{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T01:57:21Z","timestamp":1793066241764,"version":"4.5.0"},"reference-count":32,"publisher":"American Medical Association (AMA)","issue":"16","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA"],"published-print":{"date-parts":[[2025,4,22]]},"abstract":"<jats:sec><jats:title>Importance<\/jats:title><jats:p>Vitamin D deficiency is a risk factor for multiple sclerosis (MS) and is associated with the risk of disease activity, but data on the benefits of supplementation are conflicting.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To evaluate the efficacy of high-dose cholecalciferol as monotherapy in reducing disease activity in patients with clinically isolated syndrome (CIS) typical for MS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design, Setting, and Participants<\/jats:title><jats:p>The D-Lay MS trial was a parallel, double-blind, randomized placebo-controlled clinical trial in 36 MS centers in France. Patients were enrolled from July 2013 to December 2020 (final follow-up on January 18, 2023). Untreated patients with CIS aged 18 to 55 years with CIS duration less than 90 days, serum vitamin D concentration less than 100 nmol\/L, and diagnostic magnetic resonance imaging (MRI) meeting 2010 criteria for dissemination in space or 2 or more lesions and presence of oligoclonal bands were recruited.<\/jats:p><\/jats:sec><jats:sec><jats:title>Intervention<\/jats:title><jats:p>Patients were randomized 1:1 to receive oral cholecalciferol 100\u202f000 IU (n\u2009=\u2009163) or placebo (n\u2009=\u2009153) every 2 weeks for 24 months.<\/jats:p><\/jats:sec><jats:sec><jats:title>Main Outcomes and Measures<\/jats:title><jats:p>The primary outcome measure was disease activity, defined as occurrence of a relapse and\/or MRI activity (new and\/or contrast-enhancing lesions) over 24 months of follow-up, also analyzed as separate secondary outcomes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of the 316 participants enrolled and randomized (median [IQR] age, 34 [28-42] years; 70% women), the primary analysis included 303 patients (95.9%) who took at least 1 dose of the study drug and 288 (91.1%) ultimately completed the 24-month trial. Disease activity was observed in 94 patients (60.3%) in the vitamin D group and 109 patients (74.1%) in the placebo group (hazard ratio [HR], 0.66 [95% CI, 0.50-0.87]; <jats:italic>P<\/jats:italic>\u2009=\u2009.004), and median time to disease activity was longer in the vitamin D group (432 vs 224 days; log-rank <jats:italic>P<\/jats:italic>\u2009=\u2009.003). All 3 secondary MRI outcomes reported significant differences favoring the vitamin D group vs the placebo group: MRI activity (89 patients [57.1%] vs 96 patients [65.3%]; HR, 0.71 [95% CI, 0.53-0.95]; <jats:italic>P<\/jats:italic>\u2009=\u2009.02), new lesions (72 patients [46.2%] vs 87 patients [59.2%]; HR, 0.61 [95% CI, 0.44-0.84]; <jats:italic>P<\/jats:italic>\u2009=\u2009.003), and contrast-enhancing lesions (29 patients [18.6%] vs 50 patients [34.0%]; HR, 0.47 [95% CI, 0.30-0.75]; <jats:italic>P<\/jats:italic>\u2009=\u2009.001). All 10 secondary clinical outcomes showed no significant difference, including relapse, which occurred in 28 patients (17.9%) in the vitamin D group vs 32 (21.8%) in the placebo group (HR, 0.69 [95% CI, 0.42-1.16]; <jats:italic>P<\/jats:italic>\u2009=\u2009.16). Results were similar in a subset of 247 patients meeting updated 2017 diagnostic criteria for relapsing-remitting MS at treatment initiation. Severe adverse events occurred in 17 patients in the vitamin D group and 13 in the placebo group, none of which were related to cholecalciferol.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Relevance<\/jats:title><jats:p>Oral cholecalciferol 100\u202f000 IU every 2 weeks significantly reduced disease activity in CIS and early relapsing-remitting MS. These results warrant further investigation, including the potential role of pulse high-dose vitamin D as add-on therapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Trial Registration<\/jats:title><jats:p>ClinicalTrials.gov Identifier: <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/study\/NCT01817166\">NCT01817166<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1001\/jama.2025.1604","type":"journal-article","created":{"date-parts":[[2025,3,10]],"date-time":"2025-03-10T15:00:51Z","timestamp":1741618851000},"page":"1413","source":"Crossref","is-referenced-by-count":89,"title":["High-Dose Vitamin D in Clinically Isolated Syndrome