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.

Very Early Onset Inflammatory Bowel Disease (VEO-IBD) is a complex subset of IBD that uniquely affects children under six years of age [1]. This category includes neonatal onset (within the first month of life), infantile onset (before two years) and early childhood onset (between two and six years) [2]. In comparison with patients with older onset IBD, those with VEO-IBD demonstrate a more heterogeneous phenotype and the aetiology is more closely related (in approximately 25%–30% of cases) to monogenic or digenic defects involving genes associated with primary immunodeficiency [3]. Moreover, VEO-IBD patients show higher rates of positive family history, a more aggressive clinical trajectory and increased resistance to conventional therapies effective in managing IBD among older patients [4].

Firas Rinawi © Firas Rinawi

Primary sclerosing cholangitis (PSC) is less common in paediatrics than in adults, affecting 0.2–1.5 per 100,000 children (~20% the prevalence in adults). Those diagnosed in childhood are typically older than ten years, and there is a male predilection [1]. The aetiology of PSC is likely a multifactorial combination of an inherited predisposition, gut microbiome, gut–liver communication, bile homeostasis and downstream effects on the immune system which lead to biliary inflammation and fibrosis [2].

How do you make a surgeon? Not by the preliminaries, the 6-7 years of medical college and the years that follow in residency training, but by the six or seven years subsequently spent after medical school learning the surgical trade. Exactly what happens in this apprenticeship that transforms him\her from a helpless, frightened medical school graduate into a (hopefully) capable and confident surgeon?

Up to one-third of patients with Inflammatory Bowel Disease (IBD) have persistent bowel symptoms despite apparent control of intestinal inflammation [1]. These symptoms fit with irritable bowel syndrome (IBS), a type of disorder of gut–brain interactions (DGBI). DGBI respond poorly to the pharmacological agents that are typically used to target inflammation in IBD. Thus, as clinicians, our challenges are to identify IBS-like symptoms, which is more easily achieved in those with quiescent disease, and to find suitable treatments for control of non-inflammatory symptoms.

Wladzia Czuber-Dochan  © ECCO

Marie Andersson © ECCO

It is that time of year when we write to tell you, with great pleasure, about the N-ECCO Activities scheduled for the 19^th Congress of ECCO, to be held on February 21–24, 2024, in Stockholm, Sweden. As in previous years, the N-ECCO Committee has worked hard to put together a broad programme covering clinical, educational and research topics.

Hannah Gordon © ECCO

The second ECCO Guideline on Malignancy in IBD was published in JCC late last year, supported by working group leads Livia Biancone, Gionata Fiorino, Kostas Katsanos and Uri Kopylov. The ethos of this guideline was to couple evidence-based medicine with provision of practical advice, with a view to enhancing patient care worldwide. We worked alongside the ECCO Guidelines Team to undertake systematic reviews for each statement, selecting topics that are frequently relevant to patients with IBD as well as those which generate debate in the MDT.

Hannah Gordon © ECCO

The second ECCO Guideline on Malignancy in IBD was published in JCC late last year, supported by working group leads Livia Biancone, Gionata Fiorino, Kostas Katsanos and Uri Kopylov. The ethos of this guideline was to couple evidence-based medicine with provision of practical advice, with a view to enhancing patient care worldwide. We worked alongside the ECCO Guidelines Team to undertake systematic reviews for each statement, selecting topics that are frequently relevant to patients with IBD as well as those which generate debate in the MDT.

Firas Rinawi © Firas Rinawi

The 71^st ECCO Educational Workshop took place at The Westin Zagreb, Croatia, on June 16, 2023. This event brought together participants from Croatia, Slovenia, Serbia, Hungary, Bosnia and Herzegovina, and Italy. The workshop focused on the field of paediatric IBD and featured interactive discussions on various clinical scenarios and hot topics in paediatric IBD.