Efficacy of Ocrelizumab in Patients with Relapsing Multiple Sclerosis: Pooled Analysis of Two Identical Phase III, Double-Blind, Double-Dummy, Interferon Beta-1a-Controlled Studies (S49.003)

ObjectiveTo evaluate the efficacy of ocrelizumab compared with interferon beta-1a (IFNβ-1a) through pooled analysis of efficacy in OPERA I and OPERA II.BackgroundMS pathogenesis is understood to involve two distinct, but overlapping mechanisms, with early inflammation and concurrent or subsequent neurodegeneration. Ocrelizumab, a humanized monoclonal antibody that selectively targets CD20 + B cells, was superior in reducing annualized relapse rate (ARR) vs IFNβ-1a in OPERA I and OPERA II, two identical Phase III, randomized, double-blind, double-dummy trials in relapsing MS.MethodsPooled analyses of OPERA I and OPERA II efficacy were considered to be valid if treatment differences between the ocrelizumab and IFNβ-1a groups for ARR through week 96 and ≥12-week confirmed disability progression (CDP) were broadly consistent between the two studies; i.e. pu003e0.1 for study-by-treatment group interaction or p≤0.1 for study-by-treatment group interaction and both within-study treatment differences point to the same direction. Pre-specified pooled analyses included ≥12-week and ≥24-week CDP and ≥12-week confirmed disability improvement (CDI) through week 96.ResultsConsistency of baseline characteristics and treatment effects across both studies met pre-determined criteria for pooled efficacy analysis. Compared with IFNβ-1a, ocrelizumab showed a 47[percnt] reduction in adjusted ARR (pu003c0.0001) and reduced the risk of 12-week CDP by 40[percnt] (p=0.0006) and 24-week CDP by 40[percnt] (p=0.0025). In pooled analyses, the proportion of ocrelizumab-treated patients that achieved CDI at 12 and 24 weeks was 20.7[percnt] and 15.6[percnt] vs 15.6[percnt] and 11.6[percnt], respectively, for IFNβ-1a-treated patients, representing a 33[percnt] and 36[percnt] relative improvement (relative risk 1.33 [p=0.0194] and 1.36 [p=0.0343]), respectively. Ocrelizumab showed an 18.8[percnt] reduction in brain atrophy vs IFNβ-1a (p=0.0015).ConclusionsPooled analyses of OPERA I and OPERA II efficacy endpoints showed that ocrelizumab significantly suppressed disease progression and increased the proportion of patients with disability improvement over 96 weeks compared with IFNβ-1a.Supported by F. Hoffmann-La Roche Disclosure: Dr. Hauser has received personal compensation for activities with Annexon, Symbiotix, Bionure as a scientific advisory board member and from F. Hoffmann-La Roche Ltd. Dr. Arnold holds stock and/or stock options in NeuroRx Research, which sponsored research in which Dr. Arnold was an investigator. Dr. Bar-Or has received personal compensation for activities with Bayer, Bayhill Therapeutics, Berlex, Biogen Idec, BioMS, Diogenix, Eli Lilly as a consultant, speaker and advisory board member. Dr. Comi has received personal compensation for activities with Teva, Novartis, Genzyme, Merck Serono, Biogen, Bayer, Actelion, Almirall, and Serono Symposia International Foundation. Dr. Hartung has received personal compensation for activities with from Bayer, Biogen, GeNeuro, Genzyme as speaker, committee member, consultant. Dr. Lublin has received personal compensation for activities with Acorda Therapeutics, Inc., Biogen Idec, Novartis Pharmaceuticals Corp, Teva Neuroscience, Inc.,Genzyme, Sanofi, Celgene, Cognition Pharmaceuticals, Inc., Elsevier, NIH, and NMSS. Dr. Selmaj has received personal compensation for activities with Biogen Idec, Novartis, TEVA Pharmaceuticals, Roche Diagnostics Corporation, Genzyme, Synthon, Receptos, and Bayer for serving on the Scientific Advisory Board. Dr. Traboulsee has received personal compensation for activities with Genzyme and Roche. Dr. Traboulsee has received research support from Genzyme, Roche, Chugai. Dr. Klingelschmitt holds stock and/or stock options in F. Hoffmann-La Roche, Ltd., which sponsored research in which Dr. Klingelschmitt was involved as an investigator. Dr. Masterman holds stock and/or stock options in Genentech, which sponsored research in which Dr. Masterman was involved as an investigator. Dr. Fontoura has received personal compensation for activities with.F. Hoffmann-La Roche as an employee. Dr. Chin has received personal compensation for activities with Genentech, Inc. as an employee. Dr. Garren has received personal compensation for activities with F. Hoffmann-La Roche as an employee. Dr. Kappos9s institution (University Hospital Basel) has received royalty payments from Neurostatus Systems GmbH.