Sphingosine 1-Phosphate Receptor Modulators as an Induction and Maintenance Therapy for Ulcerative Colitis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Introduction: Sphingosine-1-phosphate (S1P) receptor modulators, including ozanimod and etrasimod, are currently under investigation for ulcerative colitis (UC) management. Therefore, we aim to evaluate the efficacy and safety of S1P modulators in patients with active UC during induction and maintenance periods. Methods: We conducted a systematic review and meta-analysis synthesizing randomized controlled trials (RCTs), which were retrieved by systematically searching: PubMed, Web of Science, SCOPUS, and Cochrane through May 13th, 2023. We used the fixed-effect model to pool dichotomous data using risk ratio (RR) with a 95% confidence interval (CI). Results: We included 5 RCTs with a total of 1,990 patients. S1P receptor modulators were significantly associated with increased clinical response during both induction (RR: 1.71 with 95% CI [1.50, 1.94], P= 0.00001) and maintenance phases (RR: 1.89 with 95% CI [1.33, 2.69], P= 0.0004); clinical remission rates during both induction (RR: 2.76 with 95% CI [1.88, 4.05], P= 0.00001) and maintenance phases (RR: 3.34 with 95% CI [1.41, 7.94], P= 0.006); endoscopic improvement during both induction (RR: 2.15 with 95% CI [1.71, 2.70], P= 0.00001) and maintenance phases (RR: 2.41 with 95% CI [1.15, 5.05], P= 0.02); histologic remission during both induction (RR: 2.60 with 95% CI [1.89, 3.57] [1.17, 2.10], P= 0.00001) and maintenance phases (RR: 2.52 with 95% CI [1.89, 3.37], P= 0.00001). Finally, there was no difference between etrolizumab and placebo regarding safety outcomes (Figure 1). Conclusion: S1P receptor modulators were effective as an induction and maintenance therapy for moderate to severe UC based on clinical, endoscopic, and histologic remission. Further research is therefore warranted to investigate the S1P receptor modulator’s position in UC management guidelines by head-to-head comparisons with other validated drugs, such as vedolizumab.Figure 1.: Forest Plots for meta-analyses about (A) Clinical Response (B) Clinical Remission (C) Endoscopic Improvement (D) Histologic Remission and (E) Safety outcomes of S1P receptor modulators in ulcerative colitis patients.