{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T10:46:17Z","timestamp":1782384377225,"version":"3.54.5"},"reference-count":30,"publisher":"Springer Science and Business Media LLC","issue":"7","license":[{"start":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T00:00:00Z","timestamp":1775260800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"},{"start":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T00:00:00Z","timestamp":1775260800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["2026836"],"award-info":[{"award-number":["2026836"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["2033165"],"award-info":[{"award-number":["2033165"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100019999","name":"Trish Multiple Sclerosis Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100019999","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000924","name":"Multiple Sclerosis Australia","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000924","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001782","name":"University of Melbourne","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001782","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["CNS Drugs"],"published-print":{"date-parts":[[2026,7]]},"DOI":"10.1007\/s40263-026-01287-8","type":"journal-article","created":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T17:11:07Z","timestamp":1775322667000},"page":"1011-1025","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Preserving Neurological Function in People at High and Low Risk of Aggressive Multiple Sclerosis: An Observational Cohort Study"],"prefix":"10.1007","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0371-3666","authenticated-orcid":false,"given":"Izanne","family":"Roos","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sifat","family":"Sharmin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serkan","family":"Ozakbas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raed","family":"Alroughani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Eichau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francois","family":"Grand\u2019Maison","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cavit","family":"Boz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeannette","family":"Lechner-Scott","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Buzzard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre","family":"Prat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samia J.","family":"Khoury","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Grammond","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anneke","family":"van der Walt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yolanda","family":"Blanco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Foschi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aysun","family":"Soysal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Barnett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Prevost","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Murat","family":"Terzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Gerlach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Macdonell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Jose","family":"Sa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele","family":"Spitaleri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guy","family":"Laureys","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"van Pesch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nevin","family":"John","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabetta","family":"Cartechini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riadh","family":"Gouider","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide","family":"Maimone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Ramo-Tello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne","family":"Hodgkinson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Slee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela","family":"McCombe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin","family":"Garber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose Luis","family":"Sanchez-Menoyo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdullah","family":"Al-Asmi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allan G.","family":"Kermode","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuelle","family":"Lapointe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vahid","family":"Shaygannejad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bart","family":"Van