{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T13:04:59Z","timestamp":1771851899121,"version":"3.50.1"},"reference-count":33,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2021,5,18]],"date-time":"2021-05-18T00:00:00Z","timestamp":1621296000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100013995","name":"Sanofi Genzyme","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013995","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Objective<\/jats:title>\n<jats:p>Teriflunomide is a once-daily, oral disease-modifying therapy (DMT) for relapsing forms of multiple sclerosis (MS). We studied clinical outcomes in a real-world setting involving a population-based large cohort of unselected patients enrolled in The Danish Multiple Sclerosis Registry (DMSR) who started teriflunomide treatment between 2013\u20132019.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>This was a complete nationwide population-based cohort study with prospectively enrolled unselected cases. Demographic and disease-specific patient parameters related to treatment history, efficacy outcomes, and discontinuation and switching rates among other clinical variables were assessed at baseline and during follow-up visits.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>A total of 3239 patients (65.4% female) started treatment with teriflunomide during the study period, 56% of whom were treatment-na\u00efve. Compared to previously treated patients, treatment-na\u00efve patients were older on average at disease onset, had a shorter disease duration, a lower Expanded Disability Status Scale score at teriflunomide treatment start and more frequently experienced a relapse in the 12 months prior to teriflunomide initiation. In the 3001 patients initiating teriflunomide treatment at least 12 months before the cut-off date, 72.7% were still on treatment one year after treatment start. Discontinuations in the first year were due mainly to adverse events (15.6%). Over the full follow-up period, 47.5% of patients discontinued teriflunomide treatment. Sixty-three percent of the patients treated with teriflunomide for 5 years were relapse-free, while significantly more treatment-na\u00efve versus previously treated patients experienced a relapse during the follow-up (p&lt;0.0001). Furthermore, 85% of the patients with available data were free of disability worsening at the end of follow-up.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Solid efficacy and treatment persistence data consistent with other real-world studies were obtained over the treatment period. Treatment outcomes in this real-world scenario of the population-based cohort support previous findings that teriflunomide is an effective and generally well-tolerated DMT for relapsing MS patients with mild to moderate disease activity.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0250820","type":"journal-article","created":{"date-parts":[[2021,5,18]],"date-time":"2021-05-18T17:23:11Z","timestamp":1621358591000},"page":"e0250820","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":18,"title":["Real-world outcomes for a complete nationwide cohort of more than 3200 teriflunomide-treated multiple sclerosis patients in The Danish Multiple Sclerosis Registry"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9968-549X","authenticated-orcid":true,"given":"Viktoria","family":"Papp","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mathias Due","family":"Buron","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Volkert","family":"Siersma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter Vestergaard","family":"Rasmussen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zsolt","family":"Illes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthias","family":"Kant","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia","family":"Hilt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zsolt","family":"Mezei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3019-8826","authenticated-orcid":true,"given":"Homayoun","family":"Roshanisefat","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7682-2188","authenticated-orcid":true,"given":"Tobias","family":"Sejb\u00e6k","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arkadiusz","family":"Weglewski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janneke","family":"van Wingerden","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4497-3616","authenticated-orcid":true,"given":"Svend Sparre","family":"Geertsen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9482-1771","authenticated-orcid":true,"given":"Stephan","family":"Bramow","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Finn","family":"Sellebjerg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melinda","family":"Magyari","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2021,5,18]]},"reference":[{"key":"pone.0250820.ref001","unstructured":"Sanofi-Aventis. AUBAGIO (teriflunomide) summary of product characteristics [Internet]. 2020 [cited 2020 Oct 16]. https:\/\/www.ema.europa.eu\/en\/documents\/product-information\/aubagio-epar-product-information_en.pdf."},{"key":"pone.0250820.ref002","unstructured":"Genzyme Corporation. AUBAGIO\u00ae (teriflunomide) prescribing information [Internet]. 2020. [cited 2020 Oct 16]. http:\/\/products.sanofi.us\/Aubagio\/Aubagio.pdf."