Drugs. 2023 Jul;83(10):873-891. doi: 10.1007/s40265-023-01882-9.Epub 2023 Jun 2.

Sudheer K Vuyyuru ^1 2, Lisa M Shackelton ², Jurij Hanzel ^2 3, Christopher Ma ^2 4, Vipul Jairath ^1 2, Brian G Feagan ^5 6 7

Author information

¹Department of Medicine, Division of Gastroenterology, Western University, London, ON, Canada.

²Alimentiv Inc., London, ON, Canada.

³Department of Gastroenterology, UMC Ljubljana, University of Ljubljana, Ljubljana, Slovenia.

⁴Division of Gastroenterology and Hepatology, Departments of Medicine and Community Health Sciences, University of Calgary, Calgary, AB, Canada.

⁵Department of Medicine, Division of Gastroenterology, Western University, London, ON, Canada. brian.feagan@alimentiv.com.

⁶Alimentiv Inc., London, ON, Canada. brian.feagan@alimentiv.com.

⁷Department of Epidemiology and Biostatistics, Western University, London, ON, Canada. brian.feagan@alimentiv.com.

Abstract

Inflammatory bowel disease, including Crohn's disease and ulcerative colitis, comprises multiple complex immune-mediated disorders. Early diagnosis and prompt disease control may prevent long-term complications and hospitalization. The therapeutic options have expanded in the last two decades, with the development of biologics and small molecules targeting specific pathways implicated in inflammatory bowel disease pathogenesis. The interleukin (IL)-23/Th-17 axis is one such example. Targeting IL-12/23 is effective for the treatment of both moderate-to-severe Crohn's disease and ulcerative colitis, and ustekinumab (an IL-12/23p40 antagonist) is approved for both indications. In patients with psoriasis, improved clinical outcomes were observed with agents that more selectively targeted IL-23 (IL-23p19 antagonists) compared with those that target both IL-12 and IL-23. Many specific IL-23p19 antagonists are currently being investigated in Crohn's disease and ulcerative colitis, and risankizumab has been recently approved for moderate-to-severely active Crohn's disease. In this review, we summarize the mechanisms of action and the evidence from clinical trials supporting the efficacy and safety of IL-23p19 antagonists for the treatment of inflammatory bowel disease.