Abstract
Therapeutic progress in inflammatory bowel disease (IBD) has hitherto focused on reducing inflammation to minimise long-term complications. However, strategies aimed at preventing IBD and attenuating its disease course are particularly appealing. This concept is derived from accumulating evidence for an "at-risk" preclinical state and the associations linking genetic background and numerous environmental exposures to disease pathogenesis. Trials in rheumatoid arthritis and type 1 diabetes have identified interventions to delay disease onset, modify the subsequent disease course (potentially protecting against irreversible tissue and end organ damage), and prolong normal quality of life. Prevention and interception trials have major challenges compared with therapeutic trials across a number of domains, including ethical considerations, eligibility criteria, sample size, and optimal endpoints. This Review investigates important factors in designing high-quality prevention trials and evaluates the feasibility and current progress of such trials in IBD, aiming to identify therapeutic strategies for populations at risk.