Wijmeersch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Willekens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamara","family":"Castillo-Trivi\u00f1o","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce","family":"Taylor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillaume","family":"Mathey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuelle","family":"Le Page","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerome","family":"De Seze","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aurelie","family":"Ruet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Clavelou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Berger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helene","family":"Zephir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnaud","family":"Kwiatkowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean","family":"Pelletier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thibault","family":"Moreau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Labauge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Ciron","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Lebrun-Frenay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Papeix","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilles","family":"Defer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David Axel","family":"Laplaud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Thouvenot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Stankoff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Maillart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdullatif","family":"Al-Khedr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bertrand","family":"Bourre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Casez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Am\u00e9lie","family":"Dos Santos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Philippe","family":"Camdessanche","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karolina","family":"Hankiewicz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abir","family":"Wahab","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Cabre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Heinzlef","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corinne","family":"Pottier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sol\u00e8ne","family":"Moulin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"Magy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9line","family":"Labeyrie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"In\u00e8s","family":"Doghri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Vukusic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3778-1376","authenticated-orcid":false,"given":"Tomas","family":"Kalincik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the MSBase and OFSEP Study Groups","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,4]]},"reference":[{"key":"1287_CR1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458519877810","author":"M Tintore","year":"2019","unstructured":"Tintore M, Arrambide G, Otero-Romero S, Carbonell-Mirabent P, Rio J, Tur C, et al. The long-term outcomes of CIS patients in the Barcelona inception cohort: looking back to recognize aggressive MS. Mult Scler. 2019. https:\/\/doi.org\/10.1177\/1352458519877810.","journal-title":"Mult Scler"},{"issue":"5","key":"1287_CR2","doi-asserted-by":"publisher","first-page":"1400","DOI":"10.1093\/brain\/awaa081","volume":"143","author":"CB Malpas","year":"2020","unstructured":"Malpas CB, Manouchehrinia A, Sharmin S, Roos I, Horakova D, Havrdova EK, et al. Early clinical markers of aggressive multiple sclerosis. Brain. 2020;143(5):1400\u201313. https:\/\/doi.org\/10.1093\/brain\/awaa081.","journal-title":"Brain"},{"key":"1287_CR3","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1016\/S1474-4422(17)30007-8","volume":"16","author":"T Kalincik","year":"2017","unstructured":"Kalincik T, Brown JWL, Robertson N, Willis M, Scolding N, Rice CM, et al. Treatment effectiveness of alemtuzumab compared with natalizumab, fingolimod, and interferon beta in relapsing-remitting multiple sclerosis: a cohort study. Lancet Neurol. 2017;16:271\u201381. https:\/\/doi.org\/10.1016\/S1474-4422(17)30007-8.","journal-title":"Lancet Neurol"},{"key":"1287_CR4","doi-asserted-by":"publisher","first-page":"1197","DOI":"10.1001\/jamaneurol.2021.2738","volume":"78","author":"T Spelman","year":"2021","unstructured":"Spelman T, Magyari M, Piehl F, Svenningsson A, Rasmussen PV, Kant M, et al. Treatment escalation vs immediate initiation of highly effective treatment for patients with relapsing-remitting multiple sclerosis: Data from 2 different national strategies. JAMA Neurol. 