title: Superior MRI outcomes with alemtuzumab compared with subcutaneous interferon β-1a in MS.
abstract: OBJECTIVE
  To describe detailed MRI results from 2 head-to-head phase III trials, Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis Study I (CARE-MS I; NCT00530348) and Study II (CARE-MS II; NCT00548405), of alemtuzumab vs subcutaneous interferon β-1a (SC IFN-β-1a) in patients with active relapsing-remitting multiple sclerosis (RRMS).
  
  
  METHODS
  The impact of alemtuzumab 12 mg vs SC IFN-β-1a 44 μg on MRI measures was evaluated in patients with RRMS who were treatment-naive (CARE-MS I) or who had an inadequate response, defined as at least one relapse, to prior therapy (CARE-MS II).
  
  
  RESULTS
  Both treatments prevented T2-hyperintense lesion volume increases from baseline. Alemtuzumab was more effective than SC IFN-β-1a on most lesion-based endpoints in both studies (p < 0.05), including decreased risk of new/enlarging T2 lesions over 2 years and gadolinium-enhancing lesions at year 2. Reduced risk of new T1 lesions (p < 0.0001) and gadolinium-enhancing lesion conversion to T1-hypointense black holes (p = 0.0078) were observed with alemtuzumab vs SC IFN-β-1a in CARE-MS II. Alemtuzumab slowed brain volume loss over 2 years in CARE-MS I (p < 0.0001) and II (p = 0.012) vs SC IFN-β-1a.
  
  
  CONCLUSIONS
  Alemtuzumab demonstrated greater efficacy than SC IFN-β-1a on MRI endpoints in active RRMS. The superiority of alemtuzumab was more prominent during the second year of both studies. These findings complement the superior clinical efficacy of alemtuzumab over SC IFN-β-1a in RRMS.
  
  
  BACKGROUND
  NCT00530348 and NCT00548405.
  
  
  METHODS
  The results reported here provide Class I evidence that, for patients with active RRMS, alemtuzumab is superior to SC IFN-β-1a on multiple MRI endpoints.
authors: From NeuroRx Research (D.L.A.) and Department of Neurology and Neurosurgery (D.L.A.), Montréal Neurological Institute, McGill University, Québec, Canada; Department of Biomedical Engineering (E.F.) and Mellen Center (J.A.C.), Cleveland Clinic, OH; Zagreb Medical School and University Hospital Center (V.V.B.), Croatia; Department of Clinical Neurosciences (A.J.C., D.A.S.C.), University of Cambridge, UK; 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.), Heinrich-Heine University, Düsseldorf, Germany; Department of Neurology (E.H.), First Medical Faculty, Charles University in Prague, Czech Republic; Department of Neurology (K.W.S.), Medical University of Łódź, Poland; Clinical Centre Kragujevac (M.S.), Clinic of Neurology, Serbia; Brigham and Women's Hospital Center for Neurologic Diseases (H.L.W.), Boston, MA; Sanofi Genzyme (S.L.L., D.H.M., M.A.P.), Cambridge, MA; and Evidence Scientific Solutions (D.R.T.), Horsham, West Sussex, UK. Dr. Panzara is currently with Wave Life Sciences, Cambridge, MA. douglas.arnold@mcgill.ca.
authors: Douglas L
authors: DL
authors: Arnold
authors: From NeuroRx Research (D.L.A.) and Department of Neurology and Neurosurgery (D.L.A.), Montréal Neurological Institute, McGill University, Québec, Canada; Department of Biomedical Engineering (E.F.) and Mellen Center (J.A.C.), Cleveland Clinic, OH; Zagreb Medical School and University Hospital Center (V.V.B.), Croatia; Department of Clinical Neurosciences (A.J.C., D.A.S.C.), University of Cambridge, UK; 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.), Heinrich-Heine University, Düsseldorf, Germany; Department of Neurology (E.H.), First Medical Faculty, Charles University in Prague, Czech Republic; Department of Neurology (K.W.S.), Medical University of Łódź, Poland; Clinical Centre Kragujevac (M.S.), Clinic of Neurology, Serbia; Brigham and Women's Hospital Center for Neurologic Diseases (H.L.W.), Boston, MA; Sanofi Genzyme (S.L.L., D.H.M., M.A.P.), Cambridge, MA; and Evidence Scientific Solutions (D.R.T.), Horsham, West Sussex, UK. Dr. Panzara is currently with Wave Life Sciences, Cambridge, MA.
