess unlabelled vercirnon (20mg/kg).8 healthy volunteers (5 male) were enrolled in the FTIH study. Detectable intestinal uptake of [¹¹C]vercirnon was demonstrated in all participants (Figure 1) with mean±SD standardised uptake value ratio (SUVR) 1.4±0.6 (reference abdominal aorta), and a proximal to distal gradient (SUVR jejunum 1.8±0.7/ileum 0.9±0.4/colon 0.6±0.2) consistent with CCR9 gene expression data. Test-retest variability of intestinal uptake was 9.6% (intraclass correlation coefficient 0.96), in line with values for other clinically useful PET tracers.Mean±SD injected radioactivity per PET examination was 351±105 MBq, corresponding to a radiation exposure of 1.4 mSv. This low radiation exposure (c.f. conventional FDG PET ~9 mSv) allows multiple PET examinations per participant. Administration of [¹¹C]vercirnon was well-tolerated with no serious adverse events.

Conclusion

We have developed a CCR9-specific PET tracer which potentially enables repeatable quantification of CCR9 expression in the gut. Ongoing studies will assess the effects of AZD7798 on CCR9+ cell depletion/repletion in the gut, providing critical data to support the clinical development programme.Read more P040 Prediction of endoscopic features of disease from single-cell RNA sequencing data in sigmoid colon of patients with ulcerative colitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Patients suffering from ulcerative colitis (UC) have reduced life qualities and an increased risk of developing cancer. Current treatment options are limited and have a ceiling effect with remission rates of ~35%. A possible reason is the multi-factorial aetiology, which are associated with an overactivation of the immune system and a dysbiosis of the gut microbiome. An important step towards a better understanding is the characterization of epithelial lesions. Their severity is classified by the Mayo score system based on their macroscopic appearance. While previous studies analysed cellular changes within the colon in UC patients, a detailed characterization of different UC-associated lesions are still missing, which is the aim of our study in collaboration with Sanofi Pharmaceuticals.

Methods

We recruit patients with active disease at our endoscopy unit and collect different biopsies from multiple regions within these patients to compare the reproducibility of single cell RNA sequencing (scRNAseq) results of similar appearing lesions within and between patients. For the sample preparation, we include a cellular enrichment step for immune, epithelial and stromal cells before performing 10x scRNAseq to obtain equal numbers for each cell fraction from every sampled area.

Results

Our cellular isolation strategy allows successful recovery of fibroblast, epithelial and immune cell fractions from each lesion. All expected epithelial cell types as previously described are detected in our dataset as well. Moreover, our experimental setup to obtain comparable numbers of fibroblasts, epithelial and immune cells enables us now to investigate cell-cell communication differences within different Mayo score lesions. For example, CXCL signal increased with the severity of macroscopic lesions and involves multiple cell types.

Conclusion

Our preliminary results promise exciting insights into cell-cell communications at an unprecedented depth, which identifies aberrant signalling pathway that may contribute to treatment failure in the clinics.Read more P041 Assessment of Serum Biomarkers associated with Vedolizumab Therapy Response in Inflammatory Bowel DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Vedolizumab (VDZ) is an anti α₄β₇-integrin inflammatory bowel disease (IBD) therapy postulated to reduce immune cell trafficking to the intestine. A significant proportion of patients fail to respond to VDZ. We aimed to assess the effect of VDZ on a panel serum inflammatory proteins (IPs) during induction therapy for IBD with the aim of identifying a serum biomarker of VDZ therapy response. We also aimed to gain further insights in VDZ mechanism of action by evaluating changes in serum IP concentrations during induction.

Methods

Patients commencing VDZ for IBD were prospectively recruited. All received standard VDZ induction. Baseline and week 6 serum concentrations of 54 IPs were measured by ELISA (Meso Scale Discovery, USA). Clinical outcomes were evaluated at weeks 14 and 30 of VDZ therapy. Corticosteroid-free remission (SFR) was defined as persistence of VDZ therapy, absence of corticosteroid therapy, a partial Mayo score ≤1 Ulcerative Colitis (UC) or HBI <5 Crohn’s Disease (CD). The associations between baseline serum IP concentrations and VDZ therapy outcome at weeks 14 and 30 were evaluated. Changes in IP concentrations from week 0 to week 6 of VDZ therapy were assessed. P values <0.05 following multiple test correction were considered significant in all analyses.

Results

Thirty-nine patients were included: 51% male, 51% UC, median [range]: age 52 [18.2-75.8] years; disease duration 13.4 [0.4–40.8] years; clinical Mayo subscore 4 [0–9]; and HBI 7 [1–20]. 28(72%) had received prior anti-TNF therapy. In univariate analysis, at higher baseline serum TNF-β concentration and lower IL-22, VEGF-C, and IL-7 concentrations were associated with week 14 SFR, p values p=0.003, 0.034, 0.042, and 0.045 respectively. Higher baseline serum IL-4, MDC and MCP-4 concentrations and lower baseline IL-10 concentration were associated with week 30 SFR, p=0.011, 0.026, 0.028 and 0.03 respectively. Significance was not maintained after correction for multiple testing. From baseline to week 6 post VDZ initiation, significant increases were observed in the concentration of six IPs: bFGF, eotaxin, eotaxin-3, MIP-1β, TARC and TNF-β, p=0.034, 0.0012, 0.0013, 0.043, 0.015 and 0.0077 respectively; and a significant decrease in one IP, IL-15, p=0.0004. The significant changes observed in IL-15, eotaxin, and eotaxin-3 concentrations from baseline to week 6 following VDZ initiation remained significant after multiple test correction.

Conclusion

No serum inflammatory protein was identified as a biomarker of SFR in patients receiving VDZ therapy for IBD. VDZ was observed to significantly affect serum IPs known to be involved in chemotaxis. Further study is required to identify biomarkers of VDZ therapy response.Read more P042 Significant correlation between intestinal ultrasound and magnetic resonance enterography for assessing disease activity and complications in Crohn’s diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The advantages of intestinal ultrasound (IUS) over magnetic resonance enterography (MRE) include wide availability, low cost, and the possibility of being point-of-care. We here aimed to compare the performance of IUS with MRE for assessing disease activity and complications in Crohn’s disease (CD).

Methods

Prospective longitudinal study of CD patients starting anti-TNF therapy. IUS and MRE were performed at baseline (W0) and after 1 year of infliximab therapy (W54). Bowel wall thickness (BWT) of the most affected segment (MAS) was measured in both exams (average of 4 measurements) and compared. Transmural response (TR) was defined as a reduction in 25% of BWT. All MRE were centrally reviewed by a blinded radiologist.

Results

We included 48 CD patients (48% male; median age 31 years, IQR 26-44). Ileum was the most commonly affected segment in 63% of the patients. At baseline the agreement between the two methods to select the most affected segment was moderate (k=0.581, p<0.001). At W54, 50% of patients had TR in IUS and 40% in MRE. After 1 year of therapy there was a significant decrease in median BWT in both methods (IUS: 4.88mm vs 3.22mm, MRE: 8.21mm vs 4.91mm, both p<0.001). We found a significant association between the two methods in detecting intestinal complications (stricturing or penetrating disease) on both timepoints (W0: 31.25% vs 21.73%; p<0.001; W54: 17.78% vs 20.83% ; p=0.004), and also a significant moderate to high correlation between BWT measured by IUS and MRE on both timepoints (W0:r=0.34, p=0.02; W54:r=0.58; p<0.001). The correlation was higher when the MAS was the ileum (W0 and W54: r=0.65, p<0.001).

Conclusion

We found a moderate to good agreement in the selection of MAS between IUS and MRE. There was also a moderate correlation between BWT measurements and detection of complications between the two methods, which increased when the MAS was the ileum. Our results suggest that IUS, a readily available and inexpensive tool, is accurate to evaluate disease activity and treatment response, particularly in patients with ileal disease.Read more P043 RIPK3 – a new marker for assessment of activity in Crohn’s diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

RIPK3 (Receptor Interacting Protein Kinase-3) is a key molecule involved in the process of necroptosis. Necroptosis is a regulated form of cell death that involves the activation of specific signaling pathways leading to cell lysis. The released endogenous molecules - DAMPs (Danger Associated Molecular Patterns) activate the immune system and lead to inflammation. This relationship suggests a role for necroptosis in the pathogenesis of IBD (Inflammatory Bowel Disease).

Methods

The aim of the study was to evaluate RIPK3 expression in patients with Crohn's disease (CD) according to disease activity and some clinical parameters. Tissue expression of RIPK3 in the inflamed areas of 85 patients with Crohn's disease was determined immunohistochemically. The CDAI (Crohn’s Disease Activity Index) was used to assess activity, and the Montreal Classification to determine disease location and bahavior.

Results

A correlation was found between RIPK3 expression and CDAI (p=0.038), with patients in remission having the lowest expression (154.67), while patients with severe activity had overexpression of the marker (180.0) (Fig.1).According to the localization of CD, a significant difference was found in the expression of RIPK3 (p<0.05), with the highest expression of the marker in the ileum (L1) and colon (L2) with involvement of the upper GIT (L4) – L1+L4 (225.50) and L2 + L4 (218.00). Isolated involvement of terminal ileum (L1) was characterized by the lowest expression of the marker, while patients with colonic localization (L2) had high expression of RIPK3 (184.87).Regarding disease behavior, it was found that the highest expression of the marker is in the patients with phenotype B2+B3 – both stricturing and penetrating disease, followed by inflammatory disease (B1) (Fig.2). Perianal disease further increased RIPK3 expression, with patients with concurrent perianal disease showing high expression of the marker (181.85 vs. 167.86 for those without perianal disease; p<0.05).

Conclusion

High RIPK3 expression in CD patients correlated with severe disease activity as measured by CDAI, involvement of upper GIT - L1+L4 and L2+L4, stricturing with penetrating disease - B2+B3 and concurrent perianal disease.Read more P052 Mucosal IgG-like naive B-cell expansion and maturation contribute to ulcerative colitis pathogenesisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

A higher abundance of colonic naive B-cells and IgG plasma cells is implicated in the pathogenesis of ulcerative colitis (UC) during active inflammatory episodes. However, B-cell inhibition by targeting CD20 was found to be ineffective in achieving remission in UC patients indicating that the causal role of the B-cell expansion in UC is not well understood. In this study, we performed single cell RNA-sequencing (scRNA-seq) on mucosal tissue where we interrogated the B-cells in inflamed and non-inflamed UC colon biopsies. We subsequently explored the pathogenic role of B-cells in colitis mouse models.

Methods

We collected biopsies from the colon of 5 UC patients with active inflammation and 5 UC patients showing no inflamed mucosa. Three mucosal biopsies were collected from the same colon location for each patient and processed for scRNA-seq. We acquired usable transcriptomes of 21.475 cells. In a T-cell transfer colitis mice model, we evaluated the effects of the co-transfer of naive B-cells. Both CD4⁺ T and naive B-cells were transferred into SCID mice through intraperitoneal injection in ratios of 2:1, 1:1 and 1:2 (T:B ratio). The colitis course was followed for 35 days.

Results

Differential abundance analysis relative to all immune cells confirmed a higher abundance of naive B-cells (p= 0.03) and IgG plasma B-cells (p= 0.002) in inflamed relative to non-inflamed UC patient tissue, whereas no differences in abundance of transitional B-cells and memory B-cells were found. Pseudo-time analysis indicated a higher rate of maturation in the naive B-cells in inflamed tissue. This was evidenced by higher expression of IGHG1 (p= 0.025) and IGHG3 (p< 0.001) in naive B-cells in inflamed tissue. In a T-cell transfer model, we co-transferred naive B-cells to the CD4⁺ T-cell pool into SCID mice in various ratios (2:1, 1:1 and 1:2 T to B-cells respectively) and T-cell only control. Significant increase in disease severity was observed in a 1:2 T:B ratio based on body weight loss, increase of colon density, mouse colitis histology index and histological changes by disrupted mucosa. This observation was associated to significant elevated IgG concentration in serum and colon and B-cell presence in colon through immunohistochemistry.

Conclusion

We observed significantly higher abundance of naive B-cells and IgG plasma cells in inflamed relative to non-inflamed UC colon tissue, where naive B-cells were shown to be more mature and IgG-like in inflamed condition. Notably, transferring increased ratio of naive B-cells resulted in elevated disease severity in a colitis model, demonstrating its pathogenic role. Our findings suggest that specific targeting of the IgG-like naive B-cell may be beneficial for UC patients.Read more P053 Pro-resolution Pathway in Experimental Colitis – A New Possible Therapeutic Approach for Inflammatory Bowel DiseasesWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Inflammatory bowel diseases (IBD) are idiopathic disorders characterized by chronic inflammation of the gastrointestinal tract. New therapeutic strategies involving the inflammatory process are being proposed because the usual therapies indicated for IBD may cause adverse reactions and clinical failure. Recent studies have highlighted the role of specialized pro-resolution lipid mediators (SPMs) in the active resolution of chronic inflammation. Therefore, this study aimed to investigate the SPM Resolvin D2 (RvD2) and its precursor, omega-3 polyunsaturated fatty acid, in experimental colitis induced by dextran sulfate sodium (DSS).

Methods

An experimental model with male mice of the C57BL/6J lineage was carried out. Mice were separated into a control group, and a DSS-induced colitis group (3% dilution in drinking water); both groups were subdivided and received either a standard diet or an experimental diet enriched with 20% of oil rich in omega-3. Another group of mice, after acquiring experimental DSS-induced colitis, was subdivided and treated with RvD2 or anti-TNFα. Throughout the experimental protocols, the body weight, food intake, Disease Activity Index (DAI), metabolic phenotype, and inflammatory profile of these animals were assessed by real-time PCR, ELISA, histology, Western blotting, and lipid analysis. The study was approved by the University of Campinas research ethics committee.

Results

The animals with experimental colitis induced by DSS showed an increase in TNFα and IL22 transcriptional expression besides a reduction in the enzymes involved in the endogenous biosynthesis of RvD2, such as PLA2, 15-LOX, 5-LOX, and its receptor GPR18. Dietary supplementation with omega-3-rich oil increased RvD2 and its precursor besides reducing the DAI, weight loss, colonic shortening, and the histologic colonic inflammation score. Treatment with RvD2 effectively attenuated experimental colitis, reducing TNFα transcriptional levels and p-JNK protein expression. Besides, RvD2 increased the immediate precursor of RvD2 (7,8-epoxy-17-HDHA). All of which indicates that this pathway is responsible for the observed effects.

Conclusion

Our study provided a better understanding of the molecular mechanisms involved in the exacerbated inflammatory response present in colitis. The beneficial effect of RvD2 and its precursor omega-3 may bring about a new therapeutic approach for IBD.Read more P054 R. intestinalis improves inflammatory bowel disease by preventing gut uric acid absorption through inhibiting METTL3 mediated m6A modification of SLC2A9Wed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Inflammatory bowel disease (IBD) is a chronic inflammatory disease with persistent, recurrent, unsatisfactory response, and a poor prognosis. The incidence of Chinese IBD has increased rapidly, and Westernized diets such as purine-rich foods play an important role in its rapid growth. The alteration of purine-urate metabolism by microbiota may contribute to the development of IBD.

Methods

In this study, metagenomic and metabolomic analyses were performed on fecal samples from 30 untreated IBD patients and 30 healthy controls. R. intestinalis was used to observe the effect on serum uric acid levels in mice, respectively. Body weight, colon length, disease activity score, serum uric acid levels, and electron microscopy were all assessed. The RNAseq analysis of intestinal tissue from DSS-induced colitis mice intervened with R. intestinalis and co-cultured with R. intestinalis and the normal intestinal epithelial cell line NCM460, combined with m6A antibody dot blot assay, RM2Target database, and MeRIP sequencing data analysis, provided evidence that SLC2A9 was modified by METTL3, and SRAMP database predicted the potential for SLC2A9 mRNA to be modified by m6A after R. intestinalis intervention.

Results

Multi-omics analysis revealed that the abundance of R. intestinalis was significantly decreased in untreated IBD patients, and metabolomics revealed a correlation between high uric acid levels and disease severity, while the multi-omics integrated analysis suggested a significant negative correlation between R. intestinalis and uric acid. The research team confirmed that R. intestinalis can lower blood uric acid levels in mice and found that R. intestinalis intervention can alleviate the intestinal mucosal inflammation exacerbated by uric acid treatment in a DSS-induced mouse colitis model. Butyric acid has been reported to regulate m6A, and dot blot assays showed that R. intestinalis can reduce the m6A modification level of intestinal epithelial cells, METTL3, and SLC2A9. RM2Target database identified the protein-RNA interaction of the m6A regulator (WER) for SLC2A9 mRNA, and MeRIP sequencing data further indicated that METTL3 can bind to SLC2A9 mRNA through m6A modification. Meanwhile, based on sequence prediction, the research team identified 13 potential m6A modification sites on SLC2A9 mRNA, of which 4 sites had extremely high credibility . The highest credibility site had a score of 0.694, with a modification site sequence of GGACU located on an adenosine nucleotide.

Conclusion

R. intestinalis inhibit the METTL3 mediated m6A modification of intestinal epithelial SLC2A9, reducing the expression of SLC2A9, preventing the epithelial absorption of uric acid, and relieving IBD-related colitisRead more P055 GPR43 and GPR84 play a crucial role in supporting perianal fistula formation and disease progression in Crohn’s DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Fistula complication represents one of the most disabling manifestations of Crohn’s Disease and a risk factor for more aggressive disease progression and mucinous adenocarcinoma . However, molecular mechanisms behind this transformation are completely unknown. Growing evidence supported epithelial-to-mesenchymal transition (EMT) as a critical process to replace impaired intestinal fibroblasts in repairing mucosal membrane damage. However, EMT drivers during fistula formation and progression are still not completely known. Here, we investigated whether G-protein coupled receptors serve as new drivers of EMT and fistula disease progression.

Methods

Surgical specimens (N=9) collected from perianal fistula and non-involved areas of CD patients were analyzed by bulk RNA-sequencing and Lipidomics analysis. Gene set enrichment analysis (GSEA) was used to detect the levels of differentially expressed pathways. GPR43 and GPR84 analysis was performed on perianal fistula; adenocarcinoma; and mucinous adenocarcinoma-associated (MA) CD fistula FFPE tissue section. Caco-2 cell line was stimulated for 24 h with agonists and antagonists of GPRs. Genes associated to EMT were evaluated by RT-PCR and WB.

Results

Gene sets related to the signatures of epithelial-to-mesenchymal transition, G-protein coupled receptors (GPRs), immune response, lipid oxidation were significantly enriched in the fistula compared to non-involved tissue. Among differentially GPRs expressed genes FFAR2 encoding for GPR43, sensor for Small Chain Fatty Acids (SCFAs), and GPR84 sensor for Medium Chain Fatty Acids (MCFAs), predominantly expressed in immune cells, reported to be upregulated in the context of acute inflammation. Upregulation of GPRs expression correlated positively with enzymes associated to lipid oxidation gen set including PLA2G2D, ALOX5, NR4A3, PLA2G7, ACOXL and negatively with their lipids substrates. Caco2 cells stimulated with SCFAs and MCFAs upregulated not only the expression of GPR43 and GPR84, but also of EMT-transcription factor Twist1 and PLA2G2D, all effects reverted in the presence of their antagonists. An increase expression of GPR43 and GPR84 in association with Twist1 was found in MA-CD tissue section.

Conclusion

Our results highlighted GPR43 and GPR84 as new potential factors of fistula formation that support the EMT process through increased fatty acid oxidation, which in turn fuels the activation of GPRs. However, the increase expression of both receptors in the fistula oncogenic disease progression suggests that strategies regulating lipid metabolism or targeting GPRs could pave the way for novel therapeutic approaches to prevent fistula complication in CD patients.Read more P056 Cereal intake and diet-related microbial metabolites in faeces associate with recurrence of gut inflammation during food reintroduction in children with Crohn’s disease treated with exclusive enteral nutrition; iPENS a multicentre, prospective studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Faecal calprotectin (FCAL) rises rapidly in children with Crohn’s disease (CD) following treatment with exclusive enteral nutrition (EEN). We aimed to identify clinical, dietary and diet-related microbial metabolites which associate with the recurrence of FCAL above 250 mg/kg after 21 days of food reintroduction.

Methods

Children with CD (age 6-17 years), clinically responding to EEN, were recruited, prospectively, from 11 UK hospitals (January 2020-May 2023, NCT04225689). They provided a single faecal sample before EEN completion (timepoint A) and 6 serial samples (timepoints B-G; 3, 6, 9, 12, 15, 21 days) in the first 21 days of food reintroduction. Faecal short (SCFA) and branched (BCFA) chain fatty acids were measured as proxies of fibre and protein bacterial fermentation, respectively. In faeces, pH, water content (%), Bristol stool score, total microbial load (qPCR) and starch output were measured. Clinical parameters, medications, CRP, ESR, albumin and anthropometry were recorded at EEN completion. Nutrient and food group intake was analysed with Nutritics®. Relationships with FCAL levels were explored.

Results

Thirty children provided 209/210 (99%) of expected faecal samples. FCAL (median [Q1, Q3], mg/kg) increased within 12 days of food reintroduction (EEN completion: 328 [154, 2370] vs 12 days post-EEN: 1123 (451, 2073), p<0.01) and remained high throughout follow-up. Negative correlations were observed between FCAL with acetate, whereas positive correlations were noted with BCFA (isovalerate and isobutyrate) and their ratio over acetate; the latter remained significant at all 7 timepoints (Figure 1A). Use of immunosuppressants, blood inflammatory markers, clinical and anthropometry at EEN completion were not predictive of FCAL increase post-EEN.In a subset of patients with FCAL<250 mg/kg at EEN completion, (n=13/30), subset regression using ‘end of EEN’ diet-related microbial data, generated a model with 91% accuracy to predict FCAL increase over 250 mg/kg at 21 days of food reintroduction, with isovalerate being the sole predictor of FCAL recurrence (Figure 1B). Average intake of cereal products (median [Q1, Q3], g/day) over 21 days was lower in patients who experienced an FCAL recurrence (FCAL<250mg/kg: 313 (223, 370) vs FCAL>250mg/kg: 186 (167, 217), p=0.013). Positive correlations were observed between the 21-day average intake of cereal products and concentration of SCFA at 21 days post-EEN; acetate (rho=0.38, p=0.041), butyrate (rho=0.46, p=0.0.01) and total SCFA (rho=0.41, p=0.026).

Conclusion

This study suggests that early FCAL rebound, following treatment with EEN, is related to an increased ratio of dietary protein to fibre bacterial fermentation and a lower intake of cereal products.Read more P057 Caudovirales may trigger molecular mimicry mechanisms in Crohn’s DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The gut virome is known to play a role in the development of Crohn's disease (CD), a type of Inflammatory Bowel Disease (IBD). Several years ago, Norman and colleagues observed an expansion of Caudovirales linked to CD pathogenesis, alongside a reduction in bacterial diversity. To delve deeper, we exploited the IBD TaMMA framework and observed a significantly higher abundance of Caudovirales in the CD individuals compared to healthy controls, confirming earlier findings.

Methods

To further examine the involvement of this viral species in various mucosal cell compartments, we conducted flow cytometry cell sorting (FACS) on intestinal biopsies from CD and healthy individuals. Isolated immune and non-immune cells based on population-specific markers, including CD8 and CD4 T cells, B cells, macrophages, dendritic cells, epithelium, endothelium, and fibroblasts underwent transcriptomics and metatranscriptomics.

Results

We identified higher abundance of the Proteus virus Isfahan, belonging to Caudovirales viral order, in CD dendritic cells and CD macrophages compared to their healthy counterparts. Notably, gene ontology (GO) analysis indicated that only CD dendritic cells, fibroblasts, and epithelial cells exhibited compromised biological responses to viral insults compared to their healthy counterparts. In contrast, CD macrophages displayed upregulation of molecular pathways regulating viral processes. This suggests that virome dysbiosis in these cells may contribute to CD pathogenesis by altering their biological functions. We thus wondered whether Proteus virus Isfahan encoded proteins had similarities with the human ones, somehow establishing molecular mimicry justifying the likelihood of the autoimmune nature of CD. We observed sequence homology in the Proteus virus Isfahan and the human thymidylate synthase, RECQ-like DNA helicase, and dCMP deaminase. These viral proteins are likely to be recognized by the immune system by sharing similarities with the human homologs, thus activating autoreactive immune response and establishing the persistent chronic inflammatory environment within CD mucosa. Experiments employing T helper cells in coculture with Proteus virus Isfahan proteins-overexpressing innate immune cells are ongoing to prove the autoreactive activation of the host’s immunity.

Conclusion

Given the growing evidence of viral entities as triggers for IBD, these data could pave the way for discovering viruses directly involved in CD pathogenesis and serving as the booster for molecular mimicry mechanisms, finally providing potential targets for novel intervention strategies that may improve CD management.Read more P058 The identification of three linear epitopes on infliximab all map to complementarity-determining regionsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Infliximab (IFX) is a mainstay of treatment for inflammatory bowel disease (IBD). Its use is limited by the development of anti-drug antibodies (ADA), which can cause loss of response and adverse drug reactions. The antigenic epitopes have not been clearly defined, and large antigenic areas suggested. The aim of this study was to identify clinically relevant distinct epitopes in IBD patients treated with IFX with ADA and different clinical outcomes.

Methods

Sera were pooled from 8 ADA positive IBD patients (ADA >10 AU/mL; IDKmonitor® Infliximab total ADA) treated with CT -P13 (Remsima® Celltrion Inc., Korea) exhibiting: loss of response, response with therapeutic drug levels, response with subtherapeutic drug levels and adverse drug reactions. A novel whole gene fragment library (GFL) was synthesised using pools of overlapping synthetic oligonucleotides covering the IFX heavy chain and light chain (Twist Bioscience, California, United States). This was cloned into a phage display vector to generate a library >10⁶ clones. Three rounds of selection of the GFL were performed using pooled sera. DNA from the selection outputs were analysed by next generation sequencing (NGS) (Illumina, San Diego, United States). Outputs from one round of selection using individual sera were also analysed by NGS.

Results

ADA ranged 17->600 AU/mL. 23,383 gene sequences analysed from the GFL showed complete coverage of the IFX gene. After three rounds of selection, DNA sequencing showed the enrichment of three peptides – all overlapping the IFX complementary-determining regions (CDR)- Figure 1. The three peptides enriched: heavy chain peptide 1 included heavy chain CDR 1, light chain peptide 2 overlap light chain CDR 1 and light chain peptide 3 overlap light chain CDR 2. NGS assessment of the outputs from round 1-3 using pooled ADA positive sera confirmed enrichment of the three peptides. NGS analysis of the selections on individual sera showed differences in enrichment profile of the three peptides.

Conclusion

Using ADA positive sera from IBD patients treated with IFX with differing clinical outcomes, three linear epitopes were identified from a novel whole IFX-GFL. All epitopes overlapped with CDRs which is consistent with being potential sites for neutralising ADA. NGS has suggested that individual ADA positive sera have differing recognition profiles for the selected epitopes. Identifying distinct epitopes may lead to the identification of a biomarker for loss of response to infliximab.Read more P059 GSDMB triggers intestinal inflammation via regulating BHLHA15-mediated hyperactive unfolded protein responseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Impaired intestinal epithelial barrier has been considered to be associated with an increasing variety of gastrointestinal diseases, especially inflammatory bowel disease (IBD) encompassing Crohn’s disease (CD) and ulcerative colitis (UC). Herein, we investigated the role of Gasdermin B (GSDMB) in modulating intestinal epithelial barrier integrity and proposed a promising therapeutic strategy.

Methods

We generated GSDMB (GSDMBfl/fl;Villin-Cre) intestinal epithelial-specific knock in mice to observe the functions of GSDMB in intestinal epithelial barrier. RNA-seq analysis and human and murine intestine-derived organoids were used to determine the mechanism of function of GSDMB.

Results

To interrogate the intestinal functions of GSDMB in vivo, we generated GSDMB conditional knock in mice (heterozygote: GSDMBfl/-;Villin-Cre; homozygote: GSDMBfl/fl;Villin-Cre) by crossing a mouse line containing the floxed alleles of human GSDMB and a transcriptional stop codon at the transcriptional initiation site (GSDMBfl/fl) with the mouse line expressing Cre-recombinase under control of the Villin promoter (Villin-Cre). GSDMBfl/fl;Villin-Cre mice developed spontaneous enterocolitis and exhibited aberrant intestinal barrier integrity (as shown in the figure). GSDMB prominently provoked cell death of absorptive enterocytes and affected the function of goblet cells and Paneth cells in this setting. Mechanistically, epithelial GSDMB modulated hyperactive unfolded protein response of IECs by up-regulating BHLHA15 to mediate intestinal barrier injury instead of by the invasion of pathogenic microorganisms.

Conclusion

We have uncovered an important and a previously unrecognized role of GSDMB in intestinal inflammation, which represents a potential therapeutic target for IBD.Read more P113 Differentiation between active and quiescent Ulcerative Colitis using a novel wearable patch with self-adhesive dry electrodes: discriminating the role of heart rate variabilityWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The autonomic nervous system (ANS) maintains homeostasis of the gastrointestinal tract through the brain-gut axis. Previous studies have shown a dysregulated balance between the sympathetic and parasympathetic nervous system in Ulcerative Colitis (UC) patients, in particular during and preceding active disease. This leads to decreased vagal nerve activity and manifests in reduced heart rate variability (HRV). HRV could, therefore, potentially serve as quantitative non-invasive biomarker to differentiate active from quiescent UC. We aimed to increase our understanding of autonomic function in UC, by investigating a non-invasive wearable patch device measuring HRV to assess the difference in parasympathetic and sympathetic activity between active and quiescent UC, while correcting for HRV-modulating factors depression, anxiety and fatigue.

Methods

A proprietary vital signs patch with self-adhesive dry electrodes was used to acquire ECG (single lead) and bio-impedance (2 leads) in 26 UC patients for 72 hours continuous home monitoring, to calculate heart rate, respiratory rate and HRV. Fifteen patients had quiescent UC (SCCAI ≤ 2, CRP < 5mg/l, faecal calprotectin < 250µg/g) and eleven had active disease (SSCAI > 2, CRP > 5mg/l, faecal calprotectin > 250µg/g). Patients filled out the Multidimensional Fatigue Inventory and Hospital Anxiety and Depression Score questionnaires on fatigue, depression and anxiety, kept sleep diaries and provided feedback on patch usability. Time-domain (pNN50, RMSSD, for abbreviations see Figure 1), frequency-domain (high (HF), low (LF), LF/HF ratio), as well as non-linear (SD1, SD2, SD) HRV metrics were calculated for 5-minute segments during self-reported nocturnal sleep periods.

Results

No significant differences were found in fatigue, depression, and anxiety in the active and quiescent UC patient groups. Six HRV measures were significantly lower in active than in quiescent disease (p<0.001, Figure 1), indicating lower HRV and lower vagal parasympathetic tone. LF/HF ratio did not differ (p=0.242, Figure 1), reflecting no difference in ANS balance. The patch caused skin irritation in 72% of the patients. Nevertheless, 69% of patients indicated they would wear it again.

Conclusion

A wearable vital signs patch, utilizing ECG, is able to distinguish active from quiescent UC in patients matched for fatigue, anxiety, and depression. HRV metrics across all three domains, except LF/HF ratio, were reduced in active UC, indicating reduced vagal nerve activity. Pending further longitudinal validation and clinical integration, it is envisioned that continuous HRV monitoring can support early and non-invasive detection of relapses in UC, allowing timely intervention and prevention of severe symptoms.Read more P114 Role of NLRX1 Agonist NX-13 in Reducing Visceral Hypersensitivity in Preclinical Gastrointestinal InflammationWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

NLRX1 activation reduces inflammation by decreasing oxidative stress and altering cellular metabolism within multiple cell types implicated in ulcerative colitis (UC). Colitis animal models demonstrated reduced disease severity and a phase 1b clinical trial showed signs of rapid symptom and endoscopic improvement in patients with active UC.^{1, 2} Abdominal pain driven by visceral hypersensitivity may persist in patients even after inflammation has resolved, negatively affecting their quality of life.^{3, 4} Therapeutic agents which address inflammation, epithelial healing, and visceral hypersensitivity concurrently may provide greater symptomatic relief and improved quality of life as many patients, even in remission, still complain of abdominal pain. We here describe the effects of oral NX-13 in a rat model of visceral hypersensitivity.

Methods

Rats (n=8) were dosed daily for a period of 3 days with NX-13 or vehicle. Under anesthesia, electrodes were positioned to monitor oblique abdominal muscle contraction and a colonic balloon catheter was inserted intra-anally. Visceral pain was assessed at baseline and 3 h post lipopolysaccharide injection (1 mg/kg subcutaneous) through measuring of visceromotor response (VMR) via electromyogram (EMG) recording and visual assessment of abdominal withdrawal reflex (AWR). Data are represented as median (IQR) and statistical significance determined by non-parametric Mann-Whitney U test.

Results

Compared to the vehicle control, oral NX-13 delayed the onset of muscle contraction in response to colonic distension in LPS-treated rats. Further, NX-13 treated rats experienced reduced contraction intensity and reduced sustained abdominal muscle contraction period compared to the vehicle control. Specifically, NX-13 decreased the number of AWR during colonic expansion compared to the control group (p=0.01, Fig1A). Moreover, NX-13 desensitized the VMR response by numerically increasing the minimum volume of the colonic distension balloon required to induce significant VMR. The mean minimum volume of water injected required to induce significant VMR increased 23%, from 650 μL in the vehicle group to 800 μL in the NX-13 treated rats (p=0.16, Fig1B). Lastly, NX-13 visually reduced the maximum abdominal EMG amplitude during colonic distention (p=0.19, Fig1C).

Conclusion

Adequate management of persistent pain in IBD patients with or without active bowel inflammation remains an unmet need in the treatment of IBD. The potential for NX-13 to specifically reduce visceral hypersensitivity and abdominal pain will be evaluated further in the ongoing phase 2 human NEXUS trial in patients with UC.¹Leber et al. J Immunol 203(12)²Peyrin-Biroulet et al. JCC (17)Supp³Abreu et al. JCC (14)Supp⁴Wils et al. J Clin Med 11(15)Read more DOP46 Tofacitinib for hospitalized acute severe Ulcerative Colitis – the TRIUMPH studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Tofacitinib is a rapidly acting Janus kinase (JAK) inhibitor with several case series reporting effectiveness in patients with acute severe ulcerative colitis (ASUC). However, there remains a paucity of prospective data evaluating its efficacy and rapidity of onset in ASUC.

Methods

The TRIUMPH study is a phase 4 prospective interventional trial of tofacitinib in ASUC conducted in five hospitals across Canada (Clinicaltrials.gov: NCT04925973). Patients with ASUC (biologic naïve and experienced) refractory to three days of intravenous corticosteroids (Modified Truelove-Witts Severity Index [MTWSI] > 10 despite steroids) were eligible for enrollment. Patients were treated with tofacitinib 10mg bid and assessed daily while in hospital. The primary outcome was day 7 clinical response (MTWSI reduction of > 3 from baseline and < 10). Secondary outcomes included rapidity of clinical and biomarker improvements over the first 7 days, colectomy over the course of one year, and corticosteroid-free clinical remission (total Mayo score < 2), endoscopic improvement (endoscopic Mayo score 0 or 1), and adverse events at 3, 6, and 12 months.

Results

This is an interim analysis as the study has been fully recruited with six-month follow-up available for all participants. 24 patients with ASUC were recruited and received tofacitinib 10mg bid. The mean total baseline Mayo score was 10.1 (SD 1.4) and all patients had a baseline Mayo endoscopic subscore of 2 (25%, 6/24) or 3 (75%, 18/24). One third of the patients (8/24) had previous anti-TNF failure. Day 7 clinical response was achieved in 58.3% (14/24) patients. The mean number of days to achieve clinical response was 2.4 days (SD 1.3). Marked reduction in C-reactive protein was observed in responders as soon as one day after tofacitinib initiation compared to non-responders (Figure 1). Colectomy occurred in 16.7% (4/24) patients by day 7 and 25% (6/24) by six months. At six months, 45.8% (11/24) patients remained on tofacitinib (including 78.6% (11/14) of day 7 responders), with 33.3% (8/24) having achieved endoscopic improvement and corticosteroid-free clinical remission. A total of six patients reported adverse events, one of which was considered severe (stroke at day 3 after initiation of tofacitinib).

Conclusion

Tofacitinib may be an effective induction strategy in patients hospitalized with steroid-refractory ASUC. Randomized controlled trials are needed to compare JAK inhibitors with infliximab for steroid refractory ASUC.Read more DOP47 Characterisation of endoscopic improvement in Crohn’s Disease with upadacitinib treatmentWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Upadacitinib (UPA), an oral Janus kinase inhibitor approved for the treatment of moderately to severely active Crohn’s disease (CD), demonstrated significantly higher rates of endoscopic response and remission compared with placebo (PBO) in the phase 3 induction (U-EXCEL, U-EXCEED) and maintenance (U-ENDURE) trials.¹ Improvements in the narrowing component of BL stenoses with UPA have been previously reported.² This analysis evaluated changes in the individual components of the Simple Endoscopic Score for CD (SES-CD) among patients treated with UPA vs PBO.

Methods

Data were pooled from the two induction phase 3 studies evaluating patients who received PBO or UPA 45 mg (UPA45) once daily (QD) for 12 weeks. Patients who achieved clinical response to 12 weeks of UPA45 were re-randomised in the U-ENDURE maintenance study to receive PBO, UPA 15 mg (UPA15) QD, or UPA 30 mg (UPA30) QD for 52 weeks. This analysis evaluated the mean changes from baseline (BL) in total SES-CD and four individual components (size of ulcers, ulcerated surface, affected surface, presence of narrowing), as well as improvements by disease location and prior biologic failure (bio-failure) status.

Results

Mean [SD] total SES-CD at BL was similar across treatment groups (induction: PBO 13.9 [7.5], UPA45 14.6 [7.7]). In the overall population, mean [SD] changes from BL in total SES-CD were greater with UPA45 (–6.8 [7.6]) vs PBO (–0.5 [5.7]; P < .0001) at week 12, and at week 52 with UPA15 (–9.9 [8.6]) and UPA30 (–10.3 [8.1]) vs PBO (–2.4 [5.0]; all P < .0001; Figure 1A). Similar results were observed for patients with ileocolonic and colonic disease at week 12 and week 52 (Figure 1A). For patients with prior bio-failure, mean changes from BL in total SES-CD were greater with UPA45 (–6.6 [7.9]) vs PBO (0.0 [5.8]; P < .0001) at week 12, and with UPA15 (–10.4 [9.4]) and UPA30 (–9.7 [7.2]) vs PBO (–2.8 [4.8]; all P < .0001) at week 52; similar findings were reported for patients without prior bio-failure. At week 12 and week 52, treatment with UPA resulted in greater improvements vs PBO in the individual SES-CD components of size of ulcers, ulcerated surface, and affected surface, but not for the presence of narrowing (Figure 1B).

Conclusion

In patients with moderately to severely active CD, UPA induction and maintenance treatment vs PBO improved total SES-CD, irrespective of prior bio-failure. The changes were driven by the SES-CD components of the size of ulcers, ulcerated surface, and affected surface. When evaluated by disease location, appreciable improvements occurred in patients with ileocolonic and colonic CD, as compared to ileal disease.References:1. Loftus, E. V. et al. N. Engl. J. Med. 2023;388,1966–802. Reinisch, W. et al. UEGW 2023. MP005 [Poster]Read more P215 Mir-135b, an Early Biomarker of Sporadic and IBD-Related Colorectal Carcinogenetic ProgressionWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Although the rates of IBD-related-CRC are decreasing over time, CRC is still a leading cause of mortality and reason for colectomy in patients with IBD. Among the different cancer biomarkers, microRNAs (miRs) have emerged as noninvasive tools for diagnosis, monitoring, and prognosis in tissues and biofluids of patients with IBD. Therefore, we aimed to investigate the role of miRs in the development and natural course of IBD-related CRC, in order to identify potential early biomarkers for IBD-related CRC screening and progression.

Methods

The cases were retrospectively collected from the archives of the Surgical Pathology and Cytopathology Unit at the University of Padua. We analysed 9 miRs in colonic tissue specimens of IBD patients with adenoma or dysplasia, with IBD related-CRC, other than 2 control groups of patients with sporadic CRC and of healthy subjects (HC). In addition, we included tissue samples from a colonoscopy that patients with IBD with adenoma or dysplasia underwent some years before the development of mucosal lesions (from 2 to 5 years before), therefore without evidence of adenoma or dysplasia. Results were analyzed with ThermoFisher Connected™ Software and a p-value < 0.05 was considered significant.

Results

Compared to HC, all nine analysed miRs were significantly up-regulated in patients with sCRC, with IBD-related CRC and in IBD patients with adenoma. While, only 3 miRs (miR-135b, mir-21, miR-224) were significantly upregulated in IBD patients with dysplasia (and in their own controls) compared to HC (p<0.0001). Notably, no differences in miRs expression levels were found in patients with IBD-related CRC compared to those found in patients with sCRC. Among all miRs analyzed, only miR-135b and miR-21 resulted significantly up-regulated in patients with IBD. Considering the levels of miR-135b in the tissue samples of IBD patients, we observed an evident increasing trend going from tissue specimens without lesions to those with adenoma or dysplasia and then to those with neoplastic lesions. miR-21 was significantly upregulated in patients with IBD-related CRC compared to both IBD patients with adenoma and their own control samples from a previous negative colonoscopy (p=0.003 and p=0.006, respectively). Likewise, a significant difference in miR-21 levels was observed between patients with IBD-related CRC and those with dysplasia (p=0.02).

Conclusion

miR-21 and miR-135b are involved in the carcinogenesis process of patients with IBD. They could be potential candidate biomarkers for diagnostic purpose, prognostic and predictive stratification of patients.Read more P216 Urine Metabolomic Characteristics of Anxiety and Depression Disorders in Patients with Inflammatory Bowel DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Up to 25%-35% of patients with inflammatory bowel disease (IBD) suffer from anxiety or depression. We aimed to depict the urine metabolic profile of IBD patients with anxiety and depression disorders and investigate the urinary metabolites that could characterize the mental disorders in IBD patients.

Methods

Urine samples were collected from IBD patients, and the Liquid Chromatography-Mass Spectrometry (LC-MS) was used to detect the metabolites. The Hospital Anxiety and Depression Scale (HADS) was used to assess the anxiety and depression symptoms. Least absolute shrinkage and selection operator (LASSO) regression model with 10-fold cross-validation was used to establish a metabolite-based prediction model for mental disorders in patients with IBD.

Results

Among the involved IBD patients (n=23, median age 41, women 61%), 35% had anxiety and 35% had depression. The urine metabolic profiles of IBD patients with anxiety or depression disorders were largely separated from those without mental symptoms (Figure 1 a-b). There were 36 metabolites up-regulated and 25 metabolites down-regulated in the anxiety group, while 10 metabolites up-regulated and 35 metabolites down-regulated in the depression group (Figure 1 c-d). The LASSO model identified the metabolites predicting IBD patients with mental disorders (Figure 2 a-b). Six metabolites (L-Carnitine, Riboflavin-5-phosphate, 2-Ethyl-2-phenylmalonamide, 3-Indoxyl sulphate, Sodium cholate, Tritylalcohol) were selected to construct the prediction model for anxiety, and another six metabolites (D-(-)-Glutamine, dAMP, DL-Stachydrine, dCMP, 5'-Deoxy-5'-(Methylthio)Adenosine, Sakuranin) were selected to construct the prediction model for depression in IBD patients. Both models showed excellent performances with an AUC of 0.992 (95%CI:0.97-1.00) and 0.933 (95%CI: 0.83-1.00) for predicting anxiety and depression, respectively, among patients with IBD (Figure 2 c-d).

Conclusion

We found significantly different urine metabolic profiles between IBD patients with and without anxiety and depression disorders. The specific urinary metabolites panel may become effective biomarkers for the prediction of anxiety and depression disorders in IBD patients.Figure 1.Differences of urine metabolic profile between groups. a-b. PLS-DA analysis of the urine samples from IBD patients with and without anxiety (a) or depression (b) disorders. c-d. Volcano plots showing the differential metabolites between groups.Figure 2.LASSO model constructed by urinary metabolites for predicting anxiety or depression disorders in IBD patients. a-b. Cross-validation error plots for anxiety model (a) and depression model (b). c-d. ROC curves for the prediction performance of anxiety model (c) and depression model (d).Read more P217 Rate of undetected dysplasia at colectomy in patients with IBD - What are we missing?Wed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Patients with Inflammatory Bowel Diseases (IBD) are at higher risk of developing dysplastic lesions and colorectal cancer (CRC). Despite the use of high-definition endoscopes, dysplasia is not always detected at colonoscopy. This study aims to determine the rate of dysplastic lesions detected only at colectomy in IBD patients and to identify the characteristics of patients with undetected dysplasia.

Methods

We retrospectively identified IBD patients that underwent total or sub-total colectomy at Mayo Clinic, between January 2013 and December 2022. Patients with a confirmed IBD diagnosis, with at least one colonoscopy report prior to surgery available, were included. Data collected was demographics, comorbid conditions, colonoscopy, surgery, and their pathology reports. Concordance between dysplasia found at colonoscopy and dysplasia found at surgery was evaluated, noting dysplasia sites and grade. Patients were then divided into three groups: those with at least one undetected dysplastic lesion at surgery, those with dysplasia detected at colonoscopy and no further lesions at surgery, and those without dysplasia at both.

Results

Seven hundred-four patients were included: 387 (55%) were male, 450 (64%) had ulcerative colitis, 197 (28%) had Crohn’s disease and 57 (8%) had indeterminate colitis.In 42 patients (6%) dysplasia was undetected at colonoscopy, 136 (19.3%) had dysplasia detected at colonoscopy, and 526 (74.7%) had no dysplasia at both.In the group with dysplasia detected, 40 patients (30%) had dysplasia only at colonoscopy while 96 (70%) had dysplasia at surgery as well.Among those with undetected dysplasia, in 17 (40%) dysplasia was identified only at surgery: 14 (82%) had low grade dysplasia and 3 (18%) had cancer. All cancers were stage 1. Three of these patients (18%) had primary sclerosing cholangitis and 4 (23%) had a family history of cancer. In the other 25 patients (60%), dysplasia was detected at colonoscopy but further dysplastic foci were identified at surgery. In 13 (52%) patients dysplasia was upgraded, in 2 (8%) was downgraded and in 10 (40%) the grade was confirmed. Compared to those with detected dysplasia, these patients more frequently had moderate-severe disease activity, and less frequently a prior history of dysplasia. There was no difference in age at surgery, but those with undetected dysplasia had less years of disease at colectomy.Further results are shown in Table 1.

Conclusion

The rate of dysplastic lesions found at colectomy and missed at colonoscopy is 6%. Dysplastic lesions tend to be undetected when endoscopic disease activity is more severe and regardless of the use of extensive nontargeted biopsies.Read more P218 Development of Magnetic Resonance Imaging based index to differentiate Crohn’s disease associated perianal fistula and cryptoglandular perianal fistulaWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Magnetic resonance imaging (MRI) is the standard for evaluating perianal fistulae. Perianal fistula can be the first manifestation of CD, and needs to be differentiated from non-CD associated perianal fistula. This study sought to identify the variations in MRI characteristics of perianal fistulas in patients with and without inflammatory bowel disease (IBD), considering the potential implications for treatment decisions.

Methods

This was a single-center cross-sectional analysis of patients who underwent pelvic MRI for assessment of perianal fistula between January 2021 and June 2022 at Dayanand Medical College and Hospital (DMCH), Ludhiana, India. Patients who underwent dedicated MRI fistula protocol were included. Patients with prior anal resection or anastomosis, anorectal tumor, or equivocal imaging findings that could not be definitely assessed as a fistula were excluded. The following features were assessed: anatomic type of fistula (Parks classification), luminal origin (hour clock position), anal verge distance, signs of acute inflammation, circumference of anus involved by inflammation, presence of rectal inflammation, and abscess.

Results

Between January 2022 and December 2022, a total of 287 MRI scans were conducted to assess for perianal fistulae. Out of these, 119 MRI scans met the eligibility criteria and 32(26.89%) were associated with an established clinical diagnosis of CD. A higher proportion of females had CD-associated perianal fistula compared to non-CD perianal fistula. A significantly greater percentage of CD-associated perianal fistulas exhibited supra-levator extension, multiple and branched fistula tracts, and ≥2 internal and external openings. Patients with CD had higher prevalence of concurrent perianal abscess, proctitis, anorectal strictures, and a greater number of clock hours of inflamed anal circumference, compared to patients with cryptoglandular fistula. (Table 1) On multivariate logistic regression analysis, female sex, ≥2 internal openings, proctitis and height of the mucosal origin of the fistula from the anal verge >1.85 cm independently predicted the perianal fistula to be associated with CD. We constructed the DMCH index as follows:DMCH index: (3xfemale sex) + (3x≥2 internal openings of the fistula tract) + (6xrectal wall thickening) + (2xheight of mucosal origin of the fistula from anal verge >1.85 cm)The DMCH index greater than 7 identified the perianal fistulae associated with CD with a sensitivity of 84% and specificity of 91% [Area under curve 0.91; 95% CI 0.85-0.97; P< 0.0001].(Figure 1)

Conclusion

The DMCH index identifies CD associates perianal fistula with a high level of accuracy. These findings require validation and confirmation in independent, multi-reader studies.Read more P219 Prognostic potential of mucosal proteins in Ulcerative ColitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Better prognostic measures for ulcerative colitis (UC) could significantly advance patient care. While the prognostic capacity of circulating proteins in UC has been explored, the role of mucosal proteins remains largely unknown. We examined mucosal protein markers in patients with incident ulcerative colitis and evaluated their prognostic value.

Methods

Biopsies from macroscopically inflamed colonic/rectal mucosa of adult patients in the Swedish inception cohort of IBD (SIC IBD) were obtained at diagnosis of UC. Patients were followed prospectively, and clinical data were recorded after 3 and 12 months. Disease course was categorised as indolent or aggressive at 12 months, based on a composite outcome of colectomy, hospital admission for active disease, treatment refractoriness towards ≥2 biological agents; the use of >2 courses of corticosteroids, or a cumulative dose of >2.5 g. Relative estimates of 162 protein markers were assessed in homogenised tissue supernatants, using proximity extension assay technology (Olink Proteomics, Uppsala, Inflammation and Oncology II panel). Mann-Whitney U test, with Benjamini-Hochberg correction was used to identify differentially regulated mucosal proteins in aggressive vs indolent disease course, with a 5% false discovery rate (FDR). Smoothly clipped absolute deviation regularised logistic regression models were used to identify prognostic signatures distinguishing aggressive from indolent disease course. Performance was estimated in a leave-one-out cross-validation and reported as the area under the receiver operating characteristic (ROC) curve (AUC).

Results

117 patients provided a macroscopically inflamed colonic/rectal biopsy at diagnosis of UC. Basic demographics and clinical characteristics are presented in Table 1. Relative protein levels of WFdc2 and CCL20 were significantly lower in lysates from patients developing an aggressive course vs patients developing an indolent course, while estimates of MMP1, CCL11, WISP-1, OPG, RSPO3 and VEGFR2 were higher (Figure 1A). Regularized logistic regression identified signatures restricted to 28 proteins, distinguishing aggressive from indolent UC courses, yielding an AUC of 0.68 (95% confidence interval (CI): 0.56-0.80) for left-out samples (Figure 1B). Incorporating extent of inflammation at diagnosis in the model improved the AUC to 0.71 (95% CI: 0.60-0.83).

Conclusion

We identified prognostic mucosal protein signatures associated with future course of ulcerative colitis by analysing inflamed mucosal biopsies that were obtained at diagnosis. These protein markers may highlight pathways of relevance for ulcerative colitis outcomes.Read more P220 IBD-Disk: italian translation and validation in a population-based cohortWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

As an objective endpoint in IBD Disease-Modification Trials, measures of disability and health-related quality of life have been proposed. IBD-DISK is an easy-to-use, and self-administered analogic visual tool designed for assessing disability. However, successful dissemination of this tool will require a cultural adaptation and translation process. To date, the IBD-Disk has not been validated in Italian clinical practice. Hence, we aimed to validate the IBD-Disk in an Italian population-based cohort according to the COSMIN recommendations.

Methods

The IBD-Disk italian translation and validation study was a cross-sectional multicentre study conducted in 8 Italian IBD referral centres. After forward-backward translation into Italian, patients were consecutively recruited from February 2023 to October 2023. Patients completed the following questionnaires: IBD-Disk (at baseline, T0, and after seven days, T1) and IBD-Disability Index (IBD-DI) for disability, IBDQ-32, and SF-36 for quality of life. Validation included assessment of validity, reproducibility, internal consistency. We further investigated the correlation between IBD-Disk and IBD activity and clinical factors associated with IBD-Disk.

Results

At baseline, 513 patients (237,46.2% CD; 276,53.8% UC) completed the IBD-Disk[Table.1]. Internal consistency was excellent with a Cronbach’s α of 0.93. The intraclass correlation coefficient (ICC) was 0.94 for test-retest (T0 and T1) (p< 0.001). To evaluate construct validity, the IBD-Disk was compared with the IBD-DI, revealing a significant positive correlation (r = 0.70; p < 0.001). Furthermore, it exhibited a positive correlation with both IBDQ-32(r=0.82, p< 0.001) and SF-36(r=0.093, p= 0.035). The overall IBD-Disk median score was 32(12-52), with 219(42.7%) reporting moderate-to-severe disability (IBD-DISK ≥ 40). The IBD-Disk score was significantly higher in patients with active CD disease based on HBI ≥ 5 compared to patients with inactive disease(p < 0.001). Similarly, for UC, patients with active disease, measured with a partial Mayo score ≥2, showed a higher IBD-DISK score than those in clinical remission[Fig.1]. Additionally, moderate-to-severe disability significantly increased in female [OR =2.83; 95% CI(1,97-4,07)] and in patients with active extraintestinal manifestations [OR = 1,71; 95%CI(1,23-2,81) p=0.04].

Conclusion

This study validated the IBD-Disk in a large cohort of Italian IBD patients, demonstrating that it is a valid, reliable and responsive tool for quantifying disability. This validation enables the broad implementation of IBD-DISK across Italy, facilitating its integration into the daily clinical management of IBD patients.Read more P221 Intestinal ultrasound is predictive of disease relapse in asymptomatic Inflammatory Bowel Disease patientsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Intestinal ultrasound (IUS) is a non-invasive, repeatable, and accurate disease monitoring modality that provides real-time assessment of inflammatory bowel disease (IBD). There are few data on the utility of IUS monitoring of asymptomatic patients. We assessed the ability of IUS to predict disease relapse in asymptomatic patients.

Methods

We maintain a prospectively maintained registry and database of IUS cases at our institution. We used this database to perform a retrospective analysis of IBD patients who were asymptomatic (HBI4, SCCAI2) but who had signs of active inflammation on IUS, defined by bowel wall thickness (BWT) > 3mm and/or colour Doppler signal (CDS) (modified Limberg score (mLimberg) > 0). We assessed the prevalence and time to clinical (symptomatic) relapse (HBI>4, SCCAI>2). IUS parameters and treatment change (defined as addition of steroids, immunomodulators, treatment escalation, therapy cycle or swap) were evaluated as predictors of disease relapse.

Results

40 patients (47 CD, 5 UC, 1 IBD-U; 53 IUS exams) were included. 10 patients (18.9%) relapsed within an average of 107.0 (±108.2) days. The relapsed group had a mean BWT of 4.5 (±0.3) mm vs. 3.9 (±0.5) mm in the non-relapsed group (p = 0.112), and a mean mLimberg of 1.7 (±0.3) vs. 1.3 (±0.1) (p = 0.503). Of the 53 IUS exams included in this study, 40 exams resulted in treatment change after the IUS (28 due to IUS findings alone, 12 due to other indications at a later time including elevated faecal calprotectin (FCP), breakthrough symptoms, drug level, perianal symptoms, psoriasis, allergic reaction, and bowel obstruction). Of the 40 patients who had treatment change (including dose escalation (n=16), dose de-escalation (n=4), therapy cycle or swap (n=14), or addition of steroids (n=5) or immunomodulators (n=1)), 9 (22.5%) experienced a clinical relapse, and of the other 13 patients who did not have a treatment change, 1 (7.7%) experience a clinical relapse (p = 0.257).

Conclusion

Silent inflammation identified by IUS in asymptomatic patients is associated with disease relapse in nearly 20% of patients within an average of 3.5 months. The degree of inflammation by BWT and CDS was numerically higher in the relapse group compared to those who did not relapse, although this was not statistically significant. The treatment changes incorporated in this cohort did not lead to lower rates of disease relapse. However, these findings demonstrate the prognostic value of silent inflammation as detected by IUS and the need for future prospective treat-to-target type studies using IUS.Read more P337 Proactive therapeutic drug monitoring of Adalimumab, but not HLADQ*A1 determination, predicts inflammatory bowel disease outcome and persistence of treatmentWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Anti-TNF drugs have proven effective in managing Inflammatory Bowel Disease (IBD), but a significant percentage of patients exhibit primary or secondary non-response. Therapeutic drug monitoring (TDM) is a valuable tool for optimizing patient management. HLA-DQA1*05 gene has been investigated as a potential marker for immunogenicity and loss of response to anti-TNF therapy.This prospective, multicentric study aimed to assess the clinical impact of determining Adalimumab (ADA) levels and anti-adalimumab antibodies (Abs) in IBD patients and the influence of the HLA-DQA1*05 allele on the response and maintenance of ADA treatment over a 24-month follow-up.

Methods

Patients initiating ADA treatment between October 2020 and October 2022 were enrolled. Demographic data and IBD characteristics were recorded. Clinical Activity Index, C reactive protein (CRP), faecal calprotectin (FC), endoscopy or radiological activity, Global Physician Assesment (GPA) and PRO (by IBDQ-9) were prospectively collected at baseline and at the same time that ADA levels: week 4, 10, 30 and 12 months. HLA-DQA1*05 was genotyped at baseline. Pearson coefficient was utilized to assess correlations between ADA levels and disease activity.

Results

We included 170 (age 42±17 years, 54% female) IBD patients (74% Crohn`s Disease, 24% Ulcerative Colitis and 2% Indeterminate colitis) who started ADA (85% naïve to anti-TNF). At baseline, 80% had an active disease (GPA=1); CRP and FC were 10.72 ±17.85 mg/L and 568 ±775 µg/g; PRO at baseline was 63±8.6. HLA was determined in 167 patients, of whom 71 (42%) were HLA-DQA1*05 positives. Median follow up was 17 months. No correlation between HLA and drug levels or Abs was founded. ADA levels at the end of induction was correlated with ADA levels during follow up. ADA serum concentration >7 µg/mL at weeks 4 and 10 correlated with improved clinical response at corresponding time points (p<0.001). Patients with ADA levels >7 µg/mL at week 10 demonstrated better disease control at 12 months. 41 patients stopped ADA. It was associated with active disease, low ADA levels, and adverse clinical and laboratory markers. HLA-DQA1*05 positivity did not correlate with adverse reactions or Abs during the observational period. A significative improvement in PROs in patients who started treatment with ADAL (62.73 at baseline and 69.42 at week 30) (p<0.001) was observed.

Conclusion

Early Drug level monitoring of Adalimumab may improve the management of IBD patients. PCR, CF and GPA at week 10 may predict treatment failure. ADA levels >7 µg/mL is associated with a better clinical response in short and long-term, independent of HLADQA1*05.Read more P338 The dependence of the level of Glycoprotein type 2 on the level of Zonulin in Crohn's diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Introduction. Type 2 glycoprotein (GP2) is a quantitatively predominant membrane protein of excretory granules of pancreatic acinar cells. In a number of studies, it has been demonstrated that this protein is the main antigen for pancreatic antibodies associated with Crohn's disease Zonulin – a protein that can reversibly increase the permeability of the intestinal wall by changing the structure of tight junctions of the lateral surfaces of intestinal epithelial cells. The determination of fecal zonulin is used for noninvasive assessment of increased intestinal permeability. Normal values of zonulin in stool (≤ 110 ng/ml) indicate the absence of damage to the villous surface of the intestinal mucosa and normal density of intercellular contactsThe aim of the study was to establish the dependence of the level of type 2 glycoprotein on the level of fecal zonulin (FZ) in the feces of CD patients with exacerbation of the disease.

Methods

122 patients with CD in the form of ilekolitis with exacerbation of the disease (Me age — 32 years) were examined. FZ was evaluated by ELISA (IDK ® Zonulin ELISA Kit, Immunodiagnostik AG, Germany) in ng/ml. Reference values: < 83.15 ng/ml is a variant of the norm, 83.15-110 ng/ml is an elevated level, 110 ng/ml is a high level.The level of IgG and IgA to GP2 (antibodies to glycoprotein) antigen of pancreatic centroacinar cells (Anti-GP2, IgG, IgA) was determined by ELISA. Reference values: IgG GP-2 less than 10 units/ml, Ig and GP-2 less than 5 units/ml – positive values.

Results

In the stool samples of CD patients during the period of exacerbation in 92 patients, an increase in FZ was detected, the average value was 333.4 ±16.9 ng/ml. In the blood samples of 87 patients with CD during the period of exacerbation, an increase in Ig A GP-2 was detected, the average value was 43.4±6.9 units/ml. In the blood samples of 107 CD patients during the period of exacerbation, an increase in Ig G GP-2 was detected, the average value was 17.1 ± 1.3 units/ml. There is a high correlation force between the concentration of FZ and the concentration of Ig A GP-2 (r-0.760) (p=0.010). There is a moderate correlation force (r-0.490) (p=0.023) between the concentration of FZ and the concentration of Ig G GP-2.

Conclusion

An increase in the concentration of FZ in the feces of CD patients during exacerbation significantly correlates with an increase in the concentration of Ig A GP-2 and Ig G GP-2.Read more P339 Dermatological evaluation of candidates with IBD for biological therapy - should it become part of the scheme during qualification?Wed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Oncological anxiety associated with biological therapy is a common challenge in inflammatory bowel disease (IBD) and it have raised questions about the need for dermatological assessment of the skin before starting a biological therapy to exclude cutaneous malignancies.

Methods

The aim of the study was to assess the frequency of skin cancers in IBD patients before starting biological therapy. We conducted a retrospective, single-centre evaluation on the frequency of skin cancers.

Results

A group of patients with IBD who were referred for qualification for biological treatment consisted of n = 805 patients, out of which 348 (43.2%) were female and 457 (56.8%) were male. Average age of patients was 36.84 ± 12.49 years. During qualification for biological treatment dermatological skin assessment was performed and dermal lesions were found in 15.5% (125) patients, of which 9 (1.1%) were cutaneous malignancies. Only steroid dependance and resistance differentiated in a significant way between patients with and without dermal lesions. Dermal lesions group included lower proportion of patients with steroid dependence (84.6% vs 92.9% in group without dermal lesions) and higher proportion of patients with steroid resistance (13.6% vs 7.1% in groups of patients with no dermal lesions) (V = 0.09, CI₉₅ [0.01;0.17], p = 0.022). Surprisingly, there was no effect of thiopurines on development of dermal lesions between group with and without dermal lesions 90.4% vs. 84.6%, MD = 0.06, CI₉₅ [0.01;0.12], p = 0.118. In a multivariate logistic regression model only higher BMI (OR = 1.08, CI95 [1.02;1.14], p = 0.007) was identify as a risk factor for development a dermal lesions. Additionally, as many as 9 patients were diagnosed with cutaneous malignancies, including 4 basal cell carcinomas (BCC), 4 squamous cell carcinomas (SCC) and one MSC. Only 11.4% patients complied with our strict policy of skin surveillance every 6-8 months.

Conclusion

In this study, we observed dermal lesions in 15.5% of patients, of which 1% were cutaneous malignancies. The only risk factor for dermal lesions was higher BMI. The lack of effect of thiopurines on oncological risk may indicate the need to monitor the skin condition in every patient with IBD. It is also crucial to disseminate knowledge about the need for regular skin assessments among IBD patients.Read more P340 The association between colon pseudopolyps presence and clinical adverse events in UC patients treated with biologicsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Colon pseudopolyps (aka post-inflammatory polyps) are potential marks of previous severe ulcerative colitis (UC) activity. The association between outcomes of patients treated for UC with biologics and presence (or lack of presence) of pseudopolyps, are unclear.

Methods

A single center, noninterventional retrospective cohort review study was performed on real-life data of adult patients with moderate-to-severe UC who were treated with biologics (infliximab, vedolizumab, ustekinumab) for a minimum of 6 months. The difference in first occurence of treatment failure defined as a negative composite outcome (need for steroid rescue therapy, biologic switch, IBD-related hospitalization and/or surgery) between two groups (with or without pseudopolyps) was investigated. Participants’ characteristics were assessed using descriptive statistics. Normal distribution was assessed using Kolmogorov-Smirnov and Shapiro-Wilk tests. Categorical variables were analyzed using Chi-square test and continuous variables using Mann-Whitney test. Kaplan-Meier analysis and log-rank test were used in order to assess difference in therapy duration between two groups.

Results

Total of 92 patients (51% females; smokers 17%; 24% with pseudopolyps) were included. There were no differences in key baseline characteristics such as age, sex, smoking status, extraintestinal manifestations, serum albumin and CRP as well as fecal calprotectin levels between groups of patients with or without pseudopolyps. Median duration of follow up was 18.5 months (IQR 8-37). Presence of pseudopolyps was not associated with a higher risk for treatment failure; there was no statisticaly significant difference in the occurrence (χ2(1, N =91)=1.38, p=0.31) of negative composite outcomes or time to develop negative composite factor (χ2(1, N =91)=1.57, p=0.21).

Conclusion

In our cohort we have failed to detect any association between presence of colon pseudopolyps and rates of first occurence of treatment failure in UC patients treated with biologics.Read more P341 Clinical Characteristics and Outcomes of Crohn’s Disease with Upper Gastrointestinal Involvement: A Comprehensive Retrospective Cohort StudyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Crohn's Disease (CD) affects the entire gastrointestinal tract, predominantly involving the terminal ileum and colon. However, the incidence and implications of upper gastrointestinal tract involvement in CD are often underestimated and underreported, especially in Asian populations. This study provides a comprehensive evaluation of the clinical characteristics and outcomes associated with UGI involvement in CD.

Methods

We conducted a retrospective cohort study at Chang Gung Memorial Hospital, Linkou, from January 2001 to June 2023, including CD patients with consistent follow-up records. Patients were categorized into two groups based on UGI involvement: Montreal L4 and non-L4. Comparative analyses were performed between the groups regarding baseline characteristics, new-onset complications post L4 disease diagnosis, and clinical outcomes.

Results

The study included 223 CD patients, 114 in the L4 group and 109 in the non-L4 group, with an average follow-up of 40.6 months. Initially, the L4 group showed higher smoking prevalence (21.1% vs. 5.5%, P<0.001), higher Crohn’s Disease Activity Index (CDAI) scores (302.6±85.6 vs. 272.8±106.3, P=0.023), increased stricture disease (Montreal B2) incidence (55% vs. 48.2%, P<0.001), and more frequent use of biologics (12.3% vs.3.7%, P=0.021) and proton pump inhibitors (64.9% vs. 52%, P=0.014). They also had lower albumin levels (3.6±0.8 vs. 3.9±0.7, P=0.011) and reduced peri-anal (14.9% vs. 26.8%, P=0.026) and fistulizing disease incidences (14% vs. 26.6%, P=0.016). At follow-up end, the L4 group continued to exhibit higher CDAI scores (153.6±98.7 vs. 114.4±71.8, P = 0.001), increased hospitalization rates (0.6±1.1 vs. 0.3±0.5 times/year, P=0.009), elevated C-reactive protein levels (15.2±37.8 vs. 6.9±15.1, P=0.036), and decreased albumin levels (4±0.7 vs. 4.2±0.4, P=0.018). Though they had a lower incidence of new-onset perianal fistula (6.7% vs. 3.7%, P=0.041), the L4 group had higher incidences of most new-onset CD-related complications, including strictures (44% vs. 20.2%, P<0.001), enter enteral fistulae (11.9% vs. 3.5%, P=0.036), and intraabdominal abscesses (17.4% vs. 5.3%, P=0.009).

Conclusion

CD with UGI involvement is associated with higher disease activity and an increased risk of IBD-related complications. Comprehensive assessments at diagnosis and aggressive treatments are crucial for these patients to mitigate poorer outcomes.Read more P342 Role of the Number and Location of Endoscopic Biopsies on the Detection of Granuloma in Patients with Isolated Intestinal TuberculosisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Detecting granulomas is valuable for the diagnosis of isolated intestinal tuberculosis (ITB). However, how to perform an effective endoscopic biopsy remains unclear. We aimed to explore the impact of the number and location of endoscopic biopsies on granuloma detection in patients with isolated ITB.

Methods

A prospective analysis was conducted in 50 patients with confirmed isolated ITB who underwent predetermined endoscopic biopsy and pathological tests. 50 patients with isolated ITB were included for analysis. The diagnosis was confirmed based on microbiological, endoscopic, and histopathological evidences. For each patient, eight endoscopic biopsy specimens were obtained from either ulcer bases (n=4) or ulcer margins (n=4). After fixation, the specimens were serially sectioned into 8 slices on average. The slices were then stained and examined by an experienced gastrointestinal pathologist who were blinded to the patient information.

Results

The detection rates of granulomas from 2, 4, 6, and 8 biopsy specimens were 10, 28, 50, and 82%, respectively (5/50 vs 14/50 vs 25/50 vs 41/50, P<0.00001). When 4 biopsy specimens were used, the granuloma detection rate with specimens from the ulcer base was significantly higher than that from the ulcer margin (41/50 vs 14/50, P<0.0001). 34% (17/50) of the patients had necrotising-confluent granuloma, and 12% (6/50) had confluent (>400 um) granuloma. In total, 205 granulomas were identified in 41 patients. Multi-granulomas were detected on 49 slices while mono-granulomas on were detected on 72 slices. 62.9% (129/205) of granulomas were detected in the ulcer base, 27.8% (57/205) in the lamina propria, and 9.3% (19/205) in the submucosa.

Conclusion

Using more than 8 or 4 biopsy specimens from the ulcer base improved the detection rate (over 50%) of necrotising or confluent granulomas for ITB. To improve the accuracy of diagnosis, clinicians should obtain ≥4 pieces of endoscopic biopsy from the ulcer base and conduct a deep biopsy into the lamina propria. Nevertheless, the integration of clinical characteristics and anti-TB responses is still required for suspected patients with undetected granulomas.Read more P343 Pancreato-biliary disorders in patients with inflammatory bowel diseases – a single-centre reportWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Inflammatory bowel diseases (IBD) are regarded as multisystemic disorders due to the high prevalence of extraintestinal symptoms. Hepato-pancreato-biliary involvement can be present in up to 50% of patients, due to IBD extraintestinal manifestations and complications. Our aim was to evaluate the prevalence of the pancreato-biliary diseases in patients diagnosed with IBD.

Methods

We conducted a single-centre retrospective study which included patients diagnosed with Crohn’s disease (CD) and ulcerative colitis (UC), admitted between 1 January 2018 and 1 August 2023 in the Gastroenterology and Surgery Departments of the Fundeni Clinical Institute (Romania). We analysed the medical history (including abdominal imaging - ultrasound, computed tomography or magnetic resonance imaging) of patients during hospital follow-up and we screened for pancreato-biliary disorders.

Results

We analysed 1736 patients, of which 303 patients (17%) associated pancreato-biliary involvement and 756 patients (44%) had no pancreato-biliary disorders, with both subgroups having at least one abdominal imaging scan during follow-up; 677 patients (39%) had neither history of pancreato-biliary disorders, nor abdominal imaging. 30 patients (1.72% of total; 56.6% CD, 77% male) had acute pancreatitis (93.3% mild), 66.67% being drug-induced (13 cases - azathioprine, six cases - 5-amynosalicilates, one case - metronidazole). Three patients were diagnosed with idiopathic chronic pancreatitis and one with type 2 autoimmune pancreatitis. In the subgroup that underwent abdominal imaging (1059 patients) we identified 124 patients (11.70%) with pancreatic steatosis, 11 patients (1.03%) with pancreatic cysts (one case of intraductal papillary mucinous neoplasm) and three patients (0.28%) with congenital pancreatic anomalies (two annular pancreases, one pancreas divisum). There were no patients diagnosed with pancreatic adenocarcinoma. We identified 14 patients (0.8% from total; 64.28% UC, 57.14% male) with primary sclerosing cholangitis, of which five underwent liver transplantation, one case of primary biliary cholangitis and three cases of cholangiocarcinoma. The subgroup with abdominal imaging included 46 patients (4.34%) with prior cholecystectomy and 147 patients (13.88%) with gallbladder lithiasis or sludge (59.86% CD; 53.06% male; 39.45% intestinal resection).

Conclusion

Up to one third of patients with IBD that underwent abdominal imaging associated pancreato-biliary involvement. The high risk of drug-induced acute pancreatitis in IBD has to be taken into consideration. Screening for possible extraintestinal manifestations and early diagnosis of extraintestinal complications might improve the IBD management.Read more DOP41 Mucosal single-cell profiling of Crohn's-like disease of the pouch reveal unique pathogenesis and therapeutic targetsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

After restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC), a subset of patients develop Crohn’s-like disease of the pouch (CDP), a chronic inflammatory condition that affects both the pouch body and extra-pouch organs including the pre-pouch ileum. The cellular and molecular identities of CDP are unknown, and its diagnosis and treatment remain challenging. To define the pathophysiology of CDP, we examined mucosal cells from patients after IPAA with and without CDP using single cell analyses.

Methods

Endoscopic samples from the pouch body and pre-pouch ileum of 50 patients with an IPAA were collected for single-cell RNA sequencing (scRNA-seq) or mass cytometry (or CyTOF). We analyzed immune and non-immune cells from both pouch body and pre-pouch ileum of patients with normal pouch/ileum and CDP using scRNA-seq. CyTOF was performed on mucosal immune cells from independent cohorts of patients with normal pouch/ileum, CDP, and pouchitis. Mucosal samples from patients with familial adenomatous polyposis (FAP) after colectomy and pouch formation were also analyzed by CyTOF. ScRNA-seq and CyTOF findings were independently validated using immunohistochemistry.

Results

We revealed distinct cell clusters in normal pouch body versus normal pre-pouch ileum in UC patients. Colitogenic immune cells expanded in normal UC pouch body compared to normal FAP pouch body. Compared to normal pouch/ileum, CDP pouch/ileum exhibited expanded TCR clonotypes, elevated Th17 signaling, and diminished T cell exhaustion markers. Elevated plasma cells, inflammatory fibroblasts and monocytes were noted in CDP pouch/ileum (Figure 1). CDP also harbored elevated Th17-inducing cytokines such as IL23, IL1B, and IL6 produced by myeloid cells. ScRNA-seq and CyTOF identified increased CD14+TREM1+ pathogenic monocytes in both pouch body and pre-pouch ileum of CDP. Ligand-receptor analysis further revealed a stromal – myeloid – lymphocyte circuit in CDP. Integrated analysis showed that upregulated immune mediators in CDP tissues were similar to those in CD and pouchitis, but not UC. In addition, the pouch body and pre-pouch ileum of CDP exhibited prominent activation of the unfolded protein response (UPR) across all major immune and non-immune cell compartments (Figure 2), which was not present in UC, CD or pouchitis based on reanalysis of published databases.

Conclusion

CDP demonstrates altered immune and non-immune cell populations/states in the pouch body and pre-pouch ileum. CDP represents a distinct entity of inflammatory bowel disease with extensive UPR activation, a unique feature that may serve as novel diagnostic markers and therapeutic targets using ER stress-alleviating agents including chemical chaperones.Read more DOP43 Histologic improvement, attenuation of inflammation and microbiome modulation by engineered high acetate producing Saccharomyces boulardii in DSS-induced colitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The probiotic Saccharomyces cerevisiae var. boulardii (Sb) may be optimized for therapeutic use in ulcerative colitis by enhancing its acetate production, as acetate is a key factor for its probiotic efficacy and was shown to have anti-inflammatory and barrier-protective effects in vitro (Deleu, 2023). Therefore, higher acetate producing Sb strains have been engineered which were preclinically evaluated in an acute DSS mice model of colitis.

Methods

Nine-week-old female C57/Bl6 mice (N=120) were allocated to 12 treatment groups receiving drinking water or 2.75% DSS in combination with PBS (control), Baker’s yeast (non-probiotic control), SDH1 (no-acetate Sb), ENT (transient acetate strain-probiotic Enterol control), SbP (high acetate Sb) and ENT3 (extra high acetate Sb). Disease activity including weight loss, diarrhoea and the presence of occult blood were scored daily. On day 7, the DSS groups were transferred to regular drinking water and on day 14 mice were sacrificed. Colonic tissue and faeces (0, 9, 14d) were collected for resp. histology, RNA, and 16S rRNA sequencing.

Results

Disease activity in DSS subgroups (Fig.A), determined by the area under the curve, was lower for SbP compared to PBS and Baker’s yeast (both p<0.05). Sb SDH1 showed higher disease activity compared to the Sb strains ENT, SbP and ENT3 (all p<0.05). At sacrifice, the macroscopic damage score in DSS was lower for SbP and ENT3 (both p<0.05) compared to Sb SDH1, and the colon weight/length-ratio was decreased for ENT and SbP compared to Sb SDH1 (resp. p=0.06 and p=0.08). Higher histologic inflammation was noted in the non- or transient-acetate producing strains on DSS compared to healthy PBS control (all p<0.05), whereas this increase was not observed for both high-acetate producing strains SbP and ENT3 on DSS (p=NS) indicating a production dependent response. Anti-inflammatory findings were confirmed by transcriptomic analysis of differentially expressed genes e.g. decreased expression of Tnf, Il1b and S100a8/9, predominantly expressed as calprotectin, upon stimulation with the highest acetate producing strain ENT3 (all adj.p<0.1; except PBS adj.p=0.16). Subsequent, microbial analysis showed a superior effect of ENT3 in maintaining a stable alpha diversity (p=0.58, Fig.E), which was not observed for the other strains.

Conclusion

Engineered high acetate producing Sb strains attenuated DSS-induced colitis, with its anti-inflammatory effects further supported by transcriptomic analysis and superiority in maintaining a stable microbiome composition. Together with our previous in vitro work in patient-derived organoids, these data indicate a role for high-acetate producing Sb- in attenuating intestinal inflammation.Read more DOP76 Individual and comprehensive symptom resolution after induction and maintenance therapy with risankizumab in patients with moderately to severely active Ulcerative Colitis: A post-hoc analysis of INSPIRE and COMMAND studiesWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Short-term treatment goals in ulcerative colitis (UC) are to control inflammation and reduce symptoms, while long-term goals include endoscopic healing, absence of disability and normalisation of quality of life. This post-hoc analysis examined the effect of induction and maintenance treatment with risankizumab (RZB) on UC-related symptoms of abdominal pain (AP), bowel urgency (BU), tenesmus (TN), faecal incontinence (FI), nocturnal bowel movements (NBM), and sleep interruption (SI).

Methods

Patients (pts) from the INSPIRE induction (NCT03398148) study received intravenous (IV) RZB 1200 mg or placebo (PBO) induction treatment at weeks (wks) 0, 4, and 8. Pts with a clinical response to RZB IV treatment were randomised 1:1:1 in the COMMAND maintenance (NCT03398135) study to subcutaneous (SC) RZB 180 or 360 mg, or PBO (RZB withdrawal). Each individual symptom was assessed (AP, BU, TN, FI, NBM, and SI), as well as comprehensive symptom resolution (defined as complete resolution of all 6 UC-related symptoms). Outcomes were measured at induction wks 0, 4, 8 and 12 and maintenance wks 0 and 52. Results were reported as adjusted percentage differences of resolution for each individual symptom and for comprehensive symptom resolution of RZB vs PBO and analysed based on corresponding 95% confidence intervals and p-values.

Results

A total of 975 pts (PBO IV n=325; RZB IV n=650;) were enrolled in induction and 548 (PBO [withdrawal] SC n=183; RZB 180 mg SC n=179; RZB 360 mg SC n=186) in the maintenance study. As early as wk 4 of induction, greater proportions of RZB- vs PBO-treated pts were experiencing resolution of each individual symptom (p≤0.01). These benefits persisted through the end of induction with the greatest improvements observed in NBM and SI (both p<0.001; Table). Among induction responders, differences between RZB 180 mg SC and PBO (withdrawal) SC were sustained for all symptoms through wk 52 of maintenance (p≤0.05); results were similar between RZB 360 mg vs PBO (withdrawal) SC, except for AP. A greater proportion of pts treated with RZB (21.8%) vs PBO (withdrawal) SC (9.5%) achieved complete symptom resolution by end of induction (p≤0.001) and maintenance (23.5% RZB 180 mg SC vs 14.2% PBO [withdrawal] SC p≤0.05).

Conclusion

In this post-hoc analysis, RZB showed individual and comprehensive improvement across a range of important UC symptoms at the end of induction, compared with PBO. Improvements in UC-related symptoms were observed as early as wk 4 of induction treatment and were sustained with maintenance treatment through wk 52. These benefits demonstrate the potential of RZB to achieve both short- and long-term treatment goals based on comprehensive symptom resolution.Read more DOP77 Mesenchymal stem cell therapy for refractory Crohn’s perianal fistulas: a case seriesWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Nearly one-third of patients with Crohn’s disease will develop one or multiple perianal fistulas within the first two decades after diagnosis, with the majority being complex. Treatment options are limited with high recurrence rates after both medical and surgical approaches. It has been demonstrated that a completely fibrotic tract on Magnetic Resonance Imaging (MRI) with a MAGNIFI-CD <6 is the best predictor for long-term clinical closure. Mesenchymal stem cell treatment (MST) has emerged as a new therapeutic strategy for these fistulas. The aim of the current study was to analyse the effectiveness of MST for complex Crohn’s perianal fistulas based on MRI.

Methods

Consecutive patients with complex Crohn’s perianal fistulas, previously failing both anti-TNF treatment and surgical closure, that underwent surgical closure of the internal opening with MST between December 2019 and March 2023 were included. All patients underwent a MRI preoperatively and between three to six months after MST. For the current study, MRI’s were read by an senior radiologist. The primary endpoint was radiological remission of the fistula(s) defined as a MAGNIFI-CD <6 on MRI. Secondary endpoints were clinical closure (defined as closure of the external opening(s)), recurrence rate, change of MAGNIFI-CD over time, quality of life based on the perianal disease activity index (PDAI), and serious adverse events (SAE).

Results

In total, 30 patients (16 females) with 48 fistula tracts were included with a median clinical follow-up of 20 months. Radiological remission was achieved in thirteen patients (43.3%) after a median follow-up of 5.0 months (IQR 3.0-6.0). The median MAGNIFI-CD at baseline was 15.0 (IQR 7.0-20.0) which decreased significantly to 8.0 (IQR 3.0-15.0) after treatment (p= 0.001). Clinical closure of the fistula(s) was achieved in 21 patients (70.0%). Three patients (14.3%) developed a recurrence during long-term FU. All three patients had clinically closed fistula(s), but no radiological remission. The median PDAI decreased significantly from 10.5 (IQR 7.0-14.0) to 4.0 (IQR 0.0-7.3) (p= 0.001). Overall, in this patient group one SAE occurred requiring multiple reinterventions and temporary stoma.

Conclusion

Closure of the internal fistula opening with MST is a promising treatment strategy for therapy refractory Crohn’s perianal fistulas, resulting in >40% radiological remission and clinical closure in 70%. No recurrences were seen in patients with radiological remission. MST was also associated with a significant increase in quality of life. Further research is needed to gain insight in which patients MST is most likely to induce radiological remission.Read more DOP78 Efficacy of ozanimod by patient response trajectory subgroups identified using group-based trajectory modelling: a post hoc analysis of the phase 3 True North studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Ozanimod (OZA) is approved for the treatment of adults with moderately to severely active ulcerative colitis (UC). A previous post hoc analysis of the phase 3 True North (TN) trial identified 5 discrete groups of patient (pt)-response trajectories to OZA using group-based trajectory modelling (GBTM). The current analysis further evaluated symptomatic, clinical, and mucosal outcomes in these groups.

Methods

Five trajectory groups were previously identified by GBTM using change from baseline (BL) in partial Mayo score in pts on continuous OZA treatment until W52 (OZA/OZA; N=229): super-response (Group 1; n=38), sustained improvement (Group 2; n=85), partial improvement (Group 3; n=60), fast rebound (Group 4; n=25), and slow rebound (Group 5; n=21) (Schreiber et al. Am J Gastroenterol. 2023;118:S671–2). In each of these groups, symptomatic remission and response were evaluated through W52, and results were compared with placebo (PBO). Clinical and mucosal EPs were evaluated at W10 and/or W52 using nonresponder imputation analysis.

Results

Significantly more pts in Group 1 vs PBO achieved early symptomatic response on Day (D) 5 (34.2% vs 11.1%; P=0.0002) and remission on D6 (10.5% vs 2.8%; P=0.0264). Symptomatic EPs were sustained for 52 wk in Groups 1–3, whereas Groups 4 and 5 started losing symptomatic efficacy by W18 (Figure 1). The highest proportions of symptomatic remission at W10 were achieved by pts in Groups 1 and 2 (97.4% and 75.3%) and were sustained until W52 (73.7% and 64.7%) (Figure 1A); similarly ~100% of pts in Groups 1 and 2 achieved symptomatic response by W10 and it was sustained in >80% of pts until W52 (Figure 1B). Generally, Groups 1>2>3 had sustained or increased rates of clinical and mucosal EPs from W10 to W52, whereas Groups 4 and 5 had decreased rates of clinical and mucosal EPs at W52 (Table). Corticosteroid (CS)-free remission at W52 was greatest in Groups 1>2>3. Analysis of BL parameters showed that Group 1 had the least prior CS (60.5%), immunomodulator (26.3%), and anti–tumor necrosis factor (TNF) use (23.7%).

Conclusion

This analysis shows 3 distinctly different OZA populations within the responders, with the super-response Group 1 achieving symptomatic response as early as D5. Early response was related to long-term benefits, with Group 1 (and to a lesser extent with Groups 2 and 3) being more likely to achieve disease control at W52 with OZA. These findings demonstrate the utility of personalized medicine to direct therapeutic choice but need to be confirmed in future prospective cohorts.Read more DOP79 Promising efficacy of biologicals and small molecules for microscopic colitis: results from a large real-life multicenter cohortWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Microscopic colitis (MC) is a chronic inflammatory condition of the colon, resulting in an impaired quality of life due to debilitating watery diarrhea. First-line therapy consists of budesonide, though a subset of patients is refractory or becomes budesonide- dependent. Evidence for the efficacy of biologicals or small molecules in MC is sparse and limited to small case series. Hence, we aimed to generate more real-life efficacy data.

Methods

This retrospective series was collected as part of the CONFER project by ECCO and supported by the European Microscopic Colitis Group (EMCG). Cases of MC patients treated with advanced therapies were included through a standardised collection form. Clinical response was defined as a 50% reduction in stool frequency (SF); clinical remission was defined according to the Hjortswang criteria as < 3 stools/day or < 1 watery stool/day.

Results

Ninety-nine patients were identified (Table 1), of whom all but one were previously treated with budesonide. Reasons for budesonide discontinuation included primary non-response (PNR, 16.3%), refractory disease (34.7%), budesonide dependency (38.8%), or adverse events (AE, 10.2%). In total, 165 treatment cycles with advanced therapy (47 IFX, 40 ADA, 47 VDZ, 10 UST, 14 JAK inhibitors, 7 other) were reported. First-line advanced therapies included mainly anti-TNF (76.8%) and VDZ (20.2%) (Figure 1A). Patients were exposed to anti-TNF therapy for a median of 1.4 [0.5-3.1] years, with a significant drop in SF after induction (p<0.001), resulting in 50.0% clinical remission (Figure 1B). However, 63.0% ultimately discontinued anti-TNF therapy, mainly due to PNR (37.9%), loss-of-response (LOR, 36.2%) or AE (20.7%). VDZ induced 46.8% clinical remission, reflected in a significant drop in SF (p<0.001). Though, a 59.6% discontinuation rate was observed after a median 0.6 [0.3-1.3] years, mainly due to PNR (63.0%) and LOR (22.2%). Similarly, for UST a 40.0% clinical remission rate was accompanied by 60.0% therapy withdrawal, primarily due to PNR (83.3%). In contrast, JAK inhibition resulted in 78.6% clinical remission, with a substantial drop in SF (p=0.002) and 21.4% discontinuation rate after a median exposure of 0.6 [0.3-1.6] years.

Conclusion

Almost all advanced therapies are used in budesonide refractory or dependent MC, with anti-TNF agents the most often used first-line options. However, anti-TNF discontinuation is frequent due to lack/loss of efficacy. VDZ and UST could be alternatives, but also have a substantial discontinuation rate. In this retrospective series, the small number (n=14) of JAK inhibitor treated patients had the highest remission rate, suggesting further research on the role of JAK inhibitors in MC.Read more P035 3D bioprinting of gelatin derivatives: towards novel small intestinal in vitro modelsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Despite significant progress achieved in the field of inflammatory bowel disease research, the precise cause of the disease has yet to be elucidated. Intestinal in vitro models can provide a fast and inexpensive alternative for in vivo studies. Nonetheless, many in vitro models lack the crypt or crypt-villus architecture as seen in the large and small intestine respectively and therefore fail to mimic the complexity of the gut. In this study, we aim to improve the physiology of small intestinal in vitro models by the development of hydrogels that mirror the villi and crypts of the digestive tract.

Methods

This study focused on the development of gelatin-methacryloyl-aminoethyl-methacrylate (gel-MA-AEMA)-, and gelatin-methacryloyl-norbornene (gel-MA-NB)-based biomaterial inks to fabricate 3D constructs, mimicking villi or a combination of villi and crypts, with digital light processing. The constructs were mechanically and morphologically evaluated with parallel plate rheology and cryo-scanning electron microscopy respectively. To assess the biocompatibility of the 3D constructs, a Caco-2/HT29-MTX co-culture in a 9:1 ratio was maintained for 21 days and confluency was confirmed with immunofluorescence. Gene expression, transepithelial electrical resistance (TEER) and paracellular permeability of the cells cultured on the constructs were compared to cells cultured on flat gel-MA-AEMA and gel-MA-NB hydrogels, a collagen type I coating or uncoated tissue culture plastic.

Results

Both gel-MA-AEMA and gel-MA-NB hydrogels exhibited physiologically relevant stiffness (1.9 ± 0.63 kPa and 1.64 ± 0.63 kPa respectively), but only the gel-MA-AEMA based biomaterial ink could be successfully utilized for printing constructs with villi and crypts. On all construct designs, confluency was reached and paracellular permeability of small sized marker molecules in combination with TEER measurements suggested the formation of a functional barrier over time, which was further confirmed by immunofluorescence and increased gene expression of tight junction proteins, occludin and ZO-1. The gene expression of enterocyte differentiation markers, villin-1, sucrase isomaltase and alkaline phosphatase, suggested the superior differentiation of Caco-2 cells on the ‘only villi’ and ‘villi and crypts’ constructs compared to flat hydrogels, collagen type I coating or uncoated tissue culture plastic.

Conclusion

Although both hydrogels promoted functional barrier formation and enterocyte differentiation, gel-MA-AEMA was more suited for DLP than gel-MA-NB. In addition, culturing intestinal epithelial cells on the 3D constructs ameliorated cell differentiation compared to conventional 2D setups.Read more P036 Microbiota Metabolite Butyrate Attenuates Intestinal Inflammation Through Autophagy ActivationWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Alteration of the microbiota metabolite short chain fatty acids (SCFAs) may contribute to the development of inflammatory bowel disease (IBD). Butyrate, one of the SCFAs produced by bacteria, is known to be beneficial in attenuating intestinal inflammation. However, the mechanisms underlying anti-inflammatory effects of butyrate have not yet been entirely investigated.

Methods

In vivo, wild-type C57BL/6J mice were given a gavage of sodium butyrate (SB) (0.12g/ml) for 5 days. The mice were then administered 2% dextran sodium sulfate to induce experimental colitis models. Fecal microbiota was analysed by 16S rDNA sequencing. In vitro, HCT116 cell line was used to investigate the protective roles of SB on lipopolysaccharide (LPS)-induced inflammatory response. The levels of inflammatory cytokines, intestinal tight junction and autophagy were detected by western blotting and quantitative polymerase chain reaction.

Results

We observed that SB treatment significantly attenuated colitis in rodent models with reduced tumor necrosis factor α (TNF-α), interleukin-6 (IL-6) and interleukin-1β expression, and tended to restore intestinal barrier dysfunction. Mechanically, we identified that the inclusion of SB enhanced protein level of Atg16l1, which indicated enhanced autophagy function. In vitro cell experiments also proved that mRNA levels of IL-6 and TNF-α were decreased, while autophagy-related Beclin was enhanced. Furthermore, our results revealed a distinct alteration mediated by butyrate in the gut microbiota by restored ratio of Firmicutes/Bacteroides, increasing Erysipelotrichaceae and reduced Desulfovibrio abundance.

Conclusion

This study provides the first data demonstrating that butyrate supplementation attenuates intestinal inflammation probably via promoting autophagy and regulating intestinal microbiota. Our findings provide new insights into butyrate-mediated remission of IBD and butyrate as a potential modulator for autophagy to prevent and treat IBD.Read more P037 Modelling gut complexity and disease: development of a next-generation adult stem cell based tubular gut-on-a-chip modelWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Developing effective therapies for Inflammatory Bowel Disease (IBD) necessitates advanced in vitro models that faithfully replicate the intricacies of the gut. The current challenge is to create models that encompass the 3D morphology, heterogeneity, and boundary characteristics of intestinal tissue while also being amenable to high-throughput screening. Microfluidic techniques are emerging as vital tools to introduce physiologically relevant cues into conventional cell cultures.

Methods

We present an innovative in vitro model employing human adult stem cell-derived colon organoids cultivated as perfused epithelial tubules within the MIMETAS OrganoPlate®. This microfluidic platform facilitates the simultaneous culture of up to 64 independent gut tubules on an extracellular matrix, offering continuous media perfusion without artificial membrane interference. The barrier function of the epithelial tubules is assessed in real-time through transepithelial electrical resistance (TEER) measurements. Immunostaining and 3D reconstruction of confocal images evaluate the expression of relevant epithelial markers.

Results

The tubular epithelial model of the intestinal tract demonstrated rapid cell polarization, expression of cell-specific markers, tight junction formation, and the presence of functional transporters. TEER measurements indicated functional and reproducible barrier integrity across tubules generated from different organoid donors for at least 10 days. Incorporation of additional cell types, such as patient-derived immune cells and endothelium, marks a groundbreaking advancement in understanding disease pathogenesis. The plug-and-play modularity of these models allows for flexibility in incorporating specific cell types based on the biological pathway of interest.

Conclusion

Our next-generation gut-on-a-chip model faithfully mimics the IBD phenotype and facilitates screening for potential drug targets. Combining adult human stem cell-derived intestinal organoids with microfluidic technology provides a robust platform to study physiology and disease mechanisms in patient-specific gut models. The inclusion of IBD patient-derived cells promises further refinement, enabling a more profound exploration of disease phenotypes and treatment responsiveness. Moreover, organoids, as one of the most physiologically relevant cell sources, authentically represent patient biology, enhancing the translational potential of our findings.Read more P039 Identifying Key Genes in CROHN'S DISEASE and Acute Pancreatitis: A Bioinformatics and Systems Biology ApproachWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Previous studies have shown acute pancreatitis (AP) to be the most common pancreatic disease in inflammatory bowel disease (IBD) patients, with Crohn's disease (CD) patients exhibiting significantly higher incidence than ulcerative colitis (UC) patients. However, the shared biological mechanisms remain elusive. This study aimed to identify the differentially expressed genes (DEGs) between CD and AP and explore their associated molecular mechanisms using bioinformatics approaches.

Methods

Microarray datasets GSE75214 and GSE194331 were obtained from the Gene Expression Omnibus (GEO) database. Comprehensive bioinformatics analyses, including functional annotation, pathway enrichment analysis, expression validation, drug-gene prediction, construction of TF-mRNA-miRNA regulatory networks, comparative analysis of immune infiltration between CD and AP, and correlation assessment between key genes and infiltrating immune cells, were performed after identifying the common DEGs and hub genes.

Results

55 upregulated and 12 downregulated common DEGs were screened from the datasets. Functional and enrichment analyses of these genes indicated their shared pathogenic mechanisms may be relevant to immunity, inflammation, and lipid metabolism. Fifteen hub genes (MNDA, AQP9, S100A12, FPR1, ITGAX, CSF3R, CXCR1, IL1RN, NCF2, VNN2, S100A8, S100A9, IL1B, FCGR2A, and CXCL8) were filtered by constructing the protein-protein interaction (PPI) network. Further bioinformatics analysis of the hub genes highlighted the importance of the immune system in both CD and AP again. Two overlapped immune cells, including upregulated neutrophils and downregulated T cells CD8, were discovered between CD and AP.

Conclusion

Taken together, this study revealed the common hub genes between CD and AP for the first time and constructed a miRNA-gene regulatory network. The analysis of hub genes and immune cell landscape indicated the shared biological mechanisms between CD and acute AP, providing potential therapeutic targets for acute pancreatitis in Crohn's disease patients.Read more P076 Dock2 acts as a tumour suppressor via immune cell regulation of IDO1 in Inflammatory Bowel Disease–associated colorectal cancerWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Inflammatory Bowel Disease-associated colorectal cancer (IBDCRC) is a known and serious complication of Inflammatory Bowel Disease (IBD) affecting the colon. However, relatively little is known about the pathogenesis of IBD-associated colorectal cancer in comparison with its sporadic cancer counterpart. Mutations in Dock2 occur in around 10% of IBD-associated colorectal cancers.

Methods

We used an APC-mediated mouse model of inflammation-associated tumourigenesis. VilApc^fl/+Dock2^tm1b/tm1b and VilApc^fl/+ (control) mice were subjected to chronic dextran sodium sulphate (DSS) colitis and aged. After tamoxifen induction, mice were given two seven-day rounds of 0.5% DSS, interspersed with normal drinking water, and then aged to 47 days before culling for analysis. Additionally in vitro, Apc deficient, tumourigenic colonic organoids were generated by deleting Apc from wild type and Dock2^tm1a/tm1a colonic organoids using CRISPR/Cas9.

Results

We found that loss of Dock2 increases tumourigenesis (both in terms of tumour number and tumour burden) via immune dysregulation in an APC-mediated model of inflammation-induced tumourigenesis in vivo. The increased tumourigenesis observed is associated with a CD3 and gamma delta (γδ) T-positive immune cell infiltrate, an interferon gamma signature, and a significant upregulation of Ido1 (which catalyses the conversion of amino acid tryptophan to kynurenine). In tumours from VilApc^fl/+Dock2^tm1b/tm1b mice, tryptophan is reduced whilst the metabolite xanthurenate is increased, demonstrating IDO activity. Separately in vitro, we showed that epithelial IDO1 is induced by administration of interferon gamma. We demonstrated a source of this interferon gamma as γδ T cells, which are increased in tumours of mice lacking Dock2. Critically, inhibition of IDO1 (with 1-L-MT) abrogated the increased tumourigenesis observed as a result of Dock2 loss in mice.

Conclusion

Overall, we have identified a role for γδ T cells in promoting tumour initiation via Ido1 expression, using a Dock2 model to accentuate this phenotype.Further work is now needed to both fully characterise this novel pathway in IBDCRC, and establish how immune dysregulation promotes tumourigenesis, but it opens exciting potential for a therapeutic strategy in preventing cancer as a result of Inflammatory Bowel Disease.Read more P077 The Immunometabolic Bimodal Mechanism of NLRX1 Agonist NX-13 in a Pig Model of Ulcerative ColitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

In mouse models, NX-13 is an orally active, gut-restricted NLRX1 agonist that has been shown to reduce severity of disease in multiple UC models through a novel immunometabolic, bimodal mechanism. Most preclinical UC studies rely upon rodent models, the human gastrointestinal physiology, microbiome, and immune system bear a greater similarity to that of pigs. Therefore, we sought to expand and validate our preclinical NX-13 results in mice using the dextran sulfate sodium (DSS) pig model of colitis. Here, we describe the disease severity, cellular, and biomarker results, and confirm the immunometabolic MOA observed in other species.

Methods

Pigs were randomized by weight (n=6 per group) and were administered tablets of excipient alone (placebo), NX-13 10 mg, NX-13 50 mg, or NX-13 100mg once daily. Pigs were challenged with 1% DSS in drinking water for 6 days and monitored daily for weight gain (loss). Composite disease activity score (0-12) was taken based on the sum of three subscores (0-4) for rectal bleeding, stool consistency and overall health/activity. Necropsy was conducted on day 7. Feces were collected for fecal calprotectin (FCP) quantification. Colonic tissue was macroscopically scored and collected for analysis by flow cytometry, histopathology and gene expression.

Results

Oral NX-13 treatment protected against weight loss and reduced colitis development with differences as early as day 2, becoming significant between days 4 and 6 as disease worsens in placebo treated pigs (Fig1A). NX-13 yielded a dose-dependent improvement in macroscopic lesion severity and microscopic immune cell infiltration (Fig1B). Specifically, Th1 cells (Fig1C) and TNF producing myeloid cells in the colonic lamina propria were reduced by NX-13, as well as FCP levels in stool (Fig1D) and mRNA expression in the colon (Fig1E). Oral NX-13 treatment reduced inflammatory markers including TNF, monocyte and neutrophil chemo attractants, IL-6, and IL-23 (Fig3F). Additionally, NX-13 treatment affected markers specific to the bimodal immunometabolic MOA of NLRX1 activation, namely upregulation of NLRX1 and mitochondrial metabolism gene COX3 (Fig1G), and reduction of NFkB and NLRP3 (Fig1H).

Conclusion

NX-13 demonstrated fast and clinically meaningful improvement in disease activity, and significantly impacted on key inflammatory markers in a DSS colitis model in pigs. These results align with previous murine results and observations in the phase 1b clinical program. Therefore, they can be used to generate additional mechanistic hypotheses for translational studies in the ongoing NEXUS phase 2 trial in moderate to severe UC.Read more P078 Inflammatory transcriptomic signatures and cell type compositions in colonic mucosa of ulcerative colitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Previous studies have explored transcriptomic profiles associated with active inflammation in patients with IBD patients, but consistent characteristics of gene expression and enriched pathways, particularly in Asian patients with UC, remain unconfirmed. Here, we aimed to assess distinctive transcriptomic changes associated with persistent active mucosal inflammation in Asian patients with UC despite of medical treatment.

Methods

We obtained colonic mucosa biopsies of inflamed and noninflamed tissue from 15 patients with UC and 15 healthy controls and performed RNA sequencing analysis. Utilizing publicly available single cell RNA sequencing (scRNAseq) data, we also identified cell types expressing differentially expressed genes from RNAseq data and performed data deconvolution using CIBERSORTx.

Results

Transcriptomics profiling revealed that the inflammatory transcriptomic signature was highly enriched in the colonic mucosa of UC-active compared to UC-inactive and controls. By incorporating scRNAseq data, the genes upregulated in UC-active were highly expressed in M cells, inflammatory monocytes, and inflammatory fibroblasts, while downregulated genes were prominent in BEST4+ enterocytes and WNT5B+ fibroblasts. Notably, a sub-cluster of enterocytes associated with SAA1, SLC6A14, and DUOXA2 genes exhibited high expression in UC-active. Deconvolution analysis using CIBERSORTx identified significant enrichment of natural killer cells, inflammatory monocytes, Tuft cells, inflammatory fibroblast, WNT2B+Fos-lo1, and pericytes in UC-active.

Conclusion

Our RNAseq analysis not only identified significant gene expression changes but also revealed shifts in cell type proportions associated with persistent inflammation. These findings offer valuable insights for developing novel treatment strategies for UC.Read more P079 Low-intensity Pulsed Ultrasound reflects the status of mucosal injury and repair through stage-specific miRNAs in experimental model of Ulcerative ColitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Diagnosis and therapeutic efficacy monitoring of Ulcerative Colitis (UC) are based on a multidisciplinary approach comprising symptomatology and invasive endoscopic assessment coupled to the histopathological characterization of gut tissue biopsies. New technologies that non-invasively reflect tissue-specific changes remains an unmet need. Here we exploited Low Intensity Pulsed Ultrasound (LIPUS) to induce tissue stage-specific miRNAs in circulating blood as a non-invasive approach to reflect the status of the colonic mucosa in experimental model of colitis.

Methods

Based on our previous study, LIPUS was applied at a frequency of 38 kHz and at an intensity of 0 (as control) or 150 mW/cm² for 3 min, using a device dedicated for in vivo studies. Acute and chronic colitis were induced in C57BL/6N mice (5 animals/group) by administration of 2 and 2.5% ad libitum dextran sodium sulfate (DSS) respectively in their drinking water for 7 days for the acute and three cycles of 7 days for the chronic model. miRNA array profiling was performed on extracellular vesicles (EVs) isolated from plasma of both acute and chronic models, at both active and remission state, 2 h after LIPUS stimulation. miRNA were correlated to the mucosal status by multiplexed immunofluorescence staining using Opal Multiplex IHC (CD4, CD8, CD68, pan-cytokeratin and CD31 markers) and EVs characterized by MACSplex surface epitope detection.

Results

An enrichment of EVs characterized mainly by stromal and immune cell surface markers was found in both acute and chronic inflammatory states, LIPUS stimulation significantly modulated miRNA profiles and clearly discriminated between active acute and chronic phases. 61 miRNAs in acute and 28 in chronic colitis were specifically and significantly upregulated by LIPUS in the active phase, with a fold change ranging from 2 to 1500 compared to control. Both acute and chronic disease showed a miRNA profile coherent with the active inflammatory state of intestinal mucosa. Only 10 and 23 miRNAs were upregulated in acute and chronic remission respectively. The enhancement of miR-18a-3p and miR-301b-3p in the recovery phases correlated to instetin with reduced immune cell infiltration and epithelial layer regeneration.

Conclusion

An optimal LIPUS dosage that non-invasively targets the colon induces the tissue to release specific miRNAs that reflect the mucosal status. LIPUS may open a new era of non-image ultrasound diagnostics that works as disruptive liquid biopsy allowing the detection of tissue biomarkers for monitoring IBD disease progression.Read more P154 Histological disease progression and ALK5i therapeutic efficacy in a chronic DSS-induced mouse model of IBD with intestinal fibrosisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Inflammatory bowel disease (IBD) comprises a group of intestinal disorders, including ulcerative colitis and Crohn's disease. Intestinal fibrosis, as a result of chronic inflammation, is a common complication in IBD. Many patients do not respond or do not have a sustained response to existing treatments, highlighting the large unmet need for more effective drugs in the management of IBD. Translational animal models demonstrating chronic, progressive colonic fibrosis are important tools in preclinical drug discovery for IBD. The aim of the present study was to characterize histological disease progression and therapeutic efficacy of a TGF-β type I receptor inhibitor (ALK5i) in a novel chronic DSS-induced mouse model of IBD.

Methods

10 week old male C57BL/6JRj mice received 3 cycles of DSS (2% w/v) administration in the drinking water (DSS-IBD) or normal water (CTRL). Study groups were terminated at week 1, 3 or 6. Groups terminated at week 6 received twice daily oral dosing with vehicle or ALK5i (30 mg/kg, BID). Terminal endpoints included distal colon morphometry, quantitative histological markers of inflammation and fibrosis as well as colon transcriptomics.

Results

Compared to healthy controls, the chronic DSS-IBD mouse model demonstrated clinical and histological hallmarks of progressive IBD, including mild-to-moderate weight loss, colonic hypertrophy with sustained inflammation and fibrosis in the mucosa and submucosa areas. ALK5i treatment increased colon weight/length ratio while significantly reducing fractional (%) area of alpha-1 type I collagen in the colonic mucosa and submucosa. The histopathological phenotype was supported by corresponding regulations in gene expression markers of colonic inflammation including ptprc (cd45), tnf and nos2. Alk5i therapy did not influence gene expression markers of fibrosis, suggesting that improved relative (%) levels of collagen were driven by Alk5i-stimulated tissue volume increases. Further studies are needed to establish if TGF-beta inhibitors have antifibrotic effects in the chronic DSS model of IBD complicated by fibrosis.

Conclusion

The DSS-IBD mouse model is a preclinical model with features of progressive IBD suitable for testing novel anti-fibrotic drug therapies targeted for IBD patients.Read more P155 Evaluation the role of interleukin-22 in inflammation related intestinal fibrosis: its potential influence on gut microbiota or immune systemWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The role of interleukin-22 (IL-22) in inflammation-related intestinal fibrosis remains largely unknown. Previous studies considered it as a double-edged sword between anti-inflammation and fibro-genesis in a tissue-specific manner. Therefore, we aimed to investigate the role of IL-22 in colonic fibrosis formation under inflammation.

Methods

Paraffin-embedded specimens of the colon from patients with CD undergoing surgery were obtained for Masson staining and IL-22 immunohistochemistry. In vivo, male C57B6/J mice aged 8 weeks were divided into the DSS group, DSS+IL-22 group, and control group. The two DSS groups were fed with 2% DSS for 7 days and distilled water for 14 days, repeating three times. Mice were given rIL-22 (200 ng/mouse) or phosphate-buffered saline intraperitoneally at 0, 2, 4, and 6 days after DSS administration. Colonic bacterial 16S rRNA gene sequencing assay and RNA sequencing of colon tissue were performed. In vitro, the DLD-1 cells were stimulated by LPS and treated with different gradients of rIL-22 before the scratch wound-healing migration assay.