2021;78:1197\u2013204. https:\/\/doi.org\/10.1001\/jamaneurol.2021.2738.","journal-title":"JAMA Neurol"},{"key":"1287_CR5","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1001\/jama.2018.20588","volume":"321","author":"JWL Brown","year":"2019","unstructured":"Brown JWL, Coles A, Horakova D, Havrdova E, Izquierdo G, Prat A, et al. Association of initial disease-modifying therapy with later conversion to secondary progressive multiple sclerosis. JAMA. 2019;321:175\u201387. https:\/\/doi.org\/10.1001\/jama.2018.20588.","journal-title":"JAMA"},{"key":"1287_CR6","doi-asserted-by":"publisher","first-page":"536","DOI":"10.1001\/jamaneurol.2018.4905","volume":"76","author":"K Harding","year":"2019","unstructured":"Harding K, Williams O, Willis M, Hrastelj J, Rimmer A, Joseph F, et al. Clinical outcomes of escalation vs early intensive disease-modifying therapy in patients with multiple sclerosis. JAMA Neurol. 2019;76:536\u201341. https:\/\/doi.org\/10.1001\/jamaneurol.2018.4905.","journal-title":"JAMA Neurol"},{"key":"1287_CR7","doi-asserted-by":"publisher","first-page":"1045","DOI":"10.1177\/1352458520924595","volume":"26","author":"G Arrambide","year":"2020","unstructured":"Arrambide G, Iacobaeus E, Amato MP, Derfuss T, Vukusic S, Hemmer B, et al. Aggressive multiple sclerosis (2): treatment. Mult Scler Houndmills Basingstoke Engl. 2020;26:1045\u201363. https:\/\/doi.org\/10.1177\/1352458520924595.","journal-title":"Mult Scler Houndmills Basingstoke Engl."},{"key":"1287_CR8","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2019.3365","author":"G Luna","year":"2019","unstructured":"Luna G, Alping P, Burman J, Fink K, Fogdell-Hahn A, Gunnarsson M, et al. Infection risks among patients with multiple sclerosis treated with fingolimod, natalizumab, rituximab, and injectable therapies. JAMA Neurol. 2019. https:\/\/doi.org\/10.1001\/jamaneurol.2019.3365.","journal-title":"JAMA Neurol"},{"key":"1287_CR9","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1093\/aje\/kwu125","volume":"180","author":"ME Karim","year":"2014","unstructured":"Karim ME, Gustafson P, Petkau J, Zhao Y, Shirani A, Kingwell E, et al. Marginal structural Cox models for estimating the association between \u03b2-Interferon exposure and disease progression in a multiple sclerosis cohort. Am J Epidemiol. 2014;180:160\u201371. https:\/\/doi.org\/10.1093\/aje\/kwu125.","journal-title":"Am J Epidemiol"},{"key":"1287_CR10","doi-asserted-by":"publisher","first-page":"e783","DOI":"10.1212\/WNL.0000000000011242","volume":"96","author":"T Kalincik","year":"2021","unstructured":"Kalincik T, Diouf I, Sharmin S, Malpas C, Spelman T, Horakova D, et al. Effect of disease-modifying therapy on disability in relapsing-remitting multiple sclerosis over 15 years. Neurology. 2021;96:e783\u201397. https:\/\/doi.org\/10.1212\/WNL.0000000000011242.","journal-title":"Neurology"},{"key":"1287_CR11","doi-asserted-by":"publisher","first-page":"1014","DOI":"10.1111\/ene.15706","volume":"30","author":"I Diouf","year":"2023","unstructured":"Diouf I, Malpas CB, Sharmin S, Roos I, Horakova D, Havrdova EK, et al. Variability of the response to immunotherapy among subgroups of patients with multiple sclerosis. Eur J Neurol. 2023;30:1014\u201324. https:\/\/doi.org\/10.1111\/ene.15706.","journal-title":"Eur J Neurol"},{"key":"1287_CR12","doi-asserted-by":"publisher","first-page":"769","DOI":"10.1177\/1352458506070775","volume":"12","author":"H Butzkueven","year":"2006","unstructured":"Butzkueven H, Chapman J, Cristiano E, Grand\u2019Maison F, Hoffmann M, Izquierdo G, et al. MSBase: an international, online registry and platform for collaborative outcomes research in multiple sclerosis. Mult Scler. 2006;12:769\u201374. https:\/\/doi.org\/10.1177\/1352458506070775.","journal-title":"Mult Scler"},{"key":"1287_CR13","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1177\/1352458518815602","volume":"26","author":"S Vukusic","year":"2020","unstructured":"Vukusic S, Casey R, Rollot F, Brochet B, Pelletier J, Laplaud DA, et al. Observatoire Francais de la Sclerose en Plaques (OFSEP): a unique multimodal nationwide MS registry in France. Mult Scler. 2020;26:118\u201322. https:\/\/doi.org\/10.1177\/1352458518815602.","journal-title":"Mult Scler"},{"key":"1287_CR14","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1016\/S1474-4422(20)30067-3","volume":"19","author":"A He","year":"2020","unstructured":"He A, Merkel B, Brown JWL, Zhovits Ryerson L, Kister I, Malpas CB, et al. Timing of high-efficacy therapy for multiple sclerosis: a retrospective observational cohort study. Lancet Neurol. 2020;19:307\u201316. https:\/\/doi.org\/10.1016\/S1474-4422(20)30067-3.","journal-title":"Lancet Neurol"},{"key":"1287_CR15","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1177\/1352458516657439","volume":"23","author":"M D\u2019Souza","year":"2017","unstructured":"D\u2019Souza M, Yaldizli O, John R, Vogt DR, Papadopoulou A, Lucassen E, et al. Neurostatus e-Scoring improves consistency of Expanded Disability Status Scale assessments: a proof of concept study. Mult Scler. 