Invited Lecture(JSGE)
Sat. November 4th   9:00 - 9:30   Room 2: Kobe International Exhibition Hall No.2 Building Hall (South)
Invited Lecture3
 Taking control of disease - Recent advances in IBD treatment
Stefan Schreiber
Department of Internal Medicine I and Institute Clinical Molecular Biology, Christian-Albrechts-University of Kiel, University Hospital Schleswig-Holstein
Therapeutic outcomes of IBD have greatly improved over the last decades. IBD is no longer a deadly disease, but therapeutic efficacy of currently available drugs including targeted therapies still leaves a large opportunity for improvement. IBD is a live-long, chronic disease in which uncontrolled inflammation results in destruction of the involved intestinal wall and causes significant co-morbidities in the ageing patient. Full disease control is therefore an important goal.

Therapeutic goals need to be more ambitious. STRIDE, a consensus on consequent use of singular endpoints is now followed by definition of more stringent combined endpoints. This moves the cohort-based definitions of landmark endpoint in trials to application on a patient-centric level. Individual goal should be reaching comprehensive disease control (CDC), as an innovative combined endpoint comprising symptomatic, endoscopic, histologic, IBD-Q and biochemical remission. Reaching CDC is associated with normalization of general quality of life and thus restoration of health in most patients.

The understanding of trajectories in which symptom-load is analyzed over the entire induction and maintenance time allows the definition of meaningful subpopulations within the overall population by analyzing symptom based response patterns. Re-analyses of phase III trials for vedolizumab, filgotinib and ozanimod in UC show that a group of early super-responders to therapies have a larger likelihood to achieve comprehensive disease control. This work has been pioneered by for these three agents but is now repeated in a large industrial-academic consortium funded by the International Medicine Initiative of the European Commission (3TR) across a large series of phase III trials in both UC and CD.

The separation of meaningful subpopulations by disease behavior should be underpinned by biomarkers discovery that will further enhance the definition of subpopulations and in the future will allow more rapid optimization of therapeutic choices for the individual patient.

While the armamentarium to understand therapeutic success on a patient-individual level grows, it is important to also increase choice by growing the number approved drug classes representing different mechanisms of efficacy. Three developments will be discussed as examples: anti-TL-1A representing a novel treatment target and which is accompanied by a genetic/functional signature for optimal identification of responders among patients, IL-6 trans-signaling inhibition (olamkicept) that provides a broad anti-inflammation without apparent immunosuppression and intestinal microbiome modification by enteral-release nicotinamide, which has shown efficacy reducing symptoms of COVID-19 and which is currently undergoing phase III development in early, mild-moderate UC.
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