Interleukin-23p19 Inhibitors in Inflammatory Bowel Disease: From Current Insights to Future Directions

Interleukin-23 (IL-23) is a pivotal cytokine driving intestinal inflammation in inflammatory bowel disease (IBD). The development of monoclonal antibodies selectively targeting the p19 subunit of IL-23, including risankizumab, mirikizumab and guselkumab, has significantly expanded the therapeutic landscape of IBD. Landmark phase 3 trials in Crohn’s disease (CD) and ulcerative colitis (UC) have demonstrated high efficacy and durable responses, followed by recent regulatory approvals across both indications. Notably, the SEQUENCE trial established the superiority of risankizumab over ustekinumab in achieving endoscopic and clinical endpoints in CD, underscoring the therapeutic value of IL-23p19 blockade and its differentiation from prior p40 inhibition. With additional agents in advanced development, IL-23p19 inhibitors are now emerging as a bona fide treatment class in IBD. Furthermore, IL-23p19 inhibitors display favorable safety profiles and convenient subcutaneous administration regimens, which broaden their applicability across diverse patient populations. However, key knowledge gaps remain regarding optimal treatment positioning, comparative effectiveness, and long-term disease outcomes. Precision medicine approaches will be crucial to fully exploit the potential of this drug class. For instance, early biomarkers can help monitor response, while future integration of serological and multi-omics biomarkers may enable the prediction of treatment success and guide personalized selection. This review summarizes the current knowledge base regarding IL-23p19 inhibitors in IBD, highlights their class effects and unique clinical value, and outlines a research agenda towards biomarker-driven and precision-guided use. Ultimately, IL-23p19-inhibition exemplifies how targeted immunotherapy and precision medicine can converge in order to reshape IBD management.