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 I2 and χ2 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; I2 = 57%), clinical response (RR = 1.71, 95% CI 1.46-2.02; I2 = 19%), endoscopic improvement (RR = 1.72, 95% CI 1.30-2.27; I2 = 36%), and mucosal healing (RR = 3.11, 95% CI 1.72-5.62; I2 = 54%). Beyond 40 weeks, etrasimod increased clinical remission (RR = 4.28, 95% CI 2.72-6.73; I2 = 0%), clinical response (RR = 2.20, 95% CI 1.74-2.78; I2 = 0%), endoscopic improvement (RR = 3.51, 95% CI 2.36-5.23; I2 = 0%), mucosal healing (RR = 6.93, 95% CI 3.61-13.33; I2 = 0%), and steroid-free remission (RR = 4.28, 95% CI 2.72-6.73; I2 = 0%). Any treatment-emergent adverse event was slightly higher with etrasimod (RR = 1.15, 95% CI 1.04-1.28; I2 = 0%), while serious adverse events (RR = 0.79, 95% CI 0.39-1.61; I2 = 38%) and discontinuations due to adverse events (RR = 2.17, 95% CI 0.54-8.67; I2 = 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.