Over the last decade, there has been rapid expansion of the therapeutic armamentarium, and evolution of treatment strategies, for the management of inflammatory bowel diseases (IBDs). Consequently, there is an increasing need for head-to-head or comparative efficacy trials to inform optimal positioning of therapies, and pragmatic trials comparing treatment strategies to inform treatment approach. In this review, we will discuss the current status and future of comparative efficacy clinical trials in IBD.
Pivotal phase IIIB superiority clinical trials have demonstrated superiority of vedolizumab over adalimumab for achieving clinical remission in patients with moderate-to-severe ulcerative colitis (VARSITY) and failed to demonstrate superiority of ustekinumab over adalimumab in patients with moderate-to-severe Crohn's disease (SEAVUE). Noninferiority clinical trials of biosimilars have confirmed absence of meaningful differences in safety and efficacy of biosimilar infliximab over originator infliximab, as initial therapy or switching stable patients during maintenance. Network meta-analyses, indirect treatment comparison using patient-level data from placebo-controlled trials and real-world observational studies have inform comparative effectiveness and safety of different therapies for management of IBD.
Head-to-head clinical trials are critically important to advance the field of IBD. Comparative efficacy trials are slow and expensive to conduct, may not be broadly generalizable, and are not powered for safety events or other relevant outcomes. Alternative approaches to comparative effectiveness such as network meta-analysis and well designed real-world observational studies are able to bridge gaps in clinical practice.