The Y-ECCO Interview Corner is a chance to get to know people inside ECCO. Mark Samaan has been a fixture on the Y-ECCO Committee since 2018, and is the current Chair. He is a consultant gastroenterologist with an interest in IBD clinical trials. He has had an education in IBD spanning two continents and is a keen swimmer. We sat down to talk about his experience in IBD, and what it’s like to support a football team who famously achieve very little.
Submucosal injection of the RNA nucleotide GUT-1 in active ulcerative colitis patients: A randomized, double-blind, placebo-controlled phase 2a induction trial.
Atreya R, Kuhbacher T, Waldner M, et al.
J Crohns Colitis 2023. doi: 10.1093/ecco-jcc/jjad162. Online ahead of print.
Despite an increasing number of therapeutic options for Ulcerative Colitis (UC), many patients still have disease which progresses over time, and there has been renewed interest in and improved understanding of the chronic fibrosis and remodelling that occurs in UC [1–3]. In particular, there has been a growing appreciation of both the importance of the extracellular matrix (ECM) for remodelling in UC and the potential to target the ECM with new therapeutic agents [4]. One such target is carbohydrate sulphotransferase 15 (CHST15). This is a type II transmembrane Golgi protein that biosynthesises highly sulphated disaccharide units (E-units) of chondroitin sulphate, which binds to various functional proteins and pathogenic microorganisms. Targeting this molecule in mouse models has previously been shown to offer promising signals for ameliorating colitis [5]. Based on this promising pre-clinical data, blockade of CHST15 has emerged as a potentially promising therapeutic target, and such blockade can be achieved by a silencing RNA oligonucleotide molecule called GUT-1 (previously called STNM01). A prior phase I clinical trial demonstrated the safety of GUT-1 in patients with Crohn’s Disease [6]. Accordingly, Atreya and colleagues now sought to evaluate the safety, as well as the efficacy and mode of action, of GUT-1 in patients with UC as part of a phase IIa placebo-controlled, clinical trial.
The management of Crohn’s Disease (CD) is dependent on many factors, including disease activity, site of involvement and the need to tailor treatment for each individual patient [1]. Moreover, features such as obstruction, fistulation, strictures and abscesses can all add to the complexity of CD management. While surgery has played a large role in the management of these patients, it is by no means a cure and the risk of relapse and repeat surgeries remains high [2, 3]. Accordingly, there continues to be a large unmet need for the development of novel medications that target distinct mechanisms of action in order to provide symptomatic and endoscopic control for patients with active disease. In parallel with this need to develop new medications, there has been an increasing desire for fast-acting medications, and movement towards oral administration, which may help both to reduce costs for hospitals and patients and to enhance aspects that are important to patients, such as quality of life and work productivity [4, 5].
Intestinal barrier healing is superior to endoscopic and histologic remission for predicting major adverse outcomes in Inflammatory Bowel Disease: The Prospective ERIca Trial
Mucosal healing (MH) in both Crohn's Disease (CD) and Ulcerative Colitis (UC) has been recognised as an important treatment target for many years. Indeed, the 2021 update of the Selecting Therapeutic Targets (STRIDE) consensus reaffirmed MH as the top priority among long-term treatment objectives [1]. Nonetheless, it is important to note that endoscopic inflammation may not always mirror the histological picture. Histological healing is an emerging endpoint in IBD. This is particularly true in UC, in which it represents a deeper level of recovery with some early evidence for correlation with better long-term outcomes; for CD, however, findings have been more controversial [2, 3]. Despite the increasing focus on histology, histological scoring systems are complex, with only two validated ones, both in the setting of UC, i.e. there is no validated scoring system in the context of CD.
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!
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.
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.
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.
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].
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].
Robin Dart
Gabriele Dragoni
