Interleukin-23 Inhibitors in Inflammatory Bowel Disease

Selective inhibition of interleukin-23 (IL-23) has emerged as a highly effective therapeutic strategy in inflammatory bowel disease, targeting a central pathway of chronic intestinal inflammation while preserving host defense mechanisms. Across phase II and phase III randomized controlled trials, risankizumab, mirikizumab, and guselkumab consistently demonstrated robust efficacy in both ulcerative colitis and Crohn's disease, achieving clinical remission rates approaching 40-50% in ulcerative colitis and exceeding 50% in Crohn's disease during maintenance, with parallel improvements in endoscopic and histological outcomes. Notably, mirikizumab and guselkumab showed particularly high rates of endoscopic and histological remission in ulcerative colitis, whereas guselkumab achieved some of the highest induction remission rates in Crohn's disease. These benefits were durable over time, with long-term extension studies confirming sustained remission beyond two years in a substantial proportion of patients. Across trials, IL-23 inhibitors displayed a favorable safety profile, with low rates of serious adverse events, infections, and major cardiovascular events, supporting their use in long-term disease management. Real-world evidence further reinforces these findings, demonstrating consistent effectiveness in heavily pretreated and complex patient populations, including those with prior biologic failure, comorbidities, or difficult-to-treat disease phenotypes. In particular, risankizumab has shown strong performance in multi-refractory Crohn's disease cohorts, while emerging data for mirikizumab confirm its effectiveness in real-life ulcerative colitis settings. Beyond clinical outcomes, differences in molecular structure, pharmacokinetics, and Fc-mediated interactions may contribute to subtle distinctions among agents, potentially influencing therapeutic positioning. Ongoing development of oral compounds and combination strategies targeting complementary inflammatory pathways is expected to further expand the role of IL-23 inhibition. Overall, interleukin-23 inhibitors represent a cornerstone of modern inflammatory bowel disease therapy, combining high efficacy, durable responses, and an excellent safety profile, with growing evidence supporting their use across a broad spectrum of patients.