{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T23:45:41Z","timestamp":1788479141319,"version":"build-2803163510"},"reference-count":38,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T00:00:00Z","timestamp":1744243200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"},{"start":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T00:00:00Z","timestamp":1744243200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"}],"funder":[{"DOI":"10.13039\/100005614","name":"Biogen","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005614","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Neurol Ther"],"published-print":{"date-parts":[[2025,6]]},"DOI":"10.1007\/s40120-025-00725-x","type":"journal-article","created":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T03:22:04Z","timestamp":1744255324000},"page":"895-909","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Impact of Natalizumab on Productivity and Ability to Work in Patients with Multiple Sclerosis in France: The TITAN Study"],"prefix":"10.1007","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0997-8817","authenticated-orcid":false,"given":"Patrick","family":"Vermersch","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnaud","family":"Kwiatkowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e9r\u00f4me","family":"de S\u00e8ze","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alain","family":"Cr\u00e9ange","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Texier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Fantoni-Quinton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marilyn","family":"Gros","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Ruiz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Lebrun-Frenay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"on behalf of the TITAN Investigators","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,4,10]]},"reference":[{"issue":"1","key":"725_CR1","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1111\/ene.13819","volume":"26","author":"R Dobson","year":"2019","unstructured":"Dobson R, Giovannoni G. Multiple sclerosis\u2014a review. Eur J Neurol. 2019;26(1):27\u201340.","journal-title":"Eur J Neurol"},{"issue":"18","key":"725_CR2","doi-asserted-by":"publisher","first-page":"e1810","DOI":"10.1212\/WNL.0000000000200150","volume":"98","author":"B Bebo","year":"2022","unstructured":"Bebo B, Cintina I, LaRocca N, et al. The economic burden of multiple sclerosis in the United States: estimate of direct and indirect costs. Neurology. 2022;98(18):e1810\u20137.","journal-title":"Neurology"},{"issue":"2_suppl","key":"725_CR3","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1177\/1352458517708125","volume":"23","author":"C Lebrun-Frenay","year":"2017","unstructured":"Lebrun-Frenay C, Kobelt G, Berg J, et al. New insights into the burden and costs of multiple sclerosis in Europe: results for France. Mult Scler. 2017;23(2_suppl):65\u201377.","journal-title":"Mult Scler"},{"issue":"9","key":"725_CR4","doi-asserted-by":"publisher","first-page":"5127","DOI":"10.1007\/s00415-022-11169-w","volume":"269","author":"MA Battaglia","year":"2022","unstructured":"Battaglia MA, Bezzini D, Cecchini I, et al. Patients with multiple sclerosis: a burden and cost of illness study. J Neurol. 2022;269(9):5127\u201335.","journal-title":"J Neurol"},{"issue":"11","key":"725_CR5","doi-asserted-by":"publisher","first-page":"1200","DOI":"10.1136\/jnnp-2018-318228","volume":"89","author":"J Chen","year":"2018","unstructured":"Chen J, Taylor BV, Blizzard L, et al. Effects of multiple sclerosis disease-modifying therapies on employment measures using patient-reported data. J Neurol Neurosurg Psychiatry. 2018;89(11):1200\u20137.","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"725_CR6","unstructured":"Biogen Inc. TYSABRI (natalizumab) [prescribing information]. 2023. https:\/\/www.tysabri.com\/content\/dam\/commercial\/tysabri\/pat\/en_us\/pdf\/tysabri_prescribing_information.pdf. Accessed Apr 2023."