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Objective: Compare different treatment strategies after natalizumab failure. Methods: Relapse during natalizumab with adequate follow-up was identified from the MSBase registry; natalizumab continuation was compared with switching to anti-CD20 therapies/alemtuzumab/lower-efficacy therapies and with treatment discontinuation. Primary outcome was further relapse risk; secondary outcomes included MRI activity, disability worsening, and disease-activity-free survival. Results: Anti-CD20 switching reduced relapse risk versus continuing natalizumab. No MRI or disability differences were detected; de-escalation or cessation increased relapse risk.",{"@graph":69,"@context":123},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/managing-reactivation-of-multiple-sclerosis-during-treatment-with-natalizumab/411324/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/managing-reactivation-of-multiple-sclerosis-during-treatment-with-natalizumab/411324.png","ImageObject",300,407,{"name":92,"@type":93},"Stanley","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-30","2026-09-28",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",11,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What clinical question does the study address after natalizumab failure?","Question",{"text":113,"@type":114},"It examines whether switching to alternative high-efficacy therapies provides better effectiveness than continuing natalizumab after failure, focusing on relapse outcomes and related disease activity measures.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"How were patients and treatment strategies compared?",{"text":118,"@type":114},"Patients who experienced relapse during natalizumab treatment with adequate follow-up were identified from the MSBase registry. Outcomes compared natalizumab continuation versus switching to anti-CD20 therapies, alemtuzumab, lower-efficacy therapies, or discontinuation.",{"name":120,"@type":111,"acceptedAnswer":121},"What were the key findings on relapse risk and secondary outcomes?",{"text":122,"@type":114},"Switching to anti-CD20 therapy after natalizumab failure was associated with a lower relapse risk than continuing natalizumab, while MRI activity and disability outcomes showed no differences. De-escalation or cessation increased relapse risk, and sensitivity analyses supported the primary results.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},411324,1790766208,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":140,"language":141,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":67,"update_tm":145,"read_time":146,"preview_page_count":4},2336477405376,"https://ap-avatar.wpscdn.com/davatar_29158cc5080c5b710cf443261637dec0","MULTIPLE SCLEROSIS JOURNAL  \nMSJ  \nOriginal Research Paper  \nManaging reactivation of multiple sclerosis during treatment with natalizumab  \nNathaniel Lizak, Sifat Sharmin, Dana Horáková, Eva Kubala Havrdova, Sara Eichau, Anneke van der Walt, Helmut Butzkueven, Jeannette Lechner-Scott, Katherine Buzzard, Olga Skibina, Oliver Gerlach, Alexandre Prat, Marc Girard, Pierre Duquette, Raed Alroughani, Francesco Patti, Francois Grand’Maison, Maria José Sá, Eduardo Aguera-Morales, Suzanne Hodgkinson, Pierre Grammond, Jens Kuhle, Bassem Yamout, Samia J Khoury, Serkan Ozakbas, Tunde Csepany, Nevin John, Guy Laureys, Murat Terzi, Maria Pia Amato, Cavit Boz, Abdullah Al-Asmi, Elisabetta Cartechini, Riadh Gouider, Saloua Mrabet,  \nIzanne Roos* and Tomas Kalincik*; On Behalf ofthe MSBase Study Group**  \nAbstract  \nBackground: Following natalizumab failure, it is unknown whether switching to alternative high-efficacy therapies offers superior effectiveness over continuing natalizumab.  \nObjective: To compare different treatment strategies following natalizumab failure.  \nMethods: Patients suffering a relapse during natalizumab treatment with adequate follow-up were identified from the MSBase registry. Following natalizumab failure, natalizumab continuation was compared to switching to anti-CD20 therapies/alemtuzumab/lower-efficacy therapies and treatment discontinuation. The primary outcome was the risk of further relapses. Secondary outcomes included risk of subsequent magnetic resonance imaging (MRI) activity, confirmed disability worsening and disease-activity-free survival. Multivariable proportional hazards models compared outcomes during time-varying therapy exposures. Four sensitivity analyses were conducted with varied inclusion criteria and treatment failure definitions.  \nResults: Of 1553 patients experiencing a relapse during natalizumab treatment, 1037 met the inclusion criteria. Following natalizumab failure, switch to anti-CD20 therapy was associated with a lower relapse risk (heart rate (HR) = 0.48, 95% confidence interval (CI) = 0.27–0.84) compared to continuing natalizumab; no differences were observed in MRI or disability outcomes. Treatment de-escalation or cessation was associated with increased relapse risk (HR = 1.46, 95% CI = 1.15–1.85; HR = 2.08, 95% CI = 1.22– 3.55, respectively) . We did not find evidence of a difference for switching to alemtuzumab. Sensitivity analyses replicated primary findings.  \nConclusion: This exploratory study indicates that switching to anti-CD20 therapies following natalizumab failure is associated with a >50% reduction in relapse risk. No differences were seen in secondary outcomes, despite consistent trends. Clinicians may consider anti-CD20 therapies following natalizumab failure, noting further research is needed to confirm differences in MRI and disability outcomes.  \nKeywords: Multiple sclerosis, natalizumab, disease-modifying treatment, relapses, treatment failure  \nDate received: 17 July 2025; revised: 29 October 2025; accepted: 5 November 2025  \nIntroduction  \nMultiple sclerosis (MS) is a demyelinating disease of the central nervous system characterised by distinct episodic deteriorations (relapses) and gradual progression  \nof neurological disability. Disease-modifying treatments (DMTs) have shown varying efficacy in suppressing relapses and preventing disability accumulation.  \nMultiple Sclerosis Journal 2026, Vol. 32(1) 121–133 DOI: 10. 1177/ 13524585251398682 © The Author(s), 2025.  \nArticle reuse guidelines: [sagepub.com/journals](sagepub.com/journals)permissions  \nCorrespondence to:  \nT Kalincik  \nNeuroimmunology Centre, Department of Neurology, Royal Melbourne Hospital, L7, 635 Elizabeth Street, Melbourne, VIC 3000, Australia.  \ntomas.kalincik@unimelb. [edu.au](edu.au)  \nNathaniel Lizak Sifat Sharmin  \nClinical Outcomes Research Unit (CORe), Department of Medicine, University of Melbourne, Melbourne, VIC, Australia; Neuroimmunology Centre, Department of Neurology, Royal Me","cbCaityfzjrn9cnu","https://ap.wps.com/l/cbCaityfzjrn9cnu","pdf",1376307,13,"English","# Abstract\n## Background\n## Objective\n## Methods\n## Results\n## Conclusion\n# Introduction","[{\"question\":\"What clinical question does the study address after natalizumab failure?\",\"answer\":\"It examines whether switching to alternative high-efficacy therapies provides better effectiveness than continuing natalizumab after failure, focusing on relapse outcomes and related disease activity measures.\"},{\"question\":\"How were patients and treatment strategies compared?\",\"answer\":\"Patients who experienced relapse during natalizumab treatment with adequate follow-up were identified from the MSBase registry. Outcomes compared natalizumab continuation versus switching to anti-CD20 therapies, alemtuzumab, lower-efficacy therapies, or discontinuation.\"},{\"question\":\"What were the key findings on relapse risk and secondary outcomes?\",\"answer\":\"Switching to anti-CD20 therapy after natalizumab failure was associated with a lower relapse risk than continuing natalizumab, while MRI activity and disability outcomes showed no differences. De-escalation or cessation increased relapse risk, and sensitivity analyses supported the primary results.\"}]","Managing reactivation of multiple sclerosis during treatment with natalizumab | PDF",1790588185,33]