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Alemtuzumab CARE-MS II 5-year follow-up: Efficacy and safety findings

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Coles, Alasdair J., Cohen, Jeffrey A., Fox, Edward J., Giovannoni, Gavin, Hartung, Hans-Peter, Havrdova, Eva, Schippling, Sven, Selmaj, Krzysztof W., Traboulsee, Anthony, Compston, D. Alastair S., Margolin, David H., Thangavelu, Karthinathan, Chirieac, Madalina C., Jody, Darlene, Xenopoulos, Panos, Hogan, Richard J., Panzara, Michael A., Arnold, Douglas L.·2017·Neurology
DOI 10.1212/wnl.0000000000004354PMC PMC5595276
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Abstract

OBJECTIVE: To evaluate 5-year efficacy and safety of alemtuzumab in patients with active relapsing-remitting multiple sclerosis and inadequate response to prior therapy. METHODS: In the 2-year Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis (CARE-MS) II study (NCT00548405), alemtuzumab-treated patients received 2 courses (baseline and 12 months later). Patients could enter an extension (NCT00930553), with as-needed alemtuzumab retreatment for relapse or MRI activity. Annualized relapse rate (ARR), 6-month confirmed disability worsening (CDW; ≥1-point Expanded Disability Status Scale [EDSS] score increase [≥1.5 if baseline EDSS = 0]), 6-month confirmed disability improvement (CDI; ≥1-point EDSS decrease [baseline score ≥2.0]), no evidence of disease activity (NEDA), brain volume loss (BVL), and adverse events (AEs) were assessed. RESULTS: Most alemtuzumab-treated patients (92.9%) who completed CARE-MS II entered the extension; 59.8% received no alemtuzumab retreatment. ARR was low in each extension year (years 3-5: 0.22, 0.23, 0.18). Through 5 years, 75.1% of patients were free of 6-month CDW; 42.9% achieved 6-month CDI. In years 3, 4, and 5, proportions with NEDA were 52.9%, 54.2%, and 58.2%, respectively. Median yearly BVL remained low in the extension (years 1-5: -0.48%, -0.22%, -0.10%, -0.19%, -0.07%). AE exposure-adjusted incidence rates in the extension were lower than in the core study. Thyroid disorders peaked at year 3, declining thereafter. CONCLUSIONS: Alemtuzumab provides durable efficacy through 5 years in patients with an inadequate response to prior therapy in the absence of continuous treatment. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that alemtuzumab provides efficacy and slowing of brain atrophy through 5 years.

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Figure 1 Patient disposition The disposition schematic includes participation of patients treated with alemtuzumab 12 mg in the core CARE-MS II and then enrolled in the long-term extension study. *The as-treated population (n = 435) consisted of 426 patients originally randomized to alemtuzumab 12 mg and an additional 9 patients who were randomized to alemtuzumab 24 mg but who instead received alemtuzumab 12 mg/d in the core study. **Neither death that occurred in the core study was related to treatment. CARE-MS = Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis; DMT = disease-modifying therapy.
Figure 1 Patient disposition The disposition schematic includes participation of patients treated with alemtuzumab 12 mg in the core CARE-MS II and then enrolled in the long-term extension study. *The as-treated population (n = 435) consisted of 426 patients originally randomized to alemtuzumab 12 mg and an additional 9 patients who were randomized to alemtuzumab 24 mg but who instead received alemtuzumab 12 mg/d in the core study. **Neither death that occurred in the core study was related to treatment. CARE-MS = Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis; DMT = disease-modifying therapy.CC BY-NC-ND · PubMed Central
Figure 2 Clinical efficacy and disease activity outcomes over 5 years in alemtuzumab patients (A) ARR over 5 years. Results are shown for patients who received alemtuzumab 12 mg in the core CARE-MS II study and enrolled in the extension. A post hoc analysis revealed a statistically significant difference between the ARR in year 5 and the ARR in years 0–2 (p = 0.0021), and no significant difference between ARRs in either year 3 or year 4 and the ARR in years 0–2. (B) Percentage of patients with improved (≥1.0-point decrease), stable (≤0.5-point change), or worsened (≥1.0-point increase) EDSS scores at year 5 of the extension study compared with core study baseline. Analyses are shown for all patients who received alemtuzumab 12 mg in the core study and enrolled in the extension. (C) Percentage of patients with 3-, 6-, or 12-month CDI over 5 years. Kaplan-Meier analysis of time to 3-, 6-, or 12-month CDI is shown for patients who received alemtuzumab 12 mg in the core CARE-MS II study and enrolled in the extension. (D) Proportion of patients with NEDA over 5 years. NEDA outcomes are shown for patients who received alemtuzumab 12 mg in the core CARE-MS II study and enrolled in the extension. *Baseline percentage of patients free of gadolinium (Gd)–enhancing lesions: 58%. ARR = annualized relapse rate; CARE-MS = Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis; CDI = confirmed disability improvement; CDW = confirmed disability worsening; CI = confidence interval; EDSS = Expanded Disability Status Scale; NEDA = no evidence of disease activity.
Figure 2 Clinical efficacy and disease activity outcomes over 5 years in alemtuzumab patients (A) ARR over 5 years. Results are shown for patients who received alemtuzumab 12 mg in the core CARE-MS II study and enrolled in the extension. A post hoc analysis revealed a statistically significant difference between the ARR in year 5 and the ARR in years 0–2 (p = 0.0021), and no significant difference between ARRs in either year 3 or year 4 and the ARR in years 0–2. (B) Percentage of patients with improved (≥1.0-point decrease), stable (≤0.5-point change), or worsened (≥1.0-point increase) EDSS scores at year 5 of the extension study compared with core study baseline. Analyses are shown for all patients who received alemtuzumab 12 mg in the core study and enrolled in the extension. (C) Percentage of patients with 3-, 6-, or 12-month CDI over 5 years. Kaplan-Meier analysis of time to 3-, 6-, or 12-month CDI is shown for patients who received alemtuzumab 12 mg in the core CARE-MS II study and enrolled in the extension. (D) Proportion of patients with NEDA over 5 years. NEDA outcomes are shown for patients who received alemtuzumab 12 mg in the core CARE-MS II study and enrolled in the extension. *Baseline percentage of patients free of gadolinium (Gd)–enhancing lesions: 58%. ARR = annualized relapse rate; CARE-MS = Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis; CDI = confirmed disability improvement; CDW = confirmed disability worsening; CI = confidence interval; EDSS = Expanded Disability Status Scale; NEDA = no evidence of disease activity.CC BY-NC-ND · PubMed Central
Figure 3 Brain volume loss over 5 years Median percentage yearly change in brain parenchymal fraction (BPF). Results are shown for patients who received alemtuzumab 12 mg in the core study and enrolled in the extension. CI = confidence interval.
Figure 3 Brain volume loss over 5 years Median percentage yearly change in brain parenchymal fraction (BPF). Results are shown for patients who received alemtuzumab 12 mg in the core study and enrolled in the extension. CI = confidence interval.CC BY-NC-ND · PubMed Central