Results

A positive correlation between IL-22 expression and Masson staining area was observed in the surgical specimen from CD patients (R²=0.7473) and IL-22 expression was higher in CD patients with intestinal stricture. In animal experiments, the colonic fibrosis model was successfully created and confirmed by Masson’s staining. Notably, the DSS+IL-22 group exhibited a slightly shortened colon length, greater weight reduction, and higher histopathology score than the DSS group at sacrifice. The injection of rIL-22 restored colonic microbiota abundance, notably by reducing Clostridium-sensu-stricto-1 and increasing Lachnospiraceae_NK4A136 and Turicibacter. A total of 278 genes were differentially expressed in the DSS+rIL-22 vs DSS group. We figured out that the 48 upregulated genes were mainly enriched in extracellular function, muscle contraction, and biosynthesis. The 230 downregulated genes were mainly enriched in immune response and pathway response to pathogens. The further immunoinfiltration analysis showed increased aggregation of marginal zone B cells but less infiltrated innate lymphoid cell group 1, natural killer T cell, and effector memory T cell after DSS treatment. In vitro, with longer stimulation time, the higher dose of rIL-22 induced a greater percentage of wound healing under LPS-induced inflammation.

Conclusion

We primarily revealed the potential positive correlation between IL-22 and colonic fibrosis from several aspects. The underlying mechanisms may be related to the influence on microbiota abundance classical pro-inflammatory pathways like TNF pathway and NLR pathway, immune cells or pericytes.Read more P156 Gut microbiota composition in Patients with Chron's Disease in Saudi ArabiaWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Crohn’s disease (CD) is a heterogeneous disease at the clinical, molecular, genetic, immunological, and microbial levels. The disease involves complex interactions among the host intestinal mucosa and gut microbiota, causing alterations in the microbial composition of the intestines, and leading to frequent clinical manifestations. Despite the challenge of diagnosing CD, lately, there has been an increase in the number of CD patients in Saudi Arabia. Large-scale metagenomics studies could enable the understanding of functional dysbiosis of the gut microbiome. Here, we aimed to compare the fecal microbiome of CD with the inactive form of the disease and with healthy subjects.

Methods

We analyzed 80 fecal samples from inactive CD and CD samples from Saudi patients using a 16S rRNA sequencing approach. Additionally, questionnaires were completed by CD patients, which covered multiple aspects of CD, including diagnosis, treatment, and impact on patient quality of life, further to standard demographic information.

Results

Dysbiosis was found significantly greater among CD patients compared to the inactive form of the disease, as shown with more reduced diversity. This research has also shown that certain types of bacteria (belonging to genera such as Filifactor, Peptoniphilus, and Sellimonas.) were characteristic of CD groups meanwhile, genera such as Defluviitalea, Papillibacter, and Petroclostridium) were characteristic of the control group. α. Diversity measures show that the CD groups have lower diversity and richness compared to the Control group. Smoking was found to be the most important factor affecting disease activity and microbiota dysbiosis. Age and gender were among the factors influencing the alteration of the microbiome.

Conclusion

In this project, we summarize the role of the gut microbiome and its manipulation in the development and management of Crohn's disease. This study will add great value to the amount of knowledge and help understand the relationship between microbiota and Crohn’s disease progress in Saudi Arabia.Read more P157 Differentiation of Tonsil-derived mesenchymal stem cells to intestinal stem cells-like cells for cell therapy of inflammatory bowel diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Tonsil-derived mesenchymal stem cells (TMSCs) were found to exhibit a faster growth rate compared to mesenchymal stem cells derived from other tissues. This is attributed to the relatively younger age of the tonsil tissue donors. Moreover, it has been verified that TMSCs possess the capability to undergo differentiation into endoderm lineages, giving rise to cell types like parathyroid glands and insulin-producing cells. In this study, we explored the possibility of differentiation of TMSCs into intestinal stem cells-like cells (ISC-like cells), a cell type of endoderm lineages for utilizing these cells for therapeutic applications in inflammatory bowel disease (IBD).

Methods

TMSCs were cultivated in DMEM (10% FBS) and used in the experiment when 90-100% confluency was observed. Adipose-derived mesenchymal stem cells (AMSCs) were used as the control for assessing the differentiation efficacy of TMSCs. The morphology of cells was verified at each differentiation stage, and the expression of endoderm and intestinal stem cell markers was confirmed using real-time PCR (qPCR), western blotting, and immunofluorescence (IF) staining.

Results

Subjected to 100ng/ml of Activin A for endoderm differentiation and cultured for 2 to 5 days, TMSCs exhibited an upregulation in endoderm markers (SOX17, FOXA2), as confirmed by real-time PCR. Specifically, under the influence of Activin A at 100ng/ml and cultured for 5 days, there was a significant increase in the expression of SOX17 (pre-differentiation vs. endoderm-differentiation, 0.999 vs. 3.610, P=0.0394) and FOXA2 (1.047 vs. 3.912, P=0.0297). Following the endoderm differentiation phase, the medium was changed to include 500ng/ml of FGF4 and 500ng/ml of Wnt3a for a 7-day period. Post-culture, the expression level of Lgr5, an intestinal stem cell (ISC) marker, was significantly increased in TMSCs (1.061 vs. 134.0, P<0.001). Notably, AMSCs displayed a lower expression rate compared to TMSCs (TMSCs vs. AMSCs, 134.0 vs. 9.819, P<0.001). Moreover, the spheroids formation was observed 7 days after the initiation of FGF4 and Wnt3a treatment, a phenomenon absent in AMSCs differentiation. Immunofluorescence staining for differentiation markers further validated these findings: the expression of SOX17, an endoderm marker, and the fluorescence density of LGR5, an ISC marker, were notably higher in TMSCs compared to AMSCs. Protein expression levels also confirmed the upregulation of each marker in TMSCs.

Conclusion

This study validated the potential of TMSCs to differentiate into ISC-like cells, with a higher efficiency observed compared to AMSCs. The prospect of differentiating into ISC positions TMSCs as promising candidates for use as a tool in IBD.Read more P158 Expression of IL-19 and IL-24 in intestinal mucosa of inflammatory bowel disease: An immunohistochemical studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Interleukins are considered as targets for future inflammatory bowel disease ( IBD) treatments. IL-19 and IL-24 are members of IL-10 family and through the JAK-STAT pathway induce proinflammatory cytokine production. A retrospective single center study was performed to study the IL-19 and IL-24 expression in 121 patients with moderate to severe IBD, before and after treatment with biologics.

Methods

A retrospective study of 121 patients with moderate to severe IBD was performed using immunochemistry between 1999 and 2017. This study included 72 patients with Crohn's disease (CD), 49 with Ulcerative Colitis (UC) and 20 healthy controls. The age, gender, disease extent, severity and treatment choice were recorded. Endoscopy reports before and after 12 months of treatment were retrieved. Intestinal biopsy samples were retrieved from the Histopathology Lab before and 1 year after treatment with biologics. A signed consent was received from all the patients involved and the study was approved by the Bioethics Committee of Aristotle University of Thessaloniki.The histological specimen were stained for IL-19 and IL-24 before and one year after treatment with biologics. The results were analysed using SPSS for each of the IBD groups (CD, UC) and further to subgroups depending the biologic treatment they received, anti-Tumor Necrosis Factor alpha(anti-TNFa), Vedolizumab (VDZ), Ustekinumab (USK).

Results

A statistically significant increase was found in IL-19 and IL-24 patients in IBD patients versus healthy controls (P<0.05). On the biologics treated group and the anti-TNFa subgroup, there was statistically significant increase in IL-24 expression post treatment (P<0.01). In UC patients, the IL-24 expression was significantly increased after a successful treatment in relation with Mayo score ( P<0.01). On the CD group, a reverse statistically significant correlation was found between the pre-treatment IL-19 expression and the Harvey Bradshaw Index (H.B.I.) score reduction in the anti-TNFa and the VDZ subgroups (p<0.05).

Conclusion

A possibly proinflammatory role of IL-19 was found on the CD group. This can be used as a tool in the future to assess the disease activity and support the diagnosis as a diagnostic biomarker, as IL-19 was found normal in healthy controls. An anti-inflammatory role of IL-24 was found especially in the UC group and in relation with the activity index score post-treatment. This can be used potentially as a marker of response to treatment in active UC, assisting the clinical management. Further research is needed to delineate the exact role of these interleukins in intestinal inflammation.Read more P159 Inhibition of Caspase-1 signalling subtly affect the gut microbiota and reduces Adherent-invasive Escherichia coli (AIEC)-induced inflammasome activationWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Inflammatory bowel disease (IBD), encompassing Crohn’s Disease and ulcerative colitis, is a chronic gastrointestinal disorder with increasing incidence worldwide. Microbial factors such as Adherent-invasive Escherichia coli (AIEC) have been suggested to play a significant role in the pathogenesis of IBD. The inflammasome, a multi-protein complex, senses environmental signals, including bacteria, resulting in the activation of caspase-1 leading to the subsequent maturation and secretion of IL-1β. In this study we examined the impact of AIEC on inflammasome activation and on the inhibition of Caspase-1 signaling in AIEC-colonised mice and on intestinal epithelial cells (IECs).

Methods

Human IECs (CaCO2Bee1 cells) were cultured for 3hr with AIEC (HM605 and its invasiveness mutant), washed with antibiotics and further cultured in full cell media for 13hrs, followed by analysis on cytokine and inflammasome gene expression and activation by qRT-PCR, ELISA, imaging and flow cytometry. To inhibit caspase-1 activation, cells were pre-treated for 1 hr with the caspase-1 inhibitor zVAD-fmk. To establish AIEC colonisation, C57BL/6 and IL-10-/- mice were treated with streptomycin for 24hrs followed by oral gavage of AIEC-HM605 (10-8 cfu/mL) and faecal and tissue samples were collected at 6 days post AIEC-infection. Caspase-1 inhibitor was orally gavaged every in mice. Faecal samples were prepared for 16S rRNA gene sequencing and colon tissue was analysed for cytokines and inflammasome markers by qRT-PCR and ELISA.

Results

IECs cultured with AIEC and AIEC-colonised C57BL/6 and IL-10-/- mice resulted in an increased expression and activation of both canonical (Caspase-1) and non-canonical inflammasome (caspase 4). The AIEC-induced inflammasome response was dependent on the invasiveness of AIEC. Treatment with a caspase-1 inhibitor reduced the AIEC-induced inflammasome markers in IECs and in C57BL/6 mice. No major changes in alpha or beta-diversity was detected in AIEC-colonised mice or upon Caspase-1 inhibition. AIEC-colonisation resulted in an increased abundance of Bacteroides and Alistipides and reduced abundance of Lachnospiraceae, alterations reversed by Caspase-1 inhibition.

Conclusion

We show that the invasion of AIEC in IECs and colonisation of murine intestine results in activation of caspase-1 inflammasome. AIEC colonisation provoke subtle microbiota alterations which are reversed by caspase-1 inhibition. In summary, our data supports a role of AIEC in IBD pathogenesis through the activation of caspase-1 inflammasome.Read more P160 Integrative transcriptional analysis to identify predictive biomarkers for IBD severity and subtypingWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Conventional diagnostic strategies for Inflammatory Bowel Diseases (IBD) heavily rely on invasive biopsy procedures and subjective questionnaires, thereby introducing intrinsic limitations in the context of precision medicine. By understanding the molecular mechanisms behind IBD disease biology, we aim to identify certain signalling pathways relevant for epithelial tissue regeneration under chronic inflammation conditions.

Methods

To address these limitations, we compared gene expression in a large cohort of IBD patients, utilizing the IBD Plexus database (Crohn’s & Colitis Foundation, US) as well as other publicly available datasets. We further validated our results derived from the transcriptional programs by using patient derived advanced 3D-organoid models (Hospital of Nottingham, UK). These models, derived from ulcerated and normal tissue regions of IBD patients, serve as a sophisticated platform for robust validation, bridging the gap between molecular insights and clinical applications.

Results

Our primary objective was to discern putative biomarkers that are capable of effectively stratifying IBD subtypes. We further identified the genes that were upregulated exclusively in each subtypes and the gene signature that is elevated in inflamed samples compared to non-inflamed samples. We found that either the chemokine and interleukin (IL-17) signalling pathways which have known roles in recruitment of immune cells thereby perpetuating chronic inflammation and several key chemokines influence the integrity of the epithelial barrier function and regeneration. We are also analysing non-invasive biomarkers by using samples such as blood, plasma and stool and employ machine learning methods to correlate with established clinical indicators such as sCDAI, PRO2, PRO3, and MAYO categories.

Conclusion

Hence, in identifying specific targets we can introduce novel therapeutic strategies to mitigate inflammation and restore integrity of the gut epithelial barrier. With this research we aim to improve the current IBD diagnostics landscape as well propels it towards precision medicine by offering precise subtyping and predictive markers for disease severity, ultimately contributing to more personalised and effective therapeutics interventions.Read more P161 The use of Novel Natural Treatments for Inflammatory Bowel DiseasesWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Background: Free radicals and reduced antioxidant levels lead to oxidative stress, which plays a role in causing Inflammatory Bowel Disease (IBD). IBD is a chronic gastrointestinal autoimmune condition that involves an abnormal immune response. This includes Crohn's disease (CD) and ulcerative colitis (UC). In the previous studies, we demonstrated the antioxidant effect of Inonotus obliquus (IO) and flavonoids such as quercetin and epicatechin on lymphocytes from IBD patients. In vitro studies have shown that Chaga extract is effective in reducing oxidative stress in lymphocytes of both healthy individuals and those with IBD. This suggests that Chaga extract may be a useful supplement for anyone looking to inhibit oxidative stress.

Methods

Methods: In our current study, Cord Blood Stem Cells -derived Exosomes (CBSC Exo) and their synthesised miRNAs were investigated as antioxidant/anti-inflammatory elements on lymphocytes and 3D intestinal epithelial model. There were seven miRNAs found in CBSCs Exo, and among them were two miRNAs that were identified as novel. The Peripheral Blood Monocyte Cells (PBMCs) from IBD patients and healthy individuals after challenging with H2O2 or Interleukin 6 were treated with CBSCs Exo, transfected with miRNA novels or both. The treatment method also was applied to the EpiltestinalTK 3D model from Mattek. Various techniques were utilised, including the Comet assay, Fast Microplate DNA damage assay, and CCK8.

Results

The findings of the study indicate that the administration of CBSC-derived Exo, Let-7c-mimic miRNA, Let7bSb miRNA, as well as Novel 1 and Novel 2 miRNAs on the 3D model intestine, significantly decreased the level of DNA damage when compared to the positive control H2O2 and IL6, as well as the untreated samples.

Conclusion

Conclusions: In conclusion, certain natural substances like flavonoids, Inonotus obliquus, and exosomes derived from CBSCs may have an advantage in decreasing significantly oxidative stress and DNA damage in IBD Peripheral Blood Mononuclear Cells (PBMCs) and inflamed intestinal 3D models.Read more P247 Anxiety and depression in newly diagnosed patients with Inflammatory Bowel Disease – Results from the IBSEN III studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

There are few studies assessing anxiety and depression in newly diagnosed patients with inflammatory bowel disease (IBD). The purpose of this study was to determine the prevalence of anxiety and depression in patients newly diagnosed with Crohn`s disease (CD) and ulcerative colitis (UC), and to compare anxiety and depression with the Norwegian general population.

Methods

Patients (≥18 years) were included from the Inflammatory Bowel Disease in South-Eastern Norway (IBSEN III) study, a large prospective observational inception cohort. Prevalences of anxiety and depression were assessed using the Hospital Anxiety and Depression Scale (HADS), where a dimensional sub-score of ≥8 was indicative of possible cases of anxiety (HADS-A) and depression (HADS-D). Data on the general population is retrieved from the Trøndelag Health Study (the HUNT Study), a large, population-based cohort study in Norway (N= 56041). Robust regression analyses were performed to compare HADS scores in the patients with IBD to individuals from the general population, adjusted for age and education. Prevalences of both depression and anxiety are estimated using the dichotomised HADS scores.

Results

Of the 1509 patients with a verified IBD diagnosis, 938 patients aged ≥ 18 years (62.1%) completed the HADS questionnaire (CD, 297 (31.7%), UC, 641 (68.3%). In the general population there were n= 41242 respondents of the HADS. The prevalence of anxiety in CD was 37.4% (95% CI [0.32; 0.43]) compared with 32.1% in UC (95% CI [0.28; 0.35]) and prevalence of depression was 21.9% in CD (95% CI [0.17; 0.27]), compared with 16.8% in UC (95% CI [0.14; 0.20]). In the general population, the prevalence of anxiety was 17.9 % (95% CI [0.18; 0.18]), and the prevalence of depression was 9.6% (95% CI [0.09; 0.10]), both significantly lower compared with the patients with CD and UC.Compared with the general population, male patients with CD scored significantly higher, 2.9 points higher (95% CI [2.5;3.4]) on HADS-A and 1.3 points higher (95% CI [ 0.9; 1.8]) on HADS-D. Male patients with UC scored significantly higher on HADS-A (B = 2.5, 95% CI [2.1; 2.8]) and HADS-D (B= 0.7, 95% CI [0.4; 1.0]). Female patients with CD scored significantly higher on HADS-D, B= 0.8 (95% CI [0.3;1.3]). No statistically difference between females with UC and females in the general population was found.

Conclusion

Anxiety and depression are prevalent in patients newly diagnosed with IBD, and significantly more prevalent in patients compared with the general population. Male patients especially, had significantly higher HADS scores compared with the general population. The results indicate considerable psychological impact of IBD in newly diagnosed patients.Read more P248 Feasibility, accuracy and reproducibility of the ultrasound measurement of psoas muscle compared to bioelectrical impedance analysis for the evaluation of skeletal muscle mass in patients with IBDWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Sarcopenia is characterized by the loss of muscle mass and it is a strong predictor of disability and poor outcomes in several chronic gastrointestinal diseases such as inflammatory bowel diseases (IBD). Therefore, it is useful to evaluate muscle mass in patients with chronic gastrointestinal diseases at risk for sarcopenia. Radiological evaluation of muscle mass is obtained with computed tomography (CT), magnetic resonance (MRI) and bioelectrical impedance (BIA).We aimed at assessing the feasibility, reproducibility and diagnostic accuracy of ultrasound (US) measurement of psoas muscle thickness adjusted for body mass index (BMI) compared to skeletal muscle mass (SMM) evaluated with BIA normalized to height² in the quantification of muscle mass among patients with IBD.

Methods

We enrolled a total of 86 consecutive patients with IBD (males 68.6%, mean age 50.4 ± 17.6, 7.4% with Crohn’s disease) who underwent US evaluation of psoas muscle thickness and BIA during the same day.US measurement (Philips Epiq, Bothell, USA) was performed by two sonographers, blind to each other. BIA was performed with the Seca mBCA 525 (Hamburg, Germany).A cut-off of 6.68 and 8.97 of SMM normalized to height² was considered as normal value for women and men respectively.Sensitivity, specificity, positive and negative predictive values(PPV and NPV), positive and negative likelihood ratios (LR+ andLR−) were calculated, all with the respective 95% confidence inter-vals (95% CI).The reproducibility between the US operators was evaluated by intra-class correlation coefficient(ICC) for the quantitative variables of psoas muscle.The study was approved by our local ethics committee and partially funded by the Italian Ministry of Health.

Results

US psoas muscle thickness measurement was feasible in all the 86 enrolled patients.There was a significant correlation between US measurement and BIA with a Pearson r coefficient of 0.54 (p= <0.0001). Among men a cut off of 108.18 cmxkg/m*2 showed a sensitivity of 93.5% and a specificity of 53,6% in the detection of low SMM at BIA (Figure 1). Among women a cut off of 66.9 cmxkg/m*2 showed a sensitivity of 78.5% and a specificity of 69.2% in the detection of low SMM at BIA (Figure 2).Reproducibility among the operators had an ICC of 0.95 (CI 0.93-0.96).

Conclusion

Sarcopenia is a prognostic factor of poor outcomes in IBD, therefore it is important to identify patients at risk for it. Nowadays, assessment of muscle mass and eventually sarcopenia relies on radiological techniques (CT/MRI and BIA). At this purpose we propose a simple, non-ionizing, fast and reproducible US technique that compared to BIA showed a high sensitivity and thus can be used in clinical ractice to screen for muscle mass reduction in IBD patients.Read more P249 Development and validation of a novel model to predict disease behavior progression in Crohn's disease patients with intestinal stenosisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Approximately more than half of patients with Crohn's disease (CD) develop a stenosis phenotype and are at high risk of requiring endoscopic or surgical intervention. Surgical rates vary widely among Crohn's disease patients with intestinal strictures present. The aim of this study was to stratify Crohn's disease patients with intestinal stenosis using multiple algorithms to differentiate their poor prognostic characteristics using currently available clinical indicators.

Methods

This is a single-center retrospective cohort study that retrospectively collected CD patients with intestinal stenosis admitted from October 2018 to October 2022 at the First Hospital of Sun Yat-sen University. Demographic, symptomatic, and clinical test indicators at the time of first diagnosis of intestinal stenosis at baseline in our hospital were collected. Study endpoints were penetrating phenotype, or bowel resection. Imaging or surgical data were collected from patients at every 6 months, 1 year, 2 years, and 3 years from the baseline of stenosis, thus determining whether the patients had undergone disease behavioral progression. Patients who experienced progression within 3 months were excluded. Logistics regression model, random forest model, and xgboost model were constructed based on the above information.

Results

Twenty-seven baseline variables were retrospectively collected from 288 patients for analysis (Table 1). 202 cases were in the training set and 86 cases were in the test set, in which a five-fold cross-validation was performed. According to different algorithms, we constructed logistic regression model, random forest model and xgboost model, among which the xgboost model had the best efficacy in the test set, with an AUC of 0.734 for predicting the progression of disease behaviors after 3 years of stenosis, compared to 0.687 and 0.709 for logistic regression model and random forest model, respectively (Figure 1). in terms of terms of model interpretability, the first 4 important variables for exploring xgboos, were albumin, globulin, abdominal cramps, and abdominal distension. Finally, we attempted to predict disease progression at 6 months, 1 year, and 2 years using the model with AUCs of 0.749, 0.760, and 0.784, respectively.

Conclusion

We constructed a model based on simple metrics that can accurately predict the progression of disease behaviour in patients with intestinal stenosis Crohn's disease.Read more P259 Clinical characteristics and long-term disease course in patients with Crohn’s disease diagnosed by video capsule endoscopy; A retrospective multicentre matched case-control studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Video capsule endoscopy (VCE) is a non-invasive and accurate diagnostic modality that allows for direct visualization of the small intestinal mucosa in Crohn’s disease (CD). In rare cases, lesions not detected by other diagnostic modalities in patients suspected to have CD are solely identified through VCE. We aim to evaluate the clinical characteristics and long-term outcomes of these rare cases.

Methods

A retrospective multicentre matched case-control analysis was conducted in patients with CD across three hospitals in Korea, from January 2007 to April 2023. To perform a matched case-control study, we defined cases (VCE group) as patients with normal findings at colonoscopy and cross-sectional imaging, ultimately diagnosed with CD by VCE; the controls were patients with CD diagnosed with specific findings at endoscopy or cross-sectional imaging (non-VCE group). Controls were matched to cases with a ratio of 3:1 for sex, calendar year of diagnosis, and age at diagnosis. Clinical characteristics and outcomes between the two groups were compared.

Results

Of the 3,137 patients diagnosed with CD during the study period, 24 were diagnosed solely by VCE. When compared to 72 matched patients with CD, the mean duration from symptom onset to diagnosis did not significantly differ (27.2 months [SD 10.2] vs. 25.3 months [SD 8.9], p=0.394). There was a significant difference in the proportion of Montreal behaviour (p<0.001). In the VCE group, non-stricturing and non-penetrating (B1) type and stricturing (B2) type accounted for 91.7 and 8.3%, respectively. However, there was no significant difference in the perianal fistula modifier (25% vs. 33.3%, p=0.446). Within the VCE group, 45.8% underwent the examination due to abdominal pain with diarrhoea, followed by 25.0% with perianal disease, and 20.8% with unexplained iron deficiency anaemia. Regarding capsule findings, the ileum was mostly involved (87.5%), while the jejunum and duodenum were affected in 70.8 and 16.7% of cases, respectively. Fifteen patients had two or three segments affected. The Median Lewis score was 838 [IQR 393–1803]. Concerning the cumulative incidence of clinical outcomes over 10 years, complicated behaviour, need for biologics, and CD-related hospitalization and surgery were all significantly lower in the VCE group than in the non-VCE group (p<0.005).

Conclusion

Patients diagnosed with CD solely by VCE are rare. In this study, they exhibited different clinical characteristics and a more favourable long-term disease course compared to the general population of patients with CD. This included a lower incidence of complicated behaviour, reduced need for biologics, and CD-related hospitalization and surgery.Read more P260 Clinical-ultrasound comparison of enthesis lesions in inflammatory bowel diseasesWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The objective of study was to compare the frequency of enthesis lesions in pts with inflammatory bowel diseases (IBD) according to clinical examination and ultrasound (US).

Methods

95 IBD pts were prospectively enrolled into the study: 55 pts with ulcerative colitis and 40 - with Crohn's disease. The average age of pts was 32 (26; 37) years. The average duration of the disease was 48 (12; 96) months. During clinical examination, palpation tenderness of 46 enthesis of the upper and lower extremities was assessed in each pt. According to the results of the evaluation, the number of painful entheses was calculated. US examination with power Doppler detected inflammatory (hypoechogenicity of enthesis, thickening of enthesis, presence of vascularization) and structural (erosion, enthesophyte) changes in entheses. US examination included 68 entheses of the upper and lower extremities in each pt.

Results

A total of 4370 entheses were examined clinically. Pain on palpation of entheses was noted in 49 pts (52%). The number of painful entheses was 149 (3.4%). A total of 6460 entheses were examined using US. Enthesites were found in 72 pts (76%), including vascularized enthesites in 35 pts (37%). The total number of identified enthesites was 293/6460 (4.5%), enthesites with vascularization - 62/6460 (1.0%). Structural changes in entheses were common. Erosions were determined in 76 pts (80%), the total number of enthesis erosions was 313/6460 (4.8%). Enthesophytes were detected in 37 pts (39%), the total number of enthesophytes was 91/6460 (1.4%). The number of enthesites detected by US - 72 pts (76%) significantly exceeded the number of clinically painful entheses on palpation - 49 pts (52%) (p=0.0008).

Conclusion

In pts with IBD, according to US, the frequency of detection of enthesis lesions - 72 pts (76%) was significantly higher than in clinical examination - 49 pts (52%).Read more P261 Co-infection of Clostridioides Difficile Aggravates Poor Outcomes in Inflammatory Bowel Disease with Cytomegalovirus ColitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Inflammatory bowel disease (IBD) prognosis is adversely affected by both Cytomegalovirus (CMV) colitis and Clostridioides Difficile (CD) infection. This is the first study in Asia to investigate the clinical impact and risk factors associated with their co-infection in IBD patients.

Methods

We conducted a retrospective cohort study at Linkou Chang Gung Memorial Hospital from January 2000 to May 2021, involving 53 IBD patients diagnosed with CMV colitis through colonic CMV immunohistochemistry staining. Based on stool toxin A/B tests, patients were divided into two groups: CMV only and CMV+CD co-infection. We compared baseline characteristics, clinical manifestations, risk factors, and outcomes between these groups. Logistic regression was used to analyze independent risk factors, and Kaplan-Meier methods evaluated cumulative incidence of remission rates.

Results

The study included 53 patients (37 in the CMV group and 16 in the Co-infection group). Diarrhea (93.8%) and abdominal pain (87.5%) were more prevalent in the co-infection group. Compared to the CMV group, the co-infection group had higher hospitalization times (2.5 vs. 1, p=0.005), more frequent CMV recurrences (1 vs. 0, p<0.001), and longer durations to achieve clinical (5 vs. 1 months, p<0.001), steroid-free (10 vs. 4 months, p=0.001), endoscopic (17.5 vs. 8.3 months, p=0.011), and histological remission (18 vs. 11 months, p=0.021) (Table 1-1). Kaplan-Meier analysis also indicated similar trends in Figure 1. The use of biologics was identified as an independent risk factor for co-infection (Odds Ratio 13.33, Confidence Interval 1.52-117.15, P=0.02) (Table 1-2).

Conclusion

Co-infection with CMV and CD in IBD patients leads to significantly worse outcomes. Early identification and aggressive treatment of co-infection in high-risk patients are vital for improving their prognosis.Read more P262 Differences in the Management and Demographics of Adult Inflammatory Bowel Disease in Older-Onset and Younger-OnsetWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The goal of this study was to investigate differences in the management and demographic characteristics of older-onset and younger-onset adult patients with Ulcerative Colitis (UC) and Crohn’s Disease (CD).

Methods

We retrospectively compared the management and distinguishing characteristics of UC and CD patients who were older-onset (≥60 years) and younger-onset (18-60 years) between June 1993 and October 2023.

Results

A total of 1245 patients with 56 (4.5%) older-onset adults (Male 41, 73%) and 1189 (95.5%) younger-onset adults (Male 725, 58%) were admitted to the study. The median follow-up time was 11 years (Older-onset 6 and younger-onset 11 years) for both groups. Prevalence of UC 39 (69.6%) in the older-onset group was more common than that of younger-onset group 579 (48.7%), (p=0.002). There were no significant differences between the two disease onset groups in terms of UC extension, CD location, behavior, and perianal involvement. In younger-onset, active smokers 277 (23%) was more frequent than older-onsets 6 (10%) (p= 0.003). A family history of IBD in older onsets 2 (4%) was less common than younger-onsets 155 (13%) (p= 0.037). Prior major abdominal surgery was detected similar (Older-onset 20, 35.7% and younger-onset 464, 39%). At least one extraintestinal manifestation exist was less common in older-onsets 18 (32.1%) than younger-onsets 606 (51%) (p= 0.006). Baseline partial MAYO score 7 and CDAI 302 in older-onsets, and 297 in younger-onsets were similar in both groups.Thiopurine usage 391 (32.9%) in younger-onsets was the most frequent than in older-onsets 9 (16.1%) (p=0.008). There was no difference in both groups in terms of other conventional medications. At least one biological experience was less common in older-onsets 15 (26.8%) than the younger-onsets group 586 (49.3%) (p=0.001). The two biological therapies that were used the most frequently were adalimumab (Older-onset; 6, 10.7% and younger-onset; 384, 32.8%) (p=0.001) and infliximab (Older-onset; 15, 26.8% and younger-onset; 586, 49.3%) (p=0.02).

Conclusion

Our study showed that the prevalence of UC in older-onsets was more common than younger-onsets. A family history, extraintestinal manifestation, thiopurine, and biological usage in older-onsets were less common than in younger-onsets. Major abdominal surgery was similar in both groups. Older-onset patients demonstrated significant differences in medication utilization, including less thiopurine and biological therapy compared with younger-onset groups, these utilization patterns may have long-term effects on disease outcomes. Further investigation is needed to optimize care pathways in the older-onset population.Read more P263 Clinical-Endoscopic Correlation of Postoperative Recurrence in Surgically Treated Crohn's Disease PatientsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The majority of patients with Crohn's disease (CD) require surgical intervention at some point in their disease course, particularly ileocolic resection. However, the average rate of clinical postoperative relapse is 30% at 3 years and 60% at 10 years. Endoscopic postoperative recurrence precedes clinical recurrence, highlighting the importance of conducting a colonoscopy 6 to 12 months postoperatively to establish the Rutgeerts score,which predicts the risk of clinical recurrence. The aim of this study is to correlate endoscopic findings with the clinical symptoms of these patients.

Methods

We retrospectively analyzed clinical symptoms and Rutgeerts scores of Crohn's disease patients who underwent ileocolic resection during the course of their disease, and followed at the Hepato-Gastroenterology Department of MOHAMMED VI university hospital in Oujda, Morocco, during the period [2018-2023]

Results

Sixty Crohn's disease patients underwent at least one surgical operation during the course of their disease, comprising 25 females and 35 males with a sex ratio (M/F: 1.4). The average age of our patients was 35 years [20-73]. The average time between diagnosis and the first surgery was 4 years. All these patients received postoperative medical treatment before colonoscopy, including azathioprine or methotrexate in 26 patients (43%) and anti-TNF in 34 cases (56%), with an average time of 8 months between surgery and the start of treatment. According to the Montreal classification, the ileocolic form dominated in 88% of cases, with a penetrating phenotype in 40% and a structuring phenotype in 60%. The operative indication was primarily obstructive syndromes in 85% of cases and collections in15%. The average time to perform colonoscopy after surgery was 10 months. During follow-up, 80% of patients were asymptomatic post-surgery, with Rutgeerts scores of I0-I1 in 11(23%) patients, I2 in 13 (27%) cases, I3 in 9 (19%) cases, and I4 in 15 (31%) cases.However, clinical recurrence, characterized by diarrhea, abdominal pain, or Koenig's syndrome, was observed in 20% of patients, with an average postoperative clinical recurrence time of 2 years. The endoscopic findings in these patients revealed Rutgeerts scores of I2 in 4 cases (33%), I3 in 3 cases (25%), and I4 in 5 cases (41%).

Conclusion

In summary, despite postoperative medical management, the risk of clinical recurrence isnotable. Early postoperative colonoscopy, assessing Rutgeerts scores, proves crucial inpredicting clinical recurrence risk. The observed clinical-endoscopic discordance emphasizes the need for a comprehensive approach to monitoring postoperative outcomes in Crohn's disease.Read more P264 The utility of ANCA in Ulcerative Colitis and Crohn’s Disease: A Retrospective Cohort Study in TaiwanWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Inflammatory bowel disease (IBD) includes two chronic idiopathic inflammatory diseases: ulcerative colitis (UC) and Crohn disease (CD). The diagnosis of IBD depends on clinical, endoscopic, histological, radiological and biochemical criteria, which may be invasive, time consuming and usually not accepted by patients with IBD. Antineutrophil cytoplasmic antibodies (ANCAs) is believed to be related to IBD. The aim of this study was to investigate these serological markers and the evidence for their use in the diagnosis and management of IBD in Taiwan.

Methods

We conducted a retrospective cohort study in adult IBD patients who had received the serum examinations using the medical records of China Medical University Hospital between 1 January 1980 and 31 October. 2023.

Results

A total of 301 IBD patients (194 with UC, 107 with CD) were included in this current study. A high proportion were male (IBD 70.41%; UC 65.63%, and CD 76.71%). The mean diagnostic age of these enrolled patients was 42.9 years. In our patients, the prevalence of positive anti-HCV Ab is 0.0% in UC patients and 0.96% in CD patients. However, the prevalence of positive HBsAg was 14.5% in UC patients and 9.4% in CD patients.The prevalence of pANCA was 21.2% in UC patients and 1.4% in CD patients, respectively. The prevalence of cANCA was 3.1% in UC patients and 0.0% in CD patients. This pattern of low sensitivity and high specificity for pANCA is also seen in UC patients in various cohort studies. The serum positivity of p-ANCA was significantly higher in UC patients (Figure 1). UC patients with positive p-ANCA were older than CD patients with positive p-ANCA (44.9 vs. 37.3 years). Furthermore, we found that the incidence of positive p-ANCA in UC patients with E1, E2, and E3 at diagnosis was 3.5%, 39.2%, and 57.1%, respectively (Table 1). The serum levels of ANCA-IgG were indeed higher in patients in the severe group than those in the moderate and mild groups.

Conclusion

Serological biomarkers have been demonstrated to be a series of rapid, non-invasive approaches for assessments of early diagnosis, disease activity and prognosis for IBD. ANCA may be helpful in the early diagnosis of UC and in differentiating it from CD. UC patients with positive ANCA have a higher rate of intestinal mucosal vasculitis than UC patients with negative ANCA. Furthermore, ANCA may also contributes to the pathogenesis of HBV-related systemic vasculitis. Therefore, the management of HBV-related vasculitis includes control the immune complex formation and reaction as well as antiviral agents to reduce the antigenic load resulting in reduction of inflammation. Moreover, effective biomarkers with high sensitivity and specificity need to be investigated in the future.Read more P265 Factors affecting patient perception and acceptance of colonoscopy in patients with inflammatory bowel diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Inflammatory bowel disease (IBD) is characterized by chronic idiopathic inflammation of the gut. Colonoscopy is the mainstay procedure for managing and monitoring IBD patients. However, many patients with IBD do not comply with routine or surveillance colonoscopies, and the underlying reasons have not been determined for Asian patients with IBD. Therefore, this study analyzed IBD patients' perceptions of bowel preparation and colonoscopy procedures and attitudes toward examination intervals, using a questionnaire.

Methods

This cross-sectional study included 94 patients with IBD (41 with Crohn’s disease and 53 with ulcerative colitis) presenting at one medical center between July 2020 and May 2022. The patients’ perceptions of the four components associated with the colonoscopy procedure (embarrassment, pain, use of bowel-cleansing agents, and stress) were assessed via a questionnaire. Patients were asked to indicate the frequency at which they had scheduled a colonoscopy and the frequency at which they desired to undergo the procedure.

Results

“Bowel cleansing” and “pain” were most uncomfortable during the colonoscopy procedure. Younger age and younger age at diagnosis were associated with a greater burden of bowel preparation and painful sensations. Regarding examination intervals, male patients were more compliant with colonoscopies within shorter timeframes than female patients. Additionally, younger patients and those diagnosed at an earlier age tended to prefer longer examination intervals.

Conclusion

This study provides insights into the perception of colonoscopy in Taiwanese patients with IBD. Our findings would promote the adherence to colonoscopy and facilitate early detection of major complications in high-risk and long-term IBD patients.Read more P266 Predictive tissue-based biomarkers in treatment of Inflammatory Bowel Disease with biologicals and small molecules: a systematic reviewWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The treatment landscape of inflammatory bowel disease (IBD) has changed in the past decade with introduction of new drug classes. For most drugs, only 30% of patients achieve long-term remission. Clinical implementation of predictive biomarkers to support precision medicine is lacking. As the interactions of immune system and microbiome in the colonic mucosa may hold the key to the prediction problem, we performed a systematic review to assess the status of tissue-based biomarkers in the era of biological and small molecule therapies.

Methods

A literature search was performed in Medline, Embase, the Cochrane Library, Web of science and the ECCO abstract database in July 2023. Papers were considered eligible when reporting on biomarkers, extracted from biopsies obtained during colonoscopy, that had predictive value regarding therapy success of a specific non-TNFα biological or small molecule. Two authors independently assessed eligibility and extracted the data.

Results

From 10,141 screened records with 155 papers assessed for eligibility, a total of 43 studies were included. The majority was published in the last 5 years (87%). Data on the clinical history of patients and the interval between biopsy and therapy onset was often lacking, in part while 49% of studies were published as conference abstracts. Heterogeneity in therapy success assessment regarding modality (clinical, endoscopic, and/or histologic) and interval (4-58 weeks) was striking. With 28 studies, vedolizumab is the best investigated drug. Of the 16 studies reporting on gene expression, 7 used data from the GEMINI-I/LTS trials. These studies reported a range from a single predictive gene such as TREM1 and OSM to a classifier of 267 differentially expressed genes. Studies looking at the protein level (n=7) focused mostly on target engagement. In 7 studies, biomarker discovery was performed through histological evaluation, mainly looking at mucosal eosinophil counts. One study looking at the microbiome did not find differences between responders and non-responders of vedolizumab.

Conclusion

Our systematic review shows that tissue-based predictive biomarker discovery in IBD is a young and dynamic field of research. This is reflected by the heterogeneity in how and when therapy success is assessed. Moreover, the various methods to analyze gene expression data yield vastly different results when applied to the same dataset. We therefore propose guideline development to support clinical implementation of predictive biomarkers.Read more P267 Prospective validation of the IBD - Distribution, Chronicity, Activity (DCA) histological score for Ulcerative Colitis and correlation with UCEIS and MESWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Histological assessment is not currently recognised as an independent parameter to guide personalised treatment for patients with ulcerative colitis (UC). The development of the Inflammatory Bowel Disease – Distribution, Chronicity, Activity (IBD-DCA) score allows a pragmatic approach to quantitatively evaluate mucosal injury and healing in UC, compared with other pre-existing histological scores (Lang-Schwarz et al., J Crohns Colitis, 2021). This scoring system facilitates a template-based reporting to produce consistent reports with information representing UC severity. Each domain of the IBD-DCA is scored as one of 0 (normal), 1 (mild), or 2 (moderate to severe) based on the presence of established histological UC findings (Figure 1). This project aims to prospectively validate the IBD-DCA score for routine clinical deployment and correlate with endoscopic scores – UC Endoscopic Index of Severity (UCEIS) and Mayo Endoscopic Score (MES).

Methods

Colonoscopic biopsies from patients with a previously confirmed diagnosis of UC attending one of four hospitals in a single healthcare group from August 2022 to January 2023 were reported using the IBD-DCA histological score, and the corresponding, clinician-reported UCEIS and MES scores were recorded. The histopathology reports were assessed based on the completeness of information in their respective D, C, and A domains. The proportion of reports with information fully represented by the IBD-DCA reporting template and the distribution of biopsy sites were described. The correlation between IBD-DCA with UCEIS and MES was quantified via Kendall’s tau (τ) using the R statistical package v4.3.2.

Results

Of the 151 cases reported, 70 (46.4%) patients were female and 81 (53.6%) were male. 12 patients (7.9%) had full colonic biopsies, while the remaining cases were assessed with selective biopsies. Rectal biopsy was most often performed (83.4%). The IBD-DCA components were reported for every biopsied sites in 133 (88.1%) cases. Notable correlations included UCEIS vascular pattern with histological chronicity (τ = 0.3891), UCEIS erosions/ulceration with histological activity (τ = 0.3252), and histological activity with the total UCEIS score (τ = 0.3450). MES showed the strongest correlation with histological disease distribution (τ = 0.3450)(Table 1). All p-values < 0.001.

Conclusion

These data show encouraging uptake of this simple histological reporting template in UC in daily routine use. The findings suggest that the IBD-DCA score may be a useful addition in the clinical management in patients with UC.Read more P268 Artificial Intelligence and Panendoscopy – Automatic Detection of Pleomorphic Lesions in Multibrand Device-Assisted EnteroscopyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Device-assisted enteroscopy (DAE) stands as the sole diagnostic and therapeutic procedure capable of thoroughly examining the entire gastrointestinal (GI) tract. Nevertheless, its diagnostic yield falls short in ensuring a cost-effective panendoscopy and there is still a significant interobserver variability during the procedure. Multi-layered convolutional neural networks (CNN) have proven beneficial in numerous medical applications, yet there is a noticeable gap in research regarding their implementation in DAE. The aim of this study is to develop and a validate a multidevice CNN for panendoscopic detection of pleomorphic lesions (vascular lesions, hematic residues, protruding lesions, ulcers and erosions) during DAE.

Methods

In a retrospective analysis of 338 DAE procedures conducted at two specialized centers, frames from 152 single-balloon enteroscopies (Fujifilm®), 172 double-balloon enteroscopies (Olympus®), and 14 motorized spiral enteroscopies (Olympus®) were used to construct and validate the CNN. The dataset, comprising 40,655 images, was divided into a training dataset (90% of images, n=36,599) and a validation dataset (10% of images, n=4,066). We conducted a 5-fold cross validation, during training dataset. Primary outcomes were sensitivity, specificity, accuracy, and area under the precision recall curve (AUC-PR).

Results

During the training dataset's 5-fold cross-validation, the model demonstrated a mean sensitivity of 88.7% (88.0 – 89.5%), specificity of 98.0% (97.8 – 98.1%), PPV of 92.6% (92.0 – 93.1%), PPN of 97.0% (96.8 – 97.2%), with a mean accuracy of 96.0% (95.8 – 96.2%). During validation dataset, the CNN presented 88.9% sensitivity, 98.9% specificity, 95.8% PPV, 97.1% NPV, 96.8% accuracy and AUC-PR of 0.97. The CNN processed 124 frames per second.

Conclusion

This is the first CNN that can detect pleomorphic lesions in a panendoscopic and multidevice scenario (containing the majority of DAE devices used in medical practice). The model accurately identified pleomorphic lesions throughout the GI tract, featuring a short processing frame rate that may allow its application in real-time clinical procedures. The development and application of these systems could amplify the indications and benefits of DAE, increasing its diagnostic yield and cost-effectiveness.Read more P269 Harnessing Natural Language Processing for Structured Information Extraction from Radiology Reports in Crohn's Disease: A Nationwide Study From the epi-IIRNWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Large-scale analyses of imaging in Crohn's disease (CD) hold promise for advancing research on the inflammatory burden in the bowel as well as developing predictive models of disease progression. However, the lack of structured human annotations in these datasets limits the ability use these for research. This study from epi-IIRN nationwide cohort, aims to develop and evaluate Natural Language Processing (NLP) algorithms for extracting structured information from unstructured radiology reports on CT and MR enterography.

Methods

We identified radiology reports of all patients diagnosed with inflammatory Bowel Disease (IBD) in the nationwide epi-IIRN cohort, which includes data from the four Israeli HMOs, covering 98% of the population. We developed an in-house NLP platform using a publicly available Hebrew pretrained BERT model. After annotating a small portion of the reports for validation, we fine-tuned the model on our dataset through a masked language task, followed by a few-shot approach based on the Next Sentence Prediction (NSP) pretraining objective for classification model fine-tuning. The platform extracts radiological indicators related to inflammation, stenosis, and location, including wall thickening, enhancement, lumen narrowing, and dilation in the following locations: jejunum, ileum, colon, sigmoid, and rectum. We validated our models using a 5-fold cross-validation experimental setup, employing accuracy, PPV, NPV, F1 score and Cohen’s kappa score as the evaluation metrics.

Results

We extracted 9,704 radiology reports (6,299 MRE, 2,405 CTE) of 7,062 IBD patients (5,972 were diagnosed with CD, and 1,076 with ulcerative colitis). The mean age on the first imaging study was 36.8±17.1 years and 52% were male. We selected 500 studies for being annotated for the radiological indicators. The most common label was wall thickening in the ileum (215 positive patients vs.285 negative) while the least common was lumen narrowing in the jejunum (1 positive patient vs. 499 negative). Table 1 summarizes the results and label distributions. The mean [95% CI] accuracy/PPV/NPV/F1/Cohen's kappa score averaged over all labels was 0.98 [0.95,1]/0.99 [0.96,1]/0.83 [0.56,1]/0.86 [0.6,1]/0.63 [0.16,1]. The labels with the highest F1/Cohen's kappa score were wall thickening, enhancement, and narrowing in the Ileum while the label with the lowest F1/Cohen's kappa score were dilation in the Colon and the Jejunum.

Conclusion

NLP methods can extract structured information from radiology reports with high accuracy. Few-shot approaches based on the Next Sentence Prediction can alleviate the need for large scale data annotation for training. NLP offers exciting possibilities for large-scale studies utilizing imaging data in CD.Read more P270 Male Genitourinary Dysfunction after Primary and Reoperative Ileoanal Pouch SurgeryWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the preferred surgical treatment for patients with IBD or FAP. As these diseases often manifest during adolescence or early adulthood, treatment effects on genitourinary function (GU) and sexual function are of paramount importance. However, the reoperative IPAA (R-IPAA) effects on male GU function and sexual function compared to primary IPAA (P-IPAA) are not known. Therefore, we conducted an observational survey to compare the long-term GU functionality of P-IPAA and R-IPAA long-term GU functionality male patients. We hypothesized that R-IPAA is associated with higher GU-dysfunction compared to R-IPAA.

Methods

All adult male patients who underwent IPAA at a single tertiary hospital between 1983 and 2022 were identified and demographics and clinical data were obtained from our prospectively maintained pouch registry. Patients were surveyed using validated questionnaires (Table 1). The primary outcome was composite survey scores. Patients were stratified into P-IPAA or R-IPAA groups; R-IPAA was defined as IPAA excision, reconstruction, or revision. Patients status-post prostatectomy were excluded.

Results

A total of 1,836 male patients were surveyed, and 457 (24.9%) submitted a response. After exclusion criteria, 339 responses were analyzed:296 (87.3%) P-IPAA and 38 (11.2%) R-IPAA, which included 22 redo IPAA, 9 excisions, and 7 revisions. In both groups, most patients had ulcerative colitis (89 vs. 90%). P-IPAA compared to R-IPAA had a similar age at surgery (40.8 vs. 42, p=0.59), similar age at survey (56.2 vs. 56.4, p=0.94), and a similar interval between surgery and survey (15.4 vs. 14.4, p=0.51). The P-IPAA group had less severe sexual dysfunction than the R-IPAA group (IBD-MSDS, 2.0 vs. 7.0, p=0.002). No significant difference was observed between P-IPAA and R-IPAA in erectile dysfunction (SHIM score 21 vs. 18.5, p=0.24), urinary tract symptoms (CLLS, 5.5 vs. 8.0, p=0.06), use of therapeutic aids for sexual activity (6 vs. 7, p=0.29), or orgasm ability (4 vs. 4, p=0.3). Patients with P-IPAA had a higher CGQoL (0.83 vs. 0.7, p=0.02). There were no differences between patients who had difficulty conceiving a child (4 vs. 7, p=0.5) and those who experienced infertility (3 vs. 1, p=0.43). In patients with fertility problems, no quality-of-life differences were observed between the groups (FertiQoL, 85.9 vs. 88.5, p=0.62).

Conclusion

Primary-IPAA was associated with increased sexual function and overall higher global quality of life compared to R-IPAA. No difference in erectile function, LUTS, and the need for therapeutic aids for sexual function, orgasm ability, or fertility were observed.Read more DOP44 Melatonin Ameliorates Colitis In DSS-fed Mice Via The SIRT1 PathwayWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Melatonin is an amine hormone with high content in gastrointestinal tract, which plays a positive role in anti-inflammatory. Intestinal microbiota imbalance and intestinal immune damage caused by colitis are often accompanied by a decrease in endogenous melatonin. However, whether melatonin supplementation improves colitis, and the mechanism is unclear.

Methods

The study focused on melatonin treatment of colitis in dextran sodium sulfate(DSS)-fed mice and analyzed the mechanism multidimensionally by quantitative real-time PCR, western blotting, immunofluorescence, 16s-rDNA, and mRNA-seq.

Results

The weight, colon length, and microscopic structure of the colonic crypts were improved in DSS-fed mice after melatonin supplementation. Tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), and IL-6 were significantly elevated in colon tissues of the DSS group, and this result was down-regulated in the melatonin group. Tight junction proteins(ZO-1 and occludin) in the colonic mucosa were significantly decreased in the DSS group, and improved in the melatonin group. In terms of antimicrobial peptides, melatonin supplementation significantly increased levels of defa-3, defa-4, and CRAMP. Surprisingly, our study found increased expression of SIRT1 protein in the intestinal tissues of the melatonin group. After the addition of Ex-527, a SIRT1 inhibitor, the protective effect of melatonin on DDS-fed mice disappeared, and tight junction proteins did not differ from those of the DSS group. In addition, fecal 16s-rRNA results in the control, DSS, and melatonin groups suggested some differences. The DSS group had an increase in α-diversity (Shannon's Diversity Index) and a decrease in β-diversity (PCoA) in comparison to the control group, and all of these changes were reversed in the melatonin group, but there was no significance between the three groups. At the phylum level, Firmicutes were significantly increased in the DSS-fed group, and the melatonin group reversed this change. At the genus level, the abundance of Akkermansia was decreased in the DSS group and increased with melatonin supplementation. While the abundance of Desulfovibrio, a pathogenic genus was increased in the DSS group and decreased with melatonin supplementation. Colon tissue mRNA-seq identified a number of possible pathogenic and therapeutic pathways, such as Slc7a2, a cationic amino acid transporter.

Conclusion

The study suggests that melatonin modulates the intestinal mucosal barrier through the SIRT1 pathway to alleviate colitis.Read more DOP45 Blood-derived neutrophils give rise to differentially activated populations in the mucosa of active Inflammatory Bowel Disease patientsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Infiltration of neutrophils is the main histological feature in active inflammatory bowel disease (IBD). Recent data suggests that tissue- and tumour-infiltrating neutrophils can adopt remarkably different phenotypes with potentially different functions. However, the heterogeneity of this population in IBD remains unknown.

Methods

Single-cell RNA sequencing (scRNA-seq) data was generated from colonic biopsies of 92 individuals including 6 healthy controls (HC), 36 inactive IBD, 19 active Crohn’s disease (CD) and 31 active ulcerative colitis (UC) patients. Neutrophils (6038 cells) found in the inflamed colon of CD and UC patients were analysed using a curated pipeline in Seurat (v4.0.2)¹. Posterior analysis included the FindAllMarkers function (differentially expressed genes), Jaccard index similarity and the AddModuleScore function (comparisons with literature-described neutrophils), Monocle3 algorithm (developmental trajectory) and clusterProfiler (v3.0.4; enrichment and pathway analysis). For in vitro stimulation, neutrophils were isolated from the blood of HC donors (n=4) using a double Ficoll gradient ¹. Cells and supernatants were analysed for qPCR and ELISA determinations.

Results

We identified 6 different clusters/states of colonic neutrophils (Figure 1A). In agreement with our previous results¹ we found a population of S100A12/S100A8/S100A9 neutrophils (N0), IFN-response neutrophils (N3) and CCL3/CCL4 neutrophils (N2), in addition to N1.1 and N1.2 neutrophils. N3 neutrophils were enriched in the inflamed colon of CD patients compared to UC (17.2% vs 5.8%, p-value= 0.0021; Figure 1C). Comparative analysis with published datasets revealed that N0, N1.2 and N3 resemble populations of neutrophils found in blood^2,3. In contrast, N1.1 and N2-like clusters showed some similarity to umbilical cord blood³ and tumour-infiltrating neutrophils⁴. Trajectory analysis, originating from N0 (peripheral-like) neutrophils, showed two potential branches of differentiation, with N1.2 leading towards N3 (IFN-response) and N1.1 differentiating into N2 (CCL3) neutrophils (Figure 1B). Finally, pathway analysis showed that N2 neutrophils presented enriched gene expression of the TNF signalling pathway, and together with the N1.1 state, an enrichment of the IL1β signalling pathway as well. In vitro experiments revealed that TNF, IL1β and LPS can all induce expression of CCL3 and CCL4, top differentially expressed genes of N2 neutrophils.

Conclusion

We show that active IBD is associated with a highly heterogeneous population of infiltrating neutrophils. Some of them resemble neutrophils in peripheral blood, while others most likely differentiate in response to inflammatory cues present in the colon of active IBD patients.Read more P008 Machine learning derived histological features of epithelial injury and repair in Ulcerative Colitis biopsies correlate with disease severityWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Ulcerative colitis (UC) is an incurable chronic and debilitating disease. Frequent relapse is common despite available therapeutics. Endoscopically and histologically confirmed mucosal healing is the gold standard for long term remission, but a better understanding of disease pathology is needed for all patients to achieve inflammation reduction plus epithelial repair and wound healings. Here, we describe machine learning (ML) models that exhaustively quantify the inflammatory and epithelial histologic morphology of the colonic mucosa. Model-derived features are associated with Geboes Score (GS).

Methods

ML models (IBDExploreTM, PathAI, Boston) previously trained to quantify tissue features (e.g. epithelium) and cells (e.g. lymphocytes) were deployed on 447 whole slide images (WSI) of hematoxylin and eosin (H&E)-stained UC colonic mucosa from clinical and commercial sources.Model predictions yielded >900 quantitative human interpretable features (HIFs). To identify histological features of epithelial injury and repair, further analyses focused on 212 relevant HIFs that describe the epithelial layer that were divided into 10 Feature Categories (FCs, Table 1) based on whether they describe loss of integrity, surface or crypt injury and repair.Slide-level GS (Grade Level and Subgrade 3) were assigned to each WSI based on a median consensus scores of three expert gastrointestinal pathologists. Absolute Spearman rank correlations between individual HIFs and GS were calculated and associations between HIFs and GS were assessed at the FC level.

Results

HIFs were assessed at the FC level to identify broad trends associated with GS. Goblet cell HIFs in all epithelium and in crypt epithelium had the strongest associations, and were negatively correlated with Grade Level GS; positive correlations were found with enterocytes and loss of epithelial integrity HIFs (Figure 1A). Subgrade 3 GS was most strongly, and positively, correlated with epithelial injury and repair in the crypts, and negatively correlated with goblet cells in crypt epithelium and crypt epithelium goblet cell mucin (Figure 1B). Within FCs, the HIF driving the correlation trend was identified (Table 1). Model overlay outputs allow direct visualisation of histological features (Figure 1 C,D) illustrating disparities in the composition of GS0 and GS5 epithelium, and this is supported by the computed HIF values from each WSI.

Conclusion

Quantitative HIFs describing mucosa epithelial injury and repair strongly correlate with GS. Our models produce a granular, measurable blueprint of the epithelium that can be leveraged to inform hypotheses for therapeutic target selection, mechanism of action, and disease progression and remission.Figure 1Read more P009 IL-17 mediates visceral hypersensitivity by sensitising colonic nociceptorsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Comparison of cytokine expression in colitic tissue with respective cytokine receptor expression in pain sensing neurons highlights a likely contribution of IL-17 to the production of abdominal pain during flare.To explore this pro-nociceptive potential of IL-17 in colitis we examined the ability of IL-17 to stimulate sensory neurons and the colonic afferent response to noxious distension.

Methods

IL-17 mediated sensory neuron activation: changes in the intracellular [Ca²⁺]_i within thoracolumbar (T12-L5 spinal segments) dorsal root ganglia sensory neurons were examined in cells cultured overnight and loaded with Fluo-4-AM (30min) prior to imaging. Responses were measured to IL-17 (10-300 ng/mL) alone and following pre-treatment with either TRPV1 or TRPA1 inhibitors. Afterwards cells were exposed to capsaicin (1 µM) followed by 50 mM KCl, to confirm the presence of nociceptors and neurons respectively by positive response. In a separate set of experiments the effect of IL-17 was also examine on a neuron pure cell culture in which non-neuronal cells were removes by magnet assisted cell sorting.IL-17 mediated colonic nociceptor activation: electrophysiological recordings were made of lumbar splanchnic nerve activity and the response to noxious luminal distension of the isolated colorectum (ex-vivo), perfused with carbogenated Krebs solution, examined following pre-treatment with IL-17 (50 ng/mL) alone or in the presence of respective inhibitors.All experiments were performed using tissue from male C57BL/6J mice euthanaised by rising concentration of CO₂followed by exsanguination in accordance with Schedule 1 of the UK Animals Scientific Procedures act (1986).

Results

Consistent with the ability of IL-17 to stimulate sensory neurons including those classified as nociceptors by their co-sensitivity to capsaicin, pre-treatment with IL-17 also produced a significant sensitisation of the colonic afferent response to luminal distension at noxious distending pressures. The increase in [Ca²⁺]_i produced by IL-17 in sensory neurons was blocked by pre-treament with a TRPV1 antagonist but not a TRPA1 antagonist. Furthermore, the proportion of neurons stimulated by IL-17 was comparable between standard DRG cell cultures and neuron pure cell cultures demonstrating a direct effect of IL-17 on sensory neurons. Finally, IL-17 mediated mechanosensitisation of colonic nociceptors was unaffected by TRPV1 inhibition.

Conclusion

Our findings demonstrate that IL-17 stimulates capsaicin-sensitive nociceptors and mediates visceral hypersensitivity in colonic nociceptors consistent with a causative role for IL-17 is the generation of abdominal pain in people with colitis.Read more P010 Faecal microbiota composition by shotgun metagenomic sequencing approach in a newly diagnosed cohort of inflammatory bowel disease patients: results from the IBDomics projectWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Most studies examining differences in gut microbiota composition between healthy individuals and inflammatory bowel disease (IBD) patients, have been conducted on patients receiving immunosuppressive therapy. Such treatments can modify the gut microbiome and skew research data. The IBDomics cohort is a unique population of newly diagnosed IBD patients. Our aim was to elucidate the microbiota in this cohort compared to healthy controls (HC), and the differences between patients with Crohn’s disease (CD) and ulcerative colitis (UC).

Methods

Stool samples were collected from 104 patients with CD, 145 patients with UC, within the 1^st month after the diagnosis (prior to any IBD treatment), and 49 HC. Patients were classified according to endoscopic activity, using the Simple Endoscopic Score for CD (SES-CD) and the endoscopic subscore of the Mayo index for UC. Shotgun metagenomic sequencing was used to analyze microbiota composition. Shannon index (α-diversity) and Bray-Curtis dissimilarity (β-diversity) were used as tests of within-species diversity and within-group diversity, respectively.

Results

CD patients had a statistically significant decrease in α-diversity, compared to UC and HC; in addition, an inverse relationship was observed between the severity of CD activity and microbial α-diversity. On the opposite, the UC severity had no impact on α-diversity. β-diversity between pair-wise combinations was reduced in UC vs. HC compared to CD vs. HC. This index increased directly with severity in CD patients, while there was no difference in UC patients based on endoscopic severity (Figure 1). Considering the microbial taxonomic abundance, the greatest differences in UC patients compared to HC were found in Toxoplasma gondii and Gemella morbillorum. Of these two species, the 1^st showed a direct relationship with the severity of activity and the 2^nd one decreased with disease severity. CD patients had the greatest differences in several species of Adlercreutzia and Shigella genus compared to HC (Table 1). Upon grouping CD patients by disease activity, Adlercreutzia hattorii exhibited a consistent decrease across all activity subgroups compared to HC, while Shigella flexneri displayed a significant increase in CD activity groups without notable variance among them. This suggests that the presence of these bacteria is more closely associated with the intrinsic pathology of CD rather than its severity.

Conclusion

Newly diagnosed CD patients showed notable differences in microbiota compared to UC patients and HC. However, UC microbiome is relatively close to HC. Most of the species detected in the abundance analysis contribute to dysbiosis: declining beneficial genus like Gemella and Adlercreutzia and enhancing pathogen species.Read more P134 Characterization for the similarity assessment between proposed biosimilar SB17 and ustekinumab reference product using state-of-the-art analytical methodWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

SB17 is being developed as a proposed biosimilar to ustekinumab reference product (RP), a human monoclonal antibody (IgG1 kappa immunoglobulin) that binds to the common p40 subunit of cytokines interleukin (IL)-23 and IL-12. Binding to this subunit prevents interaction with their receptor, resulting in modulation the immune system responses which play a key role in the inflammatory disease. The objective of this study was to demonstrate structural, physicochemical, and biological similarity between ustekinumab RP and SB17 using various state-of-the-art analytical methods.

Methods

Comprehensive analytical characterization was conducted with side-by-side comparison of SB17 with the EU and US ustekinumab RP using various analytical methods. Comparisons included purity, product-related impurity, charge heterogeneity, primary structure, post-translational modification, higher order structure, quantity, Fab-related biological activities (potency and binding activity), and Fc-related biological activities.

Results

Based on the analytical similarity assessment, the structural, physicochemical, and biological characterization results demonstrated that SB17 is highly similar to the EU and US ustekinumab RP. In the structural aspects, it was confirmed that there is no clinically meaningful difference between post-translational modification profiles and higher order structures of SB17 compared to the ustekinumab RP. Product-related impurities in the form of aggregates were also confirmed to be similar. SB17 has a lower of acidic and basic peaks compared with ustekinumab RP, due to the difference in producing cell line. Ustekinumab RP is expressed in an Sp2/0 cell line, whereas SB17 is expressed in CHO cell line. However, the difference between SB17 and ustekinumab RP in the charge variants is not considered clinically meaningful since equivalent biological activity was observed. In case of mechanism of action (MoA)-related biological activities, SB17 is highly similar to the EU and US ustekinumab RP with respect to overall critical and non-critical quality attributes analyzed. Moreover, similarity or lack of activity in Fc-related biological activities was also confirmed. Based on these results, SB17 is expected to have highly similar safety and efficacy as compared to ustekinumab RP.

Conclusion

In summary, the overall analytical characterization and similarity assessment results show that SB17 is highly similar to the EU and US ustekinumab RP in terms of structural, physicochemical, biophysical, biological attributes.Read more P135 Mixed probiotics containing Bifidobacterium longum and its metabolites inhibit the formation of NLRP3 inflammasomes by suppressing GBP5 expression in macrophages in ulcerative colitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Ulcerative Colitis (UC) is a non-specific chronic inflammation of the intestine. As an intestinal disease with a gradually increasing incidence in recent years and increasingly valued by medical staff, UC has a close relationship with intestinal flora. At present, domestic and foreign guidelines point out that probiotics can be used to induce remission in ulcerative colitis, but there are no clear instructions on the selection of probiotics, the use of dosage forms, and the dosage of probiotics, and there is a lack of relevant clinical and basic research. This study aims to explore the distinct therapeutic effects of mixed probiotics and individual strains of probiotics (Bifidobacterium longum), as well as elucidate the underlying mechanisms responsible for these variations.

Methods

A total of 90 patients with ulcerative colitis (UC) were enrolled in our center, who were subsequently divided into three groups: control group, single strain probiotic group (Bifidobacterium longum), and mixed probiotic group. After three months of adjuvant probiotic therapy, serum and fecal samples were collected for comparative analysis of therapeutic effects using ELISA and fecal 16s rDNA and metabolome sequence analysis. Mixed probiotic and Bifidobacterium longum were cultured in BHIs in an anaerobic chamber. The supernatant obtained after bacterial cultivation was subjected to metabolome sequence analysis. Human colonic organoids and Caco-2 cells were co-cultured with mixed probiotic and Bifidobacterium longum subsequent to inflammation induction, and cytotoxicity, permeability, and inflammatory cytokine release were assessed. THP1 cells were also to co-cultured with mixed probiotic and Bifidobacterium longum, and expression of virulence genes was analyzed using RT-qPCR, transcriptome sequencing, and western blot. GBP5 gene manipulated cell and mouse model were used to evaluate inflammation and apoptosis.

Results

The utilization of mixed probiotic therapy in patients with UC demonstrated significantly superior therapeutic efficacy compared to those receiving a single strain probiotic (Bifidobacterium longum). Differential metabolite 8-Deoxylactucinwas identified among various groups through the metabolome sequence analysis of clinical patients’ feces, bacterial culture supernatant, and mouse feces. Through in vitro and in vivo experiments, it has been demonstrated that 8-Deoxylactucin exhibits inhibitory effects on the expression of GBP5 in THP-1 cells and ameliorates inflammation.

Conclusion

Collectively, these findings indicate that mixed probiotics and its metabolites suppress GBP5 expression in macrophages in ulcerative colitis.Read more DOP37 Noninvasive assessment of gut function using transcriptional recording sentinel cellsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Bacteria within the human gut continuously adapt their gene expression to environmental conditions that are associated with diet, health, and disease. Noninvasive measurements of bacterial gene expression patterns throughout the intestine are important to understand in vivo microbiota physiology and pathophysiology. Current methods do not offer sufficient information about transient or proximal events within the intestine without using indirect or invasive approaches that disturb normal physiology and are inapplicable to clinical practice.

Methods

Here we used transcriptional recording sentinel cells that through a reverse transcriptase-Cas1–Cas2 complex record their own short-lived mRNA expression into long-lived DNA-based CRISPR arrays to report on gut function. We colonized gnotobiotic mice with E. coli sentinel cells and performed Record-seq on fecal samples to reconstruct their cellular histories as they passed along the gastrointestinal tract.

Results

Upon colonization of the mouse intestine, sentinel cells reported on diet, inflammation, and microbial interactions. Through transcriptome-scale information, Record-seq elucidated E. coli’s adaptations to intraluminal conditions including pH, oxygen levels, and ion availability. Unlike RNA-seq, Record-seq performed on stool samples retained information from proximal gut sections to noninvasively report on the luminal conditions in vivo. In a mouse model of inflammatory bowel disease, Record-seq not only diagnosed the inflammation in a severity-dependent manner but also revealed pathological gut conditions such as mucus depletion and hyperoxygenation.

Conclusion

Transcriptional recording sentinel cells noninvasively report on gut function and reveal environmental cues such as diet, inflammation, and microbial interactions, even in proximal gut sections that are otherwise unamenable to unbiased diagnostic interrogation.Read more DOP38 A rare KRT17+ population emerges from the epithelium in the inflamed intestinal mucosa of patients with Ulcerative ColitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

KRT17 is an epithelial "alarmin" that contributes to the early host innate immune response to insults. We previously found that KRT17 transcription, not detectable in the healthy colon, is up-regulated in the intestinal mucosa of patients with active ulcerative colitis (UC). Here, we aimed to characterize the epithelial cells expressing KRT17 in UC mucosa and explore the contribution of the intestinal environment in promoting the emergence of this cell population.

Methods

We conducted single-cell RNAseq (scRNA-seq) on the epithelial compartment of intestinal biopsies from a cohort of non-inflammatory bowel disease (IBD) controls and patients with active UC. Analysis was performed using our own-curated pipeline in Seurat¹. Spatial protein localization was analysed by immunofluorescence on fixed intestinal samples. To measure the modulation of KRT17 and associated markers, ex vivo air-liquid interface (ALI) epithelial cultures derived from human non-IBD organoids were used. The signatures of UC-derived organoids² were mapped onto the scRNA-seq dataset.

Results

ScRNA-seq analysis identified a rare KRT17⁺ epithelial cell population emerging in active UC characterized by the expression of KRT17 (Fig. 1A) and other alarmins (KRT6A, KRT16, S100A8), metalloproteinases (MMP1, MMP10), and inflammatory markers (SAA1, DUOX2…). KRT17 protein, absent in non-IBD colon, was expressed in the epithelium of the inflamed UC mucosa exhibiting a patchy pattern, and marked epithelial clusters with both columnar and squamous-like morphology (Fig. 1B). The ALI culture closely recapitulated the differentiated intestinal epithelium in homeostasis by showing a columnar aspect, high expression of differentiation markers, and low or undetectable expression of stem/proliferation or KRT17⁺-cell markers. Exposure of the ALI culture to hypoxic stress (by re-submersion in expansion medium) induced the expression of KRT17⁺ cell-specific and inflammation markers (Fig. 1C), and the acquisition of a squamous morphology (Fig. 1D). IBD-related IFN-ɣ and IL-22 cytokines could not fully replicate this phenotype (Fig. 1E). Lastly, we observed that genes up-regulated in UC, compared to non-IBD organoids, were predominantly expressed within the KRT17⁺ population (Fig. 1F).

Conclusion

Our results suggest that a novel KRT17+ epithelial population may arise from the intestinal cells of inflamed UC mucosa under the influence of specific environmental factors. This population could contribute to the persistence of the disease over time.References1. Garrido A. et al, Nat Commun, 20232. Dotti I. et al, Gut, 2017Read more P192 Personalizing treatment for predicting response to infliximab in children with Crohn’s disease using proteomic biomarkersWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Identifying minimally invasive diagnostic biomarkers that predict and monitor response to TNF inhibitors would enable treatment to be personalized and increase knowledge of the biological pathways associated with response or lack thereof.

Methods

Children and adolescents with Crohn’s disease who started treatment with infliximab (IFX) were enrolled in a prospective, multi-center (n=6) trial to identify biomarkers that predict response to IFX. Electronic case report forms were prepared by Studytrax (Macon, GA). Subjects <18 years of age were diagnosed with Crohn’s disease using standard clinical/pathologic criteria. Clinical evaluation and serum samples were obtained prior to initiation of IFX, after induction (dose 4), at six months, and after one year or at the time of treatment withdrawal. There were 119 subjects enrolled and 102 subjects completed induction. Non-responders (n=15) were defined prior to the 4^th infusion as having a PCDAI > 10, an elevated Physician Global Assessment (PGA) or requiring dose escalation or medication change. Responders at the 4^th infusions were either in remission (PUCAI ≤ 10) or were described as quiescent by PGA. Using the 7k SomaScan (SomaLogic; Boulder, CO) proteomics platform, quantitative protein profiles were generated from banked pre-treatment (V1) and after the three-dose induction (V2) to identify candidate protein biomarkers predictive of therapeutic response. Associations between the 7,310 proteins detected with SomaScan and response to IFX were assessed using t test. Response predictor models were developed using linear regression with backward selection. We report our preliminary findings from a discovery cohort of 56 subjects who completed induction.

Results

There were 15/56 (27%) non-responders and 41/56 (73%) responders at V2 after IFX induction. SomaScan analysis of the 56 individuals identified sets of differentially expressed proteins discriminating between non-responders and responders at both V1 and V2 and also defined protein signatures that changed from V1 to V2 for responders and non-responders, respectively. Strikingly, only responders demonstrated significant decreases in pro-inflammatory pathways at V2 compared to V1, thereby correlating well with anticipated reduced inflammation in responders. A 6-protein linear regression model performed with an AUC of 0.99 for predicting IFX response at pre-treatment V1.

Conclusion

In a discovery cohort from a multicenter, prospective trial of children and adolescents treated with infliximab, a comprehensive proteomics platform was able to identify serum proteins that are highly associated with response to infliximab and accurately predict response prior to treatment.Read more P193 Fatigued patients with Inflammatory Bowel Disease exhibit distinct systemic antibody epitope repertoiresWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Patients with inflammatory bowel diseases (IBD) frequently experience fatigue, affecting up to 80% of those with active disease and approximately 50% with quiescent disease. The exact cause of IBD-associated fatigue is often unknown, making clinical management very challenging. In this study we aimed to explore whether patients with quiescent IBD reporting fatigue exhibit specific systemic antibody responses, which could provide insight into immune reactivities underlying fatigue.

Methods

Systemic antibody epitope repertoires were profiled in 327 patients with IBD (156 Crohn’s disease [CD]; 171 ulcerative colitis [UC]) leveraging phage-display immunoprecipitation sequencing (PhIP-Seq) against 344,000 rationally selected peptide antigens. Fatigue severity was assessed on a 10-point Likert scale, ranging from 1 (no fatigue) to 10 (highest fatigue severity). Quiescent IBD was defined as clinical (Harvey-Bradshaw Index [HBI] <5 or Simple Clinical Colitis Activity Index [SCCAI] <2.5) and biochemical remission (C-reactive protein [CRP] <5 mg/L) at time of sampling. Multivariable logistic regression analyses, allowing adjustment for potential confounding factors e.g. age, sex, and smoking, were performed to identify associations between fatigue and systemic antibody responses.

Results

A total of 105 different antibody-bound peptides were associated with fatigue (nominal P-value<0.05), albeit none passed adjustment for multiple comparisons. Among these antibodies, 50 (47.6%) were found to be less frequent in highly fatigued patients (fourth quartile, Q4), while 55 (52.4%) were identified as more frequent in highly fatigued patients compared to those with low fatigue scores (first quartile, Q1). Among highly fatigued patients, antibody responses were primarily directed towards viral antigens, notably several antigens from Epstein-Barr virus (EBV), as well as bacterial antigens, including functional proteins from Streptococcus and Staphylococcus species. Fatigued patients with CD exhibited elevated systemic antibody responses against allergens, Staphylococcus, Pseudomonas aeruginosa, and Shigella spp. Fatigued patients with UC showed higher frequencies of antibody responses against herpes simplex virus (HSV), influenza viruses, and few responses against allergens and Streptococcus bacteria. These results remained materially unchanged when repeating analyses in patients with quiescent IBD.

Conclusion

This study may suggest a potential role of viral antigens, particularly EBV, in the pathophysiology of fatigue in patients with IBD. However, larger confirmatory studies are needed to validate these findings. PhIP-Seq may represent a valuable strategy to approach the investigation of immune responses underlying complex symptoms such as fatigue.Read more DOP23 The role of histology for the prediction of clinical relapse in Crohn’s Disease: A substudy of the STORI cohortWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Deep remission has become the target in the management of Crohn’s disease (CD). The role of histology in the management of CD has not yet been established. The aim of this work was to study the impact of histological inflammation on the risk of clinical relapse in patients with CD in clinical and endoscopic remission and to study the correlation between histology and endoscopic scores and biomarkers.

Methods

All patients included in STORI (1) were eligible for inclusion. Fecal calproptectin and colonoscopy with CDEIS calculation were performed at inclusion. Two biopsies, taken either from the most inflammed macroscopic area or from an area with previous inflammation in case of mucosal healing (MH) were prospectively performed. MH was defined by the absence of ulcers. Different histological scores were calculated by 2 independent pathologists: Robart, Geboes, modified Geboes, Nancy, and DCA-IBD scores. Histological remission was defined by Nancy=0 ; Geboes ≤2 ; modified Geboes of grade 0 ; Robarts ≤3, IBD-DCA of C≤1 and A=0. Clinical relapse was prospectively evaluated in the STORI trial as CDAI>250 or CDAI between 150 and 250 with an increase of 70 points during 2 successive weeks compared to the inclusion visit.(1) Louis E et al .Gastroenterology 2012

Results

Eighty biopsies (22 ileal and 58 colonic) were available from 76/115 patients included in STORI. Among the 45 patients with MH, 30 had colonic biopsies, 11 had ileal biopsies and 4 had biopsies in both locations. Among colonic biopsies 68% had histological remission according to Nancy and modified Geboes scores, 65% according to DCA-IBD and Geboes scores and 71% according to Robarts score. Among ileal biopsies 53% had histological remission according to Nancy score, 47% according to Modified Geboes, Geboes and DCA-IBD scores, and 67% according to the Robarts score. Thirty-five patients (46%) experienced a clinical relapse during the follow-up including 16/45 (36%) and 19/31 (61%) in the group with MH and without MH respectively. Histological characteristics and histological scores were not predictive of clinical relapse. In the total cohort (n=76), the CDEIS score was correlated to Nancy (p<0,001, r=0,43), Geboes (p<0,001, r=0,47) and Robarts (p<0,001, r=0,45) scores. Fecal calprotectin was correlated to Nancy (p<0,001, r=0,48), Geboes (p<0,001, r=0,45) and Robarts (p<0,001, r=0,46) scores. The histological scores of Nancy, Robarts and Geboes were highly correlated (p<0,0001 ; r > 0,9).

Conclusion

Although correlated with endoscopy and biomarkers, histology was not predictive of clinical relapse in CD patients in clinical and endoscopic remission. These findings do not support the use of histology to predict clinical relapse in CD in clinical practice.Read more P233 Cytomegalovirus colitis in patients with moderate-to-severe Ulcerative Colitis: diagnosis, clinical impact and treatment efficacyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Cytomegalovirus (CMV) colitis is a serious concern worsening the prognosis of patients with ulcerative colitis (UC), involving mainly those who are not responding to immunosuppressive therapy. CMV colitis is an independent predictor of hospitalisation and surgery. Diagnosis of CMV colitis can be obtained either via immunohistochemistry (ICH) or tissue polymerase chain reaction (PCR), possibly both.We aimed to assess the prognostic impact of CMV colitis in patients with UC and the clinical utility of testing for CMV plasma-DNA reactivation.

Methods

We conducted a retrospective, observational, monocentric study in our IBD center in Bologna.Consecutive patients hospitalized for moderate-to-severe ulcerative colitis from January 2020 to June 2023 were included. Patients were tested for CMV colitis at hospitalization, along with other concomitant infections. Diagnosis of CMV-colitis was made either by ICH on colonic mucosa histological samples or on resected colon specimens. Need of surgery was evaluated at 28, 180 and 365 days.Basal characteristics of patients according to the presence or absence of CMV organ disease were compared with Mann-Whitney, X² or Fischer tests, as appropriate.A Kaplan-Meier survival analysis was calculated to verify whether antiviral treatment for CMV organ disease had an impact on avoiding surgery.

Results

A total of 135 patients were included. CMV organ disease was present in 37 (27.4%). Around half (51.4%) were diagnosed endoscopically, and 62.2% had evidence of plasma reactivation with a median of 1008 cp/mL CMV-DNA viral load (IQR 318-2980).Differences between the two groups (CMV colitis vs non CMV) included age (p = 0.004), Charlson Comorbidity Index (CCI) (p = 0.003), refractory disease (p = 0.007), and median CMV-DNA viral load (p < 0.001).Patients with CMV colitis needed surgery in 24/37 cases within 1 year from the diagnosis, compared to 41/98 in the non-CMV group. Interestingly, among the first group, 54% of cases underwent colectomy within 28 days, whereas only 34.1% underwent colectomy in the non-CMV group (p = 0.049).At multivariable analysis, steroid refractory disease, CCI and serum CMV-DNA reactivation were associated with CMV colitis. The latter had the highest OR (17.7 p < 0.001).Kaplan-Meier showed that patients who were treated with anti-viral therapy had a significant reduction of the risk of receive surgical treatment (p<0.001) [Table 1].

Conclusion

CMV-DNA plasma reactivation is independently associated to CMV colitis. The use of anti-viral treatment is able to reduce the risk to underwent surgery, suggesting that screening of CMV colitis is mandatory in patients with moderate-to-severe UC.Read more P234 Online direct-to-public calprotectin testing in the UK: what is out there in 2023?Wed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The longest component of the time-to-diagnosis is the interval between symptom onset and an individual seeking help. Recent reports in patients with sexually transmitted infections and hepatitis C, who also suffer health related stigma and a delay in diagnosis, suggest that this barrier may be overcome by the anonymity of direct-to-public testing. We sought to characterise the availability of online direct-to-public calprotectin testing in 2023 in the UK.

Methods

We undertook an online search using the Google search engine on May 25th, 2023, with the terms "buy" or "purchase" AND "calprotectin" AND "inflammatory bowel disease". Collection kits were procured, and stool samples tested to receive follow-up advice for known positive and negative stool samples. We recorded data regarding the assay, consumer information and the clinical advice offered on return of a positive and negative test.

Results

Overall, 54.5% (6/11) of available tests were home lateral flow tests, the remainder were home collection laboratory-based tests. Of the laboratory-based tests, three were conventional enzyme-linked immunosorbent assay (ELISA) assays and two were OC sensor tests. The lateral flow tests were considerably cheaper than the laboratory-based tests (median cost £14.20 [£7.85-21.00] vs £75.85 [£59-151], p<0.0001). The median turnaround time for the laboratory tests was 14 (1-23) days. All but one provider used a positivity threshold of 50ug/g. Eight of the eleven platforms (4 lateral flow tests and 4 laboratory-based tests) explicitly stipulated testing in the setting of gastrointestinal symptoms or suggested exclusion criteria. All tests included written and pictorial instructions with the testing kit. The median Flesch Kincaid readability score for the instructions and result reporting were 54.3 (43.9-73.7) and 51.8 (12.9-64.9): equivalent to a school reading grade of 9.2 (6.2-10.8) and 11.3 (7.2-15.8), respectively. Only two of the lateral flow tests provided written recommendations about follow up of positive results, whereas amongst the laboratory-based tests, all but one provider recommended onward discussion with a general practitioner or specialist. Two providers offered private referrals or consultations and six provided safety netting advice with regards to negative results.

Conclusion

In the UK online direct-to-public calprotectin testing is already readily available from multiple providers. Consumers can choose between home-based lateral flow tests or conventional laboratory testing. Further work is needed to redefine the diagnostic accuracy of calprotectin used in this way, however, the rapid turnaround times and anonymity suggest that direct-to-public calprotectin testing could be used to reduce the time to IBD diagnosis.Read more P235 Correlation of mental and psychological status to disease activity in patients with Inflammatory Bowel Disease using The Symptom Checklist -90- Revised Questionnaire (SCL90R)Wed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Inflammatory Bowel Disease can affect mental health. There is no evidence that stress is a direct cause of the disease. Most Inflammatory Bowel Disease patients describe an emotional impact, mainly feelings of depression and anxiety. Many questionnaires used to assess anxiety in those patients including Symptom Checklist -90-Revised Questionnaire. This research aimed to investigate Correlation of mental and psychological status to disease activity in patients with Inflammatory Bowel Disease using Symptom Checklist -90-Revised Questionnaire.

Methods

The study included one hundred patients (50 Crohn's Disease patients – 50 Ulcerative Colitis patients). Detailed history taking, systemic physical examination, laboratory investigations, Colonoscopy, Symptom Checklist -90-Revised Questionnaire. A self-report psychometric instrument (questionnaire) for every patient.

Results

The mean age of Crohn’s Disease patients was 24,2 years +/- SD 3,6 years. In Ulcerative Colitis patients the mean age was 28,5 years +/- SD 7,3 years. No age or gender relation could be detected with Symptom Checklist -90-Revised Questionnaire score in both groups, The study showed a direct correlation of Crohn's Disease Activity Index (CDAI) and endoscopic activity (Simple Endoscopic Score) (SES) to Symptom Checklist -90-Revised Questionnaire. There was direct correlation of Ulcerative Colitis disease activity (Simple Clinical Colitis Activity Index) (SCCAI) and Endoscopic activity (Ulcerative Colitis Endoscopic Index of Severity) (UCEIS) to Symptom Checklist -90-Revised Questionnaire.

Conclusion

There is a direct correlation of disease activity and Endoscopic activity in Ulcerative Colitis and Crohn's Diseases to Symptom Checklist -90-Revised Questionnaire.Read more P237 Cognitive debriefing of a patient-reported outcome measure for abdominal pain and loose stool frequency in Crohn’s diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Abdominal pain (AP) and loose stools are key symptoms of Crohn’s disease (CD). Patient-reported AP and loose stool frequency (SF) items comprise two of the three patient-reported items included in the Crohn’s Disease Activity Index. These AP and SF items are referred to as "the PRO" in Lilly’s clinical trials. This study aimed to elicit in-depth information on how patients understand and respond to the PRO.

Methods

Cognitive debriefing interviews were conducted in adults and adolescents (aged 15–17 years) with moderately to severely active CD. Eligible participants self-reported disease severity but had to provide proof that they were diagnosed with CD ≥6 months ago. Participants must have received biologic and/or conventional therapy for CD and must not have had surgery to treat CD. Participants provided feedback on the PRO and described what PRO response options or score changes would reflect meaningful improvement in symptoms or denote successful treatment. Interview transcripts and field notes were analysed using a standard thematic analysis approach.

Results

17 adults and 3 adolescents participated during May–July 2023. Participants had a mean age of 38 (range=17–60) years; 70% (n=14) were female; 70% (n=14) were White. Participants had been diagnosed, on average, 10 (range=0.5–29) years ago. Most participants (n=13, 65%) reported moderate CD severity. All participants interpreted the AP item as intended, found the response options clear and easy to use, and reported that it would be easy to recall their AP severity over 24 hours. Of the 13 participants reporting AP (mild: n=6, 30%; moderate: n=7, 35%), nearly all (n=11, 85%) would consider a 1-level improvement (e.g., ‘mild’ to ‘none’ on the four-level scale) as meaningful. Most participants (n=11, 55%) would consider a treatment successful if their AP was ‘mild’; while many others (n=8, 40%) would need their AP to be completely resolved (i.e., ‘none’). All participants easily understood the SF item, interpreted it as intended, and reported that it would be easy to recall how many very soft or liquid stools they had experienced in a 24-hour period. Participants generally considered a 35.5% decrease in the number of very soft or liquid stools to be a meaningful improvement. On average, participants would consider a treatment successful if they had 1.7 (range=0–5, median=1) very soft or liquid stools per day.

Conclusion

Participants understood and easily completed the PRO. These findings support the content validity of the PRO in adults and adolescents with moderately to severely active CD and provide insights on the amount of change in AP and SF that patients would consider meaningful.Read more P238 Autoimmune comorbidities in microscopic colitis: retrospective analysis of consecutive single centre patientsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Microscopic colitis (MC) is an autoimmune inflammatory condition that causes watery diarrhoea along with other symptoms like bowel incontinence, resulting in impaired quality of life and morbidity. MC is localized to the colon, although other autoimmune disorders are known to be more prevalent among MC patients.

Methods

A retrospective analysis of consecutive MC patients treated in Lithuanian University of Health Sciences Hospital Kauno Klinikos over the last 6 years was performed. Patient information was obtained from electronic records and reviewed for demographic characteristics and diagnosed conditions.

Results

94 MC patients were treated in our centre since 2017, 46 (49 %) with collagenous colitis (CC), 39 (41.5 %) with lymphocytic colitis (LC), 2 (2.1 %) with incomplete CC and 7 (7.4 %) with incomplete LC. 77 patients were female (82 %). Median age was 59 years [44.8-70.3]. There was a tendency for men to be younger (median 42 [37-68]) than women (median 60 [50-70.5]) but not significantly (p>0.05).31 MC patients (33 %) we diagnosed with concomitant autoimmune disorders. 20 patients (21.3 %) had autoimmune thyroiditis, 7 (7.4 %) had coeliac disease, 7 (7.4 %) had autoimmune skin conditions, 5 (5.3 %) had rheumatoid arthritis, 1 (1.1 %) had spondyloarthritis and 2 (2.1 %) had autoimmune hepatitis. 9 patients (9.6 %) had 2 autoimmune conditions in addition to MC and 1 patient (1.1 %) had 3.16 (34.8 %) CC patients, 11 (28.2 %) LC patients and 4 (57 %) incomplete LC patients had autoimmune comorbidities. 3 (6.5 %) CC patients, 3 (7.7 %) LC patients and 1 (14.3) incomplete LC patient had coeliac disease. Autoimmune thyroiditis was observed in 11 (23.9 %) CC patients, 6 (15.4 %) LC patients and 3 (42.9 %) incomplete LC patients. 2 (4.3 %) CC patients and 3 (7.7 %) LC patients had rheumatoid arthritis. 5 (10.9 %) CC patients and 2 (5.1 %) LC patients has autoimmune skin disorders. The differences between CC and LC patients were not statistically significant. Both patients with autoimmune hepatitis had LC and the patient with spondyloarthritis had incomplete LC.

Conclusion

MC patients in our centre were frequently diagnosed with additional autoimmune disorders warranting vigilance in clinical practice. There was no difference between CC and LC patients. Incomplete LC patients had a higher proportion of autoimmune comorbidities and though the number of cases was low, this opens up prospects for future investigation.Read more P320 Impact of Enterography on the Outcomes of Endoscopic Balloon Dilation for Ileocolonic Anastomotic Strictures in Crohn's DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Ileocolonic anastomotic stricture (ICAS) is a common complication following surgery for complicated Crohn's Disease (CD). Endoscopic balloon dilation (EBD) has emerged as a non-invasive therapeutic modality for symptom relief and delaying surgical interventions. However, the impact of enterography, utilizing magnetic resonance imaging (MRI) or computed tomography (CT), in characterizing ICAS and its influence on short- and long-term EBD outcomes remain unclear.

Methods

This retrospective study included patients who underwent EBD for ICAS. Demographic and clinical data were collected, encompassing short-term outcomes (procedure complications and symptom improvement) and long-term outcomes (need for surgery, hospitalization, or repeat dilation).

Results

A total of 15 patients with ICAS were included in the study, with 46.7% being females, and a mean age of 41.2±15.6 years at the time of EBD. Six patients (40%) had undergone enterography six months prior to EBD. The median balloon diameter used for dilation was 15mm (range: 10mm to 17mm) and during the procedure, significant mucosal inflammation of the anastomosis (Rutgeerts Score ≥2) was observed in seven patients (46.7%). EBD was successful in 12 patients (80%) without any immediate complications. In the 12-month post-procedure period, one patient experienced hospital admission due to intestinal occlusion, one patient required abdominal surgery, and another patient underwent two additional EBD procedures. We did not observe a trend for an increased occurrence of complications in patients submitted to EBD without prior recent enterography, in the 12 months following the procedure or thereafter.

Conclusion

In this small but homogeneous cohort, our findings suggest that recent enterography does not significantly improve ICAS EBD outcomes. Therefore, our data suggest that performing enterography should not delay EBD in symptomatic CD patients with ICAS.Read more P321 Development and validation of an Integrated Risk Score for future risk of Crohn’s disease in healthy first-degree relatives: The CCC-GEM Project, a multicentre prospective cohort studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Although the cause of Crohn’s disease (CD) is unknown, recent studies have identified a number of biomarkers associated with the risk of developing CD in healthy at-risk individuals. Establishing a combined prediction model that stratifies the future risk of CD in healthy at-risk individuals is the first step towards disease prevention and a better understanding of the preclinical phase of CD.

Methods

We recruited healthy first-degree relatives (FDRs) of persons with CD from 2008-2017 as part of the global multicenter prospective Crohn’s and Colitis Canada Genetic Environmental Microbial (CCC-GEM) Project. After collecting demographic information, blood, urine, and stool samples at recruitment, participants were followed for the development of CD. A GEM-integrative risk score (GEM-IRS), using random survival forest modeling that combined the baseline variables (demographics, measures of gut inflammation – fecal calprotectin, intestinal barrier function – urinary fractional excretion ratio of lactulose to mannitol, and fecal microbiome composition and predicted functional capacities – based upon 16S rDNA sequencing and PICRUSt2) to estimate time-to-CD onset, was derived and subsequently validated in two independent testing cohorts.

Results

Among 2,619 FDRs followed for a median of 6.8 years, 61 (2.3%) developed CD. The GEM-IRS, developed on the training cohort (n= 1,170), upon validation, showed a c-statistic of 0.789 in the pooled-testing cohorts (0.786 in the North American Testing cohort (n=1,141) and 0.804 in the Israeli Cohort (n=308)). The 4^th quartile group compared to the rest had significantly increased risk of CD (hazard ratio [HR] 6.42, 95% confidence interval [CI], 3.10-13.30) in the pooled-testing cohorts (HR 5.89, 95% CI, 2.70-12.85 in North American Testing cohort; HR 10.7, 95% CI 1.24-92.65 in Israeli cohort). Furthermore, the GEM-IRS predicted CD in pre-specified subgroups of FDRs with minimal subclinical inflammation (fecal calprotectin<50 ug/g) or normal barrier function measures (lactulose/mannitol ratio<0.025), and up to 7 years before diagnosis in the pooled-testing cohort.

Conclusion

The GEM-IRS, which includes biomarkers of gut inflammation, intestinal barrier function, and the gut microbiome, is a valid risk stratification tool for predicting future development of CD in healthy first-degree relatives of persons with CD. The score may be used to guide preventative care for healthy first-degree relatives.Read more P322 Compared Efficacy of Second-Line Treatments for Ulcerative Colitis After Failure of Vedolizumab in First-Line Treatment: A Retrospective Multicenter StudyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Vedolizumab is often used as the first-line advanced therapy for patients with moderate to severe ulcerative colitis (UC). There is currently no data reporting the efficacy and safety of second-line treatments after initial vedolizumab failure. The objective of our study was to compare the efficacy of anti-TNF, ustekinumab, and tofacitinib as 2nd line treatment of UC after vedolizumab exposure.

Methods

We conducted a retrospective multicenter study in 27 French and Belgian centers. All consecutive UC patients treated with vedolizumab between January 2019 and June 2023 as the first line and who received a 2nd line of anti-TNF, ustekinumab or tofacitinib were retrospectively included. The primary outcome was clinical remission at induction (week 14) defined by a clinical partial Mayo score ≤ 2 with no subscore > 1 without investigated treatment withdrawal. Clinical response was defined as a decrease in partial Mayo score of at least 30%.

Results

Among the 163 patients included, 94 (57.7%) were treated with anti-TNF (infliximab=71 (75.5%), adalimumab=21 (22.3%), and golimumab=2 (2.1%)), 56 (34.4%) with ustekinumab and 13 (7.9%) with tofacitinib. The median duration of the disease prior to second-line initiation was 9.5 months (IQR 16.0-146.0). The median duration of treatment with vedolizumab was 6 months (IQR 3.0-12.0). At week 14, 25/66 (37.9%) patients on infliximab, 7/23 (30.5%) on SQ anti-TNF (adalimumab and golimumab), 25/57 (43.9%) on ustekinumab and 7/13 (53.8%) treated with tofacitinib were in remission (p=0.49, Chi2 test). Response rates were 52.8%, 34.8%, 50.9%, and 53.8%, respectively, for the infliximab, antiTNF SC, ustekinumab, and tofacitinib groups.The survival without treatment discontinuation att 12 months was estimated at 51.6 (95% CI [39.6%-67.2%]) for infliximab, 45.7% (95% CI [28.5%-73.1%]) for SQ anti-TNF, 40.6% (95% CI [27.2%-60.6%]) for ustekinumab and 31.2% (95% CI [12.3%-79.2%]) for tofacitinib (p=0.95, log-rank test). Second-line treatment was discontinued in 41 patients (25.3%) for primary failure, 25 (15.4%) for secondary failure. Colectomy was required in 4 patients (2.5%) during follow-up.Infliximab was discontinued in 12 patients (12.8%) due to adverse reactions, including 6 allergic reactions. Among the 23 patients on SQ anti-TNF (adalimumab and golimumab), 2 required discontinuation (8.7%) due to adverse reactions. One side effect leading to discontinuation occurred with tofacitinib (7.7%) and none with ustekinumab.

Conclusion

After the failure of vedolizumab as a first-line biologic treatment for UC, the induction efficacy, persistence, and safety of the different second-line treatments seem similar. Current efforts to increase the sample size and strengthen the analysis is ongoing.Read more P323 Defining Normal Bowel Wall Thickness on Intestinal Ultrasound in an International Multicenter Cohort of Children with Inflammatory Bowel Disease in Sustained Deep RemissionWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Intestinal ultrasound (IUS) is a non-invasive, patient-centric tool for detecting and monitoring activity in patients with inflammatory bowel disease (IBD). Bowel wall thickness (BWT) is the most important parameter for assessing IBD activity, however, normal values are extrapolated from adults. We aimed to define normal BWT in children with IBD who achieved sustained deep remission.

Methods

International, multicentre, retrospective, pediatric IUS database including IBD patients (< 18 years) without a prior history of surgery or complications who underwent IUS after achieving sustained deep remission: absence of ulcerations on ileocolonoscopy and/or transmural healing on magnetic resonance enterography or computed tomography enterography and steroid-free clinical remission from 2020-2023. Descriptive statistics summarized data as percentages for categorical variables and median [IQR] for continuous variables. Primary outcome was median BWT by segment: sigmoid colon (SC), descending colon (DC), transverse colon (TC), ascending colon (AC), and terminal ileum (TI), assessed using Kruskall Wallis. Secondary outcomes included univariate association of BWT and age, sex, disease duration, diagnosis (Crohn’s disease (CD) vs. ulcerative colitis (UC)/IBD-unspecified (IBD-U) and medication exposure.

Results

80 patients (33 (41%) female; 51 (64%) CD:26 (33%)UC:3 (4%)IBD-U, median age 15.2 [14-16.6] years) with 400 bowel segments were included. Forty (50%) received anti-tumor necrosis factor therapy (anti-TNF), 18 (23%) ustekinumab (UST), 10 (12%) mesalamine(5-ASA), 6 (8%) vedolizumab (VDZ), 5 (6%) immunomodulator monotherapy (IM), and 1 (1%) upadacitinib (UPA) (Table 1). Median BWT was 1.3 [1.0-1.6]mm for SC, 1.3 [1.1-1.7]mm for DC, 1.3 [1.0-1.6] mm for TC, 1.3 [1.0-1.6]mm for AC, and 1.3 [1.1-1.5]mm for TI (Figure 1). There was no difference in BWT between segments (p=0.7952), age (p=0.1952) or sex (p=0.781). BWT was negatively associated with disease duration (p<0.05). UC patients had a 0.16 mm thinner BWT than CD (p<0.05). Mean BWT in patients on VDZ was thinner than those on anti-TNF monotherapy (-0.19mm, p<0.05). BWT in patients on anti-TNF combination therapy was thicker than patients on anti-TNF monotherapy (0.21mm, p<0.05). There was no BWT difference between patients on IM, 5-ASA and UST compared to anti-TNF (p>0.05).

Conclusion

Normal BWT for children with IBD in deep remission is less than adults, and unaffected by age, sex and bowel segment. BWT may be affected by disease duration, phenotype and medication exposure. These findings are crucial to the standardized assessment of transmural healing in children with IBD.Read more DOP05 Bowel damage and its correlation with the disability index in patients with recently diagnosed Crohn´s DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Crohn’s disease (CD) progression can lead to bowel damage (BD) and disability. However, the longitudinal characterization of BD and disability in early CD patients remains limited.

Methods

The Crohn´s Disease Cohort (CROCO) is a multicentre, European cohort study of newly diagnosed CD patients (<12 months following diagnosis) intended to prospectively characterize BD progression and disability. At one year following inclusion (Y1), BD progression was evaluated using the Lémann Index (LI). Magnetic resonance enterography was completed by all patients, with additional endoscopy and/or pelvic MRI based on disease location. Absence of BD was defined as a LI=0, and any presence of bowel damage was indicated by LI>0. Disability was assessed using the validated IBD-disability index (IBD-DI) encompassing various domains. We report the LI at Y1 and its association with significant disease features and with the IBD-DI.

Results

Among the 261 included patients, 135 have completed the Y1 visit, with 100 having their LI calculated [57% male, median age at diagnosis of 36 years old (IQR 26-48)]. Most patients (90%) had ileal or ileocolonic involvement, 68% had inflammatory phenotype, and 11% had perianal disease. At inclusion, 7% of patients had undergone surgery (5 intestinal and 2 perianal), and 53% had initiated biological therapy within the first year of disease, primarily anti-TNF in mono or combination therapy. Of those with stricturing (B2) or penetrating (B3) behaviour, 77% and 79%, respectively, were on anti-TNF therapy. Overall, 61% of the patients exhibited some degree of BD (LI>0), yet the median LI at Y1 was low [0.6 (IQR 0-2)]. Univariate analysis revealed an association between the presence of any bowel damage at Y1 and disease behaviour at inclusion (B2 OR 3.33, 95%CI 0.84-13.18 and B3 OR 8.5, 95%CI 1.82, 39.66; p<0.01). Additionally, there was a significant association with anti-TNF therapy (OR 2.88, 95%CI 1.24-6.66, p=0.012). In a multivariate logistic model, only older age at diagnosis appeared protective against any BD (Table 1). Among those evaluated for the LI, 84 completed the IBD-DI at Y1. The median IBD-DI was 17.3 (IQR 10.7-32.6) and 30% experienced moderate-to-severe disability (IBD-DI>35). No association was observed between LI and IBD-DI at Y1 (OR 1.09, 95%CI 0.39-3.04, p=0.86) and there were no differences in the median LI across disability categories (p=0.67) (Figure 1).

Conclusion

In a cohort of newly diagnosed CD patients, one-third exhibited no bowel damage as per the LI evaluation. For those presenting any degree of damage, the global LI remained low. No association was found with disability assessed by the IBD-DI. These data add to the growing concept that early disease represents a window of opportunity.Read more DOP24 Multi-omic sequencing reveals distinctive gene expression and DNA methylation alterations as potential predictors of primary sclerosing cholangitis development in treatment-naïve paediatric Ulcerative ColitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Primary sclerosing cholangitis (PSC) is a progressive choleostatic disease and up to 80% of patients also have ulcerative colitis (PSC-UC). This presents a clinical challenge owing to difficulty in diagnosis and increased risk for developing cancer. While several multifactorial processes including inflammation and microbial dysbiosis have been associated with PSC-UC pathogenesis, the precise molecular factors that regulate the phenotype of this disease subtype remain unknown.

Methods

We applied methyl-capture sequencing and mRNA sequencing to colonic mucosal biopsies derived from the DOCHAS study (GEN-193/11), to identify transcriptomic and epigenetic differences between treatment naïve paediatric UC (n=10), PSC-UC (n=10) and healthy controls (n=10) samples.

Results

Differential gene expression between UC and PSC-UC identified 9 up-regulated genes - ADMTS14, PNCK, NLRP3, SLC6A19, DLL1, FCGR2C, KLHL17, APOB, EHBP1L1 and 5 downregulated - SLC37A2, SLC14A2, RPL27, RPS25, SLC38A4 in PSC-UC relative to UC. Importantly, we show that expression of these genes was intricately regulated by master transcriptional regulators (pro-caspases, IL7RA) and transcription factors (TFs) :AR, p53, JUND, CEBPA. Similarly, differential methylation analysis between PSC-UC and UC identified 22 differentially methylated regions (DMRs) relative to controls, where 5 were hypermethylated and 8 hypomethylated. Intriguingly, in general we show that these DMRs are largely localised in gene promoter regions as opposed to enhancers. Importantly, we show that these DMR’s identified between PSC-UC vs UC is enriched for binding sites for the TF: ASCL1, suggesting its activity likely is effected due to the altered methylation of its binding site in PSC-UC patients. Collectively, these results highlight the importance of TF’s in driving molecular differences between PSC-UC and UC paediatric patients in a treatment naïve setting.

Conclusion

In summary, for the first time this study provides a critical insight into the transcriptional differences between treatment naïve children with PSC-UC vs UC as well as highlights the intricate regulatory processes involving master transcriptional regulators, transcription factors and DNA methylation. These processes thus warrant further examination in larger cohorts to rationalise their role as diagnostic/therapeutic targets.Read more DOP25 Antibodies against Neutrophil Extracellular Traps (ANETAs) are associated with more severe disease course in Ulcerative ColitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Antibodies against Neutrophil Extracellular Traps (ANETAs) have emerged as markers in multiple autoimmune disorders (i.e. rheumatoid arthritis and systemic lupus) associated with disease activity. We investigated the presence of ANETAs and their influence on disease course in Inflammatory Bowel Disease (IBD).

Methods

Serum samples from UC (n=33), Crohn's Disease (CD; n=28), and healthy controls (HC; n=8) underwent incubation with non-lytic Neutrophil Extracellular Traps (NETs) for immunofluorescence microscopy. For clinical relevance, these patients were followed over ten years to track treatment resistance, extraintestinal manifestations, surgeries, and disease recurrence (Table 1). For functional relevance, in vitro generated NETs were exposed to ANETAs, followed by quantifying macrophage-mediated clearance of these ANETA pre-treated NETs by real-time microscopy via pHrodo for 24 hours, as well as assessing pro-inflammatory cytokine (IL-6, TNF-α, IL-8, and IL-23) genetic expression levels in these macrophages.

Results

Among UC patients, ANETA positivity correlated with high rates of treatment resistance, extraintestinal manifestations, colorectal surgeries, and recurrence of disease like pouchitis (93.3% vs. 6.7%, 61.5% vs. 38.5%; 71.4% vs. 28.6%; 87.5% vs. 12.5%, for ANETA⁺ and ANETA^- UC patients, respectively). CD patients with ANETAs exhibited high rates of resistance to treatment (75% vs 25%) and lower rates of extraintestinal manifestations, colectomy, and disease recurrence (38.1% vs 61.9%, 40% vs 60%, 33.3% vs 66.7%) (Fig 1A). Macrophages displayed robust engulfment of untreated NETs and those treated with healthy control sera, while ANETA-coated NETs exhibited reduced susceptibility to macrophage phagocytosis (Fig 1B). Gene expression analysis revealed a significant upregulation of pro-inflammatory cytokines (IL-6, TNF-α, IL-8, and IL-23) when NETs were incubated with serum from ANETA-positive individuals compared to sera from healthy controls (p<0.05).

Conclusion

ANETAs may serve as markers for a distinct subgroup of UC patients characterized by aggressive disease and poorer prognosis. The potential mechanism might involve impaired NETs clearance by, and inducing a proinflammatory response in macrophages. Discrepancies observed between UC and CD suggest diverse pathophysiological mechanisms in both diseases. Further research is imperative to comprehensively understand the underlying pathophysiology, function, and potential clinical applications of ANETAs in IBD.Read more P363 Multimodal dynamic ultrasound approach as predictor of response in patients with Crohn’s disease treated with ustekinumabWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Early prediction of the response to biological drugs in Inflammatory Bowel Diseases (IBD) is of utmost importance to allow prompt optimization of therapeutic strategies. Ustekinumab (UST) is nowadays a milestone in the treatment of Crohn’s disease (CD), but potential markers predicting its long-term efficacy are still lacking. Multimodal ultrasound (US), encompassing B-mode US, color-Doppler and contrast-enhanced US (CEUS), is a promising non-invasive technique, providing complementary information to endoscopy, due to its ability to both assess transmural healing and quantify changes in bowel microvascularization over time. The main objective of this study was to evaluate the role of multimodal US in predicting endoscopic response to UST in patients with CD. The secondary aim was to develop an US score that allows an early detection of treatment response.

Methods

We conducted a prospective monocentric study in the IBD outpatient clinic of Policlinico Agostino Gemelli in Rome, enrolling consecutive patients with moderate to severe ileal CD, who were scheduled to begin UST therapy as per clinical practice. Demographic, clinical and laboratory data were collected. Clinical activity was defined according to Harvey-Bradshaw Index. A complete US evaluation including B mode, Doppler, dynamic CEUS and elastography was perfomed at the time of induction (T0) and after 8 (T1), 16 (T2), 24 (T3) and 48 (T4) weeks of therapy. Each US parameter and their variations from baseline were correlated with endoscopic response (SES-CD reduction of at least 50% from baseline) and mucosal healing (SES-CD < 3) after 1 year.

Results

A total of 52 patients were included, 29 (55.8%) of which reached endoscopic response at T4. Median values of US parameters at the various time points were significantly different in the group who achieved endoscopic response from non reponders’ group (Figure 1). The univariate analysis showed that the percentage changes between T3 and T0 of bowel wall thickness, Limberg score (LS), mean signal intensity, rise time, wash-in rate (WiR), C reactive protein and Harvey-Bradshaw Index were associated with long-term therapeutic outcome (table 1). At the multivariate logistic regression analysis, three independent predictors of endoscopic response were selected: male sex, ∆%LS, and ∆%WiR. Based on the above parameters, we developed an US score that showed a good performance in predicting 1 year-endoscopic response (area under the curve: 0.91).

Conclusion

Multimodal ultrasound provides early predictors of the long-term therapeutic outcome in patients with CD treated with UST.Read more P364 Faecal calprotectin testing in patients presenting with lower gastrointestinal symptoms; a retrospective primary care study in the United KingdomWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Faecal calprotectin (FC) is of value in differentiating Inflammatory Bowel Disease (IBD) from other causes of lower gastrointestinal (GI) symptoms and is recommended in national guidance. This study aims to examine the role of and factors associated with faecal calprotectin requesting in primary care.

