Efficacy and safety of mirikizumab in a randomized phase 2 study of patients with Ulcerative Colitis

Sandborn WJ, Ferrante M, Bhandari BR, Berliba E, Feagan BG, Hibi T, Tuttle JL, Klekotka P, Friedrich S, Durante M, Morgan-Cox M, Laskowski J, Schmitz J, D'Haens GR

Gastroenterology. 2019;doi: https://doi.org/10.1053/j.gastro.2019.08.043. [Epub ahead of print]

Introduction

Hajir Ibraheim © Hajir Ibraheim

Interleukin-23 (IL23) contributes to the pathogenesis of chronic inflammatory diseases, including Ulcerative Colitis (UC), by maintaining and amplifying T helper 17 cells and stimulating many innate immune cells. IL-23 is a heterodimeric cytokine composed of a p40 subunit (shared by IL12) and a p19 subunit (IL-23p19). Ustekinumab, a monoclonal antibody targeting the shared p40 subunit, is effective for treatment of Crohn’s Disease (CD) and psoriasis [1–3]. However, studies in patients with psoriasis have suggested that selective targeting of the IL23 pathway by blocking IL-23p19 is more effective than ustekinumab [4, 5]. Whilst promising phase 2 results have been observed in CD patients following treatment targeting IL-23p19 [6, 7], the role of this therapeutic strategy in UC is unknown. Mirikizumab (LY3074828) is a humanised immunoglobulin G4 (IgG4)-variant monoclonal antibody that binds to the IL-23p19 subunit. The current study evaluated the efficacy and safety of mirikizumab for the treatment of patients with moderate-to-severely active UC. 

Tight control for Crohn’s Disease with adalimumab-based treatment is cost-effective: An economic assessment of the CALM trial

Panaccione R, Colombel J-F, Travis SPL, Bossuyt P, Baert F, Vaňásek T, Danalıoğlu A, Novacek G, Armuzzi A, Reinisch W, Johnson S, Buessing M, Neimark E, Petersson J, Lee W-J, D’Haens GR GR

Gut 2019 Jul 8. doi: 10.1136/gut-jnl-2019-318256 [Epub ahead of print].

Introduction

Jennie Clough © Jennie Clough

It is widely accepted that a ‘treat-to-target’ (T2T) approach of continual assessment against established biomarkers and early treatment optimisation is important in preventing progression in Crohn’s Disease (CD) [1], and in 2015 the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) programme was initiated to define a T2T approach for CD [2].

CALM was an open-label, multicentre, randomised controlled phase 3 study comparing the outcome of a ‘tight control’ (TC) adalimumab-based treatment strategy against standard clinical symptom-based management (CM) for patients with early CD [3]. Treatment of patients in the TC arm was escalated in a stepwise manner in response to elevated C reactive protein (CRP) or faecal calprotectin, even in the absence of symptoms. A significantly higher proportion of patients in the TC group achieved the primary endpoint of mucosal healing (CDEIS<4) at 48 weeks compared to the CM group (46% vs 30%).

Perhaps unsurprisingly, a TC approach led to higher rates of adalimumab usage than a conventional approach [3]. Biologics constitute a significant cost in managing Inflammatory Bowel Disease, with other major cost drivers being hospital admission and surgical management [4]. As rates of surgery and hospitalisation have decreased with the advent of biologics [5, 6], costs have shifted to outpatient care, drug acquisition and infusion unit management [7].

This study sought to model the costs of a TC versus a conventional approach, to determine whether the increased biologic costs could be offset by a reduction in hospital attendance and need for surgery, and enhanced economic outputs associated with increased wellbeing.  

Infliximab induction regimens in steroid‐refractory acute severe colitis: A multicentre retrospective cohort study with propensity score analysis

Sebastian S, Myers S, Argyriou K, Martin G, Los L, Fiske J, Ranjan R, Cooper B, Goodoory V, Ching HL, Jayasooriya N, Brooks J, Dhar A, Shenoy AH, Limdi JK, Butterworth J, Allen PB, Samuel S, Moran GW, Shenderey R, Parkes G, Lobo A, Kennedy NA, Subramanian S, Raine T

Aliment Pharmacol Ther. 2019;50:675–683. doi: 10.1111/apt.15456..

