DX09
The Effect of Ocrelizumab on Cognitive Functioning in Relapsing Multiple Sclerosis: Analysis of the Phase III IFN Beta-1a-Controlled OPERA Studies

Thursday, May 25, 2017
B2 (New Orleans Convention Center)
Aaron E Miller, MD , Corinne Goldsmith Dickinson Center for Multiple Sclerosis at Mount Sinai, New York, NY
Jerome de Seze, MD PhD , University Hospital of Strasbourg, Strasbourg, France
Stephen L Hauser, MD , University of California, San Francisco, San Francisco, CA
Ludwig Kappos, MD , University Hospital Basel, University of Basel, Basel, Switzerland
Jerry S Wolinsky, MD , McGovern Medical School, UTHealth, Houston, TX
Jian Han, PhD , Genentech Inc., South San Francisco, CA
Laura Julian, PhD , Genentech, Inc., South San Francisco, CA
Julie Napieralski, PhD , F. Hoffmann-La Roche Ltd, Basel, Switzerland
Fred Lublin, MD , Icahn School of Medicine at Mount Sinai, New York, NY
Aaron E Miller, MD , Corinne Goldsmith Dickinson Center for Multiple Sclerosis at Mount Sinai, New York, NY



Background: Cognitive impairment affects individuals with multiple sclerosis (MS) and is commonly assessed using the Paced Auditory Serial Addition Test (PASAT) and the Symbol Digit Modalities Test (SDMT), which specifically measure information processing speed and working memory. Ocrelizumab has demonstrated superiority in reducing clinical (relapse, disability, disease progression) and subclinical (lesion activity, brain atrophy) disease activity vs interferon beta-1a (IFN β-1a) in relapsing MS (RMS).

Objectives: To assess the impact of ocrelizumab vs that of IFN β-1a on measures of cognitive functioning in Phase III studies in RMS.

Methods: OPERA I and OPERA II were identical, active-controlled Phase III trials in RMS. Patients were randomized 1:1 to intravenous ocrelizumab 600 mg every 24 weeks or subcutaneous IFN β-1a 44 μg three times weekly for 96 weeks. The PASAT and SDMT were administered at baseline and every 12 weeks; analyses were conducted for the individual OPERA trials and the pooled population.

Results: In the pooled population, mean (SE) baseline PASAT scores were 42.58 (0.460) with ocrelizumab and 41.70 (0.477) with IFN β-1a, while baseline SDMT scores were 47.34 (0.641) and 47.31 (0.639), respectively. SDMT and PASAT scores were modestly correlated (0.36; p<0.0001). At Week 96, a greater improvement from baseline in mean PASAT score was observed with ocrelizumab (6.520; SE 0.35, 95% CI 5.84–7.20) than with IFN β-1a (5.651; SE 0.36, 95% CI 4.95–6.35; p=0.0531) in the pooled population. Similarly, a greater improvement from baseline in mean SDMT score was observed with ocrelizumab (5.430; SE 0.52, 95% CI 4.41–6.46) than with IFN β-1a (4.046; SE 0.54, 95% CI 3.00–5.10; p=0.0422) at Week 96 in the pooled population. Additional results in individual studies and by thresholds for clinical response will be presented.

Conclusions: A pooled analysis of Phase III trials in RMS showed that ocrelizumab consistently improved cognitive performance compared with IFN β-1a, as assessed by two different measures of information processing speed and working memory.