},{"issue":"9","key":"725_CR7","doi-asserted-by":"publisher","first-page":"899","DOI":"10.1056\/NEJMoa044397","volume":"354","author":"CH Polman","year":"2006","unstructured":"Polman CH, O\u2019Connor PW, Havrdova E, et al. A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med. 2006;354(9):899\u2013910.","journal-title":"N Engl J Med"},{"issue":"17","key":"725_CR8","doi-asserted-by":"publisher","first-page":"1390","DOI":"10.1212\/01.wnl.0000260064.77700.fd","volume":"68","author":"DH Miller","year":"2007","unstructured":"Miller DH, Soon D, Fernando KT, et al. MRI outcomes in a placebo-controlled trial of natalizumab in relapsing MS. Neurology. 2007;68(17):1390\u2013401.","journal-title":"Neurology"},{"issue":"6","key":"725_CR9","doi-asserted-by":"publisher","first-page":"660","DOI":"10.1136\/jnnp-2019-322326","volume":"91","author":"H Butzkueven","year":"2020","unstructured":"Butzkueven H, Kappos L, Wiendl H, et al. Long-term safety and effectiveness of natalizumab treatment in clinical practice: 10 years of real-world data from the Tysabri Observational Program (TOP). J Neurol Neurosurg Psychiatry. 2020;91(6):660\u20138.","journal-title":"J Neurol Neurosurg Psychiatry"},{"issue":"7","key":"725_CR10","doi-asserted-by":"publisher","first-page":"3724","DOI":"10.1007\/s12325-021-01722-w","volume":"38","author":"J Perumal","year":"2021","unstructured":"Perumal J, Balabanov R, Su R, et al. Natalizumab in early relapsing-remitting multiple sclerosis: a 4-year, open-label study. Adv Ther. 2021;38(7):3724\u201342.","journal-title":"Adv Ther"},{"issue":"9","key":"725_CR11","doi-asserted-by":"publisher","first-page":"977","DOI":"10.1007\/s40263-022-00950-0","volume":"36","author":"J Perumal","year":"2022","unstructured":"Perumal J, Balabanov R, Su R, et al. Improvements in cognitive processing speed, disability, and patient-reported outcomes in patients with early relapsing-remitting multiple sclerosis treated with natalizumab: results of a 4-year, real-world, open-label study. CNS Drugs. 2022;36(9):977\u201393.","journal-title":"CNS Drugs"},{"issue":"1","key":"725_CR12","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1056\/NEJMoa020696","volume":"348","author":"DH Miller","year":"2003","unstructured":"Miller DH, Khan OA, Sheremata WA, et al. A controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med. 2003;348(1):15\u201323.","journal-title":"N Engl J Med"},{"issue":"5","key":"725_CR13","doi-asserted-by":"publisher","first-page":"1388","DOI":"10.1007\/s00415-012-6809-7","volume":"260","author":"L Kappos","year":"2013","unstructured":"Kappos L, O\u2019Connor PW, Polman CH, et al. Clinical effects of natalizumab on multiple sclerosis appear early in treatment course. J Neurol. 2013;260(5):1388\u201395.","journal-title":"J Neurol"},{"key":"725_CR14","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1186\/1477-7525-10-155","volume":"10","author":"JJ Stephenson","year":"2012","unstructured":"Stephenson JJ, Kern DM, Agarwal SS, et al. Impact of natalizumab on patient-reported outcomes in multiple sclerosis: a longitudinal study. Health Qual Life Outcomes. 2012;10:155.","journal-title":"Health Qual Life Outcomes"},{"issue":"5","key":"725_CR15","doi-asserted-by":"publisher","first-page":"299","DOI":"10.2165\/11593770-000000000-00000","volume":"25","author":"S Olofsson","year":"2011","unstructured":"Olofsson S, Wickstrom A, H\u00e4ger Glenng\u00e5rd A, Persson U, Svenningsson A. Effect of treatment with natalizumab on ability to work in people with multiple sclerosis: productivity gain based on direct measurement of work capacity before and after 1 year of treatment. BioDrugs. 2011;25(5):299\u2013306.","journal-title":"BioDrugs"},{"issue":"5","key":"725_CR16","doi-asserted-by":"publisher","first-page":"622","DOI":"10.1177\/1352458512461391","volume":"19","author":"A Wickstrom","year":"2013","unstructured":"Wickstrom A, Nystr\u00f6m J, Svenningsson A. Improved ability to work after one year of natalizumab treatment in multiple sclerosis. Analysis of disease-specific and work-related factors that influence the effect of treatment. Mult Scler. 