2017;23:597\u2013603. https:\/\/doi.org\/10.1177\/1352458516657439.","journal-title":"Mult Scler"},{"key":"1287_CR16","doi-asserted-by":"publisher","DOI":"10.1177\/1352458519848965","author":"T Kalincik","year":"2019","unstructured":"Kalincik T, Butzkueven H. The MSBase registry: informing clinical practice. Mult Scler. 2019. https:\/\/doi.org\/10.1177\/1352458519848965.","journal-title":"Mult Scler"},{"key":"1287_CR17","doi-asserted-by":"publisher","first-page":"1642","DOI":"10.1177\/1352458516653667","volume":"22","author":"T Kalincik","year":"2016","unstructured":"Kalincik T, Butzkueven H. Observational data: understanding the real MS world. Mult Scler. 2016;22:1642\u20138. https:\/\/doi.org\/10.1177\/1352458516653667.","journal-title":"Mult Scler"},{"key":"1287_CR18","doi-asserted-by":"publisher","first-page":"3287","DOI":"10.1093\/brain\/awv258","volume":"138","author":"T Kalincik","year":"2015","unstructured":"Kalincik T, Cutter G, Spelman T, Jokubaitis V, Havrdova E, Horakova D, et al. Defining reliable disability outcomes in multiple sclerosis. Brain. 2015;138:3287\u201398. https:\/\/doi.org\/10.1093\/brain\/awv258.","journal-title":"Brain"},{"issue":"4","key":"1287_CR19","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1136\/jech.2002.006361","volume":"58","author":"MA Hernan","year":"2004","unstructured":"Hernan MA. A definition of causal effect for epidemiological research. J Epidemiol Community Health. 2004;58(4):265\u201371. https:\/\/doi.org\/10.1136\/jech.2002.006361.","journal-title":"J Epidemiol Community Health"},{"key":"1287_CR20","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1097\/00001648-200009000-00011","volume":"11","author":"JM Robins","year":"2000","unstructured":"Robins JM, Hernan MA, Brumback B. Marginal structural models and causal inference in epidemiology. Epidemiology. 2000;11:550\u201360. https:\/\/doi.org\/10.1097\/00001648-200009000-00011.","journal-title":"Epidemiology"},{"key":"1287_CR21","doi-asserted-by":"publisher","DOI":"10.2202\/1557-4679.1208","author":"Y Xiao","year":"2010","unstructured":"Xiao Y, Abrahamowicz M, Moodie EEM. Accuracy of conventional and marginal structural cox model estimators: a simulation study. Int J Biostat. 2010. https:\/\/doi.org\/10.2202\/1557-4679.1208.","journal-title":"Int J Biostat"},{"key":"1287_CR22","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2023-331499","author":"I Diouf","year":"2023","unstructured":"Diouf I, Malpas CB, Sharmin S, Roos I, Horakova D, Kubala Havrdova E, et al. Effectiveness of multiple disease-modifying therapies in relapsing-remitting multiple sclerosis: causal inference to emulate a multiarm randomised trial. J Neurol Neurosurg Psychiatry. 2023. https:\/\/doi.org\/10.1136\/jnnp-2023-331499.","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"1287_CR23","doi-asserted-by":"publisher","first-page":"1100","DOI":"10.1214\/aos\/1176345976","volume":"10","author":"PK Andersen","year":"1982","unstructured":"Andersen PK, Gill RD. Cox\u2019s regression model for counting processes: a large sample study. Ann Stat. 1982;10:1100\u201320. https:\/\/doi.org\/10.1214\/aos\/1176345976.","journal-title":"Ann Stat"},{"issue":"3","key":"1287_CR24","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1007\/s10654-019-00494-6","volume":"34","author":"TJ VanderWeele","year":"2019","unstructured":"VanderWeele TJ. Principles of confounder selection. Eur J Epidemiol. 2019;34(3):211\u20139. https:\/\/doi.org\/10.1007\/s10654-019-00494-6.","journal-title":"Eur J Epidemiol"},{"key":"1287_CR25","doi-asserted-by":"publisher","first-page":"1","DOI":"10.18637\/jss.v045.i07","volume":"45","author":"J Honaker","year":"2011","unstructured":"Honaker J, King G, Blackwell M. Amelia II: a program for missing data. J Stat Softw. 2011;45:1\u201347. https:\/\/doi.org\/10.18637\/jss.v045.i07.","journal-title":"J Stat Softw"},{"key":"1287_CR26","doi-asserted-by":"publisher","DOI":"10.1177\/1352458520925369","author":"E Iacobaeus","year":"2020","unstructured":"Iacobaeus E, Arrambide G, Amato PM, Derfuss T, Vukusic S, Hemmer B, et al. Aggressive multiple sclerosis (1): towards a definition of the phenotype. Mult Scler. 