Abstract

Targeting interleukin-23 (IL-23) represents a significant therapeutic avenue for treating ulcerative colitis (UC). What are the effectiveness and safety of selective inhibitors targeting IL-23p19 and IL-12/23p40 in individuals with moderate-to-severe UC? MEDLINE, Embase, Scopus, and Cochrane databases. A systematic search of MEDLINE, Embase, Scopus, and Cochrane databases till January 15, 2024, to identify randomized controlled trials comparing IL-23p19 and IL-12/23p40 inhibitors against placebo or active comparators in UC patients. The primary outcome was clinical remission, with secondary outcomes including clinical response, endoscopic remission, and safety profiles during induction and maintenance phases. Using a fixed-effect model, we pooled dichotomous data with risk ratio (RR) and 95% confidence interval (CI) for analysis. In 5 trials involving 1120 patients with moderate to severe UC, targeting IL-23 showed significant superiority in inducing clinical remission [RR: 2.08, 95% CI, (1.66-2.61)], endoscopic remission [RR: 1.73, 95% CI, (1.39-2.16)], and histologic remission [RR: 1.88, 95% CI, (1.34-2.64)]. Additionally, individuals treated with IL-12/23p40 or IL-23p19 antagonists maintained clinical remission [RR: 1.85, 95% CI, (1.53-2.23)], endoscopic remission [RR: 2.03, 95% CI, (1.60-2.57)], and histologic remission [RR: 1.66, 95% CI, (1.11-2.48)]. Targeting IL-23 was linked with a reduced risk of any adverse events (AE) during both induction [RR: 0.94, 95% CI, (0.86-1.02)] and maintenance phases [RR: 0.93, 95% CI, (0.86-0.99)], any serious AE during the induction phase [RR: 0.53, 95% CI, (0.36-0.78)], and withdrawal due to AEs compared to patients receiving placebo during induction [RR: 0.24, 95% CI (0.14, 0.43)]. Targeting IL-23 demonstrates efficacy and safety for inducing and maintaining clinical and endoscopic remission in moderate-to-severe UC patients.

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