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Alemtuzumab CARE-MS II 5-year follow-up: Efficacy and safety findings.
Neurology. 2017 Sep 12; 89(11):1117-1126.Neur

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.

Authors+Show Affiliations

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 (E.H.), First Faculty of Medicine, Charles University and General Hospital in Prague, Czech Republic; Neuroimmunology and Multiple Sclerosis Research, Department of Neurology (S.S.), University Hospital Zürich and University of Zürich, Switzerland; Department of Neurology (K.W.S.), Medical University of Łódź, Poland; The University of British Columbia (A.T.), Vancouver, Canada; Sanofi (D.H.M., K.T., M.C.C., D.J., M.A.P.), Cambridge, MA; Envision Scientific Solutions (P.X.), Philadelphia, PA; Envision Scientific Solutions (R.J.H.), Sydney, NSW, Australia; NeuroRx Research (D.L.A.), Montréal; Department of Neurology and Neurosurgery (D.L.A.), Montréal Neurological Institute, McGill University, Québec, Canada. M.A.P. is currently affiliated with Wave Life Sciences, Cambridge, MA. ajc1020@medschl.cam.ac.uk.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 (E.H.), First Faculty of Medicine, Charles University and General Hospital in Prague, Czech Republic; Neuroimmunology and Multiple Sclerosis Research, Department of Neurology (S.S.), University Hospital Zürich and University of Zürich, Switzerland; Department of Neurology (K.W.S.), Medical University of Łódź, Poland; The University of British Columbia (A.T.), Vancouver, Canada; Sanofi (D.H.M., K.T., M.C.C., D.J., M.A.P.), Cambridge, MA; Envision Scientific Solutions (P.X.), Philadelphia, PA; Envision Scientific Solutions (R.J.H.), Sydney, NSW, Australia; NeuroRx Research (D.L.A.), Montréal; Department of Neurology and Neurosurgery (D.L.A.), Montréal Neurological Institute, McGill University, Québec, Canada. M.A.P. is currently affiliated with Wave Life Sciences, Cambridge, MA.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 (E.H.), First Faculty of Medicine, Charles University and General Hospital in Prague, Czech Republic; Neuroimmunology and Multiple Sclerosis Research, Department of Neurology (S.S.), University Hospital Zürich and University of Zürich, Switzerland; Department of Neurology (K.W.S.), Medical University of Łódź, Poland; The University of British Columbia (A.T.), Vancouver, Canada; Sanofi (D.H.M., K.T., M.C.C., D.J., M.A.P.), Cambridge, MA; Envision Scientific Solutions (P.X.), Philadelphia, PA; Envision Scientific Solutions (R.J.H.), Sydney, NSW, Australia; NeuroRx Research (D.L.A.), Montréal; Department of Neurology and Neurosurgery (D.L.A.), Montréal Neurological Institute, McGill University, Québec, Canada. M.A.P. is currently affiliated with Wave Life Sciences, Cambridge, MA.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 (E.H.), First Faculty of Medicine, Charles University and General Hospital in Prague, Czech Republic; Neuroimmunology and Multiple Sclerosis Research, Department of Neurology (S.S.), University Hospital Zürich and University of Zürich, Switzerland; Department of Neurology (K.W.S.), Medical University of Łódź, Poland; The University of British Columbia (A.T.), Vancouver, Canada; Sanofi (D.H.M., K.T., M.C.C., D.J., M.A.P.), Cambridge, MA; Envision Scientific Solutions (P.X.), Philadelphia, PA; Envision Scientific Solutions (R.J.H.), Sydney, NSW, Australia; NeuroRx Research (D.L.A.), Montréal; Department of Neurology and Neurosurgery (D.L.A.), Montréal Neurological Institute, McGill University, Québec, Canada. M.A.P. is currently affiliated with Wave Life Sciences, Cambridge, MA.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 (E.H.), First Faculty of Medicine, Charles University and General Hospital in Prague, Czech Republic; Neuroimmunology and Multiple Sclerosis Research, Department of Neurology (S.S.), University Hospital Zürich and University of Zürich, Switzerland; Department of Neurology (K.W.S.), Medical University of Łódź, Poland; The University of British Columbia (A.T.), Vancouver, Canada; Sanofi (D.H.M., K.T., M.C.C., D.J., M.A.P.), Cambridge, MA; Envision Scientific Solutions (P.X.), Philadelphia, PA; Envision Scientific Solutions (R.J.H.), Sydney, NSW, Australia; NeuroRx Research (D.L.A.), Montréal; Department of Neurology and Neurosurgery (D.L.A.), Montréal Neurological Institute, McGill University, Québec, Canada. M.A.P. is currently affiliated with Wave Life Sciences, Cambridge, MA.