Efficacy and Safety of Etrasimod in Moderate-To-Severe Ulcerative Colitis: A GRADE-Based Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background: Etrasimod is an oral sphingosine-1-phosphate receptor modulator evaluated for induction and maintenance therapy in moderately to severely active ulcerative colitis (UC). This meta-analysis aimed to assess the efficacy and safety of etrasimod in adults with active UC. Objectives: To assess the efficacy and safety of etrasimod as induction and maintenance therapy in adults with moderately to severely active UC. Methods: A systematic review and meta-analysis of randomized controlled trials (RCTs) comparing etrasimod with placebo in adults (≥18 years) with moderately to severely active UC was conducted by searching PubMed, Embase, Scopus, Cochrane CENTRAL, and ClinicalTrials.gov through November 2025. Dichotomous outcomes were pooled as risk ratios (RRs) with 95% confidence intervals (CIs) using random-effects models; heterogeneity was assessed with I 2 and χ 2 statistics. Analyses were performed with RevMan 5.4. Results: Four RCTs, including 1239 patients (etrasimod = 826; placebo = 413) were analyzed. At 12 weeks, etrasimod significantly improved clinical remission (RR = 2.92, 95% CI 1.71-4.98; I 2 = 57%), clinical response (RR = 1.71, 95% CI 1.46-2.02; I 2 = 19%), endoscopic improvement (RR = 1.72, 95% CI 1.30-2.27; I 2 = 36%), and mucosal healing (RR = 3.11, 95% CI 1.72-5.62; I 2 = 54%). Beyond 40 weeks, etrasimod increased clinical remission (RR = 4.28, 95% CI 2.72-6.73; I 2 = 0%), clinical response (RR = 2.20, 95% CI 1.74-2.78; I 2 = 0%), endoscopic improvement (RR = 3.51, 95% CI 2.36-5.23; I 2 = 0%), mucosal healing (RR = 6.93, 95% CI 3.61-13.33; I 2 = 0%), and steroid-free remission (RR = 4.28, 95% CI 2.72-6.73; I 2 = 0%). Any treatment-emergent adverse event was slightly higher with etrasimod (RR = 1.15, 95% CI 1.04-1.28; I 2 = 0%), while serious adverse events (RR = 0.79, 95% CI 0.39-1.61; I 2 = 38%) and discontinuations due to adverse events (RR = 2.17, 95% CI 0.54-8.67; I 2 = 50%) did not differ significantly. Conclusion and Relevance: Etrasimod is effective in inducing and maintaining clinical and endoscopic remission in moderate-to-severe UC, with an acceptable safety profile.