Differentiating IL-23 Inhibitors in Crohn’s Disease

Interleukin-23 (IL-23), a member of the IL-12 family of cytokines, plays a critical role in intestinal homeostasis and inflammation and is strongly implicated in the pathogenesis of inflammatory bowel disease (IBD). Therapies targeting the p19 subunit of IL-23 have recently expanded the therapeutic options for IBD demonstrating efficacy and safety for the treatment of moderate to severe Crohn’s disease (CD). Thus, in this review, we provide an overview of agents targeting the IL-23 pathway in CD, highlighting similarities and differences of specific IL-23 inhibitors. Furthermore, we summarize key phase 3 trials and head-to-head trials, focusing on design features and interpretation. Finally, we discuss the positioning of selective IL-23 agents for CD treatment along with areas of unmet clinical needs. However, real-world data will offer additional comparative effectiveness information, data for disease subtypes, and insights into the long-term outcomes of IL-23 inhibition. Looking ahead, ongoing phase 3 studies testing p19-specific selective IL-23 inhibitors are expected to expand the therapeutic options for patients with complex phenotypes, including those with extraintestinal manifestations (EIMs), fistulas, and strictures. Advances in molecular and cellular characterization, including the development of predictive molecular biomarkers, may help guide clinical decision-making, enabling more personalized treatment approaches. Precision medicine studies may further enhance our understanding of the molecular biology of IL-23, shedding light on how these agents work in complex CD and clarify their potential complementary or synergistic effects with other therapies.