Harry Sokol is a prominent gastroenterologist at Saint Antoine Hospital and Sorbonne Université and the President of the French Group of Faecal Microbiota Transplantation. In this edition of the ECCO Interview Corner, Professor Sokol shares his journey into gastroenterology, his pioneering work on Inflammatory Bowel Disease (IBD) and the gut microbiome and his vision for the future research.
A biomarker-stratified comparison of top-down versus accelerated step-up treatment strategies for patients with newly diagnosed Crohn’s disease (PROFILE): a multicentre, open-label randomised controlled trial
There is debate on the optimal management of newly diagnosed active Crohn’s Disease (CD). The most commonly used treatment strategy around the world is a “step-up” treatment approach. This involves initial use of steroids at diagnosis to induce remission, followed by introduction of immunomodulators such as azathioprine to maintain that remission. Subsequently, if this treatment fails to control inflammation, patients are escalated to advanced therapies such as anti-TNF biological agents. When performed rapidly, this can be referred to as “accelerated step-up” treatment, and indeed in many countries this accelerated step-up approach is considered standard of care (conventional) treatment. An alternative treatment strategy is a more “top-down” approach , where there is early introduction of an advanced therapy, typically an anti-TNF agent.
Inflammatory Bowel Diseases (IBD), comprising the two most common subtypes of Crohn's Disease (CD) and Ulcerative Colitis (UC), are chronic inflammatory conditions of the gastrointestinal tract. Tumour necrosis factor (TNF) inhibitors, particularly infliximab, have been pivotal in the management of moderate to severe IBD. While effective, intravenous administration of infliximab typically involves regular visits to hospital-based infusion centres. Particularly from a patient convenience point of view, many individuals would prefer to administer medication at home without the need to attend infusion centres and without the need for intravenous administration. The development of a subcutaneous (SC) formulation of infliximab (CT-P13) aims to enhance patient convenience and adherence by allowing self-administration at home [1–3] . In the LIBERTY trials, Hanauer and colleagues sought to examine the efficacy and safety of CT-P13 SC as maintenance therapy in IBD, in two randomised, placebo-controlled phase 3 trials.
At present, disease activity in Inflammatory Bowel Disease (IBD) is primarily monitored using faecal calprotectin, serum C-reactive protein (CRP) and endoscopic examination [1]. Whilst these are powerful tools, all three approaches have notable limitations. Faecal calprotectin testing requires a patient either to provide a stool sample whilst attending clinic or to return with a sample at a later date. Serum CRP requires a blood sample to be taken by a healthcare professional and endoscopy is invasive. Interleukin (IL)-6, whilst not routinely used in clinical settings to monitor disease activity, is known to play a role in IBD pathogenesis by increasing T-cell resistance against apoptosis, resulting in chronic inflammation [2].
As we move into the final quarter of the year, this is the perfect time to reflect on our collective achievements and to set our sights on the exciting events that lie ahead.
At Y-ECCO, we’ve been diligently crafting an innovative programme for our upcoming Y-ECCO Science Workshop, designed to bring together our diverse community of basic scientists, clinicians and clinician-scientists. In the last edition of ECCO News, I offered a sneak peek at our shift from the Basic Science Workshop to a more inclusive Science Workshop. This transformation reflects our commitment to fostering collaboration and engagement among all Y-ECCO Members.
This issue's Interview Corner is dedicated to Fernando Magro, the current President-Elect of ECCO. Fernando Magro is a gastroenterologist and head of the Clinical Pharmacology Department at University Hospital São João in Porto, Portugal, where he also serves as a Professor of Pharmacology and Therapeutics. He is a founding member of the Portuguese Inflammatory Bowel Disease Group and an active researcher focusing on the management, treatment and prognosis of IBD. His dedication to ECCO is nothing new, as you'll read below. I took this opportunity to learn more about the academic and clinical journey of the person I'm glad to call my mentor.
Increased versus conventional adalimumab dose intervals for patients with Crohn’s disease in stable remission (LADI): a pragmatic, open-label, non-inferiority, randomised controlled trial
van Linschoten RCA, Jansen FM, Pauwels RWM, et al.
Adalimumab is an effective and safe treatment for Crohn’s Disease (CD). However, both patients and healthcare professionals may wish to mitigate medication exposure due to potential safety and economic concerns in the long term. Since a high relapse rate follows drug discontinuation, treatment de-escalation without actually stopping the medication may allow for decreasing drug exposure while maintaining efficacy. In two observational studies, de-escalation from a 2-week to a 3-week adalimumab dosing interval was successful in most of the patients, though reversal to a 2-week dosing interval was required in about 30% due to insufficient disease control [1, 2]. The Lengthening Adalimumab Dosing Interval (LADI) study is a pragmatic, open-label, multicentre, non-inferiority, parallel, randomised controlled trial conducted in the Netherlands and specifically designed to address this knowledge gap [3].
Withdrawal of immunomodulators or TNF antagonists in patients with inflammatory bowel diseases in remission on combination therapy: A systematic review and meta-analysis
Combination therapy with anti-TNF inhibitors (ATI) and immunomodulator (IMM) therapy remains an efficacious treatment strategy for disease control in moderate to severe Inflammatory Bowel Disease (IBD). This conclusion was largely based on the findings of landmark trials, SONIC and UC SUCCESS, which showed combination therapy to be far superior to monotherapy in achieving durable clinical and endoscopic remission in IBD [1, 2].
However, combination treatment with ATI and IMM can lead to increased risk of infection and malignancy. Whilst withdrawal of combination treatment once the patient is in disease remission can reduce the risk of treatment-related complications as well as the cost to health services, there remains a risk of relapse of previously controlled disease. At present there is no consensus amongst global clinical guidelines as to the appropriate duration of use of combination therapy. Thus, clinicians often find decisions related to withdrawal of treatment quite challenging.
The gut microbiota of patients with Inflammatory Bowel Disease (IBD) may have a role in disease aetiology and course [1]. Patients with IBD often have dysbiotic microbiota, with lower microbial diversity and cell counts, with both absolute and relative abundance of commensal microorganisms [2, 3]. Conversely, during remission following anti-inflammatory therapy, the gut microbiota has been observed to shift to a more eubiosis-like composition [3–6]. Furthermore, lower proportions of taxa with pro-inflammatory properties and mucus-degrading bacteria, as well as higher proportions of short-chain fatty acid-producing bacteria, have been associated with a higher likelihood of favourable outcomes with medical treatment [3, 5, 6]. In this study, Caenepeel and colleagues monitored changes in intestinal microbiota and stool features in order to develop and validate a predictive model to assist clinicians in determining a patient-specific therapeutic strategy.
Can you believe that it’s been only four months since the last ECCO Congress? I bet that many of you are already knee-deep in exciting research for ECCO 2025 in Berlin, so mark your calendars and keep an eye open for the abstract submission deadline. You can’t miss that, as we want to see your top-notch research! Maybe you are the next Y-ECCO Best Abstract awardee!
Maria Manuela Estevinho
Bram Verstockt
