{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T08:50:08Z","timestamp":1792227008721,"version":"4.4.0"},"reference-count":29,"publisher":"American Medical Association (AMA)","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Neurol"],"published-print":{"date-parts":[[2023,10,1]]},"abstract":"\n Importance<\/jats:title>\n Radiologically isolated syndrome (RIS) represents the earliest detectable preclinical phase of multiple sclerosis (MS) punctuated by incidental magnetic resonance imaging (MRI) white matter anomalies within the central nervous system.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To determine the time to onset of symptoms consistent with MS.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n From September 2017 to October 2022, this multicenter, double-blind, phase 3, randomized clinical trial investigated the efficacy of teriflunomide in delaying MS in individuals with RIS, with a 3-year follow-up. The setting included referral centers in France, Switzerland, and Turkey. Participants older than 18 years meeting 2009 RIS criteria were randomly assigned (1:1) to oral teriflunomide, 14 mg daily, or placebo up to week 96 or, optionally, to week 144.<\/jats:p>\n <\/jats:sec>\n \n Interventions<\/jats:title>\n Clinical, MRI, and patient-reported outcomes (PROs) were collected at baseline and yearly until week 96, with an optional third year in the allocated arm if no symptoms have occurred.<\/jats:p>\n <\/jats:sec>\n \n Main outcomes<\/jats:title>\n Primary analysis was performed in the intention-to-treat population, and safety was assessed accordingly. Secondary end points included MRI outcomes and PROs.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Among 124 individuals assessed for eligibility, 35 were excluded for declining to participate, not meeting inclusion criteria, or loss of follow-up. Eighty-nine participants (mean [SD] age, 37.8 [12.1] years; 63 female [70.8%]) were enrolled (placebo, 45 [50.6%]; teriflunomide, 44 [49.4%]). Eighteen participants (placebo, 9 [50.0%]; teriflunomide, 9 [50.0%]) discontinued the study, resulting in a dropout rate of 20% for adverse events (3 [16.7%]), consent withdrawal (4 [22.2%]), loss to follow-up (5 [27.8%]), voluntary withdrawal (4 [22.2%]), pregnancy (1 [5.6%]), and study termination (1 [5.6%]). The time to the first clinical event was significantly extended in the teriflunomide arm compared with placebo, in both the unadjusted (hazard ratio [HR],\u20090.37; 95% CI,\u20090.16-0.84;\n P<\/jats:italic>\n \u2009=\u2009.02) and adjusted (HR,\u20090.28; 95% CI,\u20090.11-0.71;\n P<\/jats:italic>\n \u2009=\u2009.007) analysis. Secondary imaging end point outcomes including the comparison of the cumulative number of new or newly enlarging T2 lesions (rate ratio [RR],\u20090.57; 95% CI,\u20090.27-1.20;\n P<\/jats:italic>\n \u2009=\u2009.14), new gadolinium-enhancing lesions (RR,\u20090.33; 95% CI, 0.09-1.17;\n P<\/jats:italic>\n \u2009=\u2009.09), and the proportion of participants with new lesions (odds ratio,\u20090.72; 95% CI, 0.25-2.06;\n P<\/jats:italic>\n \u2009=\u2009.54) were not significant.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion and Relevance<\/jats:title>\n Treatment with teriflunomide resulted in an unadjusted risk reduction of 63% and an adjusted risk reduction of 72%, relative to placebo, in preventing a first clinical demyelinating event. These data suggest a benefit to early treatment in the MS disease spectrum.<\/jats:p>\n <\/jats:sec>\n \n Trial Registration<\/jats:title>\n \n ClinicalTrials.gov Identifier:\n NCT03122652<\/jats:ext-link>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamaneurol.2023.2815","type":"journal-article","created":{"date-parts":[[2023,8,21]],"date-time":"2023-08-21T11:32:43Z","timestamp":1692617563000},"page":"1080","source":"Crossref","is-referenced-by-count":96,"title":["Teriflunomide and Time to Clinical Multiple Sclerosis in Patients With Radiologically Isolated Syndrome"],"prefix":"10.1001","volume":"80","author":[{"given":"Christine","family":"Lebrun-Fr\u00e9nay","sequence":"first","affiliation":[{"name":"Centre de Ressources et de Comp\u00e9tences Sclerose En Plaques, Neurologie Pasteur 2, CHU de Nice, Universit\u00e9 Cote d\u2019Azur, UMR2CA-URRIS, Nice, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aksel","family":"Siva","sequence":"additional","affiliation":[{"name":"Cerrahpasa School of Medicine, Istanbul University, Istanbul, Turkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Pia","family":"Sormani","sequence":"additional","affiliation":[{"name":"University of Genoa, Genoa, Italy"},{"name":"Ospedale Policlinico San Martino Instituti di Ricovero e Cura a Carattere Scientifico, Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cassandre","family":"Landes-Chateau","sequence":"additional","affiliation":[{"name":"Centre de Ressources et de Comp\u00e9tences Sclerose En Plaques, Neurologie Pasteur 2, CHU de Nice, Universit\u00e9 Cote d\u2019Azur, UMR2CA-URRIS, Nice, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lydiane","family":"Mondot","sequence":"additional","affiliation":[{"name":"Centre