Ocrelizumab efficacy in subgroups of patients with relapsing multiple sclerosis

Abstract

Objective The efficacy and safety of ocrelizumab, versus interferon (IFN) β-1a, for the treatment of relapsing multiple sclerosis (RMS) from the identically designed OPERA I (NCT01247324) and OPERA II (NCT01412333) phase III studies has been reported; here we present subgroup analyses of efficacy endpoints from the pooled OPERA I and OPERA II populations. Methods Patients with RMS were randomized to either ocrelizumab 600 mg administered by intravenous infusion every 24 weeks or subcutaneous IFN β-1a 44 µg three times per week throughout the 96-week treatment period. Relapse, disability, and MRI outcomes were analyzed for predefined and post hoc subgroups based on demographic and disease characteristics along with prior treatment using appropriate statistical tests to determine the treatment effect in subgroups and treatment-by-subgroup interactions. Results The significant treatment benefit of ocrelizumab, versus IFN β-1a, observed in the overall OPERA I and OPERA II pooled populations was maintained across most subgroup strata for all endpoints, including annualized relapse rate, disability progression, and MRI outputs. Conclusions The treatment effect of ocrelizumab versus IFN β-1a, measured by clinical and MRI outcomes, was maintained across most of the subgroups and strata of interest, and the pattern of treatment benefit across all subgroups was consistent with that from the pooled OPERA studies. Electronic supplementary material The online version of this article (10.1007/s00415-019-09248-6) contains supplementary material, which is available to authorized users.

Intrathecal, Not Systemic Inflammation Is Correlated With Multiple Sclerosis Severity, Especially in Progressive Multiple Sclerosis

“…These data are consistent with extensive genetic studies that also were unable to identify reproducible differences in MS susceptibility alleles between clinical subtypes of MS (4). The efficacy of B cell-depleting therapy (ocrelizumab) in both relapse-onset and PPMS clinical subgroups (5, 6) combined with clear and significant decline in efficacy on disability progression between young (<40 y) and older (≥40 y) relapse-onset MS patients (7), the genetic and proteomic results indicate that the MS disease process is largely overlapping, if not identical in all clinical MS subgroups and the main difference in the efficacy of current FDA-approved drugs on MS disability progression resides in the patient's age (1). The overlapping biology justifies merging PPMS and SPMS patients into a single Progressive MS (PMS) category, as is done in this study.…”

Ocrelizumab zur Behandlung der Multiplen Sklerose

“…Ferner lieferten zahlreiche retrospektive Analysen und eine Subgruppenanalyse Hinweise dafür, dass Rituximab sowohl effektiv bei aggressiver RMS bzw. progressiver MS sein kann [33][34][35][36][37][38][39] als auch den MS-Therapien der 1. Generation (i.e.…”

Anti-inflammatory and Neuroprotective Agents in Clinical Trials for CNS Disease and Injury: Where Do We Go From Here?

“…Ocrelizumab and Rituximab are two anti-CD20 antibodies used for the treatment of MS. Anti-B cell reagents such as these have been shown to reduce the relapse rate and presence of new lesions in the CNS ( 233 ). In several identically designed phase III studies, Ocrelizumab showed efficacy in treatment when compared to interferon-beta 1a with regard to improved outcomes in areas such as disability progression and suppression of new inflammatory lesions in the brain detected by magnetic resonance imaging (MRI) ( 234 ) (NCT01247324, NCT01194570, and NCT01412333). Similarly, Rituximab administration reduced inflammatory brain lesions along with a decrease in clinical relapses for 48 weeks ( 235 ) (NCT00097188).…”