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Cited by 221Multiple Sclerosis Research StudiesPolyomavirus and related diseasesChronic Lymphocytic Leukemia Research

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Alemtuzumab CARE-MS I 5-year follow-up: Durable efficacy in the absence of continuous MS therapy

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Havrdova, Eva, Arnold, Douglas L., Cohen, Jeffrey A., Hartung, Hans-Peter, Fox, Edward J., Giovannoni, Gavin, Schippling, Sven, Selmaj, Krzysztof W., Traboulsee, Anthony, Compston, D. Alastair S., Margolin, David H., Thangavelu, Karthinathan, Rodriguez, Claudio E., Jody, Darlene, Hogan, Richard J., Xenopoulos, Panos, Panzara, Michael A., Coles, Alasdair J.·2017·Neurology
DOI 10.1212/wnl.0000000000004313PMC PMC5595278
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Abstract

OBJECTIVE: To evaluate 5-year efficacy and safety of alemtuzumab in treatment-naive patients with active relapsing-remitting MS (RRMS) (CARE-MS I; NCT00530348). METHODS: Alemtuzumab-treated patients received treatment courses at baseline and 12 months later; after the core study, they could enter an extension (NCT00930553) with as-needed alemtuzumab retreatment for relapse or MRI activity. Assessments included 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). RESULTS: Most alemtuzumab-treated patients (95.1%) completing CARE-MS I enrolled in the extension; 68.5% received no additional alemtuzumab treatment. ARR remained low in years 3, 4, and 5 (0.19, 0.14, and 0.15). Over years 0-5, 79.7% were free of 6-month CDW; 33.4% achieved 6-month CDI. Most patients (61.7%, 60.2%, and 62.4%) had NEDA in years 3, 4, and 5. Median yearly BVL improved over years 2-4, remaining low in year 5 (years 1-5: -0.59%, -0.25%, -0.19%, -0.15%, and -0.20%). Exposure-adjusted incidence rates of most AEs declined in the extension relative to the core study. Thyroid disorder incidences peaked at year 3 and subsequently declined. CONCLUSIONS: Based on these data, alemtuzumab provides durable efficacy through 5 years in the absence of continuous treatment, with most patients not receiving additional courses. CLINICALTRIALSGOV IDENTIFIER: NCT00530348; NCT00930553. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that alemtuzumab durably improves efficacy outcomes and slows BVL in patients with RRMS.

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Crossref · 10.1212/wnl.0000000000004313

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Figures

Figure 1 Patient disposition Disposition schematic includes patient participation from the core CARE-MS I study through the long-term extension study. DMTs include fingolimod (n = 1), glatiramer acetate (n = 2), interferon β-1a (n = 2), interferon β-1b (n = 3), and natalizumab (n = 1). *The death that occurred in the core study was deemed not related to treatment. CARE-MS = Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis; DMT = disease-modifying therapy.
Figure 1 Patient disposition Disposition schematic includes patient participation from the core CARE-MS I study through the long-term extension study. DMTs include fingolimod (n = 1), glatiramer acetate (n = 2), interferon β-1a (n = 2), interferon β-1b (n = 3), and natalizumab (n = 1). *The death that occurred in the core study was deemed not 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 in alemtuzumab patients. Results are shown for all patients who received alemtuzumab 12 mg in the core CARE-MS I study and then enrolled in the extension. A post hoc analysis revealed no statistically significant difference between ARRs in individual extension years (years 3, 4, and 5) and the ARR in years 0–2. (B) EDSS score change in alemtuzumab patients over 5 years. Proportion of patients with improved (≥1.0-point decrease), stable (≤0.5-point change), or worsened (≥1.0-point increase) EDSS scores at year 5 compared with core study baseline. EDSS score changes are shown for all patients who received alemtuzumab 12 mg in the core study and enrolled in the extension. (C) Proportion of alemtuzumab 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 all patients who received alemtuzumab 12 mg in the core CARE-MS I study and then enrolled in the extension. (D) Proportion of alemtuzumab patients with NEDA over 5 years. Results are shown for all patients who received alemtuzumab 12 mg in the core CARE-MS I study and then enrolled in the extension. *Baseline percentage of patients Gd-enhancing lesion-free: 54%. ARR = annualized relapse rate; CARE-MS = Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis; CDI = confirmed disability improvement; CDW = confirmed disability worsening; EDSS = Expanded Disability Status Scale; Gd = gadolinium; 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 in alemtuzumab patients. Results are shown for all patients who received alemtuzumab 12 mg in the core CARE-MS I study and then enrolled in the extension. A post hoc analysis revealed no statistically significant difference between ARRs in individual extension years (years 3, 4, and 5) and the ARR in years 0–2. (B) EDSS score change in alemtuzumab patients over 5 years. Proportion of patients with improved (≥1.0-point decrease), stable (≤0.5-point change), or worsened (≥1.0-point increase) EDSS scores at year 5 compared with core study baseline. EDSS score changes are shown for all patients who received alemtuzumab 12 mg in the core study and enrolled in the extension. (C) Proportion of alemtuzumab 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 all patients who received alemtuzumab 12 mg in the core CARE-MS I study and then enrolled in the extension. (D) Proportion of alemtuzumab patients with NEDA over 5 years. Results are shown for all patients who received alemtuzumab 12 mg in the core CARE-MS I study and then enrolled in the extension. *Baseline percentage of patients Gd-enhancing lesion-free: 54%. ARR = annualized relapse rate; CARE-MS = Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis; CDI = confirmed disability improvement; CDW = confirmed disability worsening; EDSS = Expanded Disability Status Scale; Gd = gadolinium; NEDA = no evidence of disease activity.CC BY-NC-ND · PubMed Central
Figure 3 Brain volume loss over 5 years in alemtuzumab patients Median yearly percentage change in BPF is shown for all patients who received alemtuzumab 12 mg in the core CARE-MS I study and then enrolled in the extension. BPF = brain parenchymal fraction; CARE-MS = Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis.
Figure 3 Brain volume loss over 5 years in alemtuzumab patients Median yearly percentage change in BPF is shown for all patients who received alemtuzumab 12 mg in the core CARE-MS I study and then enrolled in the extension. BPF = brain parenchymal fraction; CARE-MS = Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis.CC BY-NC-ND · PubMed Central

