ClinCom Educational Courses at ECCO'23

Peter Bossuyt, ECCO Member

Peter Bossuyt

Designing, organising and performing clinical trials in IBD is a challenge. Drug development trials often follow the well-known pathways, with established endpoints and a more or less standardised study design. Things become more complicated when the clinical researcher departs from these trusted routes.  In this context, ClinCom (the Clinical Research Committee of ECCO) organised two courses during the last ECCO Congress in Copenhagen.

During the 5th School for Clinical Trialists we tackled two topics. The first session was dedicated to taboo outcomes, and this was followed by a session on treatments beyond IBD drugs.  Patients with IBD have to deal with multiple taboos, including, for example, incontinence, sexuality and stress management. The session opened with an interesting tandem talk between Wladyslawa Czuber-Dochan (IBD Nurse) and Sameer Mannick (patient with IBD). They highlighted the well-known but also often-ignored clinical problems encountered by patients with IBD. They also discussed how an open relationship between the health care professional and the patient may help in starting discussion of these issues, which have an important impact on quality of life. Fatigue is one of the main problems that patients with IBD have to cope with, even when the disease is in remission. Janneke van der Woude discussed the hurdles encountered in the assessment and quantification of fatigue in patients with IBD. Multiple pharmacological clinical trials have yielded negative outcomes, mainly because the multifactorial pathophysiology is still to be unravelled. In this context, clinical trials in IBD-related fatigue should follow a strict methodology in measuring and assessing fatigue. By combining a basic science hypothesis with (probably) multilevel clinical and pharmacological interventions, we might make progress in understanding the mechanism of fatigue in IBD.  Finally, Laurie Keefer gave a fascinating lecture on coping strategies in IBD. She highlighted the importance of positive psychology and the techniques for disease self-management. This patient-centric approach not only makes patients responsible for their own care but also strengthens their ability to cope with unplanned care. Building resilience is a key factor in this process.

Treating patients with IBD is not only about drugs. The multifactorial pathophysiology is based on the interplay between genetic predisposition, environmental factors, diet, microbiome and the immune system, to name the most important ones. Johan Van Limbergen reviewed the current knowledge on anti-inflammatory diets. Recent evolutions have broadened the spectrum of potential diets, certainly in paediatric IBD. Currently, beyond exclusive enteral nutrition or parenteral nutrition there are newer strategies like the Crohn's Disease Exclusive Diet (CDED) and the CD Treatment-With-Eating Diet (CD-TREAT), which have recently been shown to be efficacious. Also, the metabolome and microbiome changes that are induced by the different diets provide new insights into the pathogenesis of the disease. This talk provided an excellent introduction for the presentation by Jordi Guardiola on sustained eubiosis. Dysbiosis is suggested to be one of the triggers of IBD, although there is an ongoing debate on what is cause and what is consequence. Strategies to restore eubiosis, installing a new equilibrium in the GI tract, may theoretically lead to a cure for IBD. Finally, Gerhard Rogler discussed the topic of environmental and life-style changes as part of the treatment approach in IBD. Based on a large-scale experience from the Swiss IBD cohort, he highlighted the impact of factors like pollution, stress, urbanisation and physical activity on the pathogenesis of the disease. The difficulty that we face, however, is how to impact on these factors and accordingly study the impact of environmental and life-style changes in a prospective way.

During the 6th Advanced ECCO: EduCational COurse for Industry we looked into the future. We are currently facing a situation in which multiple new compounds and new monoclonal antibodies (MOAs) are becoming available for the treatment of IBD. Accordingly, more and more questions are arising on how to position the new compounds within our treatment algorithm for IBD. Britta Siegmund opened proceedings by presenting a nice overview of the compounds that have entered the market over the last two years, with the most important ones being IL-23 antagonists, selective JAK inhibitors and S1P agonists. Peter Irving subsequently discussed the rationale for positioning the existing and the newer compounds.  Many factors influence the positioning of a specific compound and there is certainly no golden recipe. Each physician has to take into account efficacy, safety, extra-intestinal manifestations, patient characteristics (clinical aspects, frailty, compliance, comorbidities etc.) and reimbursement criteria in order to make a final decision. Finally, James Lindsay discussed the future of drug development. In a competitive environment where recruitment is slowing down and resources are limited, original approaches are needed.  During the panel discussion the speakers discussed, together with representatives from pharma, the hurdles in executing clinical trials in the current context.

The second hot topic for the near future is the combination of advanced treatments for patients with IBD. Jean-Frédéric Colombel elegantly explained the mechanistic considerations to be taken into account when combining drugs. The ideal approach would be an orthogonal approach with minimal cross-talk among different MOAs. However, given the important overlap between inflammation and immune response, pure orthogonal strategies will be unlikely in IBD. Still, the best approach is to select strategies based on mechanistic data with an optimal additional effect. Peter Bossuyt then reviewed the existing data on the efficacy of combination strategies. There are several historical examples of combinations but also some recent pilot trials. The current results are not breaking the therapeutic ceiling, as we would have expected, but better mechanistic pre-work and patient selection may improve outcomes in the future. Finally, Laurent Beaugerie focused on the safety aspects of combining treatments in IBD. From the data he presented, it could be concluded that there is an increased risk for overall adverse events when combining treatments in IBD. However, the benefits often outweigh the risk in patients with severe IBD. The highest risk of severe adverse events is seen in older patients. In this group of patients, and certainly those with multiple co-morbidities, one should be extremely cautious. During the panel discussion, it was further discussed how to prioritise research into combination of treatments and how to use resources optimally.

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    Posted in ECCO News, Committee News, ECCO'23, ClinCom, Volume 18, Issue 1