Emerging therapies for ulcerative colitis

Abstract

Introduction: Despite advances in the medical management of ulcerative colitis (UC), a subgroup of patients does not respond to currently available therapies. A number of novel drugs are in late stages of clinical development or have recently received regulatory approval for UC.

Areas covered: This review focuses on three drug classes that have recently been approved or are awaiting approval for UC: antibodies against interleukin (IL)-23, sphingosine-1-phosphate receptor (S1PR) modulators, and selective inhibitors of Janus kinases (JAK). We provide an overview of their mechanism of action and summarize available evidence for their efficacy and safety. Finally, we discuss expected future challenges in UC management.

Expert opinion: The evaluated drugs have demonstrated efficacy with an acceptable safety profile. IL-23 antagonists appear to be safest with very few (serious) adverse events, while the use of S1PR modulators or JAK inhibitors has been associated with infectious and cardiovascular/thromboembolic events, albeit in low numbers. Although advances in drug development are promising, there is an urgent need for (validated) biomarkers to guide rational treatment selection. The scarcity of head-to-head trials also complicates comparisons between available drugs. Breaking the therapeutic ceiling of efficacy in UC will require marked advances in management extending well beyond drug development.

Keywords: Etrasimod; filgotinib; guselkumab; inflammatory bowel disease; mirikizumab; ozanimod; ulcerative colitis; upadacitinib.