S1P Receptor Modulators Improve Clinical Outcomes in Ulcerative Colitis: A Stratified Meta-Analysis By Prior Biological Use, Corticosteroid Exposure, and Disease Characteristics.

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.