Typical of Multiple Sclerosis"],"prefix":"10.1001","volume":"333","author":[{"given":"Eric","family":"Thouvenot","sequence":"first","affiliation":[{"name":"CHU Nimes, Service de Neurologie, Univ Montpellier, Nimes, France"},{"name":"Institut de G\u00e9nomique Fonctionnelle, Univ Montpellier, CNRS, INSERM, Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Laplaud","sequence":"additional","affiliation":[{"name":"CHU Nantes, CRC-SEP, Nantes Universit\u00e9, CIC1413, Centre de Recherche en Transplantation et Immunologie Translationnelle, Inserm U1064, Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Lebrun-Frenay","sequence":"additional","affiliation":[{"name":"CHU Nice, Universit\u00e9 cote d\u2019Azur UR2CA-URRIS, Nice, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Derache","sequence":"additional","affiliation":[{"name":"CHU Caen, CRC-SEP, Caen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuelle","family":"Le Page","sequence":"additional","affiliation":[{"name":"Clinical Neuroscience Centre, CIC_P1414 INSERM, Rennes University Hospital, Rennes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Maillart","sequence":"additional","affiliation":[{"name":"H\u00f4pitaux Universitaires Piti\u00e9 Salp\u00eatri\u00e8re \u2013 Charles Foix, Service de Neurologie, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Froment-Tilikete","sequence":"additional","affiliation":[{"name":"Hospices Civils de Lyon, Service de neurocognition et neuro-ophtalmologie, Universit\u00e9 Claude Bernard Lyon 1, Lyon, France"},{"name":"Centre de Recherche en Neurosciences de Lyon, Equipe IMPACT, Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Castelnovo","sequence":"additional","affiliation":[{"name":"CHU Nimes, Service de Neurologie, Univ Montpellier, Nimes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Casez","sequence":"additional","affiliation":[{"name":"CHU Grenoble Alpes, Service de Neurologie, La Tronche, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Coustans","sequence":"additional","affiliation":[{"name":"CH De Cornouaille, Service de Neurologie, Quimper, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne-Marie","family":"Guennoc","sequence":"additional","affiliation":[{"name":"CHRU Tours, Service de Neurologie, Tours, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Heinzlef","sequence":"additional","affiliation":[{"name":"CHI Poissy Saint Germain, Service de Neurologie, Poissy, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"Magy","sequence":"additional","affiliation":[{"name":"CHU Dupuytren 1, Service de Neurologie, Limoges, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chantal","family":"Nifle","sequence":"additional","affiliation":[{"name":"CH Versailles \u2013 Hospital Andr\u00e9 Mignot, Service de Neurologie, Le Chesnay-Rocquencourt, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"Ayrignac","sequence":"additional","affiliation":[{"name":"CHU Montpellier, Service de Neurologie, Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agn\u00e8s","family":"Fromont","sequence":"additional","affiliation":[{"name":"CHU Dijon Bourgogne, Service de Neurologie, Dijon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Gaillard","sequence":"additional","affiliation":[{"name":"CH Perpignan, Service de Neurologie, Perpignan, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Caucheteux","sequence":"additional","affiliation":[{"name":"CHU Reims, Service de Neurologie, Reims, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivania","family":"Patry","sequence":"additional","affiliation":[{"name":"CH Sud Francilien, Service de Neurologie, Corbeil-Essonnes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e9r\u00f4me","family":"De S\u00e8ze","sequence":"additional","affiliation":[{"name":"H\u00f4pital Civil, Service de Neurologie, Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romain","family":"Deschamps","sequence":"additional","affiliation":[{"name":"H\u00f4pital Fondation Adolphe De Rothschild, Service de Neurologie, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Clavelou","sequence":"additional","affiliation":[{"name":"CHU Gabriel-Montpied, Service de Neurologie, Clermont-Ferrand, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damien","family":"Biotti","sequence":"additional","affiliation":[{"name":"CHU Toulouse, Service de Neurologie, Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilles","family":"Edan","sequence":"additional","affiliation":[{"name":"Clinical Neuroscience Centre, CIC_P1414 INSERM, Rennes University