Objective: Targeting the interleukin (IL)-23 axis is an emerging treatment target for ulcerative colitis (UC), with several positive randomized controlled trials (RCTs). We aim to investigate the safety and efficacy of IL-23 inhibitors for the induction and maintenance treatment of moderate to severe UC.

Methods: A systematic review and meta-analysis synthesizing evidence from RCTs obtained from PubMed, Cochrane, Scopus, and Web of Science from inception to August 2024. We used the fixed-effects model to report dichotomous outcomes using the risk ratio (RR) with a 95% confidence interval (CI). CRD42024589935.

Results: Four records, reporting four induction trials and three maintenance trials, with 2,699 patients in the induction phase and 1,015 in the maintenance phase, were included. IL-23 inhibitors significantly increased the rate of clinical remission in the induction phase (RR: 2.19, 95%CI [1.72, 2.78]) and maintenance phase (RR: 1.55, 95%CI [1.26, 1.90]); endoscopic remission in induction phase (RR: 1.76, 95%CI [1.41, 2.18]) and maintenance phase (RR: 1.63, 95%CI [1.21, 1.85]); histo-endoscopic mucosal healing in induction phase (RR: 2.06, 95%CI [1.60, 2.64]) and maintenance phase (RR: 1.48, 95%CI [1.14, 1.90]). Also, IL-23 inhibitors significantly decreased the incidence of serious adverse events in the induction phase (RR: 0.37, 95%CI [0.26, 0.55]) and maintenance phase (RR: 0.53, 95%CI [0.33, 0.83]).

Conclusions: IL-23 inhibitors are effective as an induction and maintenance therapy for moderate to severe UC based on the significantly increased rates of clinical, endoscopic, and histological remission. Also, the safety profile of IL-23 inhibitors is favorable, with a significantly decreased incidence of serious adverse events compared to placebo.