},{"issue":"8","key":"pone.0250820.ref003","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1007\/s40265-019-01135-8","article-title":"Teriflunomide: A Review in Relapsing\u2013Remitting Multiple Sclerosis","volume":"79","author":"LJ Scott","year":"2019","journal-title":"Drugs"},{"issue":"6","key":"pone.0250820.ref004","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1007\/s40265-014-0212-x","article-title":"Teriflunomide and its mechanism of action in multiple sclerosis","volume":"74","author":"A Bar-Or","year":"2014","journal-title":"Drugs"},{"issue":"14","key":"pone.0250820.ref005","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1056\/NEJMoa1014656","article-title":"Randomized trial of oral teriflunomide for relapsing multiple sclerosis","volume":"365","author":"P O\u2019Connor","year":"2011","journal-title":"N Engl J Med"},{"key":"pone.0250820.ref006","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/S1474-4422(13)70308-9","article-title":"Oral teriflunomide for patients with relapsing multiple sclerosis (TOWER): A randomised, double-blind, placebo-controlled, phase 3 trial","volume":"13","author":"C Confavreux","year":"2014","journal-title":"Lancet Neurol"},{"key":"pone.0250820.ref007","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1016\/S1474-4422(14)70191-7","article-title":"Oral teriflunomide for patients with a first clinical episode suggestive of multiple sclerosis (TOPIC): A randomised, double-blind, placebo-controlled, phase 3 trial","volume":"13","author":"AE Miller","year":"2014","journal-title":"Lancet Neurol"},{"issue":"5","key":"pone.0250820.ref008","doi-asserted-by":"crossref","first-page":"e390","DOI":"10.1212\/NXI.0000000000000390","article-title":"Teriflunomide slows BVL in relapsing MS: A reanalysis of the TEMSO MRI data set using SIENA","volume":"4","author":"EW Radue","year":"2017","journal-title":"Neurol Neuroimmunol NeuroInflammation"},{"key":"pone.0250820.ref009","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1177\/1352458519855722","article-title":"Association of brain volume loss and long-term disability outcomes in patients with multiple sclerosis treated with teriflunomide","volume":"26","author":"T Sprenger","year":"2020","journal-title":"Mult Scler"},{"key":"pone.0250820.ref010","doi-asserted-by":"crossref","first-page":"e379","DOI":"10.1212\/NXI.0000000000000379","article-title":"Predicting long-term disability outcomes in patients with MS treated with teriflunomide in TEMSO","volume":"4","author":"MP Sormani","year":"2017","journal-title":"Neurol Neuroimmunol neuroinflammation"},{"key":"pone.0250820.ref011","doi-asserted-by":"crossref","first-page":"102438","DOI":"10.1016\/j.msard.2020.102438","article-title":"Long-term safety and efficacy of teriflunomide in patients with relapsing multiple sclerosis: Results from the TOWER extension study","volume":"46","author":"AE Miller","year":"2020","journal-title":"Mult Scler Relat Disord"},{"key":"pone.0250820.ref012","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.msard.2019.05.014","article-title":"Long-term outcomes with teriflunomide in patients with clinically isolated syndrome: Results of the TOPIC extension study","volume":"33","author":"AE Miller","year":"2019","journal-title":"Mult Scler Relat Disord"},{"key":"pone.0250820.ref013","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1177\/1756285617722500","article-title":"Oral teriflunomide in the treatment of relapsing forms of multiple sclerosis: clinical evidence and long-term experience","volume":"10","author":"AE Miller","year":"2017","journal-title":"Ther Adv Neurol Disord"},{"key":"pone.0250820.ref014","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1038\/nrneurol.2016.188","article-title":"Treatment decisions in multiple sclerosis-insights from real-world observational studies","volume":"13","author":"M Trojano","year":"2017","journal-title":"Nat Rev Neurol"},{"key":"pone.0250820.ref015","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1177\/1932296819832661","article-title":"The New FDA Real-World Evidence Program to Support Development of Drugs and Biologics","volume":"14","author":"DC Klonoff","year":"2020","journal-title":"J Diabetes Sci Technol"},{"key":"pone.0250820.ref016","doi-asserted-by":"crossref","first-page":"e028133","DOI":"10.1136\/bmjopen-2018-028133","article-title":"Use of real-world evidence in postmarketing medicines regulation in the European Union: a systematic assessment of European Medicines Agency referrals 2013\u20132017","volume":"9","author":"JP Brown","year":"2019","journal-title":"BMJ Open"},{"key":"pone.0250820.ref017","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.msard.2018.09.017","article-title":"Patient-reported outcomes in patients with relapsing forms of MS switching to teriflunomide from other disease-modifying therapies: Results from the global Phase 4 Teri-PRO study in routine clinical practice","volume":"26","author":"PK Coyle","year":"2018","journal-title":"Mult Scler Relat Disord"},{"key":"pone.0250820.ref018","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.msard.2017.07.006","article-title":"Patient-reported outcomes in relapsing forms of MS: Real-world, global treatment experience with teriflunomide from the Teri-PRO study","volume":"17","author":"PK