Methods

Retrospective open cohort study using Clinical Practice Research Datalink (CPRD Aurum) of adults aged 18 years and above with lower GI symptoms between 2015 and 2019. FC requested 30 days before to 3 months after a lower GI symptom record in primary care were included. Logistic regression model was used to explore patient level factors associated with FC testing. Referral pathways and outcomes in terms of IBD diagnoses of patients with and without FC testing were also examined.

Results

Of 741,190 symptomatic patients, only 18,320 (2.5%) patients had a FC requested in primary care: median age 38.3 (IQR 28.9-50.7); 51.4% females. The percentage of FC requests in symptomatic patients increased from 0.02% in 2010 to 4.4% in 2019 (p=0.001).FC value of <50 ug/g and 50-200 ug/g were predominantly seen in patients with abdominal pain (42.1% and 37.9% respectively) while FC > 200 ug/g was predominantly seen in patients with diarrhoea (45.3%). The only patients with a significant risk of IBD with a FC 50-200ug/g were patients with rectal bleeding (8%).Factors associated with less FC requesting included: increasing age (>70 years aOR 0.16 ( 95% CI 0.15-0.18); female (0.89,0.86-0.92); Black (0.61, 0.56-0.66) or Asian (0.75, 0.70-0.80) ethnicity; obesity (0.89,0.85-0.93); lower socioeconomic status (0.91,0.86-0.98); comorbidity score >2 (0.73,0.68-0.79); and current smoking (0.89,0.85-0.92). Patients with change in bowel habit (7.31,6.90-7.75); rectal bleeding (2.04,1.95-2.13); diarrhoea (2.88,2.78-2.99) as a presenting symptom compared to abdominal pain and ex-smokers (1.06,1.03-1.11) had more FC requests.Of patients referred with a FC >200 ug/g, 21.5% were diagnosed with IBD but only 2.9% of patients with a FC 50-200ug/g. 27.8% patients with a normal FC test result were still referred to secondary care, of which only 0.4% had IBD.

Conclusion

Despite an increase in FC requests in recent years, only 4.4% of patients with relevant lower GI symptoms had an FC requested in primary care as recommended. Despite a negative FC test, 27.8% of patients were still referred to secondary care with very few patients diagnosed with IBD (0.4%).Read more OP34 Risk of Disease Recurrence and Re-resections in Crohn's Disease Patients Undergoing Primary Bowel Resection: A Population-Based StudyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The rate of having a resection for patients with Crohn's disease (CD) have decreased over decades, while the rates of re-resections seem to have been stable around 1/3 in historic cohorts. Re-resection rates might be influenced by targeted therapies. We aimed to investigate the re-resection rates and risk of recurrence in a contemporary cohort and the effect of medical treatment on these parameters.

Methods

This population-based cohort included all CD patients undergoing primary intestinal resection between 2010 and 2020 in Eastern Denmark, with a background population of 2,730,000 (46% of the Danish population). Individual clinical characteristics, medication, surgical procedures, and complications, as well as imaging, and endoscopy results were collected. Disease recurrence was defined as a colonoscopy with SES-CD≥3, Rutgeerts score ≥2i, inflammation or stenosis on imaging (MRI, CTA, or IUS), fecal calprotectin ≥ 250 mg/kg, starting corticosteroids after resection or re-resection due to disease activity. We characterized the cohort using nonparametric statistics (median, IQR, percentages) and survival analysis. A Cox regression analysis with propensity score incorporating Montreal classification, age, gender, smoking, and types of resection (colon, ileocecal, or small bowel) was conducted to assess the effect of initiating prophylactic biologic treatment within the first year from resection.

Results

A total of 631 patients had a primary resection due to disease activity, with a median follow-up from time from diagnosis of 118 months (IQR: 69-170) (Table 1). Prior to the first resection 337 (53%) patients received immunomodulators and 249 (39%) biologics; the same numbers post-surgery were 314 (50%) and 264 (42%), respectively. A total of 256 (41%) patients were resected within two years from diagnosis while this proportion increased to 424 (67%) and 533 (84 %) after 5 and 10 years, respectively. Re-resection rates due to disease activity 5 and 10 years after primary resection were 5% and 10%. The median time from primary resection to disease recurrence was 11,3 months (IQR: 4.7-24.8) (Figure 1). Median time from first to second and second to third resection were 37 months (IQR: 15-64) and 38 months (IQR: 26-55), respectively. We found no significant difference regarding prophylactic biologic therapy within the first year of resection (n 45) based on recurrence or re-resection compared to patients not starting biologics within the first year (HR 0.40, 95%CI(0.12-1.34), p=0.14).

Conclusion

Most patients undergoing primary resection face post-surgery disease recurrence, yet 1 in 4 remain relapse-free for decades. Despite extensive biologic therapy, 15% still require further resections due to disease activity.Read more OP35 Efficacy of mirikizumab in comparison to ustekinumab in patients with moderate to severe Crohn’s disease: Results from the phase 3 VIVID 1 studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The primary objective of the VIVID-1 trial (NCT03926130) was to demonstrate efficacy and safety of mirikizumab (miri), a p19-directed anti-IL-23 antibody, compared to placebo (PBO) in patients (pts) with moderate-to-severe Crohn’s disease. Miri demonstrated statistically significant improvements in co-primary and all key secondary endpoints versus (vs) PBO¹. Here we present the results of secondary endpoints on the comparisons of miri to ustekinumab (uste), a p40 directed anti-IL-12/IL-23 inhibitor from the Phase 3, randomised, double-blind, double-dummy, active- and PBO-controlled, treat-through (TT) study, VIVID-1 (NCT03926130).

Methods

Adult pts (N=1065) were randomised 6:3:2 to miri (N=579) 900mg intravenously (IV) every 4 weeks (Q4W) to W12, then 300mg subcutaneously (SC) Q4W to W52, uste (N=287) one ~6 mg/kg IV dose, then 90mg SC Q8W to W52 or PBO (N=199). At W12 PBO responders continued PBO to W52; PBO non-responders received the same blinded miri regimen as described above (IV then SC). Efficacy of miri vs uste was assessed by the proportion of pts achieving endoscopic response and by the proportion of pts achieving clinical remission by Crohn’s Disease Activity Index (CDAI) at W52 (both gated). Additional non-multiplicity-adjusted endpoints included endoscopic remission, corticosteroid-free clinical remission by CDAI, and the composite of CDAI clinical remission and endoscopic response at W52. (Figure 1 for definitions).

Results

Baseline characteristics were overall balanced across the three treatment groups (table 1). Pts treated with miri achieved all key major secondary endpoints (p<.000001) compared to PBO (Figure 1). Miri achieved non-inferiority to uste for clinical remission by CDAI (p=0.113117) (Figure 1C). Although superiority to uste in endoscopic response was not achieved (p=0.51) (Figure 1A), in biologic failed pts miri demonstrated a numerical trend towards greater response rates compared to uste for endoscopic response and clinical remission by CDAI (Figure 1 B & D). The overall safety profile was consistent with the known safety profile of miri. The proportion of treatment emergent adverse events (TEAE) were similar for miri (78.6%) and uste (77.3%); most common TEAEs were COVID-19, anaemia, arthralgia, headache, upper respiratory tract infection, nasopharyngitis and injection site reaction. Instances of serious adverse events were comparable for miri (10.3%) and uste (10.7%).

Conclusion

In this phase 3 TT design study, miri achieved non-inferiority to uste for clinical remission by CDAI. In biologic failed pts miri had a numerical trend towards greater response compared to uste in clinical and endoscopic endpoints, with an acceptable safety profile.¹Ferrante et al., submitted to ECCO 2024Read more DOP22 Predictive biomarkers of therapeutic response in Inflammatory Bowel Disease: a step towards personalized medicineWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Inflammatory bowel diseases are complex conditions characterized by heterogeneity at clinical, immunological, molecular, genetic, and microbial levels. The most effective approaches to induce clinical remission and control inflammation in these diseases are biologic and JAK-inhibitor therapies. However, a significant proportion of patients do not respond to treatment. Consequently, the identification of predictive biomarkers of clinical response to the different available therapies could improve the selection of patients who may benefit from the most appropriate treatment.

Methods

A multiomic study (transcriptomic, proteomic, metabolomic and metagenomic) was performed in 53 patients with active Crohn´s disease (CD) and 50 patients with active ulcerative colitis (UC) before and after 14 weeks of treatment (anti-TNFα, ustekinumab, vedolizumab or tofacitinib). Responders and non-responders patients were categorized based on endoscopic findings. Samples (serum, urine, stool and intestinal biopsies) were used for RNA-seq analysis, liquid chromatography-mass spectrometry, nuclear magnetic resonance, and 16S rRNA gene sequencing.

Results

Our findings revealed multiple mRNAs, proteins and metabolites associated with the response to different treatments (Table 1). Differential gene expression analyses in intestinal tissue showed that the main differences were detected between responders versus non-responders UC patients to anti-TNF, vedolizumab and tofacitinib. Proteomic analysis found numerous differentially expressed proteins between the study groups. Additionally, ROC curves revealed two proteins with good predictive value to discriminate between CD and UC patients responders versus non-responders to anti-TNF treatment (AUC=0.81 and AUC=0.96, respectively). Metabolomics showed up-regulation of 21 lipoproteins in serum from CD patients responders to ustekinumab compared to non-responders. Metabolic analysis pathways identified enrichment in ketone and butyrate metabolism, mitochondrial electron transport chain, carnitine synthesis, and oxidation of chain fatty acids. Regarding metagenomic results, only differences were found in microbial composition in responders versus non-responders UC patients treated with anti-TNF (Figure 1).

Conclusion

This study provides early insights into shifts in gene and protein expression in intestinal tissue, alterations in serum and urine metabolites, and changes in gut microbiota as potential predictors of response to biologics and JAK-inhibitor treatment. Further research is needed to validate these results and asses their clinical significance in identifying patients most likely to benefit from each therapeutic approach.Read more P324 Urine metabolite profile characterizes clinical activity and disease extent in patients with inflammatory bowel diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Inflammatory Bowel Disease (IBD), which comprises Crohn's Disease (CD) and Ulcerative Colitis (UC), is a disorder in which complex interactions between genetic, environmental, and microbial factors trigger alterations in the immune intestinal response. On the other hand, nutrient catabolism from the diet carried out by the microbiota results in the formation of metabolites that also impact immune responses on the intestinal mucosa. Considering that IBD patients have altered microbiota compared to healthy controls (HC) and that the urinary metabolic profile of an individual is the result of a combination of genetic, dietary, and microbial components, we propose the hypothesis that the urinary metabolic profile distinguishes IBD patients from HC. The aim of the study was to compare metabolomic analysis of urine samples from HC and IBD patients.

Methods

27 patients were included [HC (n=10), UC (n=10), and CD (n=7)]. Clinical IBD activity was evaluated with partial Mayo score (UC) and Harvey-Bradshaw index (CD). Metabolites in urine were measured using gas chromatography-mass spectrometry (GC-MS). Metabolomic analysis and machine learning were performed using the MetaboAnalyst software. PLS-DA was used for multivariate analysis, and clustering separation was performed using hierarchical clustering. To identify and interpret patterns of metabolite concentration changes in a biologically meaningful way we perform Over Representation Analysis.

Results

In total, 62 organic acids were detected. Comparing UC and HC revealed 11 significantly altered metabolites (9 increased and 2 decreased). Main increased metabolites comprised lactic acid (p=0.0015), pyroglutamic acid (p=0.0147), isocitric acid (p=0.0325), and phosphoric acid (p=0.0091). Interestingly, the value of adipic and suberic acids were higher in remission vs. active patients. Furthermore, adipic acid was higher in UC patients with proctitis compared to left-side colitis/extensive colitis. Comparing CD and HC revealed only 2 significantly altered metabolites, glycolic acid (p=0.0214), and lactic acid (p=0.0111). Oxalic acid was more concentrated in CD patient with perianal disease. Finally, propionic and phosphoric acid were able to discriminate UC from CD patients. The most affected metabolic pathways were related to energy metabolism and oxidative stress, including the Warburg effect (p=0.0016), gluconeogenesis (p=0.0106), pyruvate metabolism (p=0.0197) and glutathione metabolism (p=0.0039) (Fig.1).

Conclusion

We found that the urinary metabolic profile of IBD patients differs from the HC, particularly for UC patients. These metabolites profile could be used to improve diagnosis and monitoring in patients with IBD.Read more P325 Post-COVID general health symptoms in patients with Immune Mediated Inflammatory DiseasesWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Post-COVID entails persistent symptoms following a presumed or confirmed SARS-CoV-2 infection and has a prevalence of 12.5% in the general population in The Netherlands. The aim of this study is to evaluate post-COVID general health symptoms reported by patients with Immune Mediated Inflammatory Diseases (IMIDs), given the unclear prevalence.

Methods

An online questionnaire was distributed to IMID patients at dermatology, rheumatology and gastroenterology departments in an academic and teaching hospital in Rotterdam, the Netherlands. Only patients on systemic therapy were included. General health symptoms were compared between patients with and without prior SARS-CoV-2 infection. Multivariable logistic regression, adjusted for disease-related factors and known post-COVID risk factors, was performed to assess the association between SARS-CoV-2 infection and symptom occurrence. Additionally, the self-reported prevalence of post-COVID symptoms was assessed by asking patients if they linked their symptoms to the previous SARS-CoV-2 infection.

Results

The final study population comprised 1,518 patients, of whom 58% (n=877) reported ≥ 1 SARS-CoV-2 infections (table 1). More patients with a prior SARS-CoV-2 infection reported general health symptoms compared to those without (56% vs 44%; P<0.001) (figure 1). After adjusting for potential risk factors, including age, sex, smoking, diagnosis, SARS-CoV-2 vaccination status, and immunosuppressive therapy, a consistent significant association was found between SARS-CoV-2 infection and symptoms (OR 1.53; 95%CI 1.23-1.91; P<0.001). Sub-analysis showed a significant association between self-reported COVID-19 severity and symptoms, while presumed SARS-CoV-2 variant (based on date of reported infection) and number of infections were not associated. Fatigue was the most common symptom in both patients with and without a previous SARS-CoV-2 infection, with significantly higher prevalence among patients with previous SARS-CoV-2 infection (42% vs 32%; P<0.001). After adjusting for the potential risk factors, a previous SARS-CoV-2 infection remained significantly associated with fatigue (OR 1.31; 95%CI 1.04-1.64; P=0.021). Of the patients with a prior SARS-CoV-2 infection, 14% (122 out of 877) reported post-COVID symptoms, with fatigue as the most common complaint (78%).

Conclusion

The self-reported prevalence of post-COVID general health symptoms among IMID patients on systemic therapy (14%) aligns with that of the general population. The prevalence of symptoms, particularly fatigue, is elevated in patients with a history of a SARS-CoV-2 infection. Our findings emphasize the importance of incorporating SARS-CoV-2 infection history when evaluating fatigue in IMID patients during outpatient visits.Read more P326 Impact of disease flares on resource use, health-related quality of life and productivity in untreated Crohn’s Disease patients in US: an analysis of national health and wellness survey dataWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Patients with Crohn’s Disease (CD) alternate periods of exacerbation, flares, and periods of remission. The periods of flares can be debilitating to patients causing significant discomfort impacting the patient’s health-related quality of life (HRQoL). Despite symptoms, many patients do not receive treatments for their condition thus our objective was to describe the burden related to healthcare resource utilization (HRU), HRQoL and work productivity among a real-world cohort of patients who are not receiving any prescribed medications for CD.

Methods

The 2019 National Health and Wellness US Survey (NHWS) data was analyzed. NHWS is a self-administered Institutional review board (IRB) approved, internet-based annual survey that assesses numerous health conditions, demographic characteristics, medical history, healthcare utilization, attitudes, and outcomes. Respondents currently not taking prescription treatment for CD were categorized by flare frequency as infrequent (0-2 flares/year), intermediate (3-6/year), and frequent (>1/month to <7/week). HRU included HCP visits, gastroenterologist visits, emergency room (ER) visits and hospitalizations. HRQoL was assessed using the 5-dimension EuroQoL questionnaire (EQ5D), and work activity impairment using the Work Productivity and Activity Impairment questionnaire.

Results

A total of 74,994 respondents participated in the survey, of whom 577 reported being diagnosed with CD and 231 (40.0%) of whom were not taking prescription treatment for CD. Fifty-six percent of the untreated sample reported having mild disease. Among the untreated patients, 37% reported infrequent, 21% intermediate and 42% frequent flares. The mean age of patients with frequent flares was lower than those with infrequent or intermediate flares (infrequent: 51 years; intermediate: 45 years; frequent: 41 years). The mean EQ5D summary score decreased as the frequency of flares increased (infrequent: 0.77, intermediate: 0.66 and frequent: 0.63). Patients with frequent flares had higher gastroenterologists, ER and hospitalization rates compared to patient with infrequent of intermediate flares (Table 1). Overall work impairment was reported by 40%, 52% and 63% of patients with infrequent, intermediate, and frequent flares respectively (Figure 1).

Conclusion

This real-world analysis shows up to two-thirds of untreated CD patients present intermediate or frequent flares. In addition, those with frequent flares experienced poorer HRQoL, lower work productivity, and had higher healthcare resource use. This study reveals a high level of disease burden in patients who are not receiving treatment, the majority of whom reported to have ‘mild’ disease.Read more OP30 Endothelial cell-mediated smooth muscle hyperplasia in Crohn’s disease intestinal strictures: Caveolin 1 as a potential therapeutic targetWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Intestinal stricture is a severe and common complication of Crohn’s disease (CD). Current therapies offer limited success and surgery is often needed. Smooth muscle hyperplasia and hypertrophy play a key role in CD stricture development. This study explores the transcriptomic features of fibrostenotic CD, focusing on the endothelial contribution to smooth muscle changes within intestinal strictures.

Methods

9 CD patients undergoing surgery for fibrotic strictures were prospectively enrolled. Dissected samples from the stricture and the adjacent proximal and distal non-strictured areas were obtained from fresh specimens collected directly from the operating theatre. RNA was extracted from all samples for bulk-transcriptomic analysis. Differentially expressed genes (adj. p-value <0.05) were identified and pathway enrichment analysis pinpointed relevant pathways. Subsequently, single-cell RNA sequencing (scRNAseq) analysis was performed using the 10x Chromium Controller® platform. A total of 31.195 cells were sequenced and bioinformatic analysis revealed 13 distinct clusters based on the expression of key lineage target genes. To better characterise the nature of clusters expressing stromal like markers and positioned closely in the UMAP plot, a further subclustering was performed. This resulted in 5 groups, including plasma cells, endothelial cells, fibroblasts, epithelial cells and dendritic like cells.

Results

Bulk-transcriptomic analysis identified 81 genes differentially expressed in strictures compared to both proximal and distal regions. Notably, genes associated with leukocyte and macrophage recruitment and chemotaxis, namely Platelet and Endothelial Cell Adhesion Molecule 1 (PECAM1), C-C motif Chemokine Ligand 2 (CCL2), and Endothelin Receptor Type B (EDNRB), resulted overexpressed in strictures. scRNAseq identified a distinct subset of endothelial cells (CD34+, PECAM1+). Caveolin 1 (CAV1), a gene encoding for a structural protein predominantly expressed in smooth muscle cell plasma membrane invaginations, was exclusively up-regulated in endothelial cells of ileal stricture samples. Previous research linked CAV1 to smooth muscle proliferation and fibrosis in various organs.

Conclusion

This study highlights the pivotal role of endothelial cells in CD strictures. The transcriptomic analysis shows the involvement of inflammatory targets featured genes involved in transendothelial immune cell migration. Furthermore, the up-regulation of CAV1 in endothelial cells within stricture segments suggests a mechanistic connection between endothelial cells and smooth muscle hyperplasia in intestinal strictures. CAV1 holds promise as a potential therapeutic target in fibrostenotic CD.Read more DOP06 Development of simplified scoring system to predict two-year clinical remission of patients with Ulcerative Colitis after treatment with vedolizumabWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

No prospective study had been conducted to demonstrate the efficacy of vedolizumab in patients with ulcerative colitis (UC). While several studies have identified predictive factors for achieving mucosal healing, a well-validated algorithm is lacking. We aimed to identify the predictive factors and develop a practical scoring system to assess the efficacy of vedolizumab in patients with UC.

Methods

We performed a logistic regression analysis from the data of withdrawal versus continuation of thiopurine in vedolizumab-treated patients with ulcerative colitis (VIEWS) study which is a prospective multi-center longitudinal cohort in UC patients in Australia who had clinical and endoscopic remission (Mayo score ≤ 1) at baseline and continued vedolizumab as maintenance treatment. Predictive factors of two-year steroid-free clinical remission were developed into a model that predicted the outcome of treatment. We then validated our scoring system in a separate retrospective cohort of patients with UC who received vedolizumab in routine practice during 2016-2021.

Results

The derivation cohort comprised 62 patients, with 48 patients (77.4%) maintaining clinical remission at 2 years. Patient characteristics are presented in table1. Independent predictive factors used in developing the model included combination of thiopurine continuation (OR 3.6, P-value 0.11), absence of exposure to anti-tumor necrosis factor (TNF) (OR 3.75, P-value 0.047), histologic remission at baseline (OR 10.79, P-value 0.002), and duration of UC < 5 years (OR 9.29, P-value 0.04). The final simplified score is as follows: 3x (thiopurine continuation) + 2x (absence of exposure to anti-TNF) + 3x (histologic remission at baseline) + 2x (duration of UC < 5 years) yielding the area under the receiver operating characteristic curve (AUROC) of 0.86 in the derivation cohort (figure 1). In the validation cohort, there were 43 UC patients who had been initiated and continued vedolizumab as maintenance treatment, with 30 patients (69.8%) remained in clinical remission at two years. The AUROC of validation cohort was 0.75 after applying simplified score. At a cut-off level of 4 points, the model can identify two-year clinical remission with 83% sensitivity and 54% specificity, respectively.

Conclusion

We developed the practical predictive scoring system to determine UC patients who are likely to remain in clinical remission after two years of treatment with vedolizumab. In high-risk UC patients, combination use of vedolizumab and thiopurine is strongly recommended.Read more DOP07 Monitoring disease activity by intestinal ultrasound predicts biologic treatment persistence in patients with Inflammatory Bowel DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Current biomarker-based monitoring strategies have limited efficacy in predicting risk of biologic treatment failure in inflammatory bowel disease (IBD). Endoscopic assessment identifies patients at risk of disease progression but is expensive and poorly accepted by patients. Therefore, we examined how intestinal ultrasound (IUS) performed as part of a monitoring program to predict treatment persistence to biologics in IBD patients.

Methods

Data were generated as part of a 1-year prospective, observational, cohort study of patients on biologics comparing tight monitoring to a historic cohort (‘Time It´ study). Data used in the present analysis included Harvey Bradshaw index (HBI), simple clinical colitis activity score (SCCAI), CRP, f-calprotectin (FC), IUS, and ileocolonoscopy all done at inclusion. The following definitions were used: Treatment persistence: no need for dose escalation or switching to another biologic or small molecule; IUS transmural remission (TR): bowel wall thickness ≤3mm in all bowel segments and zero color Doppler activity; endoscopic remission (ER): simple endoscopic score (SES)-CD≤2 or Mayo endoscopic score 0; clinical remission (CR): HBI≤4 or SCCAI≤2; FC remission (FCR): FC≤250; CRP remission (CRPR): CRP≤10 mg/L. Chi-square tests and Kaplan-Meier statistics were used to compare baseline measures in treatment persistent and non-persistent patients.

Results

Of the 91 patients included in 'Time It’, 77 had IUS performed and 69 ileocolonoscopy. Of the 77 patients, 61% were on maintenance treatment at inclusion and 39% were included during induction (Table 1). COVID-19 restrictions were the main reason for missing IUS or endoscopy. As expected, more patients with ER had 1-year treatment persistence (87% vs. 41%; p<0.001). However, patients with IUS TR also had better treatment persistence (78% vs. 38%; p<0.001). CR or FCR were associated with treatment persistence (p<0.05 and p<0.01, respectively), but not CRPR. Combining TR and FCR performed numerically as well as ER (treatment persistence 85% vs. 41%, p=0.002). Survival analysis of TR showed a mean treatment persistence of 318 days vs. 221 days without TR (p<0.001); corresponding treatment persistence data were 327 days vs. 230 days for combined TR and FCR; and 338 days vs. 226 days for ER (both p<0.001; Figure 1). There was no difference in mean treatment persistence between TR and ER (318 vs. 338 days; p=0.36).

Conclusion

IUS alone or combined with FCR was comparable to endoscopy to identify patients with high biologic treatment persistence. Being a non-invasive, patient friendly, cost-effective modality, IUS monitoring may improve current disease monitoring programs aiming to increase treatment persistence.Read more DOP26 Metagenomic and metabolomic profiles in IBD: understanding microbial and metabolic shifts from a large deeply phenotyped cohortWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Alterations in gut microbiota composition and functions are involved in the pathogenesis of Inflammatory Bowel Disease (IBD) and the role of specific bacterial taxa has been particularly pointed out. The role of microbiota-derived metabolites, including those produced from tryptophan, are major actors in host-microbiota interactions in health and in IBD. Large studies analyzing both gut microbiota and metabolomics data are scarce.

Methods

In the current study, we analyzed a total of 764 individuals from Saint Antoine Hospital cohort, including 447 patients with Crohn's disease (CD), 262 patients with Ulcerative Colitis (UC) and 55 healthy subjects. We performed shotgun metagenomic sequencing on fecal samples and integrated the results with deep clinical phenotyping and targeted metabolomics data encompassing 294 different molecules.

Results

We observed strong changes in the taxonomic composition and functional capabilities of the microbiota in CD and UC patients compared to healthy subjects. Besides disease itself, the most important drivers of microbiota composition were the disease location (Montreal classification), recent antibiotic treatment, disease activity (flare vs remission) and history of ileocecal resection. Interestingly, IBD diagnosis explained much more the variations of microbiota functions than taxonomy. The decrease in microbiota diversity was stronger in CD than in UC. In parallel to a decreased amount of Faecalibacterium in IBD, we also observed a decrease in the diversity of Faecalibacterium strains, with a stronger decrease in CD. Our multifactorial analysis revealed specific microbial taxa and functions affected by disease-related factors. We particularly identified many correlations between tryptophan metabolites and microbial abundance. Targeted gene analysis of tryptophan-related enzymes in metagenomes further supported these findings. A network analysis considering bacterial taxa and metabolites revealed profound alterations in IBD with some specificities between CD and UC.

Conclusion

We pointed out new microbiome and metabolome alterations associated with IBD, with some phenotype specificities. Overall, our findings provide crucial information and a substantial resource for understanding the interactions between the host and microbiome in the context of IBD.Read more DOP27 Systemic antibody responses against gut microbiota flagellins implicate shared and divergent immune reactivity in Crohn's Disease and chronic fatigue syndromeWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Patients with Crohn’s disease (CD) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) exhibit elevated antibody responses against gut microbiota flagellins. However, flagellin-specific antibody repertoires and functional roles in the diseases remain incompletely understood. Bacterial flagellins can be categorized into three types depending on their interaction with toll-like receptor 5 (TLR5): (1) "stimulator" and (2) "silent" flagellins, binding TLR5 through a conserved N-terminal motif, with only stimulators activating TLR5 due to a specific C-terminal domain; (3) "evader" flagellins of pathogens, which circumvent TLR5 activation via mutated N-terminal TLR5 binding motifs. Here we studied the characteristics, epitope binding, and sequence (dis)similarity of anti-flagellin antibody responses in CD and ME/CFS.

Methods

Since conventional antibody profiling methods like enzyme-linked immunosorbent assays [ELISAs] do not allow for large-scale measurements of antibody repertoires, we leveraged phage-display immunoprecipitation sequencing (PhIP-Seq) to characterize 344,000 rationally selected peptide antigens in 256 patients with CD, 40 patients with ME/CFS and in two equally sized groups of age- and sex-matched healthy controls from population-based cohorts in the Netherlands and U.K., respectively. Different sequence alignment strategies were employed to compare flagellin peptide structures with observed antibody-bound flagellin peptide reactivity.

Results

Both patients with CD and ME/CFS exhibited elevated antibody responses against distinct regions of flagellin peptides compared to healthy individuals (P<0.001). N-terminal binding to Lachnospiraceae flagellins was comparable in both diseases, while C-terminal binding was more prevalent in CD. N-terminal antibody-bound flagellin sequences were similar across CD and ME/CFS, resembling ‘stimulator’ and ‘silent’ flagellins more than evaders. However, C-terminal antibody-bound flagellins showed higher resemblance to stimulator than to silent flagellins in CD, but not in ME/CFS. This group of antibody-bound flagellins was exclusively identified in a subset (10-20%) of patients with CD and characterized by its strong overrepresentation (exceeding 20-fold), underscoring its potential significance in distinguishing pathophysiologic subtypes of CD.

Conclusion

Antibody binding to the N-terminal domain of stimulator and silent flagellins may impact TLR5 activation in both CD and ME/CFS patients. Furthermore, elevated antibody binding to the C-terminal domain of stimulator flagellins in CD may explain pathophysiological differences between diseases. Our results highlight the diagnostic potential of these antibody responses and their impact on innate/adaptive immunity balance.Read more DOP60 Prevalence of undiagnosed inflammatory Bowel Disease in patients with spondyloarthritis: EISER StudyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

A significant proportion of patients with inflammatory bowel disease (IBD) have concomitant rheumatological manifestations. Patients with spondyloarthritis (SpA) often report gastrointestinal symptoms, some of them being associated to IBD. However, the exact prevalence of this disorder is still controversial, and the optimal approach to its diagnosis remains unknown.

Methods

Aim: to determine the prevalence of undiagnosed IBD in patients with axial SpA and psoriatic arthritis (PA). EISER is an observational, cross-sectional study carried out in13 Spanish hospitals. Patients ≥18 years-old diagnosed with PA or SpA were selected. Patients receiving biologics or systemic steroids were excluded. Among patients ≥ 50 years, only those without valid colonoscopy in the previous 3 years were included. Rheumatologists performed a baseline visit and collected demographic, clinical data. Fecal calprotectin (FC) was determined by the Quantum Blue rapid test and this was followed by a gastroenterologist consultation. Figure 1 summarizes study protocol.

Results

A total of 559 patients were included (51% men; mean 52.2 years; mean disease duration of SpA/PA was 12.3 years). The most frequent disease was radiographic SpA (37%), followed by peripheral APs (36%). Tabla 1 shows demographic characteristics of patients. A total of 40% of patients has FC ≥ 80 ug/g. In the multivariate logistic regression analysis factors associated with a greater likelihood of FC ≥ 80 µg/g were disease duration (OR 1.021, 95%CI 1.000 to 1.042, p<0.05) and disease activity by ASDAS-CRP (OR 2.158, 95%CI 0.906 to 5.139, p<0.1), while general health status by EQ-5D-5L was associated with a lower likelihood of FC ≥ 80 µg/g (OR 0.976, 95%CI 0.960 to 0.993, p<0.01). 28 patients were diagnosed of IBD, leading to a prevalence of 5.7%, 22 out of the 248 patients with axial SpA had IBD (8.9%) and 6 out of the 246 patients with PsA (2.4%). 24 were diagnosed with Crohn’s disease (CD), 3 unclassified IBD, and 1 UC. Seven (25.0%) of these IBD patients showed symptoms. The ROC curve for FC and the diagnosis of IBD is presented in Figure 1 (AUC of 0.870 (p<0.001, 95CI% 83.7 to 89.8). The highest sensitivity(S) and specificity (Sp) corresponded to a FC level >147 µg/g (S= 85.7% and a Sp of 75.5%, a PPV of 17.4% (95%CI 14.5 to 20.8) and NPV of 98.9% (95%CI 97.3 to 99.5).

Conclusion

- 5.7% of SpA patients have undiagnosed IBD. This prevalence was higher among axial SpA than PsA patients.- CD is the most frequent IBD type observed.·- FC is a useful tool to identify patients with SpA and lesions secondary to IBD.- FC has a high NPV to rule out IBD in axial SpA patients.- Disease duration, quality of life and disease activity of SpA are associated with higher levels of FC.Read more DOP61 Up-regulated Gremlin 1 in fibroblasts from Crohn’s Disease fibrotic strictures: A potential therapeutic targetWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Fibrosis is a common complication in Crohn’s disease (CD), often leading to intestinal strictures that are refractory to available biologic drugs and require surgery. Addressing this complication remains a significant unmet need. This study aims to explore the transcriptomic signature of fibrostenotic ileal CD to identify novel therapeutic targets.

Methods

9 CD patients undergoing surgery for fibrotic strictures were prospectively recruited. All patients underwent magnetic resonance enterography, ileoscopy, and assessment of C-reactive protein and faecal calprotectin. A multidisciplinary team adjudicated the presence of fibrotic strictures, warranting surgical resection. Resected specimens were harvested directly from the operating theatre and delivered fresh to pathologists, who dissected samples from the strictured area, and the proximal and distal non-strictured regions. RNA was extracted from all samples for bulk-transcriptomic and single-cell RNA sequencing (scRNAseq) analysis, using the 10x Chromium Controller® platform. Differentially expressed genes (adj. p-value <0.05) were identified. Machine learning analyses, including PCA and PLS-DA, were employed to compare gene expression patterns among different tissue segments. Pathway enrichment analysis pinpointed relevant pathways. Further, the random forest model was constructed to evaluate the predictive significance of genes in relation to strictures, and the resulting ranked list of genes was subsequently validated through qPCR, confirming the significance of selected genes.

Results

Bulk-transcriptomic analysis revealed 64 significantly up-regulated genes in strictures, associated with inflammation, matrix remodeling, adipogenesis and cellular stress. Furthermore, 17 down-regulated genes were linked to epithelial barrier integrity. Normalised gene expression of GREM1, SERPINE1, FGF2, HDAC1 AND LY96 showed high predictive value for strictures compared to distal and proximal segments. Notably, qPCR confirmed the significant up-regulation of GREM1 expression exclusively in the ileal stricture samples (non-stricture vs. stricture: AUC 0.88, 95% CI 0.77-0.95). scRNAseq linked up-regulated GREM1 exclusively to the fibroblast cell population (THY1+, COL1A1+,ACTA2+).

Conclusion

Bulk and single-cell transcriptomics, along with qPCR validation of resected CD ileal strictures, showed the up-regulation of GREM1 in fibroblasts within stricture compared to adjacent proximal and distal intestinal samples. These findings confirmed in ileal CD previous reports from animal models, highlighting the role of GREM1 in promoting intestinal fibrosis. Therefore, GREM1 emerges an attractive target for the treatment of fibrotic strictures in CD.Read more DOP89 Unfolded protein response controls group 3 innate lymphoid cells in IBDWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Group 3 innate lymphoid cells (ILC3s) have recently emerged as important regulators and potential drug targets for IBD. However, the response of ILC3s to environmental stimuli during intestinal inflammation remains elusive. IRE1a-XBP1 serves as the regulatory hub of endoplasmic reticulum stress and the unfolded protein response (UPR) that plays a vital role in intestinal inflammation.

Methods

We generated conditional knockout Ire1a^flo/flox,Rorc-Cre (Ire1a^ΔRorc) and Rag^-/-Ire1a^ΔRorc mice with Ire1a deleted in ILC3s. Intestinal infections were induced by Citrobacter rodentium and Clostridium difficile. ILC3s-derived cytokines including IL-22 is crucial for host defense in the acute phase of C. rodentium and C. difficile infection. Dextran sodium sulfate (DSS) was given in drinking water to induce acute colitis. We recruited patients with active Crohn’s disease (CD) and collected ileal biopsies during routine colonoscopy before starting ustekinumab, a non-selective anti-IL-23 antibody. Mucosal ILC3s were isolated for analysis of ILC3s by flow cytometry.

Results

In murine intestinal ILC3s, the activity of IRE1a-XBP1 pathway follows a robust 24h circadian rhythm which parallels that of clock genes and cytokines including IL-22. XBP1s is activated in ILC3s ex vivo by vasoactive intestinal peptide, which was previous shown to orchestrate the circadian expression of IL-22 by ILC3s. IRE1a-XBP1 in intestinal ILC3s is further activated in response to IL-23 and colitis in mice, as well as in inflamed IBD tissues compared to normal tissues from healthy individuals. We further showed that IRE1a-XBP1 activation in stimulated ILC3s requires mitochondrial reactive oxygen species (mtROS) (Fig 1). Using the Ire1a^ΔRorc mice, we demonstrated that IRE1a-XBP1 is critical for cytokine expression by ILC3s. Ire1a^ΔRorc mice are highly susceptible to acute C. rodentium and C. difficile infection as well as acute DSS colitis (similar vulnerabilities were found in Rag^-/-Ire1a^ΔRorc mice compared to Rag^-/-Ire1a^flox/flox littermates). Ire1a^ΔRorc mice exhibit reduced IL-22 and IL-17A in ILC3s and impaired epithelial barrier function with diminished expression of mucins and antimicrobial peptides. The susceptibilities of Ire1a^ΔRorc and Rag^-/-Ire1a^ΔRorc mice to colitis were rescued by administration of recombinant IL-22 (Fig 2). Moreover, the frequency of XBP1s+ ILC3s in ileal mucosa from CD patients before initiation of ustekinumab positively correlates with response to therapy.

Conclusion

We demonstrate that a non-canonical mtROS-IRE1a-XBP1 pathway augments cytokine production by intestinal ILC3s. We also identify XBP1+ ILC3s as a potential biomarker for predicting responsiveness to anti-IL-23 therapies in IBD.Read more DOP90 Amphiregulin promotes colitis-associated intestinal fibrosis through activation of PI3K/AKT signaling in Intestinal fibroblastsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Intestinal fibrosis is one of the most threatening complications of Crohn’s disease (CD). Amphiregulin (AREG) expression is increased in patients with CD with fibrosis.

Methods

The role of AREG in activating intestinal fibroblasts and driving fibrogenesis is largely unexplored. In this study, fibrotic and nonfibrotic tissues were obtained from CD patients undergoing surgical resection while normal intestinal tissues were obtained from patients with diverticulum of small intestine. Fibrosis index score for fibrosis were assessed by Masson staining. AREG, collagen Ⅰ and α-SMA expression were determined in intestinal tissues of patients with CD with fibrosis or without fibrosis by qRT-PCR. Wild-type (WT) and Areg knockout (Areg^-/-) mice were induced into intestinal fibrosis by dextran sulfate sodium (DSS). We induced intestinal fibrosis in WT mice using a chronic DSS-induced colitis model with or without AREG intraperitoneal injection. The fibrotic indicators in colons were evaluated. Fibroblasts were isolated from fibrotic intestinal surgical resections of patients with CD. The effect of AREG on activation and proliferation in human intestinal fibroblasts was determined. RNA-sequencing of human intestinal fibroblasts treated with or without AREG was performed.

Results

AREG expression was increased in intestinal fibrotic sites compared with nonfibrotic sites from patients with CD. Mice with Areg deficiency represented with severer intestinal inflammation but alleviated fibrosis in colons. Although additional given AREG attenuated intestinal inflammation in mice with DSS-induced chronic colitis, it promoted more severe intestinal fibrosis. AREG promoted human intestinal fibroblast activation and proliferation by activating PI3K/AKT signaling. PI3K inhibitor suppressed AREG-induced fibroblast activation and proliferation, thus lightened intestinal fibrosis in mice. Besides, AREG promoted secretion of LPA (Lysophosphatidic acid) from intestinal fibroblast, which activated fibroblast through LPAR3/PI3K/AKT pathway.

Conclusion

These findings reveal that AREG promotes intestinal fibrotic responses in experimental colitis and human patients with CD by promoting fibroblast activation and proliferation through PI3K/AKT pathway. Moreover, LPA secreted from intestinal fibroblast induced by Areg is involved in formation of CD intestinal fibrosis. Thereby, PI3K, AKT, LPA might serve as potential therapeutic targets for fibrosis in CD.Read more P001 MicroRNA-155-5p contributes to the development of Ulcerative Colitis by regulating T lymphocyte proliferation and functionsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

MicroRNA (miRNA) is a small non-coding RNA which regulate a variety of cell functions by suppressing target mRNAs in a post-transcriptional manner. Recent works have identified an increased expression of miR-155-5p in the colonic mucosa of UC patients. However, the role of miR-155-5p in the pathophysiology of UC remains understudied. This study aims to clarify the role of miR-155-5p in development of colitis in UC patients.

Methods

MiRNA and mRNA expression profiles in colon were compared between 15 UC and 5 healthy controls by running small RNA-sequencing (smRNA-Seq) and RNA-Seq on the matched colon tissue. Candidate target genes of miR-155-5p were identified by analyzing sequencing data sets using a statistical simulation method (miRhub). MiR-155-5p expressing cells were identified by in situ hybridization in combination with immunohistochemistry on inflamed colon tissue of UC patients. The impact of miR-155-5p on colonic inflammation was tested in the dextran sulfate sodium (DSS) -induced colitis model using miR-155 deficient mice.

Results

MiR-155-5p expression was significantly higher in the inflamed colonic tissue of UC patients than in healthy controls with more pronounced up-regulation in the treatment refractory UC patients compared to the treatment naïve UC patients (UC vs. healthy controls, log2FC = 0.83, adjusted p-value = 0.014). MiRhub analysis identified 10 candidate target genes of miR-155-5p including SHANK2, MYO1D, ADD3, AHCYL2, NR3C2, MIER3, TRIM2, GPD1L, SEMA5A, and SATB2 most of which were involved in cell proliferation and immune response (NR3C2, MIER3, TRIM2, GPD1L, SEMA5A, and SATB2). In situ hybridization identified a group of CD3 positive T lymphocytes with increased miR-155-5p expression in the inflamed colonic mucosa. MiR-155 deficient mice showed attenuated DSS-induced inflammation in colon compared to the control wild type mice (colon weight/length ratio, miR-155 deficient mice vs. controls, 27.2 vs. 44.6, p<0.01).

Conclusion

MiR-155-5p may contribute to the development of colitis in UC by regulating T lymphocyte proliferation and functions.Read more P002 Regulation of miR-338-3p and miR-378a-3p in the intestinal mucosa of Crohn’s disease: Potential targets for modulating inflammationWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

A growing body of evidence suggests that epithelial cell-derived microRNAs are involved in the pathogenesis of inflammatory bowel disease (IBD). This immunological impairment leads to altered colonic epithelial permeability and the release of inflammatory cytokines, such as IL-33. In this prospective cohort study, we studied the expression of epithelial cell-derived microRNAs (miRNA) in Crohn’s disease (CD) patients compared to healthy controls. We also investigated their potential role in regulating inflammation in experimental IBD animal models.

Methods

We prospectively collected terminal ileum tissue samples via ileocolonoscopy from non-IBD healthy control (n=26), CD patients in remission (n=34) and active CD patients (n=42). CD remission was defined as clinical remission with a Crohn’s disease activity index score of less than 150 and the achievement of endoscopic mucosal healing. Both inflamed and non-inflamed lesions were sampled in the active CD patients. miRNA levels were measured by small-RNA sequencing and also validated via qRT-PCR. Diagnostic abilities of specific miRNAs found were evaluated by receiver operating characteristic (ROC) curve analysis. A signature of miRNAs was selected from RNA sequencing and qRT-PCR and single-strand mimics of these miRNAs were delivered in the 2.5% dextran sodium sulfate colitis model to determine the effect. Histologic grading and immunohistochemistry evaluation and flow cytometry analyses were performed.

Results

From the prospective study cohort of CD and non-IBD healthy control (mean follow-up period of 13.06 months), we found a distinct array of miRNAs between groups. Small-RNA sequencing of CD patients in remission and active state (both in inflamed and non-inflamed tissue) revealed distinct microRNA profiles. Through qRT-PCR validation, we found that the expression levels of miR-141-3p, miR-338-3p, miR-378a-3p, and miR-200b-3p were significantly decreased, while miR-125b-5p, miR-29b-3p and miR-155-5p were significantly increased in the inflamed tissue of active CD patients. ROC curve analysis of these miRNAs suggested that they have varying diagnostic activities related to both clinical disease activity and endoscopic inflammation status. In an IBD animal model, the delivery of miR-338-3p and miR-378-3p demonstrated an anti-inflammatory effect, as evidenced both histologically and in immunohistochemistry data, as well as in flow cytometry analyses. Consistent results were observed when these two miRNAs were combined.

Conclusion

We report miR-338-3p and miR-378a-3p as distinct features in mucosa of CD patients and these data support the promising future of use of these miRNAs as potential therapeutic targets for novel IBD therapies.Read more P023 Serological markers of intestinal barrier function in patients with primary sclerosing cholangitis after liver transplantationWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Primary sclerosing cholangitis (PSC) is a chronic cholestatic disease associated with inflammatory bowel disease. Liver transplantation (LT) is the only curative treatment for most patients with PSC. Recurrence of PSC (rPSC) is a common long-term complication after liver transplantation in this patient group, affecting graft survival and overall patient survival. There are several lines of evidence indicating that dysregulation of the microbiome and gut barrier dysfunction are key etiologic factors in the pathogenesis of PSC. The aim of this study was to evaluate serological markers of intestinal barrier function in patients with PSC after LT and in control group, to determine potential biomarkers for rPSC.

Methods

This is a cross-sectional study of patients after LT for PSC at the Institute for Clinical and Experimental Medicine, Prague. The control group consists of patients who underwent liver transplantation for alcohol-related liver disease and/or hepatocellular carcinoma. The rPSC was assessed by MRCP and/or liver biopsy according to the Mayo criteria. IBD status was assessed by endoscopy, biopsy, and faecal calprotectin. We performed ELISA for Zonulin and Reg3a. The Kruskal-Wallis and Mann-Whitney test were used to evaluate the statistical differences.

Results

A total of 85 patients were included in the study after LT for PSC and 56 controls. rPSC was detected in 18 (21.18%) patients. IBD was diagnosed in 77 (90.5%) patients, of which 3 (3.9%) were categorised as Crohn’s disease. The remainder, 82 patients, were classified as ulcerative colitis, 41.9% with right-sided predominance and 24.3% with back-wash ileitis. The IBD treatment consisted of 5-ASA in 58 patients, azathioprine in 12 patients, vedolizumab in 5 patients, anti-TNFa in 1 patient and 9 patients were on 10 mg or more of prednisone or equivalent. MayoDAI was evaluated at the time of the visit with mean 1.74 (SD ±2.06). There was a significant difference in Reg3a levels between patients with IBD and control subjects (p<0.05, Figure 1.). No significant difference in Reg3a levels was found between rPSC patients and controls (p=0.3). Interestingly, Zonulin levels were significantly higher in the control group than in PSC patients with or without IBD (p<0.001). No significant difference in Reg3a and Zonulin was found between PSC and rPSC patients and between patients in remission and with active IBD.

Conclusion

Reg3a was associated with PSC-IBD in patients with PSC after LT, but its association with rPSC is unclear and should be investigated in a prospective setting. Zonulin reached higher levels in the control group.Figure 1.:Kruskal-Wallis test for Reg3a comparing patients with PSC-IBD, no PSC and control group showed significant difference in medians (p=0.0015)Read more P024 Synergistic effect of phytochemicals combination including ginsenosides and curcumin on recovery from radiation-induced toxicityWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Radiotherapy is commonly used to treat solid cancers located in the pelvis. A considerable number of patients experience proctitis of varying severity, even for a considerable period after radiotherapy. These side effects are often long-lasting or progressively worsen despite multiple therapeutic efforts and are a primary cause of an unexpectedly low quality of life, even after successful cancer treatment. Therefore, this in vitro study, as an initial trial, evaluated the single and combined efficacy of ginsenoside, curcumin, butyric acid, and sucralfate compounds in treating radiation-induced proctitis.

Methods

Cell viability and migration assay, endothelial cell tube formation assay were performed using human colon cancer cell lines, dermal fibroblasts, keratinocytes, and human umbilical vein endothelial cells, which were exposed to radiation. In addition, Inflammatory cytokine assay for CXCL10, CCL2, CCL8, IFN-γ, IL-4, IL-12, and IL-21 is performed using human monocytes treated with LPS (lipopolysaccharide). In all assay, the single and combined efficacy of ginsenoside, curcumin, butyric acid, and sucralfate were analyzed.

Results

While the candidate compounds did not affect the proliferation and migration of cancer cells, they promoted the recovery of cell activity, including motility. They exhibited anti-inflammatory effects on human dermal fibroblasts or human umbilical vein endothelial cells within in vitro disease models. When each compound was tested, curcumin and ginsenoside were the most effective in cell recovery and promoted the migration of human dermal fibroblasts and cell restoration of human umbilical vein endothelial cells. The combination of ginsenoside and curcumin resulted in cell migration recovery of approximately 54%. In addition, there was a significant improvement in the length of the endothelial tube, with an increase of approximately 25%, suggesting that the ginsenoside-curcumin-containing combination was the most effective against radiation-induced damage. Furthermore, it was shown that the combination could alleviate radiation-induced inflammation by reducing the concentrations of IFN-γ and IL-12, associated with activated macrophages among LPS-induced inflammatory cytokines, by approximately 20% and 45%, respectively.

Conclusion

Our study provides valuable insights into using curcumin and ginsenoside as potential compounds for the effective treatment of radiation-induced injuries and highlights the promising therapeutic benefits of combining these two compounds.Read more P025 Obefazimod and its active metabolites ABX-464-N-Glu act by stabilizing protein-protein interaction among key RNA biogenesis partners, CBC and ARS2Wed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Obefazimod is an oral, once-daily, small molecule in phase 3 clinical trials for the treatment of patients with ulcerative colitis (UC). Obefazimod selectively enhances the expression of a single micro-RNA (miRNA), miR-124. miRNAs function by binding to specific mRNA targets and reducing their translation into their respective proteins. Enhanced expression of miR-124 results in a decrease in cytokines and immune cells, helping to reduce inflammation and potentially controlling the progression of chronic conditions like UC. Obefazimod and its main active metabolite, ABX464-N-Glu, bind the nuclear Cap Binding Complex (CBC) that directs cellular RNA biogenesis by recognizing co-transcriptionally the cap structure of RNA polymerase II transcripts. The CBC complex is made of Cbp20 and Cbp80, and interacts with a key partner involved in microRNA biogenesis, ARS2. Here, we explore the structural basis for targeting the CBC complex.

Methods

Microscale thermophoresis analyses were performed to determine the binding affinities between the two components of CBC, Cbp20 and Cbp80, in presence or absence of obefazimod or its metabolite ABX464-N-Glu, and their interaction with ARS2 also in presence or absence of the two molecules. Cryo-electron microscopy (cryo-EM) datasets of CBC-apo, CBC-obefazimod, CBC-ABX464-N-Glu, CBC-ARS2-Apo, CBC-ARS2-obefazimod, CBC-ARS2-ABX464-N-Glu were processed and after 2D classification and 3D refinement the different structures were solved. To understand and explore the conformational dynamics of the complex, 3D multibody refinement was performed on CBC-Apo, CBC-obefazimod and CBC:ABX464-N-Glu.

Results

The cryo-EM structures showed that obefazimod or ABX464-N-Glu bind the same location at the interface of CBC complex to act as orthosteric stabilizers of Cbp20 and CBp80. The conformational change induced by the binding of obefazimod or ABX464-N-Glu to the CBC complex strengthens the interaction between the two subunits of CBC, resulting in a more rigid structure of CBC complex. Thermophoresis revealed that the binding of obefazimod or ABX464-N-Glu improves the interaction of CBC with ARS2, a key partner of CBC to establish the fate of RNA in the cell. The cryo-EM structures of CBC-ARS2, obefazimod-CBC-ARS2 or ABX464-N-Glu-CBC-ARS2 show that ARS2 passes through the site where Obefazimod and ABX464-NGlu bind. We propose that the orthosteric effect of obefazimod or ABX464-N-Glu on CBC is maintained even when these molecules leave their binding site, allowing for better affinity of ARS2 for CBC.

Conclusion

Our results identify a unique interfacial stabilizing mode of action for anti-inflammatory drugs targeting the CBC complex enhancing its interaction with ARS2 to generate specific microRNA.Read more P026 Differential effects of tofacitinib on macrophage activation may contribute to lack of response in ulcerative colitis patientsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

We previously showed that ulcerative colitis (UC) patients refractory to tofacitinib present an increase in the activation and the pro-inflammatory profile of intestinal macrophages¹. However, the mechanism by which tofacitinib promotes further activation of macrophages in these group of patients remains unknown.

Methods

Blood monocytes from healthy individuals were cultured in the presence of M-CSF as previously described². The differentiated macrophages were treated with LPS (10ng/ml), TNF (20ng/ml) or IFNγ (5ng/ml) in the presence or absence of tofacitinib (300nM). The effect of tofacitinib on gene expression and protein production in response to each stimulus was measured by qPCR and ELISA, respectively. Single-cell RNAseq (scRNAseq) data generated in a cohort of UC patients treated with tofacitinib¹ was compared to the bulk transcriptome of monocyte-derived macrophages stimulated with LPS +/- anti-IL-10 mAb³.

Results

Monocyte-derived macrophages treated with tofacitinib significantly reduced the expression of activation markers downstream from IFNγ or TNFα. In contrast, the response to LPS was either maintained or intensified by tofacitinib as seen by the increase in expression of inflammatory marker genes including chemokines and cytokines CXCL1, CXCL5, IL1B, TNFA and IL6, and M1-like markers INHBA and CLEC5A (Figure 1A). Protein analysis of cell supernatants confirmed these observations. Compared to IFNγ and TNF, LPS drives the production of high concentrations of the anti-inflammatory IL-10 (Figure 1B) which can act on macrophages through a JAK-dependent signaling pathway. We hypothesized that by inhibiting IL-10 autocrine signaling on LPS-activated macrophages tofacitinib would promote their hyperactivation. Indeed, the transcriptional profile of LPS-stimulated macrophages treated with a blocking anti-IL-10 antibody³ highly overlapped with those genes that were upregulated in macrophages from patients refractory to tofacitinib, including IL1B, IL6, INHBA and IDO1 (Figure 1C). This overlap was not observed in responder patients.

Conclusion

Based on the combination of biopsy scRNAseq from tofacitinib-treated patients and in vitro macrophage cultures, we suggest that lack of response to tofacitinib is driven by its effect on IL-10 signaling. While IL-10 is essential to control macrophage activation when stimulated with the pathogen molecular pattern LPS, it plays no significant role when macrophages are activated with IFNγ or TNF. Hence, we hypothesize that LPS-dependent inflammation may predispose to lack of response to tofacitinib.Read more P072 LDN-071, a novel first-in-class amino acid-based PAI-1 inhibitor, significantly reduces the severity of experimental colitis in miceWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Inflammatory Bowel Diseases (IBD) are chronic inflammatory disorders characterised by alterations of acute relapses and remission. The past decades have brought substantial advances in the pharmacological management of IBD by wide range of medicines. Although, the sustained efficacy of the currently available anti-inflammatory therapies is still far from optimal. Therefore, the development of novel therapies represents a major unmet clinical need in this field. Recently the enrichment of the coagulation pathway genes and among these, Plasminogen activator inhibitor 1 (PAI-1) was described in IBD, whereas PAI-1 emerged as a link between the epithelium and inflammation. Moreover, the genetic deletion of PAI-1 impaired the severity of experimental colitis in mice. Based on these, our aim was to develop and test novel PAI-1 inhibitors for the treatment of IBD.

Methods

Novel, amino acid-based PAI-1 inhibitors were synthetized by A³SMO^® platform. The inhibitory potential and cytotoxicity effects of the peptides were determined by in vitro assays. Based on the in vitro results LDN-071 was selected for further analysis. Experimental colitis was induced in mice with 3% DSS and after the induction of colitis 10 mg/bwkg LDN-071 was administered per os for four consecutive days. The changes of body weight, spleen weight and colon length were measured. Haematoxylin eosin (HE) and Periodic acid-Schiff (PAS) staining were performed for histology. ELISA and qRT-PCR measurements were applied to analyse the mucosal cytokine expressions. In vivo toxicity of LDN-071 was determined in mice.

Results

LDN-071 significantly inhibited PAI-1 in vitro without decreasing the cell viability in a concentration range of 1µM-1mM. The administration of 10 mg/bwkg LDN-071 in the DSS-treated mice prevented the body weight loss, the development of bloody diarrhoea, the decrease of colon length and increase of the spleen weight, which were displayed by the DSS+vehicle-treated animals. The histological analysis of the colon revealed that DSS treatment induced a severe transmural inflammation, ulceration, loss of crypt structures and goblet cell depletion. Importantly, all of these parameters were significantly impaired by the administration of 10 mg/bwkg LDN-071. Additionally, mucosal gene and protein expressions of TNF-α, IL-1β and IL-6 were significantly impaired by PAI-1 inhibition. Importantly, no signs of toxicity were LDN-071 observed in mice exposed to 100 mg/bwkg LDN-071 for 7 days.

Conclusion

Our results showed that LDN-071, a novel amino acid-based inhibitor of PAI-1. It significantly reduces the severity of experimental colitis in mice. We propose that the inhibition of PAI-1 could be a potential novel therapeutic strategy in IBD.Read more P073 Enhancing the MFSD2A protein for the treatment of colitis-associated cancer: novel insights for pathogenesis and treatmentWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The intrinsic connection between inflammation and tumor promotion is well characterized and is a key pathogenic event in patients with colorectal cancer (CRC). A small fraction of patients with CRC suffers from genetic predisposition. However chronic inflammation, such as ulcerative colitis (UC), increases the risk of intestinal carcinogenesis, thus strengthening the connection between these conditions. A few years ago, our laboratory described that the intestinal endothelium isolated from actively inflamed UC patients displayed defective production of inflammation-resolving DHA-derived metabolites, by comparison with healthy controls and tissues in remission. We also reported that the Major Facilitator Superfamily Domain containing 2A (MFSD2A) participated in the production of the inflammation-resolving DHA-derived metabolites by the intestinal endothelium of patients with UC in remission, ameliorating colonic inflammation. Therefore, we hypothesized that the endothelial MFSD2A also has a role in preventing and/or counteracting cancer-associated inflammation.

Methods

Human Intestinal Microvascular Endothelial Cells (HIMEC) isolated from CRC and healthy samples were transduced with either MFSD2A protein-encoding lentiviral vectors (MFSD2A) or GFP as control, or MFSD2A targeting shRNA or its scramble, and were analyzed by lipidomics. Furthermore, Caco-2 cells co-cultured with HIMEC-MFSD2A were analyzed by FACS, evaluating their proliferation. Moreover, an orthotopic model of CRC was made intrarectally injecting CD1 nude mice with a cell mixture of Caco-2 and HUVEC overexpressing MFSD2A or GFP as control. Mice were gavaged with DHA-ethyl-ester or PBS. FACS analysis was performed on tumor and colonic samples.

Results

Lipidomic analysis revealed that the loss of MFSD2A in CRC is detrimental because there is a reduced production of pro-resolving lipids confirming that, as for UC, MFSD2A is important for the maintenance of an adequate balance between pro-resolving and pro-inflammatory phenotype. Moreover, enhancing MFSD2A expression at endothelial level limits Caco-2 cell proliferation, supporting its beneficial role. In addition, DHA administration in mice ameliorated clinical symptoms of inflammation upon intestinal endothelial MFSD2A overexpression, supporting the beneficial role of MFSD2A in vivo.

Conclusion

Tumor-associated inflammation remains a crucial hallmark of CRC. Our study seeks to identify the role of MFSD2A in the resolution phase of inflammation, pointing out alternative therapies for CRC treatment. These data suggested that MFSD2A might contrast the tumor-associated inflammation and ensure the correct balance between pro-inflammatory and pro-resolving milieu.Read more P074 Inflammatory Environment-Induced Transcriptomic Alterations in Crohn's Disease Adipose Stem CellsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Crohn’s disease (CD) is characterised by expansion of mesenteric adipose tissue, called creeping fat, which seems to be directly related to disease activity. Adipose stem cells (ASCs) isolated from the creeping fat of CD patients exhibit dysfunction, featuring impaired adipogenesis and an intensely pro-inflammatory phenotype. This study aims to explore the transcriptome of ASCs isolated from active and inactive CD subjects in comparison with healthy subjects, seeking key markers of this dysregulation.

Methods

Patients were recruited at Hospital Joan XXIII of Tarragona and Hospital Vall d’Hebron of Barcelona in accordance with the principles of the Helsinki Declaration. Transcriptome profiling was performed in ASCs isolated from adipose-tissue biopsies of visceral origin: CF and hMES in Crohn subjects (n=7, each) and hMES in inactive CD patients (n=7) and healthy control subjects (n=7). Groups were matched by age, gender, and BMI. Finally, we examined the pathways involving the differentially expressed gene (DEGs) in ASCs isolated from patients with CD with different clinical activity by gene set enrichment analysis (GSEA).

Results

Patients with CD across different clinical activity stages exhibited similar transcriptome patterns, indicating persistent ASC dysregulation even during remission state (Fig 1A). ASCs isolated from both creeping fat and mesenteric adipose tissue distant from intestinal damage displayed similar dysregulation, implying a global dysregulation of all mesenteric fat in CD. Specifically, transcriptomic analysis identified significant dysregulation of the NK2 Homeobox 3 (NKX2-3) gene in ASCs from active CD patients. Although higher NKX2-3 expression has been associated with B cells and intestinal tissues in CD^1-3, our study is the first to link elevated expression of this gene also to creeping fat. Pathway enrichment analysis revealed significant enrichment in oxidative stress and immune response pathways in active CD (Fig 1B). Furthermore, our findings indicated also an elevated NKX2-3 expression in ASCs of inactive CD compared to controls, with oxidative stress pathway up-regulation (Fig 1C). Notably, no significant DEGs were found between ASCs from active and inactive CD groups (Fig 1D), suggesting a similar profile in both states.

Conclusion

Our study reveals profound ASC dysregulation in CD, in both active and inactive phases. Elevated NKX2-3 expression, previously associated with increased risk of complications in IBD, is now demonstrated in the mesenteric adipose tissue, persisting even in inactive CD patients.Ref:1. Yamazaki K, et al Gut. 2009 Feb;58(2):228-32.2. Yu W, et al. J Crohn’s Colitis. 2009 Sep;3(3):189-95.3. Hong SN et al. Gut. 2016 May;65(5):788-96.Read more P075 Early intestinal ultrasound non-response is a prediction tool of complicated disease outcome in Crohn’s disease patients treated with infliximabWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The ultimate goal of Crohn’s disease (CD) treatment is to modify the natural course of disease and prevent complications. We aim to assess the role of intestinal ultrasound (IUS) as predictor tool for complicated disease.

Methods

Prospective longitudinal study including patients with active CD starting infliximab. Clinical, laboratorial and IUS parameters were assessed at week(W) 0, 14, 30, and 54. The IBUS-SAS score was used to assess ultrasonographic disease activity and includes, among others, bowel wall thickness (BWT) measurement. IUS response was defined as reduction in 25% in BWT and IUS remission as the normalization of BWT (≤3mm), doppler sign (≤1), stratification (BWS), and inflammatory fat in the most affected segment. Ileocolonoscopy was done at W0 and 54. Endoscopic healing (EH) was defined as SES-CD <3. We defined a composite outcome(CO) for complicated disease including development of stricturing or penetrating disease, need for bowel surgery, CD-related hospitalization, or the need to switching due to loss of response to therapy.

Results

We included 48 patients (48% male; median age 31 years, IQR 26-44). The median follow-up time was 23.5 months(M) (IQR11-38.25). The median time until the development of the outcome was 12M, IQR 9.75-15.25. During follow-up, 37.5% developed the CO (27.1% with stricturing or penetrating disease, 12,5% needed bowel surgery, 18,8% needed hospitalization and 6% switched therapy). Baseline disease behavior (B1:21,2% vs B2/B3:73.3% p<0.001) and a higher IBUS-SAS score (70.34 vs 58.80 p=0.042) were associated with development of CO during follow-up. Patients who developed the CO had a numerically higher BWT throughout the first year of therapy (W14: 5.00mm vs 3.65mm, p=0.007; W30: 4.78mm vs 3.43mm, p=0.007); a higher IBUS-SAS score was also seen at W14, W30 and W54 (57.00 vs 40.35, p= 0.03; 54.74 vs 31.00, p=0.004 and 29.84 vs 23.39, p=0.026, respectively). On survival analysis, IUS remission at W30 (HR 0.27 95% CI (0.76-0.94), p=0.04) and IUS response at W30 (HR 0.27 95% CI (0.09-0.94), p =0.015) were protective for the development of the CO. In multivariate Cox regression, the absence of IUS response at W30 (HR 4.80, 95% CI 1.03-22.45, p=0.046), and EH at W54 (HR 5.70, 95% CI 1.33-24.45, p=0.02) were independent predictors of worse outcome. The best cut-off at W30 to predict the CO was IBUS-SAS >52 (AUC 0.74) and BWT > 4.11 mm (AUC 0.75).

Conclusion

Early assessment of ultrasonographic response at W30 of therapy can help to predict prognosis in CD. Our results highlight that in the absence of significant IUS response after 6 months of therapy, we should consider treatment intensification and close monitoring to prevent complications.Read more P101 Investigating the role of gut eukaryotic virome in contributing to colorectal cancer carcinogenesisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Eukaryotic-targeting viruses have recently attracted interest in gastrointestinal diseases such as ulcerative colitis (UC) and colorectal cancer (CRC). UC and CRC share several factors influencing their etiogenesis, including intestinal dysbiosis. Our group has recently published a work pinpointing a gut virome-associated Orthohepadnaviridae protein, the Hepatitis B protein X (HBx) to correlate with UC pathogenesis and promote intestinal inflammation in mice by disrupting the epithelial barrier and shaping the gut mucosal immune environment, independently of the microbiota. Moreover, we showed that HBx induces DNA damage-related biological processes and active processes related to the Wnt pathway known to be involved in CRC carcinogenesis. Based on this evidence we hypothesize that HBx may fill the gap existing between intestinal inflammation and CRC onset by stimulating pro-inflammatory and/or pro-carcinogenic effects.

Methods

To verify this hypothesis, we evaluated the presence of HBx-transcript in CRC-derived mucosal samples. HBx positivity of CRC patient-derived mucosa was assessed by RT-PCR. Caco-2 cells, an in vitro model of the gut barrier, were transduced with HBx protein-encoding lentiviral vectors or GFP as control and were characterized for their carcinogenic and pro-inflammatory phenotypes by FACS analysis. C57BL/6 mice underwent intramucosal injections of liposome-conjugated HBx- or the control. FACS analysis and transcriptomic analysis were performed on mice colonic samples.

Results

Metatranscriptomic analysis revealed that HBx was highly enriched in CRC-derived mucosal samples as compared to healthy individuals, strengthening the link between a virome protein-induced inflammation and tumor development in patients. Moreover, HBx overexpression in Caco-2 cells directly provokes DNA damage, as assessed by the significant increase of γH2AX⁺ cells. Furthermore, since HBx was recently shown by our group as capable of inducing colitis-like symptoms in mice, we investigated whether this viral protein may induce colitis-associated cancer over time. Interestingly, experiments conducted at longer time points (from 40 to 60 days long observation) revealed that mice developed polypoid structures in the colonic mucosa, characterized by a decreased abundance of T cells, including effector T and NKT cells. Of note, in vivo HBx modulated the expression of genes involved in the activation of the proto-oncogene PIM3, further supporting the role of this viral protein on CRC onset.

Conclusion

This study introduces unconventional and innovative insights for giving CRC studies a new direction for scientific and clinical investigations, looking at the gut virome as an active component and not as a mere bystander entity of the microbiota.Read more P102 Neuron-specific gene-2 aggravates colitis and colon tumorigenesis by controlling microbial compositionWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Previous studies have shown that Neuron Specific Gene-2 (NSG-2) plays a role in exacerbating murine colitis and colitis-associated tumorigenesis. This study aimed to elucidate the role of Nsg-2 in the pathogenesis of intestinal inflammation by controlling microbial composition.

Methods

The effect of NSG-2 in acute murine colitis was evaluated using both wild-type (WT) and Nsg-2 knock-out (KO) mice. The effect of NSG-2 on colitis-associated tumorigenesis was evaluated using an azoxymethane (AOM) and 3% dextran sodium sulfate (DSS)-induced murine model. The co-housing method was used to assess the role of microbiome in colitis and colitis-associated tumorigenesis. Microbial composition was analyzed using 16S rRNA between the two groups before and after co-housing.

Results

DSS-treated WT mice showed severe colitis compared to DSS-treated Nsg-2 ^-/- mice. In addition, WT mice exposed to AOM/DSS exhibited higher tumor burdens than Nsg-2^-/- mice. After co-housing using WT and Nsg-2 ^-/- mice, the severity of colitis and colitis-associated tumorigenesis was not different between the two groups, suggesting that microbiome may play a key role in Nsg-2-related aggravation of colitis and tumorigenesis. The microbial taxonomy differed between the two groups in 16S rRNA analysis of stools collected before and after co-housing. Before co-housing, Nsg-2^-/- mice showed higher α-diversity than WT mice. Significant differences exist in the Sangeribacter Muris and Lactobacillus Taiwanensis proportion between the two groups. PCoA of beta diversity showed that the microbiome profiles between the two groups were separated before co-housing. However, after co-housing, the difference between the two groups significantly decreased.

Conclusion

Nsg-2 intensifies colitis resulting in colon tumorigenesis through microbial interaction, which suggests that Nsg-2 may have the potential as a therapeutic target for intestinal inflammation.Read more P103 Natural compounds in Ulcerative Colitis and Irritable Bowel Syndrome: Insights from immune-metabolic profilesWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) represent chronic and occasionally disabling conditions, necessitating innovative treatment strategies. Covering 14% of Ireland's landscape, bogland ecosystems house unique plant biodiversity, yielding biologically active secondary metabolites. Informed by traditional medicinal knowledge and in vitro screening for immunomodulatory potential, three plant extracts (NTP0226A, NTP0127B, NTP0206EA) were selected for exploration of their potential to treat IBD and IBS within the "Unlocking Nature’s Pharmacy from Bogland Species" project.

Methods

Patients undergoing colonoscopy were prospectively recruited in three cohorts: healthy controls, IBS, and ulcerative colitis (UC). Recto-sigmoid biopsies were collected and cultured for 24 h with treatments (Infliximab, NTP0226A, NTP0127B, NTP0206EA). Colonic tissue explants underwent real-time energy metabolism profiling and quantification of 10 inflammatory mediators using Seahorse Xfe24 analyser and multiplex ELISA, respectively. P values <0.05 were considered significant in analyses.

Results

Twenty-seven patients were recruited (6 healthy controls, 6 IBS, and 15 UC). UC patient explants exhibited elevated glycolytic metabolism and increased IL-4, IL-6, and IL-12p70 secretion compared to non-UC patients. No differences were observed between healthy controls and IBS patients. Linear regression did not show correlation between age and mitochondrial bioenergetics. There was no change in metabolism profiles of any cohort following treatment with Infliximab or the 3 novel extracts. In the UC tissue, treatment with Infliximab reduced IL-12p70 secretion (p=0.0098), this reduction was not seen in the other 2 cohorts. NTP0206EA reduced IL-10 secretion in the UC cohort (p=0.0255). In the IBS cohort; NTP0127B reduced IL-10 secretion (p=0.0048) and NTP0226A reduced IL-4 (p=0.004) and IL-6 (p=0.0219) secretion. Principal component analysis demonstrated reduced separation between the immune-metabolic profiles of UC patients and healthy controls following treatment with NTP0226A (Figure 1).

Conclusion

Using an explant model, we have shown that UC patients have a distinct immune-metabolic profile modifiable by a standard IBD therapy and novel plant extracts. Blockade of IL-6 trans-signalling has recently shown promise as an effective treatment target in IBD. Our natural extract NTP0226A reduced IL-6 secretion in IBS patients and is a promising candidate for therapeutic exploration. These findings contribute to our understanding of the complex interplay in the colonic microenvironment and highlight potential avenues for novel therapeutic interventions.Read more P104 Per- and poly-fluoroalkyl substances (PFAS) exposure in early life is associated with intestinal inflammationWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Early life environmental exposures are linked with intestinal inflammation and inflammatory bowel disease (IBD) later in life. Per- and poly-fluoroalkyl substances (PFAS) are a large class of fluorinated organic chemicals used widely in consumer products that may be risk factors for IBD; however, the association between exposure to PFAS in early life and intestinal inflammation has not yet been studied. Dried blood spots (DBS) are archived neonatal capillary blood samples collected and stored as part of the New York State neonatal screening program and a cost-effective early life environmental exposure screening resource.

Methods

We measured 135 PFAS in DBS collected at birth from offsprings of women with and without IBD [n=37 (44%) and 47 (56%), respectively] enrolled in the MEChanisms Of disease traNsmission In Utero through the Microbiome (MECONIUM) cohort between January 2015 and November 2020, using untargeted metabolomics with liquid chromatography high-resolution mass spectrometry. In a subsample (n = 46), we also measured offspring fecal calprotectin (FC) at one year. We fitted exposome-wide regression models to estimate the association between each PFAS signal in the DBS and continuous FC at one year of age. For the significant associations (nominal p-value <0.05), we further explored potential effect modification by stratifying by maternal IBD status. All models were adjusted for relevant confounders.

Results

The mean (SE) of FC at age one year was 213.9 (23.8) ug/gm. The PFAS chemicals perfluoroundecanoic acid (PFUnDA) and N-ethyl-perfluorooctane sulfonamido acetic acid (N-Et-FOSAA) were significantly associated with increased scaled and log-transformed FC per decile increase in exposures [estimate (95% CI) = 0.52 (0.13,0.91) and 0.34 (0.05,0.63), Figure A]. Associations tended to be stronger in offspring of women with IBD relative to offspring of women without IBD (Figure B). estimate (95% CI) for the associations between PFUnDA and FC were 0.86 (0.34,1.39) and 0.12 (-0.47,0.71), respectively, and between N-Et-FOSAA and FC, these were 0.54 (-0.01,1.08) and 0.31(-0.07,0.68), respectively.

Conclusion

DBS can be used to measure early life exposure to toxins, and prenatal PFAS exposure is associated with elevated FC, with a slightly stronger effect in the offspring of women with IBD. Larger prospective studies are needed to validate these associations and understand potential underlying mechanisms through which early life PFAS exposures may contribute to IBD etiology.Read more OP23 Guselkumab induction restores intestinal immune homeostasis and promotes epithelial repair in moderately to severely active Ulcerative ColitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Selective inhibition of interleukin-23 (IL-23) through antagonism of the IL-23p19 subunit has demonstrated clinical efficacy in inflammatory bowel disease, but the mechanism of action (MoA) has not been fully defined. Here we provide a detailed evaluation of the cellular and molecular MoA of guselkumab (GUS), an IL-23p19 subunit antagonist, in patients (pts) with moderately to severely active ulcerative colitis (UC) from the QUASAR Phase 2b induction study (NCT04033445).

Methods

Serum proteins were evaluated from 302 pts treated with intravenous GUS induction therapy or placebo (PBO) who had at least one paired sample at Weeks (WK) 0 and 4 or WK12. Matched colonic biopsies at WK0 and 12 were available for 255 pts. Transcriptional profiling was performed with bulk RNA sequencing (RNAseq). Transcriptional modules derived from public UC single cell RNAseq (scRNAseq) were evaluated with differential expression in the bulk RNAseq dataset. Flow cytometry and scRNAseq were performed on a subset of matched WK0 and WK12 cryopreserved biopsies from 60 pts.

Results

Both GUS induction doses were effective vs PBO in achieving key endpoints including clinical remission, endoscopic and histologic outcomes. GUS reduced serum IL-22, IFNγ and IL-17A (p<1e-05) as early as WK4, which further declined through WK12. Unsupervised analysis of tissue transcriptomic modules (n=69) revealed 57 that were significantly changed with GUS at WK12. The top 6 downregulated modules represented Th17 cell (IL-23 pathway), neutrophil, IFNγ signaling, plasma cell and inflammatory epithelial and fibroblast cell states, while modules associated with epithelial cell populations and metabolism were upregulated (all false discovery rate [FDR]<0.05). Fc-γ receptor (CD64) expression was increased at baseline in all patients and reduced at WK12. Flow cytometry demonstrated reductions of CD45+ lymphocyte and CD66+ granulocyte populations (p<0.01). Parallel scRNAseq showed a reduction of inflammatory monocytes and fibroblasts in GUS responders at WK12 while pro-healing indicators were observed at WK12 including an increase in EpCam+ cells, BEST4+ enterocytes, and ADAMDEC1+ fibroblasts (p<0.01). Module analysis indicated an increase in goblet cells (FDR<0.05) which play a role in barrier integrity.

Conclusion

GUS induction restored intestinal immune homeostasis in pts with UC who achieved key endpoints at WK12, demonstrated by resolution of inflammation associated with the IL-23 pathway and inflammatory myeloid, epithelial and fibroblast transcriptional states. GUS also promoted epithelial repair as evidenced by increases in epithelial cell population, consistent with endoscopic and histologic outcomes at WK12.Read more OP36 Risankizumab Versus Ustekinumab for the Achievement of Clinical Outcomes and Symptom Improvement in Patients With Moderate To Severe Crohn’s Disease: Results From the Phase 3b SEQUENCE TrialWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The efficacy and safety of risankizumab (RZB) and ustekinumab (UST) in patients (pts) with moderate to severe Crohn's disease (CD) refractory to prior anti-tumour necrosis factor (TNF)α therapy were compared in the SEQUENCE head-to-head study. Previously, wk24 CD activity index (CDAI) clinical remission rates (CDAI<150) were reported for 50% of pts (first primary endpoint);¹ here, the efficacy of RZB versus (vs) UST for achieving wk24 clinical remission and other symptomatic improvements in the full pt population was assessed.

Methods

SEQUENCE (NCT04524611) was an open-label, multicenter, randomised, efficacy assessment-blinded study in pts with moderate to severe CD (defined in Figure footnote) refractory to TNFα therapy. Pts in the primary efficacy analysis set were randomised 1:1 to receive RZB (intravenous [IV] 600mg induction at BL, week (wk)4 and wk8, then 360mg subcutaneous [SC] maintenance every 8 wks [Q8w], starting at wk12) or UST (single weight-based IV induction followed by a 90mg Q8w SC maintenance starting at wk8) up to wk48. A mandatory steroid taper began at wk2. Randomisation was stratified by BL steroid use and number of failed anti-TNFs. Prespecified non-ranked endpoints included CDAI clinical response and stool frequency (SF)/abdominal pain score (APS) clinical remission (definitions in Figure footnote). CDAI clinical remission at wk48 was a ranked secondary endpoint. CDAI clinical remission at wks 8 and 24, and changes from BL in avg daily APS, SF, and CDAI, were evaluated post-hoc. Binary endpoints were analysed using non-responder imputation while incorporating multiple imputation to handle missing data due to COVID-19 and/or geopolitical conflict. Continuous endpoints were analysed using a mixed-effect model with repeated measures. All P values are nominal, except for wk48 CDAI clinical remission (ranked secondary endpoint).

Results

With RZB vs UST, respectively, greater rates of CDAI clinical remission (59.6% [152/255] vs 42.6% [113/265]; P=0.0001), SF/APS clinical remission (55.7% vs 41.1%; P<0.001) and CDAI clinical response (69.8% vs 54.3%; P<0.001) were observed at wk24; similar results were observed at wk48 (Figure). Mean BL APS in the RZB and UST groups was 1.9 (both groups), SF was 5.5 and 5.6, and CDAI was 309.4 and 310.1, respectively. Least square (LS) mean changes from BL in APS, SF, and CDAI were greater with RZB vs UST and observed early as wk8 (APS: -0.9 vs -0.8; SF: -3.0 vs -2.3; P<0.001; CDAI: -136.3 vs -117.1; P<0.05) (Figure). The safety profiles of RZB and UST were consistent with published results.¹

Conclusion

In this head-to-head study, improvements in symptomatic outcomes in pts with CD were greater with RZB than UST over 48 wks of treatment.¹doi.org/10.1002/ueg2.12474Read more OP37 Effect of the HLA-DQA1*05 allele on the efficacy of ustekinumab in patients with Crohn's Disease. Multicenter study based on the ENEIDA registry of GETECCUWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

HLA-DQA1*05 carriage is associated with the development of anti-drug antibodies and loss of response (LOR) to tumour necrosis factor antagonists (anti-TNF) in patients with inflammatory bowel diseases (IBD)¹. Ustekinumab has shown very low rates of immunogenicity and presumably will not be affected by this risk. Identifying patients at high risk of treatment failure would be important when selecting therapy for IBD.The objective of this analysis was to investigate the relationship between the HLA- QA1*05 allele and ustekinumab on development of LOR and drug persistency.

Methods

This is a retrospective cohort study from a prospectively maintained ENEIDA registry. LOR was defined as recurrence or worsening of IBD related symptoms that required a change or intensification in treatment, hospitalization or surgery. Independent predictors of LOR were identified using univariate and multivariable Cox proportional hazard regression. The HLA-DQA1*05 allele was determined from a saliva sample (kit OGD-600 de DNA Genotek Oragene) and DNA extraction with the Maxwell® RSC-Stabilized Saliva DNA kits.

Results

204 patients with Crohn's disease were included. Previous exposure to biological drugs was 96% (61% ≥2 biological drugs). Basal faecal calprotectin levels were 907±970μg/g and PCR levels 16.2±25 mg/dL. The median follow-up was 417±154 days. During this period, 25%, 16% and 13% of the patients required drug intensification, hospitalization or surgery, respectively. 43% of the patients included were carriers of one or two copies of the HLA-DQA1*05 allele. The presence/absence of this allele was not associated with LOR to ustekinumab (20% vs 16%, p = ns) nor with drug withdrawal (11% vs 6%, p = ns). In the multivariate analysis (COX regression), only the number of previous biological drugs was associated with ustekinumab persistency.

Conclusion

The presence of the HLA-DQA1*05 allele is not related to LOR or persistency of ustekinumab treatment. First-line treatment with ustekinumab rather than anti-TNF agents may be considered in HLA-DQA1*05-positive patients, particularly when the use of a concomitant immunosuppressant is contraindicated.1. Sazonovs A, Kennedy NA, Moutsianas L, Heap GA, Rice DL, Reppell M, Bewshea CM, et al. PANTS Consortium. HLA-DQA1*05 Carriage Associated With Development of Anti-Drug Antibodies to Infliximab and Adalimumab in Patients With Crohn's Disease. Gastroenterology. 2020 Jan;158(1):189-199.Read more DOP14 Proctocolectomy is associated with improved transplant-free survival in patients with primary sclerosing cholangitis: results from a pooled collaborative international studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

It is hypothesized that the gut-liver axis plays a pivotal role in the aetiology of primary sclerosing cholangitis (PSC). Colectomy before liver transplantation is associated with decreased rates of recurrent PSC.¹ We previously observed that proctocolectomy with permanent ileostomy is associated with better transplant-free survival in a population-based Dutch cohort.² The aim of the present study is to confirm the effect of colectomy on PSC disease course in an international context.

Methods

We conducted a retrospective analysis on the International PSC Registry (IPSCR), comprising patients from Finland, Norway, Sweden, and the Netherlands. Endpoints were defined as liver transplantation (LT) and PSC-related death (excluding colorectal carcinoma) and were censored in the first year after colectomy to allow for a delayed protective effect. Cox proportional hazards regression was performed, with correction for the following known risk factors; sex, age at diagnosis, large or small duct PSC, features of auto-immune hepatitis, and inflammatory bowel disease (IBD) status (i.e. ulcerative colitis, Crohn’s disease or IBD unspecified). IBD status and colectomy status were included as time-dependent exposure variables, the latter stratified for extent and indication for colectomy.

Results

A total of 2595 patients were included, of which 1341 from the Netherlands, 560 from Finland, 528 from Norway, and 166 from Sweden. Of all patients 1900(73%) were diagnosed with IBD and 346(15%) had undergone a colectomy; 34(9%) hemi-, 91(26%) subtotal, and 172(50%) proctocolectomy with pouch and 65(19%) with ileostomy. During a total follow-up of 28,282 patient years, 848(33%) patients reached the endpoint LT or PSC-related death.Hazard ratio (HR) of reaching LT or PSC-related death was significantly decreased in patients with proctocolectomy (0.70(0.52-0.93)) compared to patients without colectomy with variation per country (Netherlands 0.82(0.56-1.19), Finland 0.52(0.24-1.13), Norway 0.59(0.31-1.03), Sweden 0.28(0.06-1.24)). This effect was less pronounced in case of a hemi- or subtotal colectomy (HR 0.84(059-1.20)). The effect was most pronounced in the proctocolectomy with permanent ileostomy group (HR 0.55(0.30-0.99)). Of the known risk factors only a concurrent IBD diagnosis had no significant effect on transplant-free survival.

Conclusion

Our extended data confirm that colectomy is associated with a decreased risk of liver transplantation and PSC-related death. An incremental effect was seen with the extent of the colectomy, with the most pronounced effect in the proctocolectomy group with permanent ileostomy. Our data support the putative role of the gut-liver axis in the disease course of PSC.Read more DOP15 Results of a pragmatic multicentred randomised controlled trial investigating the use of personalised golimumab dosing in Ulcerative Colitis: the GOAL-ARC study (GLM dose Optimisation to Adequate Levels to Achieve Response in Colitis)Wed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Ulcerative Colitis (UC) is a chronic inflammatory bowel disease (IBD) often leading to impaired quality of life in affected patients. Current treatment modalities include anti-tumour necrosis factor (anti-TNF) monoclonal antibodies including infliximab, adalimumab and golimumab (GLM). RCT show higher trough drug levels (DL) following induction are associated with enhanced rates of remission in maintenance. GOAL-ARC is a pragmatic RCT to examine if dose optimisation of GLM following induction in response to suboptimal DL or persistently raised faecal calprotectin (FCP) improves rates of patient continuous clinical response (pCCR) and reduces maintenance disease activity in UC

Methods

A pragmatic randomised, multi-centre two-arm investigator initiated trial (NCT0268772) . Population – Patients with moderate to severe UC requiring TNF inhibitor therapy. Intervention - one arm receiving GLM treatment as per SMPC and one arm with dose optimisation of GLM based on FCP and DL from week 6 according to a dedicated algorithm. Eligible patients were randomised in a 1:1 ratio to 1 of 2 treatment groups. Study Duration - 46 weeks. Primary end-point pCCR = absence of flare defined as no increase in modified partial Mayo (MPM) score of 2 points from week 14-46 (requiring treatment intervention). Secondary endpoints included rate of clinical response to induction (week 14), defined as a drop of MPM of 2 points or decrease of ≥30% from baseline and level of FCP and rate of mucosal healing (Mayo endoscopic subscore of 0/1) at Wk 46

Results

107 patients were enrolled (target enrolment n=135, study enrolment terminated early due to recruitment problems during and following C19 pandemic). 97 patients (median age 42) were randomised, with one patient subsequently excluded due to ineligibility. Of 96 evaluable patients, 46 were randomised to SMPC treatment and 50 were randomised to the intervention. Baseline characteristic were comparable. 28/46 (61%) achieved wk 14 clinical response with SMPC and 19/46 (41%) met the primary endpoint (pCCR wk 14-46). In the intervention arm 28/50 (56%) achieved wk 14 clinical response and 24/50 (48%) met the primary endpoint (pCCR wk 14-46). The difference between groups in the rates of pCCR was 6.7% (95% CI:-0.15,0.29) in favour of the intervention and was not statistically significant. No safety signal associated with the intervention was observed.

Conclusion

In a pragmatic RCT no significant increase in the rate of pCCR was observed with personalised dosing of GLM for treatment of moderate to severe UC. A numerical trend towards reduced loss of response during maintenance (20% with SMPC versus 8% with intervention) is observed with personalised dosing of GLM suggesting this strategy may be beneficial in some patientsRead more DOP32 CD226+TIGITneg expression identifies pathogenic inflammatory CD4+ memory T cells in severe Crohn’s Disease patients, opening up opportunities for patient-tailored treatment strategiesWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

CD4⁺ memory T cells (Tmem) drive chronicity of inflammation in Crohn’s disease (CD) and ulcerative colitis (UC). Treatments specifically targeting T cells effectively induce disease remission. However, due to disease heterogeneity and possibly variation in the Tmem response, not all patients achieve or maintain remission. As such, strategies are needed to identify and monitor the therapeutic target, i.e. the inflammatory Tmem response, in individual patients. Monitoring has been hampered by the large variety in both protective regulatory and pathogenic inflammatory Tmem phenotypes, thus, common denominators need to be identified to distinguish all inflammatory from all regulatory intestinal Tmem populations in individual patients. We have shown that the coinhibitory receptor T-cell immunoreceptor with Ig and ITIM domains (TIGIT) is a common denominator identifying regulatory gut-homing Tmem. TIGIT shares its ligands with the costimulatory receptor CD226. While TIGIT ligation inhibits Tmem responses, CD226 engagement enhances Tmem activity. We hypothesize that TIGIT and CD226 differentiate the protective regulatory from the pathogenic inflammatory intestinal Tmem in individual IBD patients.

Methods

We studied CD38⁺CD62L^neg gut-homing Tmem in blood of therapy-naive pediatric IBD patients (CD n=59; UC n=32; IBD negative controls (IBDneg) n=24).

Results

In a subgroup of CD, but not UC patients, frequencies of regulatory TIGIT⁺ gut-homing Tmem at diagnosis were strongly reduced compared to IBDneg. Of these CD patients with low TIGIT frequencies, a significantly higher proportion had severe disease, defined as failing to achieve remission after 6 months or having a disease relapse within 1 year, compared to CD with normal TIGIT frequencies. As TIGIT is a common denominator for regulatory cells, we hypothesized that gut-homing Tmem without TIGIT (TIGIT^neg) contained inflammatory Tmem. Indeed, in CD, the TIGIT^neg Tmem population contained increased frequencies of pathogenic IFNg⁺IL-17⁺-double-producing cells compared to IBDneg. As TIGIT and CD226 frequencies inversely correlated (R=-0.78, p=4.8e-05) in CD patients, we assessed whether additional monitoring of CD226 could be used to more precisely identify and monitor inflammatory Tmem in CD. As anticipated, TIGIT^negCD226⁺ gut-homing Tmem frequencies significantly increased in CD patients compared to UC patients and IBDneg. TIGIT^negCD226⁺ Tmem were more proliferative and more activated compared to IBDneg, indicating increased inflammatory function.

Conclusion

These data establish that TIGIT and CD226 can be used to enumerate and differentiate the protective regulatory from the pathogenic inflammatory gut-homing Tmem in individual IBD patients, and to identify patients with severe disease.Read more DOP33 Distinct perturbances in metabolic pathways associate with disease progression in patients with Inflammatory Bowel DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Patients with inflammatory bowel diseases (IBD) exhibit distinct shifts in circulating metabolite levels that have been associated with clinical disease activity and disease phenotype. However, there are limited data on the impact of metabolomic changes on disease progression in IBD. We aimed to understand the association of circulating metabolite levels and related pathways with the risk of disease progression in patients with IBD.

Methods

We conducted an observational cohort study using the Mount Sinai Crohn’s and Colitis Registry (MSCCR). Patients were prospectively enrolled with baseline questionnaires and biospecimens that were then linked to longitudinal electronic health record data. A total of 1,456 serum metabolites were measured in 277 patients with UC and 375 patients with CD using untargeted metabolomics. Disease progression was defined as any new steroid or biological prescriptions, IBD-related hospitalizations, or surgery. Multivariable Cox proportional hazards regression models, adjusted for age, sex, smoking, biologic use, and surgery were used to explore metabolite associations with risk of disease progression. Metabolite set enrichment analysis (MSEA) was performed to identify underlying metabolic pathways associated with disease progression.

Results

During a median 2-year follow-up time (IQR 0.3-5.1 years), 375 patients (57.5%) had a disease progression event. Among CD, 151 metabolites significantly correlated with the composite outcome (FDR<0.1). Of these, 81 (53.6%) were linked to higher risk, mainly enriched in amino acids, purine, and pyrimidine metabolism, fibrinogen cleavage peptides, and bile acid pathways. Additionally, 70 (46.4%) metabolites associated with lower risk with enrichment in fatty acid metabolism, steroid biosynthesis, histidine, tryptophan, and antioxidant pathways. In CD, aspartate metabolism was most significantly associated with increased risk and linoleic metabolism with decreased risk. In UC, 84 metabolites were significantly associated with disease progression (FDR<0.1), with 29 (34.5%) associated with increased and 55 (65.5%) with decreased risk. Metabolic pathways linked to higher risk were sphingolipid, benzoate, hydrogen sulfide, polyamine, and tyrosine metabolism, while protective metabolites were enriched in branched-chain amino acid (BCAA), steroid biosynthesis, histidine, and phenylalanine pathways. In UC, sphingolipid metabolism was prominently associated with increased risk and BCAA metabolism with decreased risk.

Conclusion

Specific metabolites and metabolic pathways are associated with risk of disease progression in patients with IBD, highlighting potential prognostic metabolite biomarkers and pathways that may be important in modulating risk of disease progression.Read more OP18 Efficacy and safety of darvadstrocel treatment in patients with complex perianal fistulas and Crohn’s Disease: results from the global ADMIRE-CD II phase 3 studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Complex perianal fistulas are a serious complication in patients with Crohn’s disease (CD). Darvadstrocel (DVS), a suspension of expanded adult allogeneic adipose-derived mesenchymal stem cells, is approved in Europe and Japan for treatment of complex Crohn’s perianal fistulas (CPF). The global ADMIRE-CD II phase 3 randomized double-blind placebo-controlled study evaluated the efficacy and safety of DVS for treatment of complex CPF.

Methods

Patients aged 18–75 years with clinically controlled, inactive or mildly active CD and complex CPF (≤2 internal openings [IO] and ≤3 external openings [EOs]) who had an inadequate, or a loss of response to immunosuppressive agents or biologics were included. Patients were randomized 1:1 to receive a local injection of DVS as a single dose (120 x 10⁶ cells/24 mL) or placebo. In all patients, fistula preconditioning included vigorous curettage and seton placement 2–3 weeks before treatment, and seton removal, a further curettage and closure of IOs immediately before treatment. The primary endpoint was combined remission (closure of all treated EOs that were draining at baseline, despite gentle finger compression, and absence of collections >2 cm confirmed by MRI) at 24 weeks. Secondary endpoints included combined remission at 52 weeks, clinical remission (closure of all treated EOs without MRI confirmation) at 24 and 52 weeks, and time to clinical remission at 24 weeks. Safety was monitored up to 52 weeks.

Results

From 19 Oct 2017 to 26 Jul 2023, 568 patients received DVS (n = 283) or placebo (n = 285) with fistula preconditioning; 56.3% of patients enrolled in Europe and Israel, and 43.7% in North America. Mean (SD) age, sex and race were similar in the DVS and placebo arms (38.4 [11.9] vs 37.7 [10.8] years; 42.8% vs 45.6% female; 85.9% vs 89.1% White). Combined remission rates at 24 weeks did not statistically differ between treatments (48.8% DVS vs 46.3% placebo) and there were no differences in secondary endpoints (Table 1; Figure 1). Based on health authority guidelines, post hoc analyses of patients randomized before COVID-19 (11 March 2020; n = 141 DVS, n = 143 placebo) were performed: combined remission rates at 24 weeks were 46.8% (DVS) and 38.5% (placebo). The safety profile for DVS was consistent with prior studies with no new safety signals (Table 1).

Conclusion

The efficacy outcomes assessed did not statistically differ between DVS and placebo, and the placebo response rate (with fistula preconditioning) was higher than expected. Post hoc analyses revealed lower placebo response rates in patients randomized before COVID-19 (similar to the pivotal ADMIRE CD I study) than the overall placebo arm. DVS was well tolerated.Read more OP31 Single-cell analyses identify immune and stromal signatures of perianal fistulizing Crohn's DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Perianal fistulas occur in ~30-40% of Crohn’s disease (CD) patients associated with high morbidity and an impaired quality of life. The management of perianal fistulizing CD is a major clinical challenge, where its underlying etiology remains poorly understood.

Methods

We recruited patients with 1) CD with perianal fistulas (PCD; n = 12); 2) CD without perianal involvement (NPCD; n = 10); 3) idiopathic perianal fistulas (IPF; n = 21). Biopsies were taken from the fistula tracts, external opening of the fistulas, and rectal mucosa during examination under anesthesia or colonoscopy. Mucosal immune cells were analyzed using mass cytometry (or CyTOF), while all cells from PCD and IPF fistula tracts (n = 5 or 6) were characterized using single-cell RNA-sequencing.

Results

CyTOF revealed a skewed mucosal immune landscape in PCD. E.g., PCD fistula tracts harbored elevated CD45RO+ T cells including Tregs with increased expression of TIGIT and CD226 compared to IPF. PCD also expanded Th17 cells in the fistula tracts and IL-17-producing CD8 T cells (Tc17) in the rectum. Altered exhaustion markers CD39 and CD127 were present in both CD4 and CD8 T cells from PCD fistula tracts, external fistula openings, and rectum compared to IPF and NPCD. Regulatory B cells (Bregs), with immunomodulatory function in the gut, were dramatically diminished in PCD compared to IPF. In addition, PCD fistula tracts, fistula opening, and rectum all exhibited substantially higher CD172+TREM1+ macrophages, which were previously found to promote luminal CD (Figure 1; only fistula tract data are shown). Using scRNA-seq, we unraveled immune and stromal cell compartments in PCD and IPF fistula tracts (Figure 2). We also identified a small mast cell population, which was diminished in PCD. Mast cells are involved in tissue repair and remodeling in other diseases, although their presence in perianal fistulas was previously unknown. Three fibroblast populations (cluster 4, 6, 7 in figure 2D), with elevated activities in interferon signaling, IL-6-JAK-STAT3 pathway, TNF signaling, as well as TGF-B and epithelial-mesenchymal transition, were dramatically increased in PCD compared to IPF. Ongoing studies are focusing on spatial transcriptomics and functional analysis of fistula-associated immune cells and fibroblasts.

Conclusion

Using single cell analysis of the fistula tracts and nearby tissues from an extensive patient population, we revealed previously unknown immune and stromal cell landscapes of PCD. Our findings highlight the pathogenic roles of IL-17 signaling, T cell exhaustion, pathogenic macrophages, and pro-inflammatory/remodeling fibroblasts in the pathogenesis of PCD. This study may open new avenues for disease-specific therapies for this challenging condition.Read more DOP04 Screening and management of fistula cancers in patients with perianal fistulising Crohn’s Disease: an expert consensusWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Fistula cancer is a rare and often devastating diagnosis in patients with perianal fistulising Crohn’s disease (CD). Fistula cancer management is a complex process requiring multi-disciplinary effort. However, given the low incidence and subsequent lack of data and clinical trials in the field, there is little to no guidance on screening and management of fistula cancer. To inform clinical practice, we developed consensus guidelines on fistula cancer in perianal fistulising Crohn’s disease by multidisciplinary experts from the international TOpCLASS consortium.

Methods

We performed a systematic review of the literature by standard methodology, using the Newcastle-Ottawa quality assessment tool. Data were retrieved from articles according to these domains: epidemiology and risk factors, clinical presentation, diagnostics, staging, and treatment. We developed consensus statements using a Delphi consensus approach. Participants included gastroenterologists, surgeons, radiologists, and pathologists. We performed two rounds of voting: (1) online survey followed by statement edits and (2) hybrid meeting with discussion until over 80% consensus was achieved for each statement.

Results

Of 550 articles identified, 99 were eligible, and 80 articles were included. The overall quality of evidence was low. Seven statements were accepted in the final consensus (Table 1).Patients with longstanding (>10 years) perianal fistulising CD should be considered at small but increased risk of developing fistula cancer, including anal squamous cell cancer (SCC) and anorectal carcinoma. Risk factors for anal SCC, including human papilloma virus (HPV), should be considered. Clinical signs and symptoms of fistula cancers are non-specific, and several case reports included asymptomatic patients. New or refractory/progressive perianal symptoms should prompt evaluation for fistula cancer. There was no consensus on timing or frequency of screening in patients with asymptomatic perianal fistula. Regarding diagnostics, multiple modalities may be required, including repeated exam under anesthesia with biopsy. Multidisciplinary team efforts were deemed central for the management of fistula cancers.

Conclusion

Clinicians managing patients with perianal fistulising CD should be aware of the risk of fistula cancers, including anal SCC and anorectal carcinoma. Our expert consensus recommends consideration of patient factors including duration of fistulas, HPV status, and perianal symptoms, and gives guidance on diagnostic modalities and treatment considerations. Multidisciplinary coordination of care is paramount, and more studies in the field are needed.Read more OP19 Extended mesenterectomy is not superior to mesenteric sparing resection in primary ileocolic resection for Crohn’s Disease in terms of postoperative endoscopic recurrence – results of an international randomised controlled trialWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Extended mesenteric resection has recently been proposed to improve clinical outcomes after an ileocolic resection (ICR) for Crohn’s disease. The aim of this study was to analyse the clinical relevance of extended mesenteric resection, up to the level of the ileocolic trunk (intervention group), compared to conventional mesenteric sparing resection (control group) with regard to postoperative outcomes in patients undergoing primary ICR for Crohn’s disease.

Methods

In an international randomised controlled trial (RCT), patients ≥16 years, were assigned 1:1 to either the intervention- or the control-group. The anastomotic technique was standardised (side-to-side stapled). To demonstrate a relevant difference of 25% in postoperative endoscopic recurrence (defined as a modified Rutgeerts score ≥i2b, according to central reading) at 6 months, a minimum of 62 evaluable patients per arm were required. Secondary outcome parameters were postoperative morbidity, histopathological outcomes and use of Crohn’s medication postoperatively.

Results

In total, of the 129 included patients, 56 (43.3%) were male with a median age of 36 (IQR 22-55). There were no statistically significant differences in baseline characteristics between the two groups. There was no difference in endoscopic recurrence rates between the two groups: 27/62 (43.5%) in the intervention group and 27/64 (42.2%) in the control group, (p=1.0) Fig 1. Median time until endoscopy was 6 months (IQR 6-7). More patients received postoperative medical prophylaxis in the intervention group (28% vs 14%). In the control group, more patients started medication after endoscopy (intervention group 20% vs control group 27%). This resulted in a similar number of patients in both groups being on Crohn’s medication after six months, 48% in the intervention group and 41% in the control group. There was no significant difference in length of resection specimen (median length colon 7cm; ileum 22.5cm), blood-loss or operative time. Overall, a postoperative complication occurred in 28%, with anastomotic leakage in 5 (3.9%).

Conclusion

This is the first RCT to present data on the effect of extended mesenteric resection during ICR for Crohn’s disease. The results of this study showed no superiority of extended mesenteric resection with regard to endoscopic recurrence or other perioperative outcomes.Read more OP27 Oxalyl-CoA decarboxylase is a major and specific virulence factor for Adherent Invasive Escherichia coliWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Adherent Invasive E. coli (AIEC) strains are found in one-third of patients with ileal Crohn’s disease (CD). To date, the bacterial genes involved in AIEC survival in the inflammatory environment are still unclear. Here, we systematically identify the genes of AIEC required for gut colonization and survival under the inflammatory conditions present in a mouse model of IBD.

Methods

We performed a transposon sequencing (TnSeq) approach using the laboratory strain E. coli K12 MG1655 and the AIEC strain LF82. We created two saturated Tn mutant libraries (3x10⁵ mutant per bank) and gavaged them to mice with and without dextran-sodium sulfate (DSS)-induced colitis. We screened for essential genes for each bacterium in both conditions in the Cecum, Colon, Ileum and Jejunum.

Results

After High-throughput sequencing, we identified oxc gene, encoding for the oxalyl-CoA decarboxylase enzyme, as crucial for the survival of LF82 but not MG1655 in the whole gastrointestinal tract in colitis setting. To confirm our TnSeq results, the effect of oxc isogenic mutant (∆oxc) and complemented strains of LF82 and MG1655 was tested.The inflammation severity was exacerbated in mice colonized with LF82WT or the complemented strain compared to LF82∆oxc. LF82∆oxc strain load decreased after colitis induction while the LF82WT and the complemented strain persisted. In a competition between LF82 WT and ∆oxc, the WT strain was able to outcompete the ∆oxc strain. This altered ability of LF82∆oxc to colonize the gut was associated with decreased bacterial motility and flagella expression.In vitro, we found a decreased resistance of different AIEC strains to oxidative stress and acidic pH compared to a collection of commensal E. coli strains. This difference was abolished in all the ∆oxc AIEC strains we built and tested, demonstrating a crucial role for this gene in the tolerance to oxidative and acidic stress. Finally, lack of oxc also caused a reduction in survival into RAW264.7 macrophages, and an altered pro-inflammatory response of the macrophage, with a significant reduction of TNF-α levels.

Conclusion

oxc plays a major role in vitro and in vivo for AIEC strains but not for laboratory or commensal strains. Further studies to (i) fully explore this role and (ii) evaluate Oxc as a therapeutic target are currently under investigation.Read more OP40 Transcriptomic signature of response to vedolizumab in patients with moderate-to-severe ulcerative colitis: Results from an international, multicentre, retrospective cohort studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Transcriptomic analysis has the potential to facilitate drug development and clinical decision making in inflammatory bowel disease. Current understanding of pharmacodynamic response to vedolizumab is limited by a lack of publicly available mucosal biopsy RNA samples/sequencing data and corresponding clinical information. We aimed to identify gene signatures associated with response to vedolizumab in ulcerative colitis (UC) patients by pooling data from 3 international sites.

Methods

Patients receiving vedolizumab for the treatment of moderate-to-severe UC at Hospital Clínic de Barcelona (IDIBAPS), Mount Sinai Hospital (MSH), and University of California, San Diego (UCSD) with baseline and post-treatment (week 14 [± 4 weeks]) mucosal biopsy RNA-sequencing data and Mayo Clinic endoscopic subscores (MCES) were eligible for inclusion. Endoscopic response was defined as an MCES <1. Demographic and clinical data were collected. Differential expressed genes (DEGs) between baseline and week 14 were identified using linear mixed models with a >1.5 or <-1.5-fold change (adjusted P-value <.05). Enrichment was performed using Reactome pathway analysis and a previously published UC gene signature (adjusted P-value <.05).¹ Analyses were performed using R version 4.3.0.

Results

Twenty-three patients were included (IDIBAPS: n=12; MSH: n=8; UCSD: n=3). Site-specific differences in sex, surgical history, and corticosteroid use were observed (Table). Analysing data by site yielded a relatively small number of DEGs between baseline and week 14 (IDIBAPS=57 [27 up-regulated, 30 down-regulated]; MSH=0; UCSD=0) among endoscopic responders (IDIBAPS: n=5; MSH: n=7; UCSD: n=2). Combining data from the 3 sites increased the number of DEGs among endoscopic responders at week 14 (n=14) to 1162 (662 up-regulated and 500 down-regulated). The down-regulated DEGs were enriched for genes involved in 37 of 103 up-regulated Reactome pathways in UC, including neutrophil degranulation, interleukin-4 and interleukin-13 signalling, interleukin-10 signalling, and integrin cell surface interactions. The up-regulated DEGs were enriched for genes involved in 1 of 39 down-regulated Reactome pathways in UC (Drug ADME).

Conclusion

We defined a pharmacodynamic signature using mucosal biopsies from UC patients who had endoscopic response to vedolizumab at week 14. The signature was enriched for several, but not all, pathways involved in UC. In addition to providing insight into vedolizumab’s mechanism of action, we underscored the utility of multi-site collaboration to access data, increase statistical power, and enhance the generalizability of research findings. Reference: 1. Linggi et al. Sci Rep 2021;11:18243.Read more DOP01 Definitions of histological abnormalities in inflammatory bowel disease: an ECCO position paperWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

High quality histological examination of ileocolonic biopsies in inflammatory bowel disease (IBD) plays a critical role in optimising clinical management, investigative studies, and clinical trials. The correct assessment of histological features can confirm the diagnosis of IBD, assist with its subclassification (as ulcerative colitis or Crohn’s disease), facilitate the estimation of disease activity and disease extent, and aid the detection of mimics and complication.However, there are surprisingly few universal definitions of each histological abnormalities and the existing definitions are often inconsistent. The main practical concern is that histological scoring schemes, or guidelines on histological diagnosis, include detailed features, and many of these features have, paradoxically, no, or vague definitions. Furthermore, interobserver variability for many histological features in IBD is significantly high, possibly reflecting lack of precision.The aim of this paper is to review and assess any existing histologcal definitions and criteria, selecting the most appropriate where possible, and modifying them or writing new definitions where necessary.

Methods

The European Crohn's and Colitis Organisation (ECCO) and the project leaders formed a panel of experts in the IBD field, composed of pathologists and gastroenterologists to explore inconsistencies in the definitions of histological abnormalities using the best resources and evidence available. The panel examined existing definitions, peer reviews publications, scoring schemes, guidelines and textbooks. An important contribution was also given by their professional experience and knowledge.

Results

The literature review process confirmed that most current existing definitions often have no evidence base and vary between sources.The panel of experts developed 40 statements on histological definitions in IBD with accompanying supporting text for each statement.

Conclusion

The statements represent expert consensus with the support of evidence where available. Further possible development of this process will include attempts to grade histological changes, aiming to improve the consistency of pathological diagnosis, a reduction in currently high rates of interobserver variability, more precision in clinical trial work and research, and to facilitate development of new guidelines and scoring schemes for IBD.Read more DOP12 Efficacy and safety of obefazimod in UC patients at weeks 48 and 96 of an open-label maintenance study among clinical responders at week 8 of the Phase 2b induction trialWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Obefazimod is an investigational, oral, once-daily, small molecule which enhances expression of microRNA-124 and is currently in phase 3 clinical trials for the treatment of patients with moderately to severely active ulcerative colitis (UC) [1]. Obefazimod demonstrated efficacy and safety in patients with UC at week-8 in a placebo-controlled, Phase 2b induction trial and in the subsequent open-label maintenance (OLM) study [2]. Here we report efficacy and safety at weeks 48 and 96 among patients who achieved clinical response at week 8 of the double-blind induction trial and compared efficacy to the overall study population.

