Abstract
Background and objective
One sphingosine-1-phosphate (S1P) receptor modulator is approved (ozanimod) and another (etrasimod) is under investigation for the induction and maintenance of remission of ulcerative colitis (UC). We aim to evaluate the efficacy and safety of S1P modulators in patients with active UC.
Methods
We conducted a systematic review and meta-analysis synthesizing randomized controlled trials (RCTs), which were retrieved by systematically searching: PubMed, Web of Science, SCOPUS, and Cochrane through May 13th, 2023. We used the fixed-effect model to pool dichotomous data using risk ratio (RR) with a 95% confidence interval (CI).
Results
Five RCTs with a total of 1990 patients were included. S1P receptor modulators were significantly associated with increased clinical response during both the induction (RR 1.71 with 95% CI [1.50, 1.94], P = 0.00001) and maintenance phases (RR 1.89 with 95% CI [1.33, 2.69], P = 0.0004); clinical remission rates during both induction (RR 2.76 with 95% CI [1.88, 4.05], P = 0.00001) and maintenance phases (RR 3.34 with 95% CI [1.41, 7.94], P = 0.006); endoscopic improvement during both induction (RR 2.15 with 95% CI [1.71, 2.70], P = 0.00001) and maintenance phases (RR 2.41 with 95% CI [1.15, 5.05], P = 0.02); and histologic remission during both induction (RR 2.60 with 95% CI [1.89, 3.57] [1.17, 2.10], P = 0.00001) and maintenance phases (RR 2.52 with 95% CI [1.89, 3.37], P = 0.00001). Finally, there was no difference regarding safety outcomes as compared to placebo in both the induction and maintenance phases.
Conclusion
S1P receptor modulators are effective in inducing and maintaining remission in patients with moderate to severe UC.
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Availability of data and materials
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MA conceived the idea. HAS and MA designed the research workflow. BA, HAS and MA searched the databases. AE, MAE, and RAY screened the retrieved records, extracted relevant data, assessed the quality of evidence, and HAS resolved the conflicts. AR performed the analysis. HAS, MA, and FJ wrote the final manuscript. BA, JGH, FAF and HG supervised the project. All authors have read and agreed to the final version of the manuscript.
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Francis A. Farraye declares the following: Consulting Fee: AbbVie, Avalo Therapeutics, BMS, Braintree Labs, Fresenius Kabi, GI Reviewers, GSK, IBD Educational Group, Iterative Health, Janssen, Pharmacosmos, Pfizer, Sandoz Immunology, Sebela, Viatris.
DSMB: Lilly, Optimize Study. The other authors declare no conflict of interest.
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Suilik, H.A., Jaber, F., Abuelazm, M. et al. Sphingosine 1-phosphate (S1P) receptor modulators as an induction and maintenance therapy for ulcerative colitis: a systematic review and meta-analysis of randomized controlled trials. Inflamm. Res. 73, 183–198 (2024). https://doi.org/10.1007/s00011-023-01829-6
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DOI: https://doi.org/10.1007/s00011-023-01829-6