Hospital, Rennes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Camu","sequence":"additional","affiliation":[{"name":"INM, UnivMontpellier, INSERM, Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanane","family":"Agherbi","sequence":"additional","affiliation":[{"name":"CHU Nimes, Service de Neurologie, Univ Montpellier, Nimes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitri","family":"Renard","sequence":"additional","affiliation":[{"name":"CHU Nimes, Service de Neurologie, Univ Montpellier, Nimes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Demattei","sequence":"additional","affiliation":[{"name":"CHU Nimes, Laboratoire de Biostatistique, Epid\u00e9miologie clinique, Sant\u00e9 Publique Innovation et M\u00e9thodologie (BESPIM), Univ Montpellier, Nimes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascale","family":"Fabbro-Peray","sequence":"additional","affiliation":[{"name":"CHU Nimes, Laboratoire de Biostatistique, Epid\u00e9miologie clinique, Sant\u00e9 Publique Innovation et M\u00e9thodologie (BESPIM), Univ Montpellier, Nimes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thibault","family":"Mura","sequence":"additional","affiliation":[{"name":"CHU Nimes, Laboratoire de Biostatistique, Epid\u00e9miologie clinique, Sant\u00e9 Publique Innovation et M\u00e9thodologie (BESPIM), Univ Montpellier, Nimes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manon","family":"Rival","sequence":"additional","affiliation":[{"name":"CHU Nimes, Service de Neurologie, Univ Montpellier, Nimes, France"},{"name":"Institut de G\u00e9nomique Fonctionnelle, Univ Montpellier, CNRS, INSERM, Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"D-Lay MS Investigators","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fr\u00e9d\u00e9ric","family":"TAITHE","sequence":"additional","affiliation":[{"name":"for the D-Lay MS Investigators"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique","family":"AUFAUVRE","sequence":"additional","affiliation":[{"name":"for the D-Lay MS Investigators"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thibault","family":"MOREAU","sequence":"additional","affiliation":[{"name":"for the D-Lay MS Investigators"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathieu","family":"VAILLANT","sequence":"additional","affiliation":[{"name":"for the D-Lay MS Investigators"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"OUTTERYCK","sequence":"additional","affiliation":[{"name":"for the D-Lay MS Investigators"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gauthier","family":"CALAIS","sequence":"additional","affiliation":[{"name":"for the D-Lay MS Investigators"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"HAUTECOEUR","sequence":"additional","affiliation":[{"name":"for the D-Lay MS Investigators"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexis","family":"MONTCUQUET","sequence":"additional","affiliation":[{"name":"for the D-Lay MS Investigators"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clarisse","family":"CARRA DALLIERE","sequence":"additional","affiliation":[{"name":"for the D-Lay MS Investigators"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"PITTION-VOUYOVITCH","sequence":"additional","affiliation":[{"name":"for the D-Lay MS Investigators"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"LANCIN GARCIA","sequence":"additional","affiliation":[{"name":"for the D-Lay MS Investigators"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laure","family":"MICHEL","sequence":"additional","affiliation":[{"name":"for the D-Lay MS Investigators"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirela","family":"FAIGHEL","sequence":"additional","affiliation":[{"name":"for the D-Lay MS Investigators"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aurelia","family":"SCHUNCK","sequence":"additional","affiliation":[{"name":"for the D-Lay MS Investigators"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandrine","family":"WIERTLEWSKI","sequence":"additional","affiliation":[{"name":"for the D-Lay MS Investigators"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Violaine","family":"TALMANT","sequence":"additional","affiliation":[{"name":"for the D-Lay MS Investigators"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flora","family":"LEJEUNE","sequence":"additional","affiliation":[{"name":"for the D-Lay MS Investigators"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loreen","family":"DELALANDE","sequence":"additional","affiliation":[{"name":"for the D-Lay MS