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Research works printed but not linked: 2

  1. LEMTRADA [summary of product characteristics] [online]. Available at: ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/003718/WC500150521.pdf. Accessed May 30, 2014.
  2. LEMTRADA (Alemtuzumab), for Intravenous Injection [prescribing information]. Cambridge, MA: Genzyme Corporation; 2014.

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Metadata

Authors
Coles, A. J., Cohen, J. A., Fox, E. J., Giovannoni, G., Hartung, H.-P., Havrdova, E., Schippling, S., Selmaj, K. W., Traboulsee, A., Compston, D. A. S., Margolin, D. H., Thangavelu, K., Chirieac, M. C., Jody, D., Xenopoulos, P., Hogan, R. J., Panzara, M. A., & Arnold, D. L.
Affiliations
  • Cleveland Clinic (US)
  • From the Department of Clinical Neurosciences (A.J.C., D.A.S.C.), University of Cambridge, UK; Mellen Center (J.A.C.), Cleveland Clinic, OH; MS Clinic of Central Texas (E.J.F.), Central Texas Neurology Consultants, Round Rock; Queen Mary University of London (G.G.), Barts and the London School of Medicine, UK; Department of Neurology and Center for Neuropsychiatry (H.-P.H.), Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany; Department of Neurology and Center for Clinical Neuroscience ...
Corresponding author
Coles, Alasdair J.
ORCID
Venue
Neurology
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2017-09-12
Volume
89
Issue
11
Pages
1117-1126
ISSN
  • 0028-3878 (ISSN-L)
  • 1526-632X
DOI
10.1212/wnl.0000000000004354
PMC
PMC5595276
OpenAlex
W2746924405
Cited by
277
References
38
Citations by year
2026: 8 · 2025: 19 · 2024: 28 · 2023: 22 · 2022: 20 · 2021: 42 · 2020: 46 · 2019: 47 · 2018: 40 · 2017: 4
FWCI
29.43
Type
journal article
Language
en
Open access
Licence
cc-by-nc-nd
Locations
  • Neurology (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • Research Publications (Maastricht University) (publishedVersion, cc-by-nc-nd)
  • Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, other-oa)
  • Queen Mary Research Online (Queen Mary University of London) (submittedVersion, cc-by-nc-nd)
  • Apollo (University of Cambridge) (submittedVersion, cc-by-nc-nd)
  • Research Publications (Maastricht University) (submittedVersion, other-oa)
  • Apollo (cc-by-nc-nd)
  • Zurich Open Repository and Archive (University of Zurich)
Funders
  • Sanofi
  • Cleveland Clinic
  • Bayer HealthCare
  • Sanofi Genzyme
Topics
  • Health Sciences › Medicine › Clinical Neurology › Multiple Sclerosis Research Studies
  • Health Sciences › Medicine › Oncology › Polyomavirus and related diseases
  • Health Sciences › Medicine › Hematology › Chronic Lymphocytic Leukemia Research
Keywords
alemtuzumab, relapsing-remitting multiple sclerosis, annualized relapse rate, disability progression, disability improvement, no evidence of disease activity, brain atrophy, adverse events, thyroid dysfunction, long-term efficacy and safety
MeSH terms
Alemtuzumab, Atrophy, Brain, Disability Evaluation, Follow-Up Studies, Humans, Immunologic Factors, Organ Size, Time Factors, Treatment Outcome, Multiple Sclerosis, Relapsing-Remitting, Kaplan-Meier Estimate, Antibodies, Monoclonal, Humanized

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