Y-ECCO
26October2023

Y-ECCO Literature Review: Maria Manuela Estevinho

Maria Manuela Estevinho

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.


Maria M. Estevinho
© Maria M. Estevinho

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].

Posted in ECCO News, Y-ECCO Literature Reviews, Committee News, Volume 18, Issue 3, Y-ECCO

26October2023

Y-ECCO Members’ Address

Mark Samaan, Y-ECCO Chair

Mark Samaan
© ECCO

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.

Posted in ECCO News, Committee News, Volume 18, Issue 3, Y-ECCO

15June2023

Y-ECCO Interview Corner: Iris Dotan

Robin Dart, Y-ECCO Member

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.

Posted in ECCO News, Committee News, Volume 18, Issue 2, Y-ECCO

15June2023

Y-ECCO Literature Review: Mohammed Tauseef Sharip

Mohammed Tauseef Sharip

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.


Mohammed T. Sharip
© Mohammed T. Sharip

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.

Posted in ECCO News, Y-ECCO Literature Reviews, Committee News, Volume 18, Issue 2, Y-ECCO

15June2023

Y-ECCO Literature Review: Joseph Sleiman

Joseph Sleiman

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.


Joseph Sleiman
© Joseph Sleiman

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.

Posted in ECCO News, Y-ECCO Literature Reviews, Committee News, Volume 18, Issue 2, Y-ECCO

15June2023

Y-ECCO Literature Review: Stephany Barreda

Stephany Barreda

Efficacy of filgotinib in patients with ulcerative colitis by line of therapy in the phase 2b/3 SELECTION trial

Dotan I, Feagan BG, Taliadouros V, et al.

J Crohns Colitis 2023 Mar 16. doi:10.1093/ecco-jcc/jjad039. Online ahead of print.


Stephany Barreda
© Stephany Barreda

Introduction

In recent years, there has been significant optimism in the field with the arrival of newer licensed therapies for patients living with IBD [1]. Alongside the welcome arrival of new therapeutics, there has also been an appreciation that many (but not all) patients may have preferences for oral medications [2]. In particular, targeting Janus kinases (JAKs) with oral small molecule treatments has proved to be a promising strategy. Indeed, tofacitinib, a pan-JAK inhibitor, was shown to have efficacy in patients with Ulcerative Colitis (UC), even in some instances where there had been loss of response or non-response to all prior licensed biologic options [3]. With growing understanding of the pathways involved in UC, preferential inhibition of JAK1 has been investigated in the field of IBD, including with the JAK1 inhibitor, filgotinib. This is a medication already licensed for some rheumatological conditions and it was recently assessed in the context of UC in the phase 2b/3 SELECTION trial – with the results having previously been published, and demonstrating superiority of filgotinib over placebo in UC [4]. In this current study, Dotan et al. assess efficacy of filgotinib based on prior treatment exposure and number of lines of therapy for instances of previous exposure to biologic therapy, based on a post-hoc analysis of data from the SELECTION trial. This study contributes to our understanding of how to sequence and position a new advanced therapy, in the context of a growing armamentarium of treatment options for patients living with UC.

Posted in ECCO News, Y-ECCO Literature Reviews, Committee News, Volume 18, Issue 2, Y-ECCO

15June2023

Y-ECCO Members’ Address

Mark Samaan, Y-ECCO Chair

Mark Samaan
© ECCO

Dear Y-ECCO Friends,

Although it still feels as though ECCO’23 has only just exited our rear-view mirrors, I’m sure many of you have moved onto preparing your abstract submissions and it’s worth remembering that the abstract submission window for ECCO’24 will soon be open! However, before getting started with that (there’s still plenty of time, after all) I would very much encourage you to take a look at the recently published IBD Communication Toolbox. Whatever type of ECCO Membership you hold, I can assure you that there’s something there for everyone.

Posted in ECCO News, Committee News, Volume 18, Issue 2, Y-ECCO

27April2023

Y-ECCO Interview Corner: Charlotte Hedin

Robin Dart, Y-ECCO Member

Robin Dart
© ECCO

The return of a physical ECCO Congress finally gave me the chance to interview people in person for ECCO News. So, after an early morning start, the outgoing Chair of Y-ECCO, Charlotte Hedin, and I sat down to talk about what led her into gastroenterology, the impact of moving country mid-career and the Y-ECCO Communication Toolbox, which has recently been made available on the ECCO e-Learning Platform.

Posted in ECCO News, Committee News, Volume 18, Issue 1, Y-ECCO

27April2023

Y-ECCO Literature Review: Dean Seah

Dean Seah

Guselkumab plus golimumab combination therapy versus guselkumab or golimumab monotherapy in patients with ulcerative colitis (VEGA): A randomised, double-blind, controlled, phase 2, proof-of-concept trial

Feagan BG, Sands BE, Sandborn WJ, et al.

Lancet Gastroenterol Hepatol 2023;8:307–20.


Dean Seah 
© Dean Seah 

Introduction

Despite a growing armamentarium of advanced therapies for Ulcerative Colitis (UC), fewer than 40% of patients maintain clinical remission at 12 months [1]. Combination therapy utilising dual biologic or small molecule agents can be considered in highly selected, medically refractory cases; however, robust data to support dual therapy in routine clinical practice are still lacking [2]. Inhibitors of TNF-α and IL-23 have demonstrated efficacy in the treatment of UC [3,4]. Data emerging from animal studies have suggested that their use in combination reduces colitis synergistically and may be more efficacious than treatment with either monotherapy [5].

This randomised double-blinded controlled phase 2 trial, named the VEGA trial, was conducted across 54 sites internationally and aimed to determine the efficacy and safety of combination therapy with guselkumab (GUS), an IL-23 p19 antagonist, plus golimumab (GOL), a TNF-α inhibitor, compared with either monotherapy in UC.

Posted in ECCO News, Y-ECCO Literature Reviews, Committee News, Volume 18, Issue 1, Y-ECCO

27April2023

Y-ECCO Literature Review: Andrea Centritto

Andrea Centritto

Point-of-care intestinal ultrasound in IBD patients: Disease management and diagnostic yield in a real-world cohort and proposal of a point-of-care algorithm

Bots S, De Voogd F, De Jong M, et al.

J Crohns Colitis 2022;16:606–615.


Andrea Centritto
© Andrea Centritto

Introduction

Intestinal ultrasound (IUS) is an inexpensive, non-invasive, safe and repeatable, dynamic cross-sectional imaging technique for IBD. It has been demonstrated to be accurate and reliable both for initial diagnosis of IBD and for follow-up monitoring [1]. Huge advantages of IUS are that it does not need any prior preparation of the patient and provides a real-time result. IUS can be performed in various hospital settings, which makes it the only point-of-care (POC) imaging technique available today [2].

The impact of POC IUS on daily decision making and the evolution in its use over the years were evaluated in this retrospective study, which included two consecutive cohorts of IBD patients in a real-world outpatient setting. The first cohort of patients, included between January 2016 and July 2018, was compared with a second cohort collected between October 2019 and December 2019.

Posted in ECCO News, Y-ECCO Literature Reviews, Committee News, Volume 18, Issue 1, Y-ECCO