{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T18:40:55Z","timestamp":1792176055291,"version":"4.4.0"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2020,11,20]],"date-time":"2020-11-20T00:00:00Z","timestamp":1605830400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold>Ozanimod has been approved for use in the treatment of relapsing forms of multiple sclerosis by the United States FDA. As a novel, orally available sphingosine 1-phosphate receptor modulator, ozanimod selectively binds to S1P1 and S1P5 receptor with high affinity, minimizing safety concerns caused by S1P<jats:sub>3<\/jats:sub>receptor activation.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold>e systematically searched PUBMED, EMBASE database, and Cochrane Library database to identify randomized controlled trials (RCTs) from inception to June 28, 2020. Trials were considered eligible if they 1) were randomized clinical trials (RCTs); 2) enrolled adult participants diagnosed with Relapsing-remitting MS; 3) compared ozanimod with placebo or any other approved DMDs that evaluated in phase III or phase II clinical trials; 4) enrolled over 100 participants; 5) provided any available information for predefined primary or secondary outcomes.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold>2917 participants from three high-quality, multi-centered randomized clinical trials were pooled in our analysis. We found that using ozanimod was significantly associated with the reduction of the annualized relapse rate during the treatment period (RR, \u22120.10 [95% CI, \u22120.15, \u22120.06]). Also, the decreased number of gadolinium-enhancing lesions at the end of the trial was relative to the treatment of ozanimod (ozanimod, 0.29; control, 0.65; RR, \u22120.20 [95% CI, \u22120.34, \u22120.06]). Compared with patients in the control group, the number of new or enlarging T2 lesions over the treatment period decreased in patients treated with ozanimod (ozanimod, 1.82; control, 3.55; RR, \u22121.12 [95% CI, \u22121.52, \u22120.71]). As to the safety endpoints, patients in the ozanimod group reported a lower rate of adverse events (ozanimod, 66.03%; control, 77.07%; RR, 0.64 [95% CI, 0.43, 0.95]). Similar incidence of infection-related TEAEs was found across treatment groups (nasopharyngitis: ozanimod, 11.19%; control, 9.83%; RR, 1.10 [95% CI, 0.77\u20131.57]; urinary-tract infection: ozanimod, 3.81%; control, 2.97%; RR, 1.29 [95% CI, 0.83\u20132.00]). No case of macular edema was noted as well as second-degree, type 2, or third-degree atrioventricular block. As for the subgroup analysis, compared with 0.5\u00a0mg ozanimod, 1\u00a0mg ozanimod is related with a significant reduction of the annualized relapse rate during the treatment period (1\u00a0mg ozanimod, 0.18; 0.5\u00a0mg ozanimod, 0.24; RR, 0.05 [95% CI, 0.01, 0.09])and a decreased number of new or enlarging T2 lesions over the treatment period (1\u00a0mg ozanimod,1.58; 0.5\u00a0mg ozanimod, 2.05; RR, 0.49 [95% CI, 0.19, 0.79]). No significant difference in causing adverse events between 1 and 0.5\u00a0mg was found.<\/jats:p><jats:p><jats:bold>Conclusions:<\/jats:bold>Our meta-analysis found that, with favorable safety performance, the use of ozanimod as a treatment of relapsing-remitting multiple sclerosis in adults was associated with a significant reduction of the annualized relapse rate during the treatment period, decreased number of gadolinium-enhancing lesions at the end of the trial, and lowered number of new or enlarging T2 lesions over the treatment period. Ozanimod 1\u00a0mg outperformed 0.5\u00a0mg dose in efficacy without increasing the risk of adverse events.<\/jats:p>","DOI":"10.3389\/fphar.2020.589146","type":"journal-article","created":{"date-parts":[[2020,11,20]],"date-time":"2020-11-20T10:13:09Z","timestamp":1605867189000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Ozanimod for Treatment of Relapsing-Remitting Multiple Sclerosis in Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials"],"prefix":"10.3389","volume":"11","author":[{"given":"Yue","family":"Sun","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanbo","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zilan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhouqing","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2020,11,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"986","DOI":"10.1177\/1352458518789884","article-title":"Ozanimod demonstrates preservation of brain volume at 1 and 2 years in two Phase 3 trials of relapsing multiple sclerosis (SUNBEAM and RADIANCE)","volume":"23","author":"Arnold","year":"2017","journal-title":"Mult. Scler. J."},{"key":"B2","first-page":"29","article-title":"Reduced brain volume loss in relapsing Multiple sclerosis with ozanimod versus interferon Beta-1a in two phase 3 trials (SUNBEAM and RADIANCE)","volume":"26","author":"Arnold","year":"2019","journal-title":"Eur. J. Neurol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1016\/s1474-4422(14)70049-3","article-title":"Safety and efficacy of fingolimod in patients with relapsing-remitting multiple sclerosis (FREEDOMS II): a double-blind, randomised, placebo-controlled, phase 3 trial","volume":"13","author":"Calabresi","year":"2014","journal-title":"Lancet Neurol."},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(14)70049-3","article-title":"Pregnancy outcomes in the ozanimod nonclinical and clinical development program","volume":"90","author":"Campagnolo","year":"2018","journal-title":"Neurology"},{"key":"B5","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1016\/s1474-4422(16)00018-1","article-title":"Safety and efficacy of the selective sphingosine 1-phosphate receptor modulator ozanimod in relapsing multiple sclerosis (RADIANCE): a randomised, placebo-controlled, phase 2 trial","volume":"15","author":"Cohen","year":"2016","journal-title":"Lancet Neurol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1021","DOI":"10.1016\/s1474-4422(19)30238-8","article-title":"Safety and efficacy of ozanimod versus interferon beta-1a in relapsing multiple sclerosis (RADIANCE): a multicentre, randomised, 24-month, phase 3 trial","volume":"18","author":"Cohen","year":"2019","journal-title":"Lancet Neurol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1009","DOI":"10.1016\/s1474-4422(19)30239-x","article-title":"Safety and efficacy of ozanimod versus interferon beta-1a in relapsing multiple sclerosis (SUNBEAM): a multicentre, randomised, minimum 12-month, phase 3 trial","volume":"18","author":"Comi","year":"2019","journal-title":"Lancet Neurol."},{"key":"B8","first-page":"266","article-title":"Cardiac safety profile of ozanimod in pooled phase 3 studies in relapsing multiple sclerosis (SUNBEAM and RADIANCE)","volume":"24","author":"Cree","year":"2018","journal-title":"Mult. 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