Methods

Patients received placebo or obefazimod 25mg, 50mg or 100mg once daily (od) during the Phase 2b, induction trial and, irrespective of their clinical response, could enter the optional 96-week OLM study with obefazimod 50mg od. Patients were followed monthly for safety and efficacy. This analysis focuses on efficacy and safety among patients who reached clinical response (decrease from baseline in the Modified Mayo score (MMS) ≥ 2 points and ≥30% from baseline, plus a decrease in rectal bleeding sub-score (RBS) ≥ 1 or an absolute RBS ≤ 1) at week 8 of double-blind induction and continued treatment in the OLM.

Results

Among the 217 patients who participated in the OLM, 57% (124/217) achieved clinical response at week 8 of the induction trial. Within this subgroup, 66% (82/124) and 60% (74/124) achieved clinical remission at weeks 48 and 96, respectively. Clinical response was achieved by 86% (107/124) and 77% (95/124), endoscopic improvement was achieved by 70% (87/124) and 64% (79/124), and endoscopic remission was achieved by 38% (47/124) and 42% (52/124) at weeks 48 and 96, respectively. The proportions of patients achieving these efficacy endpoints in this subpopulation were numerically higher than those observed in the overall study population (Table 1). No new safety findings were observed in this sub-population during the OLM.

Conclusion

A substantial proportion of patients who reached clinical response at week 8 of the induction study achieved clinical efficacy endpoints at week 48 and 96 of the open-label maintenance study. Among these patients, nearly 8 out of 10 maintained clinical response, and 6 of 10 achieved durable clinical remission for up to 96 weeks of treatment with 50 mg of once-daily obefazimod.References1. Vermeire S, et al. J Crohns Colitis. 2023; doi: 10.1093/ecco-jcc/jjad067;2. Vermeire S, et al. The Lancet Gastroenterology & Hepatology. 2022.Read more DOP13 Effect of 8 weeks of combined aerobic and resistance exercise on quality of life, muscle strength, aerobic capacity, and disease activity in patients with Inflammatory Bowel Disease; a parallel group randomized clinical trialWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Sarcopenia is prevalent in patients with IBD (inflammatory bowel disease). This study aimed to assess the effects of an 8-weeks combined aerobic and resistance training program on the quality of life, disease activity, muscle strength, and aerobic capacity in patients with IBD. (Registration ID: NCT05455762)

Methods

This study was a single-blind parallel-group randomized clinical trial. Inclusion criteria were patients 18 to 65 years old with a confirmed diagnosis of IBD. Exclusion criteria: active malignancy, consumption of systemic corticosteroids, and patients with moderate to severe physical activity more than 150 minutes/week. Patients were allocated to each group by block randomization with a 1:1 ratio. The intervention consisted of walking sessions on even days and six resistance exercises on odd days. The primary outcome was the patients' quality of life, measured by the Persian version of the ibdq-9 questionnaire. secondary outcomes included disease severity, muscle strength, 6-minute walk test, and 30-second sit-to-stand test. We measured muscle strength by a handheld dynamometer.

Results

Of 72 patients screened 64 were eligible for the study. During the follow-up period, 13 patients, 8 from the exercise group and 5 from the control group, were excluded from the study. 51 patients, 28 females and 23 males, with a mean age of 34.9 ± 10.57 were analyzed. Two groups were matched in demographic and IBD-related characteristics. Unlike the control group, the exercise group showed a significant increase in overall quality of life (40.29 to 47.75, p=0.005), particularly in intestinal and systemic symptoms domains (p=0.01 and p=0.004). the inter-group analysis found no significantly higher mean difference in QOL scores between the exercise and control groups (p=0.053). The Partial Mayo score in patients with ulcerative colitis (UC) significantly decreased in the intervention group but not in the control group. The Harvey-Bradshaw index in Crohn patients didn’t change in either group. There were no exercise-related serious complications. The 6-minute walk test distance significantly increased in the exercise group but not in the control group. The 30-second sit-to-stand test didn’t significantly change in either group. Of muscles examined (hand grip, shoulder abductor, hip flexor, knee extensor, and elbow flexor) only knee extension strength increased in both groups.

Conclusion

Combined resistance and aerobic exercise in patients with IBD is safe and can significantly improve the quality of life and aerobic capacity. This regimen also improved clinical severity in patients with UC but not in Crohn’s. Muscle strength did not significantly improve when comparing the two groups, possibly due to the short duration of the intervention.Read more DOP28 Yield of surveillance colonoscopy in patients with Primary Sclerosing CholangitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Patients with primary sclerosing cholangitis (PSC) have a higher risk of developing colorectal cancer (CRC), in particular in patients with concurrent diagnosis of inflammatory bowel disease (IBD). Therefore, strict surveillance colonoscopy in patients with PSC and PSC-IBD is recommended with consideration of random biopsies. The aim of this study was to assess the method and yield of surveillance colonoscopy in patients with PSC and PSC-IBD in routine practice in the Netherlands.

Methods

An observational cohort study was performed within the EpiPSC2 cohort in The Netherlands. Patients with a confirmed PSC diagnosis were included from January 2008 onwards. Data were collected retrospectively from the date of diagnosis until inclusion, and prospectively from that date forward. Patient demographics, PSC and IBD disease characteristics were collected at study inclusion and during annual follow-up. For this study, data collection was expanded retrospectively with colonoscopy and pathology reports. Outcomes were endoscopic surveillance technique, whether random or targeted biopsies were taken, if polypectomy was performed, dysplasia detection rate and type of dysplasia.

Results

The study population included 1,203 PSC patients, of whom 82.1% had large duct PSC, and 70.6% concomitant IBD (table 1). A total of 4,099 colonoscopies were performed in 759 individual patients, with a median of 4 colonoscopies per patient (IQR 2 – 8). The median follow-up duration was 11 years (IQR 12 – 17). In total, 11.5% (n=473) of colonoscopies were performed with chromo-endoscopy. Among the conducted colonoscopies, 2,543 included biopsies, 355 involved polypectomies, and 86 comprised both biopsies and polypectomies. Dysplasia was identified in 11.4% (341 out of 2,984) of the colonoscopies, including 14.1% indefinite for dysplasia (n=48), 75.1% low grade dysplasia (n=256), 7.6% high grade dysplasia (n=26), and 5.9% adenocarcinoma (n=20). The detection of dysplasia occurred through random biopsies in 89 colonoscopies (26.1%), targeted biopsies in 114 colonoscopies (33.4%) and polypectomy in 153 colonoscopies (44.9%) (figure 1). Dysplasia was observed in 195 (26%) individual patients, of whom 80.5% had PSC-IBD.

Conclusion

Our data highlights the importance of colonoscopic surveillance in PSC and PSC-IBD patients. Dysplasia was detected in over a quarter of patients undergoing surveillance colonoscopy. Notably, 26.1% of dysplasia cases were identified through random biopsies, emphasizing the importance of incorporating random biopsies into surveillance protocols for this specific patient population.Read more DOP29 Capsule endoscopy-guided proactive treatment versus standard treatment of patients with quiescent Crohn’s Disease: The CURE-CD randomized controlled trialWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Optimal strategies for treat-to-target in Crohn’s disease (CD) are still being sought. We aimed to examine the value of capsule endoscopy (CE) to guide proactive treatment optimization in patients with CD

Methods

A prospective randomized controlled clinical trial with temporally-restricted blinding. Patients with CD involving the small bowel who were in clinical remission (CDAI<150) for over three months were enrolled. Baseline clinical, biomarker, imaging, patency capsule and CE assessments were performed. ‘High risk’ patients, defined as CE Lewis score ≥350 were randomized to either proactive treatment optimization or continued standard care for 24 months. ‘Low risk’ patients with Lewis score<350 continued their standard care. All patients repeated CE every six months for 24 months. Primary outcome was the rate of clinical exacerbation (CDAI increase>70 points and CDAI>150 or hospitalization/surgery) in the standard-care versus the proactive-care sub-groups of high-risk patients, at 24 months. Secondary outcomes included risk of flare in the low-risk versus the standard-care high-risk arms, and predictive profiles for flare of calprotectin, MRI, intestinal ultrasound and Lewis score.

Results

Out of 118 screened patients, 60 were enrolled (20 in each of the three arms). Treatment intensification in CE-determined high-risk group, who were allocated to proactive treatment, comprised biologic dose-escalation (n=11/20), starting a biologic (8/20) or swapping a biologic (1/20) at study entry. Notably, 9/20 proactive-group patients underwent a second optimization following detected inflammation on subsequent semi-annual CE studies. Clinical exacerbation by 24 months (primary outcome) occurred in 5/20 (25%) of the high-risk proactive-treatment group versus 14/20 (70%) of the high-risk standard-care group (OR=0.14, 95%CI 0.04-0.57, p=0.006). For secondary outcomes, the rate of clinical flare in the standard-care low-risk group was numerically but not significantly lower than in standard-care high-risk group (9/20 versus 14/20, respectively, OR 0.3, 0.1-1.3, P=0.11). Among all patients continuing standard care, baseline CE Lewis score was higher among relapsers versus non-relapsers (median 450, IQR [225-900] versus 225, [135-600], respectively, p=0.03). Of 251 CE ingested, there was a single (0.4%) temporarily-retained CE, which resolved spontaneously.

Conclusion

In a randomized strategy-finding controlled trial, proactive treatment optimization based on CE findings in patients with CD in remission, proved safe and superior for prevention of disease exacerbation compared with continued standard care. NCT03555058Read more DOP64 Steroid-sparing effect of risankizumab vs ustekinumab in patients with moderately to severely active Crohn’s Disease: Post hoc results from the phase 3b SEQUENCE trialWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Corticosteroid (CS) dependency and/or resistance occurs in approximately 50% of patients with Crohn’s disease (CD).¹ In SEQUENCE, risankizumab (RZB; interleukin [IL]-23 inhibitor) demonstrated superiority over ustekinumab (UST; IL-12/IL-23 inhibitor) for the ranked secondary endpoints of CS-free clinical remission and CS-free endoscopic remission at week 48. In this post hoc analysis, we evaluate the CS-sparing effects of RZB and UST over 48 weeks in patients taking CS at baseline (BL).

Methods

SEQUENCE (NCT04524611) was an open-label, multicenter, randomised, efficacy assessment-blinded study in adults with moderately to severely active CD who previously failed ≥ 1 anti-tumor necrosis factor (TNF) therapy. Patients in the primary efficacy analysis were randomised 1:1 to receive RZB (intravenous [IV] 600 mg induction dose at weeks 0, 4, and 8, followed by a subcutaneous [SC] 360 mg maintenance dose every 8 weeks starting at week 12) or UST (single weight-based IV induction dose, followed by a SC 90 mg maintenance dose every 8 weeks starting at week 8) up to week 48. A mandatory CS taper started at week 2. CS-free outcomes (clinical remission or endoscopic remission and no CS at the assessed visit) were evaluated among patients taking CS at BL. Nominal P values were reported.

Results

The primary efficacy analysis included 520 patients (RZB, n = 255; UST, n = 265), and 24.8% (129/520) of patients were taking CS at BL. Demographics and disease characteristics were generally similar between treatment groups and between patients with and without CS use at BL. The mean (SD) daily prednisone-equivalent dose at BL was 21.4 (12.9) mg (RZB) and 19.5 (10.7) mg (UST), respectively. By week 8, more patients treated with RZB vs UST discontinued CS (75.9% vs 59.2%; nominal P < .05). Although a similar proportion of patients in either treatment group discontinued CS at week 24, more patients treated with RZB vs UST discontinued CS at week 48 (86.2% vs 57.7%; nominal P < .001). Of the patients taking CS at BL, RZB vs UST treatment resulted in higher rates of CS-free clinical remission (week 24: RZB, 44.8% vs UST, 33.8%; week 48: RZB, 56.9% vs UST, 31.0%) and CS-free endoscopic remission (week 24: RZB, 34.5% vs UST, 11.3%; week 48: RZB, 32.8% vs UST, 12.7%) (Table 1). Most patients who achieved CS-free outcomes at week 48 were CS-free for 90 days before week 48.

Conclusion

In patients with CD who previously failed anti-TNF therapy, RZB was more effective than UST for discontinuing CS use and achieving CS-free clinical and endoscopic remission.References:1. Lichtenstein G., et al. Am J Gastroenterol. 2018;113:481−517Read more DOP65 Infliximab plus azathioprine and quick steroids discontinuation versus azathioprine plus steroids in patients with acute severe Ulcerative Colitis responding to intravenous steroids: a parallel, open-label randomized controlled trialWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

In patients admitted for acute severe ulcerative colitis (ASUC) responding to intravenous (IV) steroids, the most effective treatment is unknown. In thiopurine-naive patients, thiopurines are appropriate to maintain remission according to current guidelines while the benefit of early infliximab (IFX) therapy remains to be established.

Methods

In this multicentre, parallel group, open-label randomised controlled trial, thiopurine and biologics-naïve adults admitted for ASUC defined by a Lichtiger score >10 were included between 2016 and 2021 if they responded to IV steroids. They were randomly assigned to receive either combination therapy with IFX and azathioprine (AZA) with a quick steroid discontinuation (IFX+AZA arm), or AZA and standardized steroid tapering regimen (AZA arm). The primary endpoint was treatment failure at W52, defined as absence of steroid-free clinical remission (MCS≤2 with no individual subscore >1), absence of endoscopic response (Endoscopic subscore ≤1), use of a prohibited treatment, adverse event leading to interruption of allocated treatment, colectomy or death. A sample size of 73 patients per group was initially calculated. Due to challenges in recruiting patient, the steering committee decided to prematurely terminate the study blindly of any study results, after including 64 patients.

Results

64 were randomised (32 males, age of 34.5 [26.3-50.3] years, Lichtiger score of 13.0 [12-14], CRP of 29.0 [12.8-96.8] mg/L and serum albumin of 31.2 [27.7-35.6] g/L at baseline): 32 were assigned to IFX+AZA arm and 32 to AZA arm. In ITT population, treatment failure at w52 was observed in 81.5% in the AZA arm versus 53.3% in the IFX+AZA arm (OR 3.85 [1.15-12.88], p=0.03). Components of the composite primary endpoint are given in table 1. In PP population, treatment failure at week 52 was observed in 81.5% (22/27) in the AZA arm versus 50.0% (13/26) in the IFX+AZA arm (OR 4.40 [1.28-15.18], p=0.02). In total 121 adverse events (AE) were reported in 40 patients including 23 serious AE in 18 patients (11 in the IFX + AZA arm and 7 in the AZA arm, p=0.24) and 8 leading to treatment interruption (5 in the IFX+AZA arm and 3 in the AZA arm, p=0.39). Serious AE included infectious AE in 6 cases (1 in the AZA arm and 5 in the IFX+AZA arm, p=0.20) and UC relapse in 9 (4 in the AZA arm and 5 in the IFX+AZA arm, p=0.60). No death was reported.

Conclusion

At w52, combination therapy with IFX + AZA and quick steroids discontinuation was more effective than AZA with standard steroids tapering regimen to prevent treatment failure in patients with ASUC responding to IV steroids. Combination therapy with IFX and AZA should be encouraged in ASUC patients responding to IV steroids (EudraCT 2014-005212-42; study funded by Pfizer).Read more DOP66 INSPIRE: Preliminary data from an observational post-marketing registry on the effectiveness and safety of darvadstrocel in patients with Crohn’s Disease and complex perianal fistulasWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Darvadstrocel (DVS), a suspension of expanded allogeneic adipose-derived mesenchymal stem cells, is approved for the treatment of complex Crohn’s perianal fistulas (CPF). INSPIRE (EUPAS24267) is a European observational post-approval study evaluating real-world effectiveness and safety of DVS in patients with complex CPF for up to 36 months. Here we report preliminary clinical and safety outcomes from INSPIRE.

Methods

Patients with complex CPF who had received DVS according to local standard practice were eligible to enrol. Clinical response (closure of ≥50% of external openings [EOs]) and clinical remission (closure of all EOs) of DVS-treated fistulas that were draining at baseline, were evaluated in the all-treated (AT; received ≥1 dose of DVS with an evaluation for fistula response after 6 months) and per-protocol (PP; received DVS as per label-approved guidelines) cohorts. Treatment-emergent adverse events (TEAEs), serious TEAEs and AEs of special interest were reported for the safety cohort (all patients treated with DVS).

Results

As of April 2023, 652 patients had enrolled (Table 1). Complete data to evaluate 12-month clinical response and remission were available for 134 (AT cohort) and 124 (PP cohort) patients, of whom 79.9% (AT, n = 107) and 79.8% (PP, n = 99) had a clinical response and 76.1% (AT, n = 102) and 76.6% (PP, n = 95) had clinical remission (Figure 1). From baseline to Month 12, there was a decrease in the mean (standard deviation [SD]) Perianal Disease Activity Index score (–3.5 [3.3]; n/N = 96/302 and –3.7 [3.2]; n/N = 89/249) and a decrease in the mean (SD) Harvey–Bradshaw Index for Crohn’s disease activity (-0.3 [2.8]; n/N = 102/302 and -0.4 [2.9]; n/N = 95/249) in the AT and PP cohorts, respectively. Complete safety data were available for 619 patients (median [min–max] follow-up 480 [6–1595]) days. Overall, 26% (n = 162) had ≥1 TEAE and 10% (n = 63) ≥1 serious TEAE. The most frequent TEAEs were anal abscess (6.9%), COVID-19 (1.9%) and proctalgia (1.1%). No deaths were reported. One breast cancer lymph node metastasis and one ovarian epithelial cancer were reported; both events were confounded by immunosuppressant treatment and were not considered related to DVS treatment.

Conclusion

These preliminary data are consistent with the pivotal ADMIRE-CD study and demonstrate a single dose of DVS in patients with complex CPF is associated with positive clinical outcomes in up to 80% of patients, and a favourable safety profile, both of which are maintained after 12 months. The inherent limitations of registry-based studies mean these data should be interpreted with caution. However, the ongoing INSPIRE study will provide longer follow-up data to confirm these observations with respect to any study limitations.Read more DOP67 MB310: From Clinical FMT to a Phase 1 Study with a Defined, Orally Administered Live Bacterial Therapeutic for Mild Moderate Ulcerative ColitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The composition of the gut microbiome is a key determinant in inflammatory bowel disease. Consequently, modifying the composition of the gut microbiota has the potential to transform the treatment of ulcerative colitis (UC). The clinical use of faecal microbiota transplantation (FMT) has become widespread, especially for the treatment of C. difficile associated diseases, as a method of changing the composition of the gut microbiome from a diseased to a healthy state. FMT is, by its nature, an undefined and variable therapy due to differences between donors. Microbiotica has taken a "patient-first" discovery approach to identify a defined consortium, which is being developed as a live bacterial therapeutic for treatment of mild-to-moderate UC patients in a Phase 1b clinical trial, the COMPOSER-1 study, in 2024.

Methods

A clinical trial in UC patients (Costello et al., 2019), in which patients were treated with FMT from healthy donors, showed a 32% clinical remission rate in the active treatment group, as compared to 9% in the placebo arm. Donor, pre-treatment recipient, and post-FMT recipient samples were analysed using shotgun metagenomic sequencing. All samples were analysed using Microbiotica’s precision microbiome analysis platform to identify bacteria associated with patient response. These bacteria were assessed in cellular assays using relevant human cell/cell lines including: Caco2, dendritic cells, M1 macrophages, and CD4+ T-cells.

Results

We defined a signature of therapeutic response based on bacteria that engrafted from the donor into UC patients and were associated with clinical benefit. A sub-species level analysis identified 8 bacteria, which have been developed into a defined live bacterial therapeutic, MB310. The consortium bacteria enhanced the barrier integrity of an epithelial cell monolayer, and protected the barrier from inflammatory challenge by LPS. In vitro, the bacteria also have an anti-inflammatory effect when incubated with different primary innate immune cells, dendritic cells and M1 macrophages. Specific MB310 bacteria, either directly or via metabolites, are able to regulate T-cell responses.

Conclusion

In summary, we have identified a consortium of bacteria using patient-first discovery in a successful FMT study that is being developed as a treatment for UC. The consortium of 8 bacteria is able to impact multiple disease-relevant mechanisms including epithelial barrier integrity and immunomodulation. MB310 is being advanced to a first-in-human study in 2024 to explore safety and initial signs of efficacy.Costello, et al. (2019) Jama 321.2: 156-164.Read more P007 Neutrophil function in lesional biopsies is a strong determinant of IBD severity and may relate to an altered functional state already present in circulating cellsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Neutrophils clear luminal bacteria from the intestinal lamina propria and have a protective role in Inflammatory Bowel Disease (IBD). However, their production of inflammatory cytokines, matrix metalloproteases and radical oxygen species causes irreversible tissue damage. Histological assessment of infiltrating neutrophils and indirect measurement of neutrophil-derived calprotectin in feces are used to assess disease severity in patients. Since IBD is a heterogeneous disease in terms of presentation, severity and course, we hypothesize that different patients have a different composition of their neutrophil compartment that leads to a different balance between protection and damage. We aim to study the variability in neutrophil phenotype and function and relate it to patient heterogeneity.

Methods

We analyzed endoscopic biopsies and peripheral blood samples from children diagnosed with IBD within the PIBD-SETQ cohort. Paired biopsies obtained at diagnosis were scored by a pathologist and analyzed by IHC and RNAseq. RNAseq was also performed on purified circulatory neutrophil at diagnosis and their phenotype was analyzed by whole-blood flow cytometry.

Results

At diagnosis, high numbers of infiltrating neutrophils in intestinal tissue differentiated IBD patients with high clinical disease activity, more severe endoscopic and histological disease and high plasma concentrations of IL-17. RNA sequencing of lesional intestinal biopsies revealed differential expression of genes linked to neutrophil degranulation and IL-17 signaling in the colon of IBD patients with high neutrophil infiltration. Moreover, these biopsies had high mRNA expression for Oncostatin M, a neutrophil product known to associate with therapy resistance.To assess whether circulating neutrophils were altered in IBD before entering the intestinal tissue, we performed bulk RNAseq analysis of purified circulating neutrophils from non-IBD and CD patients. Neutrophils from CD patients had increased expression of genes related to granule formation and filling (MMP9, S100A8, S100A9) and pathogen sensing (TLR5, NLRC4) but not cytokine production (IL1B, OSM), relative to non-IBD patients. Expression of CD10 was decreased in circulating neutrophils from UC and CD patients while CD16 expression was lower in UC-derived neutrophils, suggesting these cells have a more immature state.

Conclusion

We have detected changes in the maturity of neutrophils in the circulation of some IBD patients that could have functional consequences in terms of bacterial clearance and tissue damage in the intestinal mucosa. Uncovering different functional profiles in neutrophils may help dissect patient heterogeneity and provide novel targets for therapy.Read more OP14 Effect of mirikizumab on clinical and endoscopic outcomes after 1 anti-TNF failure in patients with moderately to severely active Ulcerative ColitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Mirikizumab (miri), an anti-IL-23p19 antibody, has demonstrated efficacy and safety in moderately to severely active ulcerative colitis (UC) Phase 3 trials (LUCENT-1 and -2; NCT03518086, NCT03524092) among patients who had an inadequate response, loss of response, or intolerance to conventional or advanced therapy. At the LUCENT-1 induction baseline, 41% of the population had experienced a biologic/tofacitinib failure, and 36.3% experienced at least one anti-TNF failure. Among patients with one prior anti-TNF failure only, this analysis evaluated the clinical efficacy of miri compared to placebo (PBO) in induction and maintenance therapy and the efficacy of miri in extended induction.

Methods

In LUCENT-1, UC patients were randomized to receive 3 intravenous (IV) doses of 300mg miri or PBO every four weeks (Q4W) at W0, W4, and W8 (induction population). In LUCENT 2, responders to miri induction at W12 were re-randomized to subcutaneous (SC) 200mg miri or PBO Q4W through W52 of continuous therapy (maintenance population). Patients not achieving clinical response with miri 300mg IV at W12 received extended induction treatment with open-label 300mg miri IV at W12, W16, and W20 (extended induction population). Patients responding to extended induction at W24 entered open-label maintenance and received 200mg miri Q4W SC until W52 (extended induction responders). Endpoints evaluated were clinical response, clinical remission, symptomatic remission, endoscopic remission, corticosteroid (CS)-free remission, and histologic-endoscopic mucosal remission (HEMR). Efficacy in the subgroup of patients with failure of one anti-TNF only was assessed using Cochran-Mantel-Haenszel tests at W12 (induction population) and W52 (maintenance population).

Results

At LUCENT-1 baseline, of patients who experienced anti-TNF failure, 45% of patients (n=190) had one prior anti-TNF failure only (Table 1). In the induction and maintenance populations, a significantly greater proportion of miri-treated patients achieved the following efficacy endpoints compared with PBO [miri vs. PBO, p-value]: clinical response (W12: [64.4% vs. 34.1%, p=0.001]; W52: [67.2% vs. 44.8%, p=0.03]); clinical remission (W52: [44.3% vs. 17.2%, p=0.017]); symptomatic remission (W52: [63.9% vs. 34.5%, p=0.005]) (Table 2). Among the extended induction population, 45.7% achieved clinical response at W24; 75% achieved clinical response, 30% achieved clinical remission and CS-free remission at W52 (Table 2).

Conclusion

Mirikizumab is efficacious for induction and maintenance therapy in patients with moderately to severely active UC who have failed one prior anti-TNF.Read more OP26 Programmable probiotic local delivery of anti-TNF-α nanobody to alleviate DSS-induced colitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Biological agents represented by Infliximab have brought a milestone leap forward in the treatment of IBD. However, the overall response rate of anti-TNF-α antibodies in clinical practice is just 40-60% and the adverse reactions caused by the lack of gut-selective further limit its clinical application. Systemic effects of intravenous administration may be an essential cause of paradoxical response and immune adaptive succession (secondary loss of response). Rapid advances in synthetic biology allow targeted delivery of antibody drugs via engineered probiotics to improve bioavailability while reducing the risk of systemic effects.

Methods

Here, we developed an engineered probiotic (EcN-VHH2^M3) that intelligently responds to the inflammatory marker thiosulfate and produces the anti-TNF-α nanobody VHH2^M3. At the same time, controlled release of anti-TNF-α biologic was achieved in response to colitis marker nitrate and quorum sensing mechanism. The dextran sulfate sodium (DSS)-induced colitis model was used to explore the feasibility of EcN-VHH2^M3 for the IBD treatment. The disease activity index of the subject animals was detected and evaluated. The colon length and spleen weight were measured and HE staining. Real-time polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) are used to detect cytokine expression levels in colon tissue.

Results

In vivo results showed that EcN-VHH2^M3 group significantly reduced disease activity index and restored intestinal mucosal barrier compared with control group. DSS administration resulted in hyperemia, ulceration, and thickening of the bowel wall, which were reduced in the treatment group. In addition, spleen weight and colon length were close to the control group. EcN-VHH2^M3 treatments significantly decreased the expression levels of pro-inflammatory cytokines IL-1β, TNF-α, and IFN-γ, while the expression of anti-inflammatory cytokines IL-10 and TGF-β was enhanced.

Conclusion

Inflammatory microenvironment-responsive programmable probiotics effectively alleviate DSS-induced colitis in mice and restore the intestinal mucosal barrier through the targeted release of anti-TNF-α nanobody. This study preliminarily confirmed that the controlled intestinal release of anti-TNF biologics by engineered probiotics provides a promising paradigm for IBD treatment with non-gut-selective antibodies.Figure 1.Schematic diagram of EcN-VHHM3 in the treatment of IBDRead more DOP02 Developing explicit thresholds for outcomes to inform (GRADE) Evidence to Decision frameworks for Inflammatory Bowel Disease guidelinesWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Evidence to decision (EtD) frameworks are a key recent development in Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) methodology. They aim to ensure that decisions about healthcare interventions are based on a thorough, transparent and unbiased assessment of the available evidence. Core to this is to agree the importance of outcomes to be used, the specific measures for each outcome that have the most consensus and finally to develop explicit thresholds for interpretation of effect sizes of outcomes to inform (GRADE) evidence to decision frameworks. This ensures decisions are made in an unbiased fashion and allows stakeholders to focus on discussions based on their significant experience and expertise, rather than interpretation of evidence. Therefore, our study aims to develop these thresholds for the EtD framework to establish their use in several key IBD guidelines.

Methods

This online survey using Survey Monkey was conducted by inviting experts and stakeholders from the United Kingdom and British Society of Gastroenterology. Each expert was asked to select important clinically relevant outcomes and were asked about what magnitude of the effect they consider large, moderate, small, or trivial for each of the clinical, endoscopic, radiological, biochemical, histological outcomes and adverse events. Questions were framed as neutral statements without introducing a specific direction. Response options included sliding bars going from 1 to 100% for the desirable magnitude of effect for each outcome (Figure 1). The mean average of responses of experts were calculated.

Results

A total of 89 clinical experts/stakeholders participated in this online survey. Clinical remission, clinical response, endoscopic remission, withdrawal due to adverse events, and serious adverse events were considered critical outcomes. Trivial to small, small to moderate and moderate to large thresholds were as follows - clinical remission (10%, 20% and 31%), clinical response (13 %, 24% and 36%), endoscopic remission (9%, 17% and 28%), withdrawal due to AE (7 %, 14% and 23%), serious AE (6%, 11% and 17%) (Table 1).

Conclusion

This is the first study to develop thresholds for outcomes in IBD which can be used in EtD for the development of IBD guidelines. These thresholds have been used in the development of upcoming British Society of Gastroenterology guidelines for the management of IBD.Read more DOP03 Gaps between ECCO quality standards of care and the real world: the E-QUALITY survey on processes and outcomesWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The European Crohn’s and Colitis Organisation (ECCO) Position Paper on Quality-of-Care (QoC) proposed essential standards on process and outcomes for units that manage patients with inflammatory bowel disease (IBD). The E-QUALITY taskforce investigated whether gaps between these standards and real-world practice exist.

Methods

A 74-question web survey accessible to all institutions affiliated with ECCO was developed. One delegate per institution was requested to respond. A descriptive analysis was done.

Results

From March to October 2023, 166 centres from 28 different countries replied to the survey (Fig.1).At diagnosis, disease extent is assessed by colonoscopy in 96% and completed by small bowel (SB) evaluation in 43%. At least 2 biopsies from each segment are obtained in 55%. SB investigation for Crohn’s disease (CD) takes place in 60%. 54% of centres provide access to endoscopy with deep sedation for the majority of patients. To assess treatment response, faecal calprotectin is used in 65%, endoscopy in 54%, cross-sectional imaging for CD in 36%. In the case of primary failure of any drug, therapeutic decisions are based on objective measures of inflammation in 98%. A scheduled monitoring protocol for asymptomatic patients is followed in 42%. Patients with prolonged use of corticosteroids are being switched to a steroid-sparing treatment in 84%, but there is no protocol to track or act upon high steroid exposure in 43% of centres. 72% centres monitor metabolic bone health. Only 51% of units screen IBD patients for colorectal cancer, but screening is done with high-definition endoscopy in 92%. Chromoendoscopy with targeted biopsies is performed in only 47% units. Patients with perianal fistula are managed by combined medical and surgical approach in 67%, and reassessment by clinical and endoscopy and/or pelvic MRI is done in 62%. Laparoscopic approach for intra-abdominal surgery is used in 76%, and preoperative nutritional assessment in 62%. Patients receive therapies to prevent post-operative recurrence based on risk factors in 70%, standard endoscopy within 6-12 months after surgery is done only in 52% of centres. Although only 8% of centres lack a defined protocol to manage acute severe ulcerative colitis flares, 13% lack a standard algorithm, and 36% do not involve the surgeon in this setting from day 1. 38% of centres have a paediatric to adult transition clinic.The main reason for not adhering to ECCO standards are difficulty of providing tests in a timely fashion in up to 83% of centres.

Conclusion

Our survey has revealed significant gaps between ECCO standards and real-world practice. These results will help ECCO improve initiatives to help institutions to provide standard QoC.1) Fiorino et al. JCC 2020;14:1037-48Read more DOP16 Safety of long-term ozanimod treatment for up to 4 years in patients with moderately to severely active Ulcerative Colitis: an interim analysis of the True North open-label extensionWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The 52-week, phase 3 True North (TN) study (NCT02435992) demonstrated the efficacy and safety of ozanimod (OZA), a highly selective sphingosine 1-phosphate receptor 1 and 5 modulator, in patients (pts) with moderately to severely active ulcerative colitis (UC). A prior analysis reported the long-term safety of up to 3 y of OZA in the ongoing TN open-label extension (OLE; NCT02531126; from TN baseline to OLE Week [W] 94). This analysis presents the cumulative long-term safety of OZA in TN and the TN OLE for an additional year (up to OLE W142).

Methods

The TN study design has been previously described. This analysis included all TN pts who entered the OLE from TN (clinical nonresponders at W10, lost response during maintenance, or completed maintenance at W52). Safety assessments were reported from the first dose of OZA either in TN or OLE up to OLE W142. Lab abnormalities, including absolute lymphocyte count (ALC) reductions, were reported. Exposure-adjusted incidence rates (EAIRs) per 100 patient-years (PY) were calculated for all treatment-emergent adverse events (TEAEs).

Results

A total of 823 pts entered the TN OLE (average age: 41.7 y; 59% male); 62% had left-sided UC disease. Total PY exposure to OZA at OLE W142 was 2536 y. Overall, the cumulative safety assessments did not significantly change with an additional year of OZA exposure from OLE W94 to W142 (Table). A decrease in EAIRs per 100 PY was observed in overall TEAEs (85.5 vs 87.6) and serious TEAEs (7.0 vs 7.4) at OLE W142 vs OLE W94, respectively. Notably, with an additional year of OZA exposure, TEAEs leading to treatment discontinuation remained at 2.5 EAIR/100 PY, and there were no new cases of bradycardia or atrioventricular block. One new TEAE each of herpes zoster, macular oedema, cystoid macular oedema, myocardial ischaemia, pulmonary embolism, and deep vein thrombosis were noted. COVID-19 TEAEs increased at OLE W142 (n=103; EAIR: 4.3/100 PY) from OLE W94 (n=66; EAIR: 3.0/100 PY). Reductions in ALC <500 cells/mm³ were common in the OLE (OLE W94, 54.0%; OLE W142, 56.1%); few pts had ALC <200 cells/mm³ (OLE W94, 5.3%; OLE W142, 6.5%), but these pts had no serious infections. No serious hepatic safety events were observed. One new death due to adenocarcinoma, which was unrelated to OZA, was reported.

Conclusion

The ongoing safety profile of OZA is consistent with previous analyses, with no new safety signals identified compared with previous UC analyses. Long-term use of OZA representing 2536 PYs of exposure continues to be well tolerated in pts with moderately to severely active UC.Read more DOP17 Tofacitinib versus Vedolizumab Among Bio-naïve Patients With Ulcerative Colitis: A Real-World Propensity-Weighted ComparisonWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Over the last decade, treatment options for moderate-to-severe ulcerative colitis (UC) have expanded. However, comparative studies between these agents are limited, especially among biologic naïve patients. There are sparse data comparing biologics with small molecules for IBD. We aimed to compare the efficacy, safety and persistence of tofacitinib and vedolizumab as the first advanced treatment for patients with UC.

Methods

Patients who received tofacitinib or vedolizumab as first advanced therapy for UC in NHS Lothian were included. We capped the upper age limit at 65 years to take into account regulatory guidelines for the use of JAKi as first line therapies across IMIDs. To allow treatment effect to be assessed outside of a randomized trial, we used inverse probability of treatment weighting (IPTW). This approach takes the probability of treatment assignment into account without potentially drastically reducing the analysable cohort size. The probability of treatment assignment was calculated via logistic regression using age, gender, IBD duration, Montreal extent, CRP, concomitant corticosteroids and partial Mayo score at drug commencement. Missing data for these variables were imputed using multivariate imputation by chained equations. Confounder-adjusted survival curves were created using Kaplan-Meier estimates weighted via IPTW. The Pepe and Fleming test was used to compare survival curves from drug commencement to day 1000 of treatment.

Results

We included 158 patients of whom 81 (51.2%) received vedolizumab and 77 (48.7%) tofacitinib. Median follow-up for patients on vedolizumab was 3.1 (1.6-4.8) years and for tofacitinib 1.5 (0.34-2.3) years. Baseline demographics were comparable except for disease extent (Table 1). At drug commencement there were no differences in steroid prescription (60.5% vedolizumab versus 57.1% tofacitinib), partial Mayo score, CRP or faecal calprotectin. At week 12, steroid free clinical remission was more frequent in the vedolizumab group (69% vs 51.4%, p=0.030) Figure 1B.Vedolizumab persistence was superior to tofacitinib (p=0.005) Figure 1A. Primary non-response and secondary loss of response were 9.9% and 17.3% for vedolizumab and 23.4% and 13% for tofacitinib respectively. There were no differences in the frequency of adverse events (11 [13.6%] vedolizumab vs 19 [24.7%] tofacitinib, p=0.629). However, adverse events resulting in temporary discontinuation of the drug occurred in 1 (1.2%) vedolizumab versus 11 (14.3%) tofacitinib, p=0.013.

Conclusion

We found that the persistence and tolerability of vedolizumab was superior to tofacitinib in bionaive UC, although the rates of clinical and biomarker remission were comparable. These data may help inform positioning of advanced therapy in UC.Read more DOP34 Deciphering immune-epithelial interactions in health and in Inflammatory Bowel DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Intestinal homeostasis is dependent on appropriate interactions between various compartments including immune, mesenchymal, neural, epithelial and bacteria cells. Disrupt of these interactions has been associated with the development of Inflammatory Bowel Disease (IBD).Using intestinal organoids as a starting point, we built complexity into this model by adding other cellular components to be able to study these interactions in health and disease.One of the key immune players in the intestine is Innate Lymphoid Cells (ILC). ILC precursors (ILCP) migrate to mucosa where they mature, promote homeostasis, and provide a potent, antigen-non-specific sources of cytokines. Deciphering what local stimuli drive the final stages of ILCP maturation in these tissues remains a pressing question, as ILC frequencies can become dysregulated in IBD.

Methods

Here, we develop and use co-cultures gut organoids with Innate Lymphoid Cells precursors (ILCP) and with mature intestinal Innate Lymphoid Cells (ILC).

Results

Harnessing these versatile models, we demonstrate that epithelial cells provide a complex niche capable of supporting the final maturation of all subsets including ILC1, ILC2, ILC3 and Natural Killer (NK) cells, Notably, organoid identity was sufficient to robustly recapitulate tissue-specific ILC imprints and frequencies, even in the absence of microbial stimuli, other cell types, or cytokine supplementation.In addition, we show that human gut ILC1 drive intestinal and extracellular matrix remodelling through production of TGFβ. This indicates the potential impact of ILC1 accumulation in IBD patients in driving intestinal cancer and fibrosis, two sequelae of IBD.Finally, we identify a new module of interaction between ILCs and the intestinal epithelium: goblet cells provide Notch ligands that are essential for maintenance of NC3R+ ILC3 and for their production of IL-22. In turn, ILC3 drive intestinal epithelial cells towards a secretory phenotype.

Conclusion

Taken together, our work provides unprecedented insight into in situ ILC maturation, which we show to be driven by epithelial signals, and into ILC function through deciphering new modules of ILC-epithelial interaction in health and IBD.Read more DOP35 Spatial transcriptomics reveals cellular niches associated with histological inflammation in postoperative Crohn’s DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Postoperative Crohn’s disease (CD) recurs in ~70% of patients ≤1 year following ileocolonic resection (ICR), as observed endoscopically. Current understanding of molecular determinants underlying histological intestinal inflammation in patients with postoperative CD recurrence is minimal. To address this issue, we used advanced spatial transcriptomic analyses on intestinal biopsy samples with matched histological and endoscopic assessments from neoterminal ileum, anastomosis, and colon of patients with CD who had undergone colonoscopy following ICR.

Methods

Formalin-fixed paraffin-embedded (FFPE) tissue biopsies from neoterminal ileum, anastomosis, and colon were prospectively collected from a 15-patient cross-sectional cohort with CD who underwent routine endoscopic assessment following ICR. Spatial transcriptomics was performed on samples using 10X Genomics Visium CytAssist Spatial Gene Expression for FFPE V2.0. Annotation of tissue regions of histologically active inflammation and classification of histologically inactive (Robarts Histopathology Index ≤3 with subscores of 0 for neutrophils in the lamina propria and epithelium) or active disease were performed by an expert gastrointestinal pathologist. R programming language was used for data analysis (Figure).

Results

Fourteen of the 43 (32.6%) FFPE biopsies had histological evidence of inflammation. Spatial transcriptomics clustering revealed a distinct transcriptional signature by the segregation of 4 clusters ("inflamed clusters") composed mostly (≥69%) of cells from samples defined by histologically active disease. Tissue regions identified as inflamed by expert pathologist annotation contributed to >46% of inflamed clusters’ composition and <15% of remaining clusters. Cell type decomposition and cellular niche analysis revealed immune (e.g., myeloid, T cells, and B cells) and epithelial cells in close proximity sharing a similar microenvironment in 3 inflamed clusters while the 4th cluster was composed of >90% epithelial cells. Differentially expressed genes from the inflamed clusters were similarly expressed across intestinal segments including inflamed anastomotic biopsies and were enriched for signalling pathways involving immune cells recruitment/activation, inflammatory signalling, extracellular matrix organisation, and oxidative stress response.

Conclusion

This is the first study to explore spatial transcriptomic signatures associated with histological inflammation in patients with postoperative CD recurrence. Our analysis revealed a spatial signature of cellular niches and signalling pathways arising upon histological inflammation, providing insight into therapeutic targets and biomarkers across anatomic locations and the anastomosis.Read more DOP52 Guselkumab improves symptoms of fatigue in patients with moderately to severely active Ulcerative Colitis: Phase 3 QUASAR induction study results at Week 12Wed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Fatigue is a common symptom in patients with ulcerative colitis (UC) that impairs health-related quality of life. The Phase 3 QUASAR Induction Study (NCT04033445) was a randomized, double-blind, placebo-controlled, parallel-group, multicenter study of guselkumab (GUS), an interleukin-23 p19 subunit antagonist, in patients with moderately to severely active UC. The impact of GUS IV induction on patient-reported symptoms of fatigue is reported here.

Methods

Patients were randomized 3:2 to receive GUS 200 mg IV or placebo IV at Weeks 0, 4, and 8. At baseline and Week 12, patients completed the Patient-Reported Outcomes Measurement Information System (PROMIS)-Fatigue Short Form 7a (SF7a) which includes 7 items to evaluate symptoms of fatigue (ie, tiredness, exhaustion, mental tiredness, and lack of energy) and associated impacts on daily activities (ie, activity limitations related to work, self-care, and exercise). PROMIS-Fatigue-SF7a raw scores were converted to a standard T-score based on a general US population of mean=50 and SD=10. Higher scores indicate more severe fatigue symptoms. PROMIS-Fatigue SF7a outcomes were evaluated at Week 12 based on the improvements of ≥3, ≥5 and ≥7 points from baseline in PROMIS-Fatigue SF7a T-score. A ≥7-point improvement was defined as fatigue response (multiplicity-controlled secondary endpoint). A cumulative distribution function (CDF) curve and a probability density function (PDF) plot were used to demonstrate consistency of fatigue response.

Results

Seven hundred one patients were randomized and treated in the primary analysis population (mean UC duration, 7.5yrs, Mayo endoscopy subscore=3 [severe disease], 67.9%, and mean modified Mayo score, 6.9, at baseline). The mean (SD) PROMIS-Fatigue SF7a T-scores at baseline were similar between the treatment groups: 56.0 (8.77) for GUS 200 mg IV and 56.4 (8.90) for placebo IV. At Week 12, the mean change from baseline in PROMIS-Fatigue SF7a T-score was -5.7 for GUS and -2.1 for placebo (nominal p<0.001). Compared with placebo at Week 12, a higher proportion of GUS-treated patients achieved fatigue response (Table 1) and clinically meaningful ≥3-point and ≥5-point improvements in PROMIS-Fatigue SF7a T-scores (56.8% and 49.4% vs 34.6% and 26.4%, respectively, both nominal p<0.001). Both the CDF curve and PDF plot demonstrated consistency of greater treatment effect of GUS on fatigue vs placebo (Figure 1).

Conclusion

Moderately to severely active UC patients who received GUS induction treatment showed greater improvement in patient-reported symptoms of fatigue at Week 12 compared with placebo-treated patients.Read more P115 Ustekinumab in DEVELOP: A safety analysis from an Inflammatory Bowel Disease multicenter, prospective, long-term registry of paediatric patientsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

DEVELOP is a multi-center, global, prospective, observational, longitudinal registry of long-term safety of infliximab (and other treatments) in paediatric patients (pts) with inflammatory bowel disease (IBD) <18 years (yrs) at diagnosis. Over the course of follow-up, many pts required changes in therapy. Ustekinumab (UST) is approved for treatment of Crohn’s disease (CD) in adults and is currently being evaluated for safety/efficacy in paediatric pts. This report focuses on assessment of safety of UST in paediatric pts with CD from DEVELOP.

Methods

Data included paediatric pts treated with UST from 31 May 2007 through 30 June 2022; data are collected every 6 months. The analyzed population included: all paediatric pts (all pts), pts weighing <40kg (<40kg group), and pts weighing ≥40kg (≥40kg group). Assessments included medical and treatment history, UST exposure, adverse events (AEs), serious AEs (SAEs), CD-related SAEs leading to hospitalization, IBD surgeries, serious and opportunistic infections, malignancies, and deaths.

Results

A total of 150 pts received UST (49.3% females); 31 in the <40kg group and 119 in the ≥40kg group (Table 1). Most treated pts (92.0%) were 12-17yrs. The majority (91%) of pts were initially dosed with UST every 8 weeks (q8w); at the last known dose, 64% received UST q8w and 22% q4w. Mean (SD) age of initial UST exposure was 15yrs (2.19). Prior IBD surgery was reported in 65.3% pts. The majority of pts (98%) had prior biologic therapy and 72% received ≥2 biologics prior to UST. Overall, 37/150 (24.7%) of pts discontinued UST during follow-up, with a mean (SD) time to discontinuation of 16.7 (17.00) months; 84/150 (56.0%) were exposed to UST for ≥24 months.Rates (events/100 pt-yrs) of AEs were higher in the ≥40kg group (177.62) than in the <40kg group (101.27). Rates of SAEs were slightly lower among the ≥40kg group (25.42) vs <40kg (32.67). There were no SAEs related to infusion or injection site reactions. Rates of serious infections and CD-related hospitalizations were low and similar between groups, and rates of IBD-related surgeries were similar between groups (Figure 1). One malignancy (malignant carcinoid tumor) was reported in a female (18yrs) in the ≥40kg group with a history of prior therapy with vedolizumab, methotrexate, and 6-MP. No deaths or opportunistic infections were reported.

Conclusion

The safety profile observed for this off-label use of UST in paediatric CD pts in DEVELOP was similar to that of the treated adult population, despite most paediatric pts having prior biologic exposure. No new safety signals are identified in this paediatric population.Read more P116 Gastro-resistant microparticles for the oral delivery of Phycocyanin in the Inflammatory Bowel Disease therapyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Inflammatory Bowel Disease (IBD) is a chronically relapsing inflammation of the gastrointestinal tract, with ambiguous etiology.Oral route is the most common and acceptable approach for drug administration in the IBD treatment. However, it remains a challenge to maintain the stability of the drugs during oral treatment, particularly in the gastric environment, due its harsh conditions. In this context, the antioxidant and antiinflagmmatory properties of various natural compounds, as Phycocyanin (PC), a water-soluble bioactive molecule found in algae, can be strongly affected by factors as pH and temperature, inducing PC degradation and attenuating the curative effects.In this work, we produced a gastro-resistant microparticles (MPs) as controlled release systems for PC, and we aimed to compare its efficacy with free PC effects, on rat model of IBD.

Methods

The novel pharmaceutical system (SPC) was produced by microencapsulation technique, the spray-drying technique, using soy proteins (SPs) as natural excipients, aiming to improve the stability of the active ingredient and to ensure a modified release profile of PC.Rats were divided into groups and colitis was induced by intracolonic instillation of Dinitrobenzene sulfonic acid (DNBS, 20 mg/rat). Effects of preventive oral treatment of free PC or SPC were investigated, bioavailability was assessed and then body weight loss, stool consistency, colon weight/length index, myeloperoxidase activity (MPO), macroscopic damage and disease activity index (DAI) were determined.

Results

The SPC microparticle systems showed enhanced bioavailability of Phycocyanin, resulting in increased blood concentrations. The SPC system achieved the maximum AUC value and a modified release profile, particularly for gastro-resistant types, with a delayed T_max of 5 hours, indicating their potential as a gastro-resistant formulation.Both PC and SPC pretreatments significantly ameliorated the severity of DNBS-induced colitis, however SPC pretreatment demonstrated enhanced activity vs PC.SPC rats showed a reduction of DAI, body weight loss and diarrhea incidence >15%, compared to PC (P<0.05); the ability of preventing the DNBS-induced macroscopic colonic damage and the MPO increase in SPC group were significantly higher than PC group (P<0.05) and also a tendency to improvement of colon weight/length index was observed.

Conclusion

In conclusion, the results of our research demonstrated that gastro-resistant microparticles (SPC) exhibit significantly improved therapeutic efficacy compared to orally administered free PC and can be developed as an effective new oral drug delivery system with controlled release profile in the treatment of IBD.Read more P117 Transglutaminase 2 is elevated in Crohn’s disease associated strictures and exerts profibrotic activities in myofibroblasts and experimental intestinal fibrosisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Intestinal fibrosis is a significant clinical problem in Inflammatory bowel disease (IBD). This may lead to intestinal strictures induced by excessive accumulation of extracellular matrix (ECM) produced by human intestinal myofibroblasts (HIMF). Transglutaminase (TG)2 covalently cross-links ECM-associated proteins, increases ECM stiffness and has direct pro-fibrotic effects. We investigated the role of TG2 in intestinal fibrosis in human tissues, HIMF and transgenic mouse models.

Methods

TG2 was detected in human tissues from Crohn’s disease (CD) strictures (CDs; n=10), CD non-strictured (CDns; n=20), ulcerative colitis (UC; n=10) and non-IBD controls (NL; n=14) by immunofluorescence (IF), qPCR, in-situ hybridization (ISH), and biotinylated cadaverin incorporation (BCI). Relative contribution of TG2 was measured by BCI using a TG2-selective blocking antibody (TAb). The cellular source of TG2 was evaluated by IF. HIMF ECM production was measured using a novel ECM deposition assay and TG2-inhibitors. HIMF were exposed to anti-TG2 antibody or isotype control and bulk RNA-sequencing (RNAseq) analysis was performed. Tamoxifen-inducible global Cre/TG2 floxed conditional KO (cKO) mice were used in the DSS and TNBS fibrosis models.

Results

Total TG activity was increased in CDs and UC vs. NL in the submucosa (SM) and muscularis propria (MP; P≤ 0.04). Strikingly 90-99% of TG activity were attributable to TG2 in all groups. TG2 activity correlated with fibrosis scores (P≤0.02), but not inflammation scores. TG2 amount was elevated in CDs patients vs. NL in qPCR and ISH (P≤0.05). IF revealed HIMF as the major source of TG2 in the intestine as indicated by colocalization with alpha-SMA. HIMF, invitro, produced 82–97% of active TG2. Inhibition of TG2 by cell-permeable inhibitor or Tab reduced fibronectin (FN) and collagen (COL)1 and 3 deposition by HIMF. RNAseq showed TAb-treated cells expressed 432 downregulated and 402 upregulated genes. Functional enrichment analysis showed pathways associated with fibroblast activation/proliferation, ECM, and fibrosis-associated signaling (e.g. AKT) pathways to be downregulated in TAb-treated HIMF. Associated genes included nuclear protein (NUPR1) and sphingolipid signaling pathway proteins (SMPD1 and CTSD), which may be potential targets for TG2-mediated activity in HIMF. Deletion of TGM2 prior to inducing murine DSS or TNBS experimental fibrosis did not lead to any difference in inflammation, but decreased fibrosis (picrosirius red intensity, COL1/FN expression, wall thickness) in TG2 cKO mice vs. wild type (P≤0.05).

Conclusion

TG2 is involved in inflammation-independent progression of intestinal fibrosis and may represent a future anti-fibrotic target.Read more P118 Fecal content from IBD patients disturbs epithelial functions in two model systemsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Inflammatory Bowel Diseases (IBD) result from abnormal interactions between the immune system, epithelial barrier, and gut microbiota. However, understanding the abnormal interaction between aerobic epithelia and mainly anaerobic microbiota is complicated and is limited in part by the lack of human-relevant models.

Methods

We developed a model system that is based on whole human fecal samples and human-derived epithelia to study the interactions between the gut bacteria and the epithelia. To capture patient heterogeneity, we prioritized and pooled fecal material from 10 Crohn disease (CD), 10 ulcerative colitis (UC), and 10 healthy subjects. Prioritization of samples was based on our published gut microbial health index (PMID: 35197084), matching gender and age. Monolayered epithelial cells (Caco2 cells and patient-derived colonoids) were used for the co-culturing. Measurable outputs included cell viability, epithelial integrity, and secretion of CXCL1.

Results

Fecal samples were processed by separating the supernatant, heat-killing the bacteria, and rejoining the samples (Fig. 1A). 16S sequencing showed that bacterial composition and alpha diversity (Faith) were overall preserved after the heat-killing (Fig. 1B), as seen in the original samples. The gut microbial health index was higher among the control samples and pool, compared to the IBD samples (Fig. 1C), preserving the IBD pathogenic signals. Because previous studies indicated the enrichment of salivary bacteria in IBD feces, salivary samples were also processed for comparison. We confirmed that similar amounts of bacterial DNA (as a proxy of bacterial mass) were used for coculturing as indicated by qPCR of the 16S-V4 (Fig. 1D). Co-culturing the fecal and saliva pools with Caco-2 cells revealed a significant increase in CXCL1 proinflammatory chemokine secretion to the media in comparison to no-treatment (Fig. 2A). Moreover, the UC and CD pools significantly decreased epithelial integrity [transepithelial electrical resistance (TEER)], without affecting cellular viability (Fig. 2B-D). Finally, incubation of the fecal content with colon-derived organoids (from 2 controls and 1 UC) resulted in a substantial reduction of cell viability, which was more pronounced with fecal content derived from UC patients (Fig. 2E), and this effect was noted most with the UC fecal supernatants.

Conclusion

Using a novel co-culturing system, we demonstrated the effects of fecal contents from IBD and control subjects on CXCL1 secretion and epithelial integrity in Caco2 cells, and on colonoids viability. These models will be used to identify fecal factors and interventions relevant to IBD epithelial functions.Read more P361 Neither hepatic steatosis nor fibrosis is associated with clinical outcomes in patients with intestinal Behçet’s diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Behçet’s disease (BD) and nonalcoholic fatty liver disease (NAFLD) are chronic inflammatory diseases that share pathogenetic mechanisms. In this study, we investigated whether NAFLD influences the clinical outcomes in patients with intestinal BD.

Methods

Patients with intestinal BD and available hepatic steatosis index (HSI) and fibrosis-4 (FIB-4) scores were recruited between 2005 and 2022. An HSI of ≥30 and FIB-4 of ≥1.45 were used to diagnose hepatic steatosis and significant liver fibrosis, respectively. The primary outcomes were intestinal BD-related hospitalization, surgery, emergency room visits, or the first use of corticosteroids, immunomodulators, or biologic agents for intestinal BD.

Results

A total of 780 patients with BD were selected. The prevalence of hepatic steatosis and significant liver fibrosis were 72.3% and 8.8%, respectively. Multivariate analysis showed that younger age, prior smoking history, concomitant skin lesions, higher white blood cell count, and lower serum albumin levels were independently associated with an increased risk of clinical relapse (all p <0.05), whereas hepatic steatosis and significant liver fibrosis were not (hazard ratio [HR] = 1.164, 95% confidence interval [CI] 0.923–1.468; p = 0.199 for hepatic steatosis; HR = 0.982, 95% CI 0.672–1.436; p = 0.927 for significant liver fibrosis).

Conclusion

Hepatic steatosis and liver fibrotic burden were not independently associated with clinical outcomes in patients with intestinal BD.Read more P362 Mesenteric fat proliferation and fat edema in magnetic resonance enterography as predictor of long-term disease complications in Crohn’s diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Fibrofatty proliferation of the mesenteric fat is a common finding in magnetic resonance enterography (MRE) in patients with Crohn’s disease (CD). Mesenteric fat is thought to play an active role in inflammation, fibrosis and stricture formation in CD. However, it is unclear whether these findings have a prognostic value in prediction of bowel damage and complications. We aimed to examine the association between mesenteric fat proliferation and inflammation on MRE and risk for hospital admissions and bowel surgery.

Methods

Patients with established CD diagnosis with at least 1 available MRE imaging data were followed for hospital admissions for CD exacerbation or abdominal surgery. MRE were reviewed by an expert radiologist for various characteristics (intestinal wall thickening and enhancement, stricture, or abscess formation, fibrofatty proliferation and fat edema reflecting fat inflammation).The association between mesenteric fat and outcomes was assessed using the Kaplan Meier method and log rank test. Crude and adjusted Hazard ratios (HR) with 95% confidence interval (CI) adjusting for baseline MRE characteristics (wall thickness and stricture and pre-stenotic dilatation) were estimated from the Cox proportional hazards regression model (R version 4.2.1).

Results

159 CD patient charts and MRE imaging data were analyzed. Patients’ characteristics and medication exposure at described in table 1. On initial MRE the frequency of mesenteric fat proliferation was noted in 43 (27.0%) and fat edema in 79 (49.7%). Other MRE features noted were: mild, moderate and severe wall thickening in 72 (45.5%), 47 (29.9%) and 11 (7.0%) patients, respectively. Contrast intestinal wall enhancement was present in 122 (76.7%) patients. Intestinal stricture with pre-stenotic dilatation was noted in 17 (10.7%) patients and abscess and fistula formation was seen in 10 (6.3%) and 11 (6.9%) patients, respectively. During a mean (SD) follow up of 95.7 (39.5) months, 100 (62.9%) and 40 (25.2%) patients underwent hospitalization or surgery, respectively. On survival analysis, fat proliferation was associated with hospitalizations (Fig 1A, p=0.0005) and surgery (fig 1B, p<0.0001), while fat edema was associated with abdominal surgery (Fig 1D p=0.0003) but not with hospitalization (Fig 1C p=0.28). On multivariable analysis of the associations between fat proliferation and surgery and hospitalization remained highly significant (adjusted HR (95%CI) =3.15 (1.57-6.33) and adjusted HR (95%CI) =1.77 (1.06-2.97), respectively.

Conclusion

in this analysis of baseline MRE features, mesenteric fat proliferation was independently associated with increased risk for abdominal surgery and hospital admission for disease flares.Read more OP13 Anti-integrin αvβ6 autoantibodies are increased in PSC-IBD and correlate with liver disease severityWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Anti-integrin αvβ6 autoantibodies (anti-αvβ6) are a novel biomarker of ulcerative colitis (UC) that precede disease diagnosis by up to 10 years. Given that integrin αvβ6 is also expressed on the biliary epithelium and that primary sclerosing cholangitis (PSC) co-occurs with inflammatory bowel disease (IBD) in up to 90% of patients, we aimed to determine the prevalence of anti-αvβ6 in patients with PSC and to understand the impact of anti-αvβ6 on PSC disease course.

Methods

Three cohorts of pre-liver transplant patients with PSC and controls (IBD and non-IBD) were recruited from New York, Lisbon and Miami. Anti-αvβ6 levels were measured using ELISA and normalized for serum IgG concentration. Statistical analyses across groups and clinical parameters were performed using the Kruskal-Wallis and Spearman correlation test. Multivariable linear regression was conducted to assess the association between anti-αvβ6 and liver disease severity, correcting for covariates. A mixed-effects model was applied to assess change in anti-αvβ6 over time.

Results

In total, 94 patients with PSC (53 (56.4%) PSC-UC, 20 (21.3%) PSC-Crohn’s disease (CD) and 21 (22.3%) PSC alone) and 129 controls (74 (57.4%) IBD and 55 (42.6%) non-IBD) were enrolled; table 1 shows the baseline characteristics of the patients with PSC. Follow-up samples (n=22) were collected from 1 up to 3 years after initial baseline sampling from 17 PSC patients. Median (IQR) age was similar in PSC patients (43, 33-56 years) and controls (47, 32-62 years; p=0.59). Median (IQR) anti-αvβ6 levels were significantly higher in PSC-UC (1.07, 0.48-2.65) and UC (1.83, 1.12-3.03) compared to PSC alone (0.40, 0.23-0.63; p=0.0004 and p<0.0001 respectively) and non-IBD controls (0.39, 0.17-0.65; p<0.0001 and p<0.0001 respectively). Anti-αvβ6 levels were comparable between PSC alone and non-IBD controls (p>0.999) (figure 1A). Anti-αvβ6 levels did not increase over time (p=0.23). A positive correlation between anti-αvβ6 levels and the Mayo PSC risk score (r=0.28, p=0.008) as well as alkaline phosphatase (r=0.29, p=0.007) was observed (figure 1B). These associations remain significant after correcting for covariates including age at diagnosis of PSC, gender, race/ethnicity and IBD type in a multivariable linear regression.

Conclusion

Anti-αvβ6 autoantibodies are a new biomarker of PSC-IBD and are associated with liver disease severity.Read more OP21 Spatial Transcriptomics of Pre-treatment Biopsies Revealing Molecular Maturation State and Chronic Crypt Damage, Reflecting Histological Severity, as Predictors of Primary Responsiveness to TNF-α Inhibitors in Bio-naive Ulcerative Colitis PatientsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Biologic therapies, particularly tumor necrosis factor-alpha inhibitors (TNFi), have greatly advanced the treatment of ulcerative colitis (UC), yet significant number of patients still do not respond to these treatments. For UC management, achieving both histologic and molecular healing is crucial, highlighting the need for more comprehensive therapeutic strategies. Despite extensive research, there is a significant gap in studies that simultaneously assess histologic and molecular changes at both the crypt and lamina propria (LP) levels. Our study addresses this gap by investigating TNFi-resistant UC patients, utilizing spatial transcriptomics to discern specific cell types within histologic sections and integrating these insights to enhance understanding of UC treatment responses.

Methods

We evaluated 56 patients categorized into test (n=23), validation (n=31), and healthy control groups (n=2). Each underwent biopsies at the same sites before (preTx) and after treatment (postTx), as shown in Figure 1A. This study focused on a 3-month follow-up of patients who were administered TNFi as a primary biologic therapy following resistance to conventional treatments. We used digital spatial profiling to analyze gene expression in the crypt and LP, as seen in Figures 1B and 1C. We then correlated molecular data with morphological characteristics and quantitatively evaluated histologic factors, especially crypt distortion and atrophy, reported as percentages (%).

Results

Among the study participants, 29 were classified as responders (R) to TNFi, while 25 were non-responders (non-R). A comparative analysis of gene expression between R and non-R groups revealed a differential expression pattern: 72 genes in the crypt and 105 genes in the LP across varying histologies, as shown in Figure 1D and 1E. Notably, in the preTx samples of non-R, crypts displayed significantly lower expression of genes associated with the maturation of colonocytes, including BEST4, C10orf99, CA2, CA4, CA7, PHGR1, SLC26A2, SLC26A3, LYPD8, CLCA1, and SCNN1, compared to the R group (Figure 1F). Furthermore, when correlating spatial transcriptomic data with histomorphological features, we observed that crypt distortion and atrophy were significantly more pronounced in the non-R group than in the R group in the preTx biopsy samples (Figures 1G and 1H).

Conclusion

Our study's spatial profiling unveils distinct molecular and histologic features between R and non-R to TNFi among bio-naive UC patients. The evaluation of chronic histological features such as crypt distortion, and molecular maturation status, in predicting TNFi response highlights the potential of early histologic assessment in guiding biologic therapy in the UC treatment pathway.Read more P299 Ulcerative Colitis Severity Assessment through Abdominal Ultrasonography: A Diagnostic Accuracy Meta-analysisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Ulcerative colitis, a prevalent form of inflammatory bowel disease, necessitates a precise evaluation of disease severity. While effective, traditional diagnostic methods like colonoscopy are invasive and uncomfortable for patients. Abdominal ultrasonography offers a non-invasive alternative for this assessment, but its differential accuracy in evaluating disease severity in the right and left colon is not fully explored.This study aims to assess the diagnostic accuracy of abdominal ultrasonography in determining the severity of ulcerative colitis, focusing on its performance in the right and left colon.

Methods

A systematic review was conducted in PubMed, EMBASE, and the Cochrane Library, targeting studies up to June 2023. The selection criteria included studies that used abdominal ultrasonography for ulcerative colitis severity assessment, compared against histopathology or combined clinical, endoscopic, and radiological findings. Data analysis was performed using R software (version 4.0.3) with the mada package. This analysis focused on calculating sensitivity, specificity, diagnostic odds ratio, and positive and negative Likelihood Ratios for both the right and left colon, each with a 95% Confidence Interval.

Results

The search identified 5 studies with a total of 383 ulcerative colitis patients. In the right colon, the pooled sensitivity was 73.7% (95% CI, 57.6-85.2%, I2=0%), and specificity was 99.5% (95% CI, 1.6-100%, I2=0%). The diagnostic odds ratio was extremely high at 560.1 (95% CI, 0.04-6966551), with a positive Likelihood Ratio of 148.14 (95% CI, 0.01-1713586.1) and a negative Likelihood Ratio of 0.26 (95% CI, 0.15-0.45). In the left colon, sensitivity was higher at 93.7% (95% CI, 87.2-97%, I2=49.1%) with a specificity of 73.3% (95% CI, 41.8-91.3%, I2=70.9%). The diagnostic odds ratio for the left colon was 40.96 (95% CI, 8.67-193.62), with a positive Likelihood Ratio of 3.51 (95% CI, 1.31-9.42) and a negative Likelihood Ratio of 0.08 (95% CI, 0.04-0.19).

Conclusion

Abdominal ultrasonography shows promising results in assessing disease severity in ulcerative colitis, particularly in the left colon. The high specificity in the right colon is notable, but the wide confidence intervals suggest caution in interpretation, likely due to the small sample sizes and study variability. The left colon's more consistent and reliable performance indicates its suitability for routine clinical use in this region. This study highlights the need for further research with larger patient cohorts and standardized methodologies to solidify these findings and optimize ultrasonography’s role in ulcerative colitis management.Read more P300 An Expert Delphi Consensus: Early Identification of Patients at Risk of Crohn's Disease in Perianal Fistulas and Abscesses (PREFAB) and Identification and Management of Isolated Perianal Crohn's Disease (ipCD) - Part A, PREFABWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

In ± 10% of all Crohn’s disease (CD) patients a perianal abscess (PAA) or fistula (PAF) is the manifesting symptom. The delay in diagnosis of CD, from fistula or abscess onset, is very long and associated with worse outcomes. The aim of this Delphi study was to reach consensus on a clinical decision tool to help select patients with raised suspicion of CD in PAA/PAF patients, to identify underlying CD earlier and reduce the diagnostic delay.

Methods

A panel of international experts in the field of proctology and/or Inflammatory Bowel Disease (IBD), consisting of surgeons, gastroenterologists and radiologists were invited to participate in the PREFAB part of this Delphi study. The first round was an electronic survey and the second round a virtual consensus meeting. In the first round, participants were asked to anonymously provide their opinion probing 1) the relevance and use of clinical characteristics (“Red Flags”) suggestive of underlying CD, 2) the use of faecal calprotectin (FCP) as an adjunct for screening for CD and 3) on the diagnostic work-up for IBD in PAA/PAF patients with raised clinical suspicion. In the second round, statements were paired/revised based on the feedback from the first round and presented in a final set of statements. Consensus was predefined as ≥70% agreement.

Results

A total of 30 experts participated in the first round and 25 in the second round (83.3%). Final consensus was reached for 29% of all statements in the first Delphi round and, after adjustments/merging, for all 11 statements (100%) in the second round. Ninety-seven percent of participants agreed that shortening of the delay in diagnosis by using a clinical decision tool could improve outcomes in patients with perianal disease as a first symptom. Consensus was reached on the red flags to be included in the clinical decision tool, on screening of all patients with any perianal fistula (regardless of the complexity, biological behaviour and co-existent perianal symptoms) to identify CD in an early (sub)clinical phase, on referral criteria and on the diagnostic workup and follow up of patients with raised suspicion.

Conclusion

A clinical decision tool for early identification of CD in patients with PAA/PAF as a first symptom could shorten delay in diagnosis and improve outcomes. Global consensus for this tool, including a practical and relevant algorithm for finding or excluding CD in patients with PAA/PAF as a manifesting sign, was reached within two rounds. This clinical decision tool will be validated in 2024 in a large, prospective multicenter study.Read more P301 Distinct plasma proteomic biomarkers associate with disease progression in patients with Inflammatory Bowel DiseasesWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are characterized by complex pathophysiology, phenotypic heterogeneity and disease progression. Patients with IBD show distinct shifts in circulating inflammatory proteins, which may be suggestive of biological mechanisms behind clinical disease progression. Thus far, proteomics studies in IBD have primarily focused on changes in the plasma proteome at pre- and post-diagnostic stages, as well as its genetic and phenotypic determinants. However, studies focusing on proteomic biomarkers for predicting the risk of disease progression are lacking. Here we aimed to identify plasma proteomic biomarkers associated with disease progression in patients with IBD.

Methods

In this study, a total of 83 inflammation-related plasma proteins were quantified in a cohort of 452 patients with IBD (267 with CD, 185 with UC) who participated in the 1000IBD project and had available follow-up data. Proximity extension assay technology was leveraged to measure these proteins. Disease progression outcomes, including the development of intestinal stenosis, IBD-related surgical interventions, and extraintestinal manifestations (EIMs), were extracted from electronic health records. Logistic regression analyses and Cox proportional hazards regression models were used to investigate associations between plasma proteins and the risk of disease progression outcomes.

Results

During a median follow-up of 10.3 (interquartile range [IQR] 7.6-11.1) years, 63 (23.6%) patients with CD developed intestinal stenosis, 53 (19.9%) patients with CD and 14 (7.6%) patients with UC underwent IBD-related surgery, and 120 (44.9%) patients with CD and 45 (24.3%) patients with UC developed EIMs. On multivariable analysis, macrophage colony-stimulating factor-1 (CSF-1) was most strongly associated with the presence of stricturing disease (Montreal B2 phenotype) (odds ratio [OR] per doubling in protein level 4.5, 95%CI: 1.6-12.9, P=0.005) and with a shorter stenosis-free survival (hazard ratio [HR] per doubling 4.2, 95%CI: 1.5-11.6, P=0.006). Furthermore, interferon-gamma (IFN-γ) was most strongly associated with surgery in CD (OR per doubling 1.6, 95%CI: 1.2-2.2, P=0.003) and with shorter surgery-free survival in CD (HR per doubling 1.4, 95%CI: 1.2-1.7, P<0.001) in multivariable analysis.

Conclusion

This study highlights that disease progression in IBD is associated with elevated levels of specific inflammatory plasma proteins. Specifically, CSF-1 and IFN-γ show most promise as possible proteomic biomarkers for the future development of intestinal stenosis and the risk of surgical interventions in patients with CD, respectively.Read more P302 Diagnostic Delayed is Associated with a Poor Prognosis in Patients with Crohn's DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The studies show that diagnostic delay, especially in Crohn’s disease (CD), is associated with a higher risk of complications and major surgery. We aimed to investigate timing of the diagnostic delay (DD) and its impact on the CD outcomes.

Methods

We retrospectively evaluated demographic and clinical features of CD patients between June 1993 and October 2023. Diagnostic delay was defined as the time interval from the onset of the first symptoms to the making of the CD diagnosis. The first CD related symptoms were evaluated by a review of the physician’s notes and medical record. Specific symptoms of CD included chronic or recurrent bloody or non-bloody diarrhea, and/or abdominal pain accompanied by noticeable weight loss, general weakness, and fever.

Results

514 patients with CD were included in the study. The median age of disease onset was 34.14 years (16–84 years). Male sex was 299 (58.2%). DD was detected median 13 months (5-47) (14 months in male and 12 months in female). DD was 12 months for diseases with onsets before the age of 40 and 15 months for diseases with onsets after the age of 40. DD was 25 months in isolated ileal involvement, in terminal ileal involvement was 21.5 months, ileo-colonic involvement was 20 months, and colonic location was 10 months. Ileal involvement was found to have a longer duration for DD than colonic involvement. Compared to stenosing behavior (20 months) and penetrating behavior (17 months), DD was shorter in non-stenosing non-penetrating behavior (12 months). DD was longer in perianal disease (18 months) than in those without (12 months). Current smokers had a longer duration of the DD (20 months) compared to non-smokers (11.5 months) and ex-smokers (10 months). The duration of DD (18 months) was longer in CD patients with extraintestinal manifestations than in those without (12 months).Regarding the biological treatment, CD patients who experienced multiple biologics and resistance had longer DD (24 months) than those who experienced biologic monotherapy and responded (12 months). Compared to patients who had not had surgery (12 months), DD was longer in CD patients who had undergone surgery (15 months).

Conclusion

Our study showed that ileal involvement, stenosing-penetrating behavior, perianal disease, current smoking and existing extraintestinal manifestations were connected with DD. DD was also associated with multiple biologic needed and surgery. DD may have a role a significantly increased risk of bowel damage.Read more P369 Altered fecal bile acid composition in active Ulcerative ColitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

A consistent finding in inflammatory bowel disease (IBD) is an altered composition of fecal bile acids, with an increase in primary bile acids and a decrease in secondary bile acids. It is less clear, whether fecal bile acids could prove to be biomarkers for IBD diagnosis and disease activity. The study aimed to determine correlations between eighteen fecal bile acid species and IBD entity as well as disease severity.

Methods

Eighteen fecal bile acid species were quantified from stool samples of 62 IBD patients and 17 controls using LC-MS/MS and stable isotope dilution. Bile acid levels were normalized to the dry weight of the fecal homogenates. For calculations, normalized bile acid concentrations and ratios of individual bile acid species to total bile acid levels were used. The p-values were corrected for multiple comparisons.

Results

In accordance with previous data, we showed that patients with IBD had more primary and less secondary bile acids in their stool compared to healthy controls, with greater differences when comparing healthy controls with ulcerative colitis (UC) than with Crohn´s disease (CD). In CD patients’ fecal calprotectin showed no correlations with any of the bile acids. In UC negative correlations between fecal calprotectin levels and two secondary bile acids, glycine conjugated lithocholic acid (GLCA) and hyodeoxycholic acid (HDCA), and thus total levels of secondary bile acids, existed. Comparing patients with low calprotectin levels (<50 µg/g) and patients with high calprotectin levels (>500 µg/g) in UC revealed that the latter group had lower GLCA and HDCA. Fecal bile acid levels of CD patients did not change with higher calprotectin. Moreover, serum C-reactive protein negatively correlated with the secondary bile acids HDCA, ursodeoxycholic acid, lithocholic acid, taurine conjugated lithocholic acid, deoxycholic acid and its taurine conjugated form in UC but not CD patients.

Conclusion

To distinguish between IBD subtypes, it may be helpful to note that impaired fecal bile acid homeostasis is specific to patients with active UC.Read more P370 Quality of life in inflammatory bowel diseases – is the flare all that matters?Wed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Burden in inflammatory bowel diseases (IBD) is high and affects both physical and psychological status. Short inflammatory bowel disease questionnaire (SIBDQ) is a self-administered health-related quality of life questionnaire that evaluates social, bowel, emotional and systemic dimension. Our aim is to evaluate the impact of IBD status on patients’ daily life.

Methods

We analysed 82 patients diagnosed with Crohn’s disease or ulcerative colitis or that were admitted between March 2021 and April 2022 in Fundeni Clinical Institute, Bucharest. SIBDQ consists of ten questions, with score ranging from 10 (poor) to 70 (optimal). Patients completed SIBDQ and we assessed disease status and determined biological and clinical markers.

Results

51% of patients were diagnosed with Crohn’s Disease. 79% were in clinical remission. The mean age was 39.53±12.9 years old and 52.4% were men. Mean illness duration was 8.03±7.18 years. Mean SIBDQ score was 50.25±14.51, with significantly higher scores in the remission subgroup (55.26±10.30 vs. 31.11±12.24, p<0.001) and it correlated with faecal calprotectin level (ρ=-0,502) and C-reactive protein level (ρ=- 0,531), without regard to disease type or sex. There were no correlations between SIBDQ score and Crohn’s disease or ulcerative colitis phenotype, duration since diagnosis, presence of extraintestinal manifestations or history of abdominal surgery related to IBD.

Conclusion

Patients with IBD flares have low quality of life and SIBDQ scores correlate with markers of disease severity, comparable to previously-published literature. Patients in clinical remission presented with higher SIBDQ scores, independently of IBD phenotype or previous surgery. Acute flares of IBD have a major impact on daily life, additional psychological and social support is needed in order to improve management.Read more OP10 Efficacy and safety of upadacitinib in patients with moderately to severely active Crohn’s Disease: results from the U-ENDURE long-term extensionWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Upadacitinib (UPA) is an oral Janus kinase inhibitor approved for the treatment of moderately to severely active Crohn’s disease (CD).¹ The U-ENDURE (NCT03345823) maintenance study and long-term extension (LTE) evaluate the long-term efficacy and safety of UPA maintenance therapy. Here, we report the results of the U-ENDURE LTE.

Methods

Patients (pts) completing the U-ENDURE 52-week (wk) maintenance study were eligible to participate in the LTE and continue their previously assigned treatment (placebo [PBO], UPA 15 mg [UPA15] once daily [QD], or UPA 30 mg [UPA30] QD; blinded until the last pt completed maintenance wk52). Clinical response, clinical remission, endoscopic response, endoscopic remission, as well as high-sensitivity C-reactive protein (hs-CRP) and faecal calprotectin (FCP) were evaluated as-observed up to wk48 of the LTE among pts (PBO [N = 89], UPA15 [N = 107], UPA30 [N = 173]); excluding pts who received open-label UPA30 rescue therapy. Safety was assessed in all pts (PBO [N = 223], UPA15 [N = 221], UPA30 [N = 229]) from wk0 of the maintenance study up to LTE wk204 (cut-off date: 01 Aug 2023).

Results

At LTE wk0, the SF/APS clinical remission rates were 73.0%, 78.3%, and 80.3% for PBO, UPA15, and UPA30, respectively (Figure 1A). Similar rates were reported at LTE wk0 for CDAI clinical remission (PBO 75.3%, UPA15 81.3%, UPA30 80.9%; Figure 1B) and clinical response (CR-100: PBO 79.5%, UPA15 84.9%, UPA30 84.4%). Rates of clinical remission were stable through wk48 of the LTE. Endoscopic response (PBO 32.9%, UPA15 59.6%, UPA30 66.5%) and remission rates (PBO 27.8%, UPA15 42.4%, UPA30 47.3%) at LTE wk0 were sustained through wk48 with UPA while decreased with PBO (Figure 1C-D). At LTE wk0, the mean [95% CI] change from induction BL in hs-CRP was 1.8 [–0.4, 4.1], –13.2 [–17.9, –8.6], and –12.8 [–16.8, –8.9] for PBO, UPA15, and UPA30, respectively; sustained through wk48. Similar results were observed with FCP (mean [95% CI] change from induction BL: PBO 126 [–103, 356], UPA15 –2946 [–4121, –1772], UPA30 –1871 [–2577, –1165]). Severe adverse events (AEs) and serious AEs were lower with UPA treatment compared with PBO (Table 1). The rates of most AEs of special interest were similar between UPA and PBO; however, numerically higher rates of herpes zoster, adjudicated gastrointestinal perforations, neutropenia, lymphopenia, creatine phosphokinase elevation, and hepatic disorders were reported in pts treated with UPA vs PBO (Table 1).

Conclusion

In pts completing wk48 of the LTE, sustained efficacy was observed in clinical and endoscopic endpoints with over 2 years of UPA treatment, while maintaining an overall positive safety profile in pts with CD.Reference:1. Loftus EV Jr, et al. N Engl J Med. 2023;388:1966–80Read more OP20 Postoperative endoscopic recurrence after resection of Crohn’s terminal ileitis with Kono-S or side-to-side functional end anastomosis: results of a Multicenter Prospective Randomized TrialWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

A novel anastomosis (Kono-S) was described in 2003 in Crohn’s disease. Subsequent observations have suggested that this anastomosis is associated with lower endoscopic and surgical recurrence rates. The purpose of this study was to compare the endoscopic recurrence between the Kono-S and the side-to-side functional end anastomosis at 3-6 months after resection of Crohn’s terminal ileitis.

Methods

This was a prospective multi-center randomized trial conducted at eight international centers. Patients with Crohn’s terminal ileitis requiring elective ileocecal resection were randomized to a Kono-S (Group1) or a side-to-side functional end (Group2) anastomosis (Image1). Patients were discharged on no biologicals. Exclusion criteria included age (<18), pregnancy, recurrent or multisite Crohn’s disease, and need of postoperative treatment with biologicals. Data were collected prior to and during surgery, daily after surgery until discharge, at 30 days post-op, and at 3-6 months colonoscopy. Participating surgeons were instructed in the Kono-S technique through videos. Disease clinical activity was measured by Harvey Bradshaw Index (HBI). Endoscopic remission/recurrence was graded with the modified Rutgeerts score: endoscopic remission was defined as a Rutgeerts score of 0, 1, or 2a, and a Rutgeerts score of 2b or higher was considered a recurrence. All study sites had Institutional Review Board approval, ClinicalTrial.gov # NCT03256240.

Results

We enrolled 288 Crohn’s patients (50.7% female) with a median age of 34 (18-81). 154 patients were randomized to Group 1 (Kono-S) and 134 to Group 2 (Side-to-Side). 30 days follow-up was completed on 278 (96.9%) patients. The Kono-S group had a higher percentage of past smokers (57 vs.30, p = 0.007) and current smokers (33 vs.12, p = 0.004). The mean operative time was 22 minutes longer in the Kono-S group (154 vs.132 minutes; p = 0.386). There was no mortality. 233 (81%) patients underwent a colonoscopy at 3-6 months. There was no significant difference between the two groups in terms of endoscopic recurrence (p = 0.883) and HBI (p = 0.109) or in recurrence-free survival (Log Rank Mantel-Cox test p = 0.256) (Table 1). On multivariable analysis, current smokers had significantly higher odds for endoscopic recurrence at 3-6 months (OR= 2.80, [95% CI =1.10 - 6.92], p = 0.029).

Conclusion

Kono-S and Side-to-side anastomoses have similar endoscopic recurrence rates at 3-6 months. Independently of surgical techniques, smokers had a significantly higher rate of endoscopic recurrence at 3-6 months after surgery.Read more OP28 Defective STAT3 signaling in refractory Very Early Onset Inflammatory Bowel Disease is associated with a transcriptional signature which predicts response to anti-IL23-based therapiesWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Very early onset inflammatory bowel disease (VEOIBD) has a monogenic cause in >5% of cases. IL10R deficiency is among the more common causes of monogenic IBD and presents with severe disease refractory to conventional therapies. For most VEOIBD patients, the molecular basis of disease is unknown. We employed flow cytometry and bulk RNA-sequencing to localize pathway-level dysfunction in VEOIBD patients with unknown molecular basis.

Methods

VEOIBD patients prospectively enrolled in a biorepository were screened for IL10R deficiency using a flow cytometry assay. Patient peripheral blood mononuclear cells (PBMCs) were stimulated with IL10 and control cytokine IL21 and pSTAT3 activation was measured. RNA-sequencing was performed on 115 whole blood samples, comprising VEOIBD patients with either confirmed (n=35, IL10R deficient n=4), or unknown monogenic causes (n=70), and controls (n=10). Transcriptome analysis focused on patients with abnormal STAT3 activation as determined by flow cytometry.

Results

We identified 6 patients with refractory VEOIBD and defective phosphorylation of STAT3 upon stimulation with both IL10 and IL21 by flow cytometry (Fig 1A), a result confirmed by Western blot (Fig 1B). All six "STAT3-defective" (STAT3-def) patients lacked deleterious mutations in known VEOIBD genes as determined by whole exome sequencing. Principal component analysis of blood transcriptome data showed the STAT3-def and IL10R deficient patients generally clustered together (Fig 1C). Cell-type de-convolution analysis of the blood transcriptomes was used to infer cell-type abundance and cell-type specific differentially expressed genes (DEGs) for the STAT3-def and IL10R deficient groups relative to the rest. Genes downregulated in estimated M1 macrophages from the STAT3-def group were enriched in the Hallmark pathway "IL6-JAK-STAT3 signaling." STAT3-def M1 macrophage DEGs were then projected on an adult colonic Crohn’s disease Bayesian network and extended out a path length of 1. The resulting STAT3-def subnetwork of 440 genes included the known VEOIBD genes STAT3, STAT1, TYMP, and TRIM22 (Fig 1D) and the top enriched signaling pathways included IL23, IL6, and IL12. This is of significant interest given three STAT3-def patients with disease refractory to anti-TNF and vedolizumab achieved remission with anti-IL23-based therapies (Table 1).

Conclusion

We identified 6 patients with refractory VEOIBD and a shared biochemical phenotype and blood transcriptional signature. Network analysis revealed signaling pathways targeted by existing IBD medications, including anti-IL23-based therapies. Molecular analysis of IBD patient blood has exciting potential to localize pathway-level dysfunction and guide precision medicine approaches.Read more OP29 Haematopoietic stem cell gene therapy as a treatment for severe Crohn’s Disease associated with pathogenic NOD2 genetic variantsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Pathogenic variants of the NOD2 (nucleotide-binding oligomerization domain containing protein 2) gene demonstrate the strongest genetic association to Crohn’s inflammatory bowel disease (CD), with mounting evidence linking NOD2 deficiency with poor clinical outcome. CD patients with NOD2 variants, particularly carriers of more than one risk allele, frequently present an aggressive, fistulizing and fibrostenotic disease, requiring multiple surgical resections. NOD2-deficiency is implicated to drive CD pathogenesis through failure of gut innate immunity to resolve bacterial infections and by loss of tissue homeostasis within the intestinal microenvironment. Here we present preclinical data on OTL-104, an autologous haematopoietic stemcell gene therapy (HSC-GT) which aims to stably restore NOD2 expression in gut resident macrophages, to correct immune dysfunction linked to NOD2-deficient CD pathogenesis.

Methods

We used in vitro and in vivo models of NOD2 deficiency to demonstrate the mechanism of action and the efficacy of OTL-104 autologous HSC-GT.

Results

NOD2^KO human myeloid cells differentiated in vitro from CRISPR-generated NOD2^KO CD34⁺ HSCs are unable to mount a proinflammatory cytokine response to MDP stimulation. Similarly, myeloid cells differentiated from CD34⁺ cells obtained from peripheral blood of genetically characterized NOD2-deficient CD patients, are also refractory to MDP stimulation and unable to generate a normal cytokine response profile. In both NOD2 deficient CD34⁺ derived monocyte models, transduction with a lentiviral vector (LVV) expressing NOD2 fully restores NOD2-dependent cytokine and chemokine responses, restoring an immune profile that is comparable to monocytes derived from CD34⁺ cells from NOD2 wild-type healthy donors (Figure 1).Transplantation of lineage negative (Lin^-) haematopoietic stem/progenitor cells (HSPCs) transduced with the OTL-104 LVV in NOD2^KO mice was used as an in vivo model of gene therapy for CD. Compared to WT mice, NOD2^KO mice fail to release systemic inflammatory mediators and recruit myeloid cells in response to MDP administration. Transplantation of transduced Lin^- HSPCs restores MDP-induced systemic release of IL-6 and CXCL1 as well as innate mobilization of monocyte/macrophage cells and gut associated gene expression. Key to our therapeutic approach, histopathological analysis of intestinal lamina propria from transplanted mice shows a normal biodistribution and physiological NOD2 gene expression in tissue resident cells.

Conclusion

These results confirm the impact of NOD2 deficiency in primary immune activation and demonstrates the therapeutic potential of OTL-104 HSC-GT for long-term correction of NOD2-deficient CD.Read more DOP18 Efficacy of risankizumab versus ustekinumab by baseline Crohn’s Disease location: post-hoc analysis of the SEQUENCE head-to-head trialWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

In Crohn’s disease (CD), disease location may impact treatment effect. This post-hoc analysis of the SEQUENCE head-to-head trial (NCT04524611) compared the efficacy of risankizumab (RZB), an interleukin (IL)-23 p19 inhibitor, versus ustekinumab (UST), an IL-12/23 p40 inhibitor, by CD location.

Methods

SEQUENCE was an open-label, efficacy assessment-blinded, randomized controlled trial, which enrolled patients (pts) with moderate to severe CD who previously failed ≥1 anti-tumor necrosis factor (TNF) therapy. Pts included in the primary efficacy analysis were randomised 1:1 to receive RZB (selected dosing: intravenous 600 mg induction dose administered at weeks (wks) 0, 4, and 8, followed by subcutaneous 360 mg maintenance dose every 8 wks starting at wk 12) or UST (a single weight-based induction dose administered at wk 0, followed by subcutaneous 90 mg maintenance dose every 8 wks starting at wk 8. A mandatory steroid taper began at wk 2. The primary endpoints were clinical remission (CD Activity Index <150) at wk 24 and endoscopic remission (Simple Endoscopic Score for CD ≤4 and at least a 2-point reduction versus baseline and no subscore >1 in any individual variable, as scored by a central reviewer blinded to treatment allocation) at wk 48. In this post-hoc analysis, both endpoints were evaluated in 100% of pts included in the primary efficacy analysis, stratified by baseline CD location subgroups (ileal only, colonic only, ileal-colonic). Nominal P-values were reported for treatment differences within subgroups.

Results

At baseline, majority of pts had either ileal-colonic (225 [43.3%]) or colonic (208 [40%]) CD; 87 (16.7%) pts had isolated ileal disease. At wk 24, numerically greater proportions of pts achieved clinical remission with RZB versus UST, regardless of disease location (treatment difference [95% confidence interval], P-value: ileal only, Δ0.8 [-20.1, 21.7], P=0.941; colonic only, Δ22.4 [9.2, 35.5], P=0.001; ileal-colonic, Δ18.2 [5.3, 31.0], P=0.007) (Figure). Pts randomized to RZB with colonic only disease had numerically higher rates of clinical remission relative to pts with ileal only or ileo-colonic disease. At wk 48, RZB-treated pts demonstrated numerically higher rates of endoscopic remission than UST-treated pts (ileal only, Δ22.5 [4.4, 40.6], P=0.017; colonic only, Δ18.3 [6.6, 30.0], P=0.003; ileal-colonic, Δ10.3 [-0.2, 20.9], P=0.057) (Figure). Endoscopic remission rates in the RZB-treated pts were generally similar between ileal only and colonic only CD.

Conclusion

In pts who have failed ≥1 anti-TNF therapy, RZB demonstrated greater rates of endoscopic remission compared to UST regardless of CD location, and greater rates of clinical remission in ileo-colonic and colonic CD.Read more DOP19 High dimensional profiling of IL-23-responsive cells revealed molecular signatures that predict response to anti-IL-23 therapy in patients with Crohn’s DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The interleukin (IL)-23 signaling plays a crucial role in the pathogenesis of Crohn’s disease (CD). IL-23 activates T-helper (Th) 17 cells, IL-17-secreting CD8 T (Tc)17 cells, gd T cells, nature killer (NK) T cells, and group 3 innate lymphoid cells (ILC3) to secrete proinflammatory cytokines including IL-17, IFN-g, and TNF-a. Risankizumab is the first selective IL-23 antagonist approved for moderate-severe CD. However, there is currently no biomarker to predict response to anti-IL-23 antibodies in IBD. Here, we characterized the cell type- and cytokine-specific pathways in IL-23-responsive cells that predict response to risankizumab in CD patients.

Methods

Adult patients with a history of ileal, colonic, or ileocolonic CD were included. Active CD in terminal ileum and/or colon were confirmed by colonoscopy and/or MRI. Blood samples were collected within 3 months before and 4, 8, 12, and 52 weeks after the initiation of risankizumab. Peripheral blood mononuclear cells (PBMC) were isolated and cryopreserved for batch analysis using mass cytometry (CyTOF). Pre-treatment PBMCs were stimulated ex vivo with IL-23, and stained for lineage markers to identify Th17, Tc17, gd T, NKT cells, and ILC3, as well as intracellular cytokines including IL-17, IFN-g, TNF-a, IL-22, IL-6, and GM-CSF, using a pre-optimized and validated antibody panel. The CyTOF data were analyzed using the viSNE tool in Cytobank and FlowJo. Patients’ responses were evaluated 12-40 weeks after the initiation of risankizumab based on clinical symptoms and endoscopic/radiographic assessment.

Results

Among IL-23-responsive cells, increased frequency of NKT cells was identified in the peripheral blood of non-responders before initiation of risankizumab (Figure 1A). In non-responders, Tc17 cells, gd T cells, and ILC3 demonstrated significant elevations in TNF-a, a key pathogenic mediator in CD. gd T cells from non-responders also showed increased IL-17F before treatment. In contrast, NKT cells from non-responders expressed significantly lower GM-CSF, which was previously shown to alleviate intestinal inflammation in patients and mouse models (Figure 1B). Ongoing study is investigating the cytokine production in IL-23-responsive cells after the initiation of risankizumab, as well as before and after starting ustekinumab, an anti-IL-12/IL-23 antibody.

Conclusion

High dimensional profiling of pre-treatment PBMCs revealed molecular signatures, e.g., elevated TNF-a in multiple IL-23-responsive cells, which are associated with resistance to risankizumab in CD patients. Those findings may help identify response biomarkers for IL-23 antagonists and provide a rationale for using anti-IL-23/anti-TNF combination therapy in some patients with refractory CD.Read more DOP39 Constructing butyrate-producing yeast as a cell-dependent treatment option for Inflammatory Bowel DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Intestinal microbiota dysbiosis and metabolic disruption are essential characteristics of inflammatory bowel disorders (IBD). Butyrate has been proven to regulate immune response and gut microbiota. It has been confirmed that the butyrate content in the intestinal cavity of IBD patients decreases (Fig. 1A).

Methods

In this study, gene editing was used to reconstruct the butyrate synthesis pathway and regulate related metabolic pathways in Saccharomyces cerevisiae to produce butyrate and enrich its synthesis in anaerobic environments to cope with complex intestinal conditions. A series of engineered strains were co-cultured with gut microbiota samples from six patients with mild-to-moderate ulcerative colitis and 16S ribosomal RNA sequencing was used to analyze the regulatory effect of engineered strains on intestinal microbiota in vitro. The TNBS-induced IBD mice model was used to explore the protective effect of butyrate-engineered yeasts in vivo.

Results

A series of engineered strains with different butyrate synthesis abilities was constructed to meet the needs of different patients. S. cerevisiae was engineered by introducing an exogenous butyrate synthesis pathway and regulating yeast metabolism to increase the availability of the precursors. Engineered yeast can produce up to 1.8 g/L butyrate (Fig. 1B). The modification of related metabolic pathways also focused on enhancing the synthesis of butyrate under anaerobic conditions to enable engineered yeasts to adapt to the intestinal environment. This series of engineered yeasts with different butyrate synthesis abilities regulated the intestinal microbiota of IBD patients to varying degrees, enhancing the abundance of related probiotics such as Lactobacillus and Bifidobacterium and reducing the abundance of harmful bacteria like Candidatus Bacilloplasma (Fig. 1C). Meanwhile, strains improved TNBS-induced colitis in mice by restoring butyrate content. Remarkably, the engineered strain with the second-highest butyrate yield showed the most significant therapeutic effect (Fig. 1D).

Conclusion

This study realized butyrate synthesis in S. cerevisiae and regulated related metabolic modules to adjust the butyrate production to achieve the best therapeutic effect on colitis in vivo and in vitro. In addition, the strain with the second-highest butyrate production has the best therapeutic effect. This highlights the dual role of butyrate in epithelial cell repair and suggests a therapeutic window for IBD treatment through butyrate supplementation. Selecting the most suitable strain for each patient's condition is essential for restoring butyrate levels, regulating microbiota, and promoting mucosal repair.Figure 1.Constructing butyrate-producing yeasts for the treatment of IBDRead more DOP40 Inflammatory Bowel Disease single cell atlas construction to enable cell type-specific target identificationWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Advances in single-cell technologies enable the unbiased study of cellular heterogeneity. Recently, single-cell RNA sequencing (scRNA-seq) has been utilised on intestinal and blood samples from patients with inflammatory bowel disease (IBD) and healthy individuals, often in conjunction with cell surface proteome and TCR repertoire analyses. These individual studies revealed novel cell subpopulations of immune, mesenchymal, and epithelial cells in UC and CD, but are not sufficiently powered to consistently identify granular cell subsets or establish their association with disease status and response to treatment. Integration of these studies into a unified IBD single-cell atlas would provide a more robust data foundation for therapeutic target discovery. Here, we constructed a comprehensive, multi-modal single-cell atlas of human IBD tissue, combining a large breadth of meta-analysis with the depth of single-cell resolution.

Methods

Raw data from 20 public datasets were curated and reprocessed to generate a harmonised data foundation to support downstream discovery efforts. Low-quality cells and doublets were removed using thresholds for gene number, gene count, and percentage of counts originating from mitochondrial genes, and the resulting data were normalised and adjusted for batch effects. Published clinical metadata from each study were re-annotated with controlled vocabularies. Associations between clinical metadata and cellular/molecular features were discovered using computational and ML approaches.

Results

We generated a large-scale integrated single-cell atlas for IBD comprising >500 tissue samples from >200 IBD patients and relevant controls, with harmonised clinical metadata including treatment history and response. This tissue atlas comprises >990k high-quality cells with granular annotations of 129 cell types/states. IBD inflammation and non-response to anti-TNF treatment were associated with unique transcriptional signatures in specific mononuclear phagocyte, CD4 T cell, and fibroblast subpopulations. Further prioritisation and validation of genes comprising these signatures may yield future therapeutic targets for IBD.

Conclusion

This atlas integrates single-cell data across the largest available collection of IBD patient-derived tissue samples. Leveraging high-resolution cell type annotations and harmonised clinical metadata, meta-analyses of this data foundation will broaden the understanding of IBD biology to identify novel targets and pathways for drug discovery.Read more DOP68 Natural history of isolated Crohn's Disease perianal fistulaWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Approximately 20% of patients with Crohn’s disease (CD) have perianal fistulizing CD, which are most often complex PAF. Studies have shown that 4-5% of patients with CD present with PAF without luminal disease, termed isolated perianal CD (iPCD). Little is known about their natural history.

Methods

We performed a retrospective cohort study of patients seen within the Mount Sinai Health System (New York) with an ICD-10 diagnosis code for PAF between 7/22/2008 and 7/22/2022. Medical record review was conducted to identify patients with PAF, considered as possible iPCD, who did not have evidence of luminal disease and had > 6 months of follow-up (Table 1). Demographics, comorbidities, imaging, endoscopy, surgeries, hospitalizations and medication data were collected. These patients were reviewed to determine progression to luminal disease, which was defined as any evidence of luminal ulcers, erosions, or strictures on endoscopy, histology, video capsule exam, or MRE. Descriptive and univariate analyses were performed. Complex PAF was defined by American Gastroenterological Association criteria. Complicated disease course was defined as a composite of any major CD-related surgery, PAF/IBD-related hospitalization or biologic use.

Results

Among 887 patients who presented with PAF, 62.2% (n=552) patients underwent luminal evaluation, of whom 80 patients (14.5%) were found to have no luminal disease and considered as having iPCD (Table 1). 57 of these 80 patients had >6 months follow-up. Luminal disease developed in 13 patients (23%) with a mean time to diagnosis of 4.2 +/- 3.8 years after PAF presentation. Patients who developed luminal CD were more likely to be <30 years old at PAF diagnosis (p=0.0225), had >2 fistulas on imaging (p=0.002), and have concomitant autoimmune conditions (p=0.046) (Table 2). During the follow-up period, the patients who developed luminal CDwere more likely to receive biological therapy (77% vs 16%, p<0.0001) or undergo CD/PAF-related hospitalization (62% vs 30%, p =0.0356) (Table 2). Overall, patients who developed luminal CD had a more complicated disease course (31% vs 2.3%, p=0.007) than those who did not.

Conclusion

Approximately 1 in 4 patients who presented with possible iPCD developed luminal CD at follow-up. Patients who developed luminal CD were more likely to be younger at diagnosis, had more fistula tracts, and had concomitant autoimmune conditions.Read more DOP69 Longitudinal gut microbiome dynamics in relation to disease flares in Inflammatory Bowel Disease, pilot data from the IBD-Tracker studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The pathogenetic mechanisms that lead to IBD flares are unknown and the absence of reliable predictive biomarkers results in a therapeutic approach focused on treating active flares rather than prevention. While IBD is known to be associated to changes in gut microbiota, the longitudinal dynamics of the microbiome in relation to disease flares and its biomarker potential remain poorly understood. We initiated the IBD -racker study which aims to include 100 patients with weekly fecal sampling along other biomaterials and clinical data. The aim is to elucidate patient-specific dynamics of the gut microbiome, including changes during IBD flares, strain replacements, and the potential for personalized prediction of flares based on microbiome. Here we present pilot microbiome data from the first 5 patients that completed the collection.

Methods

A comprehensive analysis of microbiome dynamics was conducted by collecting 52 weekly fecal samples, calprotectin measurements and clinical disease scores from five IBD patients. Metagenomic sequencing was employed on 248 samples, followed by biobakery4 tools for profiling of microbiome composition and function. Stability and dynamics of gut microbiota were evaluated through analysis of autocorrelation and stable states, while bacterial strains were profiled using markers and metagenomic assembly and binning based approaches. Finally, microbiome signatures associated with IBD flares were identified using multivariate generalized regression models correcting for patient-driven heterogeneity.

Results

The core gut microbiome of IBD patients (43 to 82 patient-specific highly prevalent species) is highly personalized and largely stable over time, regardless of flares (patient ID R² > 0.4 in ADONIS of microbiome composition and function). The bacterial strains of these core species cluster by patients, indicating flares do not perturb them. Despite this stability of the core microbome, ~60% of identified bacterial taxa were present in <70% of weekly samples, indicating that a large part of the microbiome is dynamic. Differential abundance analysis revealed 32 bacterial species genomic bins (e.g. Clostridia pathobionts) and one pathway significantly associated with IBD flares (FDR < 0.1). Intriguingly, several species (e.g. Faecalibacterium sp. SGB15346, Clostridium inoocum) showed switches between high and low abundance stable states correlated with flares, and certain bacteria (e.g., Blautia wexlerae) underwent strain replacement during flares, which was not reversed post flare.

Conclusion

Our results indicate that IBD flares perturb a large part of the non-core gut microbiome, implying that personalized longitudinal monitoring of microbiota has potential for prediction and monitoring of IBD flares.Read more DOP70 Prevalence and severity of bowel urgency in Crohn’s Disease: Results from the Communicating Needs and Features of IBD Experience (CONFIDE) SurveyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Bowel urgency (BU) affects patients with Crohn’s disease (CD); however, its prevalence and severity are unclear. Here, data from Communicating Needs and Features of IBD Experiences (CONFIDE) study were used to understand the burden and impact of BU among patients with moderate-to-severe CD.

Methods

CONFIDE is an online, quantitative, cross-sectional survey exploring the experiences and impact of symptoms on patients with CD or ulcerative colitis in Europe (France, Germany, Italy, Spain, and UK), United States (US) and Japan. Criteria based on previous treatment, steroid use, and/or hospitalization defined moderate-to-severe CD. Patients were asked about bowel movement deferral time with response options ranging from able to wait ≥15 minutes (mins) to sometimes unable to make it to the bathroom in time. Patients currently experiencing BU (in last month) rated BU severity in the last 3 days using the Urgency Numeric Rating Scale (NRS, 0-10), a content-validated patient-reported instrument. CD data from Europe and US are presented here using descriptive statistics.

Results

Surveys were completed by 547 European (male [M]=55.4%, mean age 38 years) and 215 US (M=54.9%, mean age 40.9 years) patients with CD. Current BU (over the past month) was reported by 38% of patients in Europe and 42.3% in US. More than one-third of all patients in both Europe and US reported that over the last 3 days, they needed to get to the bathroom within 5 mins, and 1.8% European and 2.8% US patients were sometimes unable to make it to the bathroom in time. Among patients who reported currently experiencing BU, 46% reported the need to get to the bathroom within 5 mins and 3% reported sometimes being unable to make it to the bathroom in time in both Europe and US. Shorter deferral times were reported by those with higher mean Urgency NRS scores (Table). Mean (SD) Urgency NRS scores in patients with a deferral time <5 mins vs those with a deferral time >5 mins were 7.0 (1.7) vs 6.5 (2.1) among European and 7.3 (1.5) vs 6.7 (1.9) among the US patients. Most European and US patients reported experiencing BU, BU-related accidents, and/or wearing diaper/pad/other protection due to fear/anticipation of BU-related accidents at least once a month in past 3 months (Figure).

Conclusion

Patients with moderate-to-severe CD reported similar experiences of BU in the Europe and US, with most patients reporting currently experiencing BU and wearing diaper/pad/protection due to fear of BU-related accidents at least once a month. Patients currently experiencing BU had short deferral times, often having to reach the bathroom in ≤5 mins. Given the substantial burden and impact, BU should be considered when assessing patients with CD.Read more DOP71 Efficacy of once-daily, orally administered obefazimod in patients with moderately to severely active UC at weeks 8, 48, and 96 broken down by induction treatment doseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Obefazimod (obe) is an investigational, oral, once-daily, small molecule which enhances expression of microRNA-124 and is currently in phase 3 clinical trials for the treatment of patients with moderately to severely active ulcerative colitis (UC) [1]. Obe demonstrated efficacy in patients with UC at week-8 in a phase 2b, double-blind, placebo-controlled, dose ranging, induction trial and in the subsequent open-label maintenance (OLM) study [2].

Methods

During the induction Phase 2b trial, patients received placebo or obe 25mg, 50mg or 100mg once daily (od). Irrespective of their clinical response, patients could enter the optional 96-week OLM study with obe 50mg od. Of the 222 eligible patients, 217 continued treatment in the OLM. We examine the efficacy outcomes at weeks 8, 48, and 96, for patients enrolled in the OLM according to their induction dose group.

Results

Among the 58 patients who initially received obe 25 mg during the induction period, 28% (16/58) achieved clinical remission at week 8. After switching to 50 mg in the OLM, the rate of clinical remission increased to 60% (35/58) at weeks 48 and 96. Similar trends were observed for clinical response (66% (38/58) at week 8, 85% (49/58) at week 48, and 74% (43/58) at week 96), endoscopic improvement (36% (21/58) at week 8, 60% (35/58) at week 48, and 66% (38/58) at week 96), and endoscopic remission (7% (4/58) at week 8, 28% (16/58) at week 48, and 47% (27/58) at week 96).In the group of patients who received obe 50 mg in the induction period (n= 51), 20% (10/51) achieved clinical remission at week 8. After switching to 50 mg in the OLM, the rate of clinical remission increased to 49% (25/51) at week 48 and 96. Similar trends were observed for clinical response and endoscopic improvement (Table 1).Among the 53 patients who received obe 100 mg in the induction period, 28% (15/53) achieved clinical remission at week 8. After switching to 50 mg in the OLM, the rate of clinical remission increased to 55% (29/53) at week 48 and week 96. Similar trends were observed for clinical response and endoscopic improvement (Table 1).Among the 55 patients who received placebo in the induction period, 15% (8/55) achieved clinical remission at week 8. After switching to 50 mg in the OLM, the rate of clinical remission increased to 55% (30/55) at week 48, and 45% (25/55) at week 96. Similar trends were observed for clinical response and endoscopic improvement (Table 1).

Conclusion

These findings suggest that patients with UC treated with obefazimod 50mg od after the week 8 induction period maintained efficacy and continued to improve, irrespective of their induction dose, as evidenced by higher percentages of patients reaching clinical endpoints at weeks 48 and 96 relative to week 8.Read more P015 iNKT cells immunomodulation and mucosal healing by microbiota-derived lactateWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Invariant natural killer T (iNKT) cells are unconventional, CD1d-restricted, T lymphocytes playing a critical role in mucosal immune homeostasis. iNKT cells plastically adapt their functional phenotypes to the surrounding environment and are involved in IBD pathogenesis. Although iNKT cells release proinflammatory cytokines in response to the altered gut microbiota of IBD patients, exposure to microbiota-derived metabolites can promote homeostatic IL10-mediated iNKT responses resulting in better clinical outcomes in Crohn's disease (CD) patients. Thus, understanding the mechanisms leading to iNKT cells’ functional shaping by microbiota-derived metabolites is important to design novel therapeutic approaches for IBD patients. We hypothesised that iNKT cells, serving as sentinels of tissue integrity, are the primary immune cells sensing microbiota-derived metabolic signals promoting the resolution of inflammation in IBD. In particular, here we show that microbiota-derived lactate can tightly control iNKT cell functions promoting iNKT cell-mediated mucosal tolerance while preventing T cell-mediated overt inflammation and tissue injury.

Methods

We performed immunophenotyping of iNKT cells by multiparametric flow-cytometry from surgical specimens of CD patients and correlated NKT10 responses with intra-colonic levels of lactate, gut microbiome composition and tissue injury/healing. We studied the molecular pathway determining the NKT10 phenotype in a lactate-enriched microenvironment by RNA-seq and CHIP-seq. We validated the role of NKT10 responses by microbiota-derived lactate in-vivo by using experimental colitis models.

Results

Our data suggest that microbiota-derived lactate plays a role in the epigenetic control of anti-inflammatory iNKT cell functions through histone lysine lactylation, thereby protecting from intestinal inflammation.