Introduction

Joshua McGuire © Joshua McGuire

Acute Severe Ulcerative Colitis (ASUC) is a medical emergency which necessitates a colectomy in up to 30% of cases on index presentation [1]. The first-line treatment is with intravenous corticosteroids but up to 40% of patients will fail to respond [2]. Ciclosporin and infliximab are then well-recognised options for rescue therapy to avert the need for a colectomy and, whilst there appear to be no difference in response rates between these two choices [3], many experts favour infliximab owing to convenience and familiarity [4]. Up to 55% of patients do not respond to the standard dosing regimen of infliximab extrapolated from the outpatient setting [5]. The exaggerated clearance of infliximab in ASUC is increasingly better characterised [6]; this has led to the concept of accelerated dosing regimens although the efficacy of such regimens has yet to be evaluated by randomised controlled trials. A recent meta-analysis [7] of the available cohort studies showed no benefit of accelerated induction in reducing colectomy rates in steroid‐refractory disease; however, provider bias represents a significant barrier to answering this question. Propensity score matching seeks to address this provider bias.

Dominik Bettenworth © ECCO

Dear Y-ECCO Friends,

I hope this Members’ Address finds you well.

Those who want to succeed in academia have to lead and love the life of an academic athlete. This lifestyle, together with its (daily?) exercises and training tools, has been masterfully illustrated by Eric Benchimol and Richard Keijzer in a recent article for the Mentoring, Education, and Training corner in Gastroenterology (Gastroenterology 2018;154:8–14). Indeed, the advent of technological applications has created powerful tools to improve organisation and productivity. Furthermore, social media provides valuable platforms that have substantially decreased barriers between different centres, experts from other disciplines and even colleagues from other continents, making it possible to connect in real time.  

Francesca Rosini © ECCO

Crohn’s Disease (CD) and Ulcerative Colitis (UC) are considered multisystemic diseases. They affect the gastrointestinal tract but can also involve other systems and organs. Almost 50% of patients with Inflammatory Bowel Diseases (IBDs) experience at least one extraintestinal manifestation (EIM). The principal organs and structures affected by EIMs are, amongst others, joints and bones, eyes, liver and the hepatobiliary system and skin [1].

Christianne Buskens © ECCO

Patients with Inflammatory Bowel Disease (IBD) have an increased risk of colorectal cancer (CRC), principally resulting from the pro-neoplastic effects of chronic intestinal inflammation [1]. Epidemiological studies, however, have suggested that the incidence of CRC has decreased over time [2]. This is partly because the estimated incidence in older studies was based on data from referral centres, which likely included a different patient population with more severe and complicated disease. The declining incidence has also been attributed to successful CRC surveillance programmes and in addition has been hypothesised to be a consequence of improved control of mucosal inflammation [3]. The expanding armamentarium of medical options in IBD, such as anti-TNF and anti-adhesion biologic therapies, has substantially improved our ability to control severe inflammation, theoretically decreasing the risk of CRC.

Paulo Gustavo Kotze © ECCO

The Surgeons of ECCO (S-ECCO) once more organised an international workshop outside of Europe. These international workshops constitute a tradition in Latin America, with previous meetings having been held in Brazil, Mexico and Colombia since 2013. This year, the meeting was held in Curitiba, the capital of the state of Paraná, in southern Brazil. This meeting was the result of a cooperation between ECCO and GEDIIB, the Brazilian Study Group of IBD.

Catherine Wall © ECCO

Definition of collaboration (noun): 1. the action of working with someone to produce something or 2. traitorous cooperation with an enemy!⁶.

Collaborative projects, such as topical reviews, are excellent opportunities to increase communication between ECCO Members and encourage clinicians and researchers from across disclipines to work together to achieve a common goal. Furthermore, collaborative working, in clinical practice and research, allows us to appreciate and utilise the specialised perspectives of our peers. Clinical collaboration (a multidisclipinary team) provides a structured setting where cross-discipline discussion of complex clinical cases can occur. A multidisclipinary Inflammatory Bowel Disease (IBD) model of care is recommended [1] and can be effective [2, 3]; however, the structure of the team will likely vary by site depending on the aim and expertise of each IBD service [2–4].

Rikke Edelbo © Rikke Edelbo

I would like to thank the N-ECCO Committee for awarding me the N-ECCO Travel Award, which was a great financial support and helped me for my studies in Stockholm.

My focus was primarily use of the telephone in patient contacts, patient education, management of newly diagnosed IBD patients and independent nursing activities.

Ana Ibarra  © ECCO

Once again, N-ECCO is offering an outstanding range of clinical and educational opportunities for nurses attending the ECCO’20 Vienna Congress.

The programmes for each activity continue to be developed on the basis of the evaluation forms from the previous year in order to meet your needs. Thank you so much for providing your feedback, which helps us to improve all the N-ECCO Activities.