authors: Elizabeth
authors: E
authors: Fisher
authors: From NeuroRx Research (D.L.A.) and Department of Neurology and Neurosurgery (D.L.A.), Montréal Neurological Institute, McGill University, Québec, Canada; Department of Biomedical Engineering (E.F.) and Mellen Center (J.A.C.), Cleveland Clinic, OH; Zagreb Medical School and University Hospital Center (V.V.B.), Croatia; Department of Clinical Neurosciences (A.J.C., D.A.S.C.), University of Cambridge, UK; 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.), Heinrich-Heine University, Düsseldorf, Germany; Department of Neurology (E.H.), First Medical Faculty, Charles University in Prague, Czech Republic; Department of Neurology (K.W.S.), Medical University of Łódź, Poland; Clinical Centre Kragujevac (M.S.), Clinic of Neurology, Serbia; Brigham and Women's Hospital Center for Neurologic Diseases (H.L.W.), Boston, MA; Sanofi Genzyme (S.L.L., D.H.M., M.A.P.), Cambridge, MA; and Evidence Scientific Solutions (D.R.T.), Horsham, West Sussex, UK. Dr. Panzara is currently with Wave Life Sciences, Cambridge, MA.
authors: Vesna V
authors: VV
authors: Brinar
authors: From NeuroRx Research (D.L.A.) and Department of Neurology and Neurosurgery (D.L.A.), Montréal Neurological Institute, McGill University, Québec, Canada; Department of Biomedical Engineering (E.F.) and Mellen Center (J.A.C.), Cleveland Clinic, OH; Zagreb Medical School and University Hospital Center (V.V.B.), Croatia; Department of Clinical Neurosciences (A.J.C., D.A.S.C.), University of Cambridge, UK; 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.), Heinrich-Heine University, Düsseldorf, Germany; Department of Neurology (E.H.), First Medical Faculty, Charles University in Prague, Czech Republic; Department of Neurology (K.W.S.), Medical University of Łódź, Poland; Clinical Centre Kragujevac (M.S.), Clinic of Neurology, Serbia; Brigham and Women's Hospital Center for Neurologic Diseases (H.L.W.), Boston, MA; Sanofi Genzyme (S.L.L., D.H.M., M.A.P.), Cambridge, MA; and Evidence Scientific Solutions (D.R.T.), Horsham, West Sussex, UK. Dr. Panzara is currently with Wave Life Sciences, Cambridge, MA.
authors: Jeffrey A
authors: JA
authors: Cohen
authors: From NeuroRx Research (D.L.A.) and Department of Neurology and Neurosurgery (D.L.A.), Montréal Neurological Institute, McGill University, Québec, Canada; Department of Biomedical Engineering (E.F.) and Mellen Center (J.A.C.), Cleveland Clinic, OH; Zagreb Medical School and University Hospital Center (V.V.B.), Croatia; Department of Clinical Neurosciences (A.J.C., D.A.S.C.), University of Cambridge, UK; 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.), Heinrich-Heine University, Düsseldorf, Germany; Department of Neurology (E.H.), First Medical Faculty, Charles University in Prague, Czech Republic; Department of Neurology (K.W.S.), Medical University of Łódź, Poland; Clinical Centre Kragujevac (M.S.), Clinic of Neurology, Serbia; Brigham and Women's Hospital Center for Neurologic Diseases (H.L.W.), Boston, MA; Sanofi Genzyme (S.L.L., D.H.M., M.A.P.), Cambridge, MA; and Evidence Scientific Solutions (D.R.T.), Horsham, West Sussex, UK. Dr. Panzara is currently with Wave Life Sciences, Cambridge, MA.
authors: Alasdair J
authors: AJ
authors: Coles
authors: From NeuroRx Research (D.L.A.) and Department of Neurology and Neurosurgery (D.L.A.), Montréal Neurological Institute, McGill University, Québec, Canada; Department of Biomedical Engineering (E.F.) and Mellen Center (J.A.C.), Cleveland Clinic, OH; Zagreb Medical School and University Hospital Center (V.V.B.), Croatia; Department of Clinical Neurosciences (A.J.C., D.A.S.C.), University of Cambridge, UK; 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.), Heinrich-Heine University, Düsseldorf, Germany; Department of Neurology (E.H.), First Medical Faculty, Charles University in Prague, Czech Republic; Department of Neurology (K.W.S.), Medical University of Łódź, Poland; Clinical Centre Kragujevac (M.S.), Clinic of Neurology, Serbia; Brigham and Women's Hospital Center for Neurologic Diseases (H.L.W.), Boston, MA; Sanofi Genzyme (S.L.L., D.H.M., M.A.P.), Cambridge, MA; and Evidence Scientific Solutions (D.R.T.), Horsham, West Sussex, UK. Dr. Panzara is currently with Wave Life Sciences, Cambridge, MA.
