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Alemtuzumab CARE-MS I 5-year follow-up: Durable efficacy in the absence of continuous MS therapy.
Neurology. 2017 Sep 12; 89(11):1107-1116.Neur

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.

Authors+Show 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, Düsseldorf, Germany; 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; Neuroimmunology and Multiple Sclerosis Research (S.S.), Department of Neurology, 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; Department of Clinical Neurosciences (D.A.S.C., A.J.C.), University of Cambridge, UK; Sanofi (D.H.M., K.T., C.E.R., D.J., M.A.P.), Cambridge, MA; Evidence Scientific Solutions (R.J.H.), Sydney, NSW, Australia; and Evidence Scientific Solutions (P.X.), Philadelphia, PA. M.A.P. is currently affiliated with Wave Life Sciences, Cambridge, MA. eva.havrdova@lf1.cuni.cz.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, Düsseldorf, Germany; 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; Neuroimmunology and Multiple Sclerosis Research (S.S.), Department of Neurology, 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; Department of Clinical Neurosciences (D.A.S.C., A.J.C.), University of Cambridge, UK; Sanofi (D.H.M., K.T., C.E.R., D.J., M.A.P.), Cambridge, MA; Evidence Scientific Solutions (R.J.H.), Sydney, NSW, Australia; and Evidence Scientific Solutions (P.X.), Philadelphia, PA. M.A.P. is currently affiliated with Wave Life Sciences, Cambridge, MA.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, Düsseldorf, Germany; 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; Neuroimmunology and Multiple Sclerosis Research (S.S.), Department of Neurology, 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; Department of Clinical Neurosciences (D.A.S.C., A.J.C.), University of Cambridge, UK; Sanofi (D.H.M., K.T., C.E.R., D.J., M.A.P.), Cambridge, MA; Evidence Scientific Solutions (R.J.H.), Sydney, NSW, Australia; and Evidence Scientific Solutions (P.X.), Philadelphia, PA. M.A.P. is currently affiliated with Wave Life Sciences, Cambridge, MA.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, Düsseldorf, Germany; 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; Neuroimmunology and Multiple Sclerosis Research (S.S.), Department of Neurology, 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; Department of Clinical Neurosciences (D.A.S.C., A.J.C.), University of Cambridge, UK; Sanofi (D.H.M., K.T., C.E.R., D.J., M.A.P.), Cambridge, MA; Evidence Scientific Solutions (R.J.H.), Sydney, NSW, Australia; and Evidence Scientific Solutions (P.X.), Philadelphia, PA. M.A.P. is currently affiliated with Wave Life Sciences, Cambridge, MA.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, Düsseldorf, Germany; 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; Neuroimmunology and Multiple Sclerosis Research (S.S.), Department of Neurology, 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; Department of Clinical Neurosciences (D.A.S.C., A.J.C.), University of Cambridge, UK; Sanofi (D.H.M., K.T., C.E.R., D.J., M.A.P.), Cambridge, MA; Evidence Scientific Solutions (R.J.H.), Sydney, NSW, Australia; and Evidence Scientific Solutions (P.X.), Philadelphia, PA. M.A.P. is currently affiliated with Wave Life Sciences, Cambridge, MA.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, Düsseldorf, Germany; 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; Neuroimmunology and Multiple Sclerosis Research (S.S.), Department of Neurology, 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; Department of Clinical Neurosciences (D.A.S.C., A.J.C.), University of Cambridge, UK; Sanofi (D.H.M., K.T., C.E.R., D.J., M.A.P.), Cambridge, MA; Evidence Scientific Solutions (R.J.H.), Sydney, NSW, Australia; and Evidence Scientific Solutions (P.X.), Philadelphia, PA. M.A.P. is currently affiliated with Wave Life Sciences, Cambridge, MA.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, Düsseldorf, Germany; 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; Neuroimmunology and Multiple Sclerosis Research (S.S.), Department of Neurology, 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; Department of Clinical Neurosciences (D.A.S.C., A.J.C.), University of Cambridge, UK; Sanofi (D.H.M., K.T., C.E.R., D.J., M.A.P.), Cambridge, MA; Evidence Scientific Solutions (R.J.H.), Sydney, NSW, Australia; and Evidence Scientific Solutions (P.X.), Philadelphia, PA. M.A.P. is currently affiliated with Wave Life Sciences, Cambridge, MA.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, Düsseldorf, Germany; 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; Neuroimmunology and Multiple Sclerosis Research (S.S.), Department of Neurology, 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; Department of Clinical Neurosciences (D.A.S.C., A.J.C.), University of Cambridge, UK; Sanofi (D.H.M., K.T., C.E.R., D.J., M.A.P.), Cambridge, MA; Evidence Scientific Solutions (R.J.H.), Sydney, NSW, Australia; and Evidence Scientific Solutions (P.X.), Philadelphia, PA. M.A.P. is currently affiliated with Wave Life Sciences, Cambridge, MA.