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 (E.H.), First Faculty of Medicine, Charles University and General Hospital in Prague, Czech Republic; Neuroimmunology and Multiple Sclerosis Research, Department of Neurology (S.S.), University Hospital Zürich and University of Zürich, Switzerland; Department of Neurology (K.W.S.), Medical University of Łódź, Poland; The University of British Columbia (A.T.), Vancouver, Canada; Sanofi (D.H.M., K.T., M.C.C., D.J., M.A.P.), Cambridge, MA; Envision Scientific Solutions (P.X.), Philadelphia, PA; Envision Scientific Solutions (R.J.H.), Sydney, NSW, Australia; NeuroRx Research (D.L.A.), Montréal; Department of Neurology and Neurosurgery (D.L.A.), Montréal Neurological Institute, McGill University, Québec, Canada. M.A.P. is currently affiliated with Wave Life Sciences, Cambridge, MA.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 (E.H.), First Faculty of Medicine, Charles University and General Hospital in Prague, Czech Republic; Neuroimmunology and Multiple Sclerosis Research, Department of Neurology (S.S.), University Hospital Zürich and University of Zürich, Switzerland; Department of Neurology (K.W.S.), Medical University of Łódź, Poland; The University of British Columbia (A.T.), Vancouver, Canada; Sanofi (D.H.M., K.T., M.C.C., D.J., M.A.P.), Cambridge, MA; Envision Scientific Solutions (P.X.), Philadelphia, PA; Envision Scientific Solutions (R.J.H.), Sydney, NSW, Australia; NeuroRx Research (D.L.A.), Montréal; Department of Neurology and Neurosurgery (D.L.A.), Montréal Neurological Institute, McGill University, Québec, Canada. M.A.P. is currently affiliated with Wave Life Sciences, Cambridge, MA.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 (E.H.), First Faculty of Medicine, Charles University and General Hospital in Prague, Czech Republic; Neuroimmunology and Multiple Sclerosis Research, Department of Neurology (S.S.), University Hospital Zürich and University of Zürich, Switzerland; Department of Neurology (K.W.S.), Medical University of Łódź, Poland; The University of British Columbia (A.T.), Vancouver, Canada; Sanofi (D.H.M., K.T., M.C.C., D.J., M.A.P.), Cambridge, MA; Envision Scientific Solutions (P.X.), Philadelphia, PA; Envision Scientific Solutions (R.J.H.), Sydney, NSW, Australia; NeuroRx Research (D.L.A.), Montréal; Department of Neurology and Neurosurgery (D.L.A.), Montréal Neurological Institute, McGill University, Québec, Canada. M.A.P. is currently affiliated with Wave Life Sciences, Cambridge, MA.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 (E.H.), First Faculty of Medicine, Charles University and General Hospital in Prague, Czech Republic; Neuroimmunology and Multiple Sclerosis Research, Department of Neurology (S.S.), University Hospital Zürich and University of Zürich, Switzerland; Department of Neurology (K.W.S.), Medical University of Łódź, Poland; The University of British Columbia (A.T.), Vancouver, Canada; Sanofi (D.H.M., K.T., M.C.C., D.J., M.A.P.), Cambridge, MA; Envision Scientific Solutions (P.X.), Philadelphia, PA; Envision Scientific Solutions (R.J.H.), Sydney, NSW, Australia; NeuroRx Research (D.L.A.), Montréal; Department of Neurology and Neurosurgery (D.L.A.), Montréal Neurological Institute, McGill University, Québec, Canada. M.A.P. is currently affiliated with Wave Life Sciences, Cambridge, MA.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 (E.H.), First Faculty of Medicine, Charles University and General Hospital in Prague, Czech Republic; Neuroimmunology and Multiple Sclerosis Research, Department of Neurology (S.S.), University Hospital Zürich and University of Zürich, Switzerland; Department of Neurology (K.W.S.), Medical University of Łódź, Poland; The University of British Columbia (A.T.), Vancouver, Canada; Sanofi (D.H.M., K.T., M.C.C., D.J., M.A.P.), Cambridge, MA; Envision Scientific Solutions (P.X.), Philadelphia, PA; Envision Scientific Solutions (R.J.H.), Sydney, NSW, Australia; NeuroRx Research (D.L.A.), Montréal; Department of Neurology and Neurosurgery (D.L.A.), Montréal Neurological Institute, McGill University, Québec, Canada. M.A.P. is currently affiliated with Wave Life Sciences, Cambridge, MA.