Efficacy of alemtuzumab over 6 years in relapsing-remitting multiple sclerosis patients who relapsed between courses 1 and 2: Post hoc analysis of the CARE-MS studies
Bart Van Wijmeersch, Barry A Singer, Aaron Boster, Simon Broadley, Óscar Fernández, Mark S Freedman, Guillermo Izquierdo, Jan Lycke, Carlo Pozzilli, Basil Sharrack, Brian Steingo, Heinz Wiendl, Sibyl Wray, Tjalf Ziemssen, Luke Chung, David H Margolin, Karthinathan Thangavelu, Patrick Vermersch, Bart Van Wijmeersch, Barry A Singer, Aaron Boster, Simon Broadley, Óscar Fernández, Mark S Freedman, Guillermo Izquierdo, Jan Lycke, Carlo Pozzilli, Basil Sharrack, Brian Steingo, Heinz Wiendl, Sibyl Wray, Tjalf Ziemssen, Luke Chung, David H Margolin, Karthinathan Thangavelu, Patrick Vermersch
Abstract
Background: Alemtuzumab is administered as two annual courses for relapsing-remitting multiple sclerosis (MS). Patients may relapse before completing the two-course regimen.
Objective: The objective was to evaluate 6-year outcomes in patients who relapsed between alemtuzumab Courses 1 and 2 (early relapsers).
Methods: Post hoc analysis of patients from the Comparison of Alemtuzumab and Rebif® Efficacy in Multiple Sclerosis (CARE-MS) studies who enrolled in the extension.
Results: Early relapsers (CARE-MS I: 15%; CARE-MS II: 24%) had more relapses in 1-2 years pre-alemtuzumab and higher mean baseline Expanded Disability Status Scale score than patients without relapse. Their annualized relapse rate declined from Year 1 (CARE-MS I: 1.3; CARE-MS II: 1.2) to Year 2 following Course 2 (0.3; 0.5) and remained low thereafter. Over 6 years, 60% remained free of 6-month confirmed disability worsening; 24% (CARE-MS I) and 34% (CARE-MS II) achieved 6-month confirmed disability improvement. During Year 6, 69% (CARE-MS I) and 68% (CARE-MS II) were free of magnetic resonance imaging (MRI) disease activity. Median percent yearly brain volume loss (Year 1: -0.67% (CARE-MS I); -0.47% (CARE-MS II)) declined after Course 2 (Year 6: -0.24%; -0.13%).
Conclusion: Early relapsers' outcomes improved after completing the second alemtuzumab course. These findings support administering the approved two-course regimen to maximize clinical benefit.
Clinicaltrials.gov registration numbers: CARE-MS I, II, extension: NCT00530348, NCT00548405, NCT00930553.
Keywords: Alemtuzumab; disability; disease-modifying therapy; efficacy; magnetic resonance imaging (MRI); relapsing–remitting multiple sclerosis (MS).
Conflict of interest statement
Declaration of Conflicting Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: B.V.W. received research and travel grants; honoraria for MS-expert advice; and speakers’ fees from Actelion, Bayer Schering, Biogen, Merck Serono, Novartis, Roche, Sanofi, and Teva. B.A.S. received fees for speaking and/or consulting from AbbVie, Acorda, Biogen, EMD Serono, Genentech, Novartis, Pfizer, Roche, Sanofi, and Teva and research support from AbbVie, Acorda, Alkermes, Biogen, MedImmune, Novartis, Roche, and Sanofi. A.B. received consulting fees and/or fees for non-CME services from Biogen, Mallinckrodt, Medtronic, Novartis, Sanofi, and Teva. S.B. received speaking and/or consulting fees from Bayer, Biogen, Merck Serono, Novartis, Roche, and Sanofi. O.F. received speaking and/or consulting fees from Allergan, Almirall, Bayer Schering, Biogen, Merck Serono, Novartis, Sanofi, and Teva; compensation for serving as a journal editor, associate editor, or member of an editorial advisory board for Revista Española de Esclerosis Múltiple; and research support from the Hospital Foundatión FIMABIS. M.S.F. received honoraria/consulting fees from Actelion, Bayer, Biogen, Canada Innovation, Chugai, EMD Canada, Merck Serono, Novartis, Roche, Sanofi, and Teva; support as a member of advisory board, board of directors, or other similar group from Actelion, Bayer, Biogen, Clene, Merck Serono, Novartis, Roche, and Sanofi; and fees for participation in speaker’s bureau from Sanofi. G.I. received speaking and advisory fees from Almirall, Bayer, Biogen, Merck Serono, Novartis, Roche, Sanofi, and Teva. J.L. received travel support and/or lecture honoraria from Biogen, Novartis, Sanofi, and Teva; support from scientific advisory boards from Almirall, Biogen, Novartis, Sanofi, and Teva; compensation as part of the editorial board for Acta Neuro-logica Scandinavica; and unconditional research grants from Biogen, Novartis, and Teva. C.P. received consulting and/or speaking fees, research, and travel grants from Actelion, Biogen, Merck, Novartis, Sanofi, and Teva. B. Sharrack received research and travel grants; honoraria for expert advice on MS; and speaker’s fees from Biogen, Merck, Novartis, Roche, Sanofi, and Teva. B. Steingo received consulting; speaking fees; and/or grant/research support from Acorda, Biogen, EMD Serono, Mallinckrodt, Novartis, Sanofi, and Teva. H.W. received consulting and/or speaking fees and grant/research support from Bayer, Bayer Schering Pharma, Biogen, Elan Corporation, Lilly, Lundbeck, Merck Serono, Novartis, Novo Nordisk, Sanofi, and Teva Neuroscience. S.W. received fees as consultant; principal investigator; and/or speaker from Alkermes, Asclepios, Biogen, Celgene, EMD Serono, Novartis, Roche, Sanofi, and TG Therapeutics. T.Z. received consulting and/or speaking fees from Almirall, Bayer, Biogen, Merck, Novartis, Roche, Sanofi, and Teva and grant/research support from Biogen, Novartis, Sanofi, and Teva. L.C. and K.T. receive compensation as employees of Sanofi. D.H.M. received compensation as an employee of Sanofi at the time this study was conducted and is currently an employee of Cerevance, Inc. P.V. received consulting and/or speaking fees and research support from Almirall, Bayer, Biogen, Celgene, Merck Serono, Novartis, Sanofi, Servier, and Teva.
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Source: PubMed