{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T18:12:21Z","timestamp":1791223941111,"version":"4.1.0"},"reference-count":42,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2021,10,13]],"date-time":"2021-10-13T00:00:00Z","timestamp":1634083200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Academia Espa\u00f1ola de Esclerosis M\u00faltiple y Otras Enfermedades Autoinmunes","award":["Novartis"],"award-info":[{"award-number":["Novartis"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"\n Objective<\/jats:title>\n To describe the profile of patients with multiple sclerosis (MS) treated with fingolimod in Spain and to assess the effectiveness and safety of fingolimod after 4 years of inclusion in the Spanish Gilenya Registry.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n An observational, retrospective\/prospective, multicenter case registry, including all patients with relapsing-remitting MS (RRMS) starting treatment with fingolimod in 43 centers in Spain. Analyses were performed in the overall population and in subgroups according to prior disease-modifying therapy (DMT): glatiramer acetate\/interferon beta-1 (BRACE), natalizumab, other treatment, or na\u00efve.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n Six hundred and sixty-six evaluable patients were included (91.1% previously treated with at least one DMT). The mean annualized relapse rate (ARR) prior to fingolimod was 1.12, and the mean EDSS at fingolimod initiation was 3.03. Fingolimod reduced the ARR by 71.4%, 75%, 75.5%, and 80.3%, after 1, 2, 3 and 4 years, respectively (p<0.001). This significant reduction in the ARR continued to be observed in all subgroups. After 4 years, the EDSS showed a minimal deterioration, with the EDSS scores from year 1 to year 4 remaining mostly stable. The percentage of patients without T1 Gd+ lesions progressively increased from 45.6% during the year prior to fingolimod initiation to 88.2% at year 4. The proportion of patients free from new\/enlarged T2 lesions after 4 years of fingolimod treatment was 80.3%. This trend in both radiological measures was also observed in the subgroups. Adverse events (AEs) were experienced by up to 41.6% of patients (most commonly: lymphopenia [12.5%] and urinary tract infection [3.7%]). Most AEs were mild in severity, 3.6% of patients had serious AEs.<\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n The patient profile was similar to other observational studies. The results obtained from the long-term use of fingolimod showed that it was effective, regardless of prior DMT, and it had adequate safety results, with a positive benefit-risk balance.<\/jats:p>\n <\/jats:sec>","DOI":"10.1371\/journal.pone.0258437","type":"journal-article","created":{"date-parts":[[2021,10,13]],"date-time":"2021-10-13T14:56:42Z","timestamp":1634137002000},"page":"e0258437","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":8,"title":["Four-year safety and effectiveness data from patients with multiple sclerosis treated with fingolimod: The Spanish GILENYA registry"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5050-9890","authenticated-orcid":true,"given":"J. 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Atlas of MS 3rd edition PART 1: Mapping multiple sclerosis around the world key epidemiology findings 2020 [3 February 2021]. Available from: https:\/\/www.msif.org\/wp-content\/uploads\/2020\/10\/Atlas-3rd-Edition-Epidemiology-report-EN-updated-30-9-20.pdf."},{"issue":"5","key":"pone.0258437.ref004","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1038\/s41582-019-0170-8","article-title":"Reaching an evidence-based prognosis for personalized treatment of multiple sclerosis.","volume":"15","author":"D Rotstein","year":"2019","journal-title":"Nat Rev Neurol"},{"issue":"2","key":"pone.0258437.ref005","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1097\/WNF.0b013e3181cbf825","article-title":"Mechanism of action of oral fingolimod (FTY720) in multiple sclerosi","volume":"33","author":"J Chun","year":"2010","journal-title":"Clin Neuropharmacol"},{"key":"pone.0258437.ref006","unstructured":"European Medicines Agency. Gynlenia\u2014Summary of Product Characteristics 2011 [Accessed 3 February 2021]. Available from: https:\/\/www.ema.europa.eu\/en\/documents\/product-information\/gilenya-epar-product-information_en.pdf."},{"issue":"5","key":"pone.0258437.ref007","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1056\/NEJMoa0909494","article-title":"A Placebo-Controlled Trial of Oral Fingolimod in Relapsing Multiple Sclerosis.","volume":"362","author":"L Kappos","year":"2010","journal-title":"New England Journal of Medicine"},{"issue":"6","key":"pone.0258437.ref008","doi-asserted-by":"crossref","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":"PA Calabresi","year":"2014","journal-title":"Lancet Neurol"},{"issue":"5","key":"pone.0258437.ref009","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1056\/NEJMoa0907839","article-title":"Oral Fingolimod or Intramuscular Interferon for Relapsing Multiple Sclerosis.","volume":"362","author":"JA Cohen","year":"2010","journal-title":"New England Journal of Medicine"},{"issue":"0","key":"pone.0258437.ref010","first-page":"1","article-title":"Effect of applying inclusion and exclusion criteria of phase III clinical trials to multiple sclerosis patients in routine clinical care","volume":"00","author":"KO Jalusic","year":"2021","journal-title":"Multiple Sclerosis Journal."},{"issue":"3","key":"pone.0258437.ref011","doi-asserted-by":"crossref","DOI":"10.1212\/NXI.0000000000000548","article-title":"Real-world persistence and benefit-risk profile of fingolimod over 36 months in Germany.","volume":"6","author":"T Ziemssen","year":"2019","journal-title":"Neurol Neuroimmunol Neuroinflamm"},{"issue":"9","key":"pone.0258437.ref012","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1007\/s40263-014-0185-z","article-title":"Real-world use of fingolimod in patients with relapsing remitting multiple sclerosis: a retrospective study using the national multiple sclerosis registry in Kuwait","volume":"28","author":"J Al-Hashel","year":"2014","journal-title":"CNS Drugs"},{"issue":"5","key":"pone.0258437.ref013","first-page":"157","article-title":"[Efficacy and safety of fingolimod in routine clinical practice in patients with relapsing-remitting multiple sclerosis in Spain: an intermediate analysis of the MS NEXT study].","volume":"67","author":"J Mallada-Frechin","year":"2018","journal-title":"Rev Neurol"},{"key":"pone.0258437.ref014","article-title":"[Fingolimod: effectiveness and safety in routine clinical practice. 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