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With new therapeutic agents introduced into the treatment of RMS, immediate- and long-term consequences of sequential drug use, as well as the effect of the sequence in which the drugs are given, are unclear but may affect efficacy, adverse events, and long-term immunocompetence. In the absence of clinical studies specifically addressing these concerns, observations from clinical practice are of particular value in guiding current management algorithms. Prompted by a study published by Ferraro et al. in this journal, we set out to provide an overview of the published real-world evidence on the effectiveness and safety of switching from fingolimod to another DMT in patients with active RMS. Seventeen publications reporting relevant information were identified. The literature suggests that immune cell depletion induced by alemtuzumab or ocrelizumab is associated with an increased risk of relapse and worsening disability in patients switching from fingolimod compared to patients switching from other therapeutic agents. However, the evidence reported for natalizumab and cladribine is inconclusive. While shortening of the washout period may limit early disease reactivation after fingolimod discontinuation, there is no strong evidence that the duration of the washout period or the absolute lymphocyte count at baseline are predictors of attenuated long-term efficacy. Further real-world studies are required to better understand outcomes among patients who are under-represented in controlled trials.<\/jats:p>","DOI":"10.1007\/s00415-021-10956-1","type":"journal-article","created":{"date-parts":[[2022,1,9]],"date-time":"2022-01-09T01:02:37Z","timestamp":1641690157000},"page":"2806-2818","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Neurological update: treatment escalation in multiple sclerosis patients refractory to fingolimod\u2014potentials and risks of subsequent highly active agents"],"prefix":"10.1007","volume":"269","author":[{"given":"Melanie","family":"Korsen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steffen","family":"Pfeuffer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leoni","family":"Rolfes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven G.","family":"Meuth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0614-6989","authenticated-orcid":false,"given":"Hans-Peter","family":"Hartung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,1,9]]},"reference":[{"issue":"8","key":"10956_CR1","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1001\/jama.2020.26858","volume":"325","author":"MP McGinley","year":"2021","unstructured":"McGinley MP, Goldschmidt CH, Rae-Grant AD (2021) Diagnosis and treatment of multiple sclerosis: a review. 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Steffen Pfeuffer: received travel grants from Sanofi Genzyme and Merck Serono, lecturing honoraria from Sanofi Genzyme, Mylan Healthcare, and Biogen, and research support from Diamed, Merck Serono, and the German Multiple Sclerosis Society Northrhine-Westphalia. Leoni Rolfes: received travel reimbursements from Merck Serono and Sanofi Genzyme, research support from Diamed, Merck Serono and Novartis. Her research is funded by the Interdisciplinary Center for Clinical Studies (IZKF) Muenster. Sven G. Meuth: received honoraria for lecturing and travel expenses for attending meetings from Almirall, Amicus Therapeutics Germany, Bayer Health Care, Biogen, Celgene, Diamed, Genzyme, MedDay Pharmaceuticals, Merck Serono, Novartis, Novo Nordisk, ONO Pharma, Roche, Sanofi-Aventis, Chugai Pharma, QuintilesIMS, and Teva. His research is funded by the German Ministry for Education and Research (BMBF), Deutsche Forschungsgemeinschaft (DFG), Else Kr\u00f6ner Fresenius Foundation, German Academic Exchange Service, Hertie Foundation, Interdisciplinary Center for Clinical Studies (IZKF) Muenster, German Foundation Neurology, and by Almirall, Amicus Therapeutics Germany, Biogen, Diamed, Fresenius Medical Care, Genzyme, Merck Serono, Novartis, ONO Pharma, Roche, and Teva. Hans-Peter Hartung: received fees for consulting and serving on steering and data monitoring committees from Bayer Healthcare, Biogen, CSL Behring, Celgene Receptos, GeNeuro, MedDay, MedImmune, Merck, Novartis, Octapharma, Roche, Teva, TG Therapeutics, VielaBio Horizon Therapeutics.The submitting author hereby declares that he takes responsibility for conduction and analysis of the data and that he had full access to all study data. The submitting author furthermore declares that there are no competing interests concerning these data and that the authors have all rights to publish the data. The submitted manuscript does not contain data that have been published in any other journal. The authors have no related articles under submission.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interest"}}]}}