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. 2020 Nov;26(13):1719-1728.
doi: 10.1177/1352458519881759. Epub 2019 Nov 1.

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  1 , Barry A Singer  2 , Aaron Boster  3 , Simon Broadley  4 , Óscar Fernández  5 , Mark S Freedman  6 , Guillermo Izquierdo  7 , Jan Lycke  8 , Carlo Pozzilli  9 , Basil Sharrack  10 , Brian Steingo  11 , Heinz Wiendl  12 , Sibyl Wray  13 , Tjalf Ziemssen  14 , Luke Chung  15 , David H Margolin  16 , Karthinathan Thangavelu  17 , Patrick Vermersch  18
Affiliations

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 et al. Mult Scler. 2020 Nov.

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).

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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.

Figures

Figure 1.
Figure 1.
Proportions of early relapsers and early non-relapsers. Proportions of patients with and without relapse between alemtuzumab Courses 1 and 2 in the core CARE-MS I (left) and CARE-MS II (right) studies. CARE-MS: Comparison of Alemtuzumab and Rebif® Efficacy in Multiple Sclerosis.
Figure 2.
Figure 2.
Clinical efficacy outcomes in early relapsers through 6 years. (a) ARR and proportions free of relapse, (b) proportions free of 6-month CDW, and (c) proportions achieving 6-month CDI over 6 years in patients with relapse between alemtuzumab Courses 1 and 2 in the core CARE-MS I and CARE-MS II studies. ARR: annualized relapse rate; CARE-MS: Comparison of Alemtuzumab and Rebif® Efficacy in Multiple Sclerosis; CDI: confirmed disability improvement; CDW: confirmed disability worsening; CIs: confidence intervals; EDSS: Expanded Disability Status Scale. Error bars denote 95% CIs. aKaplan–Meier estimates. bNumber at risk is the number of patients who remained on study and had yet to experience 6-month CDW or 6-month CDI. CDI is defined as ⩾1-point EDSS decrease from baseline confirmed over 6 months (CDI is assessed only in patients with baseline EDSS score ⩾ 2.0). CDW is defined as ⩾1-point EDSS increase (or ⩾1.5 points if baseline EDSS = 0) confirmed over 6 months.
Figure 3.
Figure 3.
MRI outcomes in early relapsers through 6 years. (a) Proportions free of MRI disease activity and (b) median percentage yearly change in BPF over 6 years in patients with relapse between alemtuzumab Courses 1 and 2 in the core CARE-MS I and CARE-MS II studies. Freedom from MRI disease activity was defined as the absence of new gadolinium-enhancing T1 and new/enlarging T2 hyperintense lesions. BPF: brain parenchymal fraction; CARE-MS: Comparison of Alemtuzumab and Rebif® Efficacy in Multiple Sclerosis; CIs: confidence intervals; MRI: magnetic resonance imaging. Error bars denote 95% CIs.
Figure 4.
Figure 4.
Efficacy outcomes of early relapsers and early non-relapsers through Year 6. (a) ARR during Year 6, (b) proportions free of 6-month CDW over 6 years, (c) proportions achieving 6-month CDI over 6 years, (d) proportions free of MRI disease activity during Year 6, and (e) median percentage change in BPF during Year 6 in patients with and without relapse between alemtuzumab Courses 1 and 2 in the core CARE-MS I and CARE-MS II studies. Freedom from MRI disease activity was defined as the absence of new gadolinium-enhancing T1 and new/enlarging T2 hyperintense lesions. ARR: annualized relapse rate; BPF: brain parenchymal fraction; CARE-MS: Comparison of Alemtuzumab and Rebif® Efficacy in Multiple Sclerosis; CDI: confirmed disability improvement; CDW: confirmed disability worsening; MRI: magnetic resonance imaging; CI: confidence interval; EDSS: Expanded Disability Status Scale. Error bars denote 95% CIs. aKaplan–Meier estimates. bNumber at risk is the number of patients who remained on study and had yet to experience 6-month CDW or 6-month CDI, respectively. CDI is defined as ⩾1-point EDSS decrease from baseline confirmed over 6 months (CDI is assessed only in patients with baseline EDSS score ⩾ 2.0). CDW is defined as ⩾1-point EDSS increase (or ⩾1.5 points if baseline EDSS = 0) confirmed over 6 months.
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