2020. https:\/\/doi.org\/10.1177\/1352458520925369.","journal-title":"Mult Scler"},{"key":"1287_CR27","doi-asserted-by":"publisher","first-page":"1163","DOI":"10.1177\/13524585241267211","volume":"30","author":"I Roos","year":"2024","unstructured":"Roos I, Sharmin S, Malpas CB, Ozakbas S, Lechner-Scott J, Hodgkinson S, et al. Effectiveness of cladribine compared to fingolimod, natalizumab, ocrelizumab and alemtuzumab in relapsing-remitting multiple sclerosis. Mult Scler J. 2024;30:1163\u201375.","journal-title":"Mult Scler J"},{"key":"1287_CR28","doi-asserted-by":"publisher","first-page":"458","DOI":"10.1177\/1352458512456613","volume":"19","author":"E Leray","year":"2013","unstructured":"Leray E, Coustans M, Le Page E, Yaouanq J, Oger J, Edan G. \u2018Clinically definite benign multiple sclerosis\u2019, an unwarranted conceptual hodgepodge: evidence from a 30-year observational study. Mult Scler J. 2013;19:458\u201365. https:\/\/doi.org\/10.1177\/1352458512456613.","journal-title":"Mult Scler J"},{"issue":"5","key":"1287_CR29","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1177\/1352458516662728","volume":"23","author":"T Kalincik","year":"2017","unstructured":"Kalincik T, Kuhle J, Pucci E, Rojas JI, Tsolaki M, Sirbu CA, et al. Data quality evaluation for observational multiple sclerosis registries. Mult Scler. 2017;23(5):647\u201355. https:\/\/doi.org\/10.1177\/1352458516662728.","journal-title":"Mult Scler"},{"key":"1287_CR30","doi-asserted-by":"publisher","first-page":"e1280","DOI":"10.1212\/WNL.0000000000207664","volume":"101","author":"A Cobo-Calvo","year":"2023","unstructured":"Cobo-Calvo A, Tur C, Otero-Romero S, Carbonell-Mirabent P, Ruiz M, Pappolla A, et al. Association of very early treatment initiation with the risk of long-term disability in patients with a first demyelinating event. Neurology. 2023;101:e1280\u201392. https:\/\/doi.org\/10.1212\/WNL.0000000000207664.","journal-title":"Neurology"}],"container-title":["CNS Drugs"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40263-026-01287-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s40263-026-01287-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40263-026-01287-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T09:47:04Z","timestamp":1782380824000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s40263-026-01287-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,4]]},"references-count":30,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["1287"],"URL":"https:\/\/doi.org\/10.1007\/s40263-026-01287-8","relation":{},"ISSN":["1172-7047","1179-1934"],"issn-type":[{"value":"1172-7047","type":"print"},{"value":"1179-1934","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,4]]},"assertion":[{"value":"4 September 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 March 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 April 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Izanne Roos has served on scientific advisory boards, received conference travel support and\/or speaker honoraria from Roche, Novartis, Merck, Neuraxpharm and Biogen. Sifat Sharmin did not declare any competing interests. Serkan Ozakbas did not declare any competing interests. Raed Alroughani received honoraria as a speaker and for serving on scientific advisory boards from Bayer, Biogen, GSK, Merck, Novartis, Roche and Sanofi-Genzyme. Sara Eichau has received speaker honoraria and consultant fees from Biogen Idec, Novartis, Merck, Janssen, Bristol-Meyers, Bayer, Sanofi Genzyme, Roche and Teva. Francois Grand'Maison received honoraria or research funding from Biogen, Genzyme, Novartis, Teva Neurosciences, and ATARA Pharmaceuticals. Cavit Boz received conference travel support from Biogen, Novartis, Bayer-Schering, Merck and Teva, and has participated in clinical trials by Sanofi Aventis, Roche and Novartis. Jeannette Lechner-Scott received travel compensation from Novartis, Biogen, Roche and Merck. Her institution receives the honoraria for talks and advisory board commitment as well as research grants from Biogen, Merck, Roche and Novartis. Katherine Buzzard received speaker honoraria and\/or education support from Biogen, Teva, Novartis, Genzyme-Sanofi, Roche, Merck and Alexion; she has been a member of advisory boards for Merck and Biogen. Alexandre Prat did not declare any competing interests. Samia J. Khoury received compensation for serving on the IDMC for Biogen. Pierre Grammond has served on advisory boards for Novartis, EMD Serono, Roche, Biogen idec, Sanofi Genzyme, and Pendopharm, has received grant support from Genzyme and Roche, and has received research grants for his institution from Biogen idec, Sanofi Genzyme, EMD Serono. Anneke van der Walt served on advisory boards and receives unrestricted research grants from Novartis, Biogen, Merck and Roche. She has received speaker\u2019s honoraria and travel support from Novartis, Roche, and Merck. She receives grant support from the National Health and Medical Research Council of Australia and MS Research Australia. Yolanda Blanco received speaker honoraria\/consulting fees from