For this Y-ECCO Interview Corner we met with Shaji Sebastian, who is known to everyone as Seb, on the Friday of the ECCO Congress. Seb has had a long association with ECCO. He is the outgoing Chair of ClinCom and was elected as Treasurer of ECCO at this year’s General Assembly. He is a consultant in Hull in the North of England, having got there through a somewhat circuitous route, as we will hear...
The SONIC trial yielded seminal findings showing that the combination of infliximab and azathioprine is more effective than either treatment alone for the maintenance of remission in patients with Crohn’s Disease (CD) [1]. In recent years, despite the availability of an increasing number of biologics and small molecules to treat CD, a ceiling of therapeutic efficacy has been reached [2]. Therefore, there has been a resurgence of interest in whether this therapeutic ceiling “effect” can be overcome with new treatment combinations. In the EXPLORER study, the efficacy and safety of triple combination therapy was assessed using two biologics with different modes of action in association with methotrexate for the treatment of CD.
Higher intra-abdominal visceral adipose tissue mass is associated with lower rates of clinical and endoscopic remission in patients with inflammatory bowel diseases initiating biologic therapy: Results of the Constellation Study
Despite an expanding therapeutic arsenal, a considerable proportion of patients with Crohn's Disease (CD) and Ulcerative Colitis (UC) fail to achieve or sustain therapeutic responses [1, 2]. Mechanisms contributing to this failure, particularly with respect to biologic therapy, are only partially understood [3]. Uncovering the mechanisms behind loss of response may help to enhance the efficacy of existing treatment options or to develop alternative options for the future.
Some investigations have noted an association between obesity, high intra-abdominal visceral adipose tissue (IA-VAT) mass and unfavourable outcomes in individuals with Inflammatory Bowel Disease (IBD). However, these observations have been constrained by their methodology and have to date focused only on patients having treatment with anti-tumour necrosis factor alpha (anti-TNF-α) agents [4–6], limiting their scope.
The Constellation Study by Yarur and colleagues aimed to investigate the relationship between IA-VAT in patients with IBD and the response to biologic drugs with multiple different mechanisms of action.
Patients will often ask, “What causes Inflammatory Bowel Disease?” Frustratingly, we remain unable to answer this seemingly simple question, beyond the often-quoted paradigm that unknown environmental factors trigger inflammation in genetically susceptible individuals. Although our understanding of the immune response in IBD has reached phenomenally detailed levels of resolution, the nature and identity of the initial environmental triggers of IBD have continued to remain a mystery. The strong relationship between socioeconomic development and IBD incidence is tantalising evidence of a definable environmental toxin and various substances such as processed food additives have recently been highlighted as potential suspects [1]. However, searching for the causative agent is like looking for a needle in a haystack as the candidate list includes literally every small molecule in existence!
The Y-ECCO Science Workshop celebrated its 10th edition during the recent ECCO Congress in Stockholm. Held on February 21, 2024, the workshop invited young basic scientists to present and discuss their research with peers and senior opinion leaders. This year’s edition proved a tremendous success, inspiring Y-ECCO Members with a friendly yet intellectually stimulating atmosphere and encouraging them to broaden their knowledge and to prepare for more challenging research steps.
I hope you are all doing well and enjoyed an insightful and interesting ECCO Congress in Stockholm recently. At ECCO 2024, the Y-ECCO Team had to say goodbye to our outgoing Chair, Mark Samaan, who has been exemplary in the role over the past year. On behalf of the entire Y-ECCO Community, thanks Mark! It has been an absolute pleasure working with you, while further expanding the committee under your leadership.
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.
Robin Dart
Bram Verstockt
Robin Dart
