Safety and efficacy of IL-23 inhibitors in patients with moderate to severe ulcerative colitis: a systematic review and meta-analysis of randomized controlled trials

Abstract

Background and objective Targeting the interleukin-23 (IL-23) pathway is an emerging therapeutic strategy for moderate to severe ulcerative colitis (UC). This systematic review and meta-analysis evaluated the efficacy and safety of IL-23 inhibitors for induction and maintenance therapy in UC. Methods A systematic search of PubMed, Cochrane, and Google Scholar was conducted up to May 2025 to identify randomized controlled trials (RCTs) of IL-23 inhibitors (mirikizumab, risankizumab, guselkumab) in UC. Data were analyzed using Review Manager (RevMan 5.4) with a random-effects model. Results Seven RCTs (four induction, three maintenance) including 4203 patients were analyzed. IL-23 inhibitors significantly increased clinical remission during both induction (RR 1.52) and maintenance (RR 1.62). Rates of histo-endoscopic healing were also higher with IL-23 blockade in both induction (RR 2.53) and maintenance (RR 1.81). Importantly, IL-23 inhibitors were associated with a reduced risk of serious adverse events during induction (RR 0.39), with no significant difference observed during maintenance (RR 0.68). Other outcomes, including clinical response and corticosteroid-free remission, also consistently favored IL-23 blockade. Conclusion IL-23 inhibitors provide significant improvements in clinical remission and mucosal healing, with a favorable safety profile, particularly during induction therapy in moderate to severe UC.