{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T11:39:23Z","timestamp":1791545963173,"version":"4.3.4"},"reference-count":37,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004339","name":"Sanofi","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004339","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Ther Adv Neurol Disord"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:sec><jats:title>Background:<\/jats:title><jats:p> Alemtuzumab is a disease-modifying therapy for highly active relapsing-remitting multiple sclerosis (RRMS). Sustained efficacy up to 9\u2009years was observed in the phase IIIb\/IV open-label TOPAZ clinical trial and assessed in the real-world retrospective and prospective study, TREAT-MS. <\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives:<\/jats:title><jats:p> To examine long-term efficacy and safety of alemtuzumab in participants with multiple sclerosis (MS) and highly active disease (HAD) by combining up to 13\u2009years of TOPAZ data and TREAT-MS interim data. <\/jats:p><\/jats:sec><jats:sec><jats:title>Design:<\/jats:title><jats:p> TOPAZ: Randomized participants completing core CARE-MS I and II could receive additional alemtuzumab (12\u2009mg\/day, 3 consecutive days; \u2a7e12\u2009months apart) for 11\u201313\u2009years after initiating treatment. TREAT-MS: Participants from German MS clinics were observed for 4\u2009years after last alemtuzumab treatment phase. <\/jats:p><\/jats:sec><jats:sec><jats:title>Methods:<\/jats:title><jats:p> Efficacy outcomes (annualized relapse rate (ARR), change in Expanded Disability Status Scale (EDSS), 6-month confirmed disability worsening\/improvement, magnetic resonance imaging), and adverse events (AEs) were examined. Primary HAD definition (\u2a7e2 relapses in the year prior to baseline and \u2a7e1 gadolinium-enhancing lesion at baseline), and two alternative HAD definitions were assessed. <\/jats:p><\/jats:sec><jats:sec><jats:title>Results:<\/jats:title><jats:p> More participants from CARE-MS I (28%) and II (24%) met primary HAD criteria than TREAT-MS (~14%). Mean ARR for alemtuzumab-treated HAD participants was significantly reduced in CARE-MS I and II (0.14 and 0.15, respectively, Years 3\u201313) and in TREAT-MS (0.24, &gt;2\u2009years). Stable\/improved EDSS scores were achieved by 74% of HAD participants in CARE-MS I, 67% in CARE-MS II (both Year 11), and 79% in TREAT-MS (Year 3.6), with 6-month CDI achieved by about half at Year 11 (CARE-MS I, II). Annual treatment-emergent AE incidences declined in TOPAZ and were lower in TREAT-MS. <\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion:<\/jats:title><jats:p> Sustained efficacy of alemtuzumab was observed for clinical and radiological outcomes in participants with HAD in the TOPAZ clinical trial and real-world TREAT-MS study with no new safety signals. <\/jats:p><\/jats:sec><jats:sec><jats:title>Trial registration:<\/jats:title><jats:p> ClinicalTrials.gov (CARE-MS I, NCT00530348; CARE-MS II, NCT00548405; CARE-MS Extension Study, NCT00930553; TOPAZ, NCT02255656). Paul-Ehrlich-Institut (TREAT-MS, NIS 281). <\/jats:p><\/jats:sec>","DOI":"10.1177\/17562864241306575","type":"journal-article","created":{"date-parts":[[2025,2,10]],"date-time":"2025-02-10T16:44:18Z","timestamp":1739205858000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":6,"title":["Long-term efficacy and safety of alemtuzumab in participants with highly active MS: TOPAZ clinical trial and interim analysis of TREAT-MS real-world study"],"prefix":"10.1177","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8799-8202","authenticated-orcid":false,"given":"Tjalf","family":"Ziemssen","sequence":"first","affiliation":[{"name":"Center of Clinical Neuroscience, Neurological Clinic, University Clinic Carl Gustav Carus, Technische Universit\u00e4t Dresden, Fetscherstr. 74, Dresden 01307, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann D.","family":"Bass","sequence":"additional","affiliation":[{"name":"Neurology Center of San Antonio, San Antonio, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bart","family":"Van Wijmeersch","sequence":"additional","affiliation":[{"name":"University MS Center, Hasselt-Pelt, Belgium"},{"name":"Rehabilitation and MS, Noorderhart Hospitals, Pelt, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Eichau","sequence":"additional","affiliation":[{"name":"Hospital Universitario Virgen Macarena, Seville, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Richter","sequence":"additional","affiliation":[{"name":"Zentrum f\u00fcr Neurologie und Psychiatrie, MIND, Stuttgart, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Hoffmann","sequence":"additional","affiliation":[{"name":"Klinik f\u00fcr Neurologie, Krankenhaus Martha-Maria Halle-Doelau, Halle (Saale), Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole M.","family":"Armstrong","sequence":"additional","affiliation":[{"name":"Sanofi, Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Chirieac","sequence":"additional","affiliation":[{"name":"Sanofi, Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janete","family":"Cunha-Santos","sequence":"additional","affiliation":[{"name":"Sanofi, Porto Salvo, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6875-7374","authenticated-orcid":false,"given":"Barry A.","family":"Singer","sequence":"additional","affiliation":[{"name":"The MS Center for Innovations in Care, Missouri Baptist Medical Center, St. Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,2,10]]},"reference":[{"key":"bibr1-17562864241306575","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2015.85"},{"key":"bibr2-17562864241306575","doi-asserted-by":"publisher","DOI":"10.1016\/j.msard.2019.01.039"},{"key":"bibr3-17562864241306575","doi-asserted-by":"publisher","DOI":"10.1177\/1352458512438454"},{"key":"bibr4-17562864241306575","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000005347"},{"key":"bibr5-17562864241306575","unstructured":"Sanofi Belgium. 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