Investigators"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"COULOUME","sequence":"additional","affiliation":[{"name":"for the D-Lay MS Investigators"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mickael","family":"COHEN","sequence":"additional","affiliation":[{"name":"for the D-Lay MS Investigators"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"WACONGNE","sequence":"additional","affiliation":[{"name":"for the D-Lay MS Investigators"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"MAS","sequence":"additional","affiliation":[{"name":"for the D-Lay MS Investigators"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adil","family":"MAAROUF","sequence":"additional","affiliation":[{"name":"for the D-Lay MS Investigators"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayman","family":"TOURBAH","sequence":"additional","affiliation":[{"name":"for the D-Lay MS Investigators"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V\u00e9ronique","family":"DEBURGHGRAEVE","sequence":"additional","affiliation":[{"name":"for the D-Lay MS Investigators"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"KERBAT","sequence":"additional","affiliation":[{"name":"for the D-Lay MS Investigators"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bertrand","family":"BOURRE","sequence":"additional","affiliation":[{"name":"for the D-Lay MS Investigators"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"BRASSAT","sequence":"additional","affiliation":[{"name":"for the D-Lay MS Investigators"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"CIRON","sequence":"additional","affiliation":[{"name":"for the D-Lay MS Investigators"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julien","family":"BIBERON","sequence":"additional","affiliation":[{"name":"for the D-Lay MS Investigators"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"DEVY","sequence":"additional","affiliation":[{"name":"for the D-Lay MS Investigators"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"YEUNG","sequence":"additional","affiliation":[{"name":"for the D-Lay MS Investigators"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"GOUT","sequence":"additional","affiliation":[{"name":"for the D-Lay MS Investigators"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aur\u00e9lien","family":"BENOILID","sequence":"additional","affiliation":[{"name":"for the D-Lay MS Investigators"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"COLLONGUES","sequence":"additional","affiliation":[{"name":"for the D-Lay MS Investigators"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9line","family":"LOUAPRE","sequence":"additional","affiliation":[{"name":"for the D-Lay MS Investigators"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aurelian","family":"UNGUREANU","sequence":"additional","affiliation":[{"name":"for the D-Lay MS Investigators"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"PAPEIX","sequence":"additional","affiliation":[{"name":"for the D-Lay MS Investigators"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laure","family":"DUBESSY Anne","sequence":"additional","affiliation":[{"name":"for the D-Lay MS Investigators"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damien","family":"GALANAUD","sequence":"additional","affiliation":[{"name":"for the D-Lay MS Investigators"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"VUKUSIC","sequence":"additional","affiliation":[{"name":"for the D-Lay MS Investigators"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7oise","family":"DURAND-DUBIEF","sequence":"additional","affiliation":[{"name":"for the D-Lay MS Investigators"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","reference":[{"issue":"23","key":"joi250008r1","doi-asserted-by":"publisher","first-page":"2832","DOI":"10.1001\/jama.296.23.2832","article-title":"Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis.","volume":"296","author":"Munger","year":"2006","journal-title":"JAMA"},{"issue":"Pt 7","key":"joi250008r2","doi-asserted-by":"publisher","first-page":"1863","DOI":"10.1093\/brain\/awv105","article-title":"Defining high, medium and low impact prognostic factors for developing multiple sclerosis.","volume":"138","author":"Tintore","year":"2015","journal-title":"Brain"},{"issue":"8","key":"joi250008r3","doi-asserted-by":"publisher","first-page":"1013","DOI":"10.1177\/1352458514568827","article-title":"Conversion from clinically isolated syndrome to multiple sclerosis: a large multicentre study.","volume":"21","author":"Kuhle","year":"2015","journal-title":"Mult