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Research works printed but not linked: 3

  1. LEMTRADA [Summary of Product Characteristics] [online]. Oxford, United Kingdom: Genzyme Therapeutics, Ltd. 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.
  3. Fox EJ, Arnold DL, Cohen JA, et al. Durable efficacy of alemtuzumab on clinical outcomes over 5 years in CARE-MS II with most patients free from treatment for 4 years. Mult Scler 2015;21(suppl 11):P1102.

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Metadata

Authors
Havrdova, E., Arnold, D. L., Cohen, J. A., Hartung, H.-P., Fox, E. J., Giovannoni, G., Schippling, S., Selmaj, K. W., Traboulsee, A., Compston, D. A. S., Margolin, D. H., Thangavelu, K., Rodriguez, C. E., Jody, D., Hogan, R. J., Xenopoulos, P., Panzara, M. A., & Coles, A. J.
Affiliations
  • From the Department of Neurology and Center for Clinical Neuroscience (E.H.), First Faculty of Medicine, Charles University and General University Hospital in Prague, Czech Republic; NeuroRx Research (D.L.A.), Montréal; Department of Neurology and Neurosurgery (D.L.A.), Montréal Neurological Institute, McGill University, Québec, Canada; Mellen Center (J.A.C.), Cleveland Clinic, OH; Department of Neurology and Center for Neuropsychiatry (H.-P.H.), Medical Faculty, Heinrich-Heine University,...
  • Cleveland Clinic (US)
ORCID
Venue
Neurology
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2017-09-12
Volume
89
Issue
11
Pages
1107-1116
ISSN
  • 0028-3878 (ISSN-L)
  • 1526-632X
DOI
10.1212/wnl.0000000000004313
PMC
PMC5595278
OpenAlex
W2626225244
Cited by
221
References
27
Citations by year
2026: 3 · 2025: 12 · 2024: 19 · 2023: 18 · 2022: 17 · 2021: 37 · 2020: 41 · 2019: 38 · 2018: 33 · 2017: 2
FWCI
24.48
Type
journal article
Language
en
Update notices
correction (2018-04-16)
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)
  • Research Publications (Maastricht University) (submittedVersion, other-oa)
  • Zurich Open Repository and Archive (University of Zurich)
Funders
  • Eli Lilly and Company
  • GlaxoSmithKline
  • Sanofi
  • Biogen
  • Teva Pharmaceutical Industries
  • CSL Behring
  • GW Pharmaceuticals
  • Acorda Therapeutics
  • Five Prime Therapeutics
  • Multiple Sclerosis Society of Canada
  • Multiple Sclerosis Society
  • University of Cambridge
  • Bayer HealthCare
  • Grifols
  • Genentech
  • EMD Serono
  • Sanofi Genzyme
  • Canadian Institutes of Health Research
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, long-term efficacy, treatment-naive patients, annualized relapse rate, disability progression, no evidence of disease activity, brain atrophy, adverse events, thyroid dysfunction, retreatment, Expanded Disability Status Scale, MRI activity, treatment extension
MeSH terms
Alemtuzumab, Brain, Disability Evaluation, Follow-Up Studies, Humans, Immunologic Factors, Organ Size, Time Factors, Treatment Outcome, Multiple Sclerosis, Relapsing-Remitting, Antibodies, Monoclonal, Humanized

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