Efficacy and safety of sphingosine-1-phosphate receptor modulators in the management of inflammatory bowel disease: a systematic review and meta-analysis.

To evaluate the efficacy and safety of sphingosine-1-phosphate (S1P) receptor modulators in treating ulcerative colitis (UC) and Crohn's disease (CD). Inflammatory Bowel Disease (IBD) is a chronic immune-mediated condition that remains challenging to manage. S1P receptor modulators offer a novel therapeutic approach by targeting immune cell trafficking, potentially improving disease outcomes. A systematic review and meta-analysis were conducted by searching PubMed, Scopus, and Cochrane Library major electronic databases for randomized controlled trials (RCTs) investigating S1P receptor modulators in IBD. Clinical outcomes assessed included clinical remission, clinical response, endoscopic improvement, histologic remission, and serious adverse events. Pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated using a fixed-effects model. Seven RCTs with a total of 2,597 patients were included. S1P receptor modulators significantly improved clinical remission (OR = 1.49, 95% CI: 1.21-1.84, p < 0.001), histologic remission (OR = 1.74, 95% CI: 1.31-2.31, p < 0.001), endoscopic improvement (OR = 1.58, 95% CI: 1.23-2.04, p < 0.001), and clinical response (OR = 1.27, 95% CI: 1.05-1.54, p = 0.01). The risk of serious adverse events did not significantly differ between treatment and placebo groups (OR = 1.28, 95% CI: 0.92-1.80, p = 0.14), suggesting a favorable safety profile. This meta-analysis supports S1P receptor modulators, particularly ozanimod and etrasimod, as effective and safe treatments for UC. Further studies are needed to assess long-term safety and direct comparisons with existing biologic therapies.