Targeting IL-23 for IBD: Rationale and Progress to Date

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.