Efficacy and Safety of Sphingosine 1-Phosphate Receptor Modulators for Ulcerative Colitis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

ABSTRACT

BACKGROUND AND AIMS: Sphingosine 1-phosphate receptor modulators (S1PRMs) are an effective treatment for ulcerative colitis (UC). This review summarizes all available randomized trial data on the efficacy and safety of S1PRM therapy. METHODS: Multiple publication databases were systematically searched for randomized control trials (RCTs) of adults with moderate to severe UC treated with S1PRMs. Random effects meta-analysis was performed. The risk of bias was assessed using the Cochrane Risk-of-Bias 2 tool, and the overall quality of evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. RESULTS: We identified 7 RCTs (1737 patients) involving the use of S1PRMs for moderate to severe UC. During induction, S1PRM therapy was efficacious when compared with placebo for clinical remission [RR 2.65 (95% CI 2.00, 3.53)], clinical response [RR 1.68 (95% CI 1.48, 1.91)], endoscopic improvement [RR 2.17 (95% CI 1.76, 2.68)], endoscopic normalization [RR 2.56 (95% CI 1.58, 3.83)], mucosal healing [RR 2.88 (95% CI 1.94, 4.26)], and histologic remission [RR 2.42 (95% CI 1.60, 3.66)]. Similar results were seen throughout the maintenance peroid, although fewer data were available to pool; notably, both sustained [RR 3.57 (95% CI 1.23, 10.35)] and steroid-free [RR 2.92 (95% CI 1.35, 6.33)] remission were significantly increased by S1PRM. There were no significant differences in adverse events [RR 1.02 (95% CI 0.90, 1.15)] and infections [RR 1.15 (95% CI 0.82, 1.60)] between S1PRM and placebo. CONCLUSION: Pooling of RCT data confirms that S1PRM therapy is both effective and safe for patients with moderate to severe UC.