DX21 Alemtuzumab's Effects on Disability Outcomes Occur Early in Care-MS II

Thursday, May 30, 2013
Heidi Crayton, MD , MS Center of Greater Washington, Vienna, VA
Douglas L Arnold, MD , Montreal Neurological Institute, McGill University, and NeuroRx Research, Montreal, Quebec, Canada, Montreal, QC, Canada
Jeffrey A Cohen, MD , Mellen Center, Cleveland Clinic, Cleveland, OH, USA, Cleveland, OH
Alasdair J Coles, MD , University of Cambridge, Cambridge, UK, Cambridge, United Kingdom
Christian Confavreux, MD , University Claude Bernard, Lyon, France, Lyon, France
Edward J Fox, MD , MS Clinic of Central Texas, Round Rock, TX, USA, Round Rock, TX
Hans-Peter Hartung, MD , Heinrich-Heine University, Dusseldorf, Germany, Dusseldorf, Germany
Eva Havrdova, MD, PhD , Department of Neurology, First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic, Prague, Czech Republic
Krzysztof Selmaj, MD, PhD , Medical University of Lodz, Lodz, Poland, Lodz, Poland
Howard L Weiner, MD , Brigham and Women's Hospital Center for Neurologic Diseases, Boston, MA, USA, Boston, MA
Cary L Twyman, MD , Associates in Neurology PSC, Lexington, KY, USA, Lexington, KY
Tamara A Miller, MD , Advanced Neurology of Colorado, Ft Collins, CO, USA, Ft Collins, CO
Stephen L Lake, ScD , Genzyme, Cambridge, MA, USA, Cambridge, MA
David H Margolin, MD , Genzyme, Cambridge, MA, USA, Cambridge, MA
Michael A Panzara, MD , Genzyme, Cambridge, MA, USA, Cambridge, MA
Alastair Compston, MD , University of Cambridge, Cambridge, UK, Cambridge, United Kingdom

Background: Alemtuzumab treatment significantly reduced the risk for relapse and sustained accumulation of disability compared with subcutaneous interferon beta-1a (SC IFNB-1a) in a phase 3 trial in patients with relapsing-remitting multiple sclerosis (RRMS) who had disease activity while on prior therapy and baseline Expanded Disability Status Scale (EDSS) scores ranging from 0 to 6.5 with a mean of 2.7. Alemtuzumab improved the mean disability score during the 2-year study, while the mean disability score worsened in IFNB-1a-treated patients.

Objectives: To evaluate the time course of alemtuzumab’s effects on disability in comparison to SC IFNB-1a in RRMS patients who have had disease activity on prior therapy.

Methods: CARE-MS II was a 2-year, randomized (2:1), rater-blinded trial comparing alemtuzumab to IFNB-1a in 628 active RRMS patients who had ≥ 1 relapse while on therapy. Alemtuzumab was administered 12 mg/day intravenously on 5 days at study start and on 3 days 12 months later. SC IFNB-1a was administered 44 mcg 3 times weekly for 24 months. EDSS was assessed at baseline and quarterly by blinded raters. Change from baseline was tested with a repeated measures mixed-model with covariate adjustment for geographic region and baseline EDSS.

Results: Alemtuzumab patients were significantly better than SC IFNB-1a patients on mean change from baseline EDSS as early as Month 6, with a net difference of 0.27 (P = 0.0003). Alemtuzumab group mean EDSS score remained significantly lower than the IFNB-1a group at all subsequent time points through Month 24, (net treatment group differences: Month 9: 0.33, P <0.0001; Month 12: 0.25, P =0. 0023; Month 15: 0.24, P = 0.0073; Month 18: 0.35, P =0.0002; Month 21: 0.38, P <.0001; and Month 24: 0.41, P <0.0001). Alemtuzumab patients also showed significant mean improvement compared with baseline beginning at Month 6 (all P values < 0.05), while SC IFNB-1a patients showed significant mean worsening at most time points (all Pvalues < 0.05) except Months 3, 12, and 15.

Conclusions: Alemtuzumab treatment led to disability improvement that developed early and was durable through the 2-year study period.