Merck, Biogen, Roche, Brystol, Novartis, Sanofi and Sandoz. Matteo Foschi received travel and meeting attendance support from Novartis, Biogen, Roche, Sanofi-Genzyme and Merck. Aysun Soysal did not declare any competing interests. Michael Barnett served on scientific advisory boards for Biogen, Novartis and Genzyme and has received conference travel support from Biogen and Novartis. He serves on steering committees for trials conducted by Novartis. His institution has received research support from Biogen, Merck and Novartis. Julie Prevost accepted travel compensation from Novartis, Biogen, Genzyme, Teva, and speaking honoraria from Biogen, Novartis, Genzyme and Teva. Murat Terzi received travel grants from Novartis, Bayer-Schering, Merck, and Teva and has participated in clinical trials by Sanofi Aventis, Roche, and Novartis. Oliver Gerlach did not declare any competing interests. Richard Macdonell or his institution have received remuneration for his speaking engagements, advisory board memberships, research and travel from Biogen, Merck, Genzyme, Bayer, Roche, Teva, Novartis, CSL, BMS, MedDay, and NHMRC. Maria Jose Sa received consulting fees, speaker honoraria, and\/or travel expenses for scientific meetings from Alexion, Bayer Healthcare, Biogen, Bristol Myers Squibb, Celgene, Janssen, Merck-Serono, Novartis, Roche, Sanofi, and Teva. Daniele Spitaleri received honoraria as a consultant on scientific advisory boards by Bayer-Schering, Novartis, and Sanofi-Aventis and compensation for travel from Novartis, Biogen, Sanofi Aventis, Teva, and Merck. Guy Laureys received travel and\/or consultancy compensation from Sanofi-Genzyme, Roche, Teva, Merck, Novartis, Celgene, Biogen. Liesbeth Van Hijfte received travel compensation from Merck. Vincent van Pesch received travel grants from Merck Healthcare KGaA (Darmstadt, Germany), Biogen, Sanofi, Bristol Meyer Squibb, Almirall, and Roche. His institution has received research grants and consultancy fees from Roche, Biogen, Sanofi, Merck Healthcare KGaA (Darmstadt, Germany), Bristol Meyer Squibb, Janssen, Almirall, Novartis Pharma, and Alexion. Nevin John is a PI on commercial MS studies sponsored by Novartis, Roche, Biogen, and Sanofi. He has received speaker\u2019s honoraria and consulting fees from Merck. He has had conference travel, registration reimbursement and consulting fees from Novartis. Elisabetta Cartechini has no disclosures. Riadh Gouider has received personal compensation for consulting, serving on a scientific advisory board, speaking or other activities from Biogen, Hikma, Merck, Roche, and Sanofi\/Genzyme. Davide Maimone received speaker honoraria for advisory board and travel grants from Alexion, Almirall, Bayer, Biogen, Bristol Myers Squibb, Merck, Novartis, Roche, Sanofi-Genzyme, and Teva. Cristina Ramo-Tello has received consulting fees, speaker honoraria, support for attending meetings and\/or travel, participation on advisory board and research grants for her institution from Biogen, Novartis, Sanofi, Bristol, Roche, Almirall, Janssen, Sandoz, and Merck. Suzanne Hodgkinson has received consulting fees and speaker honoraria from Biogen, Novartis, Roche, Merck, and has received grants for her Institution from Biogen, Merck, Novartis, and Roche. Mark Slee no relevant disclosure. Pamela McCombe received speakers\u2019 fees and travel grants from Novartis, Biogen, T\u2019\u00e9valua, and Sanofi. Justin Garber received conference travel support from Roche, Merck, and Novartis, received speaker honoraria from Biogen and research support from Roche. Jose Luis Sanchez-Menoyo accepted travel compensation from Novartis, Merck, and Biogen, speaking honoraria from Biogen, Novartis, Sanofi, Merck, Almirall, Bayer, and Teva, and has participated in clinical trials by Biogen, Merck, and Roche. Abdullah Al-Asmi received personal compensation for serving as a Scientific Advisor or speaker\/moderator for Novartis, Biogen, Roche, Sanofi-Genzyme, and Merck. Allan G. Kermode served on scientific advisory boards for Bayer, BioCSL, Biogen-Idec, Clene Nanomedicine, Esai, Innate Immunotherapeutics, Lgpharma, Merck, Mitsubishi Tanabe Pharma, NeuroScientific Biopharmaceuticals, Novartis, Progenis Pharma, Roche, Sanofi-Aventis, Sanofi-Genzyme, Teva, and View Health. Emmanuelle Lapointe did not declare any competing interests. Vahid Shaygannejad did not declare any competing interests. Bart Van Wijmeersch has received speaker fees, research support and travel grants from Almirall, Actelion\/Janssen, Bayer, Biogen, Celgene\/BMS, Imcyse, Merck, Novartis, Roche, Sanofi Genzyme, and Teva. Barbara Willekens received honoraria for acting as a member of scientific advisory boards\/consultancy for