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Since approval in 2017, long-term real-world data have become available which provide insight into the management of patients treated with cladribine tablets beyond year 4. Most patients remained without additional therapy, which may hint at stable disease control. However, the absence of further treatment must not necessarily be interpreted as absence of any disease activity, as MRI data are often incomplete in watch-and-wait cohorts. The observed long-term remission is likely linked to the unique mode of action, which involves rapid repopulation of lymphocytes with different dynamics amongst subsets and sustained reduction of memory B cells. The recovery of the immune system and lymphocytes preserves long-term therapeutic options with existing or upcoming drugs. In cases of mild recurring disease activity, retreatment with cladribine tablets has been shown to be effective and tolerable within the known safety profile. Unrestricted long-term management options associated with cladribine tablets include a switch to other DMTs in cases of insufficient disease control. Overall, cladribine tablets show potential of a paradigmatic shift in MS management that may enable treatment-free remission over 6\u00a0years as an achievable treatment goal in a substantial proportion of RMS patients.<\/jats:p>","DOI":"10.1007\/s00415-026-13753-w","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T02:12:40Z","timestamp":1773799960000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Treatment-free remission in MS: long-term disease control with cladribine tablets"],"prefix":"10.1007","volume":"273","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4310-3432","authenticated-orcid":false,"given":"Heinz","family":"Wiendl","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7223-3052","authenticated-orcid":false,"given":"Ralf","family":"Gold","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8940-9317","authenticated-orcid":false,"given":"Refik","family":"Pul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Ernst","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1389-5539","authenticated-orcid":false,"given":"Markus C.","family":"Kowarik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8722-9785","authenticated-orcid":false,"given":"Juliane","family":"Klehmet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ines","family":"Siglienti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"H\u00fcbschen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7479-4311","authenticated-orcid":false,"given":"Torsten","family":"Wagner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-5062-1093","authenticated-orcid":false,"given":"Judith","family":"Knaup","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1650-8875","authenticated-orcid":false,"given":"Christoph","family":"Kleinschnitz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,18]]},"reference":[{"key":"13753_CR1","first-page":"53","volume":"30","author":"S Hodgkinson","year":"2024","unstructured":"Hodgkinson S, Wiendl H, Barkhof F, Montalban X, Achiron A, Derfuss T, Chan A, Prat A, Leocani L, Schmierer K, Sellebjerg F, Vermersch P, Lehn A, Smyk A, Nolting A, Koelbach R, De Stefano N (2024) P073 clinical efficacy of cladribine tablets in patients with highly active relapsing multiple sclerosis: 36-month interim results from the extension trial to the MAGNIFY-MS study. 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Expert Opin Drug Saf 24:389\u2013394","journal-title":"Expert Opin Drug Saf"}],"container-title":["Journal of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00415-026-13753-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00415-026-13753-w","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00415-026-13753-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T01:48:23Z","timestamp":1776649703000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00415-026-13753-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,18]]},"references-count":42,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["13753"],"URL":"https:\/\/doi.org\/10.1007\/s00415-026-13753-w","relation":{},"ISSN":["0340-5354","1432-1459"],"issn-type":[{"value":"0340-5354","type":"print"},{"value":"1432-1459","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,18]]},"assertion":[{"value":"21 