de Ressources et de Comp\u00e9tences Sclerose En Plaques, Neurologie Pasteur 2, CHU de Nice, Universit\u00e9 Cote d\u2019Azur, UMR2CA-URRIS, Nice, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Bovis","sequence":"additional","affiliation":[{"name":"University of Genoa, Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Vermersch","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Lille, Inserm, Unit 1172, LilNCog, Centre Hospitalier Universitaire de Lille, F\u00e9d\u00e9ration Hospitalo-Universitaire Precise, Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Papeix","sequence":"additional","affiliation":[{"name":"Assistance Publique des H\u00f4pitaux de Paris, Piti\u00e9-Salp\u00eatri\u00e8re Hospital, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Thouvenot","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis Clinic, N\u00eemes University Hospital, N\u00eemes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Labauge","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis Clinic, Montpellier University Hospital, Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7oise","family":"Durand-Dubief","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis Clinic, Hospices Civils de Lyon, Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Husnu","family":"Efendi","sequence":"additional","affiliation":[{"name":"Neurology, Kocaeli University Faculty of Medicine, Kocaeli, Turkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuelle","family":"Le Page","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis Clinic, Rennes University Hospital, Inserm, CIC1414, Rennes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Murat","family":"Terzi","sequence":"additional","affiliation":[{"name":"School of Medicine, Neurology, Ondokuz Mayis University, Samsun, Turkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Derache","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis Clinic, Caen University Hospital, Caen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bertrand","family":"Bourre","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis Clinic, Rouen University Hospital, Rouen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Hoepner","sequence":"additional","affiliation":[{"name":"Department of Neurology, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rana","family":"Karabudak","sequence":"additional","affiliation":[{"name":"Hacettepe University Medical Faculty, School of Medicine, Ankara, Turkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e9r\u00f4me","family":"De Seze","sequence":"additional","affiliation":[{"name":"Strasbourg University Hospital, Clinical Investigation Center, INBSRM 1434, Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Ciron","sequence":"additional","affiliation":[{"name":"Toulouse University Hospital, Centre de Ressources et de Comp\u00e9tences Scl\u00e9rose en Plaques, Department of Neurology, Universit\u00e9 Toulouse III, Infinity, Inserm UMR1291, CNRS UMR5051, Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Clavelou","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis Clinic, Clermont-Ferrand University Hospital, Clermont-Ferrand, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandrine","family":"Wiertlewski","sequence":"additional","affiliation":[{"name":"Centre de Ressources et de Comp\u00e9tences Scl\u00e9rose en Plaques and Clinical Investigation Center, Inserm, Nantes University Hospital, France"},{"name":"Transplantation and Immunology Transplantation Center, Inserm, Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omer Faruk","family":"Turan","sequence":"additional","affiliation":[{"name":"School of Medicine, Uludag University, Bursa, Turkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nur","family":"Yucear","sequence":"additional","affiliation":[{"name":"Ege University Medical Faculty, Bornova, Izmir, Turkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikael","family":"Cohen","sequence":"additional","affiliation":[{"name":"Centre de Ressources et de Comp\u00e9tences Sclerose En Plaques, Neurologie Pasteur 2, CHU de Nice, Universit\u00e9 Cote d\u2019Azur, UMR2CA-URRIS, Nice, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Azevedo","sequence":"additional","affiliation":[{"name":"University of South California, Los Angeles"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Orhun H.","family":"Kantarci","sequence":"additional","affiliation":[{"name":"Mayo Clinic, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darin T.","family":"Okuda","sequence":"additional","affiliation":[{"name":"The University of Texas Southwestern Medical Center, Dallas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Pelletier","sequence":"additional","affiliation":[{"name":"Ege University Medical Faculty, Bornova, Izmir, Turkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"TERIS Study Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Branger","sequence":"additional","affiliation":[{"name":"for the TERIS Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mouloud","family":"Abrous","sequence":"additional","affiliation":[{"name":"for the