Dear Y-ECCO Friends,

I hope you are all well and that those of you who made the trip back to Copenhagen for UEGW had an interesting and enjoyable conference. We are now very much into the foothills of ECCO’24, which will take place in Stockholm in February, and I hope many of you have submitted your work for presentation there. I also hope that you will consider attending our 10th Y-ECCO Science Workshop, to be held on the afternoon of Wednesday, February 21, immediately prior to the main Congress itself. As always, we will have a mixture of established clinician-scientists presenting keynote lectures and up-and-coming Y-ECCO Members presenting their own original work. We’re looking forward to an inquisitive and collaborative atmosphere and it would be fantastic to see you all there!

Robin Dart © ECCO

Tim Raine is a consultant gastroenterologist at Addenbrookes Hospital in Cambridge and an honorary faculty member of the Wellcome Trust Sanger Institute. He is a mucosal immunologist, and alongside translational science work, he is also heavily involved in clinical trials and guideline development. Despite his relative youth, Tim has been in and around ECCO for many years and is well known to the ECCO Community. After chairing both Y-ECCO and GuiCom, he is now a member of SciCom, reflecting the breadth of his involvement with IBD. I had the opportunity to discuss his work with ECCO and his journey into life as a clinician-scientist.

Gabriele Dragoni © ECCO

Dear Y-ECCO Friends,

The Y-ECCO Mentorship Forum is an educational event designed to foster networking and prepare the career of young gastroenterologists with a particular interest in Inflammatory Bowel Disease. In June 2023, the second edition of the Forum took place in beautiful Vienna, and it certainly did not disappoint.

Anti-integrin αvβ6 autoantibodies are a novel biomarker that antedate ulcerative colitis

Livanos AE, Dunn A, Fischer J, et al.

Gastroenterology 2023;164:619–29. doi: 10.1053/j.gastro.2022.12.042.

Introduction

Biomarkers for the prediction of disease onset and disease course in Ulcerative Colitis (UC) represent an ongoing and important area of unmet need. However, discovery and validation of such biomarkers has been complicated by the wide heterogeneity in disease presentation and variability in disease course [1]. Despite many initial biomarker discovery efforts in UC focusing on biopsy-based approaches, it has increasingly been recognised that non-invasive blood-based biomarkers would likely have more clinical utility, including because of their ease of collection and high rates of patient acceptance [2, 3].

Previous studies have discovered a novel autoantibody against integrin αvβ6 (anti-αvβ6) in the serum of UC patients, with strong discriminative ability for diagnosis of UC. Integrin αvβ6 plays a critical role in maintaining epithelial barrier integrity and suppressing epithelial inflammation [4–7].

Faecal microbiota transplantation with anti-inflammatory diet (FMT-AID) followed by anti-inflammatory diet alone is effective in inducing and maintaining remission over 1 year in mild to moderate ulcerative colitis: a randomised controlled trial

Kedia S, Virmani S, Vuyyuru SK, et al.

Gut 2022;71:2401–13. doi: 10.1136/gutjnl-2022-327811.

Introduction

Microbiota are known to play a role in the pathogenesis of both Ulcerative Colitis (UC) and Crohn’s Disease (CD). Various lifestyle factors, including rural living, absence of antibiotic exposure and larger family size, have been associated with greater microbial diversity and lower risk for development of IBD [1, 2]. Conversely, dietary patterns and constituent elements of the diet have been linked to dysbiosis and increased risk of IBD [3, 4]. Despite these associations, the causal relationship between microbiota disturbance and IBD pathogenesis/disease flares remains unclear.

Current therapeutic strategies for IBD primarily focus on targeting the dysregulated immune response. However, these approaches have limitations, including a “ceiling effect” of current treatments and a high risk of relapse following withdrawal of therapy [5]. Consequently, there has been a growing interest in exploring alternative interventions, including through modulation of the gut microbiota or manipulation of dietary factors. Most of the evidence for such therapeutic approaches has focused on CD, including with the use of exclusive enteral nutrition [6]. In UC, microbiota modification has been attempted by faecal microbiota transplantation (FMT) in cohort studies and in randomised controlled trials. However, heterogeneous protocols, methods, donors, doses and intervals of FMT have all likely contributed to the conflicting evidence base for FMT in UC. Notably, however, a recent meta-analysis has suggested an overall clinical and endoscopic benefit of FMT, at least in the short term, in the treatment of UC [7].

Filgotinib for the treatment of small bowel Crohn’s disease: The DIVERGENCE 1 Trial

D’Haens GR, Lee S, Taylor SA, Serone A, Rimola J, Colombel JF; DIVERGENCE 1 Study Group.

Gastroenterology 2023;165:289–92.e3. doi: 10.1053/j.gastro.2023.03.234.

Introduction

Despite an increasing number of therapeutic options for patients with Crohn's Disease (CD), one-third of individuals develop intolerance or lose response to current pharmacological treatments, and up to half of patients require surgery within ten years of diagnosis. One of the reasons often highlighted for such figures has been the increasing understanding that different sub-types of CD may require different treatment approaches. Indeed, multiple clinical and molecular studies in recent years have demonstrated the differences between ileal and colonic CD in terms of pathophysiological mechanisms [1], as well as clinical features such as disease progression and treatment efficacy. In fact, although there is a lack of reported data on the comparative efficacy of biologics in achieving segment-specific healing in CD [2], evidence from observational studies and post-hoc analyses of interventional trials has shown that deep ulcers in the ileum are more challenging to heal than those located in the colon [3], with rates of endoscopic healing after one year of therapy ranging from 19% to 38% [4].

