Effect of Ocrelizumab on MRI Inflammatory and Neurodegenerative Markers of Disease in Patients with Relapsing Multiple Sclerosis: Analysis of the Phase III, Double-Blind, Double-Dummy, Interferon Beta-1a-Controlled OPERA I and OPERA II Studies (S49.002)

Objective: To evaluate the effect of ocrelizumab vs interferon beta-1a (IFNβ-1a) on MRI outcomes in patients with relapsing MS enrolled in two identical Phase III, randomized, double-blind, double-dummy trials (OPERA I and OPERA II). Background: In MS, there is an interdependence between inflammation and neurodegeneration, which could be mediated through B-cell and T-cell interactions. MRI is used to evaluate inflammatory and neurodegenerative markers of MS. Ocrelizumab is a humanized monoclonal antibody that selectively targets CD20 + B cells. Methods: In OPERA I and OPERA II, patients were randomized (1:1) to receive ocrelizumab 600mg via intravenous infusion every 24 weeks or subcutaneous IFNβ-1a 44μg three-times weekly over 96 weeks. Brain MRI endpoints included the total number of T1 gadolinium-enhancing lesions, new/enlarging T2 hyperintense lesions, and new T1 hypointense lesions at weeks 24, 48, and 96, and change in whole brain volume from baseline and week 24 to week 96. Results: Compared with IFNβ-1a, ocrelizumab reduced T1 gadolinium-enhancing lesions by 94[percnt] in OPERA I and 95[percnt] in OPERA II (both p<0.0001); new/enlarging T2 hyperintense lesions by 77[percnt] in OPERA I and 83[percnt] in OPERA II (both p<0.0001); new T1 hypointense lesions by 57[percnt] in OPERA I and 64[percnt] in OPERA II (both p<0.0001); and brain volume loss from baseline to week 96 by 23.5[percnt] (p<0.0001) and 23.8[percnt] (p=0.0001) and from week 24 to week 96 by 22.7[percnt] (p=0.0042) and 14.9[percnt] (p=0.0900) in OPERA I and OPERA II, respectively. Conclusions: Ocrelizumab significantly and consistently suppressed inflammatory and neurodegenerative markers of disease on MRI vs IFNβ-1a in OPERA I and OPERA II over 96 weeks, with near-complete elimination of new T1 gadolinium-enhancing lesions following the first dose. The majority of new/enlarging T2 lesions and new T1 hypointense lesions occurred before week 24 and significantly declined thereafter. Supported by F. Hoffmann-La Roche Disclosure: 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. 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. Kappos9s institution (University Hospital Basel) has received royalty payments from Neurostatus Systems GmbH. 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. Wolinsky has received royalty payments from Chemicon International through the University of Texas Health Science Center at Houston.