December 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 March 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 March 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 March 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Heinz Wiendl: receives research support from Deutsche Forschungsgemeinschaft (DFG), Deutsche Myasthenie Gesellschaft e.V., European Union, Alexion, Amicus Therapeutics Inc., Argenx, Biogen, CSL Behring, F. Hoffmann\u2014La Roche, Genzyme, Merck, Novartis, Roche, UCB Biopharma, as well as speaker and\/or consultancy fee from Alexion, Argenx, Argobio, AOCN, AstraZeneca, BGP Products Operations GmbH, Biogen, Bristol Myers Squibb, CEMCAT, Dianthus, EMD Serono Research & Development Institute Inc., Billerica, MA, USA, an affiliate of Merck KGaA, EPG Health\/Medthority, Fondazione Cariplo, Genzyme, Idorsia, Immunic, Immunovant, INmune Bio_Syneos Health, Kohlhammer, LTS, Lundbeck, Merck, MS at the Limits, Muna Therapeutics, Myrobalan Therapeutics, Neurodiem, NMSS, Novartis, Ology, PSL Group, Red Nucleus, Roche, Samsung, Sangamo, Sanofi, Springer, StreamedUp, Swiss MS Society, Teladochealth, Toleranzia, Teva, UCB, Uvet, Viatris, WebMD global. He is a member of Scientific Advisory Boards from Alexion, Argenx, Biocryst, Bristol Myers Squibb, Cellerys, Galapagos, Janssen, Merck, Novartis, Sandoz-Hexal and uniQure biopharma B.V. Ralf Gold received Research Support, and Speaker\u2019s Honoraria from Bayer Schering, Biogen-Idec, BMS, Chugai, Eisai, Genesis, Janssen, Kyverna, Merck, Nikkiso Pharma, Novartis, Roche, Sanofi-Genzyme, Sandoz, TEVA, Consulting Honoraria from ZLB Behring, Baxter, Roche, Talecris, and has personal stock options in Kyverna, Merck, Novartis, Sanofi and Roche. Refik Pul received honoraria for lecturing and consulting from Alexion, Amgen, Bayer Healthcare, Biogen, Bristol Myers Squibb\/Celgene, Chiesi, Janssen, Juvis\u00e9, Merck Healthcare Germany GmbH, Weiterstadt, Germany, an affiliate of Merck KGaA, Neuraxpharm, Novartis, Roche, Sanofi Genzyme and Viatris. He received research funds from Merck Healthcare Germany GmbH, Weiterstadt, Germany, an affiliate of Merck KGaA, Neuraxpharm, and Novartis. Michael Ernst has served on advisory boards and received speaker and consultant fees\/travel from Merck, Sanofi-Genzyme, Novartis, Biogen, Janssen, Alexion, Celgene \/ Bristol-Myers Squibb, and Roche. Travel costs and expenses were reimbursed where applicable. The speaker does not own any shares in the above-mentioned companies. Memberships: DGN, DMKG. Markus C. Kowarik has served on advisory boards and received speaker fees\/travel grants from Merck, Sanofi-Genzyme, Novartis, Biogen, Janssen, Alexion, Celgene\/Bristol-Myers Squibb and Roche. M.K. also received research grants from Merck, Roche, Sanofi-Genzyme, Novartis, Janssen and Celgene\/Bristol-Myers Squibb. Juliane Klehmet received personal compensation for consulting as well as speaker honouraria from Bayer, Biogen, Bristol Myers Squibb, Grifols, Janssen, Merck, Novartis, Roche, Sanofi Genzyme, Takeda and Teva. Ines Siglienti served on advisory boards and received speaker honouraria and travel fees from Bayer, Biogen, Merck, Roche, Bristol-Myers Squibb. Michael H\u00fcbschen, Torsten Wagner and Judith Knaup are employees of Merck Healthcare Germany GmbH, Weiterstadt, Germany, an affiliate of Merck KGaA. Christoph Kleinschnitz received honoraria for lecturing and travel expenses for attending meetings from Alexion, Almirall, Astra Zenica, Bayer, Biogen, Biontech, Boehringer Ingelheim Bristol Myers-Squibb, C.T.I., Daiichi Sankyo, Docspert, Merck Healthcare Germany GmbH, Weiterstadt, Germany, an affiliate of Merck KGaA, Mylan\/Viatris, Novartis, Pfizer, Roche, Sanofi-Aventis, Stada, Teva, Janssen-Cilag, Horizon Therapeutics, Medscape LLC, Baumgart Consultants, StreamedUp!, Hexal\/Sandoz, Agentur S\u00fcss, Viatris.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interest"}}],"article-number":"218"}}