Conclusion

On overall our data show i) how microbiota-derived lactate modulates the immunophenotype of iNKT cells, ii) the mechanisms underlying the sensing of microbiota-derived lactate by iNKT cells, iii) iNKT cells role in inflammation resolution.This work is supported by an ECCO grant '22 to Francesco StratiRead more P016 Reduction of mucosal (active) eosinophils, B cells and T cells after vedolizumab therapy in patients with ulcerative colitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Patients with ulcerative colitis (UC) are often treated with biological therapies or small molecules. Knowledge about the impact of these therapies on the intestinal and peripheral blood immune cell composition is scarce. Therefore, we investigated how advanced therapies modulate immune cell distribution in UC patients.

Methods

We included 30 UC patients (53% male, median age 42 years) who started a biological or small molecule. Before the first drug administration, mucosal colonic biopsies and a peripheral blood sample were obtained. At the end of induction, colonic biopsies and peripheral blood were sampled again. Patients starting adalimumab (n=2), infliximab (n=3), vedolizumab (n=11), ustekinumab (n=6), ozanimod (n=2) and the JAK inhibitors filgotinib (n=3) and tofacitinib (n=3) were included. Endoscopic improvement was defined as a Mayo endoscopic subscore of 0-1 at the end of induction. From the biopsies, a single-cell suspension was made. Intestinal and circulating immune cells were characterized via flow cytometry. Statistical analysis was performed using a paired t-test.

Results

Independent of the mechanism of action (MOA), patients responding to therapy showed a decrease of colonic granulocytes (neutrophils (p<0.0001) (Figure 1A), basophils (p<0.0001) (Figure 1B) and eosinophils (p=0.008) (Figure 1C)), active eosinophils (p=0.002) (Figure 1D)), B cells (p=0.05) (Figure 1E), regulatory T cells (p<0.0001) (Figure 1F) and T helper (Th) 2 cells (p=0.02) (Figure 1G), balanced with an increase of Th1 cells (p=0.03) (Figure 1H). In peripheral blood, eosinophils increased in patients not responding to therapy (p=0.05) (Figure 1I). Furthermore, we observed that only patients starting vedolizumab (n=11) showed a decrease in colonic eosinophils (p=0.02) (Figure 1J), active eosinophils (p=0.002) (Figure 1K), B cells (p=0.03) (Figure 1L) and T cells (p=0.004) (Figure 1M). Considering only non-vedolizumab patients (n=19), we did not observe this effect.

Conclusion

UC patients responding to advanced therapies showed a different intestinal immune cell distribution compared to non-responders, regardless of MOA. Vedolizumab therapy furthermore decreased several mucosal immune cell subsets that migrate to the gut through α4β7-MAdCAM-1 binding. While the effect of vedolizumab on B cells and T cells was previously described, we have now potentially identified an additional eosinophil-reducing effect in the colon.Read more P017 An activity-based chemiluminescence assay targeting granzyme A for the detection of Inflammatory Bowel DiseasesWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Inflammatory Bowel Diseases (IBD) represent a pressing global health concern lacking precise diagnostic tools for accurate patient stratification. Conventional methods, such as colonoscopy are extremely invasive whilst generic inflammatory markers (such as CRP or Calprotectin), are not specific enough and pose limitations in assessing disease activity, urging the need for novel, non-invasive diagnostic approaches which can rapidly inform clinicians on the inflammatory status of a patients bowels.

Methods

Our study focused on developing a non-invasive chemiluminescence assay targeting active granzyme A (GzmA) in stool supernatants. Employing a multifaceted approach encompassing functional, chemical, and imaging assays on human cells and gut tissue biopsies, we discerned elevated GzmA levels predominantly secreted by CD8+ T cells in inflamed gut tissues.

Results

The design of GzmA-INH, a specific inhibitor for GzmA, underscored the prevalence of active extracellular GzmA and it’s role in driving inflammation in the guts - revealing promising potential as a novel IBD biomarker. Further, we synthesized GzmA-CL, a highly reactive and selective chemiluminescent reporter for GzmA. Integrating GzmA-CL into a robust antibody-coated 96-well plate assay (Figure 1a), we analyzed 30 IBD biosamples along with healthy controls. Notably, substantially higher GzmA levels were observed in IBD patients, with discernible distinctions between ulcerative colitis (UC) and Crohn’s disease (CD) (Figure 1b). These levels correlated positively with established biomarkers, including faecal calprotectin and immune cell counts.

Conclusion

Our investigation highlighted active extracellular GzmA as a noteworthy biomarker in gut inflammation. The rapid, selective, and sensitive nature of our chemiluminescence assay presents promising prospects for precise IBD diagnosis and advancements in personalized medicine.Read more P018 Inequalities in healthcare access, experience and outcomes in adults with Inflammatory Bowel Disease: A scoping reviewWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Inflammatory Bowel Diseases (IBD) are long-term conditions requiring lifelong access to, and interactions with health services. Accumulating evidence of inequalities in health care access, experience and outcomes for individuals with IBD is apparent. However there is no existing review that systematically maps these inequalities.The purpose of this review was to map and describe the inequalities in healthcare access, experiences, and outcomes of care for adults with IBD, to identify research gaps and future research priorities in this area.

Methods

A scoping review was conducted to retrieve quantitative, qualitative, and mixed methods evidence from three electronic databases (EMBASE, Medline and CINAHL). English written articles published between 2000 and 2023 were systematically searched using a search strategy. The Joanna Briggs Institute protocol for scoping reviews was followed to perform data extraction and analysis.

Results

1343 records were identified. 51 studies met the criteria for inclusion. Studies addressed ethnic disparities of healthcare (33/51), inequalities driven by socioeconomic differences (12/51), rurality (7/51), gender (3/51), age (2/51), culture (2/51), literacy (1/51) and sexuality (1/51). The interrelationship of disparities relating to outcome, access and experience is illustrated in Figure 1. Poorer health outcomes (42/51 studies) were described in those from Black, Asian, and Hispanic ethnic groups in relation to hospital admission, readmission, emergency room attendance, length of stay, IBD-related complications, post-operative complications, treatment delay and length of stay. Deprivation, insurance status in US populations, rural location and age also affected outcome. Access inequalities (24/51 studies) were described to services, therapies and surgery but also to educational opportunities. Poor experience of care (8/51 studies) included appointment issues, lack of cultural understanding and fragmented care. A lack of research was found in the LGBTQIA+ community (1/51). No research was found to investigate inequalities in IBD patients with learning disabilities or autism.

Conclusion

Inequality affecting a wide range of population characteristics affects outcomes, access and experience in IBD care. Services need to be organised and delivered in a way that addresses this. Further research, including qualitative methods, is particularly needed to understand health experiences of underserved patient populations with IBD. The lack of research amongst LGBTQIA+ individuals, and with learning disabilities, poses a risk of creating inequalities within inequalities.Read more P048 Identification of IL36RN missense mutations in Crohn’s disease patients as a potentially new drug target for treating rare patients with over-activation of the IL36 signaling cascadeWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The interleukin 36 (IL-36) family includes the agonists IL-36α, IL-36β, IL-36γ, which activate the NF-κB pathway and the natural antagonist IL-36RA, which inhibits IL-36 signaling. While missense mutations in the gene encoding IL-36RA (IL36RN) are associated with severe skin inflammation, their role in Crohn’s disease (CD) is currently unknown. Therefore, we here investigated if IL36RN mutations contribute to inflammation in CD and whether IL-36 signaling might represent a potential drug target for personalized therapy.

Methods

Mutations in IL36RN were identified by whole exome sequencing (WES) followed by targeted Sanger sequencing. Peripheral blood mononuclear cells (PBMCs) of affected patients were analyzed by mass cytometry and serum cytokines were measured by ELISA. Identified IL36RN mutations were characterized by overexpression experiments and functional assays. Clinical and molecular responses of one IL-36RN mutant patient to combined treatment with spesolimab and certolizumab pegol was assessed by fecal calprotectin, endoscopy, RNA sequencing and mass cytometry at week 0 and 12 of treatment.

Results

In a cohort of 47 ulcerative colitis patients, 177 CD patients and 34 healthy controls, we identified 3 CD patients with heterozygous missense mutations in IL36RN (IL-36RA S113L, IL-36RA P76L and IL-36RA L133I). In the patient carrying the IL-36RA S113L variant, we detected elevated serum levels of IL-18 and IL-23, as well as an increased frequency of TH17 cells in PBMCs, suggesting an overactivation of the IL-36 pathway. Overexpression experiments showed that IL-36RA S113L causes decreased expression of IL-36RA, resulting in increased IL-36 signaling. The patient was therefore treated with 1200 mg of the IL-36R blocking antibody spesolimab every 4 weeks and 200 mg of certolizumab pegol biweekly on the basis of an Out Of Scope request. This approach resulted in reduced intestinal inflammation and a reduction in the frequency of pro-inflammatory myeloid cells in PBMCs.

Conclusion

In this study, we show that pathogenic IL36RN mutations are present in a subset of CD patients and that blocking IL-36 signaling may represent a personalized therapeutic approach for this rare subset of patients in whom conventional biologic therapies have failed.

Disclaimer

Boehringer Ingelheim was given the opportunity to review the abstract for medical and scientific accuracy as well as intellectual property considerations in relation to the potential mention of BI substances. Boehringer Ingelheim had no role in the design, analysis or interpretation of the results in this study. Spesolimab was made available on the basis of an out of scope request. Boehringer Ingelheim was given the opportunity to review this abstract as a courtesy.Read more P049 The lipidome of creeping fat in Crohn’s disease points towards a harmful microenvironmentWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

A pathognomonic observation in Crohn’s disease (CD) is the existence of mesenteric adipose tissue (MAT) wrapping around the inflamed and fibrotic intestine, so-called creeping fat. The etiology of this phenomenon is unclear, and both a protective and harmful role in disease pathogenesis and progression have been proposed. Given this conflicting evidence, we aimed to further unravel the role of creeping fat by extensive profiling of its lipidome.

Methods

We prospectively included 22 CD patients who underwent an ileocecal resection with ileocolonic anastomosis (Table 1). Perioperatively paired adipose tissue samples were collected from 3 locations: (1) creeping fat, (2) MAT close to the proximal unaffected ileum, and (3) MAT far from the diseased ileum, defined as near the base of the ileocecal artery (Fig. 1A). The lipidome of all 66 samples was profiled by quantitative mass spectrometry (targeted C18 LC-MS/MS and HILIC LC-MS/MS; Lipometrix core KU Leuven). This approach enables the detection of mediator lipids, and membrane and storage lipids, of which the latter group represents more complex chemical structures and thus a higher diversity in classification and number of species. Data analysis and paired Wilcoxon rank- sum tests were performed with Python and R 4.3.2.

Results

Across all CD adipose tissue samples, we detected 38 mediator lipid species, and 456 membrane and storage lipid species . When paired-wise comparing creeping fat with MAT far from the diseased ileum, we observed a significant decrease in 16 lipid mediators (p<0.05), namely arachidonic acid (AA), docosahexaenoic acid (DHA), 4 epoxy and 10 hydroxy mediator lipids; with hydroxy mediator X being the top downregulated in creeping fat (fold change (FC)=-2.11, p=0.0003) (Fig. 1B). While AA and DHA are (semi)-essential fatty acids and function as precursors, the other 8 decreased lipids in creeping fat are known to be anti-inflammatory, and 3 (incl. mediator X) are also anti-fibrotic. The lipid mediator profile of MAT close to the proximal unaffected ileum was similar to that of creeping fat, except for a pro-inflammatory lipid being increased in creeping fat (FC=2.30, p=0.004) (Fig. 1B). Lastly, when evaluating the membrane and storage lipid abundances both at species level (sum notation; fatty acyl composition) and at class level, no paired-wise differences among the three adipose tissue locations were found (p>0.05).

Conclusion

In this pilot lipidomics study, we did not observe any changes in storage or membrane lipids in creeping fat as compared to paired unaffected MAT. In contrast, a decrease in anti-inflammatory and anti-fibrotic lipid species along with an increase in a pro-inflammatory species points towards a harmful microenvironment within creeping fat.Read more P050 Paneth cell retinoid X receptor alpha drives metabolic gut inflammationWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The rising incidence of inflammatory bowel diseases throughout the western world could be partially explained by changes in dietary behaviour such as an increased consumption of polyunsaturated fatty acids (PUFA). In previous projects we demonstrated that PUFA induce a Crohn’s disease (CD) like gut inflammation in mice lacking antioxidant GPX4 in their intestinal epithelial cells. Cellular stress within Paneth cells has been shown to drive enteritis in mice. In this project we investigated the role of the PUFA receptor and transcription factor RXRα as driver of PUFA induced metabolic gut inflammation.

Methods

We generated mice lacking GPX4 (GPX4^ΔPC) and GPX4 as well as RXRα (GPX4/RXRα^ΔPC) specifically in Paneth cells and fed them and littermate controls a Western-style diet enriched with PUFA (PUFA-WD). Mice were treated with 9-cis retinoic acid, HX531 or a neutralizing CXCL1 antibody. MODE-K cells (murine IECs) were stimulated with PUFA and were analysed by biochemical methods including ELISA, qPCR, ChIP and RNA sequencing for mechanistical workup in vitro.

Results

When stimulated with PUFA, GPX4 deficient IECs showed an increased activation of RXRα as well as an increased transcription and production of neutrophil attracting chemokine CXCL1, the murine homologue of IL-8. This could be attenuated by ablation of RXRα or treatment with HX531, an RXRα antagonist. By using ChIP we can demonstrate that RXRα is directly binding to the promoter region of CXCL1 upon PUFA stimulation, thereby regulating its transcription. GPX4^ΔPC mice develop a CD like enteritis with mucosal to submucosal infiltration of neutrophils, macrophages, B and T cells. GPX4/RXRα^ΔPC mice were protected from PUFA induced enteritis and gut inflammation could be significantly ameliorated by treatment of GPX4^ΔPC mice with RXRα antagonist HX531 or a neutralizing CXCL1 antibody after a PUFA-WD challenge. Moreover 9-cis retinoic acid treatment dose dependently blunted CXCL1 response and attenuated PUFA induced intestinal inflammation in GPX4^ΔPC mice, thus indicating a competitive binding of PUFA to RXRα.

Conclusion

Our findings reveal, that PUFA binding to RXRα within Paneth cells regulates the transcription of cytokines and is crucially involved in the development of diet induced metabolic gut inflammation. Future studies are now warranted to prove if RXRα could be a promising new druggable target in human CD patients.Read more P051 Diets enriched in fat and sugar and sex-dependant response to colitis in a mouse modelWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Inflammatory bowel diseases (IBD) are chronic diseases characterized by inflammation of the mucosa linked to an alteration of the intestinal microbiota and overreaction of the immune system. The prevalence of IBD is increasing in industrialized countries where we find a “Western Diet” rich in refined sugars and saturated fats but low in fiber and essential unsaturated fatty acids¹. Thus, nutrition seems to be an important environmental factor involved in the occurrence of IBD, however, underlying biological mechanisms are still poorly understood². Additionally, most studies on colitis focused on males, yet diets effects are often very different according to sex. The aim of this study was therefore to study the sex-dependent effect of a diet enriched in sugar (sucrose) and a diet rich in fat in a mouse model of colitis.

Methods

Male and female, 9-weeks old C57BL/6 mice were fed 3 diets for 8 weeks: control diet (C), high-fat diet (HF), and high-fat/high-sucrose diet (HFHS). Then, colitis was induced using 3% Dextran sodium sulfate (DSS) for 5 days and kept 5 more days without DSS. The animals were monitored and weighed daily to establish a disease activity index (DAI). Blood and stools were collected monthly from the start of feeding. At the end of the protocol, a colonoscopy was carried out for each group before sacrifice and intestinal tissues were collected.

Results

DSS-induced colitis was earlier and more severe in both males and females fed high-caloric diets (both HF and HFHS). However, the HFHS diet accelerated DSS-induced colitis in males compared to the HF diet, while the HF diet led to more severe DSS-induced colitis than the HFHS diet in females. Males and females had similar weight gain following the high-caloric diets.

Conclusion

This difference in response to DSS after consumption of high-caloric diets between males and females indicates that the inflammatory mechanisms seem to differ depending on sex. Recent work reports the same sex-dependent effect in the Il10-/- mouse model³, suggesting that the sex has an impact on the pathophysiology of colitis and is essential to consider when studying IBD.

References

1. Arnone D, et al. Sugars and Gastrointestinal Health. Clin Gastroenterol Hepatol. 2022 Sep;20(9):1912-1924.e7.2. Arnone D, et al. Long-Term Overconsumption of Fat and Sugar Causes a Partially Reversible Pre-inflammatory Bowel Disease State. Front Nutr. 2021 Nov 18;8:758518.3. Maite CB, et al. The Effect of Sex-Specific Differences on IL-10-/- Mouse Colitis Phenotype and Microbiota. Int J Mol Sci. 2023 Jun 20;24(12):10364.Read more P080 High faecal pH and low total microbial load associate with normalisation of faecal calprotectin in children with Crohn’s disease treated with exclusive enteral nutrition; results from iPENS, a multicentre, prospective studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Exclusive enteral nutrition (EEN) is a main therapy for active Crohn’s disease (CD) in children, but normalisation of faecal calprotectin (FCAL) varies among patients, even in those who enter clinical remission. To better understand disease characteristics related to EEN efficacy and its mechanism of action, we compared clinical and microbial parameters between patients whose FCAL normalised against those who did not at EEN completion.

Methods

Children with CD, clinically responding to EEN, were recruited from 11 UK hospitals (January 2020- May 2023, NCT04225689) and provided a single faecal sample before EEN completion. Patients were divided in two groups according to levels of FCAL at EEN completion (FCAL<250 and FCAL>250 mg/kg). Levels of faecal short chain fatty acids (SCFA), faecal sample characteristics (pH, water content (%), bristol stool score) and total microbial load (qPCR) were compared between the two groups. Anthropometric and clinical parameters (blood inflammatory markers, use of immunosuppressants, disease duration, disease location) were also compared. Machine learning using feature elimination with data imputation for missing data was performed to identify associations between clinical, anthropometry, microbial parameters and FCAL normalisation.

Results

At EEN completion, 84 children (female, 35%) were recruited [age, median (IQR): 13.2 (11.8, 14.9 years)] with a median (Q1, Q3) FCAL of 643 (146, 2033) mg/kg. Out of 84 patients, 35 (42%) had an FCAL<250 mg/kg. Total microbial load and SCFA were measured in a subset of patients (n=44). Patients with FCAL<250mg/kg had a higher faecal pH and lower microbial load compared to those with FCAL>250mg/kg [faecal pH; FCAL<250 mg/kg: 8.3 (8.1, 8.6) vs FCAL>250 mg/kg; 7.95 (7.6, 8.3), p=0.001; microbial load (log10 16S rRNA gene copies/g): FCAL<250mg/kg: 10.7 (10.4, 10.9) vs FCAL>250mg/kg: 11.0 (10.5, 11.2), p=0.02]. Median BMI z-score was also non-significantly (p=0.052) higher in patients with FCAL<250mg/kg. The use of immunosuppressants at EEN completion, disease duration, disease location and other faecal parameters were not different between the two groups. A multicomponent random forest model (clinical, blood inflammatory markers, anthropometry, faecal parameters) predicted normalisation of FCAL with 71% accuracy (sensitivity: 69%, specificity: 71%, p=<0.001, Figure 1). Higher faecal pH, BMI z-scores and lower total microbial load were the most influential parameters relating to FCAL<250mg/kg.

Conclusion

We showed that the efficacy of EEN in reducing gut inflammation might be, at least in part, mediated via reducing gut bacterial biomass and modulating luminal pH and the downstream effects this may have on inflammatory members of the microbial community.Read more P081 The integration of transcriptomic and microbiomic data links several intestinal bacterial families with key biological functions in the development of postoperative recurrence in Crohn's diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Crohn's disease (CD) is characterized by an imbalance between the microbiota and the host. The severity of CD leads to intestinal resection. However, more than half of the patients not receiving prophylaxis experience post-operative recurrence (POR) within one year. The main objective of this study has been to improve the knowledge of the pathophysiological bases of POR through the integration of transcriptome and microbiome data.

Methods

Samples of inflamed and microscopically non-inflamed ileal mucosa were collected from patients with CD undergoing intestinal resection. The severity of POR was classified according to the Rutgeerts endoscopic index: without recurrence (i0+i1, n=12) and with recurrence (i2+i3+i4, n=8). Samples of healthy ileal tissue were also obtained from patients with colorectal cancer (n=10). Gene expression was evaluated by microarrays and organized into co-expression modules. By sequencing the V3-V4 region of the 16S rRNA gene, intestinal bacteria were identified and classified at the genus and family taxonomic level. The differential expression and correlations between the two sources of omics information were studied. Next, the analysis of pathway enrichment and clustering was carried out according to the severity of the POR and the intestinal area affected or not (graphical abstract A).

Results

The results of the integrative analysis in the uninflamed area of patients without recurrence showed that Actinomycetales negatively correlated with COX6A1 and MTRF1L, related to mitochondrial respiration (GO:0098803; q=0.004) and protein synthesis (R-HSA-72766; q=0.034) (B). These genes and bacteria also played a key role in modules 3 and 25 related to the respiratory chain. In contrast, the inflamed area of recurrent patients showed a positive correlation of the Xanthomonadaceae family in the regulation of neutrophil granules (GO:0035579; q=0.011), with the key participation of the ITGAM transcript (C). This transcript was also related to integrins (R-HSA-216083; q=0.007) in the transcriptomic analyses. In addition, Porphyromonadaceae correlated with LSR and TFF1, involved in epithelium maintenance (GO:0010669; q=0.012) and A group in the Lachnospiradaceae family correlated with CDC20 and CDT1, linked to the cell cycle (q=0.019).

Conclusion

Bacterial families, involved in butyrate production, such as Porphyromonadaceae and Lachnospiradaceae, could influence functions that remember to epithelial regeneration in recurrent patients, while Actinomycetales are associated with a normalization in energy production in uninflamed areas of resections of patients without POR. These findings reveal a potential interaction between the microbiota and the pathophysiology of POR in patients with CD.Read more P082 Downregulated apelin expression in T cells in the setting of Chronic ColitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

APJ is a G protein-coupled receptor and was originally found as an orphan receptor. Isolation of apelin (APL) from the alimentary tract was found to be the endogenous ligand for APJ. It has been reported that APL is upregulated in the colonic tissues of a murine model of acute colitis induced by dextran sodium sulfate (DSS), and thus it may be suggested to be associated with the pathogenesis of inflammatory bowel diseases (IBD) in humans. However, the mechanism and function of APL in the context of IBD are still not understood. Here, we analyzed APL expression in an animal model of chronic colitis to define its function in the pathogenesis of IBD.

Methods

Each cell type in the colonic tissue, including epithelial cells and lamina propria lymphocytes, were first isolated from wild type C57BL6 mice (WT) to assess APL expression. Next, naïve T cells isolated from WT were adoptively transferred into Rag deficient mice (Rag^-/-) to induce chronic colitis, and then APL expression was measured either in the colonic tissue or in the isolated splenic and colonic CD4⁺ T cells from these T cell-reconstituted Rag^-/- to compare with those of WT or Rag^-/- without colitis. In addition, WT naïve T cells were differentiated into either Th1, Th2 or Th17 in vitro to analyze APL expression. Finally, the Rag^-/- receiving naïve T cells were administered a synthetic APL peptide, APL-13, to assess the severity of colitis.

Results

Semi-quantitative PCR (qPCR) revealed that CD4⁺ T cells express relatively higher level of APL compared to other cell types including the epithelial cells in colonic tissue from WT. However, APL expression in the colonic tissues from the Rag^-/- induced chronic colitis was unexpectedly downregulated compared to control groups without colitis; this is not consistent with the previous report using acute DSS colitis model. Subsequently, qPCR revealed significantly decreased APL expression in the splenic and colonic T cells from Rag^-/- induced colitis compared to that of WT. APL expressions in the effecter T cells in vivo and all of the differentiated T cells in vitro were also significantly downregulated compared to naïve T cells and non-differentiated control T cells, respectively. Given these results, APL-13 was injected into the Rag^-/- that underwent T cell reconstitution to antagonize the APL downregulation. This resulted in reduced severity of colitis compared to that of vehicle control-injected group.

Conclusion

These results suggest that T cells can be one of the major sources of APL in colonic tissues, and APL downregulation in effecter T cells may lead to the development of chronic colitis. In addition, this study also suggests that APL may be a novel therapeutic target for IBD.Read more P083 Dietary-derived ω-3 and ω-6 polyunsaturated fatty acids trigger an inflammatory response in intestinal epithelial cells with chemically inhibited GPX4 activityWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The incidence of inflammatory bowel diseases (IBD) has increased drastically in recent years, which is mainly explained by environmental factors and changes in our diet. Recent studies indicated that a Western-style diet, characterized by an increased caloric intake and consumption of long-chain fatty acids such as polyunsaturated fatty acids (PUFAs), triggers inflammation in metabolic active tissues, termed metabolic inflammation. We recently demonstrated that ω-3 and ω-6 PUFAs fuel an inflammatory response in intestinal epithelial cells (IECs) with genetically reduced expression of the anti-oxidative enzyme glutathione peroxidase 4 (GPX4), and similarly a Western-style diet enriched with PUFAs triggered severe enteritis in mice with reduced GPX4 specifically in IECs (i.e., Gpx4^+/-IEC mice). Here, we investigated if PUFAs similarly trigger an inflammatory response in IECs with chemically inhibited GPX4 activity.

Methods

Experiments were performed with an immortalised murine IEC line (MODE-K) cells. Cells were stimulated with the ω-3 PUFA stearidonic acid (50 µM), the ω-6 PUFA arachidonic acid (20 µM) or a respective control and the GPX4 inhibitor (1S,3R)-RSL3 (RSL3). Cell death, production of inflammatory cytokines, stress at the endoplasmic reticulum (ER) and activation of mitogen-activated protein kinases (MAPKs) were examined.

Results

Treatment with RSL3 induced cell death in IECs in a dose dependent manner. For further experiments, we worked with 20 nM RSL3, as this concentration already induced some amount of cell death but approximately 75% of cells were still viable. Stimulation with both ω-3 and ω-6 PUFAs triggered the production of interleukin 6 (IL-6) and chemokine (C-X-C motif) ligand 1 (CXCL1) in RSL3 co-treated IECs. Moreover, co-treating of RSL3 and PUFAs induced ER stress and activation of the ER stress sensor inositol-requiring enzyme 1 alpha (IRE1α), an inflammatory signalling hub, in IECs which was paralleled by the activation of MAPKs and especially the c-Jun N-terminal kinase (JNK) branch.

Conclusion

Our findings demonstrate that the chemical inhibition of GPX4 was sufficient to fuel inflammation in IECs in response to PUFAs, which we previously similarly observed in IECs with genetic depletion of Gpx4.Read more P084 Natural extracts and omega-3 derived molecule: role in resolution of intestinal inflammationWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

In the last years there is a great interest in the characterization of natural compounds extracted from plants or omega-3 derived molecules for their possible therapeutic effects. In this scenario, the seeds of Nigella sativa and Nigella orientalis (plants with great relevance in North African traditional medicine) have shown beneficial effects in reducing inflammation. Similarly, the addition of Maresin 2 (pro-resolving mediator) to experimental animals improved symptoms in various models of inflammation. However, there is no information on the role that these potential therapies may play in the cellular and molecular processes leading to the resolution of inflammation at the intestinal level.

Methods

Eight-week-old female C57Bl/6 mice (n=30) were subjected to a DSS-induced colitis model; mice received 1.8% (weight/volume) DSS in the drinking water for 6 days followed by 6 days of regular drinking water. Mice were treated from day 5 to day 12 with vehicle, Nigella Sativa, Nigella Orientalis, and Maresin-2. After that, histology studies, flow cytometry, expression analysis and migration experiments were performed.

Results

In all the treatment groups there was a significant reduction in weight loss and improved DAI scores compared to control group. Significant differences were also observed in the epithelial score and in the infiltration score. Analysis of the immune cell infiltrate revealed that only neutrophil numbers were downregulated after the administration of the indicated treatments. Further in vivo and in vitro studies demonstrated that Nigella Sativa and Nigella Orientalis were able to decrease neutrophil viability and migration. By contrast, Mar2 seemed to affect neutrophil infiltration through indirect mechanisms and by regulating the expression of chemotactic factors

Conclusion

Overall, our study reveals novel compounds able to regulate the resolution of intestinal inflammation in vivo, and this occurs, by the modulation of neutrophil presence into the colon lamina propria.Read more P085 Tc17 cells with a distinct immune signature do not correlate with response to therapy with ustekinumab or TNF antibodies in active Crohn’s DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

IL-17 producing CD8⁺ T cells (Tc17) expressing a specific immune signature (CD6^high, CD39, CD69, PD-1, CD27^low) were shown to be associated with active Crohn’s Disease (CD) and inform flare free survival. Here, we addressed the question whether Tc17 cells and their signature also correlate with response of CD patients to therapies with antibodies targeting TNFα or IL-12/23.

Methods

Peripheral blood mononuclear cells were longitudinally collected from CD patients prior to and up to 35 weeks after initiation of therapy with either TNF antibodies or ustekinumab and CD8⁺ T cells were analyzed by flow cytometry. Results were correlated with clinical outcomes.

Results

We analyzed dynamic changes during treatment in blood samples of 36 CD patients initiating anti-TNF (n = 14) or ustekinumab therapy (N = 22). Baseline Tc17 frequencies differed between ustekinumab and anti-TNF treatment groups, with significantly higher frequencies in the ustekinumab group. This may be due to differences in the baseline patient characteristics; while ustekinumab treated patients were all previously treated with anti-TNF-antibodies, most of the anti-TNF treated patients were naïve to biologics. Indeed, Tc17 frequencies increased during anti-TNF treatment, while Tc17 frequencies were reduced at follow up in the ustekinumab group. However, Tc17 frequencies in the peripheral blood at baseline did not correlate with response to either therapy, nor did the frequencies of Tc17 cells expressing Tc17 signature proteins. The expression of Tc17 signature proteins by IL-17A producing CD8⁺ T cells did not change significantly during follow up, suggesting that the Tc17 signature was preserved during anti-TNF and ustekinumab therapy. We did not observe major changes in the production of pro-inflammatory cytokines by Tc17 cells during therapy.

Conclusion

Our data suggest that despite playing a pathogenic role in CD, Tc17 cells with a distinct immune signature do not directly correlate with response to therapy with anti-TNF agents or ustekinumab. However, anti-TNF therapy may skew CD8 T cell differentiation towards a Tc17 phenotype, which may have an impact on long term disease outcomes and should be investigated further.Read more P086 Identification of a Novel Immunometabolic Target and Agonist for PLXDC2 for Amelioration of DSS Colitis Model in MiceWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

PLXDC2 is expressed on the cell surface of macrophage, dendritic and specific mesenchymal and epithelial cells whose activation shifts cellular metabolism and reduces oxidative stress to rebalance the immune response and decrease inflammation. It’s role in IBD pathogenesis is unknown. PLXDC2 activation improves disease severity in rheumatoid arthritis models¹, while loss of PLXDC2 exacerbates the severity of disease in DSS colitis². PX-04 is a novel, first-in-class, orally active PLXDC2 agonist. Here, we report on the consequences of activating PLXDC2 using PX-04 in an acute DSS colitis model.

Methods

Mice were given DSS in drinking water for seven days to induce disruption of the epithelial layer. At project initiation, mice were 8 weeks of age and began once daily dosing with 20mg/kg of PX-04 24 hours after being placed on DSS. Mice were weighed and scored daily for 15 symptoms of disease (weight loss, diarrhea, rectal bleeding, rectal inflammation, pain, & overall behavior). Colons were collected and digested, and the resultant cellular suspensions were filtered to produce single cell suspensions. Colonic Lamina Propria Immune cells were isolated by Percoll gradient centrifugation. Cells were labeled with mixtures of extracellular (CD45, CD3, CD4, CD8, CD19, NK1.1, CD25, F4/80, CD11b, Gr1, CX3CR1, CD64) and intracellular (Tbet, RORγT, FOXP3, IFNγ, IL17, IL10, TNFα) antibodies in a sequential live staining in 96-well plates. Data was acquired using a FACS Celesta flow cytometer with FACSDiva software.

Results

Oral PX-04 treatment decreased the cumulative disease activity of mice challenged with DSS (FIG 1A). Immunologically, PX-04 affected both the adaptive and innate immune responses. First, PX-04 greatly decreased Th17 cells in the colon, while providing a slight increase to regulatory CD4+ T cells (FIG. 1C). A lower proportion of Natural Killer (NK) cells (FIG. 7D) produced IFNγ. Meanwhile, the proportion of TNF producing dendritic cells was decreased by PX-04 treatment.

Conclusion

Conclusion: PLXDC2 is expressed in cells relevant to IBD pathogenesis. PX-04, which binds to and activates PLXDC2, effectively decreases levels of effector T cells and myeloid cells, as well as overall disease severity in acute DSS colitis, warranting further investigation.¹Tubau-Juni et al. J Immunol 206(Supp)²Tubau-Juni et al. Sci Rep 10(1)Read more P087 IFN-γ-Induced Intestinal Epithelial Cell Type-Specific Cytotoxic Responses of Human Enteroids: PANoptosis and The Protective Role of Selective JAK1 InhibitorsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Interferon-gamma (IFN-γ) plays an important role in the development of intestinal injury and inflammatory bowel disease (IBD). Using human intestinal organoid (enteorid) models, this study was investigated 1) what is the major response of intestinal epithelial cells (IECs) induced by IFN-γ to elucidate; 2) which programmed cell death (PCD) pathways cause IFN-γ-induced cell death on IECs in the absence of intestinal microbiota and immune cells; 3) how the expression of cell-cell adhesion molecules in epithelial cells is altered by IFN-γ; 4) how epithelial cell differentiation is altered by IFN-γ; 5) whether there is a difference in IFN-γ-induced PCD between different epithelial cell types; and 6) which molecules can block IFN-γ-induced PCD in IECs.

Methods

Using human enteroids, the major response of IECs induced by IFN-γ was evaluated, focusing on the IFN-γ-induced PCD pathway. The intestinal epithelial cell type-specific response to IFN-γ was assessed by bulk and single-cell RNA sequencing (RNA-seq). Furthermore, the molecules to block IFN-γ-induced PCD in IECs were evaluated.

Results

As the concentration of IFN-γ in the culture media increased, disruption of organoid structure, growth arrest, and cell death were observed in IFN-γ-treated enteroids on organoid reconstitution, MTT, and EdU assay. Bulk RNA-seq and western blot were identified the activation of pyroptosis, apoptosis, and necroptosis to form the collective inflammatory cell death pathway of PANoptosis. Single-cell RNA-seq indicated that IFN-γ altered epithelial cell differentiation in human enteroids, including expansion of the intstinal stem cell (ISC) population and depletion of the enterocyte population. PCD-associated gene expression was upregulated in enterocytes and goblet cells, but not in ISCs and paneth cells. Individual PCD inhibitors may be insufficient to prevent IFN-γ-induced cytotoxicity, whereas upadacitinib interferes with the downstream signaling of IFN-γ by inhibiting the activity of JAK1 kinase, resulting in effective blocking of PANoptosis.

Conclusion

PANoptosis is the major mechanism of IFN-γ-induced IEC damage, which was blocked by a selective JAK1 inhibitor. ECs were particularly susceptible to IFN-γ-induced PANoptosis.* This work was supported by the National Research Foundation of Korea(NRF) grant funded by the Korea government(MSIT) (2022R1A2B5B02002092 and 2021R1C1C2095192) and Future Medicine 2030 Project of the Samsung Medical Center (SMO1230011).Read more P138 Novel serum markers for predicting disease activity in ulcerative colitis: results from a retrospective case-control studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Commonly used serum or faecal markers, such as C-reactive protein (CRP) and feacal calprotectin have several limitations and do not always correlate well with the degree of mucosal inflammation in the intestine as established by endoscopy. The aim of the current study was to evaluate the utility of a panel of serum markers (Visfatin, serum amyloid, LRG1, MMP-1, MMP-2, TFF3, Lipocalin-2 (NGAL), IL-6, IL-4, IL-7, IL-17) in predicting mucosal inflammation in ulcerative colitis(UC) patients.

Methods

We conducted an unmatched case-control retrospective study. Patients were selected consecutively, based on their enrollement date, from a prospective IBD cohort. We selected two groups of UC patients, each of them with active disease at baseline and different outcomes during follow-up: mucosal healing and persistant disease activity, as resulted from clinical and endoscopic evaluation. Inflammatory burden was investigated using the C-reactive protein and endoscopic activity was reported using the Mayo endoscopic score. Quality of life was also evaluated at each visit using The Short Inflammatory Bowel Disease Questionnaire (SIBDQ). Clinical disease activity was quantified using the partial Mayo score^. Clinical remission was defined as a partial Mayo score < 2. Endoscopic activity was assessed using the Mayo endoscopic score^[i] . Mucosal healing was defined as Mayo endoscopic score of 0. The selection of investigated biomarkers was based on the results of a systematic review previously published by the research team [i] State M, Negreanu L, Voiosu T, Voiosu A, Balanescu P, Mateescu RB. Surrogate markers of mucosal healing in inflammatory bowel disease: A systematic review. World J Gastroenterol. 2021 Apr 28;27(16):1828-1840. doi: 10.3748/wjg.v27.i16.1828.

Results

84 serum samples from 42 patients were retrospectively analyzed (21 patients with mucosal healing and 21 patients with persistant activity during follow-up). Lipocalin proved to be a reliable marker for the noninvasive assessment of endoscopic activity, with 90% sensitivity and 95% specificity at a cut-off level of 0,421μg/ml (AUROC 0,677). The combination of lipocalin, age, gender and BMI (Figure 1) is a good predictor of persistant activity during follow-up (AUROC 0.87, 95% CI, 0.762-0.979).

Conclusion

Our findings provide support for the use of lipocalin as a surrogate marker for mucosal inflammation. The combination of lipocalin, age, gender and BMI might be useful for guiding treatment and monitoring decisions.Figure 1Predictive value of gender, age, BMI and lipocalin for persistence of disease activity during follow-upRead more P139 A potential protective rule of Mannose Binding lectin (MBL) against SARS-COV2 infection in IBD patientsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Since the beginning of the COVID-19 pandemic, IBD patients have appeared to be less susceptible to a severe form of the disease, despite undergoing immunosuppressive treatments. Mannose binding lectin (MBL) is a humoral fluid-phase pattern recognition molecule (PRM) crucial for activating the lectin complement pathway. It is capable of binding to the spike protein and blocking SARS-CoV-2 infection. Low MBL expression has been linked to poor outcomes in both SARS and SARS- CoV-2 infections. In IBD patients, the role of MBL is controversial; low concentrations seem to predispose individuals to the development of IBD, while high concentrations have been observed in severe forms of Crohn's disease.

Methods

Since April 2020, 104 IBD patients have been enrolled, with 20% treated with mesalazine, 50% with Anti-TNFa, 20% with Vedolizumab, and 20% receiving no treatment. Additionally, 45 healthy controls (HC) from North Italy were included. Serum samples and colon biopsies from inflamed and non- inflamed mucosa were collected. Serum samples underwent an ELISA test to quantify circulating MBL concentration, and MBL gene expression in biopsies was analyzed using qPCR.

Results

Both Crohn's disease and Ulcerative Colitis patients exhibited significantly higher circulating MBL levels than HC (411.6 ± 45.5 ng/ml vs. 160.9 ± 35.3 ng/ml, p < 0.05). Patients treated with Anti-TNFa showed significantly higher circulating MBL levels compared to those not undergoing therapy (530.1 ± 76.5 ng/ml vs. 225.4 ± 61.6 ng/ml, p < 0.05) and patients receiving Vedolizumab (530.1 ± 76.5 ng/ml vs. 155.3 ± 32.1 ng/ml, p < 0.05). MBL intestinal gene expression is higher in IBD patients than HC (5.55 ± 0.9 vs. 2.36 ± 0.6; p=0.591) and tended to be elevated at similar levels in inflamed and non-inflamed mucosa (5.14 ± 1.4 vs. 5.79 ± 1.1; p=0.337), suggesting a prevalent genetic determination of MBL concentration regardless of the inflammatory background.

Conclusion

MBL appears to play a key role in SARS-CoV-2 infection. We demonstrate that IBD patients have, on average, higher circulating MBL levels than HC independently of their inflammatory status. The highest MBL levels were observed in patients treated with Anti-TNFa. These findings contribute to understanding the reported low mortality and hospitalization for COVID-19 among IBD patients treated with Anti-TNFa.Read more P140 Serum Metabolomic Biomarkers Can Identify and Characterize Associated Subtypes and Phenotypes in Inflammatory Bowel DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Metabolomics is increasingly recognized for uncovering pathophysiology and identifying diagnostic and prognostic biomarkers in inflammatory bowel disease (IBD). This study focuses on exploring comprehensive serum metabolomic profiles and corresponding specific metabolic pathways, in order to differentiate IBD patients from healthy individuals and to accurately identify IBD subtypes (Crohn's disease [CD], ulcerative colitis [UC]) through serum biomarkers with high patient acceptability.

Methods

Serum samples with matched clinical metadata were comprehensively collected from patients with IBD at Kyung Hee University Hospital, Seoul, Korea. Corresponding samples from normal controls (NCs) were obtained for comparison. Untargeted profiling was performed with Gas Chromatography-Time-Of-Flight-Mass Spectrometry, and targeted profiling of bile acids and tryptophan used Liquid Chromatography-Triple Quadrupole-Mass Spectrometry. The identification of distinct metabolites and potential biomarkers was achieved through extensive univariate and multivariate statistical analyses. Receiver operating characteristic (ROC) curves and metabolic pathway analyses were also conducted.

Results

A total of 346 subjects were analyzed, comprising 258 IBD patients (134 with CD and 124 with UC) and 88 NCs, Table 1. The patients with IBD were clearly clustered from the NCs, while IBD subgroups were not clearly separated from each other in the nontargeted profiling. Tryptophan and indole-3-acetic acid were elevated in both patients with CD and UC, while kynurenine and indole-3-propionic acid increased only in CD. Conversely, patients with UC had lower levels of indole-3-acetic acid, serotonin, and acetylcholine compared to CD. The ratio of primary and secondary bile acids was also significantly decreased in both patient groups compare with NCs. The ROC curves (Figure 1A) showed good discriminatory power for NCs vs CD (AUC:0.9738), NCs vs UC (AUC:0.9887), and UC vs CD (AUC:0.7140). Pathway analysis of the identified metabolites showed a sustained change in glyoxylate and dicarboxylate metabolism/alanine, aspartate and glutamate metabolism/glycine, serine and threonine metabolism associated with all comparisons (NCs vs UC, NCs vs CD, UC vs CD). Beta-alanine, arginine, and proline metabolism were linked to IBD compared to NCs. Glycerolipid metabolism distinctly differed between UC and CD (Figure 1B-1D). Network analysis revealed associations between metabolomic markers and specific clinical phenotypes of IBD subtypes.

Conclusion

This study demonstrates that serum metabolomic biomarkers are novel and effective tools for diagnosing IBD, as well as for identifying and characterizing its subtypes and associated phenotypes.Read more P141 Engineered probiotics treat inflammatory bowel disease by releasing all trans retinoic acid in the intestineWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

All trans retinoic acid (ATRA) is a potential candidate drug for the treatment of inflammatory bowel disease (IBD). ATRA can affect multiple pathways involved in the pathogenesis of IBD by binding to retinoic acid receptors. However, the shortcomings of poor compliance and significant side effects in patients who directly use ATRA limit its clinical application.

Methods

Here, we have developed a live biotherapeutic products (ELBPRA) based on synthetic biology methods for controllable delivery of ATRA on the gut. We first expressed four enzyme genes required for the synthesis of β-carotene, a precursor of retinoic acid, in Escherichia coli Nissle 1917 (EcN). In addition, we introduced the exogenous synthesis pathway of isopentane pyrophosphate into EcN to increase the yield of β-carotene. Then, β-carotene oxygenase and retinal dehydrogenase, were expressed in EcN to convert β-carotene into retinoic acid. However, considering the poor solubility of retinoic acid, we knocked out some genes related to vesicle formation in the EcN genome to increase extracellular production of retinoic acid. Finally, we investigated the therapeutic effect of ELBPRA using a colitis model induced by sodium dextran sulfate (DSS).

Results

ELBPRA continuously produces retinoic acid and delivers it in the form of vesicles. ELBPRA reduced weight loss and disease activity index in DSS-induced colitis. Similarly, the spleen index also demonstrates the effectiveness of ELBPRA in treating colitis. The ELBPRA intervention group reduced the degree of colon shortening in mice. In addition, ELBPRA improved crypt loss and disorder of crypt structure. Finally, we also evaluated the inflammatory cytokines in the serum. ELBPRA significantly increased the concentration of anti-inflammatory cytokine IL-10 and decreased the concentration of pro-inflammatory cytokine IL-1β and TNF-α.

Conclusion

Engineered probiotics ELBPRA can deliver retinoic acid in the form of vesicles to alleviate DSS-induced colitis in mice, which provides a safe and effective treatment strategy for ulcerative colitis.Read more P142 Genetic ablation of DNA methyltransferase 3A in myeloid cells impairs M1/M2 polarization and leads to pro-inflammatory macrophagesWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Genetic variants in the de novo DNA methyltransferase DNMT3A associate with increased risk for inflammatory bowel disease (IBD). While DNMT3A loss-of-function somatic mutations have been attributed to myelodysplasia and acute myeloid leukemia, the exact mechanisms how defective DNMT3A is linked to IBD remain elusive. Since macrophages are key gatekeepers for immune homeostasis, we aimed to characterize how DNMT3A loss affects monocytic lineage differentiation and inflammatory properties.

Methods

We generated mice lacking Dnmt3a expression in myeloid cells (Dnmt3a^LysM) using a LysM-driven cre-lox system and confirmed gene deletion by PCR and western blot of gut lamina propria CD11b⁺ enriched cells and 5-day in vitro differentiated bone marrow-derived macrophages (BMDM, 20ng/mL M-CSF). Four-day polarized BMDMs (resting: 20ng/mL M-CSF; M1: 50ng/mL LPS/IFNγ; M2: 50ng/mL IL-4/IL-13) were functionally characterized using RNA-seq, flow cytometry, and arginase and nitric oxide synthase (NOS) activities. FITC-labelled zymosan served to quantify phagocytosis, and co-culture with intestinal epithelial ModeK wounded monolayers to assess healing. To evaluate Dnmt3a loss during inflammation in vivo, colitis was induced using dextran sodium sulfate (DSS).

Results

M2 polarization induces Dnmt3a expression in wild-type (WT) BMDMs while inflammatory stimuli decrease it. Dnmt3a-deficient BMDMs differentiated with IL4/IL13 in vitro increase ERK1/2 and PI3K signaling, decrease M2 markers and upregulate inflammatory transcripts, e.g. Irg1,Tnf compared to WT cells. IL4/IL13 treated BMDMs confirmed M2 polarization defects as they acquire morphological and functional M1-like features in the absence of Dnmt3a, especially those from aged (>34 weeks old) mice, e.g. failed spindle M2 morphology, increased phagocytosis, decreased arginase and increased NOS activities. In co-cultures, IL4/IL13 treated Dnmt3a^LysM BMDMs inhibited intestinal epithelial regeneration after a scratch lesion compared to M2 WT BMDMs. Increased NOS activity was also detected in M1-polarized BMDMs from aged Dnmt3a^LysM mice. In vivo, young Dnmt3a^LysM mice display mildly increased splenic T-cell and decreased monocyte numbers. Aged Dnmt3a^LysM mice (>34 weeks) exhibit altered bone marrow morphology and hepatosplenomegaly linked to increased myeloproliferation. Dnmt3a^LysM mice already at young age displayed increased sensitivity to both acute and chronic DSS colitis.

Conclusion

Normal Dnmt3a function is required for physiological macrophage polarization. Deletion of Dnmt3a in mice leads to a pro-inflammatory skewing particularly after M2-inducing cytokines IL4 and IL13. Our findings provide insights on how DNMT3A – via its specific function in myeloid cells – contribute to IBD pathogenesis.Read more P143 Efficacy of the oral tyrosine kinase 2 (TYK2) inhibitor TAK-279 in two preclinical mouse models of colitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Tyrosine kinase 2 (TYK2), a member of the Janus kinase (JAK) family, is required for the downstream signalling of interleukin (IL) 12 and 23, and interferons (IFN) α/β, which are involved in the pathogenesis of several autoimmune diseases, including inflammatory bowel disease (IBD).¹ JAK inhibitors are approved for treatment of IBD, but their dosing levels may be limited due to adverse effects related to JAK1–3 inhibition. TAK-279 is a highly-selective, oral, allosteric TYK2 inhibitor, which binds to the JAK homology 2 pseudokinase domain of TYK2, but not JAK1–3.^1,2 This study assessed the efficacy of TAK-279 in two IL-23-dependent preclinical mouse models of colitis induced by (i) adoptive T-cell transfer (TCT) and (ii) anti-CD40 monoclonal antibody (α-CD40 mAb).

Methods

In the TCT colitis model, CD4⁺CD45RB^hi T cells were transferred to severe combined immunodeficient mice at Day 0, and disease progression followed for 48 days. In the α-CD40 colitis model, T- and B-cell-deficient Rag2^-/- mice were challenged with agonistic α-CD40 mAb at Day 0, and disease severity analyzed on Day 7. Mice were divided into four groups per model (n = 12–16 and n = 10 per group in the TCT and α-CD40 models, respectively) to receive vehicle (negative control) or TAK-279, orally, twice-daily, at doses intended to provide either 24hr IC₉₀ (high dose) or IC₅₀ (low dose) coverage, or once-weekly intraperitoneal α-IL-12/23 p40 mAb (positive control). At the end of the treatment period, colonic tissue was obtained; colon weight:length (CWL) ratio, total histology score (THS) and transcriptomic analysis were used to assess efficacy and mechanism of action. Statistical significance of differences between groups was determined using analysis of variance with Tukey’s post hoc test.

Results

In both models, TAK-279 was maximally efficacious at the IC₉₀ dose; CWL ratio and THS were significantly reduced relative to vehicle and the response was comparable with α-IL-12/23 p40. IC₅₀ dosing was not sufficient in the α-CD40 model and IC₉₀ dosing was required for significant efficacy (Figure). Transcriptomic analysis showed TAK-279-dependent downregulation of genes associated with cytokine signalling, including those related to T-helper 17 cell phenotypes and the IFN α/β pathway.

Conclusion

TAK-279 was efficacious in two preclinical mouse models of colitis and induced relevant cytokine signalling changes; IC₉₀ coverage provided maximal efficacy in both models. These results support the potential role of potent and selective TYK2 inhibition for the treatment of IBD, where TAK-279 is expected to achieve IC₉₀ coverage in humans.1. Leit S et al. J Med Chem 2023;66:10473–96.2. Gangolli EA et al. STAT 2022;1:5.Read more P144 Modulation of Immunometabolism via NLRX1 or PLXDC2: Novel Bimodal Mechanisms for the Treatment of Inflammatory Bowel DiseasesWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Immunometabolism exerts a bimodal action at the interface of extracellular immune response and intracellular metabolism. It controls both intracellular processes and extracellular inflammatory responses by regulating both cellular energy supply & demands, factors that determine how a cell responds to the extracellular signals. Hence, immunometabolic pathways represent an attractive target as a gate of entry & checkpoint for the inflammatory cascade. Nucleotide-binding oligomerization domain, Leucine Rich repeat containing X1 (NLRX1) & PLeXin Domain-Containing protein 2 (PLXDC2) have been identified in immunometabolic pathways for multiple cell types in immune mediated inflammatory diseases (IMIDs) and inflammatory bowel diseases (IBD)^2,3. The goal of this analysis was to compare these two key immunometabolic pathways.

Methods

For both programs, in vitro murine T cell & macrophage differentiation & in vivo mouse dextran sodium sulfate (DSS) colitis models, gene expression, metabolic profiles & cytokine expression were assessed.

Results

NX-13, a novel NLRX1 agonist, resulted in regulation of cellular metabolism: activation of mitochondrial genes such as mt-nd3 & odgh, and concomitant down-regulation of glucose uptake by murine T cells (Fig1A). Simultaneously, NLRX1 stabilization by NX-13 increased antioxidant enzyme expression & reduced reactive oxygen species in T cells. NX-13 specifically reduced effector T cell differentiation (Fig1B) & inflammatory cytokine expression, while Treg differentiation was increased. Ultimately, these bimodal effects converge to dampened colitis severity scores in acute DSS colitis (Fig1C). PLXDC2 activation by LABP-69 directly reduced glycolysis, reflected by decreased extracellular acidification & oxygen consumption in bone marrow-derived macrophages (BMDM) stimulated with lipopolysaccharide (LPS, Fig1D). LABP-69 also reduced superoxide levels in BMDM. Of note, PLXDC2 activation downregulated cellular expression of the inflammatory cytokines TNFα & IFNγ by T cells (Fig1E). The PLXDC2 agonist PX-04 decreased inflammation in acute DSS colitis in mice as shown by disease activity score (Fig1F).

Conclusion

Agents targeting immunometabolism demonstrate a novel, innovative concept with potential therapeutic applicability in IBD & other IMID. NLRX1 & PLXDC2 represent distinct pathways that modulate the intracellular metabolic state simultaneously with extracellular inflammation and hence can be targeted to break the inflammatory cascade to stop chronic inflammation. These bimodal MOAs will be studied further to understand how they may synergistically address multiple aspects of chronic immune diseases such as IBD.¹Chi Cell Mol Immunol (19)²Leber et al. J Immunol 203(12)³Tubau-Juni et al. J Immunol 206(Supp)Read more P145 Phagocyte responses to gut-derived C. albicans are modified in inflammatory bowel diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Fungi are a key component of the human gut microbiota and have been strongly implicated in the pathogenesis of inflammatory bowel disease (IBD). Candida albicans typically exists as a commensal yeast within healthy hosts but can form tissue-invasive filaments that secrete Candidalysin (CLYS) toxin to disrupt epithelial barriers. Dynamics of this morphological switch are influenced by genotypic and phenotypic variation of gut-resident C. albicans strains, which may impact host response and extent of mucosal inflammation.

Methods

C. albicans isolates were derived from healthy control (HC) and IBD gut biopsies. Phenotypic, genomic, and proteomic analyses were conducted on these isolates. To further understand host interplay with intestinal C. albicans under physiologically relevant conditions, a human ‘gut-on-a-chip’ system was developed to assess tissue invasion potential in vitro.

Results

IBD-derived isolates were more readily able to form filaments, displayed altered cell wall composition, and modulated expression of adhesion-associated genes including IHD1. Subsequent innate leukocyte responses to these strain-dependent profiles were investigated to understand impact on host immunity. When exposed to IBD-derived C. albicans strains, blood neutrophils from healthy donors displayed increased swarming behaviour and NETosis induction, whereas monocyte-derived macrophages released greater amounts of pro-inflammatory IL-1b. These responses were substantially diminished in neutrophils and macrophages from IBD patients, suggesting altered reactivity to fungal stimuli in disease settings. The gut-on-a-chip model system confirmed that IBD-derived strains display increased adhesion and translocation in a dynamic human gut environment.

Conclusion

Gut-adapted C. albicans strains from HC and IBD donors exhibit distinct biological profiles that impact on host immune responses and shape interactions with the gut barrier in a novel organ chip model.Read more P206 Metabolomic predictors of response to vedolizumab in Inflammatory Bowel DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Therapeutic options for patients with IBD have increased substantially over the last decades. Nevertheless, there is still an unmet need for optimization and more targeted allocation of therapies. Treatment with the anti-integrin-a4b7-antibody vedolizumab (VDZ) achieves clinical remission at week 6 in about 50 % of patients with CD and UC . Clinical decision support tools have been developed to help identify patients with a higher likelihood of responding to VDZ. Furthermore, exploratory studies reported associations of response to VDZ with differences in baseline multi-omics measurements. However, personalized selection of biologic therapies in IBD is not yet feasible in clinical practice.

Methods

IBD patients scheduled for therapy with VDZ (n=70, both biologic-naive and -experienced) were recruited and biosamples were obtained before initiating therapy. Response was assessed at week 20 using a multimodal definition incorporating clinical (Harvey-Bradshaw Index < 5 or partial Mayo Score < 2; no need for steroids after week 12) and biochemical criteria (faecal calprotectin < 250 µg/g). Metabolic assessment of baseline plasma samples was performed using a mass-spectrometry-based commercially available technique (Biocrates MxP Quant 500). Differences in absolute concentrations of 630 metabolites were measured and compared between patients responding and not responding to therapy using multivariate statistical approaches accounting for IBD subtype and patient sex.

Results

Significant differences between responders and non-responders to VDZ in the baseline concentrations of three metabolites were detected. These included acylcarnitine (HMDB00062) and a ceramide species (HMDB0004950) which were lower in patients who would respond to VDZ. Conversely, N-methylglycine (HMDB00271) was elevated in responders to VDZ. Additionally, dimensionality reduction using partial least-squares discriminant analysis (PLS-DA) revealed associations between the baseline abundance of certain primary and secondary bile acids and response to VDZ.

Conclusion

In this cohort of IBD patients undergoing therapy with VDZ, baseline host metabolomic variation was associated with response to therapy. Differences in metabolomic profiles are linked to established pathophysiologic processes in the intestine and IBD and represent intriguing possibilities for application in the context of a predictive biomarker signature for response to VDZ.Read more P207 It’s time to include capsule endoscopy to assess mucosal activity as part of the ‘treat-to-target’ strategy in Crohn’s disease: a real-life experience from a reference center in ArgentinaWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The evaluation of the small bowel (SB) in known Crohn’s disease (kCD) has a significant impact on prognosis with potential therapeutic implications. The treat-to-target strategy is widely accepted, emphasizing that endoscopic healing is associated with improved long-term outcomes. Although capsule endoscopy (CE) shows promise in monitoring the small bowel in kCD, there is limited evidence supporting routine use. The aim of this study was to investigate clinical utility of CE to assess activity and extension of kCD and to evaluate whether the results of CE modify the therapeutic decisions.

Methods

We conducted a single center retrospective cohort study. Adult patients submitted to CE for kCD from Nov-2012 to Nov-2023 were included. Data on demography, previous research, medications for IBD and follow-up were analyzed. Univariate analysis was carried out to identify CE features associated with changes in therapeutic management. A p value <0.05 was considered statistically significant.

Results

A total of 572 CE protocols were performed, of which 76 were in kCD adult patients. The mean age was 36 years (range 16–76), 59% were males and median disease duration was 5.4 years. The CE reached the cecum in 97% and retention was observed in only two patients (2.6%) without necessity of surgical removal. Thirty two of 76 CE protocols (42%) had findings consistent with mucosal activity of CD. The lesions identified by CE included ulcers 30 (39%), erythema and villous edema 21 (28%), stenosis 2 (3%) and were distributed mainly in the distal part of the SB (3rd tertile) in 27 (35%), but in 15 (20%) the proximal SB (1st and 2nd tertile) was also affected. The mean Lewis Score (LS) was 576 (135-5392). Normal or clinically insignificant inflammatory changes (LS <135) ruled out SB mucosal activity in 44 (58%) patients. The results of the CE modified therapeutic decisions in 29 (38%) patients as follows: 17 were started new biological therapy and 7 were optimized. CEs consistent with mucosal inflammatory activity (LS ≥135) were more frequently associated with changes in therapeutic management (OR: 11, 95% CI 4-35, p: 0.04). When both magnetic resonance enterography (MRE) and CE were utilized to assess SB mucosal activity, diagnostic yields of MRE and CE were 45% and 42% respectively. But of the 8 patients with proximal SB affected in CE, only 1 showed inflammatory activity in the MRE.

Conclusion

In our cohort, CE in patients with kCD added valuable clinical information and had a great impact on therapeutic decisions. These results suggest that CE could be incorporated into the treat-to-target strategy for patients with CD. However, randomized controlled trials are required to confirm this recommendation.Read more P208 Personalized Machine Learning Algorithm to Predict Ulcerative Colitis Disease Activity from Wearable DataWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Due to its ease of use and ability to determine complex information, wearables have been gaining popularity over the last decade. Smart rings such as Oura^TM present the ability to track metrics such as sleep quality, resting heart rate, body temperature, and daily activity. This is not only useful for the predicting disease activity in inflammatory bowel disease (IBD), but also to understand behavior changes that can be associated with disease activity. This study aimed to evaluate potential use for wearable data in IBD management.

Methods

Daily Oura^TM ring data of a patient with ulcerative colitis (UC) was collected from Oura^TM ring application programming interface from 2019 to 2023. Days were classified as “active disease” or “remission” based on patient symptoms, colonoscopies, and fecal calprotectin levels. Data was collected on the patient’s sleep metrics, activity levels, and daily vitals. Variables with >50% null values were not included in model training. A univariate analysis was conducted to determine features that correlated with flaring periods (p-value <0.3) [ABPM1] [AS2] to be included in model training. An XGBoost classifier was selected with the target variable being flare status. Boosting parameters were then hypertuned to optimize model performance. After hypertuning and kfold cross-validation, the model’s mean accuracy, mean logarithmic loss, and AUC was reported. Further analysis was conducted comparing remission, active disease and pre-diagnosis data.

Results

963 days were collected. 444 days were determined to be “flare” based on reported symptoms, 4 fecal calprotectin levels, 2 colonoscopies, and 1 intestinal ultrasound confirming disease activity. Remission was determined by no reported symptoms, 2 normal fecal calprotectin levels and a normal intestinal ultrasound. Generally, worse sleep quality, increased resting heart rate, increased respiratory rate, and deviations in activity levels were positively associated with disease activity. After model training with XGBoost classifier and 10-fold stratified cross-validation, the mean accuracy was 0.92 ± 0.08, mean logarithmic loss of 0.134 ± 0.11, and a mean AUC was 0.94 ± 0.02. The patient’s mean biometric values such as heart rate and respiratory appeared to recover to pre-diagnosis levels with the exception of heart rate.

Conclusion

Data from the OuraTM ring demonstrated the potential application of wearables in IBD management in a single patient with UC. The high accuracy and AUC of our XGBoost model demonstrates how individualized wearable data can be used to predict IBD flares. Prospective studies with multiple patients could be useful to consider wearables as an additional adjunct disease monitoring device in IBD.Read more P209 Work productivity and unmet needs of treated ulcerative colitis patients: A Japan National Health and Wellness Survey studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Ulcerative colitis (UC), a subset of inflammatory bowel disease (IBD), is a chronic, immune-mediated disease process which causes inflammation and ulceration of the large intestine. In Japan, the annual prevalence of UC in 2014 showed a ten-fold increase in more than 10 years. Despite current treatments, patient-reported disease challenges persist. This study investigated the disease burden and unmet needs of treated UC patients in Japan.

Methods

This cross-sectional, observational study used existing data from the online, self-administered Japan National Health and Wellness Survey conducted in 2017, 2019, and 2021. Respondents were aged ≥18 years, with self-reported UC and had undergone/were on treatment [5-Aminoslicyclic acid (5-ASA), steroids, immunomodulators (IMs), biologics (Bio)/Janus kinase inhibitors (JAKi), or others]. Data pertaining to demographics and clinical characteristics, medication adherence, health-related quality of life (HRQoL), work productivity and activity impairment (WPAI), and indirect cost were collected and analysed.

Results

Among 293 treated UC patients in Japan, most were conventional treatment users (84%) and 29% were living with UC for ≥15 years. Despite active treatment, 91% of patients reported UC as bothersome to a certain degree, 35% reported having moderate-to-severe disease severity post-treatment, and 55% reported ≥1 persisting UC symptom. Treated patients reported EuroQoL-5-dimension visual analogue scale scores of 68. Depression and anxiety were reported in ≥35% of patients and majority (68%) of employed patients reported work productivity impairment. On average, employed UC patients reported 30-40% WPAI on a weekly basis, resulting in a mean indirect cost of 1.12 million Japanese yen (€8,799) per patient annually. Males, moderate-to-severe disease activity, and low treatment adherence (<80%) were associated with increased WPAI (p<0.05). In comparison to 5-ASA users, Bio/JAKi users had the highest work impairment, while steroid and IM users had higher activity impairment (p<0.05).

Conclusion

The overall HRQoL scores were lower than the average Japanese healthy population and the indirect cost due to work productivity impairment was high, equating to approximately 1/5 of the average household income. Those with lower treatment adherence consistently reported the highest work and activity impairment. The findings implicate a high disease burden and unmet needs affecting Japanese UC patients despite currently available treatments, suggesting the importance of a new convenient treatment for optimising UC outcomes. Additionally, workplace accommodations and understanding of employers on UC could assist in improving work productivity of UC patients.Read more P210 Association between Non-Alcoholic Fatty Liver Disease and Related Factors in Patients with Idiopathic Chronic Ulcerative ColitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

UC is an immunomodulated inflammatory intestinal disease that can involve systemic or extraintestinal manifestations. Few studies have evaluated the possible association between UC and nonalcoholic fatty liver disease (NAFLD). However, the prevalence of NAFLD among patients with UC has been reported to be higher than in the general population. Objetive: To determine the frequency of NAFLD in patients with UC and the factors associated with the simultaneous presence of both diseases.

Methods

This was an observational, cross-sectional, relational, and analytical study that included 40 patients with UC. Data on demographics, clinical information, biochemical parameters, endoscopic findings, and histological features were collected for each patient. Disease activity was assessed using the Truelove and Witts scales, Mayo endoscopic scale, and Riley histological index. NAFLD was evaluated using transient elastography (FibroScan®), determining the controlled attenuation parameter (CAP) with a cutoff score of 248 dB/m to define steatosis. Hepatic fibrosis was considered when the measurement exceeded 6.5 kPa. The risk of steatohepatitis was estimated using the FAST index. Data were analyzed using the MyFibroScan® app, selecting "multi-etiology" as a parameter. Statistical analysis was performed using SPSS version 26, calculating correlation coefficients using Spearman's Rho. A value of p < 0.05 was considered significant.

Results

The clinical and demographic characteristics of the patients are described in Table 1. A positive correlation was found between CAP and Body Mass Index (r = 0.36; p = 0.02). Statistically significant differences were observed between CAP and Truelove and Witts scale (p = 0.02). Differences were also noted between kPa value (p = 0.03) and FAST index (p < 0.001) and the medical treatment used to control UC. No associations or correlations were observed between CAP, kPa, FAST index, and endoscopic or histological severity or other clinical characteristics of the patients.

Conclusion

The presence of NAFLD in patients with UC may be of metabolic origin, predominantly associated with overweight/obesity, and determined by the clinical-biochemical immunomodulated inflammatory activity of the disease and the concurrent treatment used. These findings highlight the importance of a multidisciplinary approach in the care of patients with UC.Read more P211 Impact of celiac disease on the outcome of Inflammatory Bowel DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Inflammatory bowel disease (IBD) and celiac disease (CeD) are digestive disorders that share common genetic, immunological, and environmental factors in their pathogenesis.

Objective

To investigate whether the concurrent diagnosis of CeD and IBD predisposes to a more aggressive phenotype of IBD.

Methods

A multicenter case-control study was performed including cases (celiac IBD) and controls (non-celiac IBD) (paired 1:2, matched for sex, year of diagnosis, and IBD type). CeD diagnosis was established if Marsh score was > 1. Disease phenotype and IBD outcomes, including mortality and neoplasm development, were ascertained from medical records.

Results

66 patients with celiac IBD (39 females; 30 ulcerative colitis-UC/6 indeterminate colitis-IC/30 Crohn disease-CD; age at diagnosis 30±14 years) and 132 matched non-celiac IBD patients (85 females; 68 UC/4 IC/60 CD; age at diagnosis 32±14 years) were included. The diagnosis of CeD was confirmed by gastroscopy and duodenal biopsy in 97% of cases, and the most common histological lesion was Marsh 3. Overall, there were no significant differences in the duration of IBD (median 11±8 years vs 9±8 years; p=0.81), IBD extension (UC (E1/E2/E3): 6 (20.7%)/14 (48.3%)/9 (31%) vs 19 (29.2%)/22 (33.8%)/24 (36.9%); p=0.39); CD (L1/L2/L3/L4): 17 (56.7%)/3 (10%)/8 (26.7%)/2 (6.7%) vs 27 (45%)/6 (10%)/23 (38.3%)/4 (6.4%); p=0.71), extra-intestinal manifestations (10 (15,2%) vs 20 (12,8%); p=0.96) and other autoimmune diseases (8 (12%) vs 16 (12.1%); p=1) between celiac and non-celiac IBD, respectively.In terms of disease outcome, no differences were found either globally or by IBD subtype in terms of perianal disease, use of mesalamine, exposure to immunomodulators, receipt of biologic agents, need for IBD surgery, and development of neoplasm during follow-up (Table 1). There was no mortality in any of the cohorts.

Conclusion

No significant differences in disease outcome were observed in patients with a concurrent diagnosis of CeD and IBD compared with non-celiac IBD patients. In our large multicenter cohort of patients with celiac IBD and IBD controls, coexisting CeD did not show an impact on the natural history of IBD.Read more P212 Evaluation of the accuracy of MR-Enterography and CT-Enterography in the preoperative measurement of small bowel segments affected by Crohn's Disease: a single center experienceWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The surgical treatment of Crohn's Disease (CD) must deal with heterogeneous intra-operative scenarios, multiple disease locations and the risk of short bowel syndrome related to repeated surgery. A precise preoperative assessment of the exact extension of the disease is essential to avoid extensive surgeries and to plan the best strategy.The aim of our study is to evaluate the accuracy of the pre-operative radiological assessment for predicting the intra-operative measurement of the affected bowel.

Methods

Consecutive patients underwent either first or repeated surgeries for ileocecal or ileal CD from November 2017 to April 2023 with an available preoperative radiological assessment trough (at most 3 months before) MR-Enterography (MR-E) or CT-Enterography (CT-E) were retrospectively included. Radiological examinations were performed according to standard protocols and each of them was independently reviewed by two experienced radiologists and the length of pathological small bowel segments were measured using a vessel analysis software. Radiological measurements were compared, using Pearson correlation coefficient, with those acquired by a single surgeon intra-operatively on the still vascularized pathologic small bowel segment.

Results

We included 81 patients (44% male), with a median age of 42 years [range 18-81], undergoing first (92%) or repeated surgery for fistulizing (34%) or stenosing CD.The median length of radiological measurements was 27 cm [range 3-205] while the median length of intra-operative measurements was 30 cm [range 5-165].Pearson correlation coefficient was used to analyze the variation between the measurements and there was a statistically significant positive correlation between radiological measurements and intra-operative in-vivo small bowel lenght (r2 = 0.962; p < 0.01).

Conclusion

MR-E and CT-E allow precise and accurate measurements of the extent and location of intestinal tracts involved by CD. Such information is extremely important to properly plan the surgical strategy and to be able to quantify the risk of short bowel syndrome in cases of extensive disease or repeated surgery.Read more P213 ArgesMES: A high-performance, generalizable AI model for scoring Ulcerative Colitis severity from endoscopy videosWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The Mayo endoscopic subscore (MES) is widely used to assess endoscopic disease severity assigned by human readers in Ulcerative Colitis (UC) clinical trials. AI-based automation of the MES could reduce inter-rater variability and allow for the development of more sensitive endoscopic measures. This report assesses whether a previously trained (locked) algorithm is suitable for automating full colon or segment-level MES scoring on a prospective UC clinical trial.

Methods

Endoscopy videos from two UC clinical trials (UNIFI: NCT02407236, Phase 3, 965 subjects, 3128 videos; and JAK-UC: NCT01959282, Phase 2, 211 subjects, 448 videos) were used to train an AI-based MES classifier, where 20% of the total data was retained as a holdout set. This AI model training had two steps: 1) training a feature extraction module using self-supervised learning (SSL), and 2) supervised training of a small transformer network with an attention-based classifier using SSL features to estimate full colon MES. Videos from an independent, prospective UC trial (QUASAR: NCT04033445, Phase 2b induction study, 313 subjects, 615 videos) were used to validate the locked AI model. MES scoring in QUASAR included full colon MES values and additional MES values for three left colon segments: descending colon, sigmoid colon, and rectum. Comparisons between AI-model and human reader scores were performed using AUC, Accuracy, F1 score, and Fleiss kappa. A non-inferiority test was also conducted to determine interchangeability between AI- and human-derived full colon MES values.

Results

Full colon MES on the QUASAR data showed AUC, Accuracy, and F1 scores of 0.810, 0.687, and 0.693, respectively, comparable to results obtained on the UNIFI holdout data (0.803, 0.645, and 0.647). The Fleiss kappa score was 0.682, comparable to the inter-rater agreement between two human readers-local and central readers (Fleiss kappa = 0.712). The non-inferiority test (p-value < 0.05) indicated that the AI-computed full colon MES readout was interchangeable to that of human readers. Similar performance was observed for the AI-computed segment-level MES: descending colon, sigmoid colon, and rectum as shown in Table 1. This result demonstrates the model's effectiveness at scoring the segment-level MES despite not being trained with segment level ground truth.

Conclusion

ArgesMES, an AI-based model, underwent successful prospective validation, demonstrating proficiency in automating full colon and segment-level MES scores. ArgesMES has the potential to facilitate rapid, reliable, and reproducible MES scoring at full colon and segment levels in prospective clinical trials.Read more P303 Determining the threshold for moderate-to-severe disability in inflammatory bowel disease using IBD-DiskWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The IBD-Disk is a validated 10-question visual scale, which has been shown to measure functional disability associated with inflammatory bowel diseases (IBD). The aim of this study is to assess the correlation between the IBD-Disk, the daily-life burden associated with IBD, and disease activity.

Methods

We conducted a cross-sectional study over 6 months between April and September 2023. IBD patients responded to the IBD-Disk and 2 visual analog scales (VAS): 1) Daily-life IBD burden (scored from 0 to 10, score > 5 indicates high burden) 2) Overall perceived health status (0=poor, 10=good). Means were compared using the Wilcoxon-Mann-Whitney test. The correlation of the overall IBD-Disk with daily-life IBD burden and overall health was analyzed using Spearman's correlation coefficient. The diagnostic performance of IBD-Disk in detecting severe disability was studied using the area under the Receiver Operating Characteristic (ROC) curve.

Results

We included 142 patients, 55.6% male and 72.5% with Crohn's disease. The median age of the series was 38 years [30 - 48]. The mean IBD-Disk total score was 35.7 ± 21.6. Energy, Emotion, and Sleep obtained the highest scores. Mean values for daily-life burden and self-rated overall health status were 4.9 ± 3.1 and 5.9 ± 2.6 respectively. There was a significant difference in means between the overall IBD-Disk score, IBD daily-life burden and overall health status between patients in clinical remission and patients with active disease (Table 1). We observed 43.7% patients (n=62) with a high daily-life burden. The correlation between the overall IBD-Disk score and the VAS of daily-life burden was r=0.787 (p<0.001) and was inversely related to the VAS of overall health status with a coefficient r=-0.632 (p<0.001). At an optimal overall IBD-Disk score cut-off equal to 38/100, the area under the receiver operating characteristic curve (AUROC) for high IBD daily-life burden [VAS>5] was 0.907 (95% confidence interval [CI]: 0.858-0.955; p<0.001) (Figure 1)

Conclusion

Our work has demonstrated excellent item homogeneity in the classical Arabic version of the IBD-Disk, and a good correlation between each item and the remaining total score. However, a prospective measurement of the intra-class correlation coefficient of the classical Arabic version will be necessary to assess its reproducibility over time.Read more P304 Endoscopic cuffitis is associated with severe inflammatory pouch phenotypesWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Ulcerative colitis (UC) patients who undergo ileal pouch-anal anastomosis (IPAA) without mucosectomy may develop inflammation of the rectal cuff (cuffitis). Studies have suggested that cuffitis is associated with clinical pouch inflammation (pouchitis), but it remains unclear if cuffitis is associated with specific endoscopic phenotypes of pre-pouch inflammation (ileitis), pouch body inflammation, and diffuse pouch inflammation. Therefore, this aim of this study is to identify if endoscopic cuffitis is a predictor of more severe pouch phenotypes, which may warrant earlier or more aggressive treatment.

Methods

In this cohort study, charts were reviewed of patients who underwent IPAA at a tertiary care center from 01/2010 to 12/2021. Inclusion criteria for this study were a diagnosis of UC and ≥18 years old at time of colectomy. Exclusion criteria were lack of endoscopic evaluations after the peri-operative period (defined as 6 months following ileostomy closure) and diagnoses other than UC requiring IPAA. Patients were divided into cohorts based on whether they had cuffitis identified on ≥1 endoscopy following IPAA, which was confirmed by two researchers. Outcomes for this study included pre-pouch ileitis, pouch body inflammation, and diffuse inflammation (inflammation of the pouch body, inlet, and pre-pouch ileum). A multivariate logistic regression was used to test for association between cuffitis and each outcome while controlling for potentially confounding variables suggested to be significant on univariate analyses.

Results

A total of 363 patients were included in this study with an overall median follow-up time of 2.4 (IQR 1.2-3.8) years after ileostomy closure. 149 (41.0%) patients had cuffitis on ≥1 endoscopy following IPAA. 65 (17.9%) patients developed pre-pouch ileitis (Table 1), which was significantly associated with cuffitis (aOR = 3.85; 95% CI 2.15-6.91; p < 0.0001) and age (aOR = 0.98, 95% CI = 0.96-1.00, p = 0.0254). Pouch body inflammation occurred in 201 (55.4%) patients and was associated with cuffitis (aOR = 2.69, 95% CI = 1.69-4.29, p < 0.0001), PSC (aOR = 6.60, 95% CI = 1.85-23.49, p = 0.0036), extraintestinal manifestations (EIMs) other than PSC (aOR = 2.35, 95% CI = 1.45-3.79, p = 0.0005), and age (aOR = 0.98, 95% CI = 0.97-1.00, p = 0.0359). Finally, diffuse inflammation occurred in 20 (5.5%) patients and was associated with cuffitis (aOR = 6.24, 95% CI = 2.04-19.08, p = 0.0013).

Conclusion

Endoscopic cuffitis is associated with the development of severe inflammatory pouch phenotypes. Future studies are needed to investigate whether treatment of cuffitis reduces this risk and whether the incidence of cuffitis is rising similar to pouchitis in the post-biologic era.Read more P305 The serum protein profile across the IBD spectrum: Results from the COLLIBRI consortiumWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Inflammatory bowel disease (IBD) is a heterogeneous disorder. Both subtypes, i.e., Crohn’s disease (CD) and ulcerative colitis (UC), differ in disease behaviour and inflamed gastrointestinal segments. Despite this, randomized controlled trials stratify patients based on CD and UC. Molecular characterization could uncover subtype-specific differences that could guide treatment and thereby overcome current therapeutic limitations. Therefore, we aimed to examine differences in serum inflammatory protein profiles across the IBD spectrum.

Methods

This was a cross-sectional multicentre study of adult patients (≥18 years) with IBD from one Belgian and eight Swedish hospitals in the COLLIBRI consortium. IBD diagnosis and classification was based on international criteria, according to the Montreal classification. Relative serum protein levels were assessed using proximity extension assay technology (Olink Proteomics, Uppsala, Sweden; inflammation panel). We adopted smoothly clipped absolute deviation penalized logistic regression models to discriminate CD and UC patients. Using fitted CD vs UC logistic models, we estimated probability scores of CD vs UC for each patient based on their serum protein profiles. Scores ranged from 0 to 1, where lower scores indicated a higher molecular resemblance to UC. We evaluated the performance using leave-one-out cross-validation and the area under the curve (AUC).

Results

Relative levels of 86 serum inflammatory proteins were available from 1,551 patients with IBD (CD, N=883; UC, N=639 and IBD-U, N=29) (Table 1). CD vs UC probability scores based on protein estimates for patients with UC, IBDU and different CD phenotypes (ileal CD, L1; colonic CD, L2; ileocolonic CD L3) are shown in Figure 1A. We observed a spectrum of IBD patients based on their CD vs CD probability scores with most pronounced differences between ileal CD and UC. Probability scores also differed significantly between colonic CD and ileal CD, but not between ileal and ileocolonic CD. The model performance to discriminate CD and UC yielded an AUC of 0.75. Restricting the samples to only one CD phenotype vs UC respectively resulted in the highest AUC for ileal CD (0.81), followed by ileocolonic CD (0.75) and colonic CD (0.65). Key proteins in the CD vs. UC model with higher protein estimates in UC were IL-17A, MMP10, FGF19. Contrary, CSF1, and SLAMF1, were higher in CD (Figure 1B).

Conclusion

Our results on inflammation related serum proteins advocate for a more nuanced classification of CD into ileal-predominant and colonic-predominant subtypes. Such stratification could advance our understanding of IBD pathophysiology and may provide guidance for future therapeutic approaches.Read more P306 Rectal bleeding and stool frequency are strong predictors of endoscopic and histologic activity in ulcerative colitis patients, a prospective cohort studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Rectal bleeding and increased stool frequency are the most common symptoms patients with UC report, and they are key components in most of disease activity scores. It is unclear whether the severity of patient reported outcomes (rectal bleeding or diarrhea) correlate with endoscopic or histological disease activity. The aim of this prospective study is to evaluate the role of rectal bleeding and increased stool frequency as predictors for endoscopic and mucosal activity in patients with UC.

Methods

A single-center prospective observational study was conducted from July 2012 to July 2020. Adult patients aged 18 or older, with a confirmed UC diagnosis in clinical remission for at least 3 months, presenting to the endoscopy unit for disease activity evaluation or surveillance, were included. The partial Mayo score assessed rectal bleeding and stool frequency, considering scores of zero for each as clinical remission. Active endoscopic findings were defined by an endoscopic Mayo score > 1, and active histology was assessed using the Geboes score (active disease defined as Geboes score ≥ 3.1) from rectal biopsies. Logistic regression analysis and generalized estimated equation (GEE) were employed to evaluate the predictive impact of rectal bleeding and stool frequency at different time points on endoscopic and histologic disease activity at 12 months.

Results

The study enrolled 253 patients and the analysis revealed a significant association between rectal bleeding and stool frequency scores with 12-month endoscopic and histologic activity at different time points. Rectal bleeding at 9 months (OR: 7.64, 95% CI: 1.43 - 40.90, p = 0.0175) and 12 months (OR: 19.89, 95% CI: 3.98 - 99.52, p = 0.0003) showed a significant association with active endoscopic findings at 12 month in the multivariate analysis. At 12 months, the multivariate model of rectal bleeding revealed a significant association with active histology, with OR of 11.87 (95% CI: 1.26-112.03, p = 0.0307). On the other hand, stool frequency at 12 months exhibited significant associations with the 12 months endoscopic and histologic activity with OR of 7.31 (95% CI: 2.38 - 22.49, p = 0.0005) and OR of 13.02 (95% CI: 1.60-105.74, p = 0.0163), respectively.

Conclusion

Rectal bleeding and stool frequency scores are useful tools to predict endoscopic and histological activity in UC patients.Read more P307 Novel proteomic analysis of 11,000 serum proteins distinguishes between Crohn’s disease and ulcerative colitis in pediatric patientsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

While the two main inflammatory bowel diseases (IBD), Crohn’s disease (CD) and ulcerative colitis (UC), share various clinical features, they differ in clinical, endoscopic and histological features, and may have different underlying etiopathological mechanisms, resulting in different treatment options. Consequently, the development of reliable, highly accurate, non-invasive biomarkers that differentiate CD and UC in pediatric IBD are an unmet need of paramount importance in terms of medical care, surgical intervention, and prognosis. The most advanced proteomics technology, the aptamer-based SomaScan, enables measurement of 11,000 biologically relevant proteins, including very low abundant proteins, and was tested to discover serum protein biomarkers capable of differentiating between pediatric CD and UC.

Methods

SomaScan (SomaLogic; Boulder, CO) quantitative serum protein profiles were generated from pediatric subjects diagnosed with CD (n=56) and UC (n=25) using standard diagnostic criteria. The disease location for patients with CD was 18 L1 (ileal), 9 L2 (colonic), 27 L3 (ileo-colonic) and 2 L4 (small bowel); Inflammatory phenotype (B1) occurred in 40, stricturing (B2) in 8, penetrating (B3) in 6, and B2B3 in 2. To develop highaccuracy predictors with the lowest number of proteins for discriminating CD from UC, we used machine learning and conditional logistic regression to calculate odds ratios(OR) and 95% confidence intervals(CI) per one standard deviation increase in protein levels. Area under the curve (AUC) was calculated to determine the performance of the multi-protein model in discriminating CD cases from UC cases. Ingenuity pathway analysis was conducted to identify pathophysiological pathway differences between CD and UC.

Results

There were 256 proteins that were discriminating between CD and UC with fold change >1.3 and an unadjusted p-value <0.05. Of these, 38 proteins were associated with increased odds and 218 proteins were associated with decreased odds of CD diagnosis. Compared to UC, CD cases had decreased neutrophil movement and degranulation, inflammatory response, and metabolism of reactive oxygen species but enhanced apoptosis. When we developed a multi-protein model and assessed its performance to discriminate CDs cases from UC cases, a 4-protein model showed an AUC=0.97.

Conclusion

Using the most comprehensive proteomics platform, we identified serum proteins and developed a high accuracy multi-protein model discriminating between pediatric CD and UC. The utility of SomaScan demonstrates not only the value of these diagnostic biomarkers, but also the potential to discover immune and metabolic pathways that distinguish CD from UC.Read more P308 CPa9-HNE: A NEUTROPHIL-DERIVED FRAGMENT OF CALPROTECTIN MEASURED IN SERUM CAN MONITOR ENDOSCOPIC AND CLINICAL DISEASE ACTIVITY IN ULCERATIVE COLITISWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) presenting in remitting ulcerations of the colonic mucosa and submucosa. Mucosal healing is therefore an important treatment target. While fecal calprotectin is a common biomarker used to monitor mucosal healing in UC, patient compliance is low due to a preference for serological markers. This study aimed at investigating the association of serum calprotectin [CPa9-HNE], a non-invasive neo-epitope biomarker of neutrophil activity, with both clinical and endoscopic disease activity in UC.

Methods

The cohort included 49 patients with active UC and 50 and healthy controls (HC). Endoscopic and clinical disease activity was assessed using the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) and the full Mayo score. Serum calprotectin [CPa9-HNE] was measured, reflecting a human neutrophil elastase-derived fragment of calprotectin. Spearman’s rank correlation was applied. Group differences were evaluated using Kruskal-Wallis with Dunn‘s test, bonferroni corrected for MCP. Diagnostic and discriminative capabilities were assessed using receiver operating characteristic (ROC) statistics with are under the curve (AUC).

Results

CPa9-HNE was significantly elevated in patients with UC compared to HC (ng/ml [IQR]: 32.4 [29.0–52.3] vs. 26.0 [22.6–29.0], p<0.0001) and presented acceptable discriminative capabilities (AUC [95% CI]: 0.77 [0.67–0.87], p<0.0001). CPa9-HNE showed a moderate positive correlation to UCEIS and Mayo (ρ=0.42; ρ=0.48, both p<0.01). When patients were stratified according to endoscopic disease activity (UCEIS), CPa9-HNE was significantly elevated in patients with severe disease compared to those with mild disease (ng/ml [IQR]: 55.6 [40.9–66.4] vs. 28.9 [24.6–31.1], p<0.01) and could accurately discriminate between the two groups (fig 1A-B). Similarly, when patients were grouped according to the full Mayo score, CPa9-HNE was significantly elevated in patients with mild vs. severe disease (29.1 [24.3–32.4] vs. 62.9 [55.2–67.5], p<0.01) and moderate vs. severe disease (32.0 [29.2–39.2] vs. 62.9 [55.2–67.5], p<0.01), and could accurately discriminate between the groups (fig 1C-E).

Conclusion

CPa9-HNE was elevated in patients with UC compared with healthy subjects. Furthermore, CPa9-HNE accurately discriminated between patients with mild and severe endoscopic disease based on the UCEIS score, as well as between patients with mild, moderate, and severe clinical disease activity according to the full Mayo score. These findings highlight the potential use of CPa9-HNE as a non-invasive tool to monitor both endoscopic and clinical disease activity in UC, with the potential of guiding treatment decisions and better aligning with patient preferences.Read more P309 Impact of EBV Status on decision making for advanced therapies in IBD PatientsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The CESAME study suggested that Thiopurines confer increased risk of lymphomas in IBD patients who are naïve to Epstein - Barr virus (EBV) particularly in young males. European Crohn’s and Colitis Organisation (ECCO) guidelines recommend considering EBV screening in individuals prior to initiating immunomodulator therapy. The impact of EBV serology status on decision-making processes regarding advanced therapies in IBD patients is not studied before.

Methods

Consecutive patients initiated on advanced therapies (biologics or small molecules). EBV nuclear and vca IgG status were recorded. The first advanced therapy of the positive and negative patients were compared. Proportion of the negative patients who seroconverted and the time to seroconversion were analysed.

Results

We included 491 patients (M: F 1:14). Median age of patients who had EBV serology done prior to initiating on advanced therapies was 31.5 years (range 5-84 years) .In 41 (8.35%) patients, neither nuclear nor vca IgG antibody were detected at initial screening. The median age of EBV negative patients was 26 years (range 13-51 years).30 of the EBV negative patients were males. Azathioprine/6MP was not initiated in 37 (90.24%) of the EBV negative patients. Re-testing of EBV negative patients were done at a median interval of 28 months (range 3-90 months). 5 of these retested patients (12.2%), seroconverted and in three of this patients Azathioprine was used following seroconversion.

Conclusion

A significant minority of IBD patients are EBV negative when tested as part of pre biologic screening, including in male patients above the age of 25.Thiopurine therapy was avoided in these patients. Only a fraction of EBV negative patient seroconverted on re-testing. The impact of EBV testing in treatment decision, as well as the attributable costs needs to be evaluated further.Read more P310 Intestinal ultrasound as a tool to assess treatment response in patients with Inflammatory Bowel DiseasesWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The assessment of treatment response in patients with Inflammatory Bowel Disease (IBD) is often based on clinical indices [Harvey Bradshaw index (HBI), Partial Mayo score (PMS)] and biomarkers [C - reactive protein (CRP)]. Intestinal ultrasound (IUS) has been proposed as a modality capable of objectively evaluating therapeutic response. We investigated the utility of the IUS as a tool to assess treatment response, as well as its association with HBI, PMS and CRP.

Methods

We included patients with an established diagnosis of IBD who initiated biologic agent (infliximab, adalimumab, ustekinumab, vedolizumab) or tofacitinib. Active disease on IUS was defined as an increase in bowel wall thickness (BWT) >3 mm in the most affected bowel segment, while the presence of a Doppler signal (CDS) in the bowel wall was also assessed. Treatment response on IUS was defined according to the International Bowel Ultrasound Group (IBUS) criteria: reduction in bowel wall thickness (in continuous measurements) >25% or >2.0 mm or >1.0 mm with concomitant reduction in CDS by 1 unit at week 14 ± 2 from the initiation of treatment.

Results

A total of 19 patients (11 men, 11 with Crohn's disease) underwent IUS at week 0 and week 14 ± 2, while CRP, HBI and PMS were calculated at the same time points. We included bio-naïve as well bio experienced patients (table 1). At week 0, 84.2% of patients exhibited clinical activity (HBI ≥5, PMS ≥2), median CRP was 24.7 mg /L (IQR 18.6-42.8) and median BWT was 7.1mm (IQR 6.5-7.6). At week 14 ± 2, 42.1% of patients remained clinically active, median CRP was 6.8 mg/L (IQR 4.6-20.7) and median BWT was 5.2 mm (IQR 4.6- 6.4). Overall 10/19 patients fulfilled the criteria of treatment response on IUS at week 14 ± 2. Clinical remission was observed in 8/10 patients who demonstrated therapeutic response on IUS and 3/9 patients who did not (p=0.07). Normalization of CRP value (<6mg/L) was observed in 8/10 patients who exhibited treatment response on IUS and in none of the patients who did not (p<0.001). Among the IUS parameters at baseline, a statistically significant difference was found only in the presence of fat wrapping between treatment responders and treatment non-responders (table 2). Finally, median CRP was 4.9 mg/L (IQR 2.6-6.2) in IUS treatment responders and 20.7 mg/L (IQR 10.5-28.5) in IUS treatment non-responders. (p<0.001), with median BWT being 4.7mm (IQR 3.3-5.1) and 6.4mm (IQR 6.1-6.9) respectively (p<0.001).

Conclusion

IUS represents an objective tool for evaluating treatment response in patients with IBD, which demonstrates a significant correlation with CRP but not with clinical indices of activity.Read more P311 Prevalence and impact of sarcopenia in patients with inflammatory bowel diseases: a prospective cohort studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Sarcopenia is associated with increased morbidity and mortality in IBD. The main objective of this study was to prospectively evaluate sarcopenia by combining morphological and functional criteria in an outpatient IBD population.

Methods

In a prospective cohort study, we included all IBD patients admitted to the Day Hospital (DH) of our department between March 1st and 31st, 2023. Patients with short bowel syndrome were not included. Muscle mass was assessed using a Bodystat®1500MDD dual-frequency impedance meter, and muscle function was assessed by measuring handgrip strength, Carym® digital dynamometer. Pre-sarcopenia was defined by a handgrip measurement < 16 to 26, and myopenia was defined by an appendicular muscle mass index (AMMI) < 5.5 to 7 kg/m2 or a fat-free mass index (FFMI) < 15 to 17 in women or men. Sarcopenia was defined by the association of pre-sarcopenia and myopenia. Patients were followed-up at 6 months to measure a composite criterion of disease activity combining one of the factors: FC > 250µg/g, endoscopic activity, therapeutic change, hospitalization, or IBD-related surgery.

Results

In total, 60 patients were included, median age 37 years (IQR 28-54), 55% women, with CD (52%) or UC (48%) diagnosed 9 years (4-17) ago, mostly in remission (67%, n=40). Patients with CD had ileocolic (48%), ileal (35%), or colonic (16%) involvement. Patients with UC had E1 (7%), E2 (41%), or E3 (52%) involvement. A history of digestive surgery linked to IBD was noted in 30% of cases. The biologics administered were infliximab (61%), vedolizumab (25%), or ustekinumab (14%). The BMI was 24 (21-27) and serum albumin was 41g/l (39-44). The prevalence of sarcopenia, pre-sarcopenia and myopenia was 10%, 11% and 20%, respectively. Sarcopenic patients were significantly older (59 vs. 36 years, p=0.01), with older disease (20 vs. 8 years, p=0.003), and associated joint damage (40% vs. 2%, p=0.002) and tended to involve CD more frequently (80 vs. 49%, p=0.36). There was no significant difference between biologics, BMI or albuminemia in sarcopenic patients, but vitamin D levels tended to be lower (15 vs. 43, p=0.27). Myopenia was significantly associated with a history of surgery (67 vs. 21%, p=0.004), a lower BMI (21 vs. 24, p=0.001) and a more active disease at M6 according to the composite criterion (50 vs. 21%, p=0.04 after adjustment for age, sex, and disease activity at baseline). Myopenia indices were strongly correlated with handgrip values (r=0.7, p<0.001).

Conclusion

In a prospective study of Day Hospital IBD patients, sarcopenia was identified by impedancemetry in 11% and myopenia in 20% of cases, and associated with an increase in morbidity.Read more P312 Questionnaire survey for IBD patients in Japan; A Web-based J-CUP SurveyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The prevalence of inflammatory bowel disease (IBD) in Japan has been increasing. We aimed to clarify the symptoms of patients with IBD in Japan using an internet-based questionnaire survey.

Methods

Overall, 805 patients with IBD were asked to complete an internet-based questionnaire addressing their history of disturbances in daily activities, prevalence of fecal urgency, incontinence, and treatment preferences.

Results

Responses were obtained from 447 patients with IBD (mean age: 54 years; 70% were men), comprising 363 patients with ulcerative colitis (UC) and 84 with Crohn's disease (CD). Notably, 16% of patients with UC and 35% with CD took over 1 year until the diagnosis of IBD, and 5% of patients with CD visited more than five medical institutions. Patients with CD were more likely to experience disturbances in their diet, work, travel, and outings than those with UC. Fecal urgency and incontinence were significantly more frequent in patients with CD than in those with UC (72% vs. 44%, and 50% vs. 26%, respectively). In contrast, 26% of the men and 37% of women with IBD had constipation. Acid reflux, sleep disorders, and depressive symptoms were present in approximately 30% of the patients. Oral administration was preferred.

Conclusion

Patients with IBD in Japan experience more severe disturbances in their daily activities, and these are more severe in those with CD than those with UC. In addition to fecal urgency and incontinence, care is required for constipation, acid reflux, sleep disorders, and depressive symptoms.Read more P313 Panenteric capsule endoscopy in the investigation and assessment of Crohn’s disease at a tertiary centreWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Small bowel & colon capsule endoscopy have been established in their use to visualise the gastrointestinal (GI) tract. The Panenteric Crohn’s Capsule (PCC) is an evolution of these capsules enabling simultaneous assessment of both the small & large bowel with dual cameras for expanded mucosal coverage. This study investigates the use of PCC in patients suspected for inflammatory bowel disease (IBD), specifically Crohn's disease (CD), and in reassessing patients with established CD. The primary objective is to evaluate the impact of PCC results on patients’ management.

Methods

All consecutive patients who had PCC for suspected or established CD were included in the study. Those at risk of capsule retention (previous surgery, obstructive symptoms, stricturing disease) underwent a patency capsule, unless MR enterography was done within six months of PCC. Data was collected prospectively and included demographics, indication, procedural information such as completion rates, bowel cleansing & need for subsequent colonoscopy. PCC findings were recorded and the clinical outcome based on those was assessed at the subsequent clinic follow up.

Results

In this prospective single-centre study, 95 patients (average age 34 years, range 14-84) underwent PCC from November 2020 to May 2023, 61 were females (64%). 43 procedures were conducted remotely, 52 in-hospital, & 5 as inpatients. The primary indications were suspicion of IBD (n=54, 57%) and reassessment of established CD (n=41, 43%).Among the 95 patients,68 (72%) had successful PCC procedures. 18% (17/95) required a subsequent colonoscopy, primarily for biopsy (7,7.4%). PCC findings revealed inflammation in 41 patients (43.2%), diverticular disease in 13 (13.7%), & polyps in 15 (15.8%). The data demonstrated a 51% change in management post-PCC, including treatment escalation (15.8%), treatment de-escalation due to IBD remission (10.5%), exclusion of IBD with redirection for other pathologies or IBS diagnoses (15.8%), new IBD diagnoses (5.3%), & discharged due to normal investigation without need of further investigation (3.2%).Particularly in patients undergoing PCC for CD reassessment, 66% experienced a change in the treatment plan (14 escalated treatment, 7 de-escalated treatment due to remission, 3 achieved IBD treatment response & 3 treated for symptoms found to be caused by other pathologies).

Conclusion

PCC is a single, one-stop, non-invasive GI examination, ideal for suspected or established CD patients requiring pan-gut assessment. Despite suboptimal completion rates, PCC spared a colonoscopy in 82% of patients and resulted in change of management in over half of the patients and in 2/3 of those with established CD, suggesting a promising future role in diagnosing and monitoring CD.Read more P314 Serum levels of Leucin-Rich α2 Glycoprotein predicts endoscopic mucosal healing of Crohn's diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

It has been suggested that serum levels of Leucin-Rich α2 Glycoprotein (LRG) correlate with disease activity of Crohn’s disease (CD). Small bowel capsule endoscopy (SBCE) can be performed together with ileo-colonoscopy (ICS) at the same day to assess mucosal healing in patients with clinically quiescent CD. The aim of this study was to determine the usefulness and a cut off value of LRG that indicate mucosal healing in patients with CD.

Methods

Clinically quiescent CD (CDAI<150) patients without perianal lesions received SBCE and ICS at the same day between July 2021 and August 2023 were included. Serum levels of CRP and LRG were measured in the time frame of median 23 days before or after the exam (IQR 14, 43). Endoscopic findings were evaluated by modified simple endoscopic score for CD (mSES-CD) composed of 3 variables (size of ulcers, proportion of ulcer surface and disease affected surface) of each 7 segments (jejunum, upper ileum, lower ileum, right colon, transvers colon, left colon and rectum). Mucosal healing was defined by the mSES-CD score of 0.

Results

Among 51 CD patients enrolled, 88.2% were male with the median age of 20 (IQR 22, 35) and the disease duration of 69 months (IQR 23, 35). History of small or large intestinal resection was found in 15 (29.4%) and 14 (27.4%) cases, respectively. The median CRP and LRG were 0.1 mg/dL (IQR 0.1, 0.4), and 12.3 μg/mL (IQR 8.8, 18.3), respectively. The median mSES-CD was 3 (0,6%), and 20 (39.2%) cases were score 0. There was a high correlation between LRG and CRP levels (p<0.0001, r=0.78), and the cut of value of LRG that indicates negative CRP (< 0.4 mg/dL) was 16.6 μg/mL; area under the curve (AUC) of ROC analysis 0.91, sensitivity 90.0%, specificity 84.8%. In addition, a significant correlation between LRG levels and mSES-CD was found (p< 0.0001, r= 0.65), while no correlation between CRP and mSES-CD (p=0.72, r= 0.27). The cut off value of LRG that indicates mucosal healing was 10.2 μg/mL (AUC 0.915, sensitivity 89.7%, specificity 85.7%) with positive predictive value of 92.9% and negative predictive value of 80.0%.

Conclusion

LRG can be a reasonable biomarker to monitor disease status of CD especially in clinically quiescent patients with small bowel CD. LRG values less than 10.2 μg/mL indicates endoscopic mucosal healing in patients with CD.Read more P315 Comparable un-passed patency capsule rates among Crohn’s disease patients during Clinical remission using different preparation protocolsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Patency capsule (PC) ingestion has been proven to be a useful tool in assessing small-bowel patency before ingestion of capsule endoscope. However, false positive results of un-passed PC due to colonic hypomotility/constipation, may wrongfully preclude the use of CE in this population. Therefore, we aimed to evaluate the efficacy of intense bowel-preparation protocol before PC ingestion versus standard clear fluid-diet to reduce un-passed PC rates in patients with Crohn’s disease (CD) in clinical remission.

Methods

This was a bicenter cohort of adult patients (≥18 years-old) with small-bowel CD (L1/L3) in clinical remission, who underwent PC ingestion before CE procedure. Each center regularly follows a different preparation protocol. Patients in the intense-protocol group adhered to a low-residue diet followed by a clear fluid diet for 12 hours and fasting for 12 hours before ingestion. During capsule ingestion they were also given 10mg of Bisacodyl. Drinking and eating were resumed after 2- and 4-hours post-ingestion, respectively. Clear fluids were consumed by the control group. Propensity-score matching (PSM) in a 1:1.75 ratio was performed with adjustment for age, sex, CD-duration>1year and B2/B3 disease-phenotype, with regards to the intense preparation-protocol. The primary outcome was defined as un-passed PC (i.e., the absence of PC excretion in the stool or its presence in the abdomen by abdominal X-ray within 30 hours from ingestion).

Results

269 patients were included (intense group-79, control group-190). The cohort following the PSM comprised of 212 patients (intense group-77, control group-135). Current biologic use was less common in the intense-protocol group compared to the controls (37.7% vs. 61.2%, p=0.001). Un-passed PC rates were 13.0% (10/77 patients) vs. 19.3% (26/135 patients) in the intense-protocol and the control groups, respectively (p=0.242). On univariable analysis longer disease-duration (OR 1.042, 95% CI 1.002-1.085, p=0.040) was the only variable to be associated with un-passed PC. Age≥40 was associated with increased risk for un-passed PC as well, however only borderline significance was achieved (OR 1.917, 95% CI 0.927-3.967, p=0.085). Upon multivariate logistic regression analysis, there was no clinico-demographic/disease-related variable that was independently associated with the probability for un-passed PC. Of 269 patients, there was a single subsequent CE retention in the control group, which has resolved spontaneously (0.4%).

Conclusion

Intense-preparation protocol based on low-residue diet and laxatives was not superior to clear fluid diet alone, for reducing the rates of un-passed PC and for increasing successful patency test of small-bowel, among CD patients in clinical remission.Read more P317 Diagnostic accuracy of plasma calprotectin and serum calprotectin in patients with suspected Crohn’s diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Faecal calprotectin is a sensitive marker for chronic inflammatory bowel disease (IBD), and it correlates with the endoscopic disease activity. However, patient reluctance and handling in the laboratory are limitations for the clinical use, and there is a need for new reliable blood-based biomarkers. Prior studies indicate, that serum calprotectin (SCal) and plasma calprotectin (PCal) can be used as biomarkers for IBD, and SCal correlates better with disease activity in Crohn’s disease (CD) than in ulcerative colitis. The aim of this study was to investigate the diagnostic accuracy of SCal and PCal in patients examined for CD.

Methods

Patients with clinically suspected CD were enrolled in a prospective, blinded, multicentre study examining non-invasive modalities for diagnosing CD (ClinicalTrials.gov identifier NCT03134586). Patients had a standardized work-up including ileocolonoscopy, pan-enteric capsule endoscopy and blood samples within a 2-week period. EDTA plasma was prepared less than 2 hours of sampling by centrifugation at 3000 g for 15 minutes. Samples were stored in a biobank at − 80°C until further analysis. A routine C-reactive protein (CRP) was measured on the same day. SCal and PCal were analysed in batches using the calprotectin assay product nr.1201 from Gentian (Moss, Norway) on the Cobas platform (Roche, Basel, Switzerland). Analyses were performed in an ISO 15189 accredited laboratory.

Results

126 patients were enrolled in the study: 69 % women and 31 % men with a median age of 27.5 years (Table 1). A total of 57 (45%) patients were diagnosed with CD based on the result of ileocolonoscopy and pan-enteric capsule endoscopy. Patients with CD had a mean PCal of 0.50 mg/L (95% confidence interval (CI) 0.38-0.62) compared to 0.35 mg/L (CI 0.27-0.44) in non-CD patients (P = 0.03). The mean SCal was 1.45 mg/L (CI 1.20-1.69) and 1.06 mg/L (CI 0.90-1.22) in patients with and without CD, respectively (P = 0.01). Receiver operating characteristics curves showed an AUC of 0.63 (CI 0.53-0.73) for SCal and 0.61 (CI 0.51-0.71) for PCal, which was inferior to CRP (0.76, CI 0.68-0.85, P < 0.02) (Figure 1). In patients diagnosed with CD, SCal and PCal had a moderate correlation with CRP (r_s = 0.47 and 0.55, respectively, P < 0.001), and SCal had a weak correlation with the Simple Endoscopic Score for CD (r_s = 0.29, P = 0.04) and the Crohn’s Disease Activity Index (r_s = 0.36, P = 0.03).

Conclusion

Levels of PCal and SCal are increased in patients with CD reflecting the systemic inflammatory response in this disease. However, SCal and PCal are insufficient biomarkers in patients with clinically suspected CD, and they are both inferior to CRP.Read more P318 Performance of rectosigmoidoscopy and rectoscopy to assess endoscopic and histological healing in ulcerative colitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Endoscopic and histological healing are associated with improved long term outcomes in ulcerative colitis (UC). Considering all the limitations of endoscopy, we aimed to compare the performance of complete colonoscopy, rectosigmoidoscopy (RS) and rectoscopy to assess endoscopic and histological healing in UC.

Methods

Between January 2021 and January 2023, all consecutive UC patients who underwent complete colonoscopy were prospectively included. Endoscopic activity was assessed by the Mayo Endoscopic Score (MES) on the 5 colonic segment. Endoscopic healing was defined by a MES=0 on all explored segments and histological healing was defined by a NANCY score ≤ 1 (2 biopsies/segments). The correlation between colonoscopy, RS and rectoscopy in terms of endoscopic and histological mucosal was assessed using Cohen's kappa coefficient.

Results

80 patients were included. Thirty-four patients had a MES=0 on all the 5 colonic segments. The correlation between the colonoscopy and RS was almost perfect with an index к of 0.949 for Mayo 0, and к of 0.945 for Mayo 0-1. The correlation between histological healing in RS and colonoscopy was almost perfect (к=0.877, p<0.001). Additionally, the correlation between rectoscopy and colonoscopy for the evaluation of endoscopic[mf1] and histological healing was almost perfect (к=0.826 (p < 0.001) and к=0.8 (p < 0.001), respectively).

Conclusion

RS is sufficient to assess both endoscopic healing and histological healing in UC. With a false negative rate < 10%, rectoscopy is effective to assess endoscopic and histologic healing in UC.Read more P319 Genetic polymorphism of lactose intolerance in patients with Inflammatory Bowel DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Lactase deficiency is a disorder of lactose absorption in the body due to a deficiency of lactase, an enzyme that helps break down milk sugar. . The most common cause of primary lactase deficiency is due to a polymorphism in the MCM6 gene, which affects the function of the LCT lactase gene. Normal lactose digestibility is associated with the TT genotype, and when thymine is substituted for cytosine (allele C), a decrease in lactase levels in adulthood and impaired lactose digestibility to the point of complete inability to digest lactose should be expected. Understanding the prevalence of lactose intolerance in populations with inflammatory bowel disease may have important implications, preventing unnecessary restrictive diets and thereby helping to prevent future complications, including malnutrition and the occurrence of disorders of phosphorus-calcium metabolism.

Aim Of The Study

to investigate the prevalence of lactose intolerance and to evaluate the possibilities of correlation between genotype and lesion localization in IBD

Methods

Three single nucleotide polymorphisms of the LCT gene: LCT-13910 CC, LCT-13910 CT, LCT-13910 TT were analyzed in the group of patients with IBD (128 patients; UC-62 patients, CD 66 patients) and in the control group (45 patients with IBS).