Coyle","year":"2017","journal-title":"Mult Scler Relat Disord"},{"key":"pone.0250820.ref019","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.msard.2019.03.022","article-title":"Teriflunomide real-world evidence: Global differences in the phase 4 Teri-PRO study","volume":"31","author":"PK Coyle","year":"2019","journal-title":"Mult Scler Relat Disord"},{"key":"pone.0250820.ref020","doi-asserted-by":"crossref","first-page":"1756286419835077","DOI":"10.1177\/1756286419835077","article-title":"Real-life outcomes of teriflunomide treatment in patients with relapsing multiple sclerosis: TAURUS-MS observational study","volume":"12","author":"BA Kallmann","year":"2019","journal-title":"Ther Adv Neurol Disord"},{"key":"pone.0250820.ref021","doi-asserted-by":"crossref","first-page":"3235","DOI":"10.1007\/s10072-020-04367-9","article-title":"A snapshot on patient-reported outcome measures of people with multiple sclerosis on first-line therapies in a real world setting","volume":"41","author":"R Lanzillo","year":"2020","journal-title":"Neurol Sci"},{"key":"pone.0250820.ref022","doi-asserted-by":"crossref","first-page":"305","DOI":"10.2217\/cer-2018-0135","article-title":"Comparative effectiveness of teriflunomide and dimethyl fumarate in patients with relapsing forms of MS in the retrospective real-world Teri-RADAR study","volume":"8","author":"R Zivadinov","year":"2019","journal-title":"J Comp Eff Res"},{"key":"pone.0250820.ref023","doi-asserted-by":"crossref","first-page":"102521","DOI":"10.1016\/j.msard.2020.102521","article-title":"An analysis of first-line disease-modifying therapies in patients with relapsing-remitting multiple sclerosis using the French nationwide health claims database from 2014\u20132017","volume":"46","author":"P Vermersch","year":"2020","journal-title":"Mult Scler Relat Disord"},{"key":"pone.0250820.ref024","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1177\/1352458519843055","article-title":"Pregnancy outcomes in patients with multiple sclerosis treated with teriflunomide: Clinical study data and 5 years of post-marketing experience","volume":"26","author":"S Vukusic","year":"2020","journal-title":"Mult Scler"},{"key":"pone.0250820.ref025","doi-asserted-by":"crossref","first-page":"E1811","DOI":"10.1212\/WNL.0000000000007314","article-title":"Comparative effectiveness of teriflunomide and dimethyl fumarate: A nationwide cohort study","volume":"92","author":"MD Buron","year":"2019","journal-title":"Neurology"},{"key":"pone.0250820.ref026","doi-asserted-by":"crossref","first-page":"2706","DOI":"10.3389\/fimmu.2018.02706","article-title":"Pregnancy outcomes in men and women treated with teriflunomide. A population-based nationwide Danish register study","volume":"9","author":"JB Andersen","year":"2018","journal-title":"Front Immunol"},{"key":"pone.0250820.ref027","doi-asserted-by":"crossref","first-page":"549","DOI":"10.2147\/CLEP.S99500","article-title":"The Danish multiple sclerosis treatment register","volume":"8","author":"M Magyari","year":"2016","journal-title":"Clin Epidemiol"},{"key":"pone.0250820.ref028","first-page":"e01921","article-title":"The Danish Multiple Sclerosis Registry","author":"M Magyari","year":"2020","journal-title":"Brain Behav"},{"key":"pone.0250820.ref029","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1001\/archneurol.2010.150","article-title":"Disability progression in a clinical trial of relapsing-remitting multiple sclerosis eight-year follow-up","volume":"67","author":"RA Rudick","year":"2010","journal-title":"Arch Neurol"},{"key":"pone.0250820.ref030","doi-asserted-by":"crossref","first-page":"102813","DOI":"10.1016\/j.msard.2021.102813","article-title":"Age and sex as determinants of treatment decisions in patients with relapsing-remitting MS","volume":"50","author":"P Sorensen","year":"2021","journal-title":"Mult Scler Relat Disord"},{"key":"pone.0250820.ref031","doi-asserted-by":"crossref","first-page":"238","DOI":"10.3389\/fnagi.2018.00238","article-title":"Interplay between age and neuroinflammation in multiple sclerosis: Effects on motor and cognitive functions","volume":"10","author":"A Musella","year":"2018","journal-title":"Front Aging Neurosci"},{"key":"pone.0250820.ref032","doi-asserted-by":"crossref","first-page":"1996","DOI":"10.1212\/WNL.0b013e31821e559d","article-title":"Demographic and clinical characteristics of malignant multiple sclerosis","volume":"76","author":"T Gholipour","year":"2011","journal-title":"Neurology"},{"key":"pone.0250820.ref033","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/S1474-4422(17)30470-2","article-title":"Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria","volume":"17","author":"AJ Thompson","year":"2018","journal-title":"Lancet Neurol"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0250820","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,5,18]],"date-time":"2021-05-18T17:37:57Z","timestamp":1621359477000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0250820"}},"subtitle":[],"editor":[{"given":"Sreeram V.","family":"Ramagopalan","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2021,5,18]]},"references-count":33,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2021,5,18]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0250820","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,18]]}}}