authors: Gavin
authors: G
authors: Giovannoni
authors: From NeuroRx Research (D.L.A.) and Department of Neurology and Neurosurgery (D.L.A.), Montréal Neurological Institute, McGill University, Québec, Canada; Department of Biomedical Engineering (E.F.) and Mellen Center (J.A.C.), Cleveland Clinic, OH; Zagreb Medical School and University Hospital Center (V.V.B.), Croatia; Department of Clinical Neurosciences (A.J.C., D.A.S.C.), University of Cambridge, UK; 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.), Heinrich-Heine University, Düsseldorf, Germany; Department of Neurology (E.H.), First Medical Faculty, Charles University in Prague, Czech Republic; Department of Neurology (K.W.S.), Medical University of Łódź, Poland; Clinical Centre Kragujevac (M.S.), Clinic of Neurology, Serbia; Brigham and Women's Hospital Center for Neurologic Diseases (H.L.W.), Boston, MA; Sanofi Genzyme (S.L.L., D.H.M., M.A.P.), Cambridge, MA; and Evidence Scientific Solutions (D.R.T.), Horsham, West Sussex, UK. Dr. Panzara is currently with Wave Life Sciences, Cambridge, MA.
authors: Hans-Peter
authors: HP
authors: Hartung
authors: From NeuroRx Research (D.L.A.) and Department of Neurology and Neurosurgery (D.L.A.), Montréal Neurological Institute, McGill University, Québec, Canada; Department of Biomedical Engineering (E.F.) and Mellen Center (J.A.C.), Cleveland Clinic, OH; Zagreb Medical School and University Hospital Center (V.V.B.), Croatia; Department of Clinical Neurosciences (A.J.C., D.A.S.C.), University of Cambridge, UK; 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.), Heinrich-Heine University, Düsseldorf, Germany; Department of Neurology (E.H.), First Medical Faculty, Charles University in Prague, Czech Republic; Department of Neurology (K.W.S.), Medical University of Łódź, Poland; Clinical Centre Kragujevac (M.S.), Clinic of Neurology, Serbia; Brigham and Women's Hospital Center for Neurologic Diseases (H.L.W.), Boston, MA; Sanofi Genzyme (S.L.L., D.H.M., M.A.P.), Cambridge, MA; and Evidence Scientific Solutions (D.R.T.), Horsham, West Sussex, UK. Dr. Panzara is currently with Wave Life Sciences, Cambridge, MA.
authors: Eva
authors: E
authors: Havrdova
authors: From NeuroRx Research (D.L.A.) and Department of Neurology and Neurosurgery (D.L.A.), Montréal Neurological Institute, McGill University, Québec, Canada; Department of Biomedical Engineering (E.F.) and Mellen Center (J.A.C.), Cleveland Clinic, OH; Zagreb Medical School and University Hospital Center (V.V.B.), Croatia; Department of Clinical Neurosciences (A.J.C., D.A.S.C.), University of Cambridge, UK; 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.), Heinrich-Heine University, Düsseldorf, Germany; Department of Neurology (E.H.), First Medical Faculty, Charles University in Prague, Czech Republic; Department of Neurology (K.W.S.), Medical University of Łódź, Poland; Clinical Centre Kragujevac (M.S.), Clinic of Neurology, Serbia; Brigham and Women's Hospital Center for Neurologic Diseases (H.L.W.), Boston, MA; Sanofi Genzyme (S.L.L., D.H.M., M.A.P.), Cambridge, MA; and Evidence Scientific Solutions (D.R.T.), Horsham, West Sussex, UK. Dr. Panzara is currently with Wave Life Sciences, Cambridge, MA.
