Alemtuzumab improves preexisting disability in active relapsing-remitting MS patients.

Autor:	Giovannoni G; From Queen Mary University of London (G.G.), Barts and The London School of Medicine, UK; Mellen Center (J.A.C.), Cleveland Clinic, OH; Department of Clinical Neurosciences (A.J.C., D.A.S.C.), University of Cambridge, UK; Department of Neurology and Center for Neuropsychiatry (H.-P.H.), Heinrich-Heine University, Düsseldorf, Germany; Department of Neurology and Center for Clinical Neuroscience (E.H.), First Medical Faculty, Charles University in Prague, Czech Republic; Department of Neurology (K.W.S.), Medical University of Łódź, Poland; Sanofi Genzyme (D.H.M., S.L.L., M.A.P.), Cambridge, MA; and Evidence Scientific Solutions (S.M.K.), Philadelphia, PA (at the time the work was conducted). g.giovannoni@qmul.ac.uk., Cohen JA; From Queen Mary University of London (G.G.), Barts and The London School of Medicine, UK; Mellen Center (J.A.C.), Cleveland Clinic, OH; Department of Clinical Neurosciences (A.J.C., D.A.S.C.), University of Cambridge, UK; Department of Neurology and Center for Neuropsychiatry (H.-P.H.), Heinrich-Heine University, Düsseldorf, Germany; Department of Neurology and Center for Clinical Neuroscience (E.H.), First Medical Faculty, Charles University in Prague, Czech Republic; Department of Neurology (K.W.S.), Medical University of Łódź, Poland; Sanofi Genzyme (D.H.M., S.L.L., M.A.P.), Cambridge, MA; and Evidence Scientific Solutions (S.M.K.), Philadelphia, PA (at the time the work was conducted)., Coles AJ; From Queen Mary University of London (G.G.), Barts and The London School of Medicine, UK; Mellen Center (J.A.C.), Cleveland Clinic, OH; Department of Clinical Neurosciences (A.J.C., D.A.S.C.), University of Cambridge, UK; Department of Neurology and Center for Neuropsychiatry (H.-P.H.), Heinrich-Heine University, Düsseldorf, Germany; Department of Neurology and Center for Clinical Neuroscience (E.H.), First Medical Faculty, Charles University in Prague, Czech Republic; Department of Neurology (K.W.S.), Medical University of Łódź, Poland; Sanofi Genzyme (D.H.M., S.L.L., M.A.P.), Cambridge, MA; and Evidence Scientific Solutions (S.M.K.), Philadelphia, PA (at the time the work was conducted)., Hartung HP; From Queen Mary University of London (G.G.), Barts and The London School of Medicine, UK; Mellen Center (J.A.C.), Cleveland Clinic, OH; Department of Clinical Neurosciences (A.J.C., D.A.S.C.), University of Cambridge, UK; Department of Neurology and Center for Neuropsychiatry (H.-P.H.), Heinrich-Heine University, Düsseldorf, Germany; Department of Neurology and Center for Clinical Neuroscience (E.H.), First Medical Faculty, Charles University in Prague, Czech Republic; Department of Neurology (K.W.S.), Medical University of Łódź, Poland; Sanofi Genzyme (D.H.M., S.L.L., M.A.P.), Cambridge, MA; and Evidence Scientific Solutions (S.M.K.), Philadelphia, PA (at the time the work was conducted)., Havrdova E; From Queen Mary University of London (G.G.), Barts and The London School of Medicine, UK; Mellen Center (J.A.C.), Cleveland Clinic, OH; Department of Clinical Neurosciences (A.J.C., D.A.S.C.), University of Cambridge, UK; Department of Neurology and Center for Neuropsychiatry (H.-P.H.), Heinrich-Heine University, Düsseldorf, Germany; Department of Neurology and Center for Clinical Neuroscience (E.H.), First Medical Faculty, Charles University in Prague, Czech Republic; Department of Neurology (K.W.S.), Medical University of Łódź, Poland; Sanofi Genzyme (D.H.M., S.L.L., M.A.P.), Cambridge, MA; and Evidence Scientific Solutions (S.M.K.), Philadelphia, PA (at the time the work was conducted)., Selmaj KW; From Queen Mary University of London (G.G.), Barts and The London School of Medicine, UK; Mellen Center (J.A.C.), Cleveland Clinic, OH; Department of Clinical Neurosciences (A.J.C., D.A.S.C.), University of Cambridge, UK; Department of Neurology and Center for Neuropsychiatry (H.-P.H.), Heinrich-Heine University, Düsseldorf, Germany; Department of Neurology and Center for Clinical Neuroscience (E.H.), First Medical Faculty, Charles University in Prague, Czech Republic; Department of Neurology (K.W.S.), Medical University of Łódź, Poland; Sanofi Genzyme (D.H.M., S.L.L., M.A.P.), Cambridge, MA; and Evidence Scientific Solutions (S.M.K.), Philadelphia, PA (at the time the work was conducted)., Margolin DH; From Queen Mary University of London (G.G.), Barts and The London School of Medicine, UK; Mellen Center (J.A.C.), Cleveland Clinic, OH; Department of Clinical Neurosciences (A.J.C., D.A.S.C.), University of Cambridge, UK; Department of Neurology and Center for Neuropsychiatry (H.-P.H.), Heinrich-Heine University, Düsseldorf, Germany; Department of Neurology and Center for Clinical Neuroscience (E.H.), First Medical Faculty, Charles University in Prague, Czech Republic; Department of Neurology (K.W.S.), Medical University of Łódź, Poland; Sanofi Genzyme (D.H.M., S.L.L., M.A.P.), Cambridge, MA; and Evidence Scientific Solutions (S.M.K.), Philadelphia, PA (at the time the work was conducted)., Lake SL; From Queen Mary University of London (G.G.), Barts and The London School of Medicine, UK; Mellen Center (J.A.C.), Cleveland Clinic, OH; Department of Clinical Neurosciences (A.J.C., D.A.S.C.), University of Cambridge, UK; Department of Neurology and Center for Neuropsychiatry (H.