Authors:
Barkhof, Frederik, Kappos, Ludwig, Wolinsky, Jerry S., Li, David K. B., Bar-Or, Amit, Hartung, Hans-Peter, Belachew, Shibeshih, Han, Jian, Julian, Laura, Sauter, Annette, Napieralski, Julie, Koendgen, Harold, Hauser, Stephen L.
Abstract:
Objective: To assess the onset of ocrelizumab efficacy on brain magnetic resonance imaging (MRI) measures of disease activity in the Phase II study in relapsing-remitting multiple sclerosis (RRMS), and relapse rate in the pooled Phase III studies in relapsing multiple sclerosis (RMS). Methods: Brain MRI activity was determined in the Phase II trial at monthly intervals in patients with RRMS receiving placebo, ocrelizumab (600 mg), or intramuscular interferon (IFN) β-1a (30 μg). Annualized relapse rate (ARR; over various epochs) and time to fi (...)
Objective: To assess the onset of ocrelizumab efficacy on brain magnetic resonance imaging (MRI) measures of disease activity in the Phase II study in relapsing-remitting multiple sclerosis (RRMS), and relapse rate in the pooled Phase III studies in relapsing multiple sclerosis (RMS). Methods: Brain MRI activity was determined in the Phase II trial at monthly intervals in patients with RRMS receiving placebo, ocrelizumab (600 mg), or intramuscular interferon (IFN) β-1a (30 μg). Annualized relapse rate (ARR; over various epochs) and time to first relapse were analyzed in the pooled population of the Phase III OPERA I and OPERA II trials in patients with RMS receiving ocrelizumab (600 mg) or subcutaneous IFN β-1a (44 μg). Results: In patients with RRMS, ocrelizumab reduced the number of new T1 gadolinium-enhancing lesions by Week 4 vs placebo (p=0.042) and by Week 8 vs intramuscular IFN β-1a (p<0.001). Ocrelizumab also reduced the number of new or enlarging T2 lesions appearing between Weeks 4 and 8 vs both placebo and IFN β-1a (both p<0.001). In patients with RMS, ocrelizumab significantly reduced ARR (p=0.005), and the probability of time to first protocol-defined relapse (p=0.014) vs subcutaneous IFN β-1a within the first 8 weeks. Conclusion: Epoch analysis of MRI-measured lesion activity in the Phase II study and relapse rate in the Phase III studies consistently revealed a rapid suppression of acute MRI and clinical disease activity following treatment initiation with ocrelizumab in patients with RRMS and RMS, respectively. Classification of evidence: This study provides Class II evidence that for patients with RRMS and RMS, ocrelizumab suppressed MRI activity within 4 weeks and clinical disease activity within 8 weeks.
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