authors: Krzysztof W
authors: KW
authors: Selmaj
authors: From NeuroRx Research (D.L.A.) and Department of Neurology and Neurosurgery (D.L.A.), Montréal Neurological Institute, McGill University, Québec, Canada; Department of Biomedical Engineering (E.F.) and Mellen Center (J.A.C.), Cleveland Clinic, OH; Zagreb Medical School and University Hospital Center (V.V.B.), Croatia; Department of Clinical Neurosciences (A.J.C., D.A.S.C.), University of Cambridge, UK; 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.), Heinrich-Heine University, Düsseldorf, Germany; Department of Neurology (E.H.), First Medical Faculty, Charles University in Prague, Czech Republic; Department of Neurology (K.W.S.), Medical University of Łódź, Poland; Clinical Centre Kragujevac (M.S.), Clinic of Neurology, Serbia; Brigham and Women's Hospital Center for Neurologic Diseases (H.L.W.), Boston, MA; Sanofi Genzyme (S.L.L., D.H.M., M.A.P.), Cambridge, MA; and Evidence Scientific Solutions (D.R.T.), Horsham, West Sussex, UK. Dr. Panzara is currently with Wave Life Sciences, Cambridge, MA.
authors: Miroslav
authors: M
authors: Stojanovic
authors: From NeuroRx Research (D.L.A.) and Department of Neurology and Neurosurgery (D.L.A.), Montréal Neurological Institute, McGill University, Québec, Canada; Department of Biomedical Engineering (E.F.) and Mellen Center (J.A.C.), Cleveland Clinic, OH; Zagreb Medical School and University Hospital Center (V.V.B.), Croatia; Department of Clinical Neurosciences (A.J.C., D.A.S.C.), University of Cambridge, UK; 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.), Heinrich-Heine University, Düsseldorf, Germany; Department of Neurology (E.H.), First Medical Faculty, Charles University in Prague, Czech Republic; Department of Neurology (K.W.S.), Medical University of Łódź, Poland; Clinical Centre Kragujevac (M.S.), Clinic of Neurology, Serbia; Brigham and Women's Hospital Center for Neurologic Diseases (H.L.W.), Boston, MA; Sanofi Genzyme (S.L.L., D.H.M., M.A.P.), Cambridge, MA; and Evidence Scientific Solutions (D.R.T.), Horsham, West Sussex, UK. Dr. Panzara is currently with Wave Life Sciences, Cambridge, MA.
authors: Howard L
authors: HL
authors: Weiner
authors: From NeuroRx Research (D.L.A.) and Department of Neurology and Neurosurgery (D.L.A.), Montréal Neurological Institute, McGill University, Québec, Canada; Department of Biomedical Engineering (E.F.) and Mellen Center (J.A.C.), Cleveland Clinic, OH; Zagreb Medical School and University Hospital Center (V.V.B.), Croatia; Department of Clinical Neurosciences (A.J.C., D.A.S.C.), University of Cambridge, UK; 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.), Heinrich-Heine University, Düsseldorf, Germany; Department of Neurology (E.H.), First Medical Faculty, Charles University in Prague, Czech Republic; Department of Neurology (K.W.S.), Medical University of Łódź, Poland; Clinical Centre Kragujevac (M.S.), Clinic of Neurology, Serbia; Brigham and Women's Hospital Center for Neurologic Diseases (H.L.W.), Boston, MA; Sanofi Genzyme (S.L.L., D.H.M., M.A.P.), Cambridge, MA; and Evidence Scientific Solutions (D.R.T.), Horsham, West Sussex, UK. Dr. Panzara is currently with Wave Life Sciences, Cambridge, MA.
authors: Stephen L
authors: SL
authors: Lake
authors: From NeuroRx Research (D.L.A.) and Department of Neurology and Neurosurgery (D.L.A.), Montréal Neurological Institute, McGill University, Québec, Canada; Department of Biomedical Engineering (E.F.) and Mellen Center (J.A.C.), Cleveland Clinic, OH; Zagreb Medical School and University Hospital Center (V.V.B.), Croatia; Department of Clinical Neurosciences (A.J.C., D.A.S.C.), University of Cambridge, UK; 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.), Heinrich-Heine University, Düsseldorf, Germany; Department of Neurology (E.H.), First Medical Faculty, Charles University in Prague, Czech Republic; Department of Neurology (K.W.S.), Medical University of Łódź, Poland; Clinical Centre Kragujevac (M.S.), Clinic of Neurology, Serbia; Brigham and Women's Hospital Center for Neurologic Diseases (H.L.W.), Boston, MA; Sanofi Genzyme (S.L.L., D.H.M., M.A.P.), Cambridge, MA; and Evidence Scientific Solutions (D.R.T.), Horsham, West Sussex, UK. Dr. Panzara is currently with Wave Life Sciences, Cambridge, MA.
