{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T02:42:58Z","timestamp":1776652978019,"version":"3.51.2"},"reference-count":20,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T00:00:00Z","timestamp":1774396800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T00:00:00Z","timestamp":1774396800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100004331","name":"Johnson & Johnson","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100004331","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neurol"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>In phase 3 OPTIMUM study, ponesimod demonstrated superior efficacy and acceptable safety vs teriflunomide in participants with relapsing multiple sclerosis (RMS). This long-term extension (LTE) study was designed to assess the safety and efficacy of ponesimod 20\u00a0mg (P20 mg) during extended treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Participants who completed core OPTIMUM study entered OPTIMUM-LTE; Participants receiving P20 mg once daily (OD) in core continued with the same dose (P20\u00a0mg\/P20\u00a0mg) and those receiving teriflunomide 14\u00a0mg OD switched to P20\u00a0mg (T14\u00a0mg\/P20\u00a0mg) in the LTE study. Safety assessments included treatment-emergent adverse events (TEAE). Efficacy was assessed using annualized relapse rate (ARR), time to first confirmed relapse up to end of study (EOS), confirmed disability accumulation (CDA), and magnetic resonance imaging (MRI)-based endpoints.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Of 1133 participants from core study, 877 were enrolled in 240-week LTE study (ponesimod: 439; teriflunomide:438). During LTE, 93.6% of participants in both groups experienced\u2009\u2265\u20091 TEAE; overall, serious TEAEs were experienced by 12.9% of participants (P20\u00a0mg\/P20\u00a0mg: 12.8%; T14\u00a0mg\/P20\u00a0mg: 13.0%) and TEAEs leading to study treatment discontinuation were experienced by 8.6% of participants (P20\u00a0mg\/P20\u00a0mg: 7.7%; T14\u00a0mg\/P20\u00a0mg: 9.4). In combined analysis period, mean ARR was 0.143 (95% CL: 0.123\u20130.167) for P20\u00a0mg\/P20\u00a0mg and 0.184 (95% CL: 0.158\u20130.213) for T14\u00a0mg\/P20\u00a0mg; 44.3% of participants in P20\u00a0mg\/P20\u00a0mg and 49.5% in T14\u00a0mg\/P20\u00a0mg experienced relapse. Overall, more participants in P20\u00a0mg\/P20\u00a0mg vs T14\u00a0mg\/P20\u00a0mg group achieved no evidence of disease activity (NEDA)-3 at end of LTE (17.5% vs 7.5%).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Ponesimod demonstrated extended safety and sustained efficacy over 5\u00a0years in participants with RMS, without new safety signals. Results suggest that the effects on the MS disease control are maintained with ponesimod over the LTE treatment period.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00415-026-13675-7","type":"journal-article","created":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T11:47:55Z","timestamp":1774439275000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Long-term safety and efficacy of ponesimod in participants with relapsing multiple sclerosis: results from the phase 3 OPTIMUM 5-year long term extension study"],"prefix":"10.1007","volume":"273","author":[{"given":"Xavier","family":"Montalban","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reinhard","family":"Hohlfeld","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlo","family":"Pozzilli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark S.","family":"Freedman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Till","family":"Sprenger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert J.","family":"Fox","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eva Kubala","family":"Havrdova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fred","family":"Lublin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dan","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nandini","family":"Raghavan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janice","family":"Wong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Vaclavkova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jelena","family":"Dukovski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philippe","family":"Linscheid","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michel","family":"Burcklen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ludwig","family":"Kappos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,3,25]]},"reference":[{"issue":"1","key":"13675_CR1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-018-0041-4","volume":"4","author":"M Filippi","year":"2018","unstructured":"Filippi M, Bar-Or A, Piehl F, Preziosa P, Solari A, Vukusic S, Rocca MA (2018) Multiple sclerosis. 