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, Düsseldorf, Germany; 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; Neuroimmunology and Multiple Sclerosis Research (S.S.), Department of Neurology, 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; Department of Clinical Neurosciences (D.A.S.C., A.J.C.), University of Cambridge, UK; Sanofi (D.H.M., K.T., C.E.R., D.J., M.A.P.), Cambridge, MA; Evidence Scientific Solutions (R.J.H.), Sydney, NSW, Australia; and Evidence Scientific Solutions (P.X.), Philadelphia, PA. M.A.P. is currently affiliated with Wave Life Sciences, Cambridge, MA.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, Düsseldorf, Germany; 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; Neuroimmunology and Multiple Sclerosis Research (S.S.), Department of Neurology, 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; Department of Clinical Neurosciences (D.A.S.C., A.J.C.), University of Cambridge, UK; Sanofi (D.H.M., K.T., C.E.R., D.J., M.A.P.), Cambridge, MA; Evidence Scientific Solutions (R.J.H.), Sydney, NSW, Australia; and Evidence Scientific Solutions (P.X.), Philadelphia, PA. M.A.P. is currently affiliated with Wave Life Sciences, Cambridge, MA.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, Düsseldorf, Germany; 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; Neuroimmunology and Multiple Sclerosis Research (S.S.), Department of Neurology, 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; Department of Clinical Neurosciences (D.A.S.C., A.J.C.), University of Cambridge, UK; Sanofi (D.H.M., K.T., C.E.R., D.J., M.A.P.), Cambridge, MA; Evidence Scientific Solutions (R.J.H.), Sydney, NSW, Australia; and Evidence Scientific Solutions (P.X.), Philadelphia, PA. M.A.P. is currently affiliated with Wave Life Sciences, Cambridge, MA.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, Düsseldorf, Germany; 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; Neuroimmunology and Multiple Sclerosis Research (S.S.), Department of Neurology, 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; Department of Clinical Neurosciences (D.A.S.C., A.J.C.), University of Cambridge, UK; Sanofi (D.H.M., K.T., C.E.R., D.J., M.A.P.), Cambridge, MA; Evidence Scientific Solutions (R.J.H.), Sydney, NSW, Australia; and Evidence Scientific Solutions (P.X.), Philadelphia, PA. M.A.P. is currently affiliated with Wave Life Sciences, Cambridge, MA.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, Düsseldorf, Germany; 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; Neuroimmunology and Multiple Sclerosis Research (S.S.), Department of Neurology, 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; Department of Clinical Neurosciences (D.A.S.C., A.J.C.), University of Cambridge, UK; Sanofi (D.H.M., K.T., C.E.R., D.J., M.A.P.), Cambridge, MA; Evidence Scientific Solutions (R.J.H.), Sydney, NSW, Australia; and Evidence Scientific Solutions (P.X.), Philadelphia, PA. M.A.P. is currently affiliated with Wave Life Sciences, Cambridge, MA.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, Düsseldorf, Germany; 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; Neuroimmunology and Multiple Sclerosis Research (S.S.), Department of Neurology, 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; Department of Clinical Neurosciences (D.A.S.C., A.J.C.), University of Cambridge, UK; Sanofi (D.H.M., K.T., C.E.R., D.J., M.A.P.), Cambridge, MA; Evidence Scientific Solutions (R.J.H.), Sydney, NSW, Australia; and Evidence Scientific Solutions (P.X.), Philadelphia, PA. M.A.P. is currently affiliated with Wave Life Sciences, Cambridge, MA.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, Düsseldorf, Germany; 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; Neuroimmunology and Multiple Sclerosis Research (S.S.), Department of Neurology, 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; Department of Clinical Neurosciences (D.A.S.C., A.J.C.), University of Cambridge, UK; Sanofi (D.H.M., K.T., C.E.R., D.J., M.A.P.), Cambridge, MA; Evidence Scientific Solutions (R.J.H.), Sydney, NSW, Australia; and Evidence Scientific Solutions (P.X.), Philadelphia, PA. M.A.P. is currently affiliated with Wave Life Sciences, Cambridge, MA.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, Düsseldorf, Germany; 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; Neuroimmunology and Multiple Sclerosis Research (S.S.), Department of Neurology, 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; Department of Clinical Neurosciences (D.A.S.C., A.J.C.), University of Cambridge, UK; Sanofi (D.H.M., K.T., C.E.R., D.J., M.A.P.), Cambridge, MA; Evidence Scientific Solutions (R.J.H.), Sydney, NSW, Australia; and Evidence Scientific Solutions (P.X.), Philadelphia, PA. M.A.P. is currently affiliated with Wave Life Sciences, Cambridge, MA.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, Düsseldorf, Germany; 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; Neuroimmunology and Multiple Sclerosis Research (S.S.), Department of Neurology, 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; Department of Clinical Neurosciences (D.A.S.C., A.J.C.), University of Cambridge, UK; Sanofi (D.H.M., K.T., C.E.R., D.J., M.A.P.), Cambridge, MA; Evidence Scientific Solutions (R.J.H.), Sydney, NSW, Australia; and Evidence Scientific Solutions (P.X.), Philadelphia, PA. M.A.P. is currently affiliated with Wave Life Sciences, Cambridge, MA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Randomized Controlled Trial