2013;19(5):622\u201330.","journal-title":"Mult Scler"},{"issue":"8","key":"725_CR17","doi-asserted-by":"publisher","first-page":"1095","DOI":"10.1177\/1352458513517590","volume":"20","author":"A Wickstr\u00f6m","year":"2014","unstructured":"Wickstr\u00f6m A, Dahle C, Vrethem M, Svenningsson A. Reduced sick leave in multiple sclerosis after one year of natalizumab treatment. A prospective ad hoc analysis of the TYNERGY trial. Mult Scler. 2014;20(8):1095\u2013101.","journal-title":"Mult Scler"},{"issue":"7","key":"725_CR18","doi-asserted-by":"publisher","first-page":"A400","DOI":"10.1016\/j.jval.2014.08.909","volume":"17","author":"F Kreimendahl","year":"2014","unstructured":"Kreimendahl F, Rychlik RP, Patel S, Gleissner E, Becker V. Working ability and monetarily valued productivity of patients with multiple sclerosis treated with natalizumab. Value Health. 2014;17(7):A400.","journal-title":"Value Health"},{"issue":"7","key":"725_CR19","doi-asserted-by":"publisher","first-page":"2837","DOI":"10.1007\/s10072-020-04838-z","volume":"42","author":"R Capra","year":"2021","unstructured":"Capra R, Morra VB, Mirabella M, et al. Natalizumab is associated with early improvement of working ability in relapsing-remitting multiple sclerosis patients: WANT observational study results. Neurol Sci. 2021;42(7):2837\u201345.","journal-title":"Neurol Sci"},{"issue":"1","key":"725_CR20","doi-asserted-by":"publisher","DOI":"10.1136\/bmjno-2022-000304","volume":"5","author":"L Achtnichts","year":"2023","unstructured":"Achtnichts L, Zecca C, Findling O, et al. Correlation of disability with quality of life in patients with multiple sclerosis treated with natalizumab: primary results and post hoc analysis of the TYSabri ImPROvement study (PROTYS). BMJ Neurol Open. 2023;5(1): e000304.","journal-title":"BMJ Neurol Open"},{"issue":"5","key":"725_CR21","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1177\/1352458520936239","volume":"27","author":"K Bigaut","year":"2021","unstructured":"Bigaut K, Fabacher T, Kremer L, et al. Long-term effect of natalizumab in patients with RRMS: TYSTEN cohort. Mult Scler. 2021;27(5):729\u201341.","journal-title":"Mult Scler"},{"issue":"5","key":"725_CR22","doi-asserted-by":"publisher","first-page":"353","DOI":"10.2165\/00019053-199304050-00006","volume":"4","author":"MC Reilly","year":"1993","unstructured":"Reilly MC, Zbrozek AS, Dukes EM. The validity and reproducibility of a work productivity and activity impairment instrument. Pharmacoeconomics. 1993;4(5):353\u201365.","journal-title":"Pharmacoeconomics"},{"issue":"5","key":"725_CR23","doi-asserted-by":"publisher","first-page":"962","DOI":"10.1093\/brain\/124.5.962","volume":"124","author":"J Hobart","year":"2001","unstructured":"Hobart J, Lamping D, Fitzpatrick R, Riazi A, Thompson A. The Multiple Sclerosis Impact Scale (MSIS-29) a new patient-based outcome measure. Brain. 2001;124(5):962\u201373.","journal-title":"Brain"},{"issue":"5","key":"725_CR24","doi-asserted-by":"publisher","first-page":"337","DOI":"10.3109\/07853890109002087","volume":"33","author":"R Rabin","year":"2001","unstructured":"Rabin R, de Charro F. EQ-5D: a measure of health status from the EuroQol Group. Ann Med. 2001;33(5):337\u201343.","journal-title":"Ann Med"},{"issue":"1","key":"725_CR25","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1007\/s10198-011-0351-x","volume":"14","author":"J Chevalier","year":"2013","unstructured":"Chevalier J, de Pouvourville G. Valuing EQ-5D using time trade-off in France. Eur J Health Econ. 2013;14(1):57\u201366.","journal-title":"Eur J Health Econ"},{"issue":"2","key":"725_CR26","first-page":"1","volume":"8","author":"A Bouleau","year":"2022","unstructured":"Bouleau A, Dulong C, Schwerer CA, et al. The socioeconomic impact of multiple sclerosis in France: results from the PETALS study. Mult Scler J