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 (E.H.), First Faculty of Medicine, Charles University and General Hospital in Prague, Czech Republic; Neuroimmunology and Multiple Sclerosis Research, Department of Neurology (S.S.), University Hospital Zürich and University of Zürich, Switzerland; Department of Neurology (K.W.S.), Medical University of Łódź, Poland; The University of British Columbia (A.T.), Vancouver, Canada; Sanofi (D.H.M., K.T., M.C.C., D.J., M.A.P.), Cambridge, MA; Envision Scientific Solutions (P.X.), Philadelphia, PA; Envision Scientific Solutions (R.J.H.), Sydney, NSW, Australia; NeuroRx Research (D.L.A.), Montréal; Department of Neurology and Neurosurgery (D.L.A.), Montréal Neurological Institute, McGill University, Québec, Canada. M.A.P. is currently affiliated with Wave Life Sciences, Cambridge, MA.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 (E.H.), First Faculty of Medicine, Charles University and General Hospital in Prague, Czech Republic; Neuroimmunology and Multiple Sclerosis Research, Department of Neurology (S.S.), University Hospital Zürich and University of Zürich, Switzerland; Department of Neurology (K.W.S.), Medical University of Łódź, Poland; The University of British Columbia (A.T.), Vancouver, Canada; Sanofi (D.H.M., K.T., M.C.C., D.J., M.A.P.), Cambridge, MA; Envision Scientific Solutions (P.X.), Philadelphia, PA; Envision Scientific Solutions (R.J.H.), Sydney, NSW, Australia; NeuroRx Research (D.L.A.), Montréal; Department of Neurology and Neurosurgery (D.L.A.), Montréal Neurological Institute, McGill University, Québec, Canada. M.A.P. is currently affiliated with Wave Life Sciences, Cambridge, MA.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 (E.H.), First Faculty of Medicine, Charles University and General Hospital in Prague, Czech Republic; Neuroimmunology and Multiple Sclerosis Research, Department of Neurology (S.S.), University Hospital Zürich and University of Zürich, Switzerland; Department of Neurology (K.W.S.), Medical University of Łódź, Poland; The University of British Columbia (A.T.), Vancouver, Canada; Sanofi (D.H.M., K.T., M.C.C., D.J., M.A.P.), Cambridge, MA; Envision Scientific Solutions (P.X.), Philadelphia, PA; Envision Scientific Solutions (R.J.H.), Sydney, NSW, Australia; NeuroRx Research (D.L.A.), Montréal; Department of Neurology and Neurosurgery (D.L.A.), Montréal Neurological Institute, McGill University, Québec, Canada. M.A.P. is currently affiliated with Wave Life Sciences, Cambridge, MA.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 (E.H.), First Faculty of Medicine, Charles University and General Hospital in Prague, Czech Republic; Neuroimmunology and Multiple Sclerosis Research, Department of Neurology (S.S.), University Hospital Zürich and University of Zürich, Switzerland; Department of Neurology (K.W.S.), Medical University of Łódź, Poland; The University of British Columbia (A.T.), Vancouver, Canada; Sanofi (D.H.M., K.T., M.C.C., D.J., M.A.P.), Cambridge, MA; Envision Scientific Solutions (P.X.), Philadelphia, PA; Envision Scientific Solutions (R.J.H.), Sydney, NSW, Australia; NeuroRx Research (D.L.A.), Montréal; Department of Neurology and Neurosurgery (D.L.A.), Montréal Neurological Institute, McGill University, Québec, Canada. M.A.P. is currently affiliated with Wave Life Sciences, Cambridge, MA.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 (E.H.), First Faculty of Medicine, Charles University and General Hospital in Prague, Czech Republic; Neuroimmunology and Multiple Sclerosis Research, Department of Neurology (S.S.), University Hospital Zürich and University of Zürich, Switzerland; Department of Neurology (K.W.S.), Medical University of Łódź, Poland; The University of British Columbia (A.T.), Vancouver, Canada; Sanofi (D.H.M., K.T., M.C.C., D.J., M.A.P.), Cambridge, MA; Envision Scientific Solutions (P.X.), Philadelphia, PA; Envision Scientific Solutions (R.J.H.), Sydney, NSW, Australia; NeuroRx Research (D.L.A.), Montréal; Department of Neurology and Neurosurgery (D.L.A.), Montréal Neurological Institute, McGill University, Québec, Canada. M.A.P. is currently affiliated with Wave Life Sciences, Cambridge, MA.