Novel Therapies in Inflammatory Bowel Disease: An Evaluation of the Evidence

INTRODUCTION Several new agents with diff erent mechanisms of action are being explored for use in infl ammatory bowel diseases (IBD). Some focus on optimizing existing therapies used for other indications (budesonide MMX, fecal microbiota transplantation (FMT)), whereas others work by new and novel mechanisms, including blocking cellular adhesion, manipulation of downstream infl ammatory cell signaling, or strengthening the mucosal barrier. Th is article summarizes some therapies that have recently come to market or that have shown signifi cant promise in late-phase studies of IBD. For several decades, the medical options to manage IBD were limited to corticosteroids, thiopurines, and 5-aminosalicylates. Scientifi c advances have increased our understanding of the infl ammatory pathways in IBD. Th e introduction of anti-tumor necrosis factor (anti-TNF) therapies for IBD, including Crohn’s disease (CD) and ulcerative colitis (UC), was a landmark in the treatment of IBD. Th e future looks even more promising, as several other novel treatment options have been recently identifi ed and clinical studies are underway to determine the effi cacy and safety of these therapies. Th is review will highlight some recently approved and upcoming therapies that have promise for management of IBD now and in the future. Of note is the challenge of clinical trial design and studies that have yielded positive early-phase results but do not translate into positive late-phase study outcomes. Th e reasons for this are many, including heterogeneity of patient and disease types, limitations to the instruments used to measure disease activity, high placebo response rates, and, in some cases, observed variability associated with international study sites and locations.