authors: David H
authors: DH
authors: Margolin
authors: From NeuroRx Research (D.L.A.) and Department of Neurology and Neurosurgery (D.L.A.), Montréal Neurological Institute, McGill University, Québec, Canada; Department of Biomedical Engineering (E.F.) and Mellen Center (J.A.C.), Cleveland Clinic, OH; Zagreb Medical School and University Hospital Center (V.V.B.), Croatia; Department of Clinical Neurosciences (A.J.C., D.A.S.C.), University of Cambridge, UK; 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.), Heinrich-Heine University, Düsseldorf, Germany; Department of Neurology (E.H.), First Medical Faculty, Charles University in Prague, Czech Republic; Department of Neurology (K.W.S.), Medical University of Łódź, Poland; Clinical Centre Kragujevac (M.S.), Clinic of Neurology, Serbia; Brigham and Women's Hospital Center for Neurologic Diseases (H.L.W.), Boston, MA; Sanofi Genzyme (S.L.L., D.H.M., M.A.P.), Cambridge, MA; and Evidence Scientific Solutions (D.R.T.), Horsham, West Sussex, UK. Dr. Panzara is currently with Wave Life Sciences, Cambridge, MA.
authors: David R
authors: DR
authors: Thomas
authors: From NeuroRx Research (D.L.A.) and Department of Neurology and Neurosurgery (D.L.A.), Montréal Neurological Institute, McGill University, Québec, Canada; Department of Biomedical Engineering (E.F.) and Mellen Center (J.A.C.), Cleveland Clinic, OH; Zagreb Medical School and University Hospital Center (V.V.B.), Croatia; Department of Clinical Neurosciences (A.J.C., D.A.S.C.), University of Cambridge, UK; 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.), Heinrich-Heine University, Düsseldorf, Germany; Department of Neurology (E.H.), First Medical Faculty, Charles University in Prague, Czech Republic; Department of Neurology (K.W.S.), Medical University of Łódź, Poland; Clinical Centre Kragujevac (M.S.), Clinic of Neurology, Serbia; Brigham and Women's Hospital Center for Neurologic Diseases (H.L.W.), Boston, MA; Sanofi Genzyme (S.L.L., D.H.M., M.A.P.), Cambridge, MA; and Evidence Scientific Solutions (D.R.T.), Horsham, West Sussex, UK. Dr. Panzara is currently with Wave Life Sciences, Cambridge, MA.
authors: Michael A
authors: MA
authors: Panzara
authors: From NeuroRx Research (D.L.A.) and Department of Neurology and Neurosurgery (D.L.A.), Montréal Neurological Institute, McGill University, Québec, Canada; Department of Biomedical Engineering (E.F.) and Mellen Center (J.A.C.), Cleveland Clinic, OH; Zagreb Medical School and University Hospital Center (V.V.B.), Croatia; Department of Clinical Neurosciences (A.J.C., D.A.S.C.), University of Cambridge, UK; 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.), Heinrich-Heine University, Düsseldorf, Germany; Department of Neurology (E.H.), First Medical Faculty, Charles University in Prague, Czech Republic; Department of Neurology (K.W.S.), Medical University of Łódź, Poland; Clinical Centre Kragujevac (M.S.), Clinic of Neurology, Serbia; Brigham and Women's Hospital Center for Neurologic Diseases (H.L.W.), Boston, MA; Sanofi Genzyme (S.L.L., D.H.M., M.A.P.), Cambridge, MA; and Evidence Scientific Solutions (D.R.T.), Horsham, West Sussex, UK. Dr. Panzara is currently with Wave Life Sciences, Cambridge, MA.
authors: D Alastair S
authors: DA
authors: Compston
mesh_terms: D000328:Adult; D000074323:Alemtuzumab; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects; D003287:Contrast Media; D005260:Female; D005682:Gadolinium; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D007279:Injections, Subcutaneous; D000068556:Interferon beta-1a / Q000008:administration & dosage*; D008279:Magnetic Resonance Imaging; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000000981:diagnostic imaging* / Q000188:drug therapy*; D009929:Organ Size; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D003287:Contrast Media; D007155:Immunologic Factors; D000074323:Alemtuzumab; D005682:Gadolinium; D000068556:Interferon beta-1a