Language

eng

PubMed ID

28835401

Citation

Havrdova, Eva, et al. "Alemtuzumab CARE-MS I 5-year Follow-up: Durable Efficacy in the Absence of Continuous MS Therapy." Neurology, vol. 89, no. 11, 2017, pp. 1107-1116.
Havrdova E, Arnold DL, Cohen JA, et al. Alemtuzumab CARE-MS I 5-year follow-up: Durable efficacy in the absence of continuous MS therapy. Neurology. 2017;89(11):1107-1116.
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. (2017). Alemtuzumab CARE-MS I 5-year follow-up: Durable efficacy in the absence of continuous MS therapy. Neurology, 89(11), 1107-1116. https://doi.org/10.1212/WNL.0000000000004313
Havrdova E, et al. Alemtuzumab CARE-MS I 5-year Follow-up: Durable Efficacy in the Absence of Continuous MS Therapy. Neurology. 2017 Sep 12;89(11):1107-1116. PubMed PMID: 28835401.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Alemtuzumab CARE-MS I 5-year follow-up: Durable efficacy in the absence of continuous MS therapy. AU - Havrdova,Eva, AU - Arnold,Douglas L, AU - Cohen,Jeffrey A, AU - Hartung,Hans-Peter, AU - Fox,Edward J, AU - Giovannoni,Gavin, AU - Schippling,Sven, AU - Selmaj,Krzysztof W, AU - Traboulsee,Anthony, AU - Compston,D Alastair S, AU - Margolin,David H, AU - Thangavelu,Karthinathan, AU - Rodriguez,Claudio E, AU - Jody,Darlene, AU - Hogan,Richard J, AU - Xenopoulos,Panos, AU - Panzara,Michael A, AU - Coles,Alasdair J, AU - ,, Y1 - 2017/08/23/ PY - 2016/08/09/received PY - 2017/02/23/accepted PY - 2017/8/25/pubmed PY - 2017/9/16/medline PY - 2017/8/25/entrez SP - 1107 EP - 1116 JF - Neurology JO - Neurology VL - 89 IS - 11 N2 - 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. SN - 1526-632X UR - https://www.unboundmedicine.com/medline/citation/28835401/Alemtuzumab_CARE_MS_I_5_year_follow_up:_Durable_efficacy_in_the_absence_of_continuous_MS_therapy_ L2 - http://www.neurology.org/cgi/pmidlookup?view=long&pmid=28835401 DB - PRIME DP - Unbound Medicine ER -