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 (E.H.), First Faculty of Medicine, Charles University and General Hospital in Prague, Czech Republic; Neuroimmunology and Multiple Sclerosis Research, Department of Neurology (S.S.), University Hospital Zürich and University of Zürich, Switzerland; Department of Neurology (K.W.S.), Medical University of Łódź, Poland; The University of British Columbia (A.T.), Vancouver, Canada; Sanofi (D.H.M., K.T., M.C.C., D.J., M.A.P.), Cambridge, MA; Envision Scientific Solutions (P.X.), Philadelphia, PA; Envision Scientific Solutions (R.J.H.), Sydney, NSW, Australia; NeuroRx Research (D.L.A.), Montréal; Department of Neurology and Neurosurgery (D.L.A.), Montréal Neurological Institute, McGill University, Québec, Canada. M.A.P. is currently affiliated with Wave Life Sciences, Cambridge, MA.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 (E.H.), First Faculty of Medicine, Charles University and General Hospital in Prague, Czech Republic; Neuroimmunology and Multiple Sclerosis Research, Department of Neurology (S.S.), University Hospital Zürich and University of Zürich, Switzerland; Department of Neurology (K.W.S.), Medical University of Łódź, Poland; The University of British Columbia (A.T.), Vancouver, Canada; Sanofi (D.H.M., K.T., M.C.C., D.J., M.A.P.), Cambridge, MA; Envision Scientific Solutions (P.X.), Philadelphia, PA; Envision Scientific Solutions (R.J.H.), Sydney, NSW, Australia; NeuroRx Research (D.L.A.), Montréal; Department of Neurology and Neurosurgery (D.L.A.), Montréal Neurological Institute, McGill University, Québec, Canada. M.A.P. is currently affiliated with Wave Life Sciences, Cambridge, MA.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 (E.H.), First Faculty of Medicine, Charles University and General Hospital in Prague, Czech Republic; Neuroimmunology and Multiple Sclerosis Research, Department of Neurology (S.S.), University Hospital Zürich and University of Zürich, Switzerland; Department of Neurology (K.W.S.), Medical University of Łódź, Poland; The University of British Columbia (A.T.), Vancouver, Canada; Sanofi (D.H.M., K.T., M.C.C., D.J., M.A.P.), Cambridge, MA; Envision Scientific Solutions (P.X.), Philadelphia, PA; Envision Scientific Solutions (R.J.H.), Sydney, NSW, Australia; NeuroRx Research (D.L.A.), Montréal; Department of Neurology and Neurosurgery (D.L.A.), Montréal Neurological Institute, McGill University, Québec, Canada. M.A.P. is currently affiliated with Wave Life Sciences, Cambridge, MA.No affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28835403

Citation

Coles, Alasdair J., et al. "Alemtuzumab CARE-MS II 5-year Follow-up: Efficacy and Safety Findings." Neurology, vol. 89, no. 11, 2017, pp. 1117-1126.
Coles AJ, Cohen JA, Fox EJ, et al. Alemtuzumab CARE-MS II 5-year follow-up: Efficacy and safety findings. Neurology. 2017;89(11):1117-1126.
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. (2017). Alemtuzumab CARE-MS II 5-year follow-up: Efficacy and safety findings. Neurology, 89(11), 1117-1126. https://doi.org/10.1212/WNL.0000000000004354
Coles AJ, et al. Alemtuzumab CARE-MS II 5-year Follow-up: Efficacy and Safety Findings. Neurology. 2017 Sep 12;89(11):1117-1126. PubMed PMID: 28835403.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Alemtuzumab CARE-MS II 5-year follow-up: Efficacy and safety findings. AU - Coles,Alasdair J, AU - Cohen,Jeffrey A, AU - Fox,Edward J, AU - Giovannoni,Gavin, AU - Hartung,Hans-Peter, AU - Havrdova,Eva, AU - Schippling,Sven, AU - Selmaj,Krzysztof W, AU - Traboulsee,Anthony, AU - Compston,D Alastair S, AU - Margolin,David H, AU - Thangavelu,Karthinathan, AU - Chirieac,Madalina C, AU - Jody,Darlene, AU - Xenopoulos,Panos, AU - Hogan,Richard J, AU - Panzara,Michael A, AU - Arnold,Douglas L, AU - ,, Y1 - 2017/08/23/ PY - 2016/08/09/received PY - 2017/06/22/accepted PY - 2017/8/25/pubmed PY - 2017/9/16/medline PY - 2017/8/25/entrez SP - 1117 EP - 1126 JF - Neurology JO - Neurology VL - 89 IS - 11 N2 - 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. SN - 1526-632X UR - https://www.unboundmedicine.com/medline/citation/28835403/Alemtuzumab_CARE_MS_II_5_year_follow_up:_Efficacy_and_safety_findings_ L2 - http://www.neurology.org/cgi/pmidlookup?view=long&pmid=28835403 DB - PRIME DP - Unbound Medicine ER -