Dear Y-ECCO Friends,

I trust that you have all had at least some time for rest and relaxation over the summer. It has been an eventful time for the Y-ECCO Committee as well as the delegates and faculty who joined us for our second Y-ECCO Mentorship Forum in Vienna in July. I think it is fair to say that the event was a success, and we even managed a strike or two at the bowling ice-breaker event the evening before! If this sounds like something that may be of interest to you, I’d highly recommend reading the full write-up by Y-ECCO Committee Member, Gabriele Dragoni, in this edition of ECCO News. Our next Y-ECCO Mentorship Forum is planned for summer 2025 and, with your participation, it would be great to see the initiative continue to grow.

Robin Dart © ECCO

Iris Dotan is a gastroenterologist and mucosal immunologist based at Rabin Medical Center, Israel. She is chair of the International Organization for the Study of Inflammatory Bowel Disease (IOIBD) and is well known to ECCO Members through her previous membership of SciCom, her speeches at ECCO Congress and her permanent presence on the Hearts and Minds dancefloor. During a break at the ECCO Congress in Copenhagen, I sat down with Iris to discuss her career, how mentorship has been important to her and, for anyone who has been on a Zoom call with her in the last 3 years, the origins of the beautiful painting she is usually seen sitting in front of.

Vedolizumab for the treatment of chronic pouchitis

Travis S, Silverberg MS, Danese S, et al., EARNEST Study Group

N Engl J Med 2023;388:1191–1200. doi:10.1056/NEJMoa2208450.

Introduction

Proctocolectomy is a curative treatment for medically refractory Ulcerative Colitis (UC). However, a significant number of patients prefer to have continuity of their bowel and undergo a restorative ileal pouch–anal anastomosis (IPAA), after having had an initial subtotal colectomy. Unfortunately, pouchitis is a most common complication in patients with an IPAA: 81% of patients experience pouchitis in their lifetime, with 40% experiencing it in their first year of pouch formation [1]. Multiple factors associated with pouchitis include mutations in NOD2/CARD15, genetic polymorphisms of interleukin-1 receptor antagonists [2–4], tumour necrosis factor allele 2 and toll-like receptor 1 [5].

The cause of pouchitis is multifactorial, including abnormal immune reaction to newly formed IPAA, change in the vascularity and anatomy of the bowel, faecal stasis and many other postulated factors. Single-cell analysis of CD45+ haematopoietic cells in the colon and pouch of UC patients has also highlighted genetic pathways that might contribute to the inflammation and disease severity seen in this condition [6]. However, the aetiology of pouchitis remains poorly understood and this may explain why treatment of this condition has emerged as an important area of unmet research need in the field of IBD. The treatment currently ranges from probiotics, antibiotics, steroids and immunomodulators through to use of biologics. Unfortunately, 50% of patients develop recurrent pouchitis, and up to 20% develop chronic pouchitis. Typically, cases of medically refractory pouchitis have been treated with anti-tumour necrosis factor (anti-TNF), vedolizumab and ustekinumab, but the evidence base for this approach has been very limited, typically comprising only case series and retrospective studies. Until recently, there had been no double-blind, randomised placebo-controlled trial supporting use of any therapeutic in pouchitis. Therefore, there has been significant interest in the study by Travis et al., reporting the first placebo-controlled trial for treatment of pouchitis, with use of vedolizumab. The findings from this trial help to provide evidence supporting the use of gut-selective vedolizumab for patients living with an IPAA.

Ustekinumab improves health-related quality of life in patients with moderate-to-severe Crohn's disease: Results up to week 104 of the STARDUST trial

Panes J, Vermeire S, D’Haens GR, et al., STARDUST Study Group

United European Gastroenterol J 2023 May 4. doi: 10.1002/ueg2.12384. Online ahead of print.

Introduction

The concept of treat to target (T2T) in Crohn’s Disease (CD) involves optimising therapy until a predetermined clinically relevant endpoint is met. In recent years, this endpoint has most commonly been a short-term biomarker response or endoscopic healing, but this has typically been juxtaposed with long-term patient reported outcomes (PROs) such as health-related quality of life (HRQoL) [1]. The international STRIDE-2 guidelines emphasise the need for monitoring at frequent intervals to ensure that treatment targets agreed at the commencement of any therapy are actually being achieved. One of the big unknowns of such strategies, requiring frequent monitoring, has been their cost-efficiency. However, concerns about cost have been balanced by arguments that adequate monitoring may allow earlier and more appropriate initiation of advanced therapies, which may then result in better longer-term outcomes [2].

STARDUST (NCT03107793) was a phase 3b, open-label, randomised controlled trial that compared ustekinumab (UST) T2T with standard-of-care (SoC) treatment strategies in adult patients with moderate to severe CD. The primary results from this trial have previously been reported, and it is notable that endoscopic and biomarker endpoints were not statistically different between the two treatment strategies [3]. However, it is also worth noting that while more patients in the T2T arm received q4w (4-weekly) dosing of UST (18.4% vs 0%), more patients in SoC received q8w (8-weekly) dosing (61.5% vs 38.8%). The original STARDUST trial included 440 patients, of whom 336 completed the first year of treatment and 323 (T2T, n=147; SoC, n=176) were subsequently enrolled to the long-term extension (LTE) period until week 104 (2-year mark). In this study, Panes et al. report on the HRQoL outcomes from patients in the LTE study from the STARDUST trial.