Alexion, Almirall, Biogen, Celgene\/BMS, Merck, Janssen, Novartis, Roche, Sandoz, Sanofi-Genzyme, and speaker honoraria and travel support from Biogen, Celgene\/BMS, Merck, Novartis, Roche, Sanofi-Genzyme; research and\/or patient support grants from Biogen, Janssen, Merck, Sanofi-Genzyme, and Roche. Honoraria and grants were paid to UZA\/UZA Foundation. Further, B.W. received research funding from FWO-TBM, Belgian Charcot Foundation, Start2Cure Foundation, Queen Elisabeth Medical Foundation for Neurosciences, and the National MS Society USA. Tamara Castillo-Trivi\u00f1o received speaking\/consulting fees and\/or travel funding from Almirall, Biogen, Bristol Myers Squibb, Janssen, Merck, Novartis, Roche, Sanofi-Genzyme, and Teva. Bruce Taylor received funding for travel and speaker honoraria from Bayer Schering Pharma, CSL Australia, Biogen, and Novartis, and has served on advisory boards for Biogen, Novartis, Roche, and CSL Australia. Guillaume Mathey did not declare any competing interests. Emmanuelle Le Page received fees for consulting or lectures, and invitations for national and international congresses from Biogen, Merck, Teva, Sanofi-Genzyme, Novartis, Alexion, research support from Teva and Biogen, academic research grants from PHRC and LFSEP, and travel grant from ARSEP Foundation. Jerome De Seze received consulting and lecturing fees, travel grants and unconditional research support from Biogen, Genzyme, Novartis, Roche, Sanofi Aventis, and Teva Pharma. Aurelie Ruet received honoraria for meeting speaking from Merck, Alexion, Horizon Th, and Sanofi Genzyme. A. Ruet received support for traveling from Biogen, Novartis, and Merck. Her institution received research grants from Biogen, Roche, Sanofi-Genzyme, and BMS. Pierre Clavelou received consulting and lecturing fees, travel grants, and unconditional research support from Biogen, Janssen, MedDay, Merck, Novartis, Roche, Sanofi-Genzyme, and Teva Pharma. Eric Berger received honoraria and consulting fees from Novartis, Sanofi Aventis, Biogen, Genzyme, Roche, and Teva Pharma. Helene Zephir received fees for consulting or lectures, and invitations for national and international congresses from Biogen, Merck, Teva, Sanofi-Genzyme, Novartis, and Bayer, as well as research support from Teva and Roche, and academic research grants from Acad\u00e9mie de M\u00e9decine, LFSEP, FHU Imminent, and ARSEP Foundation. Arnaud Kwiatkowski did not declare any competing interests. Jean Pelletier did not declare any competing interests. Thibault Moreau received fees as scientific adviser from Biogen, MedDay, Novartis, Genzyme, and Sanofi. Pierre Labauge received consulting and lecturing fees, travel grants and unconditional research support from Biogen, Genzyme, Novartis, Merck Serono, Roche, and Teva Pharma. Jonathan Ciron received fees for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, Novartis, Merck, Sanofi-Genzyme, Roche, Alexion, and Horizon Therapeutics. Christine Lebrun-Frenay did not declare any competing interests. Caroline Papeix did not declare any competing interests. Gilles Defer received consulting and lecturing fees for Biogen, Novartis, Genzyme, Merck-Serono, Roche, and Teva and funding for travel from Merck Serono, Biogen, Sanofi-Genzyme, Novartis, and Teva. Institution was granted support for research from Merck  Serono, Biogen, Genzyme, and Novartis. David Axel Laplaud served on scientific advisory boards for Alexion, BMS, Roche, Sanofi, Novartis, Merck, Janssen, and Biogen, received conference travel support and\/or speaker honoraria from Alexion, Novartis, Biogen, Roche, Sanofi, BMS, and Merck, and received research support from Fondation ARSEP, Fondation EDMUS, and Agence Nationale de la Recherche. Eric Thouvenot received consulting and lecturing fees, travel grants or unconditional research support from the following pharmaceutical companies: Actelion, Biogen, Janssen, Merck Serono, Novartis, Roche, Sanofi. Bruno Stankoff received consulting and lecturing fees, travel grants from Biogen Idec, Merck-Serono, Novartis, Genzyme, and unconditional research support from Merck-Serono, Genzyme, and Roche. Elisabeth Maillart received consulting and lecturing fees from Alexion, Biogen, Horizon, Janssen, Merck Serono, Novartis, Roche, Sandoz, Sanofi-Genzyme, Teva Pharmaceuticals, and research support from Biogen. Abdullatif Al-Khedr did not declare any competing interests. Bertrand Bourre served on scientific advisory boards for Alexion, BMS, Biogen, Sanofi, Janssen, Merck, Horizon, Novartis, Roche, Sandoz, and received funding for travel and honoraria from Alexion, Merck, Novartis, Sanofi, Roche, and Janssen. Olivier Casez declares support from Biogen (personal fees), Roche (personal fees, non-financial support (travelling\/congress), Merck (personal