S1P receptor modulators for moderate-to-severe ulcerative colitis: a systematic review, meta-analysis, and trial...

Area of Science:

• Gastroenterology
• Pharmacology
• Clinical Trials

Background:

• Sphingosine-1-phosphate (S1P) receptor modulators represent a novel oral treatment class for ulcerative colitis (UC).
• Existing research lacks a comprehensive synthesis of randomized controlled trials (RCTs) with robust statistical analyses like Trial Sequential Analysis (TSA) and GRADE certainty assessment.

Purpose of the Study:

• To evaluate the efficacy and safety of S1P receptor modulators in patients with moderate-to-severe UC.
• To assess the conclusiveness and certainty of the available evidence using TSA and GRADE methodologies.

Main Methods:

• A systematic literature search was conducted across major databases (PubMed, Cochrane Library, Europe PMC, Google Scholar) up to February 28, 2026.
• Included were RCTs comparing S1P receptor modulators against placebo in adult patients diagnosed with UC.
• Pooled risk ratios (RRs) were calculated using a random-effects model, supplemented by TSA and GRADE assessments.

Main Results:

• Ten RCTs were analyzed. S1P receptor modulators demonstrated superiority over placebo for induction of clinical remission, clinical response, endoscopic improvement, and histological remission (all P<0.001).
• Maintenance therapy also showed significant efficacy, though with some heterogeneity, resolved by analyzing treat-through designs.
• No increase in serious adverse events (SAEs) was observed; treatment-emergent adverse events (TEAEs) were slightly higher, primarily with etrasimod.

Conclusions:

• S1P receptor modulators offer moderate-to-high certainty evidence of efficacy in moderate-to-severe UC without increasing SAEs.
• These findings provide strong quantitative support for current guidelines recommending S1P receptor modulators as an effective advanced oral therapy for UC.