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