Scler"},{"issue":"2","key":"joi250008r4","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1002\/ana.22043","article-title":"Higher 25-hydroxyvitamin D is associated with lower relapse risk in multiple sclerosis.","volume":"68","author":"Simpson","year":"2010","journal-title":"Ann Neurol"},{"issue":"2","key":"joi250008r5","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1002\/ana.23591","article-title":"Vitamin D status predicts new brain magnetic resonance imaging activity in multiple sclerosis.","volume":"72","author":"Mowry","year":"2012","journal-title":"Ann Neurol"},{"issue":"3","key":"joi250008r6","doi-asserted-by":"publisher","first-page":"564","DOI":"10.1111\/ene.12617","article-title":"Vitamin D is associated with degree of disability in patients with fully ambulatory relapsing-remitting multiple sclerosis.","volume":"22","author":"Thouvenot","year":"2015","journal-title":"Eur J Neurol"},{"issue":"3","key":"joi250008r7","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1001\/jamaneurol.2013.5993","article-title":"Vitamin D as an early predictor of multiple sclerosis activity and progression.","volume":"71","author":"Ascherio","year":"2014","journal-title":"JAMA Neurol"},{"issue":"4","key":"joi250008r8","doi-asserted-by":"publisher","DOI":"10.1093\/braincomms\/fcac171","article-title":"Full spectrum of vitamin D immunomodulation in multiple sclerosis: mechanisms and therapeutic implications.","volume":"4","author":"Galoppin","year":"2022","journal-title":"Brain Commun"},{"issue":"20","key":"joi250008r9","doi-asserted-by":"publisher","first-page":"e1906","DOI":"10.1212\/WNL.0000000000008445","article-title":"Randomized trial of daily high-dose vitamin D3 in patients with RRMS receiving subcutaneous interferon \u00df-1a.","volume":"93","author":"Hupperts","year":"2019","journal-title":"Neurology"},{"issue":"5","key":"joi250008r10","doi-asserted-by":"publisher","DOI":"10.1212\/NXI.0000000000000597","article-title":"Cholecalciferol in relapsing-remitting MS: a randomized clinical trial (CHOLINE).","volume":"6","author":"Camu","year":"2019","journal-title":"Neurol Neuroimmunol Neuroinflamm"},{"issue":"3","key":"joi250008r11","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1007\/s13760-012-0166-2","article-title":"Preventive effect of vitamin D3 supplementation on conversion of optic neuritis to clinically definite multiple sclerosis: a double blind, randomized, placebo-controlled pilot clinical trial.","volume":"113","author":"Derakhshandi","year":"2013","journal-title":"Acta Neurol Belg"},{"issue":"4","key":"joi250008r12","doi-asserted-by":"publisher","first-page":"1206","DOI":"10.1093\/brain\/awad409","article-title":"Vitamin D did not reduce multiple sclerosis disease activity after a clinically isolated syndrome.","volume":"147","author":"Butzkueven","year":"2024","journal-title":"Brain"},{"issue":"3","key":"joi250008r13","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1159\/000515131","article-title":"The effect of different administration time and dosage of vitamin D supplementation in patients with multiple sclerosis: a meta-analysis of randomized controlled trials.","volume":"28","author":"Yuan","year":"2021","journal-title":"Neuroimmunomodulation"},{"issue":"12","key":"joi250008r14","doi-asserted-by":"publisher","first-page":"2893","DOI":"10.1007\/s00415-018-9074-6","article-title":"Vitamin D for the treatment of multiple sclerosis: a meta-analysis.","volume":"265","author":"McLaughlin","year":"2018","journal-title":"J Neurol"},{"key":"joi250008r15","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1016\/j.msard.2018.05.008","article-title":"The efficacy of vitamin D in multiple sclerosis: a meta-analysis.","volume":"23","author":"Zheng","year":"2018","journal-title":"Mult Scler Relat Disord"},{"key":"joi250008r16","doi-asserted-by":"publisher","DOI":"10.1016\/j.msard.2024.105433","article-title":"Vitamin D3 as an add-on treatment for multiple sclerosis: a systematic review and meta-analysis of randomized controlled trials.","volume":"82","author":"Mahler","year":"2024","journal-title":"Mult Scler Relat Disord"},{"issue":"6","key":"joi250008r17","doi-asserted-by":"publisher","first-page":"840","DOI":"10.1002\/ana.20703","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":"2","key":"joi250008r18","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1002\/ana.22366","article-title":"Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria.","volume":"69","author":"Polman","year":"2011","journal-title":"Ann