Journal of gastroenterology
August 2, 2026 · via Europe PMC
S1P receptor modulators for moderate-to-severe ulcerative colitis: a systematic review, meta-analysis, and trial sequential analysis.
Jomaa A, Bshara R, Alani M, +7 more, Al-Obaidi H.
AI summary — for doctors, generated from the abstract only
Across ten RCTs, S1P receptor modulators were superior to placebo for induction and maintenance in moderate-to-severe ulcerative colitis without increasing serious adverse events.
What was studied
A systematic review, meta-analysis and trial sequential analysis of ten placebo-controlled RCTs of S1P receptor modulators in adults with moderate-to-severe UC.
Key findings
- Induction clinical remission RR 2.77 (95% CI 2.17-3.55; I2 = 0%)
- Induction clinical response RR 1.69; endoscopic improvement RR 2.29; histologic remission RR 2.77
- Maintenance outcomes significant but heterogeneous (I2 48-65%), resolved in treat-through designs
- Serious AEs not increased; treatment-emergent AEs modestly higher, mainly with etrasimod
- TSA conclusive for clinical response and induction endoscopic improvement; GRADE moderate to high
Clinical relevance
Supports guideline positioning of S1P modulators as an oral advanced therapy option in UC; comparisons with other advanced therapies were not assessed.
Who should care
Limitations
Placebo-controlled trials only; some outcomes remained inconclusive on TSA.
S1P receptor modulators show consistent efficacy in moderate-to-severe UC.
This is an AI-generated summary of the published abstract, not a clinical recommendation. It may not reflect the full text or subsequent updates — verify against the original source before acting on it.
Abstract
Background and aims
S1P receptor modulators are emerging oral therapies for moderate-to-severe ulcerative colitis (UC); however, a comprehensive synthesis incorporating the largest number of RCTs to date, alongside Trial Sequential Analysis (TSA) and GRADE-based certainty assessment, remains lacking. We aim to evaluate the efficacy and safety of S1P receptor modulators in moderate-to-severe UC and assess the conclusiveness and certainty of the evidence.
Methods
PubMed, Cochrane Library, Europe PMC, and Google Scholar were searched from inception through February 28, 2026. Eligible studies were RCTs comparing any S1P receptor modulator with placebo in adults (≥ 18 years) with UC. Pooled risk ratios (RRs) with 95% CIs were estimated using a random-effects model.
Results
A total of ten RCTs were included. During induction, S1P receptor modulators were superior to placebo for clinical remission (RR 2.77; 95% CI, 2.17-3.55; I2 = 0%), clinical response (RR 1.69, 95% CI 1.52-1.87; I2 = 0%), endoscopic improvement (RR, 2.29; 95% CI, 1.91-2.75; I2 = 0%), and histological remission (RR 2.77; 95% CI, 2.11-3.63; I2 = 0%). Maintenance outcomes were similarly significant but heterogeneous (I2 = 48%-65%), fully resolved when restricted to treat-through designs. SAEs were not increased, while TEAEs were modestly higher overall during combined induction and maintenance periods, mainly with etrasimod. TSA provided supportive evidence of conclusive superiority for clinical response at both induction and maintenance, and for endoscopic improvement at induction; evidence for other outcomes remained inconclusive. GRADE certainty of evidence was moderate to high across all efficacy outcomes.
Conclusion
S1P receptor modulators demonstrated moderate-to-high certainty evidence of efficacy across all outcomes, without a significant increase in SAEs. These findings provide robust quantitative support for current guideline recommendations endorsing this oral drug class as an effective advanced therapy for moderate-to-severe UC.
DOI
10.1007/s00535-026-02485-3
PMID
42543388
Research metadata (titles, abstracts, authors, publication dates) is sourced from Europe PMC, which aggregates content from PubMed/MEDLINE, PubMed Central, and other providers under the U.S. National Library of Medicine (NLM/NCBI). NLM does not claim copyright on abstracts; the original journal publishers or authors may hold rights to the full articles. AI-generated summaries are derived only from the abstract, never the full text, and are always labeled as AI-generated.
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