Sphingosine 1-Phosphate (S1P) Receptor Modulators as an Induction and Maintenance Therapy for Moderate to Severe
Syed Anjum Ali Gardezi1, Muhammad Javaid Iqbal2, Sami Ulhaq3
1Department of Gastroenterology, Johns Hopkins Healthcare Aramco, Dhahran, Eastern Province, Saudi Arabia. sanjliajk@gmail.com.
Background:
Sphingosine-1-phosphate receptor (S1PR) modulators have emerged as a novel therapeutic class for ulcerative colitis (UC), yet their overall efficacy and safety across clinical trials have not been comprehensively evaluated. This meta-analysis assesses the impact of S1PR modulators on clinical, endoscopic, and histological outcomes in UC.
Methods:
A systematic search of PubMed, CENTRAL, Google Scholar, and ClinicalTrials.gov was conducted through November 20, 2025. Randomized controlled trials evaluating S1PR modulators in adults with UC were included. Risk of bias was assessed using the RoB 2 tool, and pooled estimates were calculated using a random-effects model.
Results:
Eight trials involving 2663 participants were included. Analysis comparing S1PR modulators with placebo included etrasimod, ozanimod, tamuzimod, and KRP203. S1PR modulators significantly improved clinical response during induction (RR 2.47; p < 0.00001) and maintenance (RR 3.30; p = 0.0002). Clinical remission was also significantly increased in both the induction (RR 1.84; p < 0.00001) and maintenance phases (RR 2.20; p = 0.0001). Endoscopic improvement was significantly enhanced during induction (RR 2.32; p < 0.00001) and remained significant in maintenance (RR 1.95; p = 0.03). Histological remission improved significantly in both induction (RR 2.59; p < 0.00001) and maintenance (RR 2.60; p < 0.00001). Mucosal healing was significantly increased in the induction (RR 2.54; p < 0.00001) and maintenance phases (RR 2.21; p < 0.00001). Adverse events were slightly increased with S1PR modulators (RR 1.13; p = 0.002), while serious adverse events (p = 0.73) and discontinuations (p = 0.67) did not differ significantly from placebo.
Conclusion:
S1PR modulators demonstrate robust efficacy during the induction phase across all key clinical and tissue-based outcomes, with more modest or variable effects during maintenance. Their safety profile remains acceptable, supporting their role as a promising therapeutic option for UC.
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