S1P Receptor Modulators Improve Clinical Outcomes in Ulcerative Colitis

Objectives: This systematic review and meta-analysis aimed to evaluate the efficacy and safety of sphingosine-1-phosphate (S1P) receptor modulators for achieving clinical remission and key outcomes in inflammatory bowel disease (IBD) patients and to examine the influence of baseline characteristics. Methods: MEDLINE (Ovid), PubMed, Web of Science, and Cochrane CENTRAL were searched until January 1, 2024. Randomized controlled trials (RCTs) evaluating S1P receptor modulators in adult IBD patients were included. Meta-analyses used inverse variance random-effects models, with stratified analyses by disease type, prior anti-TNF use, corticosteroid use, disease location, and baseline Mayo score. Results: Six RCTs involving 1744 patients (male: 58.8%; age: 41.1±13.5 y) were analyzed. S1P modulators significantly improved clinical remission versus placebo in induction (RR: 2.22; 95% CI: 1.30-3.80) and maintenance phases (RR: 2.79; 95% CI: 1.72-4.54). For UC patients, induction remission was notably higher with S1P modulators (RR: 2.69; 95% CI: 1.98-3.65). Stratified analyses indicated consistent efficacy across disease location ( P =0.15), corticosteroid use ( P =0.20), and Mayo scores ( P =0.53). Prior anti-TNF-naive patients experienced greater benefits ( P =0.04). Maintenance-phase remission rates favored etrasimod (RR: 4.26; 95% CI: 2.36-7.69) over ozanimod (RR: 2.09; 95% CI: 1.54-2.84; P =0.035). Secondary outcomes, including clinical response, endoscopic and histologic remission, mucosal healing, and corticosteroid-free remission, were also significantly improved. Overall, adverse events were more frequent with S1P modulators (RR: 1.18; 95% CI: 1.07-1.30); serious adverse events, infections, mortality, and cardiac events were comparable. Conclusions: S1P modulators improved remission rates and secondary outcomes in UC with a generally favorable safety profile. More data on CD are needed.