Neurol"},{"issue":"2","key":"joi250008r19","doi-asserted-by":"publisher","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":"Thompson","year":"2018","journal-title":"Lancet Neurol"},{"issue":"3","key":"joi250008r20","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1212\/WNL.0000000000000560","article-title":"Defining the clinical course of multiple sclerosis: the 2013 revisions.","volume":"83","author":"Lublin","year":"2014","journal-title":"Neurology"},{"issue":"7","key":"joi250008r21","doi-asserted-by":"publisher","first-page":"1242","DOI":"10.1212\/01.wnl.0000237641.33768.8d","article-title":"Treatment with interferon beta-1b delays conversion to clinically definite and McDonald MS in patients with clinically isolated syndromes.","volume":"67","author":"Kappos","year":"2006","journal-title":"Neurology"},{"issue":"10","key":"joi250008r22","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":"4","key":"joi250008r23","doi-asserted-by":"publisher","first-page":"e58","DOI":"10.1212\/CPJ.0000000000001177","article-title":"Predictors of disease activity and worsening in relapsing-remitting multiple sclerosis.","volume":"12","author":"Zhang","year":"2022","journal-title":"Neurol Clin Pract"},{"issue":"10","key":"joi250008r24","doi-asserted-by":"publisher","first-page":"1323","DOI":"10.1177\/1352458513483889","article-title":"Childhood body mass index and multiple sclerosis risk: a long-term cohort study.","volume":"19","author":"Munger","year":"2013","journal-title":"Mult Scler"},{"issue":"5","key":"joi250008r25","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1136\/jnnp.50.5.511","article-title":"A double-blind controlled trial of high dose methylprednisolone in patients with multiple sclerosis: 1. clinical effects.","volume":"50","author":"Milligan","year":"1987","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"joi250008r26","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2024.110183","article-title":"The immune cell transcriptome is modulated by vitamin D3 supplementation in people with a first demyelinating event participating in a randomized placebo-controlled trial.","volume":"262","author":"Yeh","year":"2024","journal-title":"Clin Immunol"},{"key":"joi250008r27","doi-asserted-by":"publisher","DOI":"10.1101\/2023.09.25.559400","article-title":"CITE-seq reveals inhibition of NF-?B pathway in B cells from vitamin D-treated multiple sclerosis patients.","author":"Galoppin","year":"2023","journal-title":"bioRxiv"},{"issue":"10","key":"joi250008r28","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":"1","key":"joi250008r29","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/S1474-4422(11)70262-9","article-title":"Comparison of two dosing frequencies of subcutaneous interferon beta-1a in patients with a first clinical demyelinating event suggestive of multiple sclerosis (REFLEX): a phase 3 randomised controlled trial.","volume":"11","author":"Comi","year":"2012","journal-title":"Lancet Neurol"},{"issue":"2","key":"joi250008r30","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1136\/jnnp-2024-334062","article-title":"Vitamin D affects the risk of disease activity in multiple sclerosis.","volume":"96","author":"Giordano","year":"2025","journal-title":"J Neurol Neurosurg Psychiatry"},{"issue":"12","key":"joi250008r31","doi-asserted-by":"publisher","first-page":"1173","DOI":"10.1080\/14737175.2023.2289572","article-title":"An update on combination therapies for multiple sclerosis: where are we now?","volume":"23","author":"Sorensen","year":"2023","journal-title":"Expert Rev Neurother"},{"issue":"9","key":"joi250008r32","doi-asserted-by":"publisher","first-page":"3147","DOI":"10.1093\/brain\/awac016","article-title":"How patients with multiple sclerosis acquire disability.","volume":"145","author":"Lublin","year":"2022","journal-title":"Brain"}],"container-title":["JAMA"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jama\/articlepdf\/2831270\/jama_thouvenot_2025_oi_250008_1744313618.99452.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,22]],"date-time":"2025-04-22T15:03:44Z","timestamp":1745334224000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jama\/fullarticle\/2831270"}},"subtitle":["The D-Lay MS Randomized Clinical Trial"],"short-title":[],"issued":{"date-parts":[[2025,4,22]]},"references-count":32,"journal-issue":{"issue":"16","published-print":{"date-parts":[[2025,4,22]]}},"URL":"https:\/\/doi.org\/10.1001\/jama.2025.1604","relation":{},"ISSN":["0098-7484"],"issn-type":[{"value":"0098-7484","type":"print"}],"subject":[],"published":{"date-parts":[[2025,4,22]]}}}