-P.H.), Heinrich-Heine University, Düsseldorf, Germany; Department of Neurology and Center for Clinical Neuroscience (E.H.), First Medical Faculty, Charles University in Prague, Czech Republic; Department of Neurology (K.W.S.), Medical University of Łódź, Poland; Sanofi Genzyme (D.H.M., S.L.L., M.A.P.), Cambridge, MA; and Evidence Scientific Solutions (S.M.K.), Philadelphia, PA (at the time the work was conducted)., Kaup SM; From Queen Mary University of London (G.G.), Barts and The London School of Medicine, UK; Mellen Center (J.A.C.), Cleveland Clinic, OH; Department of Clinical Neurosciences (A.J.C., D.A.S.C.), University of Cambridge, UK; Department of Neurology and Center for Neuropsychiatry (H.-P.H.), Heinrich-Heine University, Düsseldorf, Germany; Department of Neurology and Center for Clinical Neuroscience (E.H.), First Medical Faculty, Charles University in Prague, Czech Republic; Department of Neurology (K.W.S.), Medical University of Łódź, Poland; Sanofi Genzyme (D.H.M., S.L.L., M.A.P.), Cambridge, MA; and Evidence Scientific Solutions (S.M.K.), Philadelphia, PA (at the time the work was conducted)., Panzara MA; From Queen Mary University of London (G.G.), Barts and The London School of Medicine, UK; Mellen Center (J.A.C.), Cleveland Clinic, OH; Department of Clinical Neurosciences (A.J.C., D.A.S.C.), University of Cambridge, UK; Department of Neurology and Center for Neuropsychiatry (H.-P.H.), Heinrich-Heine University, Düsseldorf, Germany; Department of Neurology and Center for Clinical Neuroscience (E.H.), First Medical Faculty, Charles University in Prague, Czech Republic; Department of Neurology (K.W.S.), Medical University of Łódź, Poland; Sanofi Genzyme (D.H.M., S.L.L., M.A.P.), Cambridge, MA; and Evidence Scientific Solutions (S.M.K.), Philadelphia, PA (at the time the work was conducted)., Compston DA; From Queen Mary University of London (G.G.), Barts and The London School of Medicine, UK; Mellen Center (J.A.C.), Cleveland Clinic, OH; Department of Clinical Neurosciences (A.J.C., D.A.S.C.), University of Cambridge, UK; Department of Neurology and Center for Neuropsychiatry (H.-P.H.), Heinrich-Heine University, Düsseldorf, Germany; Department of Neurology and Center for Clinical Neuroscience (E.H.), First Medical Faculty, Charles University in Prague, Czech Republic; Department of Neurology (K.W.S.), Medical University of Łódź, Poland; Sanofi Genzyme (D.H.M., S.L.L., M.A.P.), Cambridge, MA; and Evidence Scientific Solutions (S.M.K.), Philadelphia, PA (at the time the work was conducted).
Jazyk:	angličtina
Zdroj:	Neurology [Neurology] 2016 Nov 08; Vol. 87 (19), pp. 1985-1992. Date of Electronic Publication: 2016 Oct 12.
DOI:	10.1212/WNL.0000000000003319
Abstrakt:	Objective: To characterize effects of alemtuzumab treatment on measures of disability improvement in patients with relapsing-remitting multiple sclerosis (RRMS) with inadequate response (≥1 relapse) to prior therapy. Methods: Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis (CARE-MS) II, a 2-year randomized, rater-blinded, active-controlled, head-to-head, phase 3 trial, compared efficacy and safety of alemtuzumab 12 mg with subcutaneous interferon-β-1a (SC IFN-β-1a) 44 μg in patients with RRMS. Prespecified and post hoc disability outcomes based on Expanded Disability Status Scale (EDSS), Multiple Sclerosis Functional Composite (MSFC), and Sloan low-contrast letter acuity (SLCLA) are reported, focusing on improvement of preexisting disability in addition to slowing of disability accumulation. Results: Alemtuzumab-treated patients were more likely than SC IFN-β-1a-treated patients to show improvement in EDSS scores (p < 0.0001) on all 7 functional systems. Significantly more alemtuzumab patients demonstrated 6-month confirmed disability improvement. The likelihood of improved vs stable/worsening MSFC scores was greater with alemtuzumab than SC IFN-β-1a (p = 0.0300); improvement in MSFC scores with alemtuzumab was primarily driven by the upper limb coordination and dexterity domain. Alemtuzumab-treated patients had more favorable changes from baseline in SLCLA (2.5% contrast) scores (p = 0.0014) and MSFC + SLCLA composite scores (p = 0.0097) than SC IFN-β-1a-treated patients. Conclusions: In patients with RRMS and inadequate response to prior disease-modifying therapies, alemtuzumab provides greater benefits than SC IFN-β-1a across several disability outcomes, reflecting improvement of preexisting disabilities. Classification of Evidence: This study provides Class I evidence (based on rater blinding and a balance in baseline characteristics between arms) that alemtuzumab modifies disability measures favorably compared with SC IFN-β-1a. (© 2016 American Academy of Neurology.)
Databáze:	MEDLINE
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