Results

Baseline patient demographics and genetic analysis scores for lactase deficiency and variants of genetic polymorphism and association with localization of pathological process in IBD are presented in Table 1 and Figure 1.

Conclusion

Thus, the prevalence of LCT-13910 CC was 59.4% (congenital deficiency) and LCT-13910 CT was 31.3% (age-associated deficiency). In 9.4% of patients with IBD, no deficiency was genetically identified. In patients in the control group, LCT-13910 CC was detected in 15.5%, LCT-13910 CT in 42.4%, and LCT-13910 TT in 44.4%. LCT-13910 CC variant was predominant in CD patients with small intestinal lesions (n=41; 95.3% and 62.1%, respectively), in patients with left-sided ulcerative colitis (n=14; 51.8% and 22.6%, respectively) and total lesions in ulcerative colitis (n=12; 70.6% and 19.3%, respectively).Thus, the need for a lactose elimination diet is necessary in cases with small intestinal involvement in CD, and with total and left-sided course in UC.Read more OP06 Risankizumab Maintenance Therapy in Patients With Moderately to Severely Active Ulcerative Colitis: Efficacy and Safety in the Randomised Phase 3 COMMAND StudyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Risankizumab (RZB), a monoclonal antibody targeting interleukin-23 p19, was evaluated for maintenance therapy in patients with moderately to severely active ulcerative colitis (UC) and clinical response to RZB intravenous (IV) induction treatment in a phase 3 double-blind, placebo (PBO)-controlled withdrawal (WD) maintenance study, COMMAND (NCT03398135).

Methods

Patients with moderately to severely active UC who achieved a clinical response per Adapted Mayo score after 12 or 24 weeks (wks) of RZB IV treatment in the phase 2b and phase 3 INSPIRE induction studies (NCT03398148)¹ were randomized 1:1:1 in COMMAND to RZB 180 mg (RZB180), 360 mg (RZB360), or PBO (RZB withdrawal) subcutaneous (SC) treatment every 8 wks for 52 wks. The efficacy analysis included responders to 12 wk of RZB IV, while the safety analysis included responders to 12 or 24 wk of RZB IV. The primary endpoint was clinical remission per Adapted Mayo score at wk 52. Key secondary endpoints included endoscopic improvement, HEMI, endoscopic remission, steroid-free clinical remission, maintenance of clinical remission, no bowel urgency, and no abdominal pain at wk 52.

Results

At baseline of induction, demographics and disease characteristics were similar between treatment groups; 75% of 548 patients had history of inadequate response or intolerance to ≥ 1 advanced therapy (AT). Patients receiving RZB180 (40.2%) and RZB360 (37.6%) achieved significantly higher rates of clinical remission vs WD (25.1%) (adjusted treatment difference vs WD: 16.3% and 14.2%, respectively; P ≤ .01) (Fig. 1A). Greater proportions of patients achieved endoscopic improvement, HEMI, endoscopic remission, steroid-free clinical remission, maintenance of clinical remission, no bowel urgency, and no abdominal pain with RZB180 and RZB360 vs WD (Fig. 1B). The overall rates of adverse events (AEs), and serious infections were similar among treatment groups (Table 1). Serious (presented as events/100 patient-years [E/100 PY]) (RZB180: 5.9; RZB360: 6.3; WD: 11.4) and severe AEs (RZB180: 1.6; RZB360: 4.0; WD: 8.0) were lower in the RZB arms vs WD. No active tuberculosis, adjudicated anaphylaxis, serious hypersensitivity, or adjudicated major adverse cardiovascular events were reported in any treatment group.

Conclusion

In patients with moderately to severely active UC responding to 12-week RZB induction therapy, RZB maintenance dosing with 180 mg and 360 mg SC was superior to placebo in achieving clinical remission as well as other key clinical, endoscopic, and histological-endoscopic endpoints. RZB was well-tolerated, with no new safety concerns observed.Read more OP05 Primary efficacy and safety of mirikizumab in moderate to severe Crohn’s Disease: results of the treat-through VIVID 1 studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Mirikizumab (miri) is a selective IL23p19 monoclonal antibody approved for the treatment of ulcerative colitis. The primary focus of the VIVID-1 trial (NCT03926130) was to demonstrate the efficacy and safety of mirikizumab (miri) compared to placebo (PBO) in patients (pts) with moderate-to-severe Crohn’s disease. Here we present primary efficacy and safety of miri compared to placebo (PBO) up to Week 52 (W52) from the Phase 3, randomised, double-blind, double-dummy, active- and PBO-controlled, treat-through VIVID-1 study.

Methods

Adult pts (N=1065) were randomized 6:3:2 to miri (N=579) 900mg intravenously (IV) at W0, W4, and W8, then 300mg subcutaneously (SC) every 4 weeks (Q4W) from W12 to W52, placebo (PBO) (N=199), or ustekinumab (N=287) ~6mg/kg IV at W0 and SC dose of 90mg Q8W from W8 to W48. At W12, PBO responders continued PBO to W52; PBO non-responders received the same blinded miri regimen (IV then SC) as described above. The co-primary endpoints assessing superiority of miri over PBO were composite endpoints: 1) PRO clinical response at W12 and endoscopic response at W52, and 2) PRO clinical response at W12 and clinical remission by Crohn’s Disease Activity Index (CDAI) at W52. The adjusted risk differences were calculated, and the comparison was performed by CMH test. Nonresponder imputation was used.

Results

Baseline characteristics were similar across treatment groups. 48.7% of pts in the PBO, and 48.5% in the miri, group previously failed at least one biologic. 15.6% and 18.3% of the PBO and miri groups respectively failed more than one biologic. Both co-primary endpoints (Figure 1A, 1C, all p<.000001) and all key secondary endpoints (Figure 1E, all p<.000001 except endoscopic remission at W12: p<.001 and W12 clinical remission by CDAI: p=0.001) were achieved. Robust and consistent efficacy at W52 was also demonstrated with similar response rates and treatment effect in patients with and without prior biologic failure (Figure 1B, 1D, all p<.0001). Overall safety was consistent with the known safety profile of miri (Table 1).

Conclusion

In this phase 3 CD study, miri demonstrated statistically significant and clinically meaningful improvements vs PBO in both co-primary composite endpoints and all key secondary endpoints, with an acceptable safety profile.Read more P122 Digital spatial profiling reveals the predictive characteristics in patients with immune checkpoint inhibitor-induced colitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The increasing use of immune checkpoint inhibitors (ICIs) against cancers is inevitably accompanied with immune-related adverse events (irAEs), and irAE colitis is one of the common types. The overactivation of CD8⁺ T cells plays a central role in irAEs. However, the local mechanisms related to irAE colitis remain unclear. Hence, we aimed to explore the transcriptional characteristics related to CD8⁺ T cell responses of irAE colitis.

Methods

Colon biopsy samples were collected from 6 irAE colitis patients and 5 non-irAE controls after ICIs treatment. Leveraging digital spatial profiling, 23 regions of interest (ROI) enriched with CD8⁺ T cells were selected and divided into 3 groups, which were non-irAE, pre-treatment irAE and post-treatment irAE. Differentially expressed genes (DEGs), protein-protein interaction (PPI) and weighted gene co-expression network analysis (WGCNA) were performed to identify the hub genes, and they were further verified by external single-cell RNA-seq data. Also, the immune infiltration analysis was performed (Figure 1A).

Results

Principal component analysis (PCA) indicated similar distribution among the 3 groups (Figure 1B). The comparisons of non-irAE vs. pre-treatment irAE, and pre-treatment irAE vs. post-treatment irAE yielded 105 and 210 DEGs respectively. WGCNA resulted in 14 clustering modules, with MEturquoise and MEmagenta exhibiting the highest correlation scores (Figure 1C). Importantly, 174 key genes were identified and prominently associated with various mitochondrial processes e.g. oxidative phosphorylation (Figure 1D). PPI analysis revealed a sub-module consisting of 22 nodes in MCODE. Further overlap analysis of CytoHubba and DEGs pinpointed 9 hub genes. Remarkably, COX5B was found at the intersection of both groups (Figure 1E). External single-cell RNA-seq data verified that all the hub genes were significantly highly expressed in the irAE colitis group except COX6A1 (Figure 1F). Besides, immune infiltration analyses revealed the higher levels of endothelial cells (P = 0.043) and fibroblasts (P <0.01) by SpatialDecon, and activated dendritic cells (P <0.001) by xCell in pre-treatment irAE, compared to non-irAE (Figure 1G). Further, immune cells correlation analysis demonstrated highly similar patterns of endothelial cells, fibroblasts, pDCs, and macrophages (Figure 1H).

Conclusion

COX5B related to mitochondrial processes characterized irAE colitis. Expansion of dendritic cells and stromal compartments including endothelial cells and fibroblasts may contribute to irAE development.Read more P124 Tissue Factor and Protease-Activated Receptor 2 associated genes are upregulated in patients with Inflammatory Bowel DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Tissue Factor (TF) is well known for its role in coagulation, but it is also a key mediator of inflammatory cellular signaling relating to myeloid cell migration and kinase activation. TF is upregulated during inflammation and has been implicated in IBD pathology. Its role as a therapeutic target has not been well characterized, due to concerns that inhibition may induce a coagulopathy. When activated, TF cleaves protease-activated receptor 2 (PAR2) and induces multiple intracellular signaling pathways. Our aim was to investigate TF gene expression and PAR2 activated genes by colonic segment with inflamed tissue in patients with IBD compared to non-inflamed regions, and tissue from healthy controls.

Methods

RNA seq data from colon biopsy samples taken from The Mount Sinai Crohn's and Colitis Registry (MSCCR) cohort containing 1188 subjects (431 UC, 505 CD and 252 healthy controls) were downloaded from GEO (GSE193677) and preprocessed by the Endpoint Health RNA seq Analysis Pipeline. Tissues from patients with UC and CD were included in the analysis if the endoscopic score indicated moderate to severe inflammation. Differential gene expression analysis was performed using the Wilcoxon rank test. Gene set enrichment analyses (GSEA) was performed for PAR2 associated genes¹.

Results

1,030 tissue samples, including 161 UC, 409 CD and 460 healthy control samples, were analyzed from 90, 174 and 252 subjects respectively. TF was found to be upregulated in inflamed tissue compared to non-inflamed tissue in patients with UC and CD, supporting a role for TF in inflamed lesions (Figure 1). Furthermore, PAR2-induced inflammatory related gene expression was observed in the inflamed tissue biopsies from patients with UC and CD compared to health control samples.Genes involved in inflammation, which include chemokines such as CXCL8 and chemokine receptors CXCR1, were consistently upregulated in all inflamed tissue regions isolated from patients with UC and CD (Table 1).

Conclusion

TF was found to be upregulated in inflamed tissue compared to non-inflamed tissue in patients with UC and CD, which may indicate TF contributing to tissue inflammation. TF represents a novel therapeutic target for IBD, but safety concerns with inhibiting coagulation have limited its clinical utility for inflammatory disease. To address this safety concern, EP004, a human IgG1 monoclonal antibody, targets the extracellular domain of human TF, inhibiting PAR2-induced inflammatory signaling while not altering coagulation activity. Clinical studies are required to elucidate its therapeutic effect.1. Suen, J. Y. et al. 2010. Profiling Gene Expression Induced by Protease-Activated Receptor 2 (PAR2) Activation in Human Kidney Cells. PLOS ONE 5(11): e13809.Read more P125 MIG (CXCL9) and IL22 are key biomarkers that discriminates between paediatric IBD patients and non-IBD patients in a novel biomarker modelWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The current gold standard for diagnosis of Inflammatory bowel disease (IBD) is based on clinical and endoscopic evaluation as well as histologic and radiologic evaluation. However, endoscopic evaluation can be uncomfortable and carry some risks, especially in the paediatric population that requires general anesthesia in order to perform the procedure. Our aim was to investigate whether serum biomarkers can differentiate between paediatric patients with and without IBD. Secondary aims were to determine whether there are biomarkers that can differentiate between Crohn's disease (CD) and Ulcerative colitis (UC), and whether we can predict progression to biologic treatment within one year from diagnosis using these biomarkers.

Methods

Paediatric patients undergoing a first diagnostic colonoscopy at British Columbia Children's Hospital (BCCH) between December 2019 and June 2022 were invited to participate in the study. A 2 ml blood sample was taken from each participant at the time of colonoscopy. Demographic and clinical data were collected from each patient. Blood samples were analyzed using the Legendplex^TM flow cytometry kits investigating 12 different inflammatory cytokines and chemokines associated with IBD. Eleven of them were found most significant in an initial analysis performed on 100 patients using 50 biomarkers, and CCL7 was added due to significance in previous studies. A prediction model was built via a supervised learning method to determine how well we can predict the different groups.

Results

Two hundred and forty-six paediatric patients participated in the study. Median age was 13.03 years, 92 were females (37.4%) and 155 (63.01%) were diagnosed with IBD, with 103 (66.45%) diagnosed with Crohn's disease. The AUROC using SPLS-DA classification was 0.805. MIG and Il22 were found to be the key biomarkers to discriminate between pediatric IBD patients and non-IBD patients. In a random forest analysis MIG, Il8 and Il22 were found most important for discrimination.On a univariate analysis MIG and Il18 were found statistically significant as a predictor of CD (p=0.016 for both). CXCL1 was predictive to progression to biologic treatment within one year of diagnosis (p=0.039). However, the prediction model did not predict well the subclasses nor progression to biologic treatment.

Conclusion

Using serum biomarkers can predict the diagnosis of Paediatric IBD. MIG and Il22 were found to be the key biomarkers in the prediction model.Read more P166 Optimizing PD-1 agonist signaling with membrane proximal binding of rosnilimab, a clinical stage PD-1 agonist IgG1 antibodyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Checkpoint agonism represents a promising class of therapies for the treatment of autoimmune and inflammatory diseases, including ulcerative colitis (UC), where unmet needs persist despite available therapies. Binding to membrane proximal regions of checkpoint receptors, together with Fc interactions with receptors on opposing cells, can contribute to tight immune synapse formation between the immune cell and antigen presenting cell. This has been proposed to improve potency of agonistic signaling by excluding phosphatases such as CD45 from the immune synapse and promoting receptor clustering. Optimization of these characteristics results in improved agonism and depletion, with the potential for restoration of immune balance and broader clinical outcomes. Rosnilimab was engineered to leverage these important characteristics. It is a PD-1 agonist IgG1 antibody designed to optimize inhibitory signaling through the PD-1 receptor and to deplete PD-1^high pathogenic T cells. Rosnilimab is in Phase 2 clinical development for UC and rheumatoid arthritis.

Methods

Mutations to surface exposed regions of the PD-1 extracellular domain were made and surface plasmon resonance was used to infer the epitopes of PD-1 agonist molecules from resulting changes to binding. Membrane proximal and distal binding antibodies were studied in in vitro functional assays to assess T cell proliferation and antibody-dependent cellular toxicity.

Results

Epitopes of agonistic antibodies were mapped to locations on the PD-1 receptor. The membrane proximal binding epitope of rosnilimab was confirmed and binding epitopes for other reference antibodies (ref) were identified. Rosnilimab and a membrane distally binding antibody (ref 1) were selected for comparison in functional assays. Rosnilimab demonstrated greater reduction of T cell proliferation and depletion of PD-1+ T cells compared to ref 1, consistent with the hypothesis that membrane proximal binding improves agonistic activity and target cell depletion.

Conclusion

By targeting and leveraging inhibitory immune regulatory mechanisms to modulate the pathogenic T cells driving disease, there is an opportunity to dampen the inflammatory cycle and restore immune balance via agonism. Rosnilimab binds to a membrane proximal region of the PD-1 receptor, resulting in potent reduction of T cell proliferation and depletion of PD-1^high T cells. These mechanistic data, translational in vivo and in vitro data, robust Phase 1 healthy volunteer data, and unmet needs in UC provide rationale for an ongoing global Phase 2 study of rosnilimab in UC (NCT06127043).Read more P167 Remodelling of the colonic molecular landscape in patients failing anti-TNF therapy highlights dysregulation of the extracellular matrix in ulcerative colitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

In patients with ulcerative colitis (UC) who previously failed anti-TNF therapy, subsequent treatment with other advanced therapies is generally less effective than they are in anti-TNF naïve patients. Since anti-TNF drugs are frequently used first-line in UC, drug sequencing depreciation poses a major clinical challenge. To understand potential underlying mechanisms, we compared the clinical and molecular phenotype of UC patients who failed anti-TNF therapy with those who were anti-TNF naïve.

Methods

Clinical information and mucosal gene expression profiles were collected from 262 anti-TNF naïve and 275 anti-TNF exposed individuals with moderate to severe UC enrolled in the UNIFI clinical trial programme. We assessed differences between the groups in terms of clinical parameters, gene expression levels, pathway and transcription factor activity, as well as cellular composition.

Results

Anti-TNF exposed patients had significantly increased disease duration (p=0. 000009), CRP (p=0.03), and histological severity[PN1] (p=0.002). After adjusting for these factors, we identified 1,592 genes differentially expressed (FDR < 0.05), although the expression changes were quite modest. Pathway analysis linked previous anti-TNF exposure to significant downregulation of TNF and NFkB signalling and up-regulation of extracellular matrix components, stroma-related signatures, and growth factor receptor (EGFR, MAPK, PI3K) and TGFb signalling. These data were in line with results from cellular deconvolution methods, which showed an increase in stromal cell abundance and T cell depletion following anti-TNF failure. Gene regulatory network inference suggested that the observed gene expression differences were driven by increased activity of many transcriptional regulators, including those downstream of RUNX1 and RUNX3.

Conclusion

In patients with active UC, prior anti-TNF failure is associated with molecular remodelling of the colon characterised by dysregulated ECM organisation and shifts in stromal compartments. These data provide new insights into potential mechanisms of drug sequencing depreciation and could inform novel strategies to overcome this challenging clinical phenomenon.Read more P168 Specialized pro-resolving lipid mediator Resolvin D1 and omega 6 dihomo-γ-linolenic acid are unable to solve inflammation in the creeping fat of patients with severe postoperative recurrence in Crohn's diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The ω3 derivate resolvin D1 (RvD1), and the ω6 dihomo-γ-linolenic acid (DGLA) prevent collateral damage by overcoming inflammation and enhancing microbial clearance. In Crohn's disease, the mesenteric adipose tissue becomes inflamed and hyperplasies due to transmural lesions and bacterial translocation, developing the so-called creeping fat. This tissue is unable to clear inflammation and has been linked to severer intestinal inflammation and post-operative recurrence (POR). Recently, we have described the presence of DGLA and the increase in the ω6/ω3 ratio together with pro-inflammatory mediators in the creeping fat at surgery. Our aims were study the mechanisms within the inflammatory resolution related to polyunsaturated fatty acids depending on POR severity.

Methods

Creeping fat samples were obtained in the intestinal resection of Crohn's disease patients and endoscopic POR was evaluated according to the Rutgeerts score: non recurrence (i0+i1; n=18), mild recurrence (i2; n=14) and severe recurrence (i3+i4; n=10). Mesenteric adipose tissue was also collected from patients with colorectal cancer (n=10) and severe obesity (n=11) as reference groups. RvD1 was evaluated by C18/ELISA, lipoprotein lipase (LPL) and hormone-sensitive lipase (HSL) activity by radioassay, and the free fatty acid receptor 1 (FFAR1) expression by qRT-PCR.

Results

RvD1 was increased in the creeping fat in comparison to the mesenteric adipose tissues of the reference groups (Graphical abstract A) and correlated antagonistically with pro-inflammatory mediators in non-recurrence versus severe recurrence (B). Specifically, factors such as TNF-α, CD14 or IL-18 showed significant positive correlations with RvD1 in severe recurrence while negative in non recurrence. The LPL/HSL ratio indicated greater storage of fatty acids in severe recurrence creeping fats (C), and only in these patients, DGLA negatively correlated with HSL (D) and FFAR1 (E), a receptor that was only detected in Crohn's disease (F). At the same time, this receptor antagonistically correlated with pro-inflammatory mediators such as IL-8 in the creeping fat, positively in non-recurrence and negatively in severe recurrence (G).

Conclusion

The RvD1 increase suggests a greater production of this factor from ω3, but that would be insufficient to resolve inflammation in severe recurrent creeping fat at surgery time. In this phenotype, HSL activity is linked to a lower presence of DGLA, the only anti-inflammatory ω6. In contrast, the presence of this ligand in severe recurrents seems to reduce the expression of the FFAR1, which acts on the neutrophil function. Thus, immune-inflammation derived from lipid metabolism is antagonistic among the most disparate cases of POR in the creeping fat at surgery.Read more P169 Circulating eNAMPT predicts anti-TNF response in IBD patients: possible place in therapy of anti-eNAMPT antibodyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

extracellular Nicotinamide phosphoribosyltrasferase (eNAMPT) is a cytokine with paracrine and autocrine effects on different cell types. Importantly, eNAMPT levels are increased in patients suffering of Inflammatory Bowel Diseases (IBD). Biologic drugs have been found effective in many IBD patients; however, a large proportion of patients with severe disease fail to achieve remission due to lack of drug response, loss of response, drug intolerance, or severe side effects that require cessation of therapy. Therefore, there is a clinical need for predictive response biomarkers as well as for new therapeutic strategies.

Methods

First, we investigated the expression of NAMPT in biopsies, in stools and the secretion of eNAMPT in serum in four cohorts of IBD patients. Second, we investigated if circulating eNAMPT levels correlate with the clinical response to biologics (infliximab, adalimumab, ustekinumab, vedolizumab). Clinical response is defined as a reduction of >2 points in HBI (for CD) and in pMAYO (for UC) from baseline. Third, we have developed a monoclonal anti-eNAMPT antibody and we have evaluated its preclinical efficacy in acute and chronic preclinical models of IBD.

Results

We have determined the levels of circulating eNAMPT in three cohorts of patients that were not controlled by DMARDs and were treated with infliximab (IFX, cohort 1 and 3) or adalimumab (ADA, cohort 2). Notably, we confirmed a pronounced variability through the cohorts, identifying a group of patients with eNAMPT serum levels comparable with healthy adult populations and a group that showed elevated levels of eNAMPT. Performing a ROC curve analysis, a cutoff of 4.5 ng/ml can be extrapolated to discriminate these two populations.Noteworthy, 100% patients with levels of eNAMPT below 4.5 ng/ml were responsive to infliximab/adalimumab. In contrast, anti-TNF therapy failed either at 14 or 22 weeks in some patients with high circulating levels of eNAMPT, indicating that high systemic eNAMPT might be associated with an increased risk of resistance to anti-TNF therapy. Notably, we found also that eNAMPT levels in stools of IBD patients are elevated compared to healthy subjects.Then, we have developed and validated a candidate monoclonal antibody (called C269) which bind to eNAMPT, block is cytokine activity and reduces IBD symptoms, immune infiltrate and fibrosis in DSS and DNBS models.

Conclusion

Our data demonstrate that eNAMPT serum levels correlate with the clinical response to anti-TNF therapies suggesting that eNAMPT is not a simple by- stander of IBD, and that local and serum eNAMPT could be define as a biomarker to define the responsiveness to biologics. Notably, its neutralization might be a pharmacological strategy worth investigating.Read more P170 SLC7A5 promotes the progression of Ulcerative Colitis by regulating amino acid transport and intestinal epithelial autophagyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

IBD has become a common chronic intestinal disease in China. Considering the important role of amino acid metabolism in inflammatory diseases, inhibition amino acid metabolism of inflammatory sites may be effective in alleviating UC (ulcerative colitis). SLC7A5 is involved in the progression of UC, but the mechanism of its functional regulation still needs to be investigated. In this study, we aimed to clarify the link among SLC7A5 expression in UC, mTOR pathway activation and immunoregulation.

Methods

We previously discovered through high-throughput screening that SLC7A5, as a cellular amino acid transport carrier, is significantly elevated in the colonic tissues of UC patients; in vivo experiments have demonstrated for the first time that JPH203, a specific inhibitor of SLC7A5, alleviates DSS-induced intestinal inflammation and inhibits mTOR pathway activation to promote intestinal autophagy. This study utilized model animals, transcriptomics, amino acid-targeted metabolomics assays, and macro-genome sequencing to elucidate the mechanism of SLC7A5-regulated amino acids in mTOR pathway activation and intestinal autophagy dysfunction.

Results

SLC7A5 expression is increased in the colon of UC patients and DSS-induced mice lesions. SLC7A5 inhibitor (JPH203) restrained the inflammatory responses induced by DSS. SLC7A5 deletion or inhibition dampens the release of IL-1β, IL-18, and IL-23 and the production of ROS in the LPS-induced FHC and RAW264.7 cells. Moreover, upregulating SLC7A5 expression induces mTOR signaling pathway activation in FHC cells. Deletion or inhibition of SLC7A5 efficiently blocks the SLC7A5-dependent amino acid transport, inhibits the mTOR activation, and results in the activation of autophagy.

Conclusion

Targeting SLC7A5-mediated amino acid uptake is a potentially useful immunosuppressive strategy to regulate colonic inflammation through mTOR pathway and autophagy. This study is expected to reveal the intrinsic factors of metabolic disorders promoting the UC progression from the perspective of amino acid metabolism, and to lay a new theoretical and experimental foundation for potential UC treatment.Read more P171 Rescuing Intestinal Stem Cells via TMEM219 inhibition promotes mucosal healing in Crohn’s diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Intestinal mucosa regeneration is disrupted in inflammatory bowel disease as Chron’s disease, but whether this relies on a defect in intestinal stem cells remains to be established.

Methods

Transcriptome and receptome profile in Crohn’s disease bioptic samples demonstrated a defect in intestinal stem cells (ISCs). The TMEM219 knockout mouse, in which TMEM219 expression is abrogated on ISCs was tested in dextran sulfate sodium (DSS) acute colitis model. DSS-induced chronic colitis was also used to confirm in vivo relevance for TMEM219 blockade in mucosal recovery.

Results

An increased intestinal stem cells death and dysfunction in colonic samples obtained from patients with Crohn’s disease was observed, which is controlled through the death factor TMEM219. Based on a receptome analysis, we documented large alterations in the expression of the death receptor TMEM219 in patients with Crohn’s disease, particularly in those with refractory disease and/or non responders to conventional therapy, which were paralleled by altered peripheral levels of the TMEM219 ligand, insulin-like growth factor binding protein 3 (IGFBP3). Pharmacological blockade of the IGFBP3/TMEM219 axis restored the self-renewal abilities of mini-guts generated from patients with Crohn’s disease in vitro, ameliorated DSS-induced colitis in vivo and favored mucosal healing. Genetic deletion of TMEM219 in intestinal stem cells in newly generated TMEM219^flflLGR5^cre mice restored mucosal regenerative abilities both in vitro and in vivo.

Conclusion

Our findings demonstrate that genetic and pharmacological TMEM219 blockade re-establishes intestinal self-renewal properties and offers a therapeutic opportunity for mucosal healing in inflammatory bowel disease.Read more P172 Spatial Transcriptomics Characterization of S1P Pathway Genes in Ulcerative Colitis and Crohn’s Disease Colon TissuesWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Inflammatory bowel diseases (IBD), such as ulcerative colitis (UC) and Crohn’s disease (CD) are chronic inflammatory diseases of the gastrointestinal tract, related to the confluence of environmental and immunological factors in genetically predisposed individuals. Activated T and B cells migrate from the lymphoid tissue into the circulation through the interaction of Sphingosine-1-phosphate (S1P) and the S1P1 receptor (S1P1), which can perpetuate inflammation and lead to tissue damage. Targeting of cellular migratory pathways has emerged as a novel therapeutic paradigm in IBD. The aim of this study is to characterize the S1P pathway-related genes and signaling pathways driving the pathogenesis of UC and CD.

Methods

Spatial transcriptomics analysis was performed in health volunteer (HV, n=2), UC (n=4) and CD (n=2) FFPE colon tissues using the GeoMX platform and NanoString whole transcriptome atlas (WTA) assay. The WTA panel was run on 8 samples stained with antibodies to S1P1, pan Cytokeratin, and CD45. Six regions of interests (ROIs) were selected in each sample based on the staining and each ROI were split into two areas (CD45⁺ or CD45^-). Differential gene expression and enriched pathways analysis including S1P pathway genes were performed in CD45⁺ and CD45^- segments in HV, UC and CD colon tissues.

Results

A total of 6085 and 6054 differentially expressed genes were identified from the CD45⁺ segments in UC and CD respectively, compared to HV colon (P=0.05), including the genes that are involved in T cell activation (e.g., HLA-DPA1, CCDC13), immune cell migration (e.g., ADAM15, CCL5) and tissue damage (e.g., FABP6, PDK4). Interestingly, significant differences were identified in UC and CD in S1P pathway gene expression. Specifically, SMPD1, a gene involved in generating ceramide and regulating inflammatory responses, was the most significantly up-regulated gene from both CD45⁺ and CD45^- compartments in UC compared to HV colon. While CERS2 and CERS6, genes related to S1P metabolism, were significantly down-regulated genes in CD45⁺ and CD45^- compartment in UC respectively, as compared to HV colon. Additionally, RTN4 (participates in the intestinal epithelial barrier function) and PLPP3 (dephosphorylates extracellular S1P to sphingosine) were most significantly down-regulated genes from CD45⁺ segments in both UC and CD compared to HV colon.

Conclusion

In summary, our study successfully validated the GeoMx transcriptome analysis approach in FFPE colon tissue and assessed the S1P pathway gene signature difference in HV, UC and CD colon tissues supporting the pathway’s role in IBD. Results could also facilitate the identification of potential S1P pathway UC and CD disease biomarkers.Read more P173 Characterization of the gut microbiota and the colonic immune response in acute severe ulcerative colitis : the multi-omics ITAC projectWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Limited understanding exists regarding the pathogenesis of acute severe ulcerative colitis (UC). Microorganisms are proposed as potential triggers due to the resemblances to infectious colitis and the essential role played by gut microbiota in UC-related inflammation. Our aim was to identify microbiome elements and host factors associated with acute severe UC.

Methods

This was a prospective study across three referral centers comparing two UC patient groups: acute severe hospitalized UC (as per Truelove and Witts criteria) and non-severe UC. We analyzed gut microbiota using 16S rRNA gene sequencing and conducted single-cell RNA-Seq on rectal biopsies in a subgroup of patients to uncover cellular subtypes and pathways involved in mucosal inflammation. We utilized whole blood RNA-Seq to investigate the host pathways involved in mediating systemic inflammation.

Results

Forty-one patients (23 (56%) female, median (interquartile range IQR) age 42 (34 – 57) years were included: 19 with acute severe UC and 22 with non-severe UC. Compared to patients with non-severe UC, those with acute severe UC displayed distinct gut microbiota with reduced diversity, increased Proteobacteria (Escherichia/Shigella genus), and decreased Lachnospiraceae and Ruminococcaceae. In severe cases (n=4 - 13,047 cells), single-cell RNA-Seq analysis of rectal biopsies revealed distinctive patterns compared to non-severe cases (n=5 - 18,433 cells): plasmablasts showed an altered transcriptomic profile with heightened IgG expression, and there was an expanded cluster of interleukin (IL) 26 expressing T cell population. Innate immune cells exhibited a pro-inflammatory profile marked by increased expression of the IL1B gene. In blood samples, we observed no distinct differentiation of transcriptomic profiles between severe and non-severe cases.

Conclusion

Our multi-omics study reveals key cellular and bacterial components in acute severe UC pathogenesis. We identified Proteobacteria, especially Escherichia coli as a potential pathobiont in acute severe UC. At the colonic level, we observed an increased IgG/IgA ratio, while both T cells and innate immune cells indicated a pro-Th17 mucosal environment. Enhanced systemic inflammation in acute severe UC was not reflected by specific changes in immune circulating cells. These insights may pave the way for future research focusing on microbiome modulation, interventions targeting plasmablasts, or nuanced inhibition of the Th17/IL-23 axis in acute severe UC.Read more P230 Clinical characteristics, risk factors and management of patients with inflammatory bowel disease and hidradenitis suppurativa: a nationwide multicenter study of the GETECCU ENEIDA registryWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Hidradenitis suppurativa (HS) is a relapsing skin disease. Evidence supports an association between HS and inflammatory bowel disease(IBD). Aim, to explore the characteristics of patients with IBD and HS(IBD-HS) and to compare with IBD patients without HS(controls).

Methods

Retrospective, observational, multi-centre, case-control study of the Spanish nationwide ENEIDA registry. We selected all IBD patients with HS confirmed by a dermatologist. Patients were matched 2:1 by hospital and year of diagnosis with controls. A form regarding HS was completed by researchers. Efficacy of HS therapy was defined as≥50% reduction in the number of inflammatory skin lesions.

Results

A total of 273 patients(mean age 43±12 years) with IBD-HS and 546 matched controls(mean age 53±15) were included. Diagnosis of IBD preceded HS diagnosis in 208 IBD-HS patients(77%). Female sex(62 vs 44%, p=0.0001), smoking habit(45 vs 15%, p=0.0001), Crohn disease(CD) (82 vs 54%, p=0.0001), ileocolonic CD location(46 vs 36%, p=0.0001), perianal disease(55 vs 20%, p=0.0001), extensive ulcerative colitis (59 vs 45% p < 0.05) and extraintestinal manifestations(EIM)(joint and cutaneous)(38 vs 17, p=0.0001) were more frequent in IBD-HS than among controls. Body mass index(BMI) was higher in IBD-HS vs controls(28 ±7 vs 26±4, p=0.05). Hypotiroidism (4,4 vs 1,1%, p < 0.05) and psychiatric disorders(18% vs 2%, p< 0.05) were more prevalent in IBD-HS cohort. More IBD-HS patients underwent abdominal(29 vs 23, p=0,04) and perianal (35 vs 8%, p=0.000) IBD-related surgeries. The use of biologics was more frequent in IBD-HS patients(73 vs 54%, p=0.0001). HS characteristics are shown in Table 1. HS affected mainly axillary(57%) and inguinal regions (57%) followed by genital(42%), perianal(31%), buttocks(27%) and breast(17%). Paradoxical HS was observed in 19(7%) IBD-HS patients, associated to infliximab(IFX)(4, 21%), adalimumab(ADA)(11, 58%) and ustekinumab (UST)(3,16%), leading to stop them in 7(41%) patients. Regarding HS therapy, the efficacy to treatments was: IFX(30/49, 59%), ADA(49/86, 57%), UST(31/49, 69%), and other biologic(5/14, 36%).

Conclusion

In the largest cohort of IBD-HS patients ever reported, female sex, BMI, CD, smoking, and perianal disease are risk factors for HS among IBD patients. Skin and joint EMI, abdominal and perianal IBD surgeries and need of biologic therapy are more frequent among IBD-HS patients than in controls. Notably, more than half of these patients responded to anti-TNF while 2 thirds of those treated with UST exhibited a favorable response regarding HS lesions.Read more OP08 Multi-ancestry genome-wide association study of inflammatory bowel disease identifies 125 novel loci and directly implicates new genes in disease susceptibilityWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Genome-wide association studies (GWASs) have identified 320 loci associated with inflammatory bowel disease (IBD). About 15% of these loci include genes that lie in pathways targeted by drugs currently approved to treat IBD. Thus, identifying new loci can not only provide further insights into causal biology but also reveal novel therapeutic targets.

Methods

We performed a multi-ancestry GWAS meta-analysis of 67 cohorts, from European, East Asian and South Asian populations. The final dataset included 125,992 IBD patients (59,734 with CD; 57,565 with UC) and more than 1.2 million population controls (Fig 1).Genotype imputation was undertaken using the TOPMed diverse population panel and association tests were performed using REGENIE. The results were meta-analysed using a fixed effects meta-analysis via Metal.To prioritise effector genes and generate therapeutic hypotheses, we integrated our results with bulk and single cell transcriptome data from relevant tissues and cell types. Through colocalization analyses we identified those signals driving the expression of nearby genes (cis-eQTL), suggesting that aberrant expression of these genes underpins the association.

Results

We identified 290 new independent disease susceptibility association signals. Out of these, 125 new signals are located >1Mb from any previously reported loci. Six new loci contain genes implicated in monogenic syndromes that include colitis GUCY2C, G6PC3, NFKBIA, PIK3CD, PIK3R1, ZBTB24.Up to 40% of all disease susceptibility association signals colocalize with a cis-eQTL. For instance, a new variant associated with increased risk of UC (P=8x10^-14) decreases the expression of the transmembrane mitochondrial protein TSPO in T cells, B cells, macrophages, and transverse colon. Pro-inflammatory macrophages show consistent TSPO downregulation. Loss of TSPO in mice causes exacerbated DSS-induced colitis. Ongoing clinical trials are evaluating whether targeting this gene could ameliorate the immune response in multiple sclerosis patients. We also identified a new CD susceptibility variant (P=3x10^-16) associated with increased expression of WNK1 in monocytes and macrophages. Whereas loss of WNK1 in mice show increased expression of IL-1B in response to NLRP3 inflammasome activation; it also stimulates autophagy through the upregulation of the PI3KC3 complex. Impaired autophagy has shown to be key in promoting CD susceptibility.

Conclusion

Integrating molecular data from multiple cell types and conditions not only expands our ability to determine novel candidate causal genes, it also provides additional evidence of the utility of genetics as an instrument to guide the development of new therapeutic drugs or the repurposing of existing molecules.Read more OP17 IBD ulcers are characterized by bioactive interleukin-1 and transcriptomic hallmarks of stromal cell state reprogrammingWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The programs that perpetuate the inflammation and prevent epithelial repair in Inflammatory Bowel Disease (IBD) remain unclear. Interleukin (IL)-1 plays a role in the maintenance of mucosal homeostasis but also in IBD. Expansion of IL-1 expressing myeloid cells is a hallmark of IBD tissue, including severe and anti-TNF unresponsive disease, and IL-1 expression is highly localized to ulcer beds. However, little is known about the presence of bioactive IL-1 proteins in the cell-free mucosal environment of IBD, nor whether IL-1-driven programs affect epithelial regeneration in IBD ulcers.

Methods

We established a highly sensitive assay (~500-fold greater than ELISA) to assess bioactive extracellular IL-1 from previously cryopreserved IBD biopsies. We assessed a cohort of Crohn’s Disease (CD, n=23), Ulcerative Colitis (UC, n=18) and non-IBD (n=17) patients, with biopsies from paired inflamed/uninflamed regions (primarily colon but also ileal). We assessed IL-1 bioactivity, including IL-1α vs IL-1β contributions, and performed RNA-seq of samples’ matched cellular compartments. An ulcer-associated gene signature was interrogated in a single-cell (sc)RNA-seq cohort (n=42) of very early onset (VEO)IBD including monogenic disorders, as well as publicly available IBD bulk RNA-seq datasets and scRNA-seq of mouse models of colitis.

Results

IL-1α and IL-1β bioactivity corresponded with disease and ulcer severity in CD and UC. The most extreme signals were seen in select CD patients with deep ulceration. IL-1α was the predominant contributor to total IL-1 bioactivity in most patients although several with ulcers displayed IL-1β predominance. IL-1 bioactivity correlated with IL-1 transcripts in matched RNA-seq, and weighted gene co-expression network analysis revealed a compelling ulcer-specific module. This module contained transcription factors and genes related to cell state, validated in publicly available datasets (e.g. RISK cohort of ileal CD and scRNA-seq of murine DSS colitis), that when interrogated in a scRNA-seq dataset of VEOIBD (including patients with IL-10RA mutations characterized by deep ulcers), suggests an orchestrated IL-1-driven myeloid/stromal response to epithelial ulceration involving cell state reprogramming and loss of key myofibroblast populations.

Conclusion

Mucosal ulceration in IBD is associated with bioactive IL-1α and IL-1β proteins, and transcriptomic evaluation of the same correlates with bioactive signal. An ulcer-associated gene module, validated in other datasets, sheds light on IL-1 biology in intestinal epithelial repair. Results strongly suggest the IL-1 signaling pathway being an attractive and precision-based therapeutic target in subsets of IBD patients.Read more OP25 Dual activation of GCGR/GLP1R signaling ameliorates intestinal fibrosis via metabolic regulation of histone H3K9 lactylation in epithelial cellsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Intestinal fibrosis is a significant clinical challenge in inflammatory bowel diseases, but no effective anti-fibrotic therapy is currently available. GCGR and GLP1R are both peptide hormone receptors involved in energy metabolism of epithelial cells. However, their role in intestinal fibrosis and the underlying mechanisms remain largely unexplored.

Methods

Intestinal tissues from patients with Crohn’s Disease (CD) (n=20) were obtained. AAV9-Glp1r-shRNA, AAV9-Gcgr-shRNA or AAV9-NC-shRNA were used to transfect mice. Murine colons were analyzed by single-cell RNA sequencing (seq) and metabonomics. Glycolytic metabolism of epithelial cells was analyzed with bulk RNAseq and seahorse-XF technology, while lactylation levels were verified using antibodies against diverse forms of lactylated histones. Then a range of GCGR/GLP1R dual-target ultralong-acting peptides were synthesized, and their agonistic activities were assessed in HEK293 cells that stably expressed either human GLP1R or GCGR, using a cAMP response element-driven luciferase reporter. The antifibrotic activity of the leading peptide 1907B was functionally evaluated in vitro and in vivo.

Results

GCGR and GLP1R were reduced in the stenotic ileum of patients with CD as well as in the fibrotic colon of mice with chronic colitis. In the chronic model, Gcgr/Glp1r dual knockdown worsened the degree of fibrosis in mice, and increased glycolysis-related metabolites, with lactate exhibiting the most prominent alterations. In the TGFβ1-induced epithelial cell model, exogenous and endogenous lactate induced fibrotic genes expression and overwhelming histone lactylation in H3K9 (H3K9la). Further, cells overexpressing H3.1 (K9R) exhibited lower levels of fibrotic genes and proteins after treatment with lactate compared with the H3.1 WT group. Then 1907B, the leading GCGR/GLP1R dual-target peptide, normalized the ATP production rate of glycolysis, extracellular lactate, H3K9la levels of promoters related to fibrosis genes, and further ameliorated intestinal fibrosis in vivo.

Conclusion

We uncovered the role of GCGR/GLP1R in regulating EMT involved in intestinal fibrosis via histone lactylation. Simultaneously activating GCGR/GLP1R with the novel dual agonist 1907B holds promise as a treatment strategy for alleviating intestinal fibrosis.Read more DOP08 A novel multiomic approach to unravel the mechanisms of action of biologics and tofacitinib in Inflammatory Bowel DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Inflammatory bowel diseases (IBD), which includes Crohn´s disease (CD) and ulcerative colitis (UC), are complex and heterogeneous diseases characterized by a multifactorial etiology. IBD prevalence is increasing worldwide. The availability of diverse treatments with different mechanisms of action have revolutionized the ability to achieve clinical remission and endoscopic healing. The aim of this study was to achieve a deeper understanding of the mechanism of action and response to different IBD treatments using a multiomic approach.

Methods

We analysed the metabolome of serum and urine, metagenome of stool samples and transcriptome and proteome of mucosal biopsies from 53 patients with moderate-to-severe CD and 50 UC patients initiating biologic therapy (anti-TNF, ustekinumab or vedolizumab) or tofacitinib. Patients were assessed at 14 weeks for endoscopic remission and were categorized into responders or non-responders. The methodologies employed in this study were RNA-seq analysis, liquid chromatography-mass spectrometry, nuclear magnetic resonance, and 16S rRNA gene sequencing.

Results

The multiomic analyses revealed substantial alterations in the transcriptome, proteome, metabolome and metagenome of both responders and non-responders IBD patients before and after treatment (14 weeks) to different biologics and tofacitinib (Table 1). Gene enrichment analysis showed notewhorthy differences in all study comparisons, except for patients with CD and UC who did respond to anti-TNF and tofacitinib. Functional enrichment analysis of differentially expressed proteins indicated several processes that could be potentially involved in the mechanisms of action of different treatments. More differences were observed in lipoproteins than in serum and urine metabolites in the different study comparisons. Finally, metagenomic findings indicated changes in the composition of gut bacteria communities among CD patients treated with ustekinumab and UC patients treated with tofacitinib (responders vs non-responders at 14 weeks) (Figure 1).

Conclusion

The present study provides novel insights into the mechanisms of action of different IBD treatments from a multiomic approach. Nonetheless, multiomic data integration and validation studies are needed to confirm these findings within a more extensive and independent cohort of patients.Read more DOP09 Models for predicting Crohn Disease (CD) exacerbation using serum and fecal metabolomicsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Metabolites, produced endogenously or derived from the gut microbiome, are key mediators and effectors of many cellular functions, but there are only scant data on their temporal changes along CD course. We analyzed the dynamics of serum and fecal metabolome in a prospective cohort of quiescent CD patients over 2 years or until the occurrence of a clinical flare, aiming to identify whether changes in the metabolome precede and predict a clinical relapse.

Methods

Untargeted metabolomics was performed using LC/MS. Multivariate analyses in MaAsLin2 were applied to identify differentially abundant metabolites between CD cases who relapsed and those who remained in remission. Our models used the "Leave-One-Out" approach to compensate for over-fitting bias.

Results

We included 110 serum samples and 232 fecal samples from 44 CD participants recruited in remission (mean age 31.73 years, 59% males; Table 1). The median follow-up time was 630 days (IQR 500-808). Demographic, biomarkers, and treatment exposures were not significantly different between the 11 that experienced flare during follow-up and the 33 that remained in remission throughout. We compared the metabolomics between relapsers and non-relapsers using only preflare samples after excluding samples from a particular subject in the "Leave-One-Out" approach. The top 3 metabolites in each direction and comparison and their abundance preflare in the non-relapsers and relapsers are shown (Fig. 1A-B). We then calculated a flare index for that excluded subject, using the sum peak area ratio of all metabolites that were increased and decreased preflare. A receiver operating characteristic (ROC) area under the curve (AUC) using the "individual" flare index after z-score normalization was able to predict a subsequent flare with AUC=0.73, 95% CI 0.52-0.93 for serum metabolomics (Fig. 1C) compared with AUC=0.62 (95% CI 0.40-0.84) for CRP and AUC=0.74 (95% CI 0.54-0.94) for FCP, in the same sampling cohort. For the stool sampling cohort, metabolomics predictive accuracy was AUC=0.75 (95% CI 0.5-0.99; Fig. 1D) compared with AUC=0.67 (95% CI 0.49-0.84) for CRP and AUC=0.71 (95% CI 0.55-0.86) for FCP. Survival plot analyses after selecting Youden point based on ROC (Fig. 1C-D) showed moderately better performance for fecal flare index with log-rank Hazard Ratio (HR) of 8.20 (95% CI 1.98-34.20), than for the serum with HR of 3.45 (95% CI 1.5-11.37).

Conclusion

In a prospective cohort of quiescent CD patients, we identified metabolites in the serum and feces that were incorporated in models that can predict CD flare. These can be used to guide personalized preemptive therapy intensification and provide insight into the underlying mechanism of CD flares.Read more OP03 Efficacy and safety of the oral selective sphingosine-1-phosphate-1 receptor modulator VTX002 in moderately to severely active Ulcerative Colitis: results from a randomised, double-blind, placebo-controlled, phase 2 trialWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

VTX002 is a novel oral selective sphingosine-1-phosphate-1 (S1P1) receptor modulator in development for the treatment of ulcerative colitis (UC). The efficacy and safety of VTX002 in patients with ulcerative colitis (UC) was assessed in a phase 2, multicentre, randomised, double-blind, placebo-controlled study (NCT05156125).

Methods

Adults (N=213) with moderately to severely active UC (modified Mayo score [MMS] 4-9) and inadequate response/intolerance to conventional and/or advanced (approved biologics or Janus kinase inhibitor) therapies were randomised 1:1:1 to once daily treatment with placebo (n=70), 30 mg (n=73) or 60 mg (n=70) VTX002 tablets for 13 weeks. Patients underwent a 6–8-day dose titration up to the assigned treatment dose. The primary endpoint was clinical remission (MMS stool frequency subscore ≤ 1, rectal bleeding subscore=0, and endoscopic subscore [ES] ≤ 1) at week 13. A protocol amendment limiting eligibility to patients with baseline MMS 5-9 resulted in 213 and 209 patients in the safety and efficacy populations, respectively. Key secondary endpoints were endoscopic improvement, symptomatic remission, histologic remission, and endoscopic improvement-histologic remission. Endoscopic remission and histologic-endoscopic mucosal improvement (HEMI) were also assessed (see Table 1 for outcome definitions). Adverse events (AEs) and laboratory abnormalities were assessed for safety.

Results

The primary endpoint of clinical remission at week 13 was achieved (27.9% of patients who received VTX002 60 mg vs 11.4% of patients who received placebo, ∆=16.5%, p=0.0184). Both doses of VTX002 achieved nominal statistical significance for all key secondary endpoints (Table 1).Significantly greater proportions of patients who received VTX002 60 mg achieved endoscopic remission and HEMI compared to patients who received placebo (29.4% VTX002 60 mg vs 7.1% placebo, ∆=22.3%, p=0.0012, and 32.4% VTX002 60 mg vs 10.0% placebo, ∆=22.4%, p=0.0026, respectively). A dose-dependent decrease of 67.7% and 53.9% in mean absolute lymphocyte count (ALC) from baseline was observed at week 8 for patients who received VTX002 60 mg and 30 mg, respectively. Most AEs were mild to moderate (Table 2). No AEs of bradycardia, atrioventricular block, serious infections, macular oedema, or deaths were reported.

Conclusion

The S1P1 receptor modulator VTX002 was well-tolerated and statistically superior to placebo for induction of clinical, endoscopic, histologic, HEMI, and symptomatic remission/response at week 13. These positive findings, including a dose-dependent pharmacodynamic reduction in ALC, support phase 3 development of VTX002 for treatment of UC.Read more OP16 A novel artificial intelligence-assisted Image Enhanced Endoscopy assesses accurately “vascular-healing” and predicts long-term clinical relapse in patients with ulcerative colitis: a prospective cohort studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Ulcerative colitis (UC) is a chronic specific inflammatory bowel disease that alternates between remission and relapse statuses. Microvascular finding observed in image-enhanced endoscopy (IEE) has been attracting attention to detect inflammation and predict outcomes in patients with UC; however, this requires specialist endoscopists. Artificial intelligence (AI)-assisted IEE may help to overcome this problem. We developed a novel AI-based narrow-band imaging (NBI) system, using 8853 images from 167 patients, that can be adapted to commercially available various endoscopes and determined if AI-identified ‘vascular-healing’ could predict relapse and guide treatment in patients with UC.

Methods

This prospective cohort study analyzed data from 100 patients with UC in clinical remission. The endoscopists performed colonoscopy using the AI system, which outputs identified the target mucosa as vascular-active or vascular-healing. The Mayo endoscopic subscore (MES), AI outputs, and histological assessment were recorded for six colorectal segments of each patient. Patients were then followed up for 12 months. Clinical relapse was defined as a partial Mayo score >2.

Results

The clinical relapse rate was significantly higher in the AI-based vascular-active group [23.9% (16/67)] compared with the AI-based vascular-healing group [3.0% (1/33)] (P=0.01). In a sub-analysis predicting clinical relapse in patients with MES ≤1, the area under the curve for the combination of complete endoscopic remission and vascular healing (0.70) was increased compared with that for complete endoscopic remission (MES=0) alone (0.65). Colonoscopy by a total of 27 endoscopists, comprising 11 experts and 16 trainees, evaluated 35 and 65 patients, respectively. The sensitivity, specificity, and accuracy for predicting clinical relapse did not differ significantly according to the endoscopist’s experience: 100%, 39.3%, and 51.4%, respectively, for experts and 90.0%, 38.2%, and 46.2%, respectively, for trainees (P>0.95, P>0.95, and P=0.84, respectively).

Conclusion

Colonoscopy using the AI-based NBI system for diagnosing “vascular-healing” identifies patients with UC at high risk of relapse and thus aids future disease management.Read more OP09 Oral ritlecitinib and brepocitinib in patients with moderate to severe active Crohn’s Disease: Data from the PIZZICATO umbrella studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Oral ritlecitinib (RIT; JAK3/TEC family kinase inhibitor) and brepocitinib (BRE; TYK2/JAK1 inhibitor) are being assessed in a 64-week (wk) phase 2a randomised, double-blind, induction-maintenance, umbrella study (PIZZICATO; NCT02958865) in participants (pts) with moderate-to-severe active Crohn’s disease (CD) with inadequate, loss of response or intolerance of corticosteroids, immunosuppressants or biologics. We report the efficacy and safety results from the 12-wk induction period.

Methods

Pts 18-75 years old with endoscopic confirmation of active CD with Simple Endoscopic Score for CD (SES-CD) ≥7/≥4 for isolated ileal disease, and average daily liquid/soft stool frequency (SF) ≥2.5 or daily abdominal pain (AP) ≥2.0 were included. Pts were randomised to RIT 200 mg once daily (QD) for 8 wks then 50 mg QD for 4 wks and matching placebo (PBO) in a 2:1 ratio or BRE 60 mg QD for 12 wks and matching PBO in a 2:1 ratio. Pts continued in their respective arms with open-label RIT 50 mg or BRE 30 mg QD for 52 wks. PBO arms were combined for analysis. Pts achieving SES-CD 50 (≥50% reduction in SES-CD from baseline [BL]; primary endpoint Wk 12), Clinical Disease Activity Index (CDAI) remission (CDAI<150) and CDAI-100 response for pts with BL CDAI≥220, clinical response (≥30% reduction from BL in AP or SF; neither worse than BL) and remission (SF≤1.5 and AP≤1; neither worse than BL) were assessed. Safety was also evaluated.

Results

A total of 244 pts were randomised and received treatment in the induction period with BL mean age of 34.6-36.5 years, median SES-CD 11-14, and prior biologics experience 69-76% across groups. The proportion of pts achieving SES-CD 50 was significantly higher at Wk 12 with RIT 200/50 mg QD and BRE 60 mg vs PBO (change from PBO: RIT 14.3% [90% CI, 4.0, 24.5], BRE 21.4% [10.0, 32.9]; Table). Statistical significance vs PBO was observed for RIT at Wks 8 and 12 and BRE at Wk 12 for CDAI remission, CDAI-100, clinical response and remission by SF or AP. Most treatment emergent adverse events (TEAEs) in both groups were mild or moderate. Herpes infections occurred in 1 pt in each group and serious infections in 1 pt in RIT and 2 in BRE. No deaths or malignancies occurred. No events of thromboembolism or MACE occurred for RIT. One pt on BRE had a TEAE of pulmonary embolism. There were no clinically significant observations for labs.

Conclusion

Both RIT and BRE met the primary endpoint in the induction period with significant clinical improvement vs PBO in pts with active CD. Other meaningful efficacy endpoints had similar results to the primary endpoint for both therapies. RIT and BRE had an acceptable safety and tolerability profile that was consistent with previous studies.Read more OP15 High-definition white light endoscopy with segmental re-inspection is non-inferior compared to dye-based chromoendoscopy in Inflammatory Bowel Disease: the randomized controlled HELIOS trialWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Patients with colonic inflammatory bowel disease (IBD) undergo endoscopic surveillance to detect and remove colorectal neoplasia (CRN). Although high-definition dye-based chromo-endoscopy (HD-CE) is the recommended modality in guidelines, high-definition white light endoscopy (HD-WLE) with matched procedural time may yield similar neoplasia detection rates. We designed a non-blinded, randomized controlled trial in four academic hospitals aiming to compare three endoscopic surveillance techniques in IBD patients for the outcome of CRN detection rate.

Methods

Eligible patients were aged ≥18 years and scheduled for colitis-associated CRN surveillance according to Dutch IBD surveillance guidelines. Patients were excluded in case of insufficient bowel cleansing, active colitis, or if >50% of the colon was resected. Patients were randomly assigned (2:2:1) to undergo HD-WLE with segmental re-inspection (SR), HD-CE, or single pass HD-WLE. The primary outcome was CRN detection rate, defined as the proportion of procedures in which macroscopic CRN was detected. Secondary outcomes included the number of CRN and withdrawal time. To demonstrate non-inferiority of HD-WLE with SR compared to HD-CE (one-sided testing, α=0.05, 1−β=0.8, non-inferiority (NI) margin -10%), and superiority compared to single-pass HD-WLE (two-sided testing, estimated CRN detection rate of 24% and 12%, respectively1) with Mantel-Haenszel analyses, a total of 566 patients were needed.

Results

In total, 666 patients were randomized, 563 fulfilled all study criteria and were analysed per protocol (table 1). Of these, 51.8% were male, with a median age of 51 years (interquartile range 35-63). CRN detection rates were 9.8% for HD-WLE with SR, 13.1% for HD-CE, and 6.1% for single pass HD-WLE. HD-WLE with SR was non-inferior compared to HD-CE (Δ-3.1%, lower boundary of the 95% confidence interval (CI) -8.1 not exceeding the NI margin of -10%, p<.05). HD-WLE with SR was not superior compared to single-pass HD-WLE (Δ3.7%, 95% CI -2.5:9.1%, p=0.31). A significant difference was found between arms for the number of detected CRN (n=29 vs n=36 vs n=8 for HD-WLE with SR, HD-CE and single-pass HD-WLE, respectively (p=.04)) and withdrawal time (p=.03, table 1). One advanced lesion was detected (high-grade dysplasia in the HD-CE arm).

Conclusion

In this large, randomized controlled trial, HD-WLE with SR was non-inferior compared to HD-CE for CRN detection in IBD patients. HD-WLE with SR was not superior to single-pass HD-WLE, although this may have resulted from lower than expected neoplasia yields and subsequent lower power. These results suggest that HD-WLE with SR may provide a feasible alternative to HD-CE in clinical practice (NCT04291976).¹Imperatore et al. JCC 2019;13(6):714-24Read more OP24 SPP1 in colitis-associated colon cancerWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Patients with ulcerative colitis (UC) and Crohn’s disease (CD) face a lifelong risk of developing colitis-associated carcinoma (CAC). Current insights into CAC development originate from murine CAC models, while human CAC studies primarily focus on mutational analyses. Although the mutational landscape reveals distinct patterns and frequencies compared to colorectal cancer, it falls short in elucidating the inflammatory mechanisms of CAC development. Consequently, we adopted a multi-omics approach to unravel CAC carcinogenesis, utilizing human samples from patients with CD, CD-associated CAC (CD-CAC), UC, and UC-associated CAC (UC-CAC). Findings were further validated in vitro using human colon organoids.

Methods

A Nanostring Immunology v2 panel was employed on RNA (archival FFPE sections) from 40 patients suffering from either IBD or CAC, alongside inflammation-free healthy controls (n=10 per group). Our data revealed a robust upregulation of the SPP1 (Secreted Phosphoprotein 1) gene encoding osteopontin (OPN) in CAC patients. Prospectively, we extended our methodology to an unbiased imaging-based spatial RNA in situ sequencing (ISS) approach (477 genes, Xenium, 10X Genomics) using FFPE sections from CAC and UC patients (n=3 per group). This provided insights into the spatial expression of SPP1 and its target receptors at a subcellular resolution. Findings were validated using whole FFPE section confocal microscopy. In addition, in vitro models, including human UC organoids, were analyzed by bulk RNA-Seq, RT-qPCR, and downstream functional assays.

Results

Nanostring Immunology v2 gene expression data revealed upregulation of the SPP1 gene encoding OPN (Fig 1A) and EMT transcription factors FN1 and ZEB1 in CAC patients. Xenium RNA in situ sequencing (ISS) unveiled the spatial heterogeneity of SPP1 expression in CAC (Fig 1B). Unsupervised graph-based clustering identified an SPP1+CD68+ macrophage cluster exclusively in CAC (Fig 1C), validated through OPN/CD68 immunostainings (Fig 1D). In vitro OPN stimulation across multiple human and mice colon organoid models excluded OPN as the trigger of EMT. Interestingly, Xenium ISS and immunostainings revealed a mutually exclusive spatial location of SPP1/OPN+ macrophages and CD8+ T cells (Fig 1E, F and G).

Conclusion

SPP1 is significantly upregulated in CAC (RNA and protein), expressed by CD68+ macrophages. In vitro OPN stimulation demonstrated no direct effect on intestinal epithelial organoids. The mutually exclusive spatial locations of SPP1/OPN+ macrophages and CD8+ T cells suggests a crucial role of SPP1/OPN in modulating the immunosurveillance of CAC cells by CD8+ tumour lymphocytes.Read more OP38 Should all patients with newly diagnosed inflammatory bowel diseases be screened for metabolic bone disease? Results from a Danish population-based inception cohort studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Inflammatory bowel diseases (IBD), encompassing ulcerative colitis (UC) and Crohn’s disease (CD), are associated with an increased risk of metabolic bone diseases (MBD). The aim of the current study was to evaluate for the occurrence of MBD in which all patients with newly diagnosed IBD are offered a Dual-energy X-ray absorptiometry (DXA) scan. Secondly, we aimed to identify risk factors for development of MBD.

Methods

All adult patients with newly diagnosed IBD within a catchment area corresponding to ~20% of the Danish population have since May 2021 been enrolled in an ongoing prospective population-based inception cohort, IBD Prognosis Study. Herein, all participants were, as part of the initial work-up, invited to a DXA scan at IBD diagnosis. A T-score< −2.5 standard deviations (SD) was diagnostic for osteoporosis, while a T-score between –1 and –2.5 defined osteopenia. Multivariate analyses adjusted findings for age, gender, and medication differences.

Results

A total of 316 patients with newly diagnosed IBD (UC: 178, CD: 117, unclassified IBD (IBDU): 21) received a DXA scan within 90 days (interquartile range (IQR) 51-139 days). Baseline characteristics of the population were similar to those previously described for newly diagnosed IBD.In total, 48 (27%, females (F): 26%, males (M): 28%) and 17 (10%, F: 14%, M: 5%) patients with UC were found to have osteopenia and osteoporosis, resp. The corresponding numbers for CD were 23 (20%, F: 15%, M: 24%) and nine (8%, F: 7%, M: 9%).Subgroup analysis showed a high occurrence of osteopenia in both UC and CD regardless of age group (Table 1). No difference between UC and CD was observed in terms of the risk of osteopenia (adjusted odds ratio (aOR)=1.86 (95% confidence interval (CI) 0.99-3.60) or osteoporosis (OR=1.42 (95% CI 0.53-4.08)).Low albumin level (<36 g/L) was the only factor associated with osteopenia in patients with UC (aOR=2.57 (95% CI 1.05-6.53). In patients with CD, no risk factors were identified. However, the risk of osteoporosis was independently associated with age higher than 65 years in both UC (aOR=13.4 (95% CI 3.78-51.36)) and CD (aOR=6.39 (95% CI 1.09-35.47)), while female gender was not relevant (UC: aOR=2.63 (95% CI 0.75-10.98), CD: (aOR=0.47 (95% CI 0.08-2.20)).Finally, the risk of MBD was not associated with IBD phenotype, medications, or patient-reported or endoscopic severity.

Conclusion

To our knowledge, the current study is the first evaluation of DXA scans as a screening tool for patients with newly diagnosed IBD in a population-based setting. We found a high incidence of osteopenia affecting every fourth patient at IBD diagnosis. These findings are concerning given the high risk of repeated need for systemic steroids in this patient population.Read more OP39 Vedolizumab response in ulcerative colitis associates with reduced IgG+ plasma cells and FcγR signalingWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Vedolizumab (VDZ) targets the gut-homing receptor α4β7. Despite its widespread use as a frontline therapy for ulcerative colitis (UC), its mode of action (MOA) remains unclear. Previously, we documented that response to VDZ is associated with size loss of gut-associated lymphoid tissues (GALT). To further understand drug MOA, here we aimed at defining the relationship between GALT attrition and resolution of inflammation.

Methods

Tissue immunofluorescence (IF) was performed on two independent UC cohorts (n=60, n=21) studied longitudinally pre- and post-VDZ. Peripheral blood mononuclear cells from UC patients (n=56) were examined at week 0 (pre-VDZ) and 14 (post-VDZ) by flow cytometry, while intestinal biopsies were analyzed in a subset of patients. Transcriptomic analyses were performed in a third cohort of 401 UC patients and 243 controls where bulk RNA-sequencing was performed on intestinal biopsies. Finally, data from a fourth validation cohort (n=31) was examined pre- and post-VDZ.

Results

Using IF, we examined follicular naïve B (FB) cells (IgD⁺), germinal center (GC) B cells (BCL6⁺CD3^-) and total T cells (CD3⁺), and identified three GALT types: organized aggregates (demarcated B/T cell zones) with GC, organized aggregates without GC, and poorly organized aggregates (Fig1A). When comparing pre- and post-VDZ, Responders (R) had a significant reduction in GALT organization, while no change was seen in Non-Responders (NR). The number of FB cells was significantly reduced post-VDZ in R but not in NR (Fig1B), with no change in T cells (Fig1C). The reduction in FB was validated using transcriptomic data (Fig1D). To explore potential consequences of GALT attrition, we analyzed circulating β7⁺ (GALT-generated) and β7^- plasmablasts (PB). The frequencies of β7⁺IgG⁺ and β7⁺IgA⁺ PB were significantly reduced post-VDZ in R, but not in NR (Fig1E). No change was observed in β7^- PB post-VDZ (Fig1F). Among β7⁺ PB, there was a greater reduction in IgG⁺ compared to IgA⁺ (Fig1G). Furthermore, colonic IgG⁺ plasma cells (PC) were significantly reduced post-VDZ in R but not in NR (Fig1H). To evaluate IgG-mediated proinflammatory function, we studied the expression of FcγR-pathway genes in colonic biopsies. Importantly, the FcγR-pathway was enhanced in inflamed tissues of UC patients (Fig1I-J) and was significantly reduced in R (but not in NR) post-VDZ (Fig1K).

Conclusion

Our work demonstrates a novel effect of anti-α4β7 blockade that results in intestinal lymphoid aggregate attrition through impaired recruitment of naïve B cells, leading to the suppression of IgG-driven immune responses and proinflammatory FcγR signaling. These data highlight the targeting of GALT as a novel therapeutic paradigm in IBD.Read more DOP20 Changes in systemic antibody epitope repertoires from preclinical to established Inflammatory Bowel DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Inflammatory bowel diseases (IBD), encompassing Crohn's disease (CD) and ulcerative colitis (UC), exhibit unique immunological changes early in development. Although >300 IBD-specific antibody responses have been identified¹, systemic antibody epitope repertoires of preclinical IBD remain elusive. This study aimed to profile systemic antibody responses at unprecedented depth in individuals before and after the onset of IBD, aiming to identify preclinical disease biomarkers.

Methods

This study included individuals participating in the Lifelines Cohort Study, a large prospective population-based cohort study in the Netherlands including 167,000 individuals with longitudinal follow-up. Participants without IBD at baseline were screened for any reported IBD diagnosis during follow-up (2006-2021). Individuals who reported IBD during follow-up and with available serum samples were included. Samples at baseline (pre-diagnosis) and during follow-up (post-diagnosis) were used to profile antibody repertoires against 344,000 rationally selected microbial-, food-, and immune antigens using phage-display immunoprecipitation sequencing (PhIP-Seq).

Results

A total of 178 individuals with new-onset IBD were identified (Fig. 1). Median follow-up time until diagnosis was 3.9 (IQR: 3.4-4.3) years. Most individuals reported newly developed UC (n=123, 69.1%), followed by CD (n=44, 24.7%), and undetermined IBD (IBD-U, n=11, 6.2%). A total of 5,174 antibody responses were observed in 5-95% of participants. Fifty-nine antibodies were differentially abundant (FDR<0.05) pre-diagnosis vs. post-diagnosis (Fig. 2), 14 of which (24%) were previously reported as IBD-specific¹. Thirteen were more (22%) and 46 less (78%) frequently observed post-diagnosis. Those developing UC exhibited 33 differentially abundant antibody responses, while those with CD exhibiting only four (FDR<0.05). Individuals developing IBD exhibited lower frequencies of antibody responses against EBV-associated peptides post-diagnosis, e.g. Epstein-Barr nuclear antigen-1 (EBNA-1) and capsid protein V26, and varicella-zoster virus, alongside higher antibody responses against bacterial flagellins. Individuals developing UC showed elevated antibody responses mainly against viruses (e.g. human adenovirus C, enteroviruses B/C) and particular pathogenic bacterial species (e.g. pneumococcal histidine triad proteins) post-diagnosis compared to pre-diagnosis.

Conclusion

Distinct antibody responses appear years before IBD diagnosis, indicating potential involvement in pre-clinical disease development. Furthermore, post-diagnosis, lower frequencies of antibody responses against EBV may suggest reduced immunogenicity against this virus in early disease pathogenesis.1. Bourgonje et al. Immunity. 2023.Read more DOP21 Histo-endoscopic remission (HEMR) Predicts Future Relapse in Patients with Ulcerative Colitis and is Associated with Lower Colectomy RiskWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Treating beyond clinical and endoscopic remission, aiming for histological remission, is an aspiring target in ulcerative colitis [UC]. Hence, combined histo-endoscopic endpoints are increasingly being embraced. We assessed different degrees of histologic remission in patients with UC and their association with long-term outcomes.

Methods

UC patients achieving endoscopic improvement (Mayo endoscopic score [MES] ≤1) were recruited at colonoscopy. Clinical data were retrospectively collected from medical records. Endoscopies were video-recorded and biopsies from the most affected segment were collected for histological assessment and RNAseq (in case of MES 0 rectosigmoid biopsies were collected according to previous disease extent). Geboes Score [GS] and Robarts Histopathology Index [RHI] were determined for each biopsy by two pathologists blinded to the endoscopic scores. Non-histo-endoscopic remission [NHR], histo-endoscopic mucosal remission [HEMR] and histo-endoscopic mucosal normalization [HEMN] were defined as GS ≥2B.1, GS <2B.1 and GS ≤0.1. Clinical relapse was defined as the need for dose optimization, switching therapy or initiation of corticosteroids during follow-up. Long-term outcomes were analysed using log-rank test and Cox regression.

Results

Between 2016 and 2022, a total of 172 UC patients were included (Table). Endoscopic remission (MES 0) was achieved in 104 (60.4%) patients. NHR, HEMR and HEMN were observed in 15 (14.4%), 69 (85.6%), 51 (49.0%) of MES 0 patients and 32 (47.1%), 36 (52.9%), 18 (26.5%) of MES 1 patients. During a median [IQR] follow-up of 2.8 (1.9-3.9) years, 51 (29.7%) patients relapsed, and 7 (4.0%) patients needed colectomy. Relapse- and colectomy-free survival (Figure) were significantly higher when comparing HEMR to NHR (p<0.001 for both). This difference was not observed for endoscopic score (MES 0 vs. 1) or different degrees of histologic remission (HEMN vs. HEMR). The univariate Cox regression showed that histo-endoscopic activity, clinical activity (i.e., patient reported outcomes (PRO-2) for stool frequency or rectal bleeding > 0) and prior advanced therapy failure were associated with an increased risk of relapse. The multivariate Cox regression identified histo-endoscopic activity as the only risk factor for relapse (adjusted hazard ratio [HR]) = 3.01, 95% confidence interval [1.69-5.34], p<0.001).

Conclusion

In this cohort of UC patients with endoscopic improvement, 14.4% of MES 0 and 47.1% of MES 1 patients still showed signs of histologic activity (i.e., presence of neutrophils in the lamina propria or epithelium. Histologic remission was a superior predictor of future outcome (relapse, colectomy) when compared to endoscopic remission and showed to be the sole predictor of relapse.Read more DOP80 Prevalence and factors associated with Inflammatory Bowel Disease (IBD) activity during pregnancy: updated data from the DUMBO RegistryWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

IBD remission is key for pregnancy outcomes. Previous studies have suggested a disease recurrence risk of approximately 30% in patients in remission at conception, but this could be influenced by disease control in the periconceptional period and the discontinuation of treatments for IBD during pregnancy.

Aim

To provide updated data on the incidence of disease relapse during pregnancy in IBD patients and to identify predictive factors of relapse.

Methods

Pregnant patients with IBD from DUMBO registry were included. DUMBO is a prospective, observational, and multicentre registry, endorsed by GETECCU which enrols pregnant women with IBD over 5 years in 70 centres in Spain. Study protocol is summarized in figure 1a. Relapse was defined based on the Crohn’s Disease Activity Index and the Partial Mayo Score in Crohn’s disease (CD) and ulcerative colitis (UC), respectively. Only patients in clinical remission at conception were considered for the relapse risk analysis (Cox-regression analysis). Only serious adverse events (SAE) were recorded.

Results

1,033 patients were available in DUMBO registry, 57 (5.5%) had active disease at conception. 830 patients had given birth (98% singleton), 69 had early termination (48 of them miscarriages), and 134 pregnancies were still ongoing. The probability of having active disease at each trimester was higher in patients with active disease at conception (table 1a). Seven patients underwent surgery due to IBD during pregnancy (3 abdominal and 4 perianal surgery); all of them were in remission at conception. The proportion of patients with severe infections during pregnancy was higher in patients with active disease during pregnancy (2.8% vs. 0.8%, p<0.05); there were no differences in other SAE based on the activity. 73 out of 976 patients in remission at conception relapsed throughout pregnancy or puerperium (figure 1b, table 1b). The proportion of patients who withdrew treatment during pregnancy, excepting mesalamine, was similar between relapsers and non-relapsers (table 1c). To have UC vs. CD (Hazard ratio=3, 95% confidence interval=1.8-5.3) was the only variable associated with the risk of relapse.

Conclusion

The risk of having active disease during pregnancy was higher in patients with activity at conception. The risk of relapse in patients in remission at conception was lower than previously described. The risk of relapse was 3-fold higher in UC than in CD. Since most relapses occur from the second trimester of gestation onwards, and serious complications (including surgery) can occur also in patients in remission at conception, monitoring IBD during this period should be closely conducted.Read more DOP81 Rosnilimab, a novel PD-1 agonist monoclonal antibody, reduces T cell proliferation, inflammatory cytokine secretion, and PD-1high expressing CD4 and CD8 T cells: Results from a Phase 1 healthy volunteer clinical trialWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Programmed cell death protein 1 (PD-1) is expressed on activated T cells and is a key co-inhibitory node in immune regulation. By targeting regulatory mechanisms to modulate immune cells driving disease, there is an opportunity to restore immune balance. Rosnilimab is a PD-1 agonist antibody designed to reduce T cell proliferation and inflammatory cytokine secretion and deplete PD-1^high T follicular helper, T peripheral helper, and T effector cells. It is being studied for ulcerative colitis (UC), where PD-1+ T cells are prevalent in inflamed lamina propria (>40%) and the periphery. The primary objective of this healthy volunteer Phase 1 study was to assess the safety and tolerability of single ascending doses (SAD) and multiple ascending doses (MAD) of rosnilimab. Findings from pharmacokinetic (PK) and pharmacodynamic (PD) assessments are summarized.

Methods

This single-centre study included 14 cohorts in SAD and 3 cohorts in MAD. Each cohort had 8 participants (6 active, 2 placebo [PBO]). Cohorts were enrolled sequentially in each phase. Intravenous (IV) and subcutaneous (SC) administration were assessed in SAD; SC route was assessed in MAD.

Results

A total of 144 participants were enrolled; 90 to active SAD cohorts, 18 to active MAD cohorts, and 30 and 6 to SAD and MAD PBO cohorts, respectively. Rosnilimab was well tolerated with no dose-limiting toxicities or deaths. Two serious adverse events were reported in SAD (deemed unrelated to treatment) and 0 in MAD. PD-1 expressing cells were reduced by ~50% in both CD4+ and CD8+ subsets, in a dose-dependent manner and in correlation with full receptor occupancy (RO) through Day 30 in SAD. PD activity was rapid with sustained reduction in PD-1+ T cells, and ex-vivo stimulation resulted in reduced T cell functional activity. This reduction was maximized on PD-1^high expressing T cells: ~90% reduction vs baseline. There was no significant impact on the overall total T cell or regulatory T (Treg) cell numbers, resulting in restoration of T cell composition to a less activated state and a positive shift in the Treg:Teff ratio. An antigen-specific functional T cell assay measuring ex vivo interferon-gamma release in response to antigen challenge was inhibited up to ~90% vs baseline and the response lasted for more than 30 days following a single dose. Rosnilimab had a favourable PK profile consistent with full RO, a 2-week half-life, and dose-proportional exposure in IV and SC dosing.

Conclusion

Rosnilimab demonstrated favourable safety, PK, and PD activity. The role of PD-1 in UC pathophysiology coupled with these results and translational data, demonstrate proof of mechanism and support progression into a Phase 2 study of rosnilimab in UC. (NCT06127043)Read more OP07 Consistent IBD treatment approaches across South Asian and White ethnicities despite phenotypic variations: a study of 33,157 patients using the IBD BioResourceWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The current evidence suggests ethnic distinctions in IBD phenotype, and differences in the provision of treatment have been reported. This multi-centre cohort study utilised the UK IBD BioResource dataset to evaluate phenotypic differences between South Asian (SA) and White (WH) IBD, and to explore if these were associated with differences in treatment.

Methods

Phenotypic and outcome data were extracted from the IBD BioResource. Chi² (categorical data) and Mann-Whitney U (continuous data) tests were used. Propensity score matching (PSM) accounted for age at diagnosis, sex, smoking status, disease location and behaviour and perianal disease (CD). Differences in medication use (multivariable logistic regression) and surgical outcomes (Kaplan-Meier and Cox regression analysis) were assessed in propensity-matched (PM) cohorts.

Results

33,157 (31,932 WH; 1225 SA) individuals were included (48.1% CD, 45.4% UC, 6.5% IBD-U). UC was the predominant disease subtype in SA (UC, SA 57.3% vs WH 44.9%, p<0.001). SA were younger at diagnosis [CD, SA 24 (IQR 17-36) vs WH 26 (IQR 19-39) years, p<0.001; UC, SA 29 (IQR 22-38) vs WH 35 (25-48) years, p<0.001]. SA CD had less ileal disease (SA 30.3% vs WH 38.4%, p_adj=0.008), and more perianal involvement (SA 38.5% vs WH 32.3%, p=0.009) than WH. SA CD had less stricturing disease (SA 16.9% vs WH 25.6%, p_adj<0.001). SA UC were more likely to have extensive disease (SA 41.7% vs WH 34.1%, p_adj<0.001). Initial analyses in non-PSM cohorts showed that fewer SA CD underwent surgery [SA (n=157,37.4%) vs WH (n=7532,50.4%), p<0.001], and that similar proportions of SA (n=33,5.1%) and WH (n=747,5.5%; p=0.15) UC underwent a colectomy.PSM was used to match 355 SA to 355 WH in CD, and 525 SA to 525 WH in UC. Variables were well-balanced. There were no differences in 5-ASA, corticosteroid, thiopurine, anti-TNF or Vedolizumab use (Table 1). In CD, 126 (36.5%) SA and 152 (44.7%) had surgery. Survival analysis in CD showed no difference in the time to surgery (Fig 1A, log-rank 0.28). SA ethnicity was not associated with increased risk of surgery in CD (HR 0.82, 95% CI 0.63-1.07, p=0.14). In UC, 25 (4.8%) and 37 (7.1%) WH had a colectomy. There was no significant difference in the time to colectomy (Fig 1B, log-rank 0.12) nor was SA ethnicity associated with an increased risk of having a colectomy (HR 0.65, 95% CI 0.39-1.11, p=0.12).

Conclusion

In the largest analysis of SA IBD to date, we have demonstrated phenotypic differences associated with ethnicity. Accounting for these variations, we have shown comparable provision of medical and surgical treatment in SA and WH. These findings indicate consistent care of IBD patients from different ethnic backgrounds in the UK.Read more DOP87 Characterization of pathologic fibroblast and macrophage cell populations in colonic Crohn’s Disease with spatial transcriptomicsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Single-cell transcriptomic data of the human intestine has shed new light on the cellular composition and heterogeneity present in healthy and diseased tissues. Nonetheless, little information is currently available on their spatial distribution within tissue structures and cellular neighborhoods, which is particularly relevant to infer the function of disease-specific cell types. Here, we apply spatial transcriptomics to healthy control (HC) and Crohn’s disease (CD) intestinal samples and provide a map of cell types across healthy and diseased colon.

Methods

Fresh frozen colonic sections from HC (n=1) and CD (n=3) patients were placed onto 10X Visium slides, which feature thousands of spatially barcoded spots, each capable of capturing RNA from 10-15 cells. To retrieve single-cell resolution, spots were deconvoluted according to the Cell2location approach using our previously generated human single cell RNA sequencing (scRNAseq) dataset¹ as a reference. For validation and further analysis at single-cell resolution, a panel of 100 genes was measured using single molecule fluorescent in situ hybridization (Molecular Cartography) (Fig. 1A).

Results

Deconvolution analysis revealed the cellular composition of each spot across all four different tissue sections including epithelial, stromal and immune cell types. Here, we focused on studying the location and diversity of fibroblasts and macrophages given their plasticity during inflammation^1,2. The most abundant fibroblast cell type in CD were the inflammation-associate (IAFs) and the GREM1+ subepithelial fibroblasts. These two subsets showed a distinct gene signature and location, suggesting different functions (Fig. 1B). Most GREM1+ fibroblasts co-expressed FGFR1 and were in proximity with endothelial cells (VWF+) expressing the VEGF receptor 2 KDR, highlighting a potential pro-angiogenic role of GREM1+ fibroblasts³ (Fig. 1C). Remarkably, GREM1 was abundantly expressed by CCL19+ fibroblastic reticular cells and TNC+ stromal cells, underlying the potential heterogeneity of GREM1+ fibroblasts. Regarding macrophages, we could identify an inflammation-specific population expressing PLA2G2D and PTGDS. These macrophages were mainly localized within granulomas surrounding M1 macrophages (Fig. 1D). While their function is unknown, their signature suggests they might be modulating inflammation through the production of anti-inflammatory lipid mediators⁴.

Conclusion

Using two different ST technologies, we resolved the tissue distribution of cell populations previously identified by scRNAseq and reveal their potential function based on their spatial location.Read more DOP88 Lipids drive myofibroblast activation and the epithelial-mesenchymal transition process in Crohn’s DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Fibrostenosis represents one of the major clinical complications of Crohn’s Disease (CD). However, the molecular mechanisms underlying intestinal fibrogenesis remain poorly understood and anti-fibrotic therapy has not yet been developed. Growing evidences supports that oxidative stress and the epithelial-mesenchymal transition (EMT) process contribute to the development and progression of fibrosis. Here, we assessed the role of lipids in fibrogenesis and whether mitochondria dysfunction can support fibrosis formation.

Methods

Spatial metabolomics analysis and adipophilin (ADFP) staining were performed on surgical specimens from fibrotic ileum and the surrounding region (healthy) derived from CD patients. Fibroblasts isolated from fibrotic and healthy ileum and human induced pluripotent stem cell-derived intestinal organoids (iHOs) were treated for 1-3 weeks with lipid mix (2%) and analyzed by RNA sequencing. Pathways significantly modulated were validated by RT-PCR, WB, FACS analysis, and proliferative, migratory and contraction assays, and mitochondrial functions by Seahorse analyzer.

Results

Spatial metabolomics revealed a significant accumulation of lipids characterized by very long-chain fatty acids in the fibrotic area compared to surrounding healthy regions, which was further confirmed by ADFP staining. RNA-seq analysis showed overlapping dysregulated pathways between healthy fibroblasts stimulated with lipids and fibrotic fibroblasts, in particular genes related to cell cycle, cytoskeletal reorganization, migration, contractility and cell metabolism (oxidative stress) which were further confirmed by functional assays. Among the genes related to oxidative stress, lipid stimulation significantly decreased NFE2L2 and promoted an increase in CPT1A, gene encoding for a fatty oxidation mediator. Moreover, lipid-stimulated fibroblasts showed a reduction in mitochondrial respiration, particularly basal and maximal respiration, and spare respiratory capacity by Seahorse analysis. On the other hand, long exposure of iHOs to lipids promoted the EMT process through the upregulation of TWIST, ZEB, VIM, and S100a4.

Conclusion

Lipid stimulation induced myofibroblast activation through oxidative stress and alteration of mitochondrial metabolism, and increased the expression of EMT transcription factors in intestinal epithelial cells (iHOs) that may support fibroblast-mediated pro-fibrotic activity. These data indicate that regulators of fatty acid oxidation involved in the fibrotic process may represent new potential targets for the treatment of fibrostenotic CD patients.Read more P027 Involvement of PD-L1 in myenteric plexitis associated with postoperative recurrence of Crohn's diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Despite a growing therapeutic armamentarium, post-operative recurrence (POR) in Crohn’s disease (CD) remains frequent. The presence of myenteric plexitis at the proximal margin of ileocolonic resection has been recognized as a risk factor for early POR. They are defined by the accumulation of immune cells in contact with the ganglia of the myenteric plexus.In preliminary work, we have shown an increase in the number of T lymphocytes (TL) in contact with enteric glial cells (EGC) in patients with CD depending on ICAM-1/LFA-1 pathway. As CD is classically associated with a Th1 immune response, the aim of this work was to study the impact of EGC/CD4⁺ TL contacts on Th1-type cytokine production (IFNγ and its transcription factor Tbet) and to identify molecules that may be involved in these regulations.

Methods

In vitro in rats, the impact of EGC/CD4⁺ TL co-culture on IFNγ production was studied by ELISA and qPCR of the transcription factor Tbet. The expression and regulation of PD-L1, a candidate molecule, was then analyzed in murine and human EGC by qPCR and immunohisto/cytochemistry.

Results

While EGC alone produced only a small amount of IFNγ, there was a significant reduction in IFNγ production in EGC/CD4⁺ TL co-cultures compared with CD4⁺ TL alone. Yet the proportion of CD4⁺ TL cells capable of producing IFNγ was significantly increased in contact with EGC, as was their survival. In parallel, Tbet was downregulated in CD4⁺ TL in contact with EGC. These results suggested the involvement of PD-L1, a molecule known to negatively regulate cytokine production (notably IFNγ) and Tbet expression.Expression of PD-L1 mRNA and its protein was demonstrated in murine and human EGC and was upregulated under pro-inflammatory conditions. Analysis of transmural sections at the proximal margin of ileocolonic resection from patients (n=15 controls, n=14 CD without POR, n=15 CD with POR) showed PD-L1 expression in myenteric ganglia that was restricted to EGC (no neuronal expression) (Figure 1A). PD-L1 fluorescence intensity in myenteric ganglia at the proximal resection margin was significantly lower in CD patients with POR than in controls (∆13.5%; p=0.012) (Figure 1B).

Conclusion

Lower IFNγ production in EGC/CD4+ TL co-cultures associated with reduced Tbet expression by TL in contact with EGC suggest a role of PD-L1 in myenteric plexitis. PD-L1 expression has been demonstrated in murine and human EGC, with significantly lower expression in myenteric ganglia located at the proximal resection margin of CD patients with POR compared with controls. Blocking the ICAM-1/LFA-1 pathway and/or restoring the PD-1/PD-L1 loop could be of interest for developing strategies to prevent and/or treat POR in CD patients.Read more P028 A pathogenic role of activated mucosal-associated invariant T cells in an animal model of Inflammatory Bowel DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

It is known that the mucosal-associated invariant T (MAIT) cells are the innate-like T cells that are restricted by the major histocompatibility complex-related molecule 1 (MR1), and that these cells express a semi-invariant T cell receptor. We have previously reported that the activation status of the circulating MAIT cells in patients with Ulcerative Colitis (UC) is associated with disease activity, and these cells infiltrate the inflamed colonic mucosa. These findings imply that MAIT cells are involved in the pathogenesis of Inflammatory Bowel Disease (IBD). However, the role of MAIT cells in the setting of IBD has not been revealed. Therefore, we investigated the role of MAIT cells in an animal model of UC.

Methods

To this end, we utilized MR1 deficient mice (MR1^-/-), which lack MAIT cells, and isobutyl 6-formyl pterin (i6-FP), which is a synthetic antagonistic MR1 ligand. MR1^-/- on the C57BL/6 background, their littermate wild-type controls, and C57BL/6 mice were sensitized by rectal administration of oxazolone to induce colitis. These were then administered an oral i6-FP. Splenocytes (SPL) and colonic lamina propria lymphocytes (LPL) were isolated from mice receiving i6-FP to measure cytokine production. MR1^-/-, i6-FP-treated mice and their controls were orally administered FITC-dextran to analyze intestinal permeability. The peripheral blood mononuclear cells (PBMC) from the patients with UC were also isolated to study the effect of i6-FP on cytokine production by MAIT cells.

Results

MR1 deficiency or i6-FP treatment resulted in reduced severity of oxazolone-induced colitis. Mice treated with i6-FP resulted in reduced MAIT cell production of pro-inflammatory cytokines such as IFN-g and TNF in both SPL and colonic LPL. Similar results were also observed in PBMC isolated from the patients with UC when incubated with i6-FP. Although MR1 deficiency resulted in increased intestinal permeability, i6-FP administration did not affect gut integrity in mice.

Conclusion

The current studies indicate that MAIT cells have a pathogenic role in colitis and suppressing activation of these cells may reduce the severity of colitis without affecting gut integrity. Thus, MAIT cells may be potential therapeutic targets for IBD including UC.Read more P029 Loss of adipose tissue protects mice from intestinal inflammationWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Crohn’s disease (CD) is associated with creeping fat, characterized by hyperplasia of mesenteric adipocytes and increased secretion of various adipokines, including leptin. Leptin can promote intestinal inflammation by inducing pro-inflammatory cytokines such as TNFα in murine and human lymphocytes. Recent meta-analyses have shown that increased body mass index (BMI) increases the risk of developing CD. However, whether the surgical removal of mesenteric fat could improve the outcome of CD patients and the impact of fat-derived signals on intestinal autoimmunity remain elusive.

Methods

To decipher the role of adipose tissue in the regulation of intestinal autoimmunity, we investigated here how the absence of adipose tissue affects epithelial barrier functions and immune cell homeostasis. Therefore, we studied lipoatrophic Pparg^fl/fl-Adipoq^-Cre mice, that completely lack adipose tissue, under steady-state conditions and after induction of chronic dextran sodium sulfate (DSS)-mediated inflammation, as well as in allogeneic fat transplantation models. We characterized our models using flow cytometry, RNA sequencing, immunohistochemistry, western blot analyses, ELISA and calcium measurements.

Results

At steady state, lipoatrophic mice showed a decrease in CD4 IL-17⁺ T cells in the ileum, and lower frequencies of CD8 T cells and CD4 FoxP3⁺ cells in the colon, suggesting that fat-derived signals are required for proper T cell homeostasis in mice. To understand how the absence of adipose tissue affects the severity of intestinal inflammation, we challenged lipoatrophic or WT littermates with 3 cycles of 1.5% DSS, which induced weight loss in both WT and lipoatrophic mice. However, only fat-proficient WT mice developed severe colitis, whereas lipoatrophic animals had significantly reduced intestinal inflammation and displayed disturbances in the differentiation and function of pro-inflammatory T cells including Th1 and Th17 cells. Importantly, these defects in T cell function could be rescued by allogeneic transplantation of adipose tissue from lean wild-type mice but not by adipose tissue from leptin-deficient ob/ob mice, highlighting that the role of the adiopokine leptin as an important pro-inflammatory factor in IBD.

Conclusion

Taken together, our data demonstrate that adipose tissue acts as an important regulator of intestinal autoimmunity by controlling the differentiation and function of pro-inflammatory T cells through the secretion of adipokines including leptin. We believe that these observations may help explain why obese individuals with higher BMI may be at a higher risk of developing intestinal inflammation and Crohn’s disease.Read more P030 Gut-host metabolites and microbiota interactions in a murine model of checkpoint inhibitor induced colitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The advent of Immune Checkpoint Inhibitors (CPIs) has revolutionised cancer treatment by bolstering anti-tumour immune responses. However, the clinical success of CPIs is hampered by immune-related adverse events (irAEs), with colitis posing a common and formidable challenge. Despite this, the precise mechanisms triggering CPI-induced colitis remain elusive. Recognising the influence of gut microbiota on CPI therapy response and colitis development, this study seeks to unravel the intricate details of these mechanisms to facilitate the development of targeted therapies.

Methods

Utilising a murine model of CPI-induced colitis, we combined CPI therapy with faecal microbial transplant (FMT) of colitogenic bacteria. FMT induced colitogenic bacteria in wild-type mice, followed by weekly injections of anti-CTLA4 and anti-PD1 for 3 weeks. Metataxonomic data, obtained through 16S rRNA gene amplicon sequencing, and metabolomic profiles, captured by ¹H-NMR spectroscopy, were analysed. Alpha and beta diversity, as well as differential expression of taxa, were assessed using 16S data. Metabolomics data underwent multivariate and univariate analyses to identify metabolic profiles and differential metabolites. Pathway analysis was conducted with MetaboAnalyst. Correlation analyses were performed between bacterial taxa at the family level and metabolite concentrations.

Results

After one week of FMT and CPI treatment, distinct profiles in faecal metabolome and microbiome were observed through Principal Component Analysis (PCA) and Principal Coordinates Analysis (PCoA) for beta-diversity, respectively. Altered metabolites included increased trimethylamine, methylamine, pyruvate, and cytidine, along with reduced tryptophan and proline. Changes in bacterial composition were noted, with increased Bacteroides, Faecalibaculum, Mucispirillum, and Roseburia, and decreased Muribaculum. Metabolic differences persisted after 3 weeks of treatment, revealing additionally decreased acetate, propionate and tyramine. Pathway analysis highlighted profound alterations in tyrosine, alanine, aspartate and glutamate metabolism, pyrimidine metabolism and glycolysis. Desulfovibrionaceae was positively correlated with dimethylamine, glycine and valine. Bacteroidaceae was positively correlated with propionate and butyrate.

Conclusion

This study provides novel mechanistic insights into the metabolite and microbiota-metabolism pathways associated with CPI-induced colitis. The alterations in short-chain fatty acids (SCFA), amino acids, and the SCFA-producing bacteria and colitogenic bacteria shed light on the metabolic changes underlying CPI colitis. Targeting these microbiomes and metabolites could offer promising avenues for enhancing clinical outcomes during CPI therapy.Read more P068 Recapitulation of human colonocytes in situ by human colon organoids in vitro and after orthotopic transplantationWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The intestinal epithelium plays a central role in human health and disease, and several chronic inflammatory disorders associate with a weakened epithelial barrier. The organoid model allows the cultivation, expansion and analysis of non-immortalized intestinal epithelial cells and has been instrumental in studying epithelial behavior in homeostasis and disease. Recent advances in human organoid transplantation into mouse and human lay the base for models to study human epithelial cell behavior within the intestinal tissue context, and promise novel therapeutic approaches for diseases such as short bowel syndrome and inflammatory bowel disease. It remained unclear how organoid transplantation into the colon would affect epithelial phenotypes and protein expression, which is key to assess the suitability of this model to study human epithelial cells in situ and safety aspects upon transplantation into human recipients.

Methods

To address this, we employed state-of-the-art deep visual proteomics to compare human colonic epithelial stem and differentiated cells in vivo, upon transplantation in situ, and to organoids cultured in vitro.

Results

We find that organoids transplanted into the murine colon closely resemble human intestinal epithelial cells in vivo compared to organoids grown in vitro, indicating that organoid culture induces a transient shift in epithelial phenotypes, which is reversible upon reintroduction into the mucosa. Phenotypic differences between epithelial cells in vitro and in situ/in vivo were largely driven by hallmarks of high proliferation and lower functional differentiation in organoids, likely due to culture conditions.

Conclusion

Taken together, we demonstrate that transplanted epithelial cells in situ represent a physiological, relevant model for studying functional aspects of mature colonocytes compared to the organoid model. We furthermore show that the proliferative phenotype of organoids in vitro is a transient state driven by culture conditions, which is reversible upon reintroduction into the mucosal environment. This is an important consideration regarding the safety of organoid transplantation into humans as a potential therapeutic strategy.Read more P069 Ultra-processed food intake and dietary insufficiencies are common in adults with Crohn’s Disease in remission. The INTICO 2 StudyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Adults with Crohn’s Disease (CD) may have dietary restrictions and micronutrient inadequacies. Consumption of ultra processed foods (UPF) has been associated with an increased need for IBD-related surgery and is a growing area of research. This study aimed to investigate the habitual diet of adults with CD during disease remission to understand the nutritional adequacy, diet diversity and diet quality.

Methods

196 adult CD outpatients in remission (Harvey Bradshaw Index <5 and calprotectin <250µg) were recruited from a single UK IBD centre outpatients as part of the INTICO 2 observational study. Seven-day food diaries were electronically recorded using Nutritics® (Libro) software. UPF intake was determined using NOVA Score . Data cleaning was undertaken by a dietitian prior to analysis to identify input errors. NOVA Score¹ criteria was utilised to determine UPF intake. Product ingredient lists were examined using supermarket websites and ‘Open food Facts’ by two research dietitians to assign a NOVA score. Consensus on NOVA Scoring was achieved, and a data dictionary was prospectively updated to justify the assigned score.

Results

97% (189/195) of those who underwent food diary analysis had at least one micronutrient below the LNRI. The intake was below the LNRI for a mean of 6 (SD 4.2) micronutrients per subject. The number of subjects who failed to meet the LNRI from diet (with and without inclusion of usual supplements) is listed for each micronutrient in table 1. Of note, 93% (181/195) of subjects failed to meet the SACN recommended 30g of fibre per day (median intake 17.7g). 33% of dietary intake was classified as UPF (Nova 4) and 13% processed (NOVA 3).

Conclusion

Both micronutrient insufficiencies and UPF intake are common in a CD remission population and should be considered alongside one another in studies of dietary intake. UPF intake should be interpreted with caution as NOVA does not account for nutritional content. Blanket recommendations to avoid UPFs need to be carefully considered within this already nutritionally vulnerable population as avoidance of UPF products such as fortified cereals or oral nutritional supplements could lead to increased dietary inadequacies.References:Monteiro, C.A. et al, P. 2019. Ultra-processed foods, diet quality, and health using the NOVA classification system. Rome, FAO.Table 1:Nutrient intake below LRNI (n=195)NutrientsWith supplements %(n)Supplements removed %(n)Copper 73 (142) 83 (162) Selenium 68 (132) 73(142) Folate (DFE) 52 (102) 70 (137) Iodine 35 (69) 42 (82) Magnesium 34 (67) 40 (77) Zinc 23 (44) 28(55) Iron 22 (43) 27 (53) Riboflavin 20 (38) 24 (46) Calcium 20 (39) 24(46) Vitamin A 17 (34) 21 (40) Read more P070 The influence of Crohn’s disease-derived blood plasma upon anabolic signaling responses to leucine stimulation in skeletal muscle cells in vitroWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Many Crohn’s Disease (CD) patients have low muscle mass and function (sarcopenia), yet the precise drivers of this pathophysiology are unclear. Positive muscle protein balance is driven by essential amino acids (EAA) that stimulate muscle protein synthesis (MPS), with the EAA leucine (L) playing a key role. However, if circulating factors in CD impact muscle anabolic responses to feeding remain unclear. Our aims were to use plasma from healthy human volunteers (HV) and active CD patients to investigate the impact on anabolic signaling and responses to feeding.

Methods

HV were 32 ± 4 y with a BMI 24 ± 1 and CD 26 ± 3 y with a BMI 23 ± 1 disease duration 5 ± 1 y faecal calprotectin 720 ± 12 ug/g. C2C12 myotubes were treated with 4 conditions of media conditioned with 5% plasma from HV or CD, in addition to being treated ± 5mM L for 4 hrs. Protein content was quantified via nanodrop and muscle anabolic signaling measured via immunoblotting for p-mTORC1 (Ser2448), p-4E-BP1 (Thr37/46) and p-P70S6K1 (Thr389).

Results

Immunoblotting revealed no difference in mTORC1 phosphorylation between HV and CD (HV:18.9 ± 2.7 AU, CD: 19.9 ± 3.2 AU), with no change in response to L treatment (HV:18.0 ± 2.4 AU, CD: 16.6 ± 2.3 AU). There was no difference in P70S6K1 phosphorylation between HV and CD (HV: 33.7 ± 3.2 AU, CD: 28.0 ± 4.7 AU) with both groups showing significant increases in phosphorylation with L treatment (HV: 56.4 ± 4.2 AU (P<0.05), CD: 54.5 ± 9.2 AU (P<0.001)). There was no difference in 4EBP1 phosphorylation between HV and CD (HV: 49.8 ± 6.4 AU, CD: 64.6 ± 7.5 AU) with only HV showing a significant increase in phosphorylation with L (HV: 105.5 ± 8.7 AU (P<0.0001), CD: 47.8 ± 5.3 AU). There was difference in total protein concentration between HV and CD, or with L treatment.

Conclusion

We found CD derived blood plasma did not impact the leucine stimulated increase in P70S6K1 phosphorylation but did result in blunted phosphorylation of 4EBP1. These disparities in anabolic signaling indicate that systemic factors in CD may impact muscle anabolic responses to feeding. Yet, the relationship between anabolic markers and rates of MPS remains complex.Read more P071 Neonatal levels of inflammatory markers in individuals who later develop early onset Inflammatory Bowel DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The early life period is suggested to be important in development of Inflammatory Bowel Disease (IBD). Studies in babies from mothers with IBD observed increased faecal calprotectin and changes in the microbial compartments compared to babies from healthy mothers^1,2, which suggests that changes in early life might be associated with later disease development. Prospective studies of IBD risk following early life changes at the molecular level are sparse. We aimed to investigate if individuals with early onset (EO) IBD had changes in systemic inflammatory markers shortly after birth.

Methods

We measured the concentration of 9 cytokines in a cohort of 464 neonatal dried blood spot samples stored at the Danish National Biobank from individuals who later developed EO IBD (median age of diagnosis 11 years), as well as matched controls. Individuals who developed IBD were identified through the use of the Danish National Patient Registry. Uni- and multivariate logistic regression with adjustment for birth year, sex, and gestational age was conducted to assess the association between 6 of the inflammatory markers with later disease development (INF-γ, TNF-α, IL-1β, IL-4, IL-6 and IL-17a). Further exploratory analyses were performed investigating risk of very early onset (VEO) IBD (onset from 0-5 years) in 88 cases and their matched controls.

Results

No significant association with EO IBD was observed for any of the cytokines in uni- and multivariate models when adjusting for multiple testing. In the exploratory analysis of VEO IBD, increased IL-4 was associated with significantly reduced risk of IBD (OR=0.992, p-value=0.023) and increased IL-17a was borderline-significantly associated with increased risk of IBD (OR=1.002, p-value=0.063) in a multivariate logistic model including all 6 cytokines. This association did not remain significant when adjusting for multiple testing, which may reflect limited power.

Conclusion

In our unique study of 464 dried blood spots from later IBD patients and controls, we could not find an association between measured cytokines and EO IBD. In contrast, patients with VEO IBD had decreased levels of IL-4 and increased levels of IL-17a. This sub-cohort was small, and significance disappeared after adjusting for multiple testing. Still, we find it important to report these findings, as they are novel and may inspire future studies into the aetiology of VEO IBD.1. Kim, E. S. et al. Longitudinal Changes in Fecal Calprotectin Levels Among Pregnant Women With and Without Inflammatory Bowel Disease and Their Babies. Gastroenterology (2021)2. Torres, J. et al. Infants born to mothers with IBD present with altered gut microbiome that transfers abnormalities of the adaptive immune system to germ-free mice. Gut (2020)Read more P093 Innovating in IBD care: what do patients and informal caregivers value? Preliminary results of a narrative inquiryWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Given the increasing incidence, evolving treatment goals, and the need for tight and holistic monitoring, transformation in delivery of Inflammatory Bowel Disease (IBD) care is warranted. To innovate successfully, it is crucial to consider the values of healthcare professionals (HCP) and healthcare services, as well as the patient’s and informal caregiver’s perspective. This study aims to explore what patients with IBD and their informal caregivers value in Dutch IBD care.

Methods

In total, approximately 16 patients and 8 informal caregivers from an academic and a general hospital will be included. Respondents are recruited purposefully. Data collection will take place until data saturation is reached. The interviews are focused on real-life experiences and stories of respondents with regard to IBD. Interviews are conducted face-to-face or digitally, audio recorded and transcribed verbatim. Independent coding was executed by three researchers. A deductive thematic analysis approach was used, guided by the Picker Principles of Person Centred Care.

Results

Semi-structured narrative interviews were conducted with 8 IBD patients and 4 informal caregivers, i.e. family members, between June-September 2023. All Picker principles came across in the narratives. Respondents said that it is important to receive an effective treatment, minimizing intestinal symptoms and to function as good as possible with IBD. Involving patients in their treatment plan and paying attention to non-medical aspects, e.g. impact on work and social relationships, was relevant to respondents. Patients and caregivers valued easy and accessible communication with their HCP, the feeling to be heard, and immediate action of the HCP when required. A trustful relationship, fostered through e.g. regular face-to-face contact, was highlighted as important. Some respondents appreciated the use of eHealth tools, as these facilitate remote care if desired. Moreover, providing informal caregivers with information about the disease, treatment and impact on daily life was suggested as beneficial in supporting patients with IBD.

Conclusion

IBD patients and their informal caregivers value shared decision making, fast access to reliable healthcare advice, immediate action when needed, the feeling to be heard and a trustful relationship with their HCP when receiving IBD care in the Netherlands. These values and insight in the (shared)-values of all relevant stakeholders within the Dutch context will facilitate the development of valuable innovation and successful implementation. The perspectives of other stakeholders, such as HCPs, policymakers, health insurers, pharmaceutical companies, and eHealth providers, will be explored in an extensive qualitative study.Read more P094 Lack of DNA methyltransferase DNMT3A in fibroblasts impairs cell growth and wound healingWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Fibrotic scarring is an untreatable pathological wound-healing complication that invalidates correct organ function. However, pathomechanisms leading to intestinal fibrosis during inflammatory bowel disease (IBD) are not fully understood. Since the de novo DNA methyltransferase DNMT3A has been associated with increased risk for IBD and alters epithelial homeostasis, we sought to characterize how DNMT3A loss might affect fibroblasts, the key mesenchymal cells involved in wound healing.

Methods

We stably depleted Dnmt3a in 3T3 fibroblast cell line using CRISPR-Cas9 technology and subsequently selected GFP-positive clones using FACS sorting. Cell cultures were performed in vessels with or without 0.2% gelatin coat. Reverse transcription quantitative PCR, western blot, and immunofluorescence were used to confirm Dnmt3a gene deletion and characterize wild-type (WT) and knockout cells (KO). Wound healing assays in the presence or absence of tissue repair cytokine TGF-β served to quantify and assess cell capacity of wound closure.

Results

3T3 fibroblasts lacking Dnmt3a acquire an activated myofibroblast phenotype (characterized by increased α-SMA expression) that also overexpress tissue remodelling matrix metalloproteinase Mmp3, and the inflammation-induced necroptosis marker RIPK3 when compared to their WT counterparts. In addition, Dnmt3a-depleted 3T3 cells grow overlapped in tightly aggregated foci (fig. 1), and when seeded in vessels without the gelatin coat, they form spheroids. To assess healing properties, the closure of a wound (gap) in a cell monolayer was monitored. While WT 3T3 fibroblasts closed the gap within 48h, Dnmt3a KO 3T3 cells were unable to refill the empty space and formed aggregated foci in the vicinity of the wound (fig. 1). When the wound healing assay was repeated in the presence of TGF-β, WT cells nearly closed the gap within 24h whereas Dnmt3a KO 3T3 still failed to grow.

Conclusion

We conclude that Dnmt3a is crucial for fibroblast homeostasis and correct wound healing. Furthermore, TGF-β signalling is impaired when Dnmt3a is lacking. Thus, additional characterization of Dnmt3a depletion in fibroblasts will deepen the understanding of fibrosis and point towards new therapeutic approaches for this untreatable complication.Read more P095 Accelerated degradation of gut barrier-protecting 3-aminobenzoic acid exacerbate colitis in Inflammatory Bowel DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Disruption of intestinal epithelial cell (IEC) barrier function is crucial for the development of inflammatory bowel disease (IBD). Decreased diversity and compositional changes in intestinal bacteria, namely dysbiosis, impair IEC barrier function in IBD, but the underlying mechanism is not fully understood. This study aims to identify the impact of dysbiosis-driven changes in intestinal bacterial metabolites on IEC permeability in patients with IBD.

Methods

Caco2 cells were cultured on the trans-well inserts and stimulated with a library of intestinal bacterial metabolites. Proportional changes of trans-epithelial electrical resistance (TEER) were calculated at 48 hours after stimulation (ΔTEER%) and the permeation of 70-kDa FITC-dextran was evaluated using a Qubit fluorometer. Fecal samples were collected from 10 IBD patients with active colonic inflammation (5 ulcerative colitis and 5 Crohn’s disease) and 5 healthy controls (non-IBD, NIBD). Fecal bacteria-derived metabolites were quantified by LC-MS/MS and compared between IBD patients and NIBD controls. 16SrRNA-based metagenomic analysis was performed on the same fecal samples using QIIME2 followed by a PICRUSt2-based functional analysis of microbial communities. Anti-inflammatory effect of 3-aminobenzoic acid (3-ABA) was examined in C57BL/6 mice using a dextran sodium sulfate (DSS)-induced colitis model.

Results

Among 119 intestinal bacterial metabolites, 4-ABA decreased epithelial permeability the most with the highest ΔTEER% value (control vs. 4-ABA, 1.8 vs. 30.9 %, p<0.05). 3-ABA, one of three structural isomers of ABA, also decreased epithelial permeability in a dose dependent manner with higher ΔTEER% value than 4-ABA and reduced permeation of FITC-dextran (control vs. 3-ABA, 8.3 vs 3.4 nM, p<0.05). Fecal level of 3-ABA was significantly lower in IBD patients than in NIBD controls (7.0 vs. 505.0 μM). Functional prediction of intestinal microbiota demonstrated that IBD patients were significantly more enriched with the bacteria involved in the degradation of ABA than NIBD controls. Rectal administration of 3-ABA significantly improved body-weight loss, shortening of colon length, histologic scores, and the expression of inflammatory cytokines in mice with DSS-induced colitis (control vs. 3-ABA; body-weight loss,15.33 vs. 18.91 g; colon length, 6.11 vs. 7.35 cm; histologic score, 2.14 vs 0.60).