TERIS Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00e9l\u00e8ne","family":"Z\u00e9phir","sequence":"additional","affiliation":[{"name":"for the TERIS Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Petit","sequence":"additional","affiliation":[{"name":"for the TERIS Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Vukusic","sequence":"additional","affiliation":[{"name":"for the TERIS Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9line","family":"Gelet","sequence":"additional","affiliation":[{"name":"for the TERIS Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clarisse","family":"Carra-Dalli\u00e8re","sequence":"additional","affiliation":[{"name":"for the TERIS Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"Ayrignac","sequence":"additional","affiliation":[{"name":"for the TERIS Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e9lanie","family":"Russello","sequence":"additional","affiliation":[{"name":"for the TERIS Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Laplaud","sequence":"additional","affiliation":[{"name":"for the TERIS Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alina","family":"Gaultier","sequence":"additional","affiliation":[{"name":"for the TERIS Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabienne","family":"Le Fr\u00e8re","sequence":"additional","affiliation":[{"name":"for the TERIS Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9line","family":"Callier","sequence":"additional","affiliation":[{"name":"for the TERIS Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia","family":"Caillon","sequence":"additional","affiliation":[{"name":"for the TERIS Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eglantine","family":"Gueydan","sequence":"additional","affiliation":[{"name":"for the TERIS Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9line","family":"Louapre","sequence":"additional","affiliation":[{"name":"for the TERIS Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damien","family":"Galanaud","sequence":"additional","affiliation":[{"name":"for the TERIS Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aurelian","family":"Ungureanu","sequence":"additional","affiliation":[{"name":"for the TERIS Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvie","family":"Coudoin","sequence":"additional","affiliation":[{"name":"for the TERIS Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Hebant","sequence":"additional","affiliation":[{"name":"for the TERIS Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel","family":"Gerard","sequence":"additional","affiliation":[{"name":"for the TERIS Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Vimont","sequence":"additional","affiliation":[{"name":"for the TERIS Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damien","family":"Biotti","sequence":"additional","affiliation":[{"name":"for the TERIS Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrice","family":"Bonneville","sequence":"additional","affiliation":[{"name":"for the TERIS Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noellie","family":"Freitas","sequence":"additional","affiliation":[{"name":"for the TERIS Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taskin","family":"Duman","sequence":"additional","affiliation":[{"name":"for the TERIS Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erhan","family":"Kilic","sequence":"additional","affiliation":[{"name":"for the TERIS Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melih","family":"Tutuncu","sequence":"additional","affiliation":[{"name":"for the TERIS Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ugur","family":"Uygunoglu","sequence":"additional","affiliation":[{"name":"for the TERIS Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sena","family":"Destan","sequence":"additional","affiliation":[{"name":"for the TERIS Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sedat","family":"Sen","sequence":"additional","affiliation":[{"name":"for the TERIS Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Friedli","sequence":"additional","affiliation":[{"name":"for the TERIS Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franca","family":"Wagner","sequence":"additional","affiliation":[{"name":"for the TERIS Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lea","family":"Weber","sequence":"additional","affiliation":[{"name":"for the TERIS Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annaig","family":"Tchoubar","sequence":"additional","affiliation":[{"name":"for the TERIS Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilie","family":"Dumont","sequence":"additional","affiliation":[{"name":"for the TERIS Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asli","family":"Eryilmaz","sequence":"additional","affiliation":[{"name":"for the TERIS Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanguy","family":"Roman","sequence":"additional","affiliation":[{"name":"for the TERIS Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Pelletreau","sequence":"additional","affiliation":[{"name":"for the TERIS Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aur\u00e9lie","family":"Grateau","sequence":"additional","affiliation":[{"name":"for