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.  

Charlotte Hedin © ECCO

Professor Fiona Powrie is the Director of the Kennedy Institute of Rheumatology at the University of Oxford. Her work has been seminal in defining the mechanisms that govern and regulate immune responses in the gut. Her research has revealed the pivotal role of regulatory T cells, interleukin-10, interleukin-23 and transforming growth factor-β (TGF-β) in intestinal inflammation.

No association between pseudopolyps and colorectal neoplasia in patients with inflammatory bowel diseases

Mahmoud R, Shah SC, Ten Hove JR, Torres J, Mooiweer E, Castaneda D, Glass J, Elman J, Kumar A, Axelrad J, Ullman T, Colombel JF, Oldenburg B, Itzkowitz SH; Dutch Initiative on Crohn and Colitis

Gastroenterology. 2019;156:1333–44.e3.

Introduction

Sailish Honap © Sailish Honap

Patients with Inflammatory Bowel Disease (IBD) are at an increased risk of developing high-grade dysplasia and colorectal carcinoma [1, 2]. The risk of carcinogenesis, driven by chronic inflammation, increases with several factors, including duration and anatomic extent of colitis, family history and the presence of primary sclerosing cholangitis (PSC). European clinical guidelines for colonoscopy surveillance in this high-risk cancer population also suggest a shorter surveillance interval for those with post-inflammatory polyps (PIPs), also known as pseudopolyps [3–5]. PIPs are a common finding, more so in Ulcerative Colitis (UC) than in Crohn’s Disease, and are formed after alternating cycles of inflammation and regeneration of the epithelial mucosa. However, data are conflicting and evidence is lacking in this field as previous case control studies have reported up to a 2.5-fold increased risk [6, 7] whereas a more recent cohort study showed no significant association between PIPs and colorectal neoplasia (CRN) [8]. The authors of this study aimed to use a large cohort study to further define the risk of CRN and PIPs in patients with Inflammatory Bowel Disease.  

Crohn’s Disease exclusion diet plus partial enteral nutrition induces sustained remission in a randomized controlled trial

Levine A, Wine E, Assa A, Boneh RS, Shaoul R, Kori M, Cohen S, Peleg S, Shamaly H, On A, Millman P, Abramas L, Ziv-Baran T, Grant S, Abitbol G, Dunn KA, Bielawski JP, Van Limbergen J

Gastroenterology. 2019;157:440–50.

Introduction

Paul Harrow © Paul Harrow

Exclusive enteral nutrition (EEN) is a safe and effective induction treatment for Crohn’s Disease (CD). It is recommended as first-line induction therapy in children and adolescents [1]. However, enteral nutrition is less well tolerated than other options like corticosteroids. A recent meta-analysis found three times as many patients withdrew from enteral nutrition therapy compared to corticosteroids even in the supported setting of clinical trials [2]. There is a clear need for a more acceptable dietary intervention. However, our understanding of the role of diet in CD is incomplete and to date specific diets have not been proven to induce remission. 

Ustekinumab exposure-outcome analysis in Crohn’s Disease only in part explains limited endoscopic remission rates

Verstockt B, Dreesen E, Noman M, Outtier A, Van den Berghe N, Aerden I, Compernolle G, Van Assche G, Gils A, Vermeire S, Ferrante M

J Crohns Colitis. 2019;13:864–72.

Introduction

Samantha Campbell © Samantha Campbell

Ustekinumab is licenced to treat moderate-severe Crohn’s Disease (CD) [1]. Ustekinumab induction is administered via intravenous (IV) infusion at a dose of 6 mg/kg at week 0, followed by a subcutaneous (SC) maintenance injection of 90 mg at week 8.

The UNITI programme demonstrated that ustekinumab can induce and maintain clinical remission. However, there is a paucity of real-life data in patients with CD receiving the mentioned IV induction and SC maintenance dosing of ustekinumab. Real-life data on therapeutic drug monitoring and biomarkers, such as faecal calprotectin, remain a relatively unexplored area with ustekinumab, with discrepancies in the literature [2, 3]. . 

Dominik Bettenworth © ECCO

Dear Y-ECCO Friends,

I hope you all are doing well.

During my summer leave, I read a book on the time horizon principle. The author supposes that the productivity of the most successful people on the planet results from the balance between three core components: Time for yourself, relationships and work. As you all, hopefully, have had sufficient time for yourself and your family during your holidays, here are some ways to expand your (professional) relationships and work skills:  

Charlotte Hedin © ECCO

Early clinical trials, the advent of biologics and the IBD Nurse and how the clinical presentation of IBD has changed over a 46-year career: The interviewee in this issue is Professor David Rampton, who has had a long career as an IBD clinician and researcher in East London. Respected by colleagues and patients alike, his career has spanned an era during which much has changed in IBD.

Rates and characteristics of postcolonoscopy colorectal cancer in the Swedish IBD population: What are the differences from a non-IBD population?

Stjärngrim J, Ekbom A, Hammar U, Hultcrantz R, Forsberg AM

Gut 2018 Dec 15; doi: 10.1136/gutjnl-2018-316651

Introduction

Rohit Rao  © Rohit Rao

Individuals with IBD have an increased risk of colorectal cancer (CRC) [1, 2]. In an effort to address this, societal guidelines recommend surveillance colonoscopy 8–10 years after diagnosis and at varying intervals thereafter, depending on risk [3, 4]. A 2017 Cochrane systematic review [5] demonstrated a benefit in this strategy, noting reductions in the development of both CRC and the rate of CRC‐associated death. Despite this, dysplasia detection is challenging and CRC still accounts for 10%–15% of all IBD deaths [6, 7]. Of further concern is the reported increased rate of post-colonoscopy colorectal cancer (PCCRC) in IBD.