Abstract and Introduction
Background: The landscape of inflammatory bowel disease (IBD) treatment is rapidly expanding with the development of new therapeutic options.
Aim: To review the mechanisms of action and the available clinical trial data on emerging drug therapies for IBD.
Methods: Pubmed, Medline and Cochrane databases were queried up to July 2021 using keywords "inflammatory bowel disease," "IBD," "Crohn's disease," "ulcerative colitis" and "trial," "phase" and "study." In addition, we manually reviewed the grey literature including clinical trial registries and abstracts from major gastroenterology conferences in 2020 and 2021 to include pertinent information.
Results: In ulcerative colitis (UC), phase 2b and/or phase 3 studies met primary endpoints for S1P receptor agonists (estrasimod, ozanimod), anti-IL-23 agent (mirikizumab), anti-lymphocyte trafficking agents (ontamalimab, subcutaneous vedolizumab), JAK inhibitors (upadacitinib, filgotinib) and TLR9 agonist (cobitolimod). In Crohn's disease (CD), anti-IL-23 agents (risankizumab, mirikizumab, guselkumab), JAK inhibitors (upadacitinib, filgotinib) and anti-lymphocyte trafficking agents (ontamalimab, etrolizumab) met primary endpoints in randomised controlled clinical trials.
Conclusion: Several new IBD drug therapies have positive efficacy and safety data in early clinical trials, and there are several drugs in the therapeutic pipeline. As more treatments for CD and UC are approved for clinical use, research to assess predictors of response to therapy and head-to-head trials is needed to inform providers on how to best position therapeutic options for patients with IBD.
Inflammatory bowel diseases (IBD), consisting of Crohn's disease (CD) and ulcerative colitis (UC), are chronic inflammatory conditions of the gastrointestinal tract. Most patients with these conditions require long-term pharmacological therapy to induce and to maintain remission. These treatments reduce the risk of flare and the need for corticosteroids, hospitalisation and surgery. Currently, approved biological and small molecule therapies for IBD are anti-TNF drugs (infliximab, adalimumab, golimumab, certolizumab), anti-integrin therapies (vedolizumab, natalizumab), anti-IL-12/23 therapy (ustekinumab), JAK inhibitor (tofacitinib) and S1P modulator (ozanimod).
Despite the available treatments, many patients are in need of new options due to nonresponse, loss of response or intolerance to therapies. Research involving new IBD therapies is expanding rapidly with the development of drugs with novel mechanisms of action, more convenient modes of administration and possibly more favourable safety profiles. Many of these treatments are showing promising data in clinical trials. In this review, we describe novel and emerging drug therapies for CD and UC and summarise available data.
Aliment Pharmacol Ther. 2022;55(7):789-804. © 2022 Blackwell Publishing