Efficacy and safety of guselkumab for inflammatory bowel diseases: a systematic review and meta-analysis of randomized controlled trials.

Abstract

Crohn's disease and ulcerative colitis are chronic inflammatory bowel diseases (IBDs) driven by the interleukin-23/Th17 pathway. Guselkumab, a selective interleukin-23p19 monoclonal antibody, has shown promise in phase II/III trials. This systematic review and meta-analysis aimed to synthesize its efficacy and safety versus placebo in moderate-to-severe IBD. PubMed/MEDLINE, Embase, Cochrane CENTRAL, and Scopus were searched from inception to February 2026. Guselkumab (intravenous induction, 200-1200 mg) was compared with placebo. Random-effects models pooled outcomes as risk ratios with 95% confidence intervals (CIs). Heterogeneity (I2) and evidence certainty were assessed. Seven randomized controlled trials were included. Guselkumab significantly improved week-12 clinical remission (risk ratio: 2.77, 95% CI: 2.30-3.34; P < 0.00001; I2 = 0%), with consistent benefits in ulcerative colitis (risk ratio: 3.09) and Crohn's disease (risk ratio: 2.62). Clinical response also improved (risk ratio: 2.34, 95% CI: 1.99-2.76; P < 0.0001). In ulcerative colitis, endoscopic improvement reached a risk ratio of 2.57, symptomatic remission risk ratio 2.40, and histologic-endoscopic improvement risk ratio 2.96 (all P < 0.0001, I2 = 0%). In Crohn's disease, endoscopic response reached a risk ratio of 2.46 and PRO-2 remission risk ratio 2.78 (both P < 0.0001). Any adverse events were comparable between groups (risk ratio: 0.99), while serious adverse events (risk ratio: 0.57; P = 0.004) and discontinuations (risk ratio: 0.50; P = 0.001) were significantly reduced versus placebo. Guselkumab delivers consistent clinical and endoscopic benefits in both ulcerative colitis and Crohn's disease with a favorable safety profile, positioning it as a valuable new option in IBD management.