Conclusion

Accelerated degradation of luminal 3-ABA by intestinal bacteria may disrupt intestinal epithelial barrier function and exacerbate colitis in patients with IBD.Read more P096 Human extrachromosomal circular DNA is an emerging biomarker in Inflammatory Bowel DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Inflammatory Bowel Diseases (IBD) are chronic multifactorial disorders, which affect the gastrointestinal tract, including Ulcerative Colitis (UC) and Crohn’s Disease (CD). The existence of extrachromosomal circular DNA fragments (eccDNA) is well established, and it arises from all parts of the genome. eccDNA has mainly been studied in the context of cancer and not in relation to other diseases, and it has become a promising diagnostic and prognostic biomarker for different types of cancer. Herein, we investigate for the first time the role of eccDNA in IBD.

Methods

Forty consecutive IBD patients (19 CD, 21 UC) and 13 HC were enrolled, who underwent screening colonoscopy were prospectively enrolled at our center in this observational, case-controlled study. In IBD patients, disease activity was assessed using PMS and MES for UC, and HBI and SES-CD for CD. Colonic biopsies were collected from both inflamed and healthy mucosa in IBD patients and from HC. eccDNA was enriched, sequenced, and identified with Circle Finder from intestinal biopsies.

Results

Colonic mucosal samples from IBD patients showed increased average of eccDNAs, across all chromosomes than samples from HC. Furthermore, there was a slight yet significant tendency for larger eccDNAs in IBDs compared to HCs. Focusing on eccDNA coming from genic elements ("genic eccDNAs"), approximately 60% were fragments from protein coding genes, 32% from non-coding RNAs and 8% from pseudogenes. IBD patients had, on average, significantly more genic eccDNAs in their intestines as compared to HC. Moreover, IBD in remission had fewer eccDNAs in their intestines than active disease, although not statistically significant. eccDNAs from phosphodiesterase genes and genes involved in lipid metabolism were enriched in patients with active IBD than patients in remission. eccDNA from inflamed mucosa (both in UC and in CD) show an enrichment of genes related to inflammatory and immune pathways, such as MAPK, mTOR, ErB, Rap-1 and cGMP (SPOKE3, GRID2, DLEU1, ITGA8, NRG1).

Conclusion

We are the first to uncover an IBD-specific pattern of eccDNA production. Furthermore, we identified genic hotspots which characterize active vs. inactive disease and inflamed vs. healthy colonic tissue. We propose that eccDNA identification could be a promising new diagnostic marker for IBD patients.Read more P097 Spatially resolved insights into fistulating Crohn's disease pathogenesis: Unveiling molecular heterogeneityWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Crohn's disease (CD) frequently results in fistula development in approximately 40% of patients due to sustained, transmural inflammation within the bowel wall. Despite advanced treatments, recurrence of fistulae affects one third of patients. Understanding its pathogenesis is crucial for targeted treatments, yet remains poorly defined. This study employs spatial transcriptomic and single-cell RNA-sequencing (scRNA-seq) technologies to characterise human fistulating CD tissue pathology.

Methods

Unbiased FFPE spatial transcriptomics (10x Visium) were applied to surgically resected, full-thickness (FT) tissue from 20 CD-associated fistulae cases and 15 controls. Subsequently, selected cases underwent further analysis using custom 500-plex MERFISH subcellular resolution spatial transcriptomics (Vizgen MERSCOPE). Additionally, a reference single-cell cohort encompassing patients with fistulating, stricturing, and inflammatory CD phenotypes, along with healthy controls, was generated. Optimisation of scRNA-seq for resected FT ileal tissue enabled the isolation and profiling of epithelial, immune, and stromal populations (10x Chromium). Computational analysis facilitated the spatial localisation of single-cell clusters enriched in fistula CD tissue, identifying key parameters linked to fistula development.

Results

The scRNA-seq data revealed diverse CD-specific cellular states adopted by intestinal fibroblasts, with IL11+ fibroblasts prominently expressing CD82, COL7A1, MMP1, CHI3L1, suggestive of pro-fibrotic signalling and regenerative morphogen pathways. This coincided with the expansion of a CD-specific subpopulation of pericytes (CCL19/CCL21) involved in leucocyte migration. Spatial profiling of CD fistula tracts by Visium and MERSCOPE unveiled an enrichment of key epithelial developmental transcription factors (e.g., GRHL3) and localised the pro-fibrotic signature displaying increased IL11 and MMP expression, along with perturbed WNT signalling within the fistula stroma. Active proliferation (HOPX, MKI67) was observed at the base of fistula tracts and within the stroma. Transcriptomic characterisation depicted a gradual loss in stem cell signature (LGR5, ASCL2, SMOC2) and supporting telocytes (POSTN) toward the leading edge of the fistula, signifying abnormal epithelium loss.

Conclusion

This pioneering study integrates multi-modal spatial transcriptomics and single-cell profiling to unveil the intricate cellular and molecular landscape in FT, fistulating CD pathology. Spatial analyses elucidate specific mechanisms involved in epithelial loss, stromal remodelling, and perturbed WNT signalling pathways within fistulating tissue, outlining a course of disrupted regenerative processes in fistulating CD.Read more P098 The Endoscopic Severity Score Map (ESSM): An Artificial Intelligence scoring system providing accurate, objective and localised measurements of endoscopic disease severity in ulcerative colitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Commonly used scoring schemes as the Mayo Endoscopic Subscore (MES) account for disease severity only at specific (i.e., the worst) segments and do not capture disease extent. However, for an accurate assessment of disease severity in patients with ulcerative colitis (UC), the measure of the precise extent of disease activity is necessary. Alternative systems that include disease extent have been proposed (Balint 2018), but their implementation is prohibited by the time and cost constraints of comprehensively scoring each location along the entire colon. Here, we present the Endoscopic Severity Score Map (ESSM), a scoring system based on Artificial Intelligence, capable of providing an assessment of disease severity and extent in UC in a fully automated manner.

Methods

The ESSM consists of 3 main elements (Fig. 1): 1) a quality algorithm which selects readable frames from a colonoscopy video, 2) a scoring system which assigns an MES to each readable frame (Gutierrez Becker 2020) and 3) a camera localisation algorithm that assigns each frame to an anatomical location within the colon (Yao 2022). The ESSM was trained and tested using 4,306 sigmoidoscopy videos from phase III Etrolizumab clinical trials (Hickory NCT02100696, Laurel NCT02165215, Hibiscus I NCT02163759, Hibiscus II NCT02171429 and Gardenia NCT02136069).

Results

We evaluate the performance of the ESSM by first assessing the agreement of scoring as compared to centrally read MES. The agreement between central reading and the ESSM at the colon section level was high (quadratic-weighted kappa k=0.81; Tab. 1). This was comparable to the agreement between central and local reading (k=0.84), suggesting that the ESSM shows levels of inter-rater variability comparable to experienced readers. Finally, we found correlations between the average ESSM at all anatomical locations and other disease activity markers to be moderate to high: faecal calprotectin rs=0.24, CRP rs=0.29, stool frequency rs=0.49, rectal bleeding rs=0.43 and physician global assessment rs=0.47 (Tab. 1).

Conclusion

Here, we introduced the ESSM, a fully-automated AI-based scoring system that enables accurate, objective and localised assessment of disease severity in UC. In brief, we show that the ESSM compares well with central reading (at the colon section level) and has clinical relevance when compared to other markers of disease activity. This tentatively suggests that the ESSM has the potential to augment the current way of assessing disease severity, both in clinical trials and everyday clinical practice.Read more P099 Neutrophil extracellular traps enhance profibrotic activity of intestinal fibroblasts in Crohn's disease through TLR2/NF-kB pathwayWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Neutrophil extracellular traps (NETs) consist of DNA filaments and cytoplasmic protein granules, extruded by neutrophils after PAD4-dependent activation. NETs release occurs early during inflammation in various immune-related diseases, further aggravating tissue injury and contributing to fibrosis. Our aim was to investigate the potential profibrotic effect of NETs in Crohn’s disease (CD).

Methods

NETs and activated fibroblasts were labelled by multiplex immunofluorescence staining on unaffected, inflamed and fibrotic ileum derived from patients with stricturing CD undergoing ileocaecal resection. Intestinal fibroblasts isolated from unaffected CD ileum were co-cultured with NETs for 24 hours to analyse their transcriptome and quantify collagen released with SIRCOL®. Fibroblast migratory activity was investigated with a scratch test. Immunofluorescence intensity of collagen and fibroblast activation protein (FAP) was quantified using the Operetta® Analysis System. Transfection of fibroblasts with NF-kB-luciferase reporter plasmid was performed to evaluate the TLR2/NF-kB pathway, and a specific TLR2 inhibitor (TL2-C29) tested. Finally, mice with selective deletion of PAD4 in neutrophils (PAD4^fl/flMRP8Cre⁺) were subjected to chronic Dextran Sulphate Sodium (DSS) colitis to assess the role of PAD4-mediated NETosis in intestinal fibrosis development.

Results

We found spatial tissue distribution of clusters of NETs adjacent to FAP⁺ fibroblasts in ileal ulcerations in patients with active CD. Transcriptomics demonstrated upregulation of various profibrotic processes in fibroblasts stimulated with NETs, including TGFβ-receptor signalling pathway, positive regulation of collagen metabolic process, and TLR-signalling pathways. This correlated with increased proliferation rate (p<0.0001), slower wound healing capability (p<0.0001) and higher collagen release in the medium (p<0.01) in the NET-treated group, as well as higher expression of collagens and FAP. Among TLR genes, TLR2 was found upregulated after stimulation with NETs (p=0.02). Transfection data showed significant upregulation (p<0.05) of NF-kB in the NETs-treated group, whereas its expression and soluble collagen release decreased with the addition of the TLR2 antagonist TL2-C29. In line, a significantly lower amount of collagen deposition was observed in the colon of PAD4^fl/flMRP8Cre⁺ mice subjected to chronic DSS colitis, as well as modulation of MMP2/TIMP2 balance and reduced fibroblast activation.

Conclusion

NETs may represent an early trigger of intestinal fibroblast activation via the TLR2/NF-kB axis. As NETs are early players during inflammation, blocking PAD4 may reduce inflammation and thus fibrogenesis in CD.Read more P100 Salivary exosomes aggravate colitis via oral-gut axisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Inflammatory bowel disease (IBD) is a chronic intestinal immune-dysfunctional disease, while the presence of persistent triggering factors leading to relapsing and remitting inflammation in IBD remains undetermined. The oral cavity is one of the most frequently affected extraintestinal organ in IBD, and literature highlights the oral cavity's influence on gastrointestinal conditions. The understanding of alternative mechanisms in the long-distance interaction between the oral cavity and gut is limited. Exosomes exist in various bodily fluids and facilitate intercellular communication. Thus, we aimed to further explore the role of salivary exosomes in aggravating colitis via bridging oral cavity and gut.

Methods

Salivary exosomes were obtained from active IBD patients, remission IBD patients, and healthy donors using ultracentrifugation. In vivo, we established a dextran sulfate sodium (DSS)-induced colitis model to investigate the possible role and mechanisms of salivary exosomes. In vitro, THP-1 cells and Caco-2 cells were stimulated with salivary exosomes respectively and the expression of related inflammatory factors was detected. Moreover, our investigated the immune regulatory mechanism of salivary exosomes by analyzing their microRNA profiles.

Results

DIL-labeled salivary exosomes accumulated in mouse colon at 6 hours post-gavage, indicating their ability to reach and accumulate in the colon through the "oral-gut axis" (Figure 1A). Salivary exosomes of active IBD patients (active IBD-Sexos) exacerbated colitis in DSS mouse, while salivary exosomes derived from remission IBD patients or healthy donors not (Figure1B). The potential mechanisms may include remodeling of macrophage phenotypes by activating the NF-κB signaling pathway (Figure1D-F), impairment of intestinal mucosal barrier function (Figure1C), and modulation of the intestinal microbiota. Co-culture of THP-1 cells and Caco-2 cells with active IBD-Sexos were shown to raise inflammation in macrophages, which lead to increased release of inflammatory factors and promoted macrophage M1 polarization(Figure1G-K). We found 35 differentially expressed microRNAs in active IBD-Sexos compared to exosomes from both remission IBD patients and healthy donors (Figure1L). Specifically, miR-223 regulates the inflammatory response of IBD. MiR-119b-5p and miR-203-5p impact the NF-κB signaling pathway.These microRNAs promote inflammation, suggesting a possible role of salivary exosome delivery in IBD pathogenesis.

Conclusion

In conclusion, our study provides evidence that salivary exosomes play a significant role in the communication between the oral cavity and gut, beyond microorganisms or immune cells, with the potential to exacerbate intestinal inflammation in IBD (Figure1M).Read more P214 Effects of rectal stump proctitis on short-term postoperative complications after proctectomy and ileal pouch-anal anastomosis for Ulcerative ColitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Inflammation of the rectal stump (proctitis) after subtotal colectomy with ileostomy for ulcerative colitis (UC) is common. Proctitis may affect the postoperative outcomes of ileal pouch-anal anastomosis (IPAA). This study aims to explore associations between rectal stump proctitis and short-term postoperative complications (POCs) after proctectomy and IPAA for UC.

Methods

This retrospective single-centre study included patients who underwent proctectomy, IPAA and protective ileostomy for UC from 2000-2023. Data were retrieved from our prospectively-maintained database. Exclusion criteria were dysplasia or cancer (103 pts), missing pathology results (50 pts), undetermined colitis or Crohn’s Disease features at proctectomy (18 pts). All patients underwent three-staged IPAA and were divided into four groups according to the rectal stump proctitis status at pathology: remission, mild, moderate, and severe proctitis. A stepwise binary logistic regression analysis was performed for each short-term outcome. Models included variables with a different distribution according to the outcome (p-value ≤0.1).

Results

We included 785 patients who underwent proctectomy and IPAA. At pathology, remission was achieved by 162 (20.6%) patients, while proctitis of the rectal stump was mild in 211 (26.9%), moderate in 246 (31.3%), and severe in 166 (21.1%) patients, respectively. Table 1 details population characteristics and outcomes according to the proctitis status. Patients with moderate and severe proctitis received more preoperative biologics and ongoing systemic steroids at surgery. While they underwent previous abdominal surgery less frequently, the laparoscopy rate was lower with a longer postoperative length of stay. At multivariate (Table 2), Medical POCs were independently associated with ongoing antibiotics (OR 2.29 [1.01-5.20] p=0.047) and ASA score≥3 (OR 1.93 [1.11-3.35] p=0.019). Surgical POCs were independently associated with ongoing systemic steroids (OR 2.09 [1.19-3.68] p=0.011, while ongoing antibiotics (OR 0.2 [0.04-0.86] p=0.031) and laparoscopy (OR 0.53 [0.28-1.00] p=0.049) were protective. Intra-abdominal septic complications (IASCs) and abdominal/pelvic abscesses were independently associated with the proctitis status (OR 1.1 [1.06-2] p=0.018 and OR 1.56 [1.08-2.25] p=0.017, respectively).

Conclusion

Rectal stump proctitis was independently associated with postoperative abdominal and pelvic abscesses and IASCs after proctectomy and IPAA for UC. The association between proctitis and IPAA’s long-term outcomes and pouch failure need to be further explored.Read more OP01 PROFILE: a multi-centre, randomised, open-label, biomarker-stratified clinical trial of treatment strategies for patients with newly-diagnosed Crohn’s diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Clinical outcomes differ substantially between patients with Crohn’s disease and there is variability in how newly-diagnosed patients are managed. Recent interest has focused on developing biomarkers to predict outcomes and guide therapy. PROFILE was designed to evaluate the clinical utility of a blood-based prognostic biomarker in patients randomised to "top-down" or "accelerated step-up" treatment strategies for newly-diagnosed Crohn’s disease.

Methods

PROFILE (PRedicting Outcomes For Crohn's dIsease using a moLecular biomarker, ISRCTN 11808228) was an open-label, biomarker-stratified, randomised controlled trial. It enrolled adults with newly-diagnosed active Crohn’s disease (Harvey Bradshaw Index ≥7 and C-reactive protein > upper limit of normal or faecal calprotectin ≥200 ug/g, plus endoscopic evidence of active inflammation) in 40 UK hospitals. Following biomarker testing patients were randomised to "top-down" (infliximab/immunomodulator) or "accelerated step-up" (conventional) treatment stratified by: biomarker subgroup (termed IBDhi/IBDlo), endoscopic inflammation (mild/mod/severe) and extent (colonic/other). The primary endpoint was sustained steroid and surgery-free remission to week 48. The key secondary endpoint was endoscopic remission (absence of ulcers). The full analysis population (equivalent to ‘intention-to-treat’) was analysed.

Results

386 patients were randomised from 29 December 2017 to 5 January 2022. Median time from diagnosis to trial enrollment was 12 days (0-191). Primary outcome data were available for 379 eligible participants. Sustained steroid and surgery-free remission was significantly more frequent in "top-down" (79% of 189 patients) compared to the "accelerated step-up" arm (15% of 190 patients), with an absolute difference of 64% (95% CI=57-72%, p<0.001). There was no biomarker-treatment interaction effect (absolute difference 1%, 95% CI=-14 - +14%, p=0.944). Endoscopic remission at week 48 was greater in "top-down" vs "accelerated step-up" (67% vs 44%, 95% CI=11-36%, p<0.001), with no biomarker-treatment interaction. Incidence of adverse events (including disease flares) and serious adverse events was lower in "top-down" vs "accelerated step-up" (168 vs 315; 16 vs 25 respectively), with fewer complications requiring abdominal surgery (1 vs 10, odds ratio=0.095, 95% CI=0.001-0.505) and no increase in infections.

Conclusion

"Top-down" treatment with combination infliximab/immunomodulator achieved substantially higher sustained steroid and surgery-free remission compared to "accelerated step-up". The biomarker did not show clinical utility in PROFILE. "Top-down" should now be considered standard-of-care for patients with newly-diagnosed active Crohn’s disease.Read more P194 Health-related quality of life and fatigue in newly-diagnosed inflammatory bowel diseases: findings from a prospective population-based inception cohort, IBD Prognosis StudyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Patients with inflammatory bowel diseases (IBD) often experience impaired quality of life (QoL) and fatigue. In the current study, we aimed to investigate QoL and fatigue at the time of IBD diagnosis and determine their association with the disease presentation.

Methods

Incident adult patients (≥18 years old) with newly diagnosed ulcerative colitis (UC) or Crohn’s disease (CD) according to the Copenhagen IBD Criteria were included in the IBD Prognosis Study, a prospective, population-based, inception cohort representing approximately 20% of the Danish population (1.1 million). QoL was assessed using EQ-5D-5L and Short inflammatory Bowel Disease Questionnaires (SIBDQ), while fatigue was assessed using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scale. A severe disease presentation was defined by the need for glucocorticoids, immunomodulators, biologics, or surgery within three months of disease. Multivariable logistical regression analyses were conducted by adjusting for gender, age, and disease phenotype.

Results

Out of the original cohort, 203 (65.9%) and 116 (57.7%) patients with incident UC and CD, respectively, responded to the questionnaires without differences between responders and non-responders.The mean EQ-5D-5L index values were significantly lower in patients with UC (0.82, SD 0.17) and CD (0.79, SD 0.23), compared to the Danish background population (both p<0.001). The difference between UC and CD was also statistically significant (p<0.001). Further, more than every third of patients reported severely reduced SIBDQ (UC 29.6%, CD 43.1%, p=0.04).Severe fatigue was experienced frequently at the diagnosis (UC 26.1%, CD 30.2%, p=0.43), and was more common compared to the control group (means: UC 37.2 (SD 12.0), CD 35.3 (SD 11.5), control group: p<0.001).Female gender and extensive UC were independently associated with severely impaired SIBDQ and fatigue in patients with UC, while EIMs were associated with both outcomes in UC and CD (Table 1). Finally, severely reduced SIBDQ and severe fatigue were independently associated with a severe disease presentation, as well as IBD-related hospitalization specifically, in both UC and CD (Figure 1).

Conclusion

In this prospective population-based inception cohort of newly diagnosed IBD, we found a high proportion of patients with severely impaired generic QoL, SIBDQ, and fatigue compared to healthy controls. This study emphasizes the importance of addressing these negative symptoms in patients with IBD and their prognostic impact on the disease presentation.Ref:1. Jensen MB et al., Scand J Public Health. 2023. doi: 10.1177/14034948211058060.2. Montan I et al., Value Health. 2018. doi: 10.1016/j.jval.2018.03.013.Read more P195 Prevalence and factors associated with fatigue in patients with inflammatory bowel diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Inflammatory bowel disease (IBD) is a group of pathologies characterized by symptoms that can be distressing and incapacitating. Fatigue is one of the complaints most frequently reported by patients. However, few studies have analyzed the determinants of fatigue in IBD. The aim of our work is to estimate the prevalence of fatigue, and to identify the factors associated with it in IBD patients.

Methods

Fatigue and nine other dimensions of IBD-related disability were assessed in a cross-sectional survey, including patients followed and hospitalized between March and September 2023, using the IBD-Disk questionnaire. Fatigue and severe fatigue were defined by an "Energy" sub-score > 5 and > 7 respectively. The correlation between Energy and the other IBD-Disk items was analyzed using Pearson's correlation coefficient. Determinants of fatigue were assessed using the Chi-2 test and multinomial logistic regression.

Results

We included 166 patients, 53.6% were men, and 69.3% were Crohn's disease carriers. Mean age was 39 ± 12.7 years. More than two-thirds (69.9%) lived in urban areas. IBD was active in 48.8% of cases. A total of 59% of patients were on biotherapy for maintenance treatment. The mean IBD-Disk total score was 36.4 ± 21. The Energy subscore obtained the highest score (4.9 ± 2.9). The prevalence rates for fatigue and severe fatigue were 42.2% and 22.9% respectively. Significant correlations were observed between fatigue and all other dimensions of IBD-related disability assessed by the IBD-Disk (p<0.001). The strongest correlations were observed between fatigue and defecation regulation (r=0.642), fatigue and work and study (r=0.630), and between fatigue and sleep (r=0.620) (Table 1). In univariate analysis, factors significantly associated with fatigue and severe fatigue were female gender (p=0.040 and 0.047 respectively), disease activity and hospitalization (p<0, 001 each), anemia (p=0.005 and 0.014 respectively), elevated CRP (p<0.001 and 0.030 respectively), hypoalbuminemia (p<0.001 and 0.042 respectively) and absence of biotherapy treatment (p=0.02 and 0.01 respectively). Living in an urban area was also associated with fatigue (p=0.015). In multivariate analysis, the independent risk factors predictive of fatigue were female gender, urban origin, hospitalization at the time of interview, and clinical disease activity. Independent risk factors for severe fatigue in multivariate analysis were female gender and clinical disease activity (Table 2).

Conclusion

The causes of fatigue are multiple and go beyond the clinico-biological elements associated with IBD, also encompassing social, geographical and sleep disturbance aspects. This underlines the need for a holistic approach to the management of IBD patients.Read more P196 Pregnancy and perinatal outcomes of Inflammatory Bowel Disease mothers in Taiwan - a nationwide health and welfare databases analysisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The incidence of inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), has exhibited a consistent rise in recent years across Asia and Taiwan. Existing literature suggests that women with IBD may experience suboptimal perinatal outcomes. However, the specific relationship between IBD in pregnant Taiwanese women and the subsequent health outcomes of their newborns remains unclear. This study aims to meticulously examine the association between maternal IBD and perinatal outcomes using extensive and representative health databases in Taiwan.

Methods

We utilized four large national representative health and welfare databases: 1) Maternal and Child Health Database, 2) Birth Certificate Database, 3) National Health Insurance Database, and 4) Catastrophic Illness Database. Data spanning from 2004 to 2018 were linked using encrypted personal IDs to establish a birth cohort during this period. Mothers identified with a registered IBD diagnosis (CD: ICD 9=555, ICD 10= K50.00-K50.919; UC: ICD 9=556.0-556.6 and 556.8-556.9, ICD 10= K51.00-K51.919) in the Catastrophic Illness Database were defined as cases, with a comparison group of healthy pregnant women matched 1:10 in the same birth year and maternal age. Statistical analyses were done by chi-square tests and conditional logistic regression models.

Results

Among the 3,059,647 births between 2004 and 2018, 146 newborns (126 UC; 20 CD) were born by mothers with a registered IBD diagnosis (Figure 1). No statistically significant differences were observed in stillbirth, preterm birth, cesarean delivery, low birth weight, small-for-gestational-age (SGA), large-for-gestational-age (LGA), and low Apgar scores when compared to the 1,460 matched healthy mothers (Table 1). The only significant difference was observed in the incidence of hypertensive disorders of pregnancy, with a lower prevalence in the IBD group compared to the control group (4.1% vs. 13.6%; p=0.001). Multivariate conditional logistic regression analysis disclosed no significant differences in the aforementioned perinatal outcomes. Subgroup analysis demonstrated that no difference was noted between the CD and UC groups.

Conclusion

Through this comprehensive analysis of long-term health and welfare databases in Taiwan, we found comparable perinatal outcomes between women with IBD and matched healthy women. The birth outcomes are also improved compared with previous studies. This may be associated with advancements in medical management for IBD in recent years. Further research is needed to explore the long-term neurodevelopmental outcomes of these newborns.Read more P197 Exploring diet categorisations and their influence on flare prediction in IBD, using Sparse Group LASSOWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Diet is an important environmental factor that may affect flare occurrence in inflammatory bowel disease (IBD), but analyses are hindered by its complexity. Different a priori and a posteriori dietary assessment tools can be used, such as dietary quality scores and dietary pattern analyses. The Sparse Group LASSO (SGL) might be a novel method combining an a priori and an a posteriori approach. In this study, we aim to explore the SGL method to study whether different food categorisations, representing different dietary patterns, can predict flares in patients with IBD.

Methods

Baseline data on habitual dietary intake and longitudinal data on disease course was collected over a period of 24 months from two cohorts from the Northern and Southern provinces of the Netherlands. Collected food items were classified into 22 food groups. These were further classified into 3 diet categorisations, representing different dietary patterns: model 1. Plant vs animal vs mixed; model 2. Potentially healthy vs neutral vs potentially unhealthy; model 3. Ultra-processed vs not ultra-processed. The SGL parameter ‘lambda’ identifies important groups using a priori group information, while allowing for only a subset of variables within a group to be important predictors.

Results

Of 724 eligible patients, 427 were in remission at baseline and could be included in the SGL analyses. 106 patients (65.1% female, 34% ulcerative colitis, mean age 43.3 ± 14.7 years) developed a flare within 11.2 ± 6.6 months of follow-up. There was a significant higher crude food intake of red meat (p=0.028) and vegetables (p=0.027) in patients who developed a flare compared to those remaining in remission. Prediction models were moderate with AUC varying between 0.425 and 0.542 for model 1, 0.512 and 0.562 for model 2 and 0.451 and 0.612 for model 3 (Table 1). All models showed red meat, legumes and vegetables as the first selected predicting variables. Unexpectedly, legumes and vegetables predicted a higher risk on flares independently of their categorisation. This was robust in our data and confirmed by Kaplan-Meier survival analyses. Notably, clinical confounders sex and kilocalorie intake had the highest predictive values in all 3 models.

Conclusion

Categorisation of the same food groups and food items in different ways influences the predictive value of the SGL method. For the present study, categorising according to ultra-processed and not ultra-processed achieved the best prediction model, though still moderate. The current exploration of the SGL method showed that food might not be the most important predictor of flares in IBD. However, red meat, legumes and vegetables were the most important dietary influencers in these cohorts.Read more P295 Early sonographic improvement predicts the middle-term efficacy of molecular-targeted medications for Ulcerative ColitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Today molecular-targeted medications (MTMs) are widely used for ulcerative colitis (UC). Predicting the efficacy of MTMs early after induction remains a crucial clinical challenge. Intestinal ultrasound (IUS) is now considered a non-invasive, promising monitoring tool for UC. It can assess the disease activity of UC in the whole colon safely and repeatedly. Here, we hypothesized that over time IUS assessment can predict the MTM efficacy early, contribute to early clinical decision-making on whether to continue or switch MTMs, and reduce the burden of colonoscopy (CS) recommended to be scheduled at around 6 months after the induction.

Methods

We analyzed 44 patients who started an MTM for active UC, underwent IUS at baseline and 3 months, and took CS at 6 months after the induction. The clinical disease activity and endoscopic activity at 6 months were assessed with Lichtiger index (LI) and Mayo endoscopic subscore (MES), respectively. Clinical remission was defined as a LI ≤ 3. Endoscopic improvement (EI) was defined as a MES = 0 or 1. In addition to the assessment of sonographic findings, such as bowel wall thickness (BWT), bowel wall stratification including submucosa index (SMI), bowel wall flow with modified Limberg score (mLS), Milan Ultrasound Criteria (MUC), UC-IUS index (UII), Kyorin Ultrasound Criterion for UC (KUC-UC; BWT<3.8mm with SMI<50%) were evaluated.

Results

Patients who achieved steroid-free clinical remission (SFCR) showed better improvement in BWT, %BWT, and mLS in 3 months compared to those who did not achieve SFCR (p<0.01 for each). The improvement in MUC and UII was also observed in patients who achieved SFCR at 6 months (p<0.001 for both). In ROC analyses, the area under the curve for SFCR at 6 months was 0.80 with BWT, 0.80 with %BWT, 0.81 with mLS, 0.85 with MUC, and 0.85 with UII. Among the 44 patients, 7 patients achieved MUC≤ 6.2, estimating MES=0/1, at 3 months, and 6 out of 7 patients demonstrated EI at 6 months (positive predictive value [PPV]=87.5%). Meanwhile, 4 patients satisfied KUC-UC at 3 months and all of them achieved SFCR and EI at 6 months (PPV=100%).

Conclusion

Our study suggests that patients who achieved sonographic improvement in 3 months can continue an ongoing MTM therapy and that patients who demonstrated sonographic findings estimating EI at 3 months can postpone CS at 6 months.Read more P296 Preclinical protein signatures in blood predict Crohn's disease and Ulcerative colitis several years before the diagnosisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

We aimed to identify protein signatures predictive of a future diagnosis of inflammatory bowel disease (IBD).

Methods

We conducted a case-control study, nested within large population-based cohorts with biorepositories. Samples were obtained from individuals who later in life were diagnosed with IBD (preclinical cases) and compared with age and sex-matched individuals who remained free from IBD during follow-up (controls). Using proximity extension assays (Olink, Uppsala), we measured 176 proteins. We applied regularized logistic regression to identify protein signatures of preclinical disease in serum from the discovery cohort (n=312). Their performance was validated in an external preclinical cohort (n=222). The biological relevance of identified proteins was further assessed in an inception cohort (n=144). Finally, we used an IBD twin cohort (n=327) to examine the impact of genetic and shared environmental factors on identified proteins.

Results

We identified 34 proteins associated with preclinical Crohn’s disease (CD) in the discovery cohort (P_{false discovery rate} <0.10), with 9 confirmed in the validation cohort (P_{false discovery rate} <0.05). For preclinical ulcerative colitis (UC), 45 proteins were identified and 12 validated (Fig. 1A-B). In the discovery cohort, a signature of 29 proteins differentiated preclinical CD cases from controls with an AUC of 0.85 (Fig. 1G). Its performance was confirmed when applied to the preclinical validation cohort (AUC=0.84, Fig. 1H). Moreover, the signature had excellent capacity to differentiate newly diagnosed CD from healthy controls in the inception cohort (AUC = 0.99, Fig. 1I). The preclinical UC signature had a significant, but albeit lower, predictive capacity in the discovery (AUC=0.77), validation (AUC=0.67) and inception cohort (AUC=0.90, Fig. 1G-I).15 of 17 proteins associated with preclinical IBD demonstrated significantly higher intra-pair correlation coefficients in healthy monozygotic- compared to dizygotic twin pairs, indicating an influence from genetic factors on the regulation of these protein markers. The preclinical signature for CD demonstrated an AUC of 0.87 when comparing twins with preclinical CD (n=10) to matched external healthy twins. However, its predictive capacity was lower when comparing preclinical CD twins with their healthy twin siblings (AUC=0.58), i.e., when accounting for genetic and shared environmental factors. The difference in AUC estimates in the twin cohort was not significant (P=0.07).

Conclusion

We identified protein signatures for predicting clinical onset of CD and UC, validated across independent cohorts. Specifically for CD, the preclinical signature offers significant potential for early detection.Read more P297 Differences in disease characteristics and treatment exposures between pediatric- and adult-onset Ulcerative ColitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

previous studies highlighted differences between pediatric-onset ulcerative colitis (pUC) and adult-onset UC (aUC), showing a more severe phenotype in pUC. However, most studies lacked prolonged follow-up, and some were conducted prior to the biologic era. We utilized a large cohort database to compare disease characteristics and treatment exposures between pUC and aUC.

Methods

Single-center IBD registry from the Sheba Medical Center was used and included aUC (age ≥ 18 years) and pUC (age ≥ 6 and < 18 years) patients diagnosed between 2000 and 2022. Data were retrieved from the medical record to a computerized and periodically updating registry in a unified manner. Retrieved data included demographics, clinical disease characteristics and phenotype, and prescribed treatments during routine clinical follow-up. We used descriptive statistics, T-test, and chi-square test for between-group analyses.

Results

This study included 1332 UC patients, of them 682 were females (51.2%, Table 1). The cohort comprised 1058 aUC and 274 pUC patients. The median (IQR) age at diagnosis for pUC was 14.9 (12.5-16.8) years and 31.7 (23.6-48.9) years for aUC. Disease duration and the interval from diagnosis to last follow-up were similar between pUC and aUC, with a median (IQR) disease duration of 8.9 years (4.6-14.2) in pUC and 8.5 (4.5-14.1) in aUC, and a median interval from diagnosis to last follow-up of 7.3 years (3.5-12.3) in pUC and 7.3 years (3.4-13.0) in aUC. Significantly more pUC presented with pancolitis: 59.1% vs. 39.4% in aUC (p<0.00001), (Table 1). During long-term follow-up, treatment exposures also varied significantly between pUC and aUC (Figure 1); 61.3% of pUC were treated with systemic steroids vs. only 42.4% in the aUC group. Thiopurines were used in 40.5% of pUC vs. only 16.7% of aUC, and biological therapy was used in 46.0% of pUC vs. 34.1% of aUC. Time to initiation of biologic treatment was shorter in pUC with a median (IQR) of 33.0 months (15.0-71.3) vs. 36.6 months (15.8-96.1) in aUC (p=0.04). Finally, the number of biologics lines used was also higher in pUC vs. aUC ((mean of 2.1±1.4 vs. 1.8±1.0, p=0.01). Limiting the comparison to only UC patients who presented with pancolitis included 163 pUC and 417 aUC. Within this more severe UC phenotype, exposure to steroids and thiopurines was still significantly higher in pUC vs. pUC, but exposure to a biologic was similar with 54.6% of pUC vs. 50.1% of aUC.

Conclusion

pUC presents with more pancolitis, considered a more severe form of UC. This more aggressive presentation at diagnosis likely leads to a higher rate of exposure to systemic steroids, thiopurines, and biologics during a median of ~7 years of follow-up.Read more P332 The role of Handgrip Strength in Nutritional Status Assessment of Patients with Inflammatory Bowel Disease. A cross-sectional studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Inflammatory bowel disease (IBD) has been extremely prevalent in recent years. Multiple factors such as chronic inflammation, insufficient nutrient intake, malabsorption and high energy requirements during disease flares increase the risk of malnutrition and impaired body composition leading to complications such as thromboembolism, prolonged hospital stay and surgery. Nutritional status assessment through screening tools, anthropometry and body composition analysis requires experienced personnel and is time consuming. The purpose of this single center cross-sectional study is to assess nutritional status of patients with IBD and investigate various methods for the early detection of malnutrition.

Methods

Eligible participants were patients diagnosed with Corhn’s disease (CD) or ulcerative colitis (UC) from August to October 2023. Exclusion criteria comprised corticosteroid or diuretic treatment and high output stoma or fistulas. Nutrition status was assessed with Subjective Global Assessment (SGA). Body composition analysis was performed with bioelectric impedance analysis (BIA, Bodystat Quadscan 4000). Handgrip strength (HGS) was measured to detect reduced muscle activity through Jamar dynamometer. BIA derived values were compared to reference values from epidemiological studies. Quality of life impairment evaluated through Inflammatory Bowel Disease Questionnaire (IBDQ). Data was analyzed with SPSS Statistics 29.0.1.

Results

104 patients were included (68 with CD, 36 with UC) with a mean age of 46 years (20-79). Based on body mass index (BMI) of the examined sample: 2% were underweight, 47% normal, 31% overweight and 18% obese. Body composition analysis revealed high level fat mass in 50% of females and in 48% of males. Fat free mass index (FFMI) was found low in 30% of females and in 17.5% of males, respectively. Not significant differences were observed between patients with CD and UC. Malnutrition assessment through SGA revealed 7 (6%) severely and 10 (7%) moderately malnourished patients. HGS was negatively strongly correlated with SGA (R²=0.52) and the percentage of fat mass (R²=0.51), whereas positively moderately correlated with FFMI (R²=0.48) and IBDQ score (R²=0.30).

Conclusion

A large percentage of patients with IBD appear to have disturbed body composition and higher levels of fat mass compared to healthy population. Handgrip strength measurement is a fast and cost-effective method of muscle function assessment that correlates well with nutritional status and quality of life. Further studies are needed to validate these findings and incorporate handgrip strength measurement in every day clinical practice to detect malnourished patients.Read more P334 The longitudinal analysis of fecal microbiota in response to ustekinumab treatment in patients with Crohn’s diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Emerging evidence supports that treatment of Crohn’s disease (CD) can alter the intestinal microbiota, which can play a significant role in the pathogenesis and therapeutic outcomes of CD. Ustekinumab (UST) has also been reported to modify the intestinal microbiota during a short-term treatment period. However, the long-term impact of UST treatment on the intestinal microbiota has rarely been studied.

Methods

We prospectively enrolled patients with CD who were planning to start UST treatment and collected fecal samples before (baseline) and after UST administration at week 20 and week 52. Fecal bacterial taxonomic diversity and composition were analyzed through 16S ribosomal ribonucleic acid (rRNA) gene amplicon sequencing. The difference in the intestinal microbiota between clinical remitters and non-remitters defined by Crohn’s disease activity index (CDAI) was investigated, along with the longitudinal changes in the intestinal microbiota.

Results

A total of 124 fecal samples acquired from 43 patients were analyzed (median age 30 years, male 76.7%, median CDAI at baseline 183.2). Clinical remission was observed in 34.9% (n=15/43), 61.0% (n=25/41), and 60.0% (n=24/40) at baseline, week 20, and week 52, respectively. Shannon’s alpha diversity index increased significantly at week 20 and week 52 compared to baseline (both P<0.001). Compared to non-remitters, a significant increase of Shannon’s alpha diversity index was also observed among remitters (P=0.044) across all time points, while no significant difference was noted at each time point. The beta diversity analysis based on the Bray-Curtis distance revealed a significant difference among remitters at week 20 (P=0.027), however, there were no significant differences at other time points. Compared to the baseline, the abundance of the Firmicutes phylum was higher at week 20 (P=0.048) and 52 (P=0.019). The Lactobacillus genus (P=0.042), and Lactobacillus gasseri group (P=0.016) were significantly less abundant in remitters, while the Lachnospiraceae family (P=0.017) was more abundant in remitters. At week 20, Bifidobacterium genus (P=0.027) and Bifidobacterium pseudolongum group (P=0.040) were significantly more abundant in remitter while the Lactobacillus genus was less abundant (P=0.009) in remitter (Figure 1).

Conclusion

The alteration of fecal microbiota after UST treatment may have the potential to serve as a biomarker for predicting clinical remission.

Financial Support

This study was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (NRF-2021R1A2C2095096), the grant (2020IT0012) from the Asan Institute for Life Sciences, Seoul, Korea and the grant (CR 2017-4) from CELLTRION PHARM, Inc., Chungcheongbuk-do, Korea.Read more P335 Development and validation of a Belgian set of quality indicators for inflammatory bowel diseasesWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Quality indicators are standardized, evidence-based measures of health care quality, categorised as structure (to assess the care setting), process (to assess high-quality care actions by healthcare professionals) or outcome indicators (results of actions undertaken by healthcare professionals). Several quality indicator sets have been developed to standardise, measure and optimise IBD care. Our aim was to develop and validate a set to assess IBD care in Belgium and to select a subset of indicators with room for improvement that can be used to implement and improve care in clinical practice.

Methods

The importance of 221 quality indicators (49 structure, 135 process and 37 outcome) identified through literature was scored on a 10-point Likert scale in a two-round modified Delphi exercise by IBD experts. In a third round, the experts indicated and ranked their top 10 indicators with most room for improvement benefitting the patient in the Belgian healthcare system to agree on an improvement subset. In parallel, patient perspectives were collected through two linguistic patient focus groups, one in Flemish (6 participants) and one in French (4 participants). A final consensus meeting was organised to discuss 1) the patient perspectives gained through the focus groups, 2) the results of two Delphi scoring rounds and 3) the results of the additional ranking round. Indicators scoring ≥7 by ≥80% of the participants during the second scoring round, or based on agreement during the consensus meeting, were included in the final set.

Results

Thirty-two experts (11 IBD nurses and 21 clinicians including 2 paediatricians) participated in all three voting rounds, of which 19 also participated in the consensus meeting (6 IBD nurses and 13 IBD clinicians including 2 IBD paediatricians). In total, 199 quality indicators were agreed upon to assess IBD care in Belgium (41 structure, 123 process and 35 outcome). Eighteen (3 structure, 14 process and 1 outcome; Table) were retained in the improvement subset, related to patient characteristics, endoscopy guidelines, infection prevention, steroid use, the IBD care team, services provided in the IBD clinic, the documentation of patient characteristics, the care pathway and the monitoring of disease activity. The decision to include the latter five themes was driven by the importance to patients, which was evident from the patient focus groups.

Conclusion

An evidence and consensus based set of quality indicators was developed and validated - including an improvement subset - allowing Belgian IBD centres to evaluate quality of provided care, set up quality improvement projects and potentially launch a benchmarking study.Read more P336 Exploring Extracellular Matrix Markers in Ulcerative Colitis: Degradation and Formation InsightsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The gold standard for assessing disease activity in ulcerative colitis (UC) is endoscopy, which is uncomfortable for the patient, and only evaluates the superficial layers of the colon. Intestinal extracellular matrix (ECM) remodeling is highly dynamic during disease activity and blood spillover of ECM components might reflect transmural disease burden. The aim of this study was to evaluate baseline serum markers of ECM formation (PRO-C11, PRO-C22, and PRO-C7) and degradation (C7M) to assess disease activity and treatment response in UC.

Methods

Forty-nine UC patients with active disease and 50 healthy controls (HC) were included. All underwent endoscopy and blood sampling at inclusion. UC patients additionally had fecal calprotectin (FCP) measured at baseline and had treatment adjusted at the discretion of the attending physician. Subsequent follow up of UC patients included clinical activity score, FCP, and blood samples at 3 and 6 months as well as an endoscopy at 6 months. Ulcerative Colitis Endoscopic Index of Severity (UCEIS), total Mayo score (TMS), and disease extent (E1-E3) was registered. Response was defined as a reduction from severe to moderate or mild disease based on TMS. If no follow-up endoscopy was performed (n=9), partial Mayo was used. Spearman’s correlation and one-way-ANOVA with Turkey correlation and correction for multiple testing were applied for statistical analysis.

Results

All markers of ECM degradation and formation were elevated in patients with severely active UC measured by both UCEIS and TMS compared to HC (adjusted p<0.0001 for each marker). CM7 and PRO-C22 differentiated moderate from severe UC by TMS (p<0.0001) and UCEIS (p<0.05) (Figure 1A-B). Baseline C7M, PRO-C7, and PRO-C11 correlated with CRP (Spearman’s: r=0.82, p<0.0001; r=-0.45, p=0.0012; and r=-0.33, p=0.032, respectively). None of the markers correlated with FCP. Elevated C7M, PRO-C7, and PRO-C11 levels for E3 could differentiate E3 from E1 (Difference ng/ml: 3.89 (SE of diff: 1.47), 13.15 (4.55), 10.08 (4.09), respectively, all p<0.05) (Figure 1C-E). Remission was achieved in 18/49 patients at 6 months. Both C7M and PRO-22 exhibited acceptable discriminative capabilities at baseline for 6-month TMS between remission and non-remission (AUC 0.72 (95% CI 0.58-0.87) p=0.01 and AUC 0.68 (95% CI 0.53-0.83) p=0.04, respectively) (Figure 1F-G).

Conclusion

This study demonstrates that ECM markers correlate with disease activity, disease extent, and predict future disease outcome in UC. ECM markers hold great promise as they provide a 'window' into transmural tissue remodeling and inflammatory and fibrotic burden, warranting further investigation.Read more OP02 IL23R-CAR-Tregs: creating a therapeutic breakthrough for Crohn’s DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Regulatory T cells (Tregs) are key immunomodulators to maintain immune homeostasis and self-tolerance, including in the intestine. Disrupted immune homeostasis is associated with Crohn’s Disease (CD) pathogenesis. As a living drug, Treg therapy is a promising treatment for restoring immune balance and achieving durable tissue tolerance in the diseased intestine. By targeting a disease-relevant protein, Interleukin-23 receptor (IL23R), we engineered Tregs expressing IL23R-chimeric antigen receptor (CAR) to create IL23R-CAR-Tregs for treating CD.

Methods

IL23R protein expression in CD intestine was verified by immunohistochemical analysis. Tonic signaling and CAR-specific activation were quantified during the IL23R-CAR screening. The IL23R-CAR-Treg phenotype was assessed by monitoring the expression of FoxP3 and Helios transcription factors, and the demethylation status of FoxP3 Treg-specific demethylated region (TSDR). The suppressive function of IL23R-CAR-Tregs was evaluated using in vitro assays and a colitis mouse model. The functionality of IL23R-CAR-Tregs were further assessed using intestinal biopsy-derived cells from CD patients in an in vitro activation assay. Transcriptomic and proteomic analyses were performed to associate molecular profiles with IL23R-CAR-Treg activation.

Results

Our highly potent IL23R-CAR lead candidate displays negligible tonic signalling and a strong signal-to-noise ratio. The resulting IL23R-CAR-Tregs maintain their regulatory phenotype with high FoxP3 and Helios expression and TSDR demethylation during in vitro expansion, CAR-specific stimulation, and in the presence of proinflammatory cytokines. In accordance with their regulatory phenotype, IL23R-CAR-Tregs exhibit CAR-dependent suppressive activity, promote a tolerogenic environment, and protect mice from colitis. The expression of IL23R was also confirmed in the intestinal mucosa from CD patients. Importantly, IL23R-CAR-Tregs elicit activation following exposure to intestinal biopsy-derived cells from CD, demonstrating the engagement and potency of IL23R-CAR towards their target in CD. We also identified molecular profiles that correlated with IL23R-CAR activation and, more broadly, showed their potential to monitor IL23R-CAR-Treg activity in CD patients.

Conclusion

Our results demonstrate that an IL23R-CAR-Treg product could be a promising therapy for CD patients, with the potential long-term benefits of immune tolerance.Read more OP12 Mirikizumab improves fatigue, bowel urgency, and quality of life in patients with moderately to severely active Crohn’s Disease: Results from a phase 3 clinical trialWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Mirikizumab (miri), an anti-IL-23p19 antibody, is approved for the treatment of ulcerative colitis and under development for Crohn’s disease (CD). We investigated how miri impacted fatigue, bowel urgency, and health-related quality of life (HRQoL) through 52 weeks in patients with moderately to severely active CD in the Phase 3 VIVID-1 study.

Methods

In the treat-through VIVID-1 (NCT03926130) study, patients (N=1065) with moderately to severely active CD and a Simple Endoscopic Score for CD (SES-CD) score ≥7 (or ≥4 for patients with isolated ileal disease) and failure to biologic and/or conventional therapy were randomized in a 6:3:2 ratio to receive miri (N=579) (a single 900mg intravenous (IV) dose at W0, W4, and W8 followed by a subcutaneous (SC) dose of 300 mg at W12 and then every 4 weeks), ustekinumab (N=287) (6mg/kg IV at W0 and SC dose of 90mg at W8 and then every 8 weeks), or PBO (N=199). At W12 PBO responders continued PBO to W52; PBO-non-responders received the same blinded miri regimen as described above. This analysis focuses on results in patients randomized to either miri or PBO. The change from baseline for Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Urgency Numeric Rating Scale (UNRS), and Inflammatory Bowel Disease Questionnaire (IBDQ) total and domain scores (bowel symptoms, systemic symptoms, emotional function, social function) were analyzed through W52. IBDQ response (≥16-point improvement from baseline) and remission (total score ≥ 170) rates were also analyzed at W12 and W52. For binary variables, adjusted risk differences were compared between miri and PBO using the Cochran-Mantel-Haenszel (CMH) test. For continuous variables, least squares mean changes from baseline were compared between treatment groups using ANCOVA.

Results

Significant improvement in mean change from baseline to W12 and W52 were observed with miri for FACIT-F, UNRS, and IBDQ total and domain scores (all p<0.000001 at W52) (Figure 1&2). Miri-treated patients showed improved UNRS scores versus PBO as early as W8 with statistical significance sustained to W52 (Figure 1B). At W12 and W52, a greater percentage of miri-treated patients achieved IBDQ response (W12: p<0.000001; W52: p<0.000001) and remission (W12: p<0.000001; W52: p<0.000001) compared to PBO (Figure 2A&B).

Conclusion

Treatment with miri resulted in improvements in fatigue, bowel urgency, and HRQoL at W12 and W52 in patients with moderately to severely active CD.Read more OP22 Topical Sphingosine-1-Phosphate (S1P) Receptor 1 Modulation Regulates Gut Angiogenesis in Inflammatory Bowel DiseasesWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

S1P receptor (S1PR)1/5 modulators have been tested successfully in clinical development programs in ulcerative colitis (UC), leading to their FDA approval. They are believed to act through lymphocyte redistribution in peripheral lymphoid tissue and reduced numbers of circulating lymphocytes, but evidence from other organs suggests potential additional mechanisms of action.

Methods

A post-hoc analysis of the phase 3 trial of the S1PR1/5 modulator Ozanimod in patients with moderately to severely active UC was performed assessing an association of absolute lymphocyte count (ALC) with efficacy. Expression levels of S1PRs were analyzed in human intestinal tissues and primary cells using qPCR and/or immunohistochemistry (IHC). Effects of S1P, S1PR1/5 modulators and S1P1 knockdown on migration, proliferation, cytokine production, downstream signaling (immunoblot), tube formation of human intestinal microvascular endothelial cells (HIMEC) was evaluated. S1P and S1PR1/5 modulators were examined in a murine matrix plug angiogenesis model and with topical and systemic S1PR1/5 modulator therapy in dextrane sodium sulfate (DSS) colitis in vivo.

Results

Baseline ALC and relative or absolute ALC reductions were neither correlated with nor predictive of clinical or endoscopic outcomes. In murine DSS colitis topical therapy with a S1PR1/5 modulator ameliorated colitis but did not alter peripheral lymphocyte numbers. S1PR1 gene and protein expression was increased in UC and Crohn’s disease (CD) patients and predominantly expressed on HIMEC. S1P promoted HIMEC migration, proliferation, tube formation, IL-8 secretion, indicative of pro-angiogenic responses in vitro. Modulation of S1PR1/5 and knockdown of S1PR1 markedly inhibited these pro-angiogenic functions in the presence of high concentrations of S1P, but enhanced angiogenesis when low S1P concentrations were present. S1PR5 had no effect on angiogenesis. In the murine plug assay, S1PR1 induced angiogenesis. In acute DSS colitis, treatment of S1PR modulator by enema reduced blood vessels, but left lymphatics unaffected.

Conclusion

We present a novel mechanism of action of S1PR1 modulators in IBD intestinal tissue, potentially explaining a disconnect between ALC and efficacy observed in a post-hoc analysis of the phase 3 Ozanimod UC trial. The data presented suggest that S1P induced angiogenesis is attenuated by S1PR1 modulation in HIMEC from IBD patients when S1P levels comparable to blood were present. In the presence of S1P at concentrations consistent with lymph fluid angiogenesis was increased. Together with reduced numbers of circulating lymphocytes, this may contribute to efficacy of S1PR1 modulators in IBD patients.Read more OP32 TWIST1-mediated fibroblast activation protein (FAP)-expressing fibroblasts drives fibrosis in Crohn’s DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Stricturing Crohn’s disease (CD) is a distinct clinical phenotype, characterised by the development of fibrotic strictures within the GI tract. These strictures result from chronic inflammation, leading to the accumulation of collagen and scar tissue, causing narrowing of the affected intestinal segments. Due to a lack of anti-fibrotic medication, up to 70% of patients with CD will require surgery in their lifetime, while up to 40% of patients need repetitive resections within 10 years.

Methods

To understand inflammation-induced fibrosis, full-thickness ileal punch biopsies from CD patients (n=10) and colorectal cancer (CRC) patients (n=5) undergoing ileocecal resection (ICR), were profiled using single-cell RNA sequencing (scRNA-seq) on the 10x Genomics platform. Flow cytometry was performed to confirm scRNA-seq findings. Intestinal fibroblasts were cultured in the presence of NicheNet-predicted cytokines or supernatant of FACS-sorted myeloid cells. To confirm the pro-fibrotic role of TWIST1 in fibroblasts, both Harmine (TWIST1 inhibitor)-treated wild-type mice and COL1A2^CrexTWIST1^fl/fl mice were subjected to chronic dextran sulphate sodium (DSS)-induced colitis.

Results

Using scRNA-seq, we identified a specific subset of FAP-expressing fibroblasts enriched in fibrotic surgical CD specimens. Flow cytometry confirmed a significant increase of these cells in the inflamed and stenotic ileum, compared to proximal uninflamed ileum and unaffected control ileum from CRC patients undergoing ICR. Computational methods identified TWIST1 as a key transcription factor, mediating fibroblast activation and extracellular matrix (ECM)-regulatory phenotypes. Myeloid cell-derived inflammatory signals were predicted to induce this specific fibroblast activation, resulting in collagen deposition and tissue fibrosis. Intestinal fibroblasts cultured with inflammatory monocyte supernatant or pro-inflammatory cues expressed higher levels of TWIST1, FAP, and COL3A1. After inhibiting TWIST1 with Harmine, collagen expression and ECM accumulation were decreased in fibroblasts. In addition, in chronic DSS colitis, wild-type mice treated with Harmine showed a reduction in collagen deposition. COL1A2^CrexTWIST1^fl/fl mice showed improved disease activity, compared to their littermate controls.

Conclusion

Our findings suggest that TWIST1 serves as a central mediator in the activation of fibroblasts, promoting excessive collagen deposition in ileal CD. Targeting TWIST1 may reduce tissue remodelling and prevent fibrosis in CD.Read more OP33 Mechanistic insights on the role of ultra processed foods as a trigger/fuel for IBDWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Ultra processed foods (UPFs) are a heterogeneous category of products that contain food additives and/or have undergone several industrial processes. The higher intake of UPFs seen in industrialized countries has been associated with increased incidence of inflammatory bowel diseases (IBD), mainly Crohn’s disease (CD). However, the specific mechanisms through which the UPFs can induce or maintain intestinal inflammation are still unknown. Therefore, most dietary interventions for IBD essentially exclude all UPFs from the menu, increasing the difficulty of long-term compliance of these diets. The main focus of my research is the study of which components may be detrimental in UPFs, in the hope that we can limit the number of UPFs that we need to exclude from our diets.

Methods

To understand the mechanism of action of UPFs, a translational approach is needed with complementary pre-clinical and clinical studies. We used organoid cultures from patients with CD to test the impact of food additives on the intestinal epithelium (e.g. permeability, pro-inflammatory effect). These organoid cultures are more physiologically relevant than immortalized cell lines, which lack several important aspects (e.g. genetic background, complex assembly of different cells). The results of the first tests with this platform have been submitted to ECCO (EC24-1418). Additionally, we established several protocols and collaborations to run well designed dietary intervention studies to explore the mechanisms of action of these food additives in humans. In the FOAM study, we explored the effects of 5 emulsifiers in an double blind randomized placebo controlled trial. The results of the FOAM study have also been submitted to ECCO (EC24-0858). We also explored the acceptance, feasibility, and compliance of an emulsifier free diet in healthy volunteers (EC24-1181).

Results

Our results support the need to better understand the role of food additives and UPFs in IBD, and the need for better evidence supporting the detrimental role of food additives.

Conclusion

Compliance is an important issue to consider in all dietary interventions, more than in pharmacological interventions. Strategies focusing on improving the compliance of dietary interventions can have a big impact in the applicability of these interventions in therapeutic and/or prophylactic settings. However, the current knowledge on the possible detrimental role of UPFs does not allow to pinpoint which UPFs are detrimental and which might have no effect on intestinal inflammation. Hence, there is an unmet need for pre-clinical and clinical studies focusing on the mechanisms through which these UPFs might play a role in intestinal inflammation.Read more DOP10 Risankizumab Versus Ustekinumab for the Achievement of Endoscopic Outcomes in Patients With Moderate-to-Severe Crohn’s Disease: Results From the Phase 3b SEQUENCE TrialWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The SEQUENCE study compared the efficacy and safety of risankizumab (RZB) and ustekinumab (UST) in patients (pts) with moderate-to-severe Crohn's disease (CD) who previously failed ≥1 anti-tumour necrosis factor (TNF)a therapies. The second primary endpoint of SEQUENCE, week (wk) 48 endoscopic remission, demonstrated superiority of RZB versus (vs) UST.¹ Here, additional endoscopic and clinical/endoscopic composite outcomes are reported.

Methods

SEQUENCE (NCT04524611) was an open-label, multicenter, randomised, efficacy assessment-blinded study. Pts had a baseline (BL) CD Activity Index (CDAI) of 220-450, average (avg) daily stool frequency ≥4 and/or avg daily abdominal pain score ≥2, and Simple Endoscopic Score for CD (SES-CD) ≥6 (≥4 for isolated ileal disease). Pts in the primary efficacy analysis set were randomised 1:1 to receive RZB (intravenous [IV] 600mg induction at BL, wk4 and wk8, then 360mg subcutaneous [SC] maintenance doses every 8 wks [Q8w], starting at wk12) or UST (single weight-based IV induction followed by a 90mg Q8w SC maintenance treatment starting at wk8) up to wk48. Randomisation was stratified by BL steroid use and number of failed anti-TNFa therapies. A mandatory steroid taper began at wk2. Here, we assessed at wks 24 and 48 endoscopic remission (SES-CD ≤4 and at least a 2-point reduction versus BL and no subscore >1 in any individual variable, as scored by a central reader), mucosal healing (SES-CD ulcerated surface subscore of 0 in pts with SES-CD ulcerated surface subscore ≥1 at BL, as scored by a central reader), and deep remission (endoscopic remission + clinical remission [CDAI<150]); all were prespecified, non-ranked endpoints, except for wk48 endoscopic remission (second primary endpoint). Treatment differences were adjusted for the randomisation stratification factors. Missing data were handled using non-responder imputation while incorporating multiple imputation to handle missing data due to COVID-19 and/or geopolitical conflict. P values were reported as nominal, except for wk48 endoscopic remission.

Results

With RZB vs UST, a greater proportion of pts achieved endoscopic remission (wk24: 29.4% vs 17.4%, P= 0.001; wk48: 31.8% vs 16.2%, P<0.0001), mucosal healing (wk24: 25.1% vs 14.4%, P<0.01; wk48: 30.2% vs 12.1%, P<0.0001), and the composite endpoint of deep remission (wk24: 22.0% vs 10.2%, P< 0.001; wk48: 22.7% vs 10.9%, P<0.001) at wk24 and wk48 (Figure). The safety profiles of RZB and UST were consistent with published results.¹

Conclusion

Exploration of endoscopic outcomes demonstrated that pts with moderate-to-severe CD and prior anti-TNFa failure showed greater achievement of endoscopic remission, mucosal healing, and deep remission with RZB compared to UST.¹doi.org/10.1002/ueg2.12474Read more DOP11 Disease clearance after 16 weeks of treatment with vedolizumab in patients with moderate to severe Ulcerative Colitis: An interim analysis from the VERDICT trialWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Disease clearance in ulcerative colitis (UC) is defined as concurrent achievement of clinical, endoscopic, and histologic remission.¹ Regardless of the drug used in clinical trials, no more than 20% of patients reach disease clearance after 1 year; thus, it is a high bar to achieve with a potential for disease modification.² VERDICT is a continuing, randomised, controlled trial (NCT04259138) with a primary objective of determining the optimal treatment target in moderately-to-severely active UC, by comparing target Group 1 (corticosteroid-free [CSF] symptomatic remission), target Group 2 (CSF symptomatic remission + endoscopic improvement), and target Group 3 (CSF symptomatic remission + endoscopic improvement + histologic remission). Patients follow treatment algorithms that feature early introduction of vedolizumab (VDZ) with no dose escalation before week 16 and no week 10 dosing. Here we report the achievement of CSF disease clearance at week 16 in Group 3.

Methods

CSF disease clearance was defined as achievement of a CSF Mayo rectal bleeding subscore=0 + endoscopic improvement (Mayo Endoscopic Score [MES] ≤1) + histologic remission (Geboes score <2B.0). VDZ 300 mg was administered intravenously following a treatment algorithm based upon baseline UC treatment until assigned treatment target was reached at week 16. Results are summarized overall and by bio-exposure status.

Results

As of 18 Aug 2023, 553 patients were enrolled in VERDICT with 253 assigned to target Group 3. The group had a mean age of 41.2 years (standard deviation [SD] 14.3), mean disease duration of 7.3 years (SD 7.8), and 42% were female (Table). In total, 216 (85%) were bionaïve, 159 (63%) had a baseline MES of 3, and 129 (51%) were receiving concomitant corticosteroids. Figure 1 shows the breakdown of the 253 patients. At time of analysis, remission target status was unavailable for 30 bionaïve and 11 bio-exposed patients. Among the 212 patients with observed data, 86 (41%) achieved CSF remission, including 77 (41%) of the 186 bionaïve patients with data and 9 (35%) of the 26 bio-exposed patients with data. Corresponding values of achieving CSF disease clearance in the intention-to-treat population were 34% (86/253), 36% (77/216), and 24% (9/37), respectively. All patients with disease clearance were receiving VDZ treatment from baseline.

Conclusion

At week 16, 41% of patients enrolled in the target group of CSF symptomatic remission + endoscopic improvement + histologic remission had achieved CSF disease clearance, with a numerically higher percentage in bionaïve compared to bio-exposed.

References

1 D’Amico et al. Inflamm Bowel Dis. 2023 doi:10.1093/ibd/izad1592.2 Colombel et al. Gastroenterol Hepatol. 2021;17:233Read more DOP30 Cross-ethnic microbiome analyses identify shared and specific signals for Northern Indian IBD patientsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Clinical manifestation of the inflammatory bowel disease (IBD) shows considerable variation across the world. We hypothesized these differences may be influenced by geographical differences in gut microbiome. To test this, we investigated the correlation between gut microbiota and the disease phenotypes of IBD in a cohort form the Northern part of India.

Methods

Stool samples and clinical metadata were collected from 226 IBD patients (198 ulcerative colitis and 28 Crohn’s disease) and 66 controls from a population cohort from the Northern India. We used metagenomic shotgun sequencing to determine diversity, composition and function of the gut microbiota of the participants. Microbiome was then associated to IBD and its subtypes and clinical metadata (e.g. medication use, drug response, and disease activity). We replicated our results in 436 IBD patients and 903 population controls from the Netherlands analyzed using an identical workflow and used machine learning to assess how well do the Indian IBD signals generalize to Dutch IBD.

Results

We identified reduction in microbiome diversity and changes in beta diversity in Indian IBD patients (FDR < 0.05, replicated in Dutch population) and identified that 319 taxa and 71 biochemical pathways are altered in Indian patients (FDR < 0.05). Of note, 39% of these signals were replicated in the Dutch cohort (at FDR < 0.05 level). We identified strong dysbiosis shared across Indian and Dutch IBD patients, characterized by expansion of opportunistic pathogens (e.g. Genera Clostridium, Streptococcus and Lactobacilli) and oral bacteria (e.g. Streptococcus oralis and Bifidobacterium dentium) as well as reduction in butyrate producers such as Faecalibacterium prausnitzii, Roseburia hominis and Blautia massiliensis. In addition, we found novel pathobionts specific to the Indian cohort (including oral bacteria from Genus Scardovia and Oribacterium; Actinomyces dentalis and Klebsiella pneumoniae). Machine-learning models trained on the Indian cohort were highly predictive in the Indian test set (Sensitivity 0.84, Specificity 0.95) and generalized to Dutch cohort (Sensitivity 0.77, Specificity 0.69).In addition to IBD-associated dysbiosis, we identified links between medication use and gut microbiota independent of the disease activity: use of Tofacitinib (used by 26 UC patients) was linked to decrease in Lactobacilliales and increase in Clostridia, while Prednisolone and Azathioprine associated to reduction in Roseburia and increase in Streptococcus and Granulicatella.

Conclusion

The IBD patients from Northern India show gut dysbiosis similar to European patients, but also show enrichment in India-specific pathobionts. The microbiome-based diagnostic models generalize across these populations.Read more DOP31 Gene correlation network analyses reveal transcript modules and pathogenic mechanisms associated with resistance and response to ustekinumab therapy in Ulcerative ColitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Precision medicine in ulcerative colitis (UC) remain elusive. The heterogeneity in patients’ mucosal transcriptomic profiles suggests that stratification based on molecular mechanisms might be possible, which may link to treatment response. We interrogated a dataset of ustekinumab-treated patients treated to determine transcript modules (TMs) in active UC, investigate pathogenic pathways and consider which cells might be driving ustekinumab resistance.

Methods

Pre-treatment mucosal transcriptomes and outcome data were available for 358 ustekinumab-treated patients enrolled in the UNIFI programme. Modules of co-expressed genes were defined with weighted gene correlation network analysis (WGCNA) and their functional roles and regulatory interactions inferred with Fisher tests. Multivariate regression was used to test the ability of clinical and transcriptomic data to predict treatment resistance. Further insights into the cellular and molecular features of ustekinumab resistance were gauged from the analysis of single cell data (Single Cell Portal accession SCP259). Analyses were performed in R 4.2.3 (Vienna, Austria).

Results

WGCNA generated 23 transcript modules (TMs) whose correlation with mucosal healing ranged from -0.26 to 0.25. The three TMs most negatively correlated with response comprised genes enriched in neutrophil degranulation, extracellular matrix activity and endoplasmic reticulum function. The modules correlating highest with response were enriched in genes involved in mitochondrial function. The constituents of the ustekinumab resistance-related modules are regulated by a hierarchy of transcription factors downstream of NFKB1, AHR, JUN and RELA. They are also densely connected by regulatory protein-protein interactions (Figure 1). A multivariate model including TM1 enrichment score and clinical variables predicts resistance with area under the curve 0.76 (95% confidence interval: 0.69–0.82). Notably, TM1 included TREM1 and OSM, which were previously associated with anti-TNF resistance. Surmising that cell populations co-expressing these genes might be key to ustekinumab resistance too, we identified TREM1+ OSM+ inflammatory monocytes (IMs). These showed higher expression of genes such as IL1B, IL8 and CXCL2 compared to other IMs, and increased activity in pathogenic processes including interleukin (IL)10, IL4 and IL13 signalling and G-protein-coupled receptor signalling.

Conclusion

Gene co-expression analysis identified transcripts and molecular mechanisms associated with response and predictive of resistance to ustekinumab. TREM1+ OSM+ IMs may be key to driving resistance, suggesting an important role for innate immunity. These findings are important for developing precision medicine approaches in UC.Read more DOP48 Faecal microbiota transplantation in active Ulcerative Colitis: Key lessons from a randomized controlled trial halted for futilityWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Rigorous donor preselection on microbiota level, strict anaerobic processing, and repeated FMT administration were hypothesized to improve FMT outcomes for induction of remission in UC in the RESTORE-UC trial, for which we here report on the clinical results and observed microbial changes.

Methods

The RESTORE-UC trial was a multi-centric double-blind, sham-controlled randomized trial. Patients with moderate to severe UC (total Mayo 4-10, endoscopic subscore ≥2) were randomly allocated to receive 4 weekly anaerobic-prepared allogenic or autologous donor FMT. Allogenic healthy donors were selected after a rigorous screening by microbial cell count, enterotype, and the abundance of specific genera. The primary endpoint was steroid-free clinical remission (total Mayo ≤2, no subscore >1) at week 8. A pre-planned futility analysis was performed after 66% (n=72) of intended inclusions (n=108). Quantitative microbiota profiling (n=44) was performed at weeks 0 and 8.

Results

In total, 72 patients were included of which 66 received at least one FMT (allogenic-FMT n=30 and autologous-FMT n=36, Fig. A). At week 8, resp. 3 and 5 patients reached the primary endpoint (p=0.72), indicating no treatment difference of at least 5% in favour of allogenic-FMT. Hence, the study was stopped due to futility. The procedure was well tolerated, and only 2 SAE were observed.Microbial analysis showed no significant differences in baseline microbiome composition between treatment groups. However, numerically more enterotype transitions upon allogenic-FMT compared to autologous-FMT (Fig. B), and more transitions were observed when patients were treated with a different enterotype than their own at baseline (p=0.01). Primary response was associated with lower total Mayo scores, lower bacterial cell counts (Fig. C,D) and a tendency to more Bact 2 prevalence at baseline, independently from FMT origin. At the allogenic donor side, a positive association was suggested between stool moisture and treatment success (Wilcoxon test, p=0.057; Fig. F). However, no indications pointed towards a highly effective ‘superdonor’ profile.

Conclusion

The RESTORE-UC trial comparing preselected allogenic to autologous FMT did not meet its primary endpoint of steroid-free clinical remission at week 8. Notably, participants exhibited more severe disease, aligning with recent guidelines recommending FMT for mild to moderate cases (Lopetuso & Deleu et al., 2023). In addition, our findings support adding microbial load and dysbiosis to the patient inclusion criteria based on a pre-treatment microbiome screening. Next to patient-selection, further research should additionally consider sterilized sham-control, increased frequency, density, and viability of FMT prior to administration.Read more DOP49 Guselkumab improves health-related quality of life as measured by PROMIS-29 in patients with moderately to severely active Ulcerative Colitis: Phase 3 QUASAR induction studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Patients (pts) with ulcerative colitis (UC) suffer from symptoms that impair health-related quality of life (HRQoL). The Phase 3 QUASAR induction study (NCT04033445) evaluated the efficacy and safety of guselkumab (GUS), an IL-23 p19 subunit antagonist, in pts with moderately to severely active UC who had demonstrated inadequate response, loss of response, or intolerance to conventional and/or advanced therapies (ie, tumor necrosis factor-alpha antagonists, integrin receptor antagonists, and/or Janus kinase inhibitors). Here we report the effect of GUS IV induction on HRQoL at Week (Wk) 12 as measured by the Patient-Reported Outcomes Measurement Information System (PROMIS)-29.

Methods

Pts were randomized 3:2 to receive GUS 200 mg IV or placebo (PBO) IV at Wks 0/4/8. PROMIS-29 consists of 7 domains (anxiety, depression, fatigue, pain interference, sleep disturbance, physical function, and social participation) and a pain intensity numeric rating scale (NRS, range 0-10). The raw score of each domain was converted into a standardized T-score based on a general population mean of 50 and standard deviation (SD) of 10. Higher scores indicate better outcomes for physical function and social participation and worse outcomes for all other domains. The physical component summary (PCS) and mental component summary (MCS) scores were calculated based on the domain T-scores for physical and mental HRQoL, with higher scores representing better outcomes. Minimum clinically meaningful improvement was defined as a ≥3-point improvement in the pain intensity NRS score, a ≥5-point (one-half SD of the population) improvement in each domain, and a ≥5-point improvement in the PCS/MCS scores. More stringent thresholds (eg, ≥7- or ≥9-point improvements) were also examined and will be presented.

Results

Among the primary analysis population, baseline mean PROMIS-29 domain scores were similar between treatment groups, with functional domain scores <50 and symptom domain scores >50, indicating impaired HRQoL (Table). GUS-treated pts achieved a greater mean change from baseline at Wk 12 in each domain T-score, the pain intensity NRS score, and the PCS/MCS than PBO-treated pts. Additionally, the percentage of pts achieving minimum clinically meaningful improvement at Wk 12 was greater for GUS vs PBO in each domain, the pain intensity NRS score, and the PCS/MCS scores (Figure).

Conclusion

Pts with moderately to severely active UC treated with GUS IV induction experienced broad and clinically meaningful improvements in HRQoL as measured by the PROMIS-29 at Wk 12.Read more DOP50 PINPOINT: The epidemiology of paediatric-onset Inflammatory Bowel Disease in the United Kingdom – a prospective, national, cohort studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Paediatric inflammatory bowel disease (PIBD) incidence and prevalence is increasing worldwide. Robust epidemiology can inform new aetiological hypothesis, inform healthcare provision and improve patient outcomes. The last prospective United Kingdom (UK) PIBD incidence study was performed in 1999 (5.2/100,000/yr); we aimed to update this incidence data and to provide a robust prevalence figure for PIBD prospectively across the UK.

Methods

Robust site selection identified all units in the UK providing endoscopy services for paediatric patients. Patients were included if they were diagnosed with Crohn’s disease (CD), ulcerative colitis (UC) or IBD-unclassified (IBD-U) less than 16yrs of age while a permanent UK resident. A custom-built spreadsheet was used to record basic demographics prospectively from June 2021 – December 2022 (18 months). A point prevalence study on 28^th February 2023 was also performed capturing all patients under 16yrs of age living in the UK. A subset of patients was approached to provide consent for future clinical note review, data linkage and future contact (the PINPOINT cohort). Multiple data points were triangulated to avoid duplicate records. Data was securely collated electronically by the IBD Registry (www.ibdregistry.org.uk) and basic descriptive statistics performed in R v4.1.3. Publicly available population data was used to calculate rates.

Results

All 34 selected sites prospectively recorded cases; all were diagnosed by ileocolonoscopy. During the study 2,243 new diagnoses were recorded (1,050 patients [47%] also consented to join the PINPOINT cohort). UK PIBD incidence was 12.1/100,000/yr (England/Wales 11.7/100,000/yr, Northern Ireland 12.7/100,000/yr, Scotland 17.2/1000,000/yr). CD (56%) was more prevalent than UC (33%) and IBDU (11%). Median age at diagnosis was 12.9yrs (IQR 10.6-14.5). There was a male preponderance (62%) with CD, IBDU and UC having male to female ratios of 1.8, 1.7 and 1.4 respectively. With regard to ethnicity 72% of patients identified as white; those of other ethnicities were diagnosed younger (12.1yrs vs 13.0yrs; p<0.001) and had a higher incidence of UC (38.5% vs 30.3%; p=0.003). Regarding prevalence, 6,116 patients aged less than 16 years were identified as living with IBD on 28^th February 2023 giving a UK prevalence of 49.6/100,000 (England/Wales 48.7/100,000, Northern Ireland 53.3/100,000, Scotland 58.6/1000,000).

Conclusion

There has been over a two-fold rise in PIBD incidence across all regions of the UK since 1999 with the first accurate prevalence figure mirroring this rise. Further detailed analysis of epidemiological trends using these data and the PINPOINT cohort are merited to drive improved care for this growing group of patients with high healthcare needs.Read more DOP51 Risk of kidney failure in patients with Inflammatory Bowel Disease undergoing colectomy: a nationwide cohort studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Inflammatory bowel disease (IBD) is frequently accompanied by kidney complications. Potential triggers or subpopulations at high-risk of kidney problems are not well elucidated. We hypothesized that surgical interventions, specifically colectomy, might in part explain this risk.

Methods

A nationwide Swedish cohort study comprising 82,052 individuals with biopsy-proven IBD diagnosed during 1965-2017, with follow-up until 2019. We investigated the association between incident colectomy (time-varying exposure) and future risk of kidney failure (diagnosis of end-stage kidney disease or death due to chronic kidney disease) using Cox proportional hazard models. We also examined the impact of partial vs. total colectomy and the presence of a stoma. Covariates included age, sex, education level, and selected comorbidities.

Results

Over a median follow-up of 14 years, 15,922 individuals underwent colectomy, and 952 kidney failure events occurred. Colectomy was associated with an increased relative risk of kidney failure (adjusted hazard ratio [aHR] 1.60; 95% CI 1.39-1.84). Compared to periods without colectomy, undergoing total colectomy (aHR 1.82; 95% CI 1.54-2.15) and colectomy with the presence of a stoma (aHR 2.40; 95% CI 1.75-3.28) showed higher risks versus partial colectomy or colectomy without a stoma, respectively. Subgroup analyses revealed higher kidney failure risk in patients with ulcerative colitis and those aged ≥40 years at IBD diagnosis. In absolute risks, at 30-year after colectomy, 8.9% of patients with IBD had kidney failure, with an absolute risk difference of 4.5% (95% CI 1.9-7.0%).

Conclusion

In people with IBD, rates of kidney failure are higher among those undergoing colectomy, particularly following total colectomy or colectomy with a stoma. This study identifies a high-risk population that may benefit from established protocols for kidney function monitoring/surveillance and referral to nephrologist care.Read more P003 Metabolic Reprogramming in Intestinal Fibrosis: Integrating Metabolomics, Single-Cell Transcriptomics and Isotope TracingWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

This study aims to systematically elucidate the metabolic landscape of intestinal fibrosis in Crohn's disease, revealing the key reprogrammed metabolic pathways in the fibrotic microenvironment.

Methods

We collected normal and fibrosis tissues from 122 Crohn's disease patients undergoing surgery for fibrosis-induced intestinal obstruction, and established DSS/TNBS-induced murine intestinal fibrosis model. To measure metabolites level in normal and fibrotic tissues, untargeted metabolomics was performed. C13-labeled glutamine was used for metabolic tracing to delineate metabolic fluxes in vitro and in vivo. We performed integration analysis by merging metabolomics and metabolic tracing data with established single-cell transcriptomic profiles. Isolation and further validation of human intestinal stromal cells were carried out, and gene expression was assessed using qRT-PCR and immunofluorescence.

Results

Significant metabolic heterogeneity was observed between normal and fibrotic tissues, with differential metabolites enriched in glucose and amino acid metabolism. Notably, intermediates of glycolysis were significantly increased, while tricarboxylic acid (TCA) cycle intermediates were decreased in fibrotic regions (p<0.05). Amino acids were broadly downregulated in fibrosis, whereas glutamate and glutamine were highly enriched (p<0.05). Mechanistic insights into these changes were provided by isotope tracing, revealing enhanced glycolysis and weakened TCA flux attributed to transition from TCA intermediate α-KG to glutamate. Moreover, catabolism of glutamine to glutamate was enhanced. Glutamate from above pathways converted to proline, which is the ingredient of extracellular matrix (ECM).Single-cell transcriptomic analysis indicated a high enrichment of genes related to glutamine metabolism in stromal cells, with significant upregulation of enzymes such as GLS (Glutaminase) and PYCR1 (Pyrroline-5-carboxylate Reductase 1) involved in glutamine and proline synthesis. Immunofluorescence and qRT-PCR confirmed the upregulation of GLS and PYCR1. Further experiments using primary stromal cells and murine models demonstrated that inhibiting GLS activity reduced ECM synthesis, alleviating intestinal fibrosis.

Conclusion

In intestinal fibrosis, glycolysis and glutamine catabolism enhanced. Stromal cells utilized the reprogrammed metabolic pathway to synthesize glutamate, thereby promoting pathological ECM anabolism. Targeting the key enzyme GLS represent a potential therapeutic strategy for intestinal fibrosis.Read more P004 Functional interrogation of the stem cell graft reveals heterogeneity that may determine clinical outcomes after hematopoietic stem cell transplant for refractory Crohn's DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

For the treatment of refractory Crohn’s disease (CD) autologous stem cell transplant (auto-SCT) is unparalleled in its ability to induce clinical and endoscopic remission. Auto-SCT is unique as a cellular therapy aimed to reset immune pathophysiology to a pre-disease state using hematopoietic stem cells (HSC). To date no studies in any cohort have defined the mucosal and peripheral immune response to auto-SCT or analyzed HSC functions.

Methods

Patients with CD were enrolled in a Phase IIa study of auto-SCT (NCT03219359) with 16 patients transplanted (2018-2023). Patients underwent a standard mobilization regimen with cyclophosphamide and G-CSF. Mononuclear cells from the mobilized stem cells of 9 patients were isolated and then analyzed for phenotyping using flow cytometry. For xenograft studies, CD34+ selected stem cells from 6 patients were injected into NOD.Cg-Prkdc^scid Il2r^gtm1Wjl/SzJ (NSG) mice to assess engraftment and differentiation potential by flow cytometry of cells from bone marrow at multiple time points.

Results

At 6 months from auto-SCT, 15/16 patients had an endoscopic response (Total SES-CD decrease ≥ 50%) and 11/16 were in endoscopic remission (total SES-CD ≤ 4, no sub-score >1). Phenotyping of the stem cell graft demonstrated variability between patients but overall there was predominance in short-term HSCs and lineage committed progenitors rather than long-term HSCs (LT-HSC). There was variable engraftment of the CD34+ cells that were transplanted in NSG mice and 2 of the patients who had inadequate engraftment also were noted to have suboptimal clinical results, 1 with disease relapse and 1 without clinical response after auto-SCT. Of those with engraftment, we found a predominance of myeloid populations emerging early and sustaining and emergence of B cells at 8 weeks.

Conclusion

Here we report the first ever study of the stem cell graft using a xenograft model to understand therapeutic mechanisms of auto-SCT for refractory CD. These results show tremendous functional variation in mobilized stem cell populations from patients with CD and a complete lack of LT-HSCs, which have greater self-renewing potential. This suggests that the efficacy of auto-SCT for refractory CD may be due in part to the HSCs transplanted and not just the conditioning regimen (i.e. chemotherapy). These studies suggest the response to stem cell transplant may depend on the presence of functional HSC populations and perhaps the lack of long-term response is due to the lack of LT-HSC in all patients.Read more P005 Exosome miR-132-3p derived from Adipose Stem Cells in Creeping fat Regulates RASA1/ERK1/2-dependant Lymphatic Functions and Improve Colitis and MesenteritisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Creeping fat (CrF) is an important pathological characteristics of Crohn’s disease (CD) and characterized by lymphangiogenesis and abnormal lymphatic functions. Adipose tissue derived stem cells (ADSCs) can regulate surrounding cells function by delivering exosomes (exo). However, whether CrF-ADSC-exo could affect lymphatic endothelium to regulate lymphatic functions, and further influence procession of mesenteritis and colitis remains elusive.

Methods

Paired CrF and uninvolved mesenteric adipose tissue (uMAT) samples were collected from CD patients during operation, and exosomes were separated by ultra-centrifugation. Human lymphatic endothelial cells (HLECs) were cultured in vitro and evaluated the abilities in proliferation, migration and tube formation. IL-10 KO mice was used for assessing the treatment of CrF-ADSC-exo in experimental colitis and mesenteritis.

Results

ADSC-derived exosomes from paired CrF and uMAT samples were confirmed to transfer to LEC by immunofluorescence microscope. In vitro, CrF-ADSC-exo effectively stimulated HLECs in proliferation, migration and tube formation. In vivo, CrF-ADSC-exo injection increased lymphangiogenesis in MAT and improved lymphatic drainage, and further alleviated colitis and mesenteritis in IL-10 KO mice. We next adopted high-throughput sequencing of paired CrF-ADSC-exo and uMAT-ADSC-exo, and validated significantly high expression of miR-132-3p in CrF-ADSC-exo. In vitro, upregulation or downregulation of miR-132-3p in HLECs stimulated or inhibited the lymphatic abilities in proliferation, migration and tube formation, respectively. Mechanically, we demonstrated that CrF-ADSC-exo regulated lymphatic function through miR-132-3p-RASA1-ERK1/2 axis by western blot. CrF-ADSC-exo miR-132-3p improved lymphatic drainage function in MAT and reduced inflammatory colon and mesentery in IL-10 KO mice. The higher level of miR-132-3p in CrF from CD patients was tightly correlated with inflammatory mediators expressions when compared with uMAT and healthy MAT.

Conclusion

Our study discovers that CrF-ADSC-exo improves lymphatic functions and alleviates colitis and mesenteritis through miR-132-3p/RASA1/ERK1/2 axis, which discloses new role of CrF involved in CD procession and provides novel insight for CD treatment.Read more P006 Development of a Crohn's disease molecular activity score to identify region-specific chronically inflamed and non-inflamed processesWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Crohn’s disease (CD) is characterized by significant heterogeneity in disease location and other clinical factors, making it challenging to define the underlying molecular mechanisms associated with disease. Here, we provide a detailed molecular characterization of baseline ileal and colonic tissue from patients enrolled in the GALAXI Ph2b study of guselkumab in CD (NCT03466411) and explore the association of regional molecular profiles with endoscopic and histologic severity.

Methods

Baseline biopsies from 241 patients were obtained from rectum (R), splenic flexure (SF), and terminal ileum (TI). Paired biopsies within a region were processed for histology and RNA sequencing (RNAseq). Cell-type specific transcriptional modules were used to evaluate differential expression and to create a disease severity axis. Principal component analysis (PCA) was applied to modules with the highest correlation with paired Global Histologic Activity Scores (GHAS) per region and the resulting PC1 was used to define an objective tissue-based molecular activity score (MAS) to identify inflamed and uninflamed tissue. Inflamed tissue was used to assess regional molecular profiles which were correlated with paired regional histology scores defined by GHAS and endoscopic severity defined by Simple Endoscopic Score for CD (SES-CD).

Results

Modules specific to inflammatory myeloid and epithelial transcriptional states, and IL-23 and interferon response pathways, were highly correlated with paired GHAS. Applying this subset of modules as a MAS revealed a bimodal distribution of inflamed and non-inflamed biopsies. MAS identified 114/241 (47.3%), 85/229 (37.1%) and 114/229 (49.8%) inflamed biopsies in the R, SF, and TI, respectively. Regional molecular profiles of inflamed biopsies demonstrated increased mRNA expression of IL-23p19 (IL23A) and Fc-γ receptor 1 (CD64) (p<0.001), and enrichment of inflammatory modules across locations. Local MAS per region showed highest correlations with paired baseline GHAS, followed by SES-CD in the segment (Figure 1 and Table 1). Notably MAS provides higher resolution to identify representative biopsies for affected regions.

Conclusion

Application of the MAS to identify inflamed tissue enabled identification of key immune and inflammatory related processes across the ileum and colon that were associated with the IL-23 pathway, and baseline regional endoscopic and histologic severity. By identifying inflamed baseline samples, molecular changes associated with treatment can be more accurately defined in future analyses to better understand regional heterogeneity in CD.Read more P031 Microbiota-driven appendiceal B lymphocytes aggravate DSS-induced murine colitis through facilitating colonic CD4+ T cells polarizationWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The appendix is an immunological organ sustaining a microbiome inoculum that plays a vital role in intestinal mucosal immunity and colonic microbiome stability. Previous studies have proposed the appendix exerts effects on ulcerative colitis (UC)’s pathogenesis, but the nature and basis underlying this connection remain unclear. B lymphocytes account for the largest proportion of appendiceal immunocytes and activate in the experimental colitis model, we systematically investigated how appendiceal B lymphocytes (appB) participate in UC’s pathogenesis and provided rational evidence for appendectomy and B cell immunotherapy being used in UC treatments.

Methods

The chronic colitis model was established in C57BL/6J mice by three cycles of 2% dextran sodium sulfate (DSS) treatment. Bulk RNA sequencing and 16S rRNA sequencing were used to explore appB’s characteristics and the potential causes of appB activation in DSS-induced colitis. Adoptive appB transfer and intravital imaging were used to evaluate appB’s homing and functional features in DSS-induced chronic colitis. Magnetic microbead-based cell sorting and cells experiments in vitro were used to investigate the underlying mechanisms of appB’s activation and effects on DSS-induced chronic colitis. Flow cytometry was used to assess the colonic mucosal adaptive immunity alterations in colitis mice adopted appB.

Results

Firmicutes and Bacteroidetes are the dominant phylum in the normal appendix, while Firmicutes, Verrucomicrobia, and Proteobacteria are prominent in the colitis appendix. The appendiceal IgG⁺ B cells expended in colitis mice compared with the normal mice; and the DSS colitis appB (DSS_appB), compared with the normal control appB (NC_appB), had much more potential to migrate to the colon and fired the gut flare, accompanied by the increment of CD19⁺ IgG⁺ cells, CD4⁺ IFN-γ⁺ cells and CD4⁺ IL-17⁺ cells in the colonic lamina propria in colitis mice. In vitro, DSS_appB secreted more inflammatory cytokines (IFN-γ, IL-6) than NC_appB under the stimulation of Toll-like receptor agonist analogs (Pam3CSK4, LPS, and ODN1826); DSS_appB facilitated colonic CD4⁺ T cells to secrete IFN-γ and IL-17 by up-regulating surface marker (CD80/86) and secreting IFN-γ and IL-6.

Conclusion

In DSS-induced chronic colitis mice, appB activated, driven by appendiceal microbiota,migrated to the colonic lamina propria and aggravated colitis through facilitating CD4+ Tcells polarize to Th1 and Th17 by up-regulating CD80/86 and secreting IFN-γ and IL-6 (Figure 1). Our research provides evidence for the connection between the appendix and UC, and we propose that appendectomy or B cell immunotherapy is promising to treat UC.Read more P032 Exploring the genetic sequence of action across the natural history of IBDWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

We have been very successful at identifying genetic variants associated with inflammatory bowel disease (IBD). From a single locus by the early 2000s, we now know about over 300 regions involved in IBD susceptibility. However, we face two main gaps of knowledge. First, we ignore the mechanisms by which they lead to disease. Second, we ignore their role through the natural history of the disease (e.g., prognosis). To address these gaps, we must integrate inferences from other omic techniques and characterize the genetic sequence of action that takes place across the distinct stages of the disease.

Methods

We have processed publicly available important studies of the genomics and transcriptomics of IBD to make inferences about the sequence of action of genes involved. In total, we processed the large IBDGC GWAS, five transcriptomics and two proteomic datasets (Table 1). We studied different phases of the disease: preclinical, debut and remission, both in Crohn’s disease and ulcerative colitis. We selected sets of genes associated with stages of IBD by the mentioned omics and looked for the overlaps. Last, we performed transcriptome-wide association studies (TWAS) to study the gene expression levels determined genetically in each individual.

Results

We report three main observations from this omic-wide exploration on the genetic sequence of action in IBD. First, we observed a lack of overlap in the gene lists that are relevant in each stage (Figure 1). For instance, just 6.4% of genes discovered by GWAS are differentially expressed at the time of diagnosis and/or remission e.g., NOD2, C2, CCL2, IL27, CSF2, CCL11 and BACH2. In turn, gene signatures discovered through transcriptomics are not particularly enriched for GWAS signals. Second, the genetic risk of each individual, measured through polygenic risk scores, does not correlate with the clustering of patients detected molecularly using gene expression. Third, TWAS analysis reveals an intriguing twist, since we observe large differences between the genetically determined component and the actual gene expression observed in each stage.

Conclusion

Although the genetic makeup of an individual influences expression of key genes involved in IBD, many other genes not detected in genetic studies (GWAS) conform the backbone of molecular alterations present at the time of diagnosis. This global observation challenges the conventional assumption, implying that different actors play a leading role in each stage. Moreover, genetic predisposition is not a strong determinant of the molecular heterogeneity observed in patients across stages. We conclude that the gene regulation dynamics across the natural history of IBD are more intricate than usually assumed.Read more P033 Unrevealing new potential key mechanisms implicated in inflammatory bowel disease by multiomic approachWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Inflammatory bowel diseases (IBD), comprising Crohn´s disease (CD) and ulcerative colitis (UC), are characterised by chronic, relapsing and remitting inflammation of the gastrointestinal tract. Despite significant efforts to understand the pathogenetic mechanisms of IBD, the elucidation of its etiopathology and progression remains incomplete. This study aimed to clarify IBD pathogenesis using a multiomic approach in serum, urine, intestinal tissue and stool samples.

Methods

We performed a multiomic analysis (transcriptomic, proteomic, metabolomic and metagenomic) in a discovery cohort of 53 patients with active CD, 50 patients with active UC, and 33 healthy controls (HC). Proteomic analysis of intestinal tissue was performed by liquid chromatography-mass spectrometry, serum and urine samples were used for metabolome study using nuclear magnetic resonance spectroscopy, and metagenomic analysis of stool samples was performed by 16rRNA gene sequencing.

Results

Gene expression profiles showed a detailed transcriptome landscape of intestinal tissue in patients with CD and UC. A total of 4,105 proteins were identified in mucosal biopsies, of which 2,128 were differentially expressed (DE) between CD and HC, 2,715 proteins DE in UC compared with HC, and 1,653 proteins DE between CD and UC. Metabolomic analyses revealed metabolites and pathways related to ketone, amino sugar and methyl histidine metabolism, Warburg effect, and ammonia recycling deregulated in IBD patients. Moreover, metagenomic results indicated that CD and UC differ in their microbial populations according to beta diversity. In comparison to HC, the microbial population in CD was different, and its alpha diversity was significantly lower (Figure 1).

Conclusion

The results showed that some analytes identified could play essential roles in the pathogenesis of CD and UC. New potential key mechanisms that could help to understand the information of omics layers that underlies the pathogenesis of IBD have been outlined.Read more P034 Peripheral immune cell activity and biopsy gene expression in chronic pouchitis patients treated with tofacitinib: early induction results from the STOPit trialWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The Study of TOfacitinib for the treatment of chronic PouchITis (STOPit) is an investigator-initiated, open-label induction, double-blind, placebo-controlled, maintenance withdrawal study to determine the effectiveness of tofacitinib at inducing and maintaining remission in patients with chronic pouchitis. In this interim assessment, we evaluated blood samples and biopsy gene expression collected during the open-label induction period to discover biomarkers of initial clinical response.

Methods

We collected blood (n = 10 pairs, n = 5 non-responders) and biopsies (n = 21 pairs, n = 9 non-responders) at baseline and after 8 weeks of tofacitinib induction therapy (all participants received 10 mg twice daily induction). We classified patients as responders if they achieved a decrease of ≥ 2 in their modified pouchitis disease activity index after 8 weeks. Bulk peripheral blood mononuclear cells (PBMCs) and memory CD4+ T cells (TMEMs) were isolated from whole blood samples. Cytokines induced by stimulation in the presence or absence of tofacitinib were assessed in culture supernatants by bead array (PBMCs stimulated with PMA/Io or LPS, TMEMs stimulated with CD3/CD28 tetramer). Gene expression was measured in biopsies by qPCR in the pouch and pre-pouch ileum at both time points.

Results

At baseline, non-responders produced more IL-17 from both their PBMCs stimulated with PMA/Io and TMEMs stimulated with tetramer than responders, but responders secreted more IL-12p70, MCP, IL-10 and IL-8. Tofacitinib inhibited stimulation-induced IL-10 and IL-6 secretion in PBMCs in both responders and non-responders but failed to reduce IFNγ and TNF secretion selectively in non-responders only. All cytokine responses investigated in TMEMs, including IFNγ and TNF, were inhibited by tofacitinib in both responders and non-responders, suggesting the PBMC cell type refractory to inhibition with tofacitinib in non-responders is not TMEMs. Baseline biopsy ileal gene expression of IL18, HES1 and CXCL10 was decreased in responders compared to non-responders, while MMP7 was increased. Clinical response to tofacitinib led to a reduction in pouch expression of GLIS3, G0S2 and WNT5a from baseline to week 8 whereas these genes were unchanged or increased in non-responders.

Conclusion

Baseline functional immune cell responses and biopsy gene expression may discriminate chronic pouchitis patients' response to tofacitinib therapy and point to a mechanism underlying non-responsiveness. Recruitment for this trial is ongoing, allowing us to bolster and expand our findings with increasing sample sizes.Read more P060 Increased metabolic activity of faecal Sutterella Wadsworthensis at IBD onset is associated with an increased risk of escalation to biologic therapies - Results from the Birimingham Inception Cohort StudyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Gut microbiome disruption is an established characteristic of IBD. The lack of treatment naïve longitudinal microbiome data makes it challenging to separate the influence of potential confounders. We present detailed stool metagenomics analysis from a treatment naïve cohort of IBD patients seen in our rapid-access IBD inception clinic.

Methods

Stool collected in DNA Genotek OM-200 kits was collected pre-diagnosis, alongside a faecal calprotectin (FCP). Microbial DNA was extracted. Libraries were prepared using NEBNext Ultra II FS DNA Library Prep Kit, NEBNext Multiplex Oligos and sequenced using an Illumina NextSeq550. Data processing was undertaken using the HUMAnN 3.0 workflow. After quality control, a median of 3.6 million reads per sample were obtained. Abundance was mapped to the ChocoPhlAn database and functional pathways derived from MetaCyc. Diversity analysis was undertaken in Vegan, with MaAsLin2 for taxa differences. A False discovery Rate (FDR) <0.2 was considered relevant, <0.05 highly significant.

Results

A total of 45 CD and 33 UC inception patients were included. There was no significant difference in alpha diversity (Shannon; UC median 2.58[IQR 0.8], CD 2.69[1.04] p=0.36) or differential clustering for beta diversity. Shannon alpha diversity significantly associated with FCP across IBD (n=74, Spearman’s Rho [SR] -0.33 p=0.004) and endoscopic severity in both IBD subtypes (UCEIS n=30 SR -0.37 p=0.047, SESCD n=44 SR -0.35 p=0.016). Across IBD, patients going on to require biologic therapy had a significantly lower baseline Shannon (BioYes 2.26[0.98], BioNo 2.77[0.88] p=0.02, split by IBD subtype in Figure 1).Across IBD, increased FCP associated with depletion of two strains of Faecalibacterium Prausnitzii (SGB15318, log2 fold change[L2FC] -1.2 FDR 0.09; SGB15342 L2FC -1.1 FDR 0.15) alongside Roseburia Intestinalis (SGB4951 L2FC -0.7 FDR 0.09). R.Intestinalis also negatively correlated with Harvey Bradshaw Index (L2FC -0.93 FDR 0.02), whilst F.Prausnitzii (SGB15342) did with UCEIS (L2FC -2.3 FDR 0.05).82 metabolic pathways correlated with UCEIS (FDR <0.2, 8 <0.05), with 89 for SESCD (6 <0.05). Increased activity of Sutterella Wadsworthensis associated positively with UCEIS (5 pathways). On initial comparison across IBD, no significant signal was seen for future biologic utilisation. However, if analyses were corrected for baseline inflammation (derived by FCP), increased activity of S.Wadsworthensis was again seen (Table 1).

Conclusion

Reduced alpha diversity at IBD onset associated with increased disease severity and future utilisation of biologic treatment. Increased activity of S.Wadsworthensis associated with an increased risk of future biologic requirement above that explained by mucosal inflammation alone.Read more P061 The macrophage-specific role of PTPN23 in Acute and Chronic ColitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Single nucleotide polymorphisms within the gene locus encoding PTPN2, are associated with Crohn’s disease and ulcerative colitis. We have previously shown that, deletion of PTPN2 results in PTPN23 upregulation in intestinal epithelial cells (IEC) in vivo. PTPN23 is known to be involved in endosomal sorting and responsible for epidermal growth factor receptor (EGFR) internalization from the cell surface and thus negatively controls EGFR signalling in epithelial cells. Though PTPN23 is highly expressed in IEC and intestinal macrophages, nothing is known about its function in myeloid cells and its role in intestinal inflammation.

Methods

Experimental colitis was induced in PTPN23^fl/flLysMCre^+/- (KO) and PTPN23^fl/flLysMCre^-/- (WT) littermates by administration of 2% DSS in drinking water for 7 days (acute colitis) or for 4 cycles of 1.5% DSS for 7 days followed by 10 days recovery, each (chronic colitis). Immune cells were isolated from spleen and colon lamina propria from KO and WT mice and PTPN23 expression was detected by qPCR of RNA isolated after cell sorting with flow cytometry.

Results

The mRNA expression of PTPN23 in untreated WT mice was significantly higher in macrophages isolated from the lamina propria of the colon than in those isolated from spleen (p=0.0279).PTPN23^fl/flLysMCre^+/- (KO) mice were protected from DSS-induced acute colitis when compared to their WT littermates. This was apparent by a lack of DSS-induced weight loss (p=0.02); longer colon length (p=0.01), reduced endoscopic colitis scores (p=0.0016) and lower spleen weights (p=0.0063) in KO mice. In HE staining of colon tissue, the loss of crypts was less pronounced in KO mice. On mRNA level a lower expression of the pro-inflammatory cytokines interleukin 6 (IL-6) (p=0.0117) and tumour necrosis factor α (TNFα) (p=0.0024) was observed in KO compared to WT mice, supporting a reduced inflammatory response.In chronic colitis the same trends was observed, however the effects were less pronounced. WT mice lost more weight during the DSS cycles compared to KO mice, whereas no difference in weight development was detected between the genotypes in water control groups. Higher MEICSs scores were observed in WT compared to KO mice (p<0.0001) and loss of colonic crypts was more pronounced in HE stained colon samples in WT mice than KO mice.

Conclusion

PTPN23 deletion in myeloid cells results in protection from DSS-induced acute and chronic colitis. Additionally, a higher expression in intestinal macrophages compared to macrophages isolated from the spleen suggest a specific role in the intestinal immune system.Read more P062 Characterization of UC1 and UC2 patients: towards personalized medicine in Ulcerative ColitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Ulcerative colitis (UC) is a highly heterogeneous chronic inflammatory bowel disease (IBD) that primarily affects the colon. Although there are some available classifications, mostly based on clinical parameters, the lack of a molecular stratification prevents full comprehension of the diagnostic and prognostic heterogeneity of patients, and thus from correctly predicting their response to available treatments. We have recently developed an unbiased stratification of UC patients (UC1/UC2) based on their transcriptomic profiles (Czarnewski P; et al. Nature Communications, 2019), which holds great potential for the design of personalized medicine in IBD. However, further characterization is necessary to validate it and consolidate its clinical application.

Methods

To achieve this goal, we used bulk and single-cell RNA sequencing (sc-RNAseq) datasets from a prospective cohort of Swedish IBD patients to understand whether UC1 and UC2 are different diseases or states of the same disease, and to deeply characterize the cellular composition of UC1 and UC2 patients. In addition, we took advantage of murine spatial transcriptomics datasets of colonic tissues at steady state or during mucosal healing, to get insights into the spatiotemporal dynamics of UC1/UC2 transcriptional profiles.

Results

A longitudinal analysis of UC1/UC2 transcriptomic profiles as well as gene module analysis revealed that UC1 and UC2 profiles are fluctuant during the course of disease, eventually representing different stages of the same disease. scRNAseq analysis allowed us to identify specific cell types characterizing UC2 patients.[FC1] Finally, while genes defining UC2 patients distributed homogenously within the murine mouse colon at steady state and during mucosal healing, UC1 genes primarily mapped within damage/regeneration regions.

Conclusion

This study details the differences in immune cell composition and molecular pathways in UC1 and UC2 patients, contributing to a more comprehensive understanding of the new molecular stratification system we have developed for ulcerative colitis patients.Read more P063 Interleukin-8 mucosal transcript as predictor of response to Vedolizumab treatment in Ulcerative Colitis: preliminary results from a prospective studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Vedolizumab (VDZ) is a safe, well tolerated and efficient biologic agent used for the treatment of inflammatory bowel disease (IBD), as confirmed by phase 3 randomised controlled trials. However, primary non-response and secondary loss-of-response to VDZ represent a clinically significant problem. The objectives of the present study are to assess the differences in mucosal gene expression profiles of patients with Ulcerative Colitis (UC) prior to VDZ initiation and to identify transcriptomic biomarkers capable of discriminating responders and non-responders to VDZ treatment.

Methods

Mucosal samples were collected during colonoscopy from patients with UC prior to VDZ initiation. The minimum extension of disease for study inclusion was left-sided colitis (E2 Montreal), and patients had at least moderate flare of clinical activity based on the total Mayo Score. Patients were dichotomized based on clinical response at week 10 in responders and non-responders. Clinical response at week 10 was defined as a decrease with >50 percent for both rectal bleeding score and stool frequency score according to the latest STRIDE-II recommendations for short-term targets. A commercially available panel of primers for 84 genes associated with IBD were assessed on mucosal samples through quantitative PCR.

Results

Eight patients with previous failure to anti-TNF agents, were sampled prior to VDZ initiation. We identified 3 responders and 5 primary non-responders at week 10 after VDZ treatment initiation. We found 15 genes up-regulated in non-responders compared to responders with a trend towards statistical significance (p=0.057). The highest fold-change was obtained for CXCL8.

Conclusion

We identified 15 mucosal transcripts differentially expressed in VDZ primary non-responder UC patients. Of those, the highest fold change was observed for CXCL8. Enlarging the cohort might contribute to achievement of statistical significance for the data presented. CXCL8 up-regulation seems to predict lack of response to VDZ treatment and represents an interesting future therapeutic target in UC.Read more P064 Investigating the genotoxic effect of reduced glutathione, n-acetylcysteine, human umbilical cord-derived mesenchymal stem cell exosomes and let-7 miRNA mimics in human lymphocytes and EpiIntestinal cellsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The current treatments for IBD frequently do not provide sufficient control over the disease, warranting the investigation of alternative therapeutic options with minimal risk of side effects. In IBD, the overgeneration and insufficient removal of reactive oxygen species (ROS) leads to oxidative stress. Reduced glutathione (GSH) and n-acetylcysteine (NAC) are antioxidants which may possess therapeutic potential in IBD, by modulating endogenous mechanisms that decrease ROS production or increase antioxidant enzymes. Additonally, exosomes from human umbilical cord blood derived mesenchymal stem cells (hucMSCs-exo) may be used to treat IBD. These are a subset of extracellular nanosized membrane vesicles which participate in intercellular communication by delivering their contents, such as functional miRNAs to recipient cells, thereby influencing the physiological and pathological processes in various diseases. The therapeutic potential of exosomes can be enhanced through the overexpression of the let-7 family of miRNAs.

Methods

The EpiIntestinal tissue model is a physiologically relevant predictor of drug-induced GI toxicity. EpiIntestinal cells and lymphocytes from 3 IBD patients were transfected with 50 μL miRNA mimics and inhibitors, and treated with 50μL hucMSC-exo, and 50 μL 1mM GSH and NAC. Next, in comparison to negative controls, single-stranded DNA damage was assessed in peripheral blood mononuclear cells (PBMCs) from IBD patients using the fast microplate DNA damage assay, and double-stranded DNA damage was assessed in EpiIntestinal cells using the alkaline Comet assay. In addition, the viability of healthy and IBD lymphocytes was assessed following treatment with selected concentrations of hucMSC-exo, GSH and NAC.

Results

Double-stranded DNA damage was significantly reduced in EpiIntestinal cells compared to the negative control following treatment with hucMSC-exo, GSH, NAC, and miRNA mimics for let-7a-5p, -7b-5p, -7c-3p, -7d-3p and -7d-5p. In addition, single-stranded DNA damage was reduced in IBD PBMCs compared to the negative control following treatment with hucMSC-exo, and let-7b-5p and -7c-3p mimics, but was increased following treatment with inhibitors for let-7b-5p, -7c-5p and two novel miRNAs. Additionally, GSH, NAC and hucMSC-exo increased cell viability in treated versus untreated lymphocytes from healthy individuals and IBD patients.

Conclusion

Selected concentrations of HucMSC-exo, GSH, NAC and/or let-7 miRNA mimics reduced DNA damage and increased cell viability in treated versus untreated cells which may reduce the risk of colorectal cancer in IBD patients.

Acknowledgements

Our gratitude goes to the MatTek Team for generously granting us a SMI-100-FT EpiIntestinal kit in support of this research.Read more P065 The evolution of inflammatory bowel disease can be monitored through multi-omics characterization of gut tissuesWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The aim of the study is to dissect the mechanisms associated with the evolution of Inflammatory Bowel Disease (IBD), including Crohn’s Disease (CD) and Ulcerative Colitis (UC) in both pediatric and adult patients, along with the severity of the disease and the risk to develop malignancy.

Methods

A multiomics approach, including miRNA (N=700), gene expression (N=800 genes) (nCounter platform; Nanostring) and methylation (Infinium Methylation Epic Bead Chip kit, Illumina), was utilized to characterize the gut tissue biopsies from pediatric (N=20) and adult (N=18) IBD patients. Moreover, a cohort of patients with gut malignancies with history of IBD were also enrolled in the study. Additionally, the role of Natural Killer Group 2D ligands (NKG2DLs) along with different stages of IBD (remission, mild, moderate and severe) were investigated.

Results

Differential miRNA and gene signatures were found by the comparison of tissues from pediatric and adult patients with different stages of the disease. N=83 miRs were significantly differentially detected between pediatric and adult patients (P<0.05). miR-630, miR-493-3p and miR-370-3p were found over-expressed in adult vs. pediatric gut tissues. These miRs are involved in epithelial-to-mesenchymal transition (EMT) through the WNT/β-catenin pathway. These miRNAs can also regulate cell proliferation, cell adhesion and migration and cancer development. Interestingly, miR-20a and miR-34a, which are known modulators of NKG2DLs expression were upregulated in tissues from severe vs. mild disease. The gene expression analysis highlighted, among multiple differentially detected pathways in tissues with different grades of IBD, genes, such as SMAD4, EGR1, CHUCK and JAG1, associated with inflammation, stemness, immune regulation, cell proliferation and migration. Through qPCR analyses, the higher expression of the NKG2DLs MICB was detected in tissues from left or right sides, respectively for both pediatric and adult patients while similar observation occurred for MICA only in adult patients. Soluble NKG2DLs were also detected in the plasma of IBD patients, with in some cases differences (P<0.05) in patients vs. healthy donors. sULBP3 correlated with the presence of active inflammation in adult IBD tissues. Confocal imaging of IBD tissues showed upregulation of stemness-associated markers (e.g., LGR5) and NKG2DLs (ULBP-1 and ULBP-3) in adult vs. pediatric patients.