the TERIS Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanica","family":"Mathieu","sequence":"additional","affiliation":[{"name":"for the TERIS Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarhan","family":"Yaiche","sequence":"additional","affiliation":[{"name":"for the TERIS Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix","family":"Rintelen","sequence":"additional","affiliation":[{"name":"for the TERIS Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Firmino","sequence":"additional","affiliation":[{"name":"for the TERIS Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aymeric","family":"De Chastenier","sequence":"additional","affiliation":[{"name":"for the TERIS Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amel","family":"Gheribenblidia","sequence":"additional","affiliation":[{"name":"for the TERIS Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Burcu","family":"Zeydan","sequence":"additional","affiliation":[{"name":"for the TERIS Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","reference":[{"issue":"9","key":"noi230058r1","doi-asserted-by":"publisher","first-page":"800","DOI":"10.1212\/01.wnl.0000335764.14513.1a","article-title":"Incidental MRI anomalies suggestive of multiple sclerosis: the radiologically isolated syndrome.","volume":"72","author":"Okuda","year":"2009","journal-title":"Neurology"},{"issue":"7","key":"noi230058r2","doi-asserted-by":"publisher","first-page":"841","DOI":"10.1001\/archneurol.2009.119","article-title":"Association between clinical conversion to multiple sclerosis in radiologically isolated syndrome and magnetic resonance imaging, cerebrospinal fluid, and visual evoked potential: follow-up of 70 patients.","volume":"66","author":"Lebrun","year":"2009","journal-title":"Arch Neurol"},{"issue":"9","key":"noi230058r3","doi-asserted-by":"publisher","first-page":"800","DOI":"10.1212\/01.wnl.0000335764.14513.1a","article-title":"Incidental MRI anomalies suggestive of multiple sclerosis: the radiologically isolated syndrome.","volume":"72","author":"Okuda","year":"2009","journal-title":"Neurology"},{"issue":"6","key":"noi230058r4","doi-asserted-by":"publisher","first-page":"840","DOI":"10.1002\/(ISSN)1531-8249","article-title":"Diagnostic criteria for multiple sclerosis: 2005 revisions to the \u201cMcDonald Criteria\u201d.","volume":"58","author":"Polman","year":"2005","journal-title":"Ann Neurol"},{"issue":"3","key":"noi230058r5","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0090509","article-title":"Radiologically isolated syndrome: 5-year risk for an initial clinical event.","volume":"9","author":"Okuda","year":"2014","journal-title":"PLoS One"},{"issue":"2","key":"noi230058r6","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1002\/ana.v88.2","article-title":"Radiologically isolated syndrome: 10-year risk estimate of a clinical event.","volume":"88","author":"Lebrun","year":"2020","journal-title":"Ann Neurol"},{"issue":"2","key":"noi230058r7","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1002\/ana.v79.2","article-title":"Primary progressive multiple sclerosis evolving from radiologically isolated syndrome.","volume":"79","author":"Kantarci","year":"2016","journal-title":"Ann Neurol"},{"issue":"1","key":"noi230058r8","doi-asserted-by":"publisher","DOI":"10.1177\/2055217319836664","article-title":"Oligoclonal bands increase the specificity of MRI criteria to predict multiple sclerosis in children with radiologically isolated syndrome.","volume":"5","author":"Makhani","year":"2019","journal-title":"Mult Scler J Exp Transl Clin"},{"issue":"2","key":"noi230058r9","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1177\/1352458517751049","article-title":"ECTRIMS\/EAN guideline on the pharmacological treatment of people with multiple sclerosis.","volume":"24","author":"Montalban","year":"2018","journal-title":"Mult Scler"},{"issue":"10","key":"noi230058r10","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2021.28271","article-title":"Risk factors and time to clinical symptoms of multiple sclerosis among patients with radiologically isolated syndrome.","volume":"4","author":"Lebrun-Fr\u00e9nay","year":"2021","journal-title":"JAMA Netw Open"},{"issue":"3","key":"noi230058r11","doi-asserted-by":"publisher","first-page":"604","DOI":"10.1002\/ana.v93.3","article-title":"Dimethyl fumarate delays multiple sclerosis in radiologically isolated syndrome.","volume":"93","author":"Okuda","year":"2023","journal-title":"Ann Neurol"},{"key":"noi230058r12","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/j.msard.2015.11.006","article-title":"Pooled safety and tolerability data from 4 placebo-controlled teriflunomide studies and extensions.","volume":"5","author":"Comi","year":"2016","journal-title":"Mult Scler Relat Disord"},{"issue":"10","key":"noi230058r13","doi-asserted-by":"publisher","first-page":"920","DOI":"10.1212\/WNL.0000000000002441","article-title":"Long-term safety and efficacy of teriflunomide: 9-year follow-up of the randomized TEMSO