Evolution of Clinical Trials in Inflammatory Bowel Diseases.

PURPOSE OF REVIEW: Since the first clinical trial of cortisone in ulcerative colitis in 1955, remarkable progress has been made in the design and conduct of clinical trials in inflammatory bowel diseases (IBD). In this review article, we will discuss evolution of clinical trials in IBD over the last 3-5 years.

RECENT FINDINGS: Recognizing limitations intrinsic to clinical disease activity indices in IBD, regulatory authorities have recommended evaluating co-primary endpoints of patient-reported outcomes and endoscopic disease activity in clinical trials. Biomarker-enriched trial enrolment and central endoscopy reading have emerged as critical events in trial recruitment and outcome assessment and have driven placebo response rates down. While trials of novel biologic therapies and advanced small molecules continue at an accelerated pace, pragmatic comparative efficacy trials of treatment strategy aimed at optimizing current therapies (such as early combined immunosuppression [REACT], tight disease control [CALM], therapeutic drug monitoring [TAXIT, TAILORIX]) have directly informed clinical practice. With emphasis on value-based care and population health management, multi-pronged remote monitoring, self-management, and telemedicine approaches in the era of smartphones have re-emerged with promise. Non-conventional therapies such as fecal microbiota transplantation, though still experimental, have provided insight into disease pathogenesis and offered hope for microbial manipulation strategies for treating these complex diseases. Clinical trials have rapidly evolved over the last 5 years not only focusing on novel therapies but also optimizing existing treatment approaches and population health management. Over the next decade, these trials will continue to advance the field, and be readily translatable into clinical practice.