Exp Transl Clin. 2022;8(2):1\u201310.","journal-title":"Mult Scler J Exp Transl Clin"},{"issue":"2","key":"725_CR27","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1097\/MRR.0b013e32835c79ea","volume":"36","author":"S Schiavolin","year":"2013","unstructured":"Schiavolin S, Leonardi M, Giovannetti AM, et al. Factors related to difficulties with employment in patients with multiple sclerosis: a review of 2002\u20132011 literature. Int J Rehabil Res. 2013;36(2):105\u201311.","journal-title":"Int J Rehabil Res"},{"issue":"8","key":"725_CR28","doi-asserted-by":"publisher","first-page":"1029","DOI":"10.1016\/j.jval.2012.07.010","volume":"15","author":"BI Glanz","year":"2012","unstructured":"Glanz BI, D\u00e9gano IR, Rintell DJ, et al. Work productivity in relapsing multiple sclerosis: associations with disability, depression, fatigue, anxiety, cognition, and health-related quality of life. Value Health. 2012;15(8):1029\u201335.","journal-title":"Value Health"},{"issue":"7","key":"725_CR29","doi-asserted-by":"publisher","first-page":"994","DOI":"10.1177\/1352458518781971","volume":"25","author":"J Chen","year":"2019","unstructured":"Chen J, Taylor B, Palmer AJ, et al. Estimating MS-related work productivity loss and factors associated with work productivity loss in a representative Australian sample of people with multiple sclerosis. Mult Scler. 2019;25(7):994\u20131004.","journal-title":"Mult Scler"},{"issue":"1\u20132","key":"725_CR30","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1016\/j.jns.2009.06.004","volume":"285","author":"N Putzki","year":"2009","unstructured":"Putzki N, Yaldizli O, Tettenborn B, Diener HC. Multiple sclerosis associated fatigue during natalizumab treatment. J Neurol Sci. 2009;285(1\u20132):109\u201313.","journal-title":"J Neurol Sci"},{"issue":"4","key":"725_CR31","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0035843","volume":"7","author":"P Iaffaldano","year":"2012","unstructured":"Iaffaldano P, Viterbo RG, Paolicelli D, et al. Impact of natalizumab on cognitive performances and fatigue in relapsing multiple sclerosis: a prospective, open-label, two years observational study. PLoS ONE. 2012;7(4): e35843.","journal-title":"PLoS ONE"},{"issue":"3","key":"725_CR32","doi-asserted-by":"publisher","first-page":"e58643","DOI":"10.1371\/journal.pone.0058643","volume":"8","author":"A Svenningsson","year":"2013","unstructured":"Svenningsson A, Falk E, Celius EG, et al. Natalizumab treatment reduces fatigue in multiple sclerosis. Results from the TYNERGY trial; a study in the real life setting. PLoS ONE. 2013;8(3):e58643.","journal-title":"PLoS ONE"},{"issue":"3","key":"725_CR33","doi-asserted-by":"publisher","first-page":"120","DOI":"10.7224\/1537-2073.2012-043","volume":"15","author":"J Wilken","year":"2013","unstructured":"Wilken J, Kane RL, Sullivan CL, et al. Changes in fatigue and cognition in patients with relapsing forms of multiple sclerosis treated with natalizumab: the ENER-G study. Int J MS Care. 2013;15(3):120\u20138.","journal-title":"Int J MS Care"},{"issue":"2","key":"725_CR34","doi-asserted-by":"publisher","first-page":"105","DOI":"10.2165\/01312067-200902020-00006","volume":"2","author":"SA Kamat","year":"2009","unstructured":"Kamat SA, Rajagopalan K, Stephenson JJ, Agarwal S. Impact of natalizumab on patient-reported outcomes in a clinical practice setting: a cross-sectional survey. Patient. 2009;2(2):105\u201312.","journal-title":"Patient"},{"issue":"1","key":"725_CR35","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1111\/ene.12204","volume":"21","author":"O Outteryck","year":"2014","unstructured":"Outteryck O, Ongagna JC, Brochet B, et al. A prospective observational post-marketing study of natalizumab-treated multiple sclerosis patients: clinical, radiological and biological features and adverse events. The BIONAT cohort Eur J Neurol. 