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Alemtuzumab improves preexisting disability in active relapsing-remitting MS patients

2016; Lippincott Williams & Wilkins; Volume: 87; Issue: 19 Linguagem: Inglês

10.1212/wnl.0000000000003319

1526-632X

Gavin Giovannoni, Jeffrey Cohen, Alasdair Coles, Hans-Peter Hartung, Eva Havrdová, Krzysztof Selmaj, David Margolin, Stephen Lake, Susan M. Kaup, Michael Panzara, D. A. S. Compston, Douglas L. Arnold, Jeffrey Cohen, Alasdair Coles, Alastair Compston, Christian Confavreux, Edward Fox, Hans-Peter Hartung, Eva Havrdová, Krzysztof Selmaj, Howard L. Weiner, Hillel S. Panitch, David B. Clifford, Jack P. Antel, Frederik Barkhof, David R. Snydman, Leslie J. DeGroot, Douglas B. Cines, Ralph B. D’Agostino, Benjamin Greenberg, Jörg Krauss, Volker Limmroth, Clyde Markowitz, Robert T. Naismith, David Tabby, Norma Deri, Karyn Boundy, Simon Broadley, Michael Dreyer, Suzanne Hodgkinson, John O. King, Richard Macdonell, FAFRM RACP, Pamela McCombe, Mark Paine, Stephen W. Reddel, Raymond Schwartz, Steve Vucic, MD. Karl Vass, PhD Dominique Dive, Bénédicte Dubois, Christian Sindic, Dagoberto Callegaro, Maria Lúcia Brito Ferreira, Marcio Mena Barreto Martins, Charles Peter Tilbery, Charles Ayotte, Donald Brunet, Mark Freedman, François Grand’Maison, François Jacques, Marcelo Kremenchutzky, Anthony Traboulsee, MD Licia Antonelli, Vesna Brinar, Mario Habek, Spomenka Kiđemet Piskač, Zlatko Trkanjec, Anton Vladić, Ivana Kovářová, Ivan Rektor, Radomír Taláb, Marta Vachová, Thor Petersen, Mads Ravnborg, Per Soelberg Sørensen, Michel Clanet, Pierre Clavelou, de Sèze, Marc Debouverie, Gilles Edan, Catherine Lubetzki, Thibault Moreau, Patrick Vermersch, Karl Baum, Judith Haas, Bernhard Hemmer, Ulrich Herrlinger, Wolfgang Köhler, G. Ochs, Martin Stangel, Hayrettin Tumani, Péter Urbán, Uwe K. Zettl, Tjalf Ziemssen, Anat Achiron, Arnon Karni, Adi Vaknin Dembinsky, Antonio Bertolotto, Ruggero Capra, Giancarlo Comi, Luca Durelli, Angelo Ghezzi, Gianluigi Mancardi, Maria Giovanna Marrosu, Carlo Pozzilli, Noemí Santos Caballero, Claudia Venzor Mendoza, J. Villanueva, Raymond Hupperts, Erik van Munster, Wojciech Kozubski, Krzysztof Selmaj, Z Stelmasiak, Evgeniy Robertovich Barantsevich, DMedSc, Anna N. Belova, Alexey Boyко, Е. И. Гусев, N A Malkova, Semen V. Perfiliev, И Е Повереннова, A A Skoromets, I. D. Stolyarov, E Z Yakupov, И. А. Завалишин, Evica Dinčić, Jelena Drulović, Čongor Nadj, Gordana Tončev, Rafael Arroyo González, Guillermo Izquierdo‐Ayuso, Óscar Fernández, Xavier Montalbán, Jan Lycke, Anders Svenningsson, Tetyana Kobys, Tetyana Nehrych, Natalia P. Voloshyna, Gavin Giovannoni, David Rog, Neil Scolding, Basil Sharrack, Nuhad E. Abou Zeid, Mark Agius, Ann Bass, G. Kim Bigley, Roberto Bomprezzi, Aaron Boster, Christine Boutwell, Tiffany J. Braley, Mark Cascione, Gary Clauser, Joanna Cooper, Heidi Crayton, Jeffrey Dunn, Keith R. Edwards, Stanton B. Elias, Bradley K. Evans, Mark H. Fletcher, Corey C. Ford, E. Frohman, Suzanne Gazda, Thomas Giancarlo, Jeffrey Gitt, Steven A. Glyman, Andrew Goodman, Christopher Gottschalk, Malcolm Gottesman, Erica Grazioli, Mark Gudesblatt, Ajay S. Gupta, Joseph Herbert, William Honeycutt, Bruce L. Hughes, Samuel F. Hunter, Todd J. Janus, Adil Javed, Davis E. Jones, Burk Jubelt, Lily Jung Henson, Omar Khan, Mariko Kita, S Kirzinger, Stephen Krieger, Stanley J. Krolczyk, Christopher LaGanke, Enrico C. Lallana, Ellen Lathi, Neil Lava, Sharon Lynch, Bennett-Irving Machanic, Silva Markovic‐Plese, David H. Mattson, Daniel D. Mikol, Aaron Miller, Tamara Ann Miller, Alireza Minagar, Galen W. Mitchell, Harold L. Moses, Donald Negroski, Gabriel Pardo, Mary Ann Picone, Jana Lízrová Preiningerová, Kottil Rammohan, Claire Riley, Peter Riskind, Syed Rizvi, M.E.E. van Rossen, Ted L. Rothstein, Vernon Rowe, Walter Royal, John Schaeffer, Christopher A. Sheppard, Richard Shubin, Scott Silliman, B. Singer, Lee Stein, Brian Steingo, H. R. Sullivan, Timothy Thoits, Ben Thrower, Cary Twyman, Anand Vaishnav, Stephen G. Vincent, Timothy R. Vollmer, Stephen R. Waldman, Leslie P. Weiner, Jeanette Wendt, Dean M. Wingerchuk, Sibyl Wray, Daniel Wynn,

Immunotherapy and Immune Responses

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.