Conclusion

The ongoing integration of data from multi-omics and the expression of immune-related molecules can lead to the identification of candidate molecular mechanisms associated with the evolution of IBD.Read more P066 Serum amyloid A – A Novel Biomarker of Ulcerative Colitis Disease ActivityWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Despite recent advancements in the treatment of ulcerative colitis (UC), a substantial number of patients fail to achieve long-term remission. Persistent histological activity has been linked with poorer treatment outcomes. Histological remission is now an accepted treatment target; however there remains significant variability in the interpretation of UC histology. As such, there is a need for novel biomarker identification to aid assessment and ultimately predict disease relapse. Serum amyloid A (SAA) is an acute-phase protein, of which serum levels have shown promise as a biomarker in IBD¹. This study aims to explore the utility of SAA levels in UC colonic tissue as a diagnostic biomarker for disease activity and progression.

Methods

Two cohorts were prospectively recruited, including healthy controls and UC patients. Sigmoid biopsies were collected and tissue explants generated. Tissue-conditioned media from these explants was collected and secreted SAA quantified using 54 V-plex ELISA. Demographic information, disease characteristics, endoscopic Mayo scores and disease progression were documented. Endoscopic remission was defined as a Mayo endoscopic sub-score ≤1. Disease progression was defined as the requirement for corticosteroid therapy, UC-related hospitalisation, UC-related surgery or the introduction of a new immunomodulatory agent in follow-up period. P values <0.05 were considered significant in analyses.

Results

The two cohorts included 11 healthy controls and 16 UC patients (endoscopic remission n=6). Active UC patients demonstrated significantly higher SAA concentrations than healthy controls (p=0.0013) and those in endoscopic remission (p=0.02). There was no significant difference in SAA concentrations between healthy controls and UC patients in remission (p=NS). UC patients in the lowest SAA concentration quartile had a significantly longer time to disease progression (p=0.0462) (Figure 1).

Conclusion

Quantification of SAA secretion in IBD ex-plants has potential as a biomarker of UC activity and progression. Further investigation of SAA as a biomarker in IBD is warranted.

References

1. Chen R, Chen Q, Zheng J, Zeng Z, Chen M, Li L, et al. Serum amyloid protein A in inflammatory bowel disease: from bench to bedside. Cell Death Discov. 2023;9(1):154.Read more P067 Volumetric Assessment of Treatment Response in Newly Diagnosed Crohn Disease: A Pilot StudyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Traditionally, mural thickness and disease length have been the radiological standards for assessing Crohn's Disease (CD) severity and treatment response. Our study aimed to evaluate and compare these linear measurements with volumetric ones in newly diagnosed pediatric CD, as well as to assess the concordance between manual and semi-automated volumetric methods.

Methods

In this single-center, prospective study, 20 children with newly diagnosed ileal CD treated with anti-TNF therapy from Dec 2018 to Oct 2021 (8 females; median age=14.5 years) underwent dedicated research MRI examinations at three timepoints – diagnosis (baseline) as well as 6 weeks and 6 months into therapy. For each exam and using T2-weighted Single Shot Fast Spin Echo (SSFSE) images, a single radiologist measured maximum bowel wall thickness (BWT, mm) and length of disease (cm). The inflamed ileum was manually segmented to measure tissue volume (ml) (Entrolytics; Motilent, London, UK). Semi-automated 3D volumetric measurements of the inflamed ileum (GI Seg tool) were created using the same platform. Estimated maximum BWT also was automatically calculated from manually-edited algorithmically generated masks. Mixed-effects models evaluated measurement changes over time. Intra-class correlation assessed absolute agreement between manual and automated volumetric assessments.

Results

BWT decreased over time with treatment (0.76 vs. 0.58 vs. 0.45 cm; p<0.0001), with a 24% decrease from baseline to 6 weeks and a 41% decrease from baseline to 6 months. Similarly, there was a significant decrease in length of disease over time (19.2 vs. 12.2 vs. 8.0 cm; p=0.002), with a 36% decrease from baseline to 6 weeks and a 58% decrease from baseline to 6 months. Manual volumetric measurements also showed a significant treatment response (19.8 vs. 11.6 vs. 5.1 ml; p<0.0001), with a 41% decrease from baseline to 6 weeks and a 74% decrease from baseline to 6 months. Using the semi-automated segmentation tool, the volume of inflamed bowel also decreased significantly over time (24.0 vs. 15.1 vs. 9.1 ml; p=0.0007), decreasing 37% between baseline and 6 weeks and 62% between baseline and 6 months. There was good agreement between manual and semi-automated volumetric bowel assessments (ICC=0.78 [95% CI: 0.57-0.88]). ICC between manual and code-estimated Max BWT was 0.60 [95% CI: 0.42, 0.72] with a strong positive correlation (r=0.839; p <0.001) between these two methods as shown in the Figure.

Conclusion

Volumetric assessments, along with automatic measurements of bowel wall thickness, show promise in accurately assessing treatment response in pediatric CD. These methods might provide more consistent and repeatable measurements, essential for long-term disease monitoring and management.Read more P126 Differential granulocyte populations as therapeutic targets in fistulaWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Despite the recent increase in therapeutic options in IBD care, treatment of perianal disease and in particular fistula remains highly challenging. Specific targeted medical therapy is not currently available, and a majority of patients fails to respond to surgical intervention. In contrast, cryptoglandular fistula show much higher response rates with closure in up to 80-90% of patients. Interestingly, the most present cell type in fistula, the granulocyte, is also the least studied due to their fragile nature. To fill this void, we evaluated granulocytes in perianal fistula and those present in the blood.

Methods

Curettage material of 18 fistula (Crohn n=15 and cryptoglandular n=5) was obtained and processed by mass cytometry. Two additional samples were obtained (1 Crohn, 1 cryptoglandular) together with matching blood samples and assessed by single cell RNASeq.

Results

As expected, granulocytes formed the majority of all cells in all fistula (mean 64%). Cryptoglandular fistula displayed significantly more granulocytes than Crohn’s related fistula. Single cell analysis showed 4 subsets: Subset 1 was the main subset in blood, and expressed high levels of LAMTOR4. Interestingly, although found both in blood and fistula, abundance was much higher in blood (80 vs 10%) and signaling cascades differed. In blood, activity was associated with degranulation, IL8 activity and migration. In fistula, a very strong IFNa/b signature was present. Subset 2 expressed high MMP9, and showed degranulating activity. Subsets 3 and 4 were almost exclusively found in the fistula tracts, and were defined by expression of PI3 and LRG1 respectively. Pathway analysis showed the PI3+ population to have strong cytokine signaling but little degranulating or migratory activity. Conversely, the LRG1+ population showed little cytokine activity, but stronger degranulating activity and integrin signaling. The two populations also expressed distinctive chemokine receptors, with PI3+ cells expressing high levels of CXCR4, while LRG1+ express CXC1 and CXCR2, suggesting differntial recruiment and potential modulation. In that light, it is interesting to note the proportion of PI3+ and LRG1+ cells differed between patients, with the majority of Crohn derived cells being PI3+ while the cryptoglandular fistula mainly contained LRG1+ cells.

Conclusion

Granulocytes form the main cellular component of fistula tracts in both Crohn and cryptoglandular fistula. Four different subsets of granulocytes could be identified, of which the two main subtypes in fistula tracts appear to differ significantly both in phenotype, activity and method of recruitment. This data may be a starting point for specific interventions in this highly abundant but often overlooked cell type.Read more P127 Sphingosine-1-Phosphate Receptor Blockade with Etrasimod alters Lymphocyte Trafficking in Crohn's Disease: Insights from High-Dimensional Phenotypic MappingWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The blockade of lymphocyte trafficking from the lymph nodes (LNs) towards the intestinal mucosa is an effective approach for the treatment of ulcerative colitis (UC). Etrasimod is an oral, once-daily (QD), selective sphingosine 1-phosphate (S1P)1,4,5 receptor (S1PR) modulator, which is currently also under investigation for Crohn’s disease (CD).The therapeutic mechanism of action of S1PR modulators in the context of inflammatory bowel disease (IBD) is not completely understood. It is hypothesized that both B and T- cell populations are affected by this treatment and are retained in the peripheral LNs, reducing circulating lymphocytes and resulting in fewer immune cells available to traffic in the gastrointestinal tract. Etrasimod has been reported to induce a partial and selective reduction of lymphocyte subsets in the blood of healthy subjects, but the direct effect of S1PR modulators on LN leukocytes has not been evaluated. The aim of this study was to investigate changes in leukocyte subpopulations in peripheral LNs and peripheral blood (PB) in response to S1PR inhibition with etrasimod in patients with CD.

Methods

CD patients with moderate to severe disease activity, participating in the Phase 2, double-blinded, non-placebo-controlled portion of the CULTIVATE trial, were eligible for this sub-study. At baseline and after 14 weeks of etrasimod induction treatment (2 or 3 mg/day), 10cc of PB and 4 ultrasound guided biopsy samples of an inguinal LN were obtained. The isolated peripheral blood mononuclear cells (PBMCs) and LN leukocyte populations, were analyzed at single cell level via high-dimensional immunophenotyping through mass cytometry (CyTOF) at both timepoints.

Results

We observed that in the LNs, the numbers/percentages of naïve, central and effector memory T-helper cells, as well as, of CD8⁺ naïve T-cells were increased after treatment with etrasimod. There was a decrease in the proportion of these cell populations in peripheral blood. Circulating naïve and memory B-cells were reduced, while these subsets where also slightly reduced in the LN compartment. Innate immune cell populations were not significantly altered.

Conclusion

Etrasimod induction treatment resulted in an increase of both naïve and central memory T-lymphocyte subsets in inguinal LNs, with a corresponding decrease in the periphery. The effect on the frequency of B-cells was not consistent in the LNs and PB, while innate immunotypes and T-regs, were not significantly affected. Despite the limited sample size, these selective effects were consistent with previously published PB immunophenotyping studies with etrasimod.This study was conducted as a collaboration between Amsterdam UMC and Pfizer.Read more P128 Salt-Inducible Kinase 2 is a promising therapeutic target in patients with ulcerative colitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Salt-Inducible Kinases (SIKs) are a family of 3 serine/threonine kinases which represent promising therapeutic targets in a number of inflammatory diseases including ulcerative colitis (UC). Their catalytic activity is highly phosphoregulated in response to changes in cellular homeostasis. Inactivation of SIKs results in proinflammatory cytokine downregulation and the concomitant upregulation of anti-inflammatory IL-10. Of the three isozymes, SIK2 is the most active in myeloid cells and is thought to be the key driver of IL-10 production. Selective pharmacological inhibition of SIKs has thus far proved challenging: a number of SIK inhibitors have previously been developed and whilst they have demonstrated biological activity in UC, dosing has been limited due to potential side effects underlining the need for improved selectivity. We hypothesized that more selective inhibition of SIK2 represents a promising approach in ulcerative colitis.

Methods

We sought to examine the effects of inhibiting SIK2 with a potent small molecule in both in vitro cell cultures and in ex vivo biopsies from UC patients. CD14⁺ monocytes were isolated from donor PBMCs and differentiated into hMDMs (monocyte-derived macrophages) and moDCs (monocyte-derived DCs). Cultures were treated with compound followed by LPS stimulation for 4 hours (hMDMs) or maturation for 48 hours (moDCs). To recapitulate the disease microenvironment ex vivo, a colonic explant culture model was used: colonic biopsies were collected from patients with active (Mayo 1 /2) and inactive UC and cultured in the presence of compound or control for 24-48h. Supernatants were assayed for cytokine and chemokine release. Cells or biopsies were lysed for qPCR. Surface markers were assessed by flow cytometry

Results

Using more SIK2-selective small molecules, we show that SIK inhibition modulates inflammatory and immunometabolic pathways in human myeloid cells. Furthermore, SIK2 inhibition drives a tolerogenic phenotype in dendritic cells, as demonstrated by suppression of proinflammatory cytokines and chemokines such as TNFα and the CC/CXC chemokine family as well as downregulation of activation markers such as CD80 and 83; functionally these modulated DCs can suppress Th1 CD4 T cell IFNγ production. Modulation of cytokine and chemokine production by SIK2 inhibition was also observed in colonic explant cultures from UC patients with a reduction in levels of TNFα and the CC chemokine family.

Conclusion

In both myeloid cellular cultures and UC biopsies, SIK2 inhibition modulates an inflammatory environment into a pro-resolution state supporting the therapeutic potential of SIK2 inhibition in UC.Read more P129 Anastomotic healing is functionally not impaired after ileocecal resection in a mouse model of Crohn's-like ileitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Anastomotic leakage (AL) is a serious complication after gastrointestinal surgery that seems to occur more frequently in patients with CD than in non-IBD patients. Nucleotide-binding oligomerisation domain-containing protein 2 (NOD2) is a risk gene for CD. We have recently demonstrated that Nod2-deficent mice have impaired anastomotic healing after ileocecal resection (ICR) even in the absence of a Crohn's phenotype. It is not yet understood how CD itself affects anastomotic healing. SAMP1/YitFc mice spontaneously develop Crohn's-like ileitis and show a defect in the NOD2 receptor.With this study we aimed to investigate whether anastomotic healing is altered after ICR in experimental ileitis.

Methods

SAMP1/YitFc mice (n=17) with histologically manifest ileitis and parental controls (AKR, n=12) were subjected to ICR. Intestinal continuity was established by end-to-end ileocolic anastomosis. On day 5, the strength of the anastomosis was assessed by bursting pressure (BP) measurement. Anastomotic healing was evaluated macroscopically using the anastomotic healing score (AHS). Hydroxyproline content and collagenase activity in the anastomosis were determined. The inflammatory status was determined by mRNA expression of inflammatory cytokines in mesenteric lymph nodes (MLN) and spleen tissue.

Results

25% of the AKR mice and 29% of the SAMP1/YitFc mice developed perioperative complications. Leakage rate was not higher in mice with ileitis. Functionally, anastomoses were not impaired in SAMP1/YitFc mice (BP SAMP1 93 mmHg vs. AKR 123 mmHg) and AHS did not differ between the groups. However, mice with ileitis were more prone to microscopic abscess formation. Collagenase activity and hydroxyproline content in the anastomotic tissue did also not differ significantly. Preoperatively, mice with ileitis expressed increased IL4 and INF-γ mRNA levels in the MLN compared to AKR controls. After ICR, the local expression of IL4, TNF-α, lysozyme 1 and IL2 was significantly decreased in SAMP1/YitFc mice (p<0.05 SAMP1 d0 vs. d5, MLN). Resection induced significantly increased expression of IL4, lysozyme 1 and IL2 in the spleen of AKR mice, but not in SAMP1/YitFc mice (p<0.05 AKR ICR vs. SAMP1 ICR d5).

Conclusion

The SAMP1/YitFc mouse is a suitable model to study mechanisms of anastomotic healing under the influence of experimental chronic ileitis. Ileitis alone was not a risk factor for impaired healing. Ongoing studies address the local effects of therapeutic immunomodulation on the healing process of the anastomoses.Read more P130 High serum lipocalin-2 expression at the diagnosis in children with ulcerative colitis: a pilot studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The identification of new biomarker is a main challenge in inflammatory boweldisease. Lipocalin-2 (LCN-2) is a pleiotropic mediator of various inflammatory processes. We determined the serum levels of LCN-2 in a cohort of newly diagnosed UC children, and we compared them with healthy controls.

Methods

Prospective cross-sectional observational study conducted at the Pediatric Gastroenterology, hepatology, and nutrition Unit of the Umberto I Hospital in Rome and at the IBBC – Institute of Biochemistry and Cell Biology – CNR in Rome. All children aged 6-18 years of age, newly diagnosed with UC at the Pediatric Gastroenterology and Liver Unit, Sapienza University of Rome, were consecutively enrolled. Blood withdrawal was conducted upon diagnosis. Human serum LCN-2 (Cat. No. DY1757) was measured using a sandwich enzyme-linked-immunosorbent assay (ELISA) kits (R&D Systems, Minneapolis, MN, USA), according to the protocols provided by the manufacturer. Clinical, demographic, biochemical and endoscopic data were recorded.

Results

Thirty-two children with a new diagnosis of UC [11 (34%) female, mean age 12,7 ± 4] and 38 age- and sex-matched healthy control [21 (55%) females, mean age 11.71 ± 4] were consecutively enrolled. Serum LCN-2 levels were significantly higher in cases compared to controls (280 ± 152 ng/mL vs 66 ± 55 ng/mL), p < 0,001]. Among UC children, significantly higher LCN2 levels were measured in pancolitis (363.7± 155.2 ng/mL) compared to proctitis, left-sided and extensive colitis (184.9 ± 74.65 ng/mL; p = 0.0003). A significant inverse correlation was observed between LCN-2 and albumin levels at the diagnosis by the Spearman coefficient correlation (r = −0.455; P = 0.03) and a significant direct correlation was observed between LCN-2 and CRP values at the diagnosis (r = 0.44; p <0.05).

Conclusion

Serum LCN-2 levels are significantly higher in children with UC compared to the healthy control group, with the highest levels observed in children with the most extensive disease. Such results as well as and its correlation with the actual disease monitoring tool, make this protein an interesting candidate biomarker.Read more P131 Therapeutic effects of KPG-818 in a trinitrobenzene sulfonic acid - induced mouse Crohn's/Ulcerative Colitis modelWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Immunomodulatory drugs have the potential therapeutic benefit not only in malignancy but also in diseases characterized by an inflammatory phenotype. In inflammatory bowel diseases (IBD), colonic inflammation results from dysregulation of the mucosal immune responses to intestinal flora together with genetic and environmental factors. Inflammatory cytokines are implicated in pathogenesis of IBD. Treatments for IBD that improve clinical outcomes and limit adverse effects are needed.KPG-818 is a novel generation of lenalidomide derivative and small molecule immunomodulatory drug. KPG-818 is currently under clinical development for therapy of multiple myeloma, lymphoma (phase 1), and systemic lupus erythematosus (SLE) (phase 2a). Remarkable immunomodulatory effects of KPG-818 are observed in SLE patients. In preclinical studies, KPG-818 significantly inhibits inflammatory cytokines interleukin-6 and TNF-α in human peripheral blood mononuclear cells, inhibits tumor growth in multiple myeloma and lymphoma xenograft tumor models. Here we report the significant therapeutic effects of KPG-818 in a chronic Crohn’s/ulcerative colitis mouse model.

Methods

Trinitrobenzene Sulfonic Acid (TNBS) was intra-colonially administered to induce Balb/c mouse Crohn’s/ulcerative colitis model at 50 mg/kg, once a week for 4 weeks. KPG-818 was orally administered at doses of 0.03, 0.12, 0.4, and 1.0 mg/kg, once a day for 6 consecutive weeks. Upadacitinib served as a positive control drug. Vehicle solution served as a negative control. To evaluate the therapeutic effects of the KPG-818, disease activity index (DAI) of ulcerative colitis, the degree of weight loss, fecal morphology, and rectal bleeding were scored once every other day for six consecutive weeks. At the end of the study, colonic samples were collected for gross observation and scoring of macroscopic damage, measurement of length and weight, and histopathological diagnosis and scoring. At the end of study, peripheral blood samples were also collected for analyses of immune cells and cytokines.

Results

Compared to the vehicle control, KPG-818 significantly improved the body weight loss, disease activity of ulcerative colitis, gross degree of colorectal injury, pathological lesions of colorectal tissue, inhibited the inflammatory cytokines in a dose-response manner. The effective dose was as low as 0.03 mg/kg. KPG-818 showed similar therapeutic effects to Upadacitinib.

Conclusion

In this mouse model of chronic Crohn’s/ulcerative colitis, KPG-818 showed remarkable therapeutic effects in a dose-dependent manner. These data encourage the clinical evaluation of KPG-818 in inflammatory bowel diseases.Read more P132 Overexpression of miR-376a-3p in exosomes circulating in peripheral blood of patients with Crohn's diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

MicroRNAs (miRs) can modulate the development and/or progression of chronic inflammation in patients with Crohn's disease (CD), influencing the efficacy of treatments.

Aim

The objective was to assess the miRs content of circulating exosomes in the peripheral blood of patients with CD to identify new biomarkers useful in disease management.

Methods

Patients with CD diagnosed and followed up at the Hospital General Universitario de Alicante and healthy controls were included. Extracellular vesicles were isolated from serum and exosomes were quantified by "Nanoparticle Tracking Analysis" (NTA), confirmed by Transmission Electron Microscopy (TEM) and by specific markers (Tsg101, CD63, CD81) by Western blot, performing an expression analysis of a non-targeted panel of human miRs from exosomal RNA. Patient and control samples were also subjected to enzyme-linked immunosorbent assay (ELISA) measurement of different target-predicted protein substrates.

Results

Thirty patients and ten controls were included in the study. Patients were 42±9 years old, disease duration 62±9 months, 40% women and 80% showed ileal or ileocolonic involvement. Six patients (20%) had perianal disease. Ninety-three per cent were undergoing biological treatment with infliximab (IFX, n=13), adalimumab (ADA, n=8) or ustekinumab (USTE, n=7). A significant increase in exosome concentration was observed in the serum of patients vs controls. NTA and TEM confirmed the size and purity of the obtained exosomes. The distribution in the expression of miRs and its differential analysis showed a significant increase in miR-376a-3p as well as a reduction in miR-20a-5p in patients vs. healthy controls. Functional analysis of miR-376a-3p determined its interaction with gene targets involved in autophagy (ATG4C), TGF-b signaling (ACVR1C) and cell survival (PIK3R1, IGF1R). Protein levels of these substrates indicated the potential control of TGF-beta signaling pathway by the downregulation of ACVR1C, and the increase in survival pathway measured by IGFR1 presence in patient’s serum.

Conclusion

CD patients show a higher number of circulating exosomes, with an overexpression of miR-376a-3p. The involvement of this microRNA in different intracellular signaling pathways suggests its participation in the unbalance of the immune activity present in CD.Read more P133 In vitro pharmacological profile of GLPG3667 suggests differentiation from the TYK2 inhibitors deucravacitinib and TAK-279 at their clinical dose regimensWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Tyrosine kinase 2 (TYK2), a Janus kinase (JAK) family member, is attracting a lot of interest as a new target to treat patients with autoimmune and inflammatory diseases, including inflammatory bowel disease, and several inhibitors are currently in clinical development. In vitro pharmacological profiling of TYK2 inhibitors has been employed to evaluate potency and selectivity; however, such data are best viewed in relation to clinical exposure levels. We compared expected levels of inhibition of TYK2-dependent and -independent pathways for deucravacitinib, TAK-279 and GLPG3667 at their respective clinical dose regimens and demonstrate that relevant differences exist between these compounds.

Methods

Potency of the TYK2 inhibitors was compared for TYK2-dependent pathways (IFNα, IL-12), TYK2-independent pathways (IL-6, IL-2, GM-CSF) and the anti-inflammatory IL-10 pathway in in vitro human whole blood assays using STAT phosphorylation (flow cytometry) and cytokine release (ELISA). Sigmoidal Emax models were fitted to the concentration–inhibition data from healthy donors to estimate IC₅₀, Emax and Hill slope for each assay and compound. The obtained relationships were subsequently coupled to the clinical pharmacokinetic (PK) profiles of the compounds (population PK model for GLPG3667, published PK metrics such as C_avg for the other compounds) to estimate the level of inhibition of the various pathways at clinically relevant dose regimens.

Results

Human whole blood assays performed for various JAK pathways demonstrated that all TYK2 inhibitors display selectivity for TYK2 over the JAK1–3 family members, with TAK-279 being the most selective. At exposure levels associated with its clinical dose of 150 mg once daily, GLPG3667 showed inhibition of the IFNα and IL-12 pathways, similar to the expected inhibition for deucravacitinib at its clinical dose regimens, without a measurable impact on TYK2-independent pathways. TAK-279 showed the most sustained inhibition of TYK2-dependent pathways. GLPG3667 showed no measurable inhibition of IL-10-mediated signalling up to the highest concentration tested (~10-fold above clinical concentrations), while inhibition was observed with deucravacitinib and TAK-279 at concentrations corresponding to the respective clinical dose regimens.

Conclusion

At concentrations corresponding to its highest anticipated clinical dose, GLPG3667 shows selective inhibition of TYK2-mediated signalling, with a level of inhibition similar to deucravacitinib clinical dose regimens. While GLPG3667 did not show any impact on IL-10-mediated signalling, inhibition of this anti-inflammatory pathway is expected for the allosteric TYK2 inhibitors at their clinical exposure levels.Read more P182 Hepatic lesions in chronic inflammatory bowel disease revealed by liver biopsy during surgeryWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Chronic inflammatory bowel diseases are complicated in 10 to 30% cases by hepatobiliary abnormalities, the aim of this study was to evaluate the prevalence of histological liver abnormalities and demonstrate the advantages of performing a systematic liver biopsy during surgery.

Methods

from 2018 to 2022,twenty patients underwent surgery for inflammatory bowel disease (IBD) with systematically liver biopsy during the procedure .

Results

Twenty IBD patients were operated (sex ratio M / F: 1.5),the mean age was 31.7 years, during a mean follow-up of three years before surgery ; occlusive syndrome was the dominated indication of surgery in 90% cases, and acute colitis in 10% cases,two patients had cytolysis,and one patient had cholestasis,four patients had radiologically steatosis.Histologically,fourteen patients had small duct cholangitis (chronic or subacute portitis, portal fibrosis),five patients had steatosis and one patient presented with primary sclerosing cholangitis .

Conclusion

peroperative liver biopsy identify liver diseases in an early diagnosis and as a result medical treatment was adapted and regular surveillance of the liver was ensured.Read more P183 Therapeutic Effects of Curcumin and Ginsenoside Combination in a Animal Model of Radiation ProctitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Although various preventive and therapeutic modalities have been proposed to manage radiation-induced proctitis, there are no universally accepted preventive measures for effective treatment. This study aimed to investigate using an animal model whether the combination of curcumin and ginsenoside could be an effective treatment or preventive agent for progressive rectal inflammation caused by radiation.

Methods

C57BL/6 mice were exposed to gamma irradiation at 27 Gy (3 Gy/min) in the lower abdominal (rectal) region, establishing an animal model with acute radiation proctitis. A combination hydrogel containing 5 mM curcumin and 1 mM ginsenoside Rh1 was prepared and administered into the inflammed rectum of the murine model. This administration was repeated every 2 to 3 days after radiation exposure for a total of 6 times. Two weeks after radiation exposure, the mice were sacrificed to obtain the irradiated tissue samples. The histological and molecular evaluations were performed using H&E staining, Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) analysis, Proliferating Cell Nuclear Antigen (PCNA) staining, immunohistochemistry, and qPCR.

Results

The murine group treated with the combination hydrogel of curcumin and ginsenoside showed significant restoration of the damaged rectal mucosa induced by radiation, including recovery of the mucosal layer and villi, mitigation of epithelial loss, and repair of crypt damage, compared to control group. Additionally, at the cellular level, a comparative analysis of apoptosis and proliferation within the tissues through TUNEL and PCNA staining demonstrated the combination hydrogel not only significantly inhibited cell death but also significantly increased cell proliferation. The gene expression of inflammatory cytokines in rectal tissue, including IL-6 and IFN-γ was significantly decreased in the treatment group. The infiltration of immune cells including T cells (CD4) and macrophages (CD68), which are important components in the pathogenesis of radiation proctitis, as shown by immunohistochemistry of tissue samples, was significantly reduced in the treatment group compared to the control group.

Conclusion

These promising results suggest that the combination of curcumin and ginsenosides has therapeutic potential for the management of radiation proctitis and provide valuable insights into new therapeutic strategies in clinical applications.Read more P184 Challenging Barriers in Inflammatory Bowel Disease: First Observational Analysis of Double Biological Therapy in MexicoWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Inflammatory bowel disease is a chronic inflammation of the GI tract, despite advances in treatment with biologic therapy, some patients may develop an inadequate response, known as refractory IBD (rIBD).Given this reality, the approach of double biological therapy (DBT) has emerged to effectively address and improve control of inflammation, providing them with an additional therapeutic option

Methods

Pilot prospective observational study evaluateing response to DBT in patients with refractory IBD

Results

A total of 7 patients with rIBD who received DBT were included, the average age was 29 ± 9, all female. The average duration of illness before starting dual therapy was 8 ± 2years. Patients had received an average of 2 previous biological treatments, 4 (57%) had a history of surgery related to IBD, 5 (71%) and 2(29%) had a history of stenosis and fistulas respectively and 100% used steroids and immunomodulators before starting DBT. Four DBT combinations were evaluated: CERTOLIZUMAB+VEDOLIZUMAB (group 1), USTEKINUMAB+VEDOLIZUMAB (group 2), INFLIXIMAB+USTEKINUMAB (group 3) and INFLIXIMAB+VEDOLIZUMAB (group 4).Group 1 included 1 patient with improvement in clinical activity, with a decrease in endoscopic activity from i4 to i2 by Rutgeerts criteria and Nancy index 1.Group 2 included 4 patients showed improvement in clinical and endoscopic activity, there was a reduction in clinical activity by CDAI from 225 to 66, and improvement in endoscopic activity from L1 B2 to L1 B1, i0 L2 B3P to i0 L1 B1 and i3 L3 B2 to i2 L3 B1 with different activity rates, Nancy's histology that varied from 0 to 3.Group 3 included 1 patient showed a reduction in clinical activity by CDAI from 210 to 166, endoscopic activity also decreased from i0 L2B3P to i0 L1 B1 with Nancy index of 2.Group 4 includes 1 with a decrease in clinical activity by Truelove-Witts from 2 to 2, endoscopic activity also decreased from 8 to 5 accordingto UCEIS with Nancy index of 1.In all groups, a reduction in the use of steroids was observed and no cases of infections associated with dual biological therapy were reported

Conclusion

This prospective observational pilot study represents the first analysis in Mexico and, to our knowledge, in Latin America, on the use of DBT in patients with rIBD who showed clinical, endoscopic and histopathological improvement in the majority of cases. It is important to recognize the limitations of this study, such as its pilot design and sample size. This pioneering study in refractory IBD presents encouraging results that suggest clinical and endoscopic benefits in the treated patients. These results justify the conduct of larger studies to strengthen the evidence and provide a solid basis for thepotential use of this therapy in clinical practiceRead more P185 Food avoidance and dietary restrictions in patients with Inflammatory Bowel DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Nutrition has a key role in IBD, more so in Crohn’s disease (CD) than ulcerative colitis (UC) and studies have shown that patients restrict or avoid certain dietary items; not necessarily due to medical advice. This could be detrimental to nutritional status by causing weight loss, disordered eating and nutritional deficiencies.

Methods

An online survey was carried out amongst IBD patients attending a teaching hospital in an urban area in the UK. Ten questions were asked and the survey was sent to 100 patients with their consent.

Results

The total survey response rate was 38%. Only 8% of patients had a long diagnosis due to diagnosis when a child, and although all restricted their diet still, this did not seem to show significance (p = 0.597). There was no significant difference between IBD type and whether the patient restricted their diet or not (p = 0.107). Notably, we did find that the most common reason for avoiding dietary items was patients ‘feel it helps symptoms’ (less so the ‘advised by clinician’ choice), however there was no significant difference between types of IBD and dietary exclusion reasons (p = 0.721). The most common dietary avoidances were spicy foods, followed by caffeine and fibre. There was a significant difference between CD and UC patients and the dietary groups they limited (p = 0.006), with there being a difference between CD and UC patients specifically for fibre (p = 0.027), for gluten/wheat (p = 0.0002) and for dairy (p = 0.077), however the latter did not reach significance. Of note, there is no difference in how long patients avoided dietary items, showing restriction is widespread irrespective of disease status (active or in remission).

Conclusion

Our survey indicates that food avoidance is commonplace among IBD patients, and the common foods avoided are spicy foods, caffeine and fibre, more so with CD than UC. These appear self-induced without medical advice, and this could have a detrimental impact on nutritional status. This is important information which merits further studies, perhaps with a larger sample size.Read more P186 Comparative Analysis of Clinical Phenotypes and Pathogenic Features between Late-Onset and Infantile-Onset Monogenic Inflammatory Bowel DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Previous research on monogenic IBD (m-IBD) has mainly focused on very-early-onset IBD (VEO-IBD) and Montreal classification A1 type IBD patients. In non-A1 type (age > 16y) late-onset IBD patients, some individuals also exhibit IBD manifestations due to monogenic mutations. Here we systematically review the literature, using infantile-onset monogenic IBD patients as a control, to explore the genetic characteristics, clinical presentations, and treatment strategies of late-onset monogenic IBD.

Methods

Based on the onset age of IBD, m-IBD was categorized into infantile-onset (IO, <2 years) and late-onset (LO, >16 years as non-A1 type based on Montreal classification) groups. A systematic review was conducted to analyze the gastrointestinal (GI) clinical features of detailed cases published from January 1990 to June 2023 and to summarize the correlation between genetic pathogenesis and onset ages.

Results

512 m-IBD cases (398 IO and 114 LO) associated with 87 genes were included. Of these genes, 25 out of 87 genes were found to cause both IO and LO conditions. Crohn’s disease (CD) was the predominant type of IBD, account for 42.2% of IO and 44.7% of LO cases. Difficult-to-treat IBD patients showed similar rates (17.4% for IO and 13.0% for LO). However, infantile-onset cases were predominantly associated with complex perianal disease (13.5%), while late-onset cases were linked to postoperative recurrence following surgical resections (10.6%). Anti-inflammatory medicine and biologics were the main strategies, but in infantile-onset (IO) cases, immunosuppressants (57.9%), parenteral nutrition (26.8%), gastroenterostomy (20.2%), and HSCT (24.6%) were more frequently utilized compared to late-onset (LO) cases, where intestinal resection (37.8%) was more prevalent. Homozygosity was the predominant zygosity type (39.9% in IO and 39.3% in LO), while heterozygosity was more prevalent in LO cases (28.9%) compared to IO cases (13.3%) (p<0.05). Most of the genes associated with median onset ages of IBD before 2 years were causative genes for primary immunodeficiency (PID), whereas significantly lower rate of PID genes mutation was found in LO cases (26/27, 96.3% vs. 6/11, 54.5%, p= 0.005).

Conclusion

m-IBD patients predominantly present with CD, ulceration and atypical pathology, colon involvement, and difficult to treat regardless of onset ages, but vary in terms of family history, GI symptoms, location of the lesion, polyps and villous atrophy, type of complications, treatment options, and type of Difficult-to- treat IBD.Read more P187 Validation of Disease Severity Index for Predicting Complicated Disease in Crohn’s Disease: A comparison study with Lémann IndexWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The recently developed Disease Severity Index (DSI) provides a comprehensive assessment of structural bowel damage (BD) in addition to short-term signs and symptoms. We aimed to evaluate DSI in identifying patients with Crohn’s disease (CD) at high risk of disease progression, compared to Lémann Index (LI).

Methods

This was a retrospective observational study. The consecutive patients with CD in a referral center between 2017 and 2019 were reviewed. DSI and LI were calculated at diagnosis. A complicated CD course (composite outcome of corticosteroid dependency, treatment escalation, CD-related hospitalization, and surgery) and associated risk factors were further analyzed.

Results

The median LI and DSI of included 300 patients were 1.63 (interquartile ranges [IQR], 1.25-3.13) and 42 (IQR 32-51), respectively. 152 patients (50.7%) experienced a complicated disease course (median 5.1 months; IQR 1.1-20.2). DSI (AUC 0.67; 95% CI 0.60-0.72) showed a better performance in predicting a complicated course of CD over LI (AUC 0.57; 95% CI 0.50-0.62; P=0.01). The cumulative probability of complicated CD course in severe patients was higher compared to those with ‘mild CD’ (P<0.001) when stratified by a cut-off value (DSI>43). The Cox analysis identified DSI>43 (HR 2.18; 95% CI 1.54-3.09; P<0.001), B2/3 vs. B1 (HR 2.80; 95% CI 1.99-3.94; P<0.001), and a higher level of CRP (HR 1.01; 95% CI 1.00-1.02; P=0.005) as independent prognostic factors for complicated CD. In contrast, LI was not associated with complicated CD (P=0.164).

Conclusion

Higher DSI was validated to be associated with a complicated disease outcome. DSI might play a better role than LI in identifying patients at high risk of disease progression.Read more P188 Cumulative inflammatory burden as a risk factor for colorectal neoplasia in inflammatory bowel disease patients with primary sclerosing cholangitis: a multi-center case-control studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Inflammatory bowel disease (IBD) patients with concomitant primary sclerosing cholangitis (PSC-IBD) have a 25-year cumulative risk of up to 50% to develop colorectal neoplasia (CRN). Mucosal inflammation is an important driver of CRN, but it is unknown whether this also applies to PSC-IBD patients. We aimed to assess the impact of chronic mucosal inflammation per colonic segment on CRN risk in PSC-IBD patients.

Methods

This is a multi-center case-control study including cases with PSC-IBD and CRN and controls with PSC-IBD without CRN. Subjects were included from 8 medical centers in Canada and the Netherlands. Exclusion criteria were a CRN diagnosis prior to IBD or PSC diagnosis, familial CRC syndromes, and <2 available colonoscopy reports. Data was collected on demographics, IBD and PSC disease characteristics, CRN lesions, and endoscopy reports between 1977 and 2023. Pan-colonic and segmental (right colon, transverse colon, left colon, rectum) endoscopic cumulative inflammatory burden scores were calculated as the sum of (mean) endoscopic inflammation severity between colonoscopies x length of the surveillance interval until index procedure. The index procedure was the colonoscopy during which CRN was detected (cases) or randomly selected and matched for disease duration (controls). The primary outcome was a CRN diagnosis, secondary outcomes were CRN grade and location, time to CRN (Kaplan-Meier curve), pan-colonic cumulative inflammatory burden, cumulative inflammatory burden per colonic segment harboring CRN, and colonic surgery.

Results

We included 335 PSC-IBD patients (224 UC, 101 CD) with a median follow-up of 8 years (IQR: 5.0-14.0) and 6 endoscopies (IQR: 4.0-8.0). Median disease duration was 19.5 years for IBD (IQR: 11.0-26.0) and 13 years for PSC (IQR: 7.0-19.0). Advanced neoplasia (HGD or CRC) was found in 35 out of 102 cases (34%). Fifty-six (55%) cases were diagnosed with > 1 lesion, and 43 (42%) had ≥ 1 right-sided lesion. Median time to index CRN was 17 years (IQR: 8.0-24.0). Sixty-six patients underwent (sub)total colectomy or proctocolectomy, including 49 (74%) due to CRN diagnosis. There was no difference in pan-colonic cumulative inflammatory burden scores (mean scores: 4.7 (cases) and 3.7 (controls); P=0.21, 95%-CI: -2.52-.56) and segmental scores (mean scores: 4.9 (cases) and 4.1 (controls); P=0.27, 95%-CI: -2.29-.65) between cases and controls. Mortality was 13% (n=45.)

Conclusion

In this large multi-center cohort study, the risk for CRN-associated colectomy in PSC-IBD was high, while pan-colonic and segmental cumulative inflammatory burden scores were not associated with CRN risk.Read more P189 Lifestyle and psychosocial factors in IBD; prevalence and patients’ perspectiveWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Lifestyle and psychosocial factors impact mucosal inflammation and subjective well-being in Inflammatory Bowel Disease (IBD) patients. Better understanding of the relevancy of these factors within the IBD population, including prevalence and patients' perspective, may enhance systematic implementation of lifestyle interventions in regular care. This collaborative study with the Dutch patient organisation aimed to estimate the prevalence and patients’ perspectives on lifestyle and psychosocial factors in an outpatient cohort of IBD patients.

Methods

A multicentre cross-sectional study was conducted, enrolling IBD patients who utilized the remote monitoring platform myIBDcoach in 2022. Patients reported on clinical disease activity, lifestyle and psychosocial factors on this platform. A nationwide online survey was distributed by the Dutch patient organisation for IBD in April 2022 to assess patients’ perspectives regarding the impact of lifestyle and psychosocial factors on intestinal complaints, motivation to make changes, and need for and satisfaction with support in this regard from the hospital.

Results

In the multicentre myIBDcoach cohort (n=460), 16.3% adhered to a specific diet (Table 1). Two third (67.4%) did not comply with the Dutch healthy exercise norm and smoking was prevalent in 9.3%. About one-third experienced at least regularly poor sleep (33.8%), at least occasionally emotional distress (33.9%), and high perceived stress (36.7%). In the nationwide survey (n=1148), most (58.3-75.7%) patients believed that stress, unhealthy food, poor sleep, minimal or no exercise, and symptoms of anxiety and depression could lead to intestinal complaints (Fig. 1A). Around 70% of patients were taking action or were motivated to do so regarding their diet, stress, and physical activity (Fig. 1B). About 30% had no intention of addressing social support, and 22.8% were unwilling to change their alcohol use. Less than one-fifth received support from the hospital regarding these various factors (Fig. 1C). When support was received, most patients expressed satisfaction. Although desired, approximately 20% lacked support concerning stress, physical activity, diet, and sleep.

Conclusion

There is considerable scope for improvement in lifestyle and psychosocial factors among individuals with IBD, highlighting the need for systematic integration of these factors into clinical care. From the patient's viewpoint, widespread recognition of the impact of these factors emerged, with most expressing openness to initiating changes across various areas. These insights emphasize the potential for implementing targeted interventions, particularly in areas where patients indicated a need for additional support.Read more P255 Association of penetrating disease and hypoalbuminemia with Crohn's disease anastomotic recurrence in the biological era: results of a long-term experience from a tertiary IBD centerWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Crohn's disease (CD) anastomotic recurrence remains a clinical challenge with significant consequences. Its relationship with perioperative factors is controversial. This study investigates factors associated with surgical and endoscopic recurrence in a large historical cohort during the biological era.

Methods

Retrospective series of consecutive patients who underwent primary ileocecal resection for CD and the subsequent follow-up at our institute between 2004 and 2021. Follow-up or surgery for recurrence carried out in other centres were exclusion criteria. Primary outcome: identifying the variables associated with the surgical recurrence defined the need for surgery for the recurrence of disease at the site of the previous anastomosis. Secondary outcome: identifying the variables associated with the endoscopic recurrence, according to Rutgeert's score. Univariate comparisons and multivariable Cox regression survival analyses were performed accordingly.

Results

Out of 417 patients followed in our centre with a median follow-up time of 85 months (IQR 47-114), 170 presented with an endoscopic recurrence after a median time of 46 months (IQR 13-79). Surgical recurrence was observed in 65 patients at a median time of 85 months (IQR 47-114). The five-year surgical and endoscopic recurrence-free survival rates were 92.7% and 68%, respectively, while the 10-year surgical and endoscopic recurrence-free survival rates were 78% and 47%, respectively (Figure 1).At the multivariate Cox regression, the risk of endoscopic recurrence was significantly associated with male gender (HR 1.47, 95%CI 1.03–2.09, p=0.03) and current smoking (HR 1.47,95%CI 1.03–2.09, p=0.03). Penetrating disease behavior was significantly associated with a lower risk of both endoscopic (HR 0.71, 95%CI 0.5–0.99, p=0.04) and surgical recurrence (HR 0.44, 95%CI 0.25–0.8, p=0.007), as well as the albumin levels at the time of primary surgery (HR for endoscopic recurrence: 0.7, 95%CI 0.52 –0.92, p=0.01; HR for surgical recurrence 0.6, 95%CI 0.36–0.96, p=0.03) (Table 1).

Conclusion

The role of penetrating disease as a risk factor for recurrence should be reassessed in the biological era. Hypoalbuminemia could represent a useful indicator in the stratification of patients at high risk of recurrence.Read more P256 Relationship and sexuality in Inflammatory Bowel Disease: results from a patient questionnaireWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Health-related quality of life has been studied for almost 30 years in patients with Inflammatory Bowel Disease (IBD). However, the knowledge concerning consequences of illness like fatigue, psychological illness, and relationship and sexuality is still sparse.The aim of this study was to gather more information about the IBD patient´s view concerning relationship and sexuality and how patients experience the support and help from the healthcare professionals.

Methods

A questionnaire was sent digitally to all members with an IBD diagnosis in the Swedish patient association. The questionnaire contained seven questions. Four of them concerned background data (age, gender, diagnosis, IBD-surgery). The final three questions concerned relationships and sexuality and were qualitatively analyzed with content analysis.

Results

Out of 2274 patients who received the questionnaire, a total of 556 answered (24%). The median age was 55 years of age, 69% were women, 46% had ulcerative colitis, 45% Crohn´s disease, 6% microscopic colitis, and 3% had a mixed form. A total of 36% had undergone surgery due to IBD.Question 5: "What kind of problems have you experienced regarding relationships and sexuality?" A total of 78% stated some kind of problem. The most common physical problems were pain (14%), incontinence/urgency (11%), and gas/bloating (9%). The most frequent psychological problems were fear of leakage (13%), decreased sexual drive (11%), and loss of energy (8%). Several patients described that their sexual life always needed to be carefully planned, and some described that they avoided having a partner because of difficulties to initiate relationships.Question 6: "What kind of help and support from the healthcare do you want?" A total of 64% wished that healthcare professionals raised questions concerning relationships and sexuality as an equal natural part as the rest of health status.Question 7: "Have you spontaneously raised questions concerning relationships and sexuality in your contacts with healthcare professionals?" A total of 84% answered no. Reasons stated were that it was felt uncomfortable, embarrassing, due to lack of time and that other concerns were prioritized. Some patients expressed that they had no contact with their healthcare center at all.

Conclusion

A total of 78% of the patients answering this questionnaire acknowledged that they experienced physical issues and fears concerning relationships and sexuality, mostly due to pain and leakage. A more active support was wanted from 64% of the patients, but only 14% had themselves raised the topic to health care professionals. More knowledge and awareness concerning relationships and sexuality are needed to ensure person-centered care for all IBD-patients.Read more P257 Clinical characteristics and outcome of Hirschsprung's disease-associated inflammatory bowel disease: experience from 33 years of practice in a single institutionWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Hirschsprung-associated Inflammatory Bowel Disease (H-IBD) is a very rare condition, occurring in approximately 2% of individuals with Hirschsprung's disease. The etiology remains unclear. In a recent study by Wang et al., nine genes were identified as consistently overexpressed in patients with both Crohn's disease and Hirschsprung's disease. Notably, all of them possess proinflammatory properties (IL1B, IL10, CXCL10, ICAM1, EGR1, FCGR3A, S100A12, S100A9, and FPR1). This suggests that chronic inflammation in HD patients may be involved in the progression to IBD. However, due to its low prevalence, there is currently a lack of knowledge about its course and response to treatment. In this study, we aimed to describe our initial experience with H-IBD by analyzing 378 patients operated on for HD at our institution.

Methods

We retrospectively reviewed all patients who underwent operation for HD from January 1989 to December 2021 in a single institution. Of 378 patients, 13 patients were suspected of H-IBD. The diagnosis of H-IBD was based on the criteria described in Sutthatarn et al. We analyzed patient characteristics and outcome.

Results

Of the 13 patients, 8 (61.5%) were boys. All patients had a final diagnosis of total colonic aganglonosis (TCA, long segment HD). One patient was accompanied by an imperforate anus and this patient got colonic segmental resection. Duhamel was performed in 4 patients, endorectal pull-through in 5 patients, and Swenson in 1 patient. Seven patients underwent a re-do pull-through operation. H-IBD was diagnosed by bloody stools in 4 patients, diarrhea in 5 patients, repeated Hirschsprung-associated enterocolitis (HAEC) in 3 patients and iron-deficiency anemia in 1 patient. Seven patients started treatment, and all but one with recurrent flare-ups improved. Immunologics were used in 2 patients, and the remaining patients were maintained with steroids, mesalazine, and antibiotics. Additional surgeries for H-IBD were not performed in all patients.

Conclusion

In our experience, H-IBD was diagnosed in 13 of the 46 children operated on with TCA. (28.3%) Progression to H-IBD should be suspected in patients with recurrent postoperative HAECs and poor response to antibiotic therapy. In addition, in patients older than 5 years of age who require stoma formation due to diarrhea or hematochezia, it may be helpful to screen for the possibility of H-IBD and initiate appropriate therapy.Read more P258 Correlation between patient-reported disease activity, physician’s global assessment and quality of life in Inflammatory Bowel DiseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

As a chronic disease, patients’ perspectives on their disease status and quality of life is an essential part of inflammatory bowel disease (IBD) management. Patient reported outcomes should be the standard of measure for signs and symptoms evaluation. We aimed to evaluate the correlation between patients’ self-assessment of disease activity, activity scores and the physician’s global assessment.

Methods

A unicentric cross-sectional study was conducted. The Short Inflammatory Bowel Disease Questionnaire (SIBDQ) was administered to consecutively evaluated IBD patients in the outpatient setting. Additionally, a pilot questionnaire containing items related to disease activity was also applied to both the patients and the attending physician.Disease activity was categorized as remission, mild, moderate, or severe. Remission was defined as Harvey Bradshaw Index (HBI) ≤ 4 for Crohn's disease or Mayo Clinic Subscore (MCS) ≤ 2 for ulcerative colitis.Correlations between patient's perspective on disease activity, attending physician’s global assessment, activity scores and patient's quality of life were assessed using Spearman’s rank correlation coefficient.

Results

A total of 105 patients were included (female: 52%; mean age: 44±15 years), of whom 68% had Crohn's disease. 71% percent of patients were receiving biological therapy (table 1).A quarter of the patients (n=27) perceived their disease to be in remission, of whom 56% were indeed in deep remission and 19% in endoscopic remission (table 1). A statistically significant positive correlation was observed between patient self-assessment and HBI scores (mean=2.5±6.5 points, r=0.400, p=0.001) and MCS scores (mean=3.4±4.0 points, r=0.574, p<0.001).Among patients who did not consider themselves in remission, 42% rated the activity of their disease as mild, 23% as moderate, and 9% as severe. The attending physician assessed 26% with mild disease, 22% with moderate disease, and 18% with severe disease (table 1). There was a statistically significant positive correlation between patient and physician assessments (r=0.374; p<0.001).The mean score on the SIBDQ was 28±11 points (table 1), and a statistically significant positive correlation was found between patient self-assessment of disease activity and the SIBDQ (r=0.508, p<0.001).

Conclusion

These observational data suggest a weak correlation between patient-reported disease activity and the physician’s global assessment. Divergent perceptions of disease activity between patients and physicians may compromise patient-engagement. Furthermore, the moderate correlation observed with overall quality of life supports the importance of alignment patients and physicians to improve the quality of care provided.Read more P275 Fecal calprotectin, intestinal ultrasound, and their combination for the diagnosis of Crohn’s diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The diagnosis of inflammatory bowel disease (IBD) is often challenging in clinical practice and performed by ileocolonoscopy, an invasive and costly procedure. We aimed to evaluate the diagnostic accuracy of fecal calprotectin (FC) and intestinal ultrasound (IUS),independently and in combination, as screening tools for adults with suspected IBD to reduce the number of unnecessary endoscopic procedures.

Methods

We conducted a retrospective monocentric study that included consecutive adult patients with (i) ileocolonoscopy for suspected IBD between January 2021 and June 2023 who had either (ii) IUS and/or (iii) a FC test within three months. Bowel wall thickness (BWT) (normal value ≤ 3mm) and the color Doppler signal (CDS) was evaluated for all segments. The presence of lymphadenopathy, loss of stratification, stricture, and fistula was also recorded.

Results

In total, 119 patients (69% females) with a median age of 32 years (IQR, 24.0-41.0) were included. The most common symptoms were abdominal pain (n=88, 75%) and chronic diarrhea (n=89, 75%). Among the 119 patients, 74 (62%) had IUS, 101 (82%) had a FC test, and 56 (47%) had both. Forty patients (34%) had a diagnosis of IBD, including 31 (26%) withCD and 9 (8%) with UC. By ROC curve analysis, the best threshold of FC to diagnose IBD was117 ug/g (Se 97%, Sp 73%, PPV 67%, NPV 98%, AUC 0.88, 95%CI [0.81; 0.94], p=0.006).Using this threshold, only 3% of patients were misclassified as non-IBD. Screening by measuring FC levels would result in a 48% reduction in the number of adults requiring endoscopy. Abnormal IUS was significantly associated with a diagnosis of IBD (OR 5.6, 95%IC[2.1; 16.2], P=0.0008). The association of a BWT > 3 mm and a positive CDS was associated with a Se, Sp, PPV, and NPV of 48%, 100%, 100%, and 75%, respectively, but 52% of patients were misclassified as non-IBD. The combination of a BWT > 3 mm, CDS, and FC > 117 ug/ghad a Se, Sp, PPV, and NPV of 44%, 100%, 100%, and 69%, respectively. For patients with anormal IUS and FC < 117 ug/g, 4% were misclassified as non-IBD.

Conclusion

The combination of FC and IUS is a useful screening strategy to identify patients who truly require endoscopy for suspected IBD. Calprotectin is a highly effective test for ruling out IBD. Conversely, relying solely on IUS lacks the discriminative power to safely rule out IBD.However, it shows a high PPV and is a potent tool for diagnosing IBD.Read more P276 Predictive value of changes in 3D volumetry in perianal fistulas in patients with Crohn’s disease under biologic therapy. A pilot studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Changes in the 3D volumetry of perianal fistulas measured by magnetic resonance (MR) could be an imaging biomarker of interest. The objective of the study is to determine the value of volumetric changes in perianal fistulas in patients with Crohn's disease (CD) after biological treatment to predict subsequent clinical outcomes.

Methods

Retrospective single-center pilot study. We have included CD patients with perianal fistulas who started biological therapy between 2012-2020 and have 1) both pre- and post-treatment (3-18 months) pelvic MR and 2) follow-up after post-treatment MR of at least 2 to 5 years. According to the last visit, patients were categorized as clinically active (perianal discharge) or in remission (absence of draining). Using an specific software (vEUA, Motilent, London), we calculated the 3D volumetry of the fistulas, the active component (hypersignal on T2) and the fibrotic component (hyposignal on T2). We compared MR volumetric changes between both pre and post treatment MRs and calculated the value of MR volumetric changes in predicting clinical remission using a multivariate stepwise logistic regression analysis.

Results

Among the 24 patients included, 13 were in perianal clinical remission in the last follow-up. The percentage (%) of volumetric changes in the active component was significantly higher in patients achieving perianal clinical remission compared to non-responder patients (82.5% vs 38.7%, p=0.007). The % of change of the fibrotic component was also significantly higher in patients achieving perianal remission (120% vs 34%, p=0.03). The % of change of the active component was identified as predictor of clinical remission (OR 1.06 [1.02-1.11] P=0.008). A reduction of ≥16% of the active MR component has a sensitivity of 85% and specificity of 82% to predict clinical perianal remission on the long-term.

Conclusion

Changes in the 3D volumetry on MR of perianal fistulas have value in predicting clinical response. The decrease in the active component could be therefore a good biomarker to define therapeutic targets in fistulizing perianal CD.Read more P277 Interobserver agreement of current and new proposed endoscopic scores for postoperative recurrence in Crohn’s diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The modified Rutgeerts’ score (mRS) is widely used for the assessment of endoscopic postoperative recurrence (ePOR) in Crohn’s disease (CD) after ileocolic resection to guide therapeutic decisions. To improve the validity and prognostic value of this endoscopic assessment, two new scores have been proposed. This study assessed the interobserver agreement of the current (mRS) and new endoscopic scores for ePOR in CD.

Methods

Sixteen academic and non-academic IBD specialists assessed endoscopic videos (n=71) of postoperative CD patients (n=66) retrieved from nine Dutch centers. Each video was assessed for the degree of inflammation by four gastroenterologists using the mRS, REMIND score (separate score of anastomosis and neoterminal ileum) and anatomic score (separate score of lesions at the anastomotic line, ileal body, ileal inlet, neoterminal ileum, colonic and/or ileal blind loop). Interobserver agreement was assessed using Fleiss’ weighted kappa.

Results

Fleiss’ weighted kappa for the mRS was 0.67 (95% confidence interval [CI] 0.59–0.74). The weighted kappa for the REMIND score was 0.73 (95% CI 0.65–0.80) for lesions in the neoterminal ileum and 0.46 (95% CI 0.35–0.58) for anastomotic lesions. In the anatomic score, the weighted kappa for lesions in the ileal body, ileal inlet, neoterminal ileum, colonic and ileal blind loop was 0.61 (95% CI 0.49–0.73), 0.63 (95% CI 0.54–0.72), 0.61 (95% CI 0.49–0.74), 0.83 (95% CI 0.62–1.00) and 0.68 (95% CI 0.46–0.89), and 0.44 (95% CI 0.32–0.55) for lesions at the anastomotic line.

Conclusion

The interobserver agreement of the mRS is substantial. Similarly, the interobserver agreement is substantial for lesions in the neoterminal ileum according to both the REMIND and anatomic score, whereas only moderate for anastomotic lesions. Since therapeutic decisions in clinical practice are based on these assessments and these scores are used as outcome measure in clinical studies, further improvement of agreement is essential.Read more P278 Radiation exposure in patients with inflammatory bowel diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Radiological imaging plays an important role in diagnosis and follow-up of patients with IBD. Due to the progressive character of the disease, repeated imaging may be necessary. A cumulative effective dose (CED), meaning the total diagnostic radiation received, of 75 mSv is often described as the risk level one needs to try not to exceed. However, data on cumulative exposure are limited in IBD. In this retrospective study, we analysed the cumulative radiation exposure of patients with IBD in a Belgian tertiary referral centre.

Methods

Electronic health records (EHRs) from all IBD patients followed at the tertiary referral centre between January 1^st 1990 and December 31^st 2021 were searched for examinations with radiation exposure and received doses in house or in any of 27 collaborating Nexuz hospitals working with the same EHR. Both the annual effective dose (AED) and CED were calculated. A sub-analysis of patients diagnosed after January 1^st 2007 was performed, as detailed radiation doses were maintained prospectively from that date onwards.

Results

In total, 3429 IBD patients were included. The median (IQR) AED was 0.39 (0.01-1.66) mSv/year, and was higher in patients with CD than in patients with UC [0.58 (0.01-1.81) vs. 0.17 (0.01- 1.24) mSv/year, p=0.028]. During the first 20 years after diagnosis, the received CED were found higher in patients with CD than UC (Figure, p<0.01). In 5.5% of patients, a CED ≥75 mSv was reached after a median (IQR) of 24 (13-34) years of follow-up. Sub-analysis of 1633 patients diagnosed after January 1^st 2007 showed a median (IQR) AED of 0.44 (0.01- 2.12) mSv/year, again higher in patients with CD than in patients with UC [0.82 (0.02-2.38) mSv/year vs. 0.12 (0.01-1.47) mSv/year respectively, p=0.040]. Here, 3.3% patients reached a CED ≥75 mSv during a median (IQR) of 9 (6-12) years of follow-up. Most common reasons for high radiation exposure were comorbidities like malignancy and postoperative complications. Chart review by an IBD expert showed that the indication for most of these examinations was appropriate and that no alternative examination was available in a timely manner.

Conclusion

Up to 5.5% of patients with IBD were exposed to a CED of ≥75 mSv. Although most decisions to perform imaging with radiation exposure were appropriate, vigilance for unconsidered and excessive imaging should be maintained.Read more P353 Optimal Interval for Therapeutic Drug Monitoring in Patients with Inflammatory Bowel Disease Receiving Stable Infliximab Maintenance TreatmentWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Recent studies suggest that proactive therapeutic drug monitoring (TDM) in patients with inflammatory bowel disease (IBD) receiving infliximab (IFX) improves clinical outcomes. However, as proactive TDM may lead to increased medical costs, we aimed to determine the optimal interval for TDM during infliximab maintenance therapy in IBD patients.

Methods

We conducted a retrospective analysis of a prospective cohort comprising 103 patients with IBD on IFX maintenance therapy who went through proactive TDM between February 2020 and May 2023. Following dose optimization till achieving a therapeutic trough level (TL) of 3 to 10 ug/mL, we applied the Kaplan-Meier (KM) method to calculate the time to subtherapeutic IFX TL (two consecutive IFX TLs below 3 ug/mL).

Results

90% of patients had a sustained therapeutic IFX TL for 10.3 months, whilst 80% had it for 14.3 months. In multivariable analysis, IFX TL at enrollment had a association with the risk of subtherapeutic IFX TL (P=0.025). Persistence rates for therapeutic IFX TL were significantly lower in patients with IFX TL from 3 to 5 µg/mL at recruitment than in those with IFX TL >5 µg/mL (P=0.017). For patients who had IFX TL between 3 to 5 µg/mL upon enrollment, the percentage of those who maintained therapeutic IFX TL was 80% after 12.0 months. The group with IFX TL greater than 5 µg/mL had a persistence rate of 90% after 12.3 months.

Conclusion

These results suggest that conducting annual measurement of IFX TL in patients with IBD who are on stable maintenance therapy with IFX, which may reduce the cost of proactive TDM.Read more P354 Tryptophan metabolites as predictive biomarkers for dietary therapy outcomes in paediatric Crohn's diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Crohn's disease (CD) exclusion diet combined with partial enteral nutrition (CDED+PEN) and exclusive enteral nutrition (EEN) are effective in inducing remission in mild-to-moderate paediatric CD. While tolerance is higher with CDED+PEN than with EEN, a subset of patients still does not achieve remission. Diet-induced remission at week 6 was associated with changes in tryptophan (Trp) metabolism.¹ Our aim was to investigate whether baseline Trp metabolites could predict dietary therapy outcomes in paediatric CD.

Methods

In total, 26 mild-to-moderate treatment-naive paediatric CD patients from a prior randomized controlled trial ², were classified as having remission 6 (R, n =19 (CDED+PEN=10 and EEN=9)) and No-Remission (NR, n=7 (CDED+PEN=3 and EEN=4)) following 6 weeks of CDED+PEN or EEN therapy, based on the Paediatric Crohn’s Disease Activity Index (PDCAI) score (≤10 remission, >10 no remission). We performed targeted quantitative analysis of 21 tryptophan metabolites in baseline faecal samples from both groups, utilizing liquid chromatography coupled with quadrupole mass spectrometry. Receiving Operator Characteristic Curve (ROC) and Random Forest Analysis were used to assess the predictive power of Trp metabolites for dietary outcomes.

Results

Baseline clinical characteristics were comparable between R and NR. Baseline fecal kynurenine was significantly higher in NR compared to R for CDED+PEN (p=0.02) (Fig 1A) and EEN (p=0.04) (Fig 2A). ROC analysis highlighted the robust predictive power of kynurenine for CDED+PEN (area under the curve (AUC)=0.97) (Fig 1B) and EEN (AUC=0.88) (Fig 2B) induced remission. Random Forest analysis corroborated these observations. Ratios of Trp metabolites were compared to investigate different downstream Trp pathways. The ratio serotonin/kynurenine was the strongest predictor of CDED+PEN-induced remission (AUC=1) (Fig 1C). The ratio 5-OH-Tryptophan/kynurenine (AUC=0.88) (Fig 2C) predicted EEN-induced remission. When data from CDED+PEN and EEN were combined, kynurenine (AUC=0.91) and the ratios of quinolinic acid/kynurenine (AUC=0.93) and kynurenine/indole-3-acetic acid (AUC=0.88) demonstrated strong predictive performance for dietary therapy in general (Fig 3A,B and C).

Conclusion

Baseline faecal kynurenine has potential as a prognostic biomarker for dietary therapies. Trp metabolite ratios, notably serotonin/kynurenine for CDED+PEN and 5-OH-tryptophan/kynurenine for EEN, showed promising predictive capabilities. If confirmed in validation studies, baseline faecal Trp markers may be able to provide much needed guidance to personalize dietary intervention within the management of paediatric CD.

References

1. Gastroenterology. 2022 Oct;163(4):922-936. 2. Gastroenterology. 2019 Aug;157(2):440-450.Read more P355 Correlation of Intestinal Ultrasound with histological activity in patients with Ulcerative ColitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Histological remission in ulcerative colitis (UC) is considered a therapeutic target predictive of favorable clinical outcomes. Intestinal ultrasound (IUS) represents an imaging tool that is well correlated with endoscopy and can accurately define disease activity in UC. There is a major gap in the international literature examining the potential link between activity indices on IUS and histological findings in UC¹. We aimed to evaluate the correlation of the Milan Ultrasound Criteria (MUC) with Nancy Histological index (NIH) in patients with UC.

Methods

We performed a cross-sectional study that included consecutive patients with established diagnosis of UC. All patients underwent colonoscopy with biopsy samples, as well as IUS within 3 days of one another. Endoscopic activity was defined as an endoscopic mayo score (EMS) > 0, while histological activity was defined as NHI > 1². Active disease on IUS was calculated on the most affected bowel segment by MUC [MUC = 1.4 × Bowel wall thickness (BWT) in mm) + 2 × Bowel Wall Flow (BWF); BWF = 1 if present, or BWF = 0 if absent] ³. Activity on IUS was defined as a MUC score > 6.2. For maximum accuracy, the most affected bowel segments on endoscopy and IUS were matched. On the day of endoscopy, partial mayo score (PMS) was calculated (PMS >1 corresponded to clinical activity), and C-reactive protein (CRP) was recorded.

Results

A total of 45 patients were included (table 1). We observed a strong correlation between MUC and endoscopic activity [ρ: 0.802 (p< 0.001)], as well as between MUC, PMS and CRP [ρ: 0.743 (p< 0.001) and ρ: 0.798 (p< 0.001)] respectively. We revealed a strong correlation between MUC and NHI [ρ: 0.811 (p< 0.001)]. A MUC > 6.2 possessed 74.3% sensitivity, 90% specificity, 96.3% PPV and 50%, NPV (p<0.001) in predicting histological activity (Nancy>1). At the optimal cut-off value of 5.67, MUC displayed a sensitivity of 97.1% and a specificity of 90% [(AUC: 0.973, 95% CI: 0.918-1.000, (p<0.0001) – fig 1] in predicting histological activity (NHI>1), in patients with UC.

Conclusion

Intestinal ultrasound represents a promising non-invasive tool that can accurately define histological activity in patients with UC. Further studies are needed to confirm the aforementioned results.Read more P356 Long-term outcome of UC patients in clinical remission with different level of mucosal activity: real world, retrospective, multicontinental studyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

In contrast to the increasingly rigorous endpoints of clinical trials of ulcerative colitis (UC), Mayo endoscopic score (MES) ≤ 1 is mostly set as target during clinical follow-up, but long-term outcomes may differ according to different level of healing. Therefore, our study aimed to compare the long-term outcomes of UC patients in clinical remission with different MES and UCEIS scores in real-life condition.

Methods

UC patients in clinical remission (defined by pMayo<2 with no rectal bleeding) who underwent colonoscopy between 2016-2020 were consecutively enrolled in this multicenter retrospective study. Mayo and UCEIS endoscopic scores were evaluated and clinical and demographic data were collected at baseline. Clinical flare, colectomy, hospitalization and treatment modifications were recorded during at least 3 year of follow-up. Primary outcome was the clinical flare, while secondary outcomes were hospitalization, colectomy, new biological initiation and biological dose escalation during follow-up. Outcomes were compared with Log-rank test and survival characteristics were plotted.

Results

In total, 156 UC patients were enrolled with a median age of 46.0 (IQR 35.5-58.0), while male/female ratio was 49.4 % (Table 1.). Near to half of the patients (44.9%) had MES>0 endoscopic activity at baseline. Non zero baseline MES (Figure 1.; p = 0.002; MES 0 vs 1 p = 0.004) and UCEIS (p < 0.001; UCEIS 0 vs. 1 p = 0.016) scores were associated with higher rate of clinical flare. Higher baseline MES (p = 0.042) and UCEIS (p = 0.008) scores were coupled with increased risk of hospitalization. Colectomy rates were low. Increased baseline UCEIS (p = 0.003), but not MES score was coupled with new biological treatment initiation, while only UCEIS score was associated with biological treatment intensification (>4; p = 0.008).

Conclusion

Our study suggests differentiating between complete MH from MES 1 as long-term outcomes were more favorable in case of lower endoscopic scores. Consequently, targeting complete MH should be considered to achieve deep remission and disease clearance.Read more P357 Automated assessment of histological disease activity in Ulcerative Colitis using a deep learning algorithmWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Assessment of histological disease activity in patients with ulcerative colitis (UC) is becoming more important. Therefore, the DCA score was developed for use in clinical practice. Distribution (D), chronicity (C) and activity (A) are each scored on a three-point scale with distribution being dependent on the percentage of biopsy area affected by inflammatory changes. A major problem for implementation of any score is interobserver heterogeneity. To overcome this hurdle, we developed a deep learning algorithm to automatically compute the DCA score.

Methods

A retrospective cohort was created consisting of 117 adult patients with ulcerative colitis from which biopsies were taken during a colonoscopy performed in the setting of routine clinical evaluation (training set of 537 slides). From 75 cohort patients, an additional set of biopsies was available (test set of 299 slides). An expert gastrointestinal pathologist performed the DCA score. The model was trained on H&E-stained whole slide images scanned at 40x (0.243-μm pixel) resolution. Training was performed in a weakly supervised multiple-instance learning setup, using slide-level labels without region of interest annotations. The features from the convolutional neural network-based model trained at 2.5x, 5x, and 10x magnification were incorporated using a random forest classifier for final prediction. Model accuracy was evaluated using the test set.

Results

The algorithm differentiates between normal and inflamed with an accuracy of 90.9% (Table 1). Model performance from features aggregated across all magnification levels (i.e., 2.5x, 5x, and 10x) was superior to features from individual levels. This can be explained with the help of GradCam heatmaps (Figure 1), where we show that features learned at different magnification levels correspond to different aspects of histological changes in UC. The multiple instance approach did not appear to detect crypt abscesses, which may have resulted in a relatively poor performance in differentiating A1 from A2. The model accuracy for the 9-class DCA was 64.8%.

Conclusion

The algorithm first appears to assess architectural distortions at lower magnification and then the presence of cellular elements like neutrophils at higher magnification. This closely mirrors the approach of pathologists. The present model automates the scoring process and by supporting the daily diagnostic practice highlights the potential of deep learning technologies in assessment of histological disease activity in UC.Read more P358 Impact of end-ileostomy versus ileal pouch-anal anastomosis on graft-survival following liver transplantation for primary sclerosing cholangitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

IBD-PSC patients may require both liver transplantation and ileoanal pouch (IPAA) construction. Recently, concerns have been raised regarding an increased rates of hepatic artery thrombosis, biliary strictures, and graft loss in individuals who underwent IPAA after liver transplantation compared to those who underwent end-ileostomy (EI). We hypothesized that graft survival was not negatively affected by IPAA compared with EI.

Methods

A prospectively maintained database from a large tertiary center was searched for patients meeting the inclusion criteria for liver transplantation, primary sclerosing cholangitis, ulcerative colitis, and total colectomy with IPAA or EI. Univariate analysis and Kaplan-Meier survival curves were calculated.

Results

Between January 1990 and December 2023, 55 patients met inclusion criteria. Of these, 46 (83.6%) underwent IPAA, and 9 (16.4%) underwent EI. The average age at colectomy (41.7 vs. 45.7 years; p=0.44), sex distribution (female: 26.1% vs. 22.2%, p=1), and MELD score before transplantation (20.3 vs. 14; p=0.06) were comparable between patients with IPAA and EI patients. The rates of re-transplantation (21.7% vs. 22.2%; p=1), hepatic artery thrombosis (8.7% vs. 0; p=1), episodes of acute rejection (32.6% vs. 44.4%; p=0.7), chronic rejection (4.3% vs. 11.1%; p=0.42), recurrence of primary sclerosing cholangitis (23.9% vs. 22.2%; p=1), and biliary complications (21.7% vs. 33.3%; p=0.43) were similar between the IPAA and EI groups, respectively. None of the EI patients developed parastomal varices. Survival analyses for time to re-transplantation (p=0.97), overall survival (p=0.3), and time to graft loss or mortality (p=0.73) were similar.

Conclusion

In contrast to a previous study, we observed similar rates of liver transplant graft loss, biliary complications, and recurrent PSC after IPAA compared to those after end-ileostomy. IPAA may be associated with an increased rate of hepatic artery thrombosis.Read more P359 Persistence of severe fatigue in adults with Crohn's disease in remissionWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Fatigue is a frequent manifestation in patients with Inflammatory Bowel Disease (IBD), including those in remission. The persistence of fatigue over time in inactive disease is not well known. We aimed to determine the prevalence and continuation of severe fatigue at baseline and at 12 months follow-up in a cohort of patients with Crohn’s disease (CD) in remission.

Methods

Adult patients with CD in remission, defined by age ≥18 years, HBI <5 and faecal calprotectin <250mcg/g, were recruited to the INTICO2 observational study. Baseline assessment included SF36, FACIT-F and IBD Control patient-reported outcome measures. After 12 months in routine care, participants were invited to repeat FACIT-F. Severe fatigue was defined as scoring FACIT-F <30. Baseline data was analysed for factors associated with the persistence of severe fatigue at 12 months.

Results

A total of 198 patients were studied at baseline, of which 141 completed both baseline and 12-month assessments. The correlation between FACIT-F scores at baseline and 12 months was r = 0.79 (p < 0.001). Twenty-five (17.7%) patients were severely fatigued at both baseline and 12-month follow-up, and 99 (72.1%) were not severely fatigued at either time. Of the 34 patients severely fatigued at baseline, 9 (26.5%) were not severely fatigued at 12 months. From the 107 patients who were not severely fatigued at baseline, 12 (7.5%) became severely fatigued at 12 months. Participants with ongoing severe fatigue at baseline and 12 months had significantly worse SF36 Mental Health scores, 64 v 80 (p <0.001), and more night waking due to IBD, 32.0% v 7.1% (p = 0.011), at baseline assessment than those not severely fatigued at either assessment, see Table 1. Eight patients had a clinical disease flare during the 12-month follow-up period.

Conclusion

Most patients in this cohort in remission continued to have similar fatigue severity at 12-month follow-up. A higher proportion of severely fatigued patients at baseline improved at 12 months than non-severely fatigued patients at baseline developing severe fatigue at 12 months. Factors at baseline associated with persistent severe fatigue were worse mental health and poor sleep secondary to IBD. These may represent areas where intervention could improve reported fatigue levels in remission.Read more OP04 Endoscopic healing in paediatric IBD perpetuates a persistent signature characterized by pathogenic Th17 cells and tissue-associated molecular and microbial drivers of diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Endoscopic healing (EH) is the major long-term treatment target for inflammatory bowel diseases (IBD) in adults and paediatric patients. However, EH may not represent disease clearance. Hence, risk of relapse remains high and treatment discontinuation after reaching EH often results in disease exacerbation. We aimed to identify persistent cellular, molecular and microbial drivers of IBD under EH and longitudinally collected endoscopic biopsies from paediatric patients for analysis of single T-cell and bulk transcriptomics as well as mucosa-associated microbiota.

Methods

We followed disease trajectories of paediatric IBD patients treated according to international guidelines and collected mucosal biopsies from the terminal ileum (TI) and sigmoid colon (SC) at baseline (T1) and after approximately 3-12 months (T2) to assess EH. Non-IBD controls showed no macroscopic or histologic signs of inflammation. Host RNA and bacterial DNA were simultaneously extracted from single biopsies for bulk RNA-seq, and 16S rRNA seq. A second biopsy was used for isolation of lamina propria mononuclear cells (LPMCs), followed by CD45⁺, CD3⁺ cell sorting and single T-cell analysis (10X Genomics). Data were quality controlled and integrated.

Results

217 biopsies (135 simultaneous extraction of host RNA and bacterial DNA; 82 single T-cell analysis) from 32 paediatric IBD patients (mean age 13 ± 3.5 years, 21 Crohn’s disease [CD], 11 ulcerative colitis [UC]; T1 = 32, T2 = 32, T > 2 = 6) and 5 non-IBD controls were analysed. Time between T1 and T2 averages 40 ± 22 weeks. At baseline, 15 patients (14 CD, 1 UC) were newly diagnosed and 31/32 patients had active mucosal inflammation. Twenty-two patients (71%) achieved EH at T2 (SES-CED ≤2 and absence of ulcerations), mostly on anti-TNF therapy. One patient (EH at T1) experienced relapsing disease within 10 weeks after discontinuing medication. In the bulk RNA-seq, we identified 299 differential expressed genes (DEGs; corrected p-value <0.05, FC >2.0), such as DUOX2, SAA2-SAA4, FCGR3B and NOS2, that are associated with active IBD and remained upregulated in EH in contrast to non-IBD controls. In addition single cell analysis revealed an IBD-specific pathogenic Th17 cluster that continued to exist in EH and showed high correlation with top DEGs after data integration. 16S rRNA gene seq highlighted highly individual mucosa-associated bacterial profiles and a reduced α-diversity in active and EH compared to non-IBD controls.

Conclusion

A persisting IBD signature in EH reflects ongoing cellular, molecular and microbial activity in comparison to non-IBD controls despite EH and mucosal regeneration. These markers may provide targets for future or sequential therapies.Read more OP11 Exploring the potential clinical utility of NUDT15 pharmacogenetic testing in clinical practice: a ‘focused reverse phenotyping’ study in the UK IBD BioresourceWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

In a previous study we recruited patients with inflammatory bowel disease (IBD) and a history of thiopurine induced myelosuppression (TIM) and identified associated variants in NUDT15. This widely used phenotype-first approach, is limited by ascertainment and recall bias, which impacts understanding of penetrance, expressivity, and variant pathogenicity that are key to clinical implementation. The United Kingdom (UK) National Institute for Health Research (NIHR) IBD Bioresource allows investigators to select large numbers of subjects based on genomic variants of interest, rather than phenotypes, to overcome these biases. Using this ‘focused reverse phenotyping’ approach we sought to investigate the cumulative 6-month risk of myelosuppression in patients with NUDT15 variants.

Methods

Cases and controls were identified from whole exome sequencing data. Cases included all participants with a loss of function NUDT15 variant (*2, *3, *4, *5, *6 and *9). Control subjects were selected based on wild-type carriage of NUDT15 and TPMT, matched for ethnicity. Our primary outcome measure was time to TIM.Myelosuppression was defined as a white cell count (WCC) <3.5x10⁹/L or a neutrophil count <2.0x10⁹/L that occurred within six months of achieving the maximum thiopurine dose, or in the absence of blood test results, a decision to reduce the dose of or withdraw the thiopurine due to myelosuppression. Severe myelosuppression was defined as a WCC <2.5x10⁹/L or neutrophil count <1.0x10⁹/L and a decision to either reduce the dose of or stop the thiopurine.

Results

We screened 23,082 patients recruited to the UK NIHR IBD bioresource with whole exome sequence data and identified 451 patients with a loss of function NUDT15 variant. We matched, based on ethnicity, these patients to 916 controls. Overall, 271/21,136 (1.3%) Caucasians and 127/1,089 (11.7%) South Asian carried an NUDT15 variant allele. 239/451 (60%) cases had a history of thiopurine exposure. The median weight-adjusted maximum thiopurine dose amongst cases and controls was 1.78 and 1.79 mg/kg/day, respectively.The time to myelosuppression was shorter in patients with NUDT15 variants as shown in Figure 1. The risk of myelosuppression, severe myelosuppression, and hospitalisation was also higher in patients with NUDT15 variants as shown in table 1.

Conclusion

In this reverse phenotyping study, the time to myelosuppression was significantly shorter in patients who carried a loss of function NUDT15 variant. The overall risk of myelosuppression was lower than previously observed in phenotype-first studies. Prior to implementation further analysis of the cost-effectiveness of NUDT15 testing is required.Read more P250 Geriatric impairments associate with mortality and hospitalisations during follow-up in older IBD outpatientsWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

We aimed evaluate the association between impairments found in a geriatric assessment and the risk for adverse outcomes in older patients with Inflammatory Bowel Disease (IBD).

Methods

In a prospective multicenter cohort study, a geriatric assessment was performed at baseline in 405 older (≥ 65 years) patients with IBD. Linear-and cox regression analyses were used to study the association between impairment in five geriatric domains measured in the geriatric assessment (somatic-, functional-, mental-, and social domain, physical capacity) and adverse outcomes occurring during 18 months of follow-up. Adverse outcomes were defined as all-cause-, acute-, and IBD-related hospitalisations and all-cause mortality. All analyses were adjusted for age, sex and biochemical disease activity (C-reactive protein ≥10 mg/L and/or fecal calprotectin ≥250 μg/g).

Results

Of 405 patients at baseline (median age: 70 years), 11 patients (2.7%) died and follow-up was conducted in 356 patients (87.9%). During 18 months, 136 all-cause hospitalizations occurred in 96 patients (23.7%), of which 103 (75.7%) were acute, occurring in 74 patients (18.3%). Forty-one hospitalizations (30.1%) in 28 patients (6.9%) were IBD-related. The number of impaired domains at baseline was independently associated with mortality (p=0.001, B=2.76), all-cause hospitalisation (p=0.016, B=1.28) and acute hospitalisation (p=0.02, B=1.3), but not with IBD-related hospitalisation (p=0.06, B=1.37). On domain level, mortality was associated with impaired mental- (p=0.002, B=8.9) and physical domains (p=0.006, B=9.5), all-cause hospitalisation with an impaired somatic domain (p=0.002, B=2.13), and acute hospitalisation with an impaired somatic domain (p=0.02, B=2.49).

Conclusion

Geriatric impairments in geriatric assessment are independently associated with adverse outcomes in older patients with IBD, including an increased risk of mortality, all-cause and acute hospitalizations. Therefore, this study provides the first prospective evidence for the predictive value of the geriatric assessment, enhancing risk stratification in older patients with IBD.Read more P251 Proactive Therapeutic drug monitoring of Infliximab, but not HLA-DQA1*05, predicts clinical outcome in inflammatory bowel diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

While anti-TNF drugs effectively manage Inflammatory Bowel Disease (IBD), treatment failure rates exceed 40%. Monitoring drug levels, antibodies (Abs), and HLA-DQA1*05 allele typing could optimize patient care. The aim of this study is to evaluate the clinical impact of Infliximab (IFX) and Abs monitoring in IBD patients and to understand the influence of the HLA-DQA1*05 allele on IFX treatment response and maintenance.

Methods

We conducted a multicenter, observational study involving patients initiating IFX treatment between October 2020 and October 2022. Demographic, clinical, analytical, and endoscopic data, along with disease activity indicators, were prospectively collected. IFX and Abs levels were measured at weeks 6, 14, 30, and 12 months. HLA-DQA1*05 genotyping was performed at baseline. Statistical tests assessed correlations between IFX levels and disease activity.

Results

Ninety-three IBD patients (45±17 years, 46% female) initiated IFX treatment, mostly anti-TNF naïve (90%). At baseline, 91% had an active disease (GPA = 1) and 85,7% a FC > 150 mg/kg. PRO at baseline was 59.22±8.72. Median follow up was 15 months. HLA was determined in 91 patients, of whom 35 (38.5%) where HLA-DQA1*05 positive. IFX levels > 7 µg/mL correlated with improved disease outcomes in week 6, 14 and 30. In this way, IFX levels > 7 µg/mL in week 6 were associated with CRP < 5 mg/L (p = 0.008), FC <150 mg/kg (p = 0.011) and GPA = 0 (p = 0.0016) in week 6 and with GPA = 0 (p = 0.042) in week 14. IFX levels > 7 µg/mL in week 14 were associated with GPA = 0 (p = 0,001) and FC <150 mg/kg (p = 0,0015) in week 14 and with GPA = 0 (p = 0,019) and FC <150 mg/ kg (p = 0,027) in week 30. IFX levels > 3 µg/mL at 12 months follow-up were associated with FC < 150 mg/kg (p = 0,001). PRO was used to evaluate patients’evolution, and progressive improvement in scores at weeks 0, 14 and 30 was observed (p > 0.001). IFX levels > 7 µg/mL at week 14 were associated with a better PRO score at week 14. Discontinuation (40%) within the first year linked to higher CRP and FC at week 0 and active disease at weeks 6, 14, and 30.

Conclusion

Early IFX monitoring at weeks 6 and 14 optimizes IBD management. IFX levels > 7 µg/mL indicate better short and long-term clinical outcomes and drug durability, irrespective of HLA-QDA1*05 status.Read more P252 Male Genitourinary Dysfunction after Minimally Invasive and Open Ileoanal PouchWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the preferred surgical treatment for IBD or FAP. As these diseases often manifest during adolescence or early adulthood, treatment effects on genitourinary function (GU), sexual function, and fertility are of paramount importance. However, the difference in male GU function and sexual function after minimally invasive IPAA (MIS-IPAA) compared to open-IPAA are unclear. We conducted an observational survey to compare long-term GU functionality in male patients’ post MIS-IPAA or open-IPAA.

Methods

All adult male patients who underwent IPAA at a single tertiary hospital between 1983 and 2023 were identified, and demographics and clinical data were obtained from our prospectively maintained pouch registry. Patients were surveyed using validated questionnaires (Table 1). The primary outcome was the composite survey scores. Patients were stratified into MIS-IPAA (laparoscopic, robotic, single-incision surgery) or open-IPAA groups based on the mode of pelvic/rectal dissection. Reoperative IPAA procedures (revisions, redo, and excisions), incomplete surveys, patients with permanent ileostomy, and status post prostatectomy were excluded.

Results

A total of 1,836 patients were surveyed, and 457 (24.9%) submitted a response. After exclusion criteria, 296 responses were analyzed: 236 (79.7%) open-IPAA and 60 (20.3%) MIS-IPAA. In both groups, most patients had ulcerative colitis (88 vs. 89%). Compared to open-IPAA, MIS-IPAA had a similar age at surgery (40.6 vs. 40.9, p=0.88), younger age at survey (48.2 vs 58.2, p<0.001), and shorter interval between surgery and survey (7.7 vs. 17.4, p<0.001). Male MIS-IPAA patients were able to achieve orgasm more successfully than those with open-IPAA (5 vs. 4, p=0.001). No significant difference was observed between MIS- and open-IPAA in erectile function (SHIM score 22.5 vs 21, p=0.22), IBD-specific male sexual dysfunction (IBD-MSDS, 3 vs. 2, p=0.19), lower urinary tract symptoms (LUTS) (CLLS, 4 vs. 6, p=0.16), or use of therapeutic aids for sexual activity (6 vs. 6, p=0.7). There was no difference in global quality of life (CGQoL, 0.83 vs 0.80, p=0.6). There were no differences between the patients who had difficulty conceiving a child (4 vs. 7, p=0.46) and those who experienced infertility (1 vs. 2, p=0.54). Patients experiencing infertility showed no difference in quality of life between the MIS- and open-IPAA groups (FertiQoL, 84.9 vs 85.9, p=0.64).

Conclusion

Minimally invasive IPAA had a higher preservation of orgasm ability than did open IPAA. There was no difference in erectile function, LUTS, need for therapeutic aids for sexual function, or fertility between MIS and open approach to pelvic dissection in IPAA.Read more P253 Knowledge and acceptability of the Lémann Index to measure progressive intestinal damage in Crohn’s disease: results from an international cross-sectional surveyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Chronic inflammation in Crohn’s disease (CD) predisposes to progressive structural bowel damage (SBD). The Lémann index (LI) is a prospectively validated tool that captures extent and severity of strictures, penetrating disease and surgery to generate a SBD score.¹ It is earmarked as a potential outcome measurement tool for CD modification trials. Understanding perceived barriers and knowledge gaps is critical to its wider adoption.

Methods

We conducted a multinational, cross-sectional study (March to October 2023) to determine SBD and LI knowledge, and LI acceptability. An online survey link (REDCap) was distributed to clinicians by email through GI professional societies and snowball sampling. The questionnaire included 23 items, 5 sections (demographic, SBD knowledge, LI perception and knowledge, future LI adoption, and optional case) and responses (binary, 5-point Likert scale, 10-point visual analogue scale (VAS) and free-text) were captured on Excel.

Results

From 170 respondants: 82 (48%) were female; 142 (82.4%) from Europe, 13 North America (7.6%) and 13 Asia (7.6%). Most were IBD specialists (121; 71.2%), General Gastroenterologists (36; 21.2%), managing >40 CD patients per month (60; 35.3%). 88 (51.8%) questionnaires were incomplete (≥1 questions were unanswered). From completed responses, 99 (92.5%) knew about SBD, 97 (90.7%) rated it ‘’very’’ and ‘’fairly’’ important to measure SBD in clinical trials and 82 (76.6%) in clinical practice; 5 (4.7%) felt it was ‘’not important’’. Most agreed LI would improve long-term outcomes in CD (55; 55%) and show achievement of treatment targets (74; 74.7%). More (43; 42.6%) replied it was ‘’very difficult’’ or ‘’difficult’’ to complete the LI for each patient; 36 (36%) felt that it took ‘’significant’’ or ‘’a lot’’ of effort (Figure 1). Most (86; 80.4%) were untrained in calculating the LI; 73 (68.2%) felt it was ‘’very’’ and ‘’fairly’’ important to receive training. Most reported intestinal ultrasound instead of MR enterography to be important (VAS scores 8-10) for encouraging LI calculation in future clinical trials (53; 54.6%) and clinical practice (49; 52.7%) (Figure 2). Lack of time (80.2%), automated calculation methods (64.2%) and dedicated radiologist (50.6%) were the top 3 perceived barriers to wider adoption.

Conclusion

Most respondents had baseline knowledge of SBD and perceived the LI to be important in future long term CD research and clinical practice. Interventions to improve training and automation are needed to facilitate wider adoption of the LI.

Reference

1. Pariente B, et al.Validation and Update of the Lémann Index to Measure Cumulative Structural Bowel Damage in Crohn's Disease.Gastroenterology.2021 Sep;161(3):853-864.e13.Read more P254 Outcomes of endoscopic and histologic remission in ulcerative colitis under advanced therapyWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Current expert-based recommendations suggest that clinical and endoscopic remission should be pursued as treatment targets in ulcerative colitis (UC). However, combined endoscopic and histologic remission may be associated with improved outcomes.

Methods

Retrospective single-center cohort study including consecutive patients with UC under advanced therapy (biologics and small molecules) with endoscopic and histologic evaluation. We evaluated the rates of hospitalization, surgery, steroid-free remission, and treatment discontinuation after 1-year of follow-up according to the type of remission. Endoscopic remission was defined as a Mayo endoscopic subscore of 0. Histologic remission was defined as the absence of ulcers, erosions and neutrophils in the lamina propria.

Results

One hundred and six patients were included. Thirty-five patients (33.0%) achieved combined endoscopic and histologic remission, 21 patients (19.8%) endoscopic but not histologic remission and 50 patients (47.2%) did not achieve endoscopic remission. At the end of 1-year, 85 patients (79.4%) achieved steroid-free remission, 14 (13.0%) required hospitalization, 4 (3.7%) surgery, 15 (14.1%) discontinued treatment. A compound outcome was reached by 31 (29.2%) patients.In multivariate analysis including age at diagnosis, age at biologic, type of advanced treatment, disease duration, immunomodulation, previous biologic exposure and type of remission, only the type of remission was associated with a lower chance of reaching any unfavourable outcome (reference no remission) - combined endoscopic and histologic remission (OR 0.162 95%CI 0.05-0.528, P=0.003) and isolated endoscopic remission (OR 0.286 95%CI 0.084-0.971, P=0.045). Kaplan-Meier analysis showed longer outcome-free survival in patients with combined endoscopic and histologic remission.

Conclusion

Achieving combined endoscopic and histologic remission is associated with better clinical outcomes after 1 year of advanced treatment compared to no remission. However, we could not confirm a significant advantage of combined endoscopic and histologic remission over endoscopic remission alone.Read more P345 Application of bowel sound computational analysis in inflammatory bowel diseaseWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Inflammatory bowel disease(IBD) is a chronic disease. Although colonscopy is the gold standard for assessing activity, itcarries a considerable discomfort. We evaluate the value of bowel sound computational analysis (BSCA) as a tool in assist diagnosis and severity in Crohn’s disease(CD) and ulcerative colitis (UC).

Methods

We used homemade BSCA as a tool in assist bowel sound(BS). Five minutes recordings were taken for patients. The BS activity, sound duration, peak frequency (Hz) and bowel sound index (SI) was recorded.

Results

We enrolled 16 CD, 22 UC and 20 healthy controls. In CD patients, BS peak frequency was significantly higher than UC and controls (p=0.01). In UC patients, BS SI was significantly higher than CD and controls (mean 2024 V/min vs 1687 and 1181, p=0.04 and 0.01, respectively). We further evaluated the relation between these two parameters and the degree of severity. In CD patients, BS peak frequency were higher in patients with CDAI over 150 than CDAI under 150 (mean 370.7 Hz vs 358.2 Hz, p=0.045). In UC patients, BS SI was significantly higher in patients with mayo score(MS) larger than 6,compare to MS 3-5, MS 0-2, and controls (mean 2269 V/min vs 1863,1638, and1181, P all=0.01).

Conclusion

CD patients had higher BS peak frequency and UC patients had higher bowel sound index. These characteristic of BS changes seemed correlated to the severity of IBD.Read more P346 Assessing Brain Morphology in Functional Gastrointestinal and Inflammatory Bowel Disorders Using Functional Magnetic Resonance Imaging (fMRI)Wed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Functional gastrointestinal disorders (FGIDs) and non-specific inflammatory bowel diseases (IBD) are increasingly common in young adults. Studies have shown abnormal interhemispheric interactions in FGIDs and altered Default Mode Network (DMN) connectivity in brain regions linked to gastric sensations and emotional regulation. This study explores these neural mechanisms in FGIDs and IBDs, focusing on chronic visceral pain and its association with DMN reorganization.

Methods

The study included patients with functional dyspepsia (FD), N=18; irritable bowel syndrome (IBS), N=20 and IBD, N=18 alongside a control group of 18 healthy volunteers. Selection criteria included the Rome III Criteria for FGIDs and various diagnostic tests for IBDs. MRI scans were conducted using a 3T Achieva TX Scanner, applying standard T1 and T2 sequences without contrast agents. Functional imaging utilized T2 Gradient Echo-Planar Imaging.

Results

DMN analysis showed no anterior-posterior split. Significant differences were observed in the IBD group compared to controls, particularly in the left superior frontal gyrus. When comparing all patient groups with controls, increased DMN connectivity was noted in the left cingulum and supplementary motor area. These areas were also significant when comparing only FGIDs patients with controls, indicating altered DMN connectivity in these disorders. Please see: Figure 1 and Table 1.

Conclusion

The study highlights differences in DMNs between patient and control groups, especially in the left superior frontal gyrus, left cingulum, and left supplementary motor area. All disease groups showed variations from controls in the DMN pattern within the left cingulum. Significant differences in the DMN of the supplementary motor area were observed in functional gastric disease groups compared to controls. These findings suggest a link between brain areas involved in sensorimotor processes and symptoms of FD and IBS, providing insights into the neural basis of these conditions. Despite varied changes, common features differentiating the entire study group from healthy controls were identified. This condensed version focuses on the key aspects of your original text, ensuring that the main findings and methodology are clearly presented within the character limit.Read more P347 A Trend Analysis of Inflammatory Bowel Disease in Non-Endemic Era (1993-2023)Wed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

In this study, we aimed to evaluate the demographic and epidemiological trends of Ulcerative Colitis (UC) and Crohn’s Disease (CD) in non-endemic era for inflammatory bowel disease (IBD) during the past three decades.

Methods

UC and CD patients who had follow-up at least 6 months between June 1993 and February 2023 were evaluated retrospectively. Electronic medical databases, personal queries and IBD registries have all been used to collection data on the clinical and demographic characteristic of all patients.

Results

A total of 1549 adult patients with UC and CD were admitted to study. UC was diagnosed in 873 (56.4%) patients (Male 538, 61.6%) and CD was diagnosed in 676 (43.6%) patients (Male 404, 59.8%). The median follow-up duration was 8.3 years for UC patients and 6.8 years for CD patients. In patients with UC, proctitis was 154 (17.6%), left sided colitis was 410 (47%) and extensive colitis was 309 (35.4%). In CD patients, ileal involvement was found in 297 (43.9%), colonic in 76 (11.2%), ileo-colonic in 299 (44.2%) and isolated upper GI involvement in 4 (0.6%) cases. 529 (78.3%) patients had non-stenosing non-penetrating behavior, 45 (6.7%) had stenosing behavior, 102 (15.1%) had penetrating behavior, as well as 196 (29%) patients had perianal disease. Mesalazine 658 (75.4%) and thiopurine 397 (45.5%) were the most frequently used conventional treatments for UC, while thiopurine 304 (45%) was most commonly used for CD patients. In the last two-decade, proportion of the biologic usage were 27.9% and 32.1% in UC patients 28.5% and 31.4% in CD patients respectively. Over the three decades, abdominal surgery was 49.2%, 27.8% and 36.3% in CD and colectomy rates was 2.0%, 2.7% and 3.7% in UC patients.While the rate of UC patients has slightly decreased to 98 (61.6%), 401 (58.5%) and 374 (53%) frequency of CD patients has increased to 61 (38.4%), 284 (41.5%) and 331 (47%). Over the course of three decades, there were more UC patients than CD patients, however proportion of UC/CD has been continuously decreased (1.61, 1.41 and 1.13) for three decades respectively.

Conclusion

Our study showed that the frequency of UC and CD has significantly increased during the previous three decades in non-endemic era for IBD. While the frequency of UC patients has slightly decreased, that of CD patients has steadily increased over the past three decades. Although the use of biologics has significantly increased, proportions of the abdominal surgeries and colectomies has not prominently changed.Read more P348 Increased pre-treatment faecal calprotectin concentration predicts resistance to ustekinumab induction in ulcerative colitisWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Rates of resistance to advanced therapy remain high in ulcerative colitis (UC). Pre-treatment predictors of poor outcomes would provide valuable information for treating clinicians so other therapies could be given or early treatment switches could be considered if response is inadequate. We investigated whether baseline, pre-treatment faecal calprotectin (FCP) can predict resistance to ustekinumab.

Methods

Clinical outcomes at week 8, including clinical remission, endoscopic healing and mucosal healing were determined in patients enrolled in the UNIFI phase 3 placebo-controlled trial program, investigating the efficacy of ustekinumab for moderate-to-severe UC (GSE206285), in whom FCP concentrations were available at baseline, prior to initiation of treatment. Clinical outcomes were defined in patients with FCP < 250mcg/g, 250 – 999mcg/g, 1000 – 1999mcg/g and >= 2000mcg/g. Chi-squared test was used to assess statistical significance. Area under the receiver operating characteristics curve (AUROC) analyses were used to determine the ability of faecal calprotectin level to predict treatment resistance. Analyses were performed using R 4.2.3 (Vienna, Austria) and GraphPad Prism 10.0.3 (Massachusetts, United States).

Results

Outcome data and linked faecal calprotectin levels were available for 340 patients. FCP values ranged from 15 – 25249mcg/g. The median FCP value was 1402mcg/g (interquartile range: 600.8 – 2772.0mcg/g). In general, all clinical outcome measures were progressively worse with increasing FCP concentrations. For the respective FCP cut-offs, 22.0%, 19.3%, 11.3% and 6.7% achieved clinical remission; 39.0%, 24.1%, 20.6% and 16.0% achieved endoscopic healing; and 29.3%, 16.9%, 15.5% and 7.6% achieved mucosal healing (Figure 1). ROC analyses revealed that pre-treatment FCP predicts resistance to ustekinumab therapy for all stated outcomes, including clinical remission (AUROC: 0.66, P=0.001), endoscopic healing (AUROC: 0.63, P=0.0013) and mucosal healing (AUROC: 0.65, P=0.0005).

Conclusion

Increasing concentrations of pre-treatment FCP predicts resistance to ustekinumab therapy in moderate-to-severe UC. Patients with FCP >= 2000mcg/g were significantly less likely than those with FCP <1000 mcg/g to achieve clinical remission or mucosal healing. Since neutrophils are the main producers of FCP, these data build on other emerging data indicating that excessive accumulation of mucosal neutrophils is associated with treatment resistance in IBD.Read more P349 Communicating Needs and Features of IBD Experiences (CONFIDE) Survey: Descriptive Comparison of Experiences of Bowel Urgency among Patients with Ulcerative Colitis in Canada, Europe, and the USWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Bowel urgency is a disruptive symptom affecting daily lives of patients with moderate-to-severe ulcerative colitis (UC). Previous analyses from the Communicating Needs and Features of IBD Experiences (CONFIDE) survey reported bowel urgency as a common and impactful symptom of UC in the United States (US) and Europe. This study used data from the CONFIDE survey to descriptively compare the prevalence and impact of bowel urgency in patients with UC across US, Europe, and Canada.

Methods

Online, quantitative, cross-sectional surveys were conducted among patients with UC in the US, Europe (France, Germany, Italy, Spain, UK), Japan, and Canada. Criteria based on previous treatment, steroid use, and/or hospitalization defined moderate-to-severe UC. Descriptive comparisons of data from US, Europe, and Canada are presented.

Results

Surveys were completed by 82 Canadian, 556 European, and 200 US patients with UC. Across geographies, most patients were receiving advanced therapies at the time of survey completion (Canada:73%, Europe:54%, US: 77%; Table). Similar to the findings in Europe and US, bowel urgency was among the top three most common symptoms currently (in the last month) experienced by Canadian patients (Canada:31%, Europe:30%, US:47%; Figure 1a). Due to fear/anticipation of bowel urgency-related accidents, 60% Canadian patients reported wearing diaper/pad/other protection, at least once a month in the past 3 months, similar to European (65%) and US (69%) patients. Among Canadian patients who ever experienced bowel urgency (n=46, 56%), most (78%) reported doing so at least once a month in past 3 months with similar frequencies observed among US and European patients; proportion of patients experiencing bowel urgency at least once a week was higher among US (79%) and European (71%) patients than Canadian patients (48%) (Table). Among patients receiving advanced therapies, similar patterns were observed (Table). Most patients in all three populations reported bowel urgency and bowel urgency-related accidents among the top five most common reasons for declining participation in work/school, social events, and sports/physical exercise (Figure 1b).

Conclusion

These descriptive analyses suggest that although the overall prevalence and burden of bowel urgency in Canada are similar to those in the US and Europe, a numerically lower proportion of Canadian patients with moderate-to-severe UC experienced bowel urgency at least once a week in past 3 months. Despite receiving advanced therapies, patients experience bowel urgency and related diaper/protection use across geographies. These findings highlight the clinical importance of evaluating and treating bowel urgency to improve the quality of life of patients with UC across geographies.Read more P350 Development of consensus statements for transitional care for adolescents with Inflammatory bowel disease throughout Australia and New ZealandWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

The incidence of paediatric inflammatory bowel disease (IBD) is rising, and as such there is an increasing need to support adolescents with IBD as they from transition from paediatric to adult care. The use of a structured process for transition is well supported in the literature, however, variation in the delivery of transitional care for adolescents with IBD has been identified across Australis and New Zealand. The aim of this study was to develop consensus statements, based on evidence and expert opinion, to guide transitional care services in IBD.

Methods

The consensus statements were developed using a modified UCLA-RAND methodology. An IBD expert steering committee was formed, and then a systematic literature review conducted to grade the available evidence and inform initial development of consensus statements. A multi-disciplinary group was formed comprising 16 participants [clinicians, nurses, surgeons, psychologists], that voted anonymously on the level of appropriateness and necessity for each consensus statement, as well as provided general feedback for each. Scoring was facilitated using Likert scales [1=lowest, 9=highest] with a median ≥7 required for inclusion.

Results

Fourteen consensus statements were devised by the Steering committee (Table 1). Key recommendations including the use of a structured transition programme and transition coordinator. Statements recommended assessment of mental health and transition readiness, and outlined discussion points regarding lifestyle, environment and psychosocial factors to be held with adolescents. The importance of allied health input, the age for transition, recommendations for clinical communication and handover were highlighted, as well as considerations for individual patients. In the first voting round by the multi-disciplinary group each statement reached a median score of ≥ 8 for appropriateness, and ≥7 for necessity. An online meeting with both groups was held to discuss voting results and refine statements.Table 1. Final consensus statements to guide transition of children with inflammatory bowel disease in Australasia.

Conclusion

There is an identified need for guidance in paediatric to adult transitional care for adolescents with IBD. Consensus statements were developed by a multi-disciplinary group, supported by published evidence, to provide this guidance. The planned publication of the consensus process and statements will facilitate standardize delivery of IBD transitional care within Australasia.Read more P351 The Histo-endoscopic Spectrum in Ulcerative Colitis reveals a Distinct Mucosal Transcriptome for Histo-endoscopic RemissionWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

Aiming for histological remission on top of endoscopic remission, is an aspiring target in ulcerative colitis [UC]. We investigated the mucosal transcriptional profiles in UC patients with varying depths of histologic activity as compared to healthy controls.

Methods

UC patients with endoscopic improvement (Mayo endoscopic score [MES] 0 or 1) were recruited. Endoscopies were video-recorded and biopsies from the most affected segment were collected for histological assessment and bulk RNAseq (Illumina HiSeq 4000, single read). Geboes Score [GS] was determined by two pathologists blinded for endoscopic scores. The included patients were divided into endoscopic improvement with histologic activity [EIHA] (MES ≤1, GS ≥2B.1) and histo-endoscopic mucosal remission [HEMR] (MES ≤1, GS <2B.1). We distinguished a subpopulation within the HEMR group that we labelled as histo-endoscopic mucosal normalization [HEMN] (MES ≤1, GS ≤0.1).As comparators, 50 healthy individuals [HV] and 50 UC patients with active disease (MES 2-3, independent, matched by treatment) [AD] were included. Normalised RNA counts were analysed by principal component analysis [PCA] and differential expression analysis. Genes with a |log₂ FC|>1 and a FDR <0.05 were considered as differentially expressed [DEG], and were selected for pathway analysis (R 4.3.2, DEseq2; QIAGEN IPA).

Results

In this study cohort 172 patients were included (Table). PCA analysis showed clustering patterns for each study group (Figure). In particular, separation along the PC1 axis tended to follow the different degrees of histo-endoscopic activity. Interestingly, besides inflammatory and tissue remodeling markers (e.g., DUOX2, MMP 3, CHI3L1) for PC1 and epithelial and metabolic markers (e.g., SLC9A3, LPIN3) for PC2, the gene with the highest variance for both PC1 and PC2 was Aquaporin-8 (AQP8). This gene encodes for a water transporter at the apical surface of the colon, and its mucosal expression level indeed follows a spectrum of histo-endoscopic activity (Figure).Differential expression analyses identified 1261 DEG in HEMN, 1684 DEG in HEMR (not HEMN), 2178 DEG in EIHA, all compared to HV. A total of 1014 overlapping DEG were identified for all these comparisons, being enriched for pathways related to inflammation, metabolic epithelial functions (lipid metabolism, bile acid regulation) and wound healing.

Conclusion

UC patients with histo-endoscopic remission have a mucosal transcriptional profile which significantly differs from that of healthy individuals, even in UC patients whose biopsies appear normal upon histological evaluation. The histo-endoscopic spectrum of the mucosal transcriptome in UC is nicely illustrated by the gene expression of Aquaporin-8 (AQP8).Read more P352 Comparison of Radiation Dose, Image Quality, and Diagnostic Performance between Hybrid Iterative Reconstruction and Deep Learning Reconstruction for CT Enterography of IBDWed, 24 Jan 2024 00:00:00 GMT by

Abstract

Background

CT enterography (CTE) is recommended as one of the preferred methods for patients with inflammatory bowel disease (IBD), especially in primary hospitals that lack MRI equipment. However, the potential risk of radiation derived from using CTE during the life-long follow-up is an important issue for these patients. This study aimed to compare the radiation dose, image quality, and diagnostic performance of CTE for IBD using hybrid iterative reconstruction (HIR) and deep learning reconstruction (DLR).

Methods

We prospectively collected data on low dose CTE reconstructed by HIR and DLR in patients with IBD between February 2023 and September 2023, and retrospectively enrolled IBD patients who underwent conventional dose CTE reconstructed by HIR between June 2019 and June 2022 as controls. The CTE examinations were performed within 2 weeks of bowel histologic evaluation (the reference standard of bowel inflammation). The objective and subjective image quality and the image features were evaluated by two IBD radiologists. The radiation dose, image quality, and diagnostic performance was compared between the two dose protocols.

Results

The preliminary study included 36 patients in the low dose group with HIR and DLR and 40 patients in the conventional dose group with HIR. There were no significant differences in demographic data of patients between the two groups (all P>0.05). The sensitivity, specificity, and diagnostic accuracy for detecting active inflammation were 71.4% (43.3%), 83.3% (80.0%), and 75.0% (52.5%) for the low dose group with DLR (HIR), respectively, and 84.4%, 62.5%, and 80% for the conventional dose HIR group. Low dose group with DLR resulted in significantly increased objective and subjective image quality and diagnostic confidence for active inflammation compared to low dose group with HIR (all P<0.05), with no inferiority to conventional dose group with HIR (all P>0.05). The dichotomous inter-reader reliability (k) for the entire group was 0.88. Low dose group resulted in a significant reduction in radiation exposure (mean [± SD], 2.20 ± 0.29 mSv) compared to conventional dose group (4.85 ± 1.96 mSv; P<0.001).

Conclusion

Low dose CTE with DLR significantly improved image quality compared to low dose CTE with HIR, and maintained similarly high diagnostic performance as conventional dose CTE with HIR. Importantly, the low dose CTE with DLR significantly reduced the radiation dose, improving the safety of CTE application in the life-long follow-up of patients with IBD.Read more