2014;21(1):40\u20138.","journal-title":"The BIONAT cohort Eur J Neurol"},{"issue":"6","key":"725_CR36","doi-asserted-by":"publisher","first-page":"1215","DOI":"10.1007\/s00415-011-6339-8","volume":"259","author":"A Melin","year":"2012","unstructured":"Melin A, Outteryck O, Collongues N, et al. Effect of natalizumab on clinical and radiological disease activity in a French cohort of patients with relapsing-remitting multiple sclerosis. J Neurol. 2012;259(6):1215\u201321.","journal-title":"J Neurol"},{"key":"725_CR37","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/j.clineuro.2016.07.001","volume":"149","author":"V van Pesch","year":"2016","unstructured":"van Pesch V, Sindic CJ, Fern\u00e1ndez O. Effectiveness and safety of natalizumab in real-world clinical practice: review of observational studies. Clin Neurol Neurosurg. 2016;149:55\u201363.","journal-title":"Clin Neurol Neurosurg"},{"key":"725_CR38","doi-asserted-by":"publisher","DOI":"10.1016\/j.msard.2022.104216","volume":"68","author":"D Ontaneda","year":"2022","unstructured":"Ontaneda D, Mowry EM, Newsome SD, et al. Benefits of early treatment with natalizumab: a real-world study. Mult Scler Relat Disord. 2022;68: 104216.","journal-title":"Mult Scler Relat Disord"}],"container-title":["Neurology and Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40120-025-00725-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s40120-025-00725-x\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40120-025-00725-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,19]],"date-time":"2025-05-19T13:58:25Z","timestamp":1747663105000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s40120-025-00725-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,10]]},"references-count":38,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,6]]}},"alternative-id":["725"],"URL":"https:\/\/doi.org\/10.1007\/s40120-025-00725-x","relation":{},"ISSN":["2193-8253","2193-6536"],"issn-type":[{"value":"2193-8253","type":"print"},{"value":"2193-6536","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,10]]},"assertion":[{"value":"3 December 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 March 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 April 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Patrick Vermersch: personal compensation for consulting from AB Science, Biogen, BMS-Celgene, Imcyse, Merck, Novartis, Roche, Sanofi, and Teva. Honoraria and support for meetings from Biogen, Janssen, Merck, Novartis, Roche, and Sanofi. Research grants from Merck, Sanofi, and Roche. Arnaud Kwiatkowski: personal compensation for consulting from Biogen, Merck, Novartis. Honoraria from Biogen, Merck, Novartis, Roche, and Sanofi; for meetings from Biogen, Janssen, Novartis, Roche, and Sanofi; for participation in advisory board from Novartis. Alain Cr\u00e9ange: grants or contracts from Alexion, Biogen, BMS, Merck, Novartis, and Roche. Honoraria and support for meetings from Alexion, Biogen, and Novartis. Payment for expert testimony from Merck. Marilyn Gros and Marta Ruiz: employees of and may hold stock and\/or stock options in Biogen. Nathalie Texier, J\u00e9r\u00f4me de S\u00e8ze, Christine Lebrun-Frenay and Sophie Fantoni-Quinton have nothing to disclose.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of Interest"}},{"value":"The TITAN study was approved by the French Consultative Committee on Data Processing in Health Research; approved by the French Expert Committee on Health Research, Studies, and Evaluations (Comit\u00e9 Consultatif sur le Traitement de l\u2019Information en mati\u00e8re de Recherche dans le domaine de la Sant\u00e9 [CCTIRS]); and authorized by the French Data Protection Commission. The study was conducted in accordance with local French laws, including the French Data Protection Act (Informatique et Libert\u00e9s) and French Expert Committee on Health Research, Studies, and Evaluations (Comit\u00e9 d\u2019Expertise pour les Recherches, les Etudes et les Evaluations dans le domaine de la Sant\u00e9 [CEREES]).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical Approval"}}]}}