fees, non-financial support (travelling\/congress), Novartis (personal fees, non-financial support (travelling\/congress), Jansen (personal fees), and Sanofi (personal fees). Am\u00e9lie Dos Santos did not declare any competing interests. Jean-Philippe Camdessanche received consulting and lecturing fees from Akcea, Alexion, Alnylam, Argenx, Biogen, Bristol Myers Squibb, CSL-Behring, Genzyme, Grifols, Laboratoire Fran\u00e7ais des Biotechnologies, Merck-Serono, Natus, Novartis, Pfizer, Pharmalliance, UCB Pharma, Teva, SNF-Floerger; travel grants from Akcea, Alexion, Alnylam, Argenx, Biogen, CSL-Behring, Genzyme, Grifols, Laboratoire Fran\u00e7ais des Biotechnologies, Merck-Serono, Natus, Novartis, Pfizer, Teva, and SNF-Floerger. Karolina Hankiewicz did not declare any competing interests. Abir Wahab received expert testimony fees from Roche and travel grants from Biogen. Philippe Cabre did not declare any competing interests. Olivier Heinzlef received consulting and lecturing fees from Bayer Schering, Merck, Teva, Genzyme, Novartis, Almirall, and Biogen Idec, travel grants from Novartis, Teva, Genzyme, Merck Serono, and Biogen Idec, and research support from Roche, Merck, and Novartis. Corinne Pottier did not declare any competing interests. Sol\u00e8ne Moulin did not declare any competing interests. Laurent Magy did not declare any competing interests. C\u00e9line Labeyrie did not declare any competing interests. In\u00e8s Doghri did not declare any competing interests. Sandra Vukusic reports lecturing fees, travel grants, and research support from Biogen, BMS-Celgene, Janssen, Merck, Novartis, Roche, Sandoz, and Sanofi-Genzyme. Tomas Kalincik served on scientific advisory boards for MSIF and WHO, BMS, Roche, Janssen, Sanofi, Genzyme, Novartis, Merck, Neuraxpharm, and Biogen; received conference travel support and\/or speaker\u2019s honoraria from WebMD Global, Eisai, Novartis, Biogen, Roche, Genzyme, Teva, BioCSL, and Merck, and received research or educational event support from Biogen, Novartis, Genzyme, Alexion, Roche, Celgene, and Merck.\u00a0Tomas\u00a0Kalincik\u00a0is an Editorial Board member of\n                      CNS Drugs\n                      . He was not involved in the selection of peer reviewers for the manuscript nor any of the subsequent editorial decisions.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"IR and TK conceived and designed the study. IR contributed data, performed the analyses and visualisation, interpreted the results, and drafted the first version of the manuscript. TK contributed to data acquisition and interpretation, provided methodological oversight, and critically revised the manuscript for important intellectual content. SS contributed to study design, interpretation of results, and manuscript review. SV contributed to study design, data acquisition, interpretation of results, and manuscript editing. SO, RA, SE, FG, CB, JLS, KB, AP, SJK, PG, AVdW, YB, MF, AS, MB, JP, MT, OG, RM, MJS, DS, GL, VvP, NJ, EC, RG, DM, CR, SH, MS, PM, JG, JLSM, AA, AGK, EL, VS, BVW, BW, TCT, BT, GM, ELP, JDS, AR, PC, EB, HZ, AK, JPel, TM, PL, JC, CLF, CP, GD, DAL, ET, BS, EM, AAK, BB, OC, ADS, JPC, KH, AW, PCa, OH, CPo, SM, LM, CLab, and ID contributed to data acquisition and\/or participant recruitment and reviewed and edited the manuscript. All authors have read and approve the final version of the manuscript and agree to be accountable for the work.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Authors\u2019 Contributions"}},{"value":"The MSBase and OFSEP registries are data processors and warehouses data from individual principal investigators who agree to share their datasets on a project-by-project basis. External party access to data is subject to reasonable requests and solely at the discretion of the principal investigators. Permission for data access must be sought individually from the respective principal investigators.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Availability of Data and Material"}},{"value":"The study was approved by the Melbourne Health Human Research Ethics Committee and local ethics committees. Written informed consent was provided by patients. Requirements of the French Data Protection Agency were fulfilled.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical Approval"}},{"value":"Written informed consent was provided by patients. Requirements of the French Data Protection Agency were fulfilled.","order":6,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to Participate"}},{"value":"Not applicable.","order":7,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for Publication"}},{"value":"Not applicable.","order":8,"name":"Ethics","group":{"name":"EthicsHeading","label":"Code Availability"}}]}}