study.","volume":"86","author":"O\u2019Connor","year":"2016","journal-title":"Neurology"},{"issue":"10","key":"noi230058r17","doi-asserted-by":"publisher","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":"Miller","year":"2014","journal-title":"Lancet Neurol"},{"issue":"14","key":"noi230058r18","doi-asserted-by":"publisher","first-page":"1293","DOI":"10.1056\/NEJMoa1014656","article-title":"Randomized trial of oral teriflunomide for relapsing multiple sclerosis.","volume":"365","author":"O\u2019Connor","year":"2011","journal-title":"N Engl J Med"},{"issue":"3","key":"noi230058r19","doi-asserted-by":"publisher","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":"Confavreux","year":"2014","journal-title":"Lancet Neurol"},{"issue":"2","key":"noi230058r20","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1016\/S1474-4422(11)70274-5","article-title":"Clinically isolated syndromes.","volume":"11","author":"Miller","year":"2012","journal-title":"Lancet Neurol"},{"issue":"8","key":"noi230058r21","doi-asserted-by":"publisher","first-page":"980","DOI":"10.1016\/j.neurol.2021.04.011","article-title":"Infections and multiple sclerosis: recommendations from the French Multiple Sclerosis Society.","volume":"177","author":"Papeix","year":"2021","journal-title":"Rev Neurol (Paris)"},{"issue":"12","key":"noi230058r22","doi-asserted-by":"publisher","first-page":"1098","DOI":"10.1056\/NEJMoa1114287","article-title":"Placebo-controlled phase 3 study of oral BG-12 for relapsing multiple sclerosis.","volume":"367","author":"Gold","year":"2012","journal-title":"N Engl J Med"},{"issue":"12","key":"noi230058r23","doi-asserted-by":"publisher","first-page":"1087","DOI":"10.1056\/NEJMoa1206328","article-title":"Placebo-controlled phase 3 study of oral BG-12 or glatiramer in multiple sclerosis.","volume":"367","author":"Fox","year":"2012","journal-title":"N Engl J Med"},{"key":"noi230058r24","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awad073","article-title":"The radiologically isolated syndrome: revised diagnostic criteria.","author":"Lebrun-Fr\u00e9nay","journal-title":"Brain"},{"issue":"2","key":"noi230058r25","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1177\/1352458512451510","article-title":"Onset of progressive phase is an age-dependent clinical milestone in multiple sclerosis.","volume":"19","author":"Tutuncu","year":"2013","journal-title":"Mult Scler"},{"issue":"6","key":"noi230058r26","doi-asserted-by":"publisher","first-page":"968","DOI":"10.1212\/01.wnl.0000237354.10144.ec","article-title":"Baseline MRI predicts future attacks and disability in clinically isolated syndromes.","volume":"67","author":"Tintor\u00e9","year":"2006","journal-title":"Neurology"},{"issue":"8","key":"noi230058r27","doi-asserted-by":"publisher","first-page":"2276","DOI":"10.1093\/brain\/awz156","article-title":"Early imaging predictors of long-term outcomes in relapse-onset multiple sclerosis.","volume":"142","author":"Brownlee","year":"2019","journal-title":"Brain"},{"issue":"13","key":"noi230058r28","doi-asserted-by":"publisher","first-page":"1393","DOI":"10.1212\/WNL.0000000000003152","article-title":"The contemporary spectrum of multiple sclerosis misdiagnosis: a multicenter study.","volume":"87","author":"Solomon","year":"2016","journal-title":"Neurology"},{"issue":"22","key":"noi230058r29","doi-asserted-by":"publisher","first-page":"e2527","DOI":"10.1212\/WNL.0000000000007573","article-title":"\u201cBetter explanations\u201d in multiple sclerosis diagnostic workup: a 3-year longitudinal study.","volume":"92","author":"Calabrese","year":"2019","journal-title":"Neurology"},{"key":"noi230058r14","unstructured":"European Medicines Agency. ICH topic E6 (R1) guideline for good clinical practice. Accessed February 10, 2023. https:\/\/www.ema.europa.eu\/en\/documents\/scientific-guideline\/ich-e6-r1-guideline-good-clinical-practice_en.pdf"},{"key":"noi230058r15","unstructured":"World Medical Association. WMA Declaration of Helsinki\u2014ethical principles for medical research involving human subjects. Accessed February 10, 2023. https:\/\/www.wma.net\/policies-post\/wma-declaration-of-helsinki-ethical-principles-for-medical-research-involving-human-subjects\/)."},{"key":"noi230058r16","unstructured":"Aubagio. Summary of product characteristics. https:\/\/www.ema.europa.eu\/en\/documents\/product-information\/aubagio-epar-product-information_en.pdf"}],"container-title":["JAMA Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamaneurology\/articlepdf\/2808741\/jamaneurology_lebrunfrnay_2023_oi_230058_1695756359.26781.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,9]],"date-time":"2023-10-09T11:04:09Z","timestamp":1696849449000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamaneurology\/fullarticle\/2808741"}},"subtitle":["The TERIS Randomized Clinical Trial"],"short-title":[],"issued":{"date-parts":[[2023,10,1]]},"references-count":29,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2023,10,1]]}},"URL":"https:\/\/doi.org\/10.1001\/jamaneurol.2023.2815","relation":{},"ISSN":["2168-6149"],"issn-type":[{"value":"2168-6149","type":"print"}],"subject":[],"published":{"date-parts":[[2023,10,1]]}}}