No Evidence of Disease Activity on Ocrelizumab Treatment in Patients With Early Relapsing Multiple Sclerosis: Pooled Analysis of the Phase III OPERA Studies (P4.391)

Objective: To assess the proportion of patients with early relapsing multiple sclerosis (RMS) with no evidence of disease activity (NEDA) following treatment with ocrelizumab vs interferon beta-1a (IFNβ-1a). Background: Ocrelizumab is a humanized monoclonal antibody that selectively targets CD20+ B cells. In two identical phase III trials in RMS (OPERA I and OPERA II), ocrelizumab was superior to IFNβ-1a in reducing clinical and magnetic resonance imaging disease activity. Effective treatment early in MS is critical for optimal short- and long-term patient outcomes. Design/Methods: In the OPERA trials, patients were randomized 1:1 to receive intravenous ocrelizumab 600 mg every 24 weeks or subcutaneous IFNβ-1a 44 mg three times weekly for 96 weeks. Exploratory analysis of pooled data from the OPERA trials evaluated NEDA (defined as no protocol-defined relapse, confirmed disability progression events, T1 gadolinium-enhancing lesions, or new/enlarging T2 lesions) in patients with early RMS (defined as MS symptom onset ≤2 years and no previous disease-modifying treatment). Results: A total of 221/827 (26.7%) ocrelizumab-treated patients and 206/829 (24.8%) IFNβ-1a–treated patients met the definition of early RMS. Baseline demographics and disease characteristics were balanced between treatment arms in this patient subgroup (mean [standard deviation]: age (years), ocrelizumab 34.7 [9.23], IFNβ-1a 34.2 [8.93]; disease duration since MS symptom onset (years), ocrelizumab 1.0 [0.49], IFNβ-1a 0.9 [0.49]; disease duration since MS diagnosis (years), ocrelizumab 0.5 [0.36], IFNβ-1a 0.5 [0.34]; baseline Expanded Disability Status Scale score, ocrelizumab 2.2 [1.03], IFNβ-1a 2.1 [1.07]). Over 96 weeks, a greater proportion of patients [95% CI] achieved NEDA with ocrelizumab (47.6% [40.6–54.6%]) vs IFNβ-1a (28.0% [21.8–34.9%]), representing a 76% increase (p Conclusions: In patients with early RMS, ocrelizumab increased the proportion of patients achieving NEDA vs IFNβ-1a, a finding consistent with the overall OPERA populations. These results reflect the benefits of ocrelizumab intervention early in the disease course. Study Supported by: Sponsored by F. Hoffmann-La Roche Ltd. Disclosure: Dr. Havrdova has received personal compensation for activities with Biogen, Merck Serono, Novartis, Sanofi-Genzyme, and Teva as an speaker. Dr. Havrdova has received research support from Biogen. 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. Honeycutt has received personal compensation for activities with MS Pharmaceutical and NIH as a speaker. Dr. Kappos has reveived personal compensation for activities with University Hospital Basel as an advisory board member. Dr. Kappos has received research support from Swiss Multiple Sclerosis Society, Swiss National Research Foundation, European Union, Gianni Rubatto Foundation, Novartis Research Foundation, and Roche Research Foundation. Dr. Selmaj received personal compensation for activities with Biogen, Novartis, TEVA, Roche, Genzyme, Synthon, Receptos, and Bayer. Dr. Wolinsky has received personal compensation for activities with AbbVie, AcademicCME, Alkermes, Bayer HealthCare, Forward Pharma A/S, Novartis, Roche/Genentech, Sanofi Genzyme, Takeda, Teva Pharmaceuticals, and WebMD. Dr. Wolinsky has received royalty payments from University of Texas Health Science Center at Houston. Dr. Belachew has received personal compensation for activities with La Roche, Ltd. as an employee. Dr. Belachew has received stock and/or stock options from Biogen Idec. Dr. Bernasconi has received personal compensation for activities with F Hoffmann-La Roche Ltd. and Santhera Pharmaceuticals AG as a consultant. Dr. Buffels has received personal compensation for activities with F. Hoffmann-La Roche Ltd as an employee. I am an employee of F.Hoffman-La Roche Ltd. And Genentech Inc.,,,,,, Dr. Wei has received personal compensation for activities with F. Hoffmann-La Roche Ltd. as an employee. Dr. Traboulsee has received personal compensation for activities with Genzyme and Roche as a consultant. Dr. Traboulsee has received research support from Genzyme, Roche, and Chugai.