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R.H. has received personal fees from Novartis, Sanofi, Merck, Biogen, Teva, Janssen\/Johnson-Johnson, and Roche during the conduct of the study. C.P. has served on scientific advisory boards for Novartis, Merck, Biogen, Sanofi\u2010Genzyme, Roche, Janssen, Alexion, has received funding for travel and speaker honoraria from Merck, Serono, Biogen, Sanofi\u2010Genzyme, Roche, Almirall, Janssen, Alexion and Novartis, and receives research support from Merck, Biogen, Novartis and Almirall. M.S.F. has received research or educational grants from Sanofi-Genzyme Canada, has received honoraria or consultation fees from Alexion\/Astra Zeneca, BiogenIdec, EMD Inc.\/EMD Serono\/Merck Serono, Find Therapeutics, Hoffman-La Roche, Novartis, Quanterix, Sanofi-Genzyme, and Teva Canada Innovation, is a member of company advisory boards, boards of directors or similar for Alexion\/Astra Zeneca, Atara Biotherapeutics, Bayer Healthcare, Celestra Health, EMD Inc.\/Merck Serono, Find Therapeutics, Hoffman-La Roche, Actelion\/Janssen (J&J), Novartis, Sanofi-Genzyme, and Setpoint Medical, and has participated in a company-sponsored speaker\u2019s bureau for EMD Serono and Sanofi-Genzyme. T.S.\u2019s employer received compensation for speaking and advisory board\/consulting activities from Actelion, Janssen, Eli Lilly, Merck-Serono, Roche, Novartis, Sandoz, Sanofi-Genzyme, and Teva. R.F. has served as a consultant or advisory board member in recent years for Arrowhead Pharmaceuticals, Astoria Biologica, Biogen, Bristol-Myers Squibb, Cognito, Eli Lilly, F. Hoffmann-La Roche, Galvani, Immunic, Inmune Bio, Innocare Pharma, Kiniksa, NGM Bio, Novartis, Pfizer, Population Council, Sanofi, Siemens, TG Therapeutics, Tr1X Inc, Ventus, and Viracta; has received clinical trial contracts awarded to his institution from Sanofi and Synaptogenix; has participated in data and safety monitoring for AB Science; and has been employed by Janssen Pharmaceuticals. E.K.H. received grants or contracts from Czech Ministry of Education\u2014project Cooperatio LF1, research area Neuroscience and the project National Institute for Neurological Research (Programme EXCELES, ID project No LX22NPO5107), payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Actelion (Janssen\/J&J), Biogen, Celgene (BMS), Merck, Novartis, Roche, Sanofi and Teva and for participation on a Data Safety Monitoring Board or Advisory Board from Actelion (Janssen\/J&J), Biogen, Celgene (BMS), Merck, Novartis, Roche and Sanofi. F.L. received funding for research from Novartis, Actelion, Biogen, Sanofi, NMSS, NIH and Brainstorm Cell Therapeutics; consulting agreements\/advisory boards\/DSMB: Biogen, EMD Serono, Novartis, Teva, Actelion\/Janssen, Sanofi\/Genzyme, Acorda, Roche\/Genentech, MedImmune\/Viela Bio, Receptos\/Celgene\/BMS, TG Therapeutics, Medday, Atara Biotherapeutics, Mapi Pharma, Apitope, Orion Biotechnology, Brainstorm Cell Therapeutics, Jazz Pharmaceuticals, GW Pharma, Mylan, Immunic, Population Council, Avotres, Neurogene, Banner Life Sciences, Labcorp, Entelexo Biotherapeutics and NeuraLight; stock options: Avotres and NeuraLight; Speaker: Sanofi (non-promotional). D.N., N.R., J.W., A.V., J.D., P.L., M.B. are employees of Actelion Pharmaceuticals, a Janssen Pharmaceutical company of Johnson & Johnson and may hold stock in Johnson & Johnson. LK received research support to the institution (University Hospital Basel, Basel, Switzerland) including steering committee, advisory board, and consultancy fees from Actelion (Janssen), Bayer, Biogen, Bristol Myers Squibb, GSK, Janssen, Japan Tobacco, Merck, Novartis, Roche, Sanofi, Santhera, and Shionogi, and TG Therapeutics; speaker fees from Bayer, Biogen, Merck, Novartis, Roche, and Sanofi; support of educational activities from Allergan, Bayer, Biogen, CSL Behring, Desitin, Merck, Novartis, Pfizer, Roche, Sanofi, Shire, and Teva; license fees for Neurostatus platform access; and grants from Bayer, Biogen, EU, InnoSwiss, Merck, Novartis, Roche, Swiss Multiple Sclerosis Society, and Swiss National Research Foundation.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interest"}},{"value":"This retrospective database analysis study did not involve any collection, transmission, or use of participants' identifiable data. An institutional review board (US) or independent ethics committee (Europe) approved the study protocol and amendments at each participating center. The study was conducted under the ethical principles of the Declaration of Helsinki and was consistent with the local Ethical Guidelines for Medical and Biological Research Involving Human participants.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}],"article-number":"234"}}