Ocrelizumab associated with lower progression rates for primary progressive multiple sclerosis: The ORATORIO trial

1. A significant decrease in the rate of clinical and MRI progression was observed for Primary progressive multiple sclerosis (PPMS) patients that received ocrelizumab.

2. Rates of infections, infusion-related reactions, and neoplasms were higher in PPMS patients who received ocrelizumab, although there was a nonsignificant decrease in serious adverse events in patients who received ocrelizumab.

Evidence Rating Level: 1 (Excellent) 

Study Rundown: Primary progressive multiple sclerosis (PPMS) is a form of multiple sclerosis characterized by progressive neurologic decline that begins at the onset of symptoms. As B cells have been implicated in the pathogenesis of PPMS, this study investigated the efficacy and safety of the anti-CD20 monoclonal antibody ocrelizumab in patients with PPMS.

The rates of clinical progression at 12, 24, and 120 weeks were significantly lower in patients who received ocrelizumab compared to placebo at all three time points. There were significant reductions in the progression of T2-hyperintensities and loss of brain volume on MRI at 120 weeks in patients who received ocrelizumab versus placebo. The rates of any adverse event, serious adverse events, adverse events that led to discontinuation of the trial agent, death, infusion-related reactions, serious infections, and neoplasm were higher in patients who received ocrelizumab, although the rates of serious adverse events did not differ significantly between groups.

Click to read the study, published today in NEJM

Relevant Reading: B cell immunobiology in disease: evolving concepts from the clinic

In-Depth [randomized controlled trial]: The ORATORIO study was a phase 3, multi-centre, randomized, parallel-group, double-blind, placebo-controlled, trial. At 12 weeks, disability progression was confirmed in 32.9% of patients in the ocrelizumab group versus 39.3% of patients who received placebo (HR 0.76; 95%CI 0.58 to 0.98; p = 0.03). At 24 weeks, disability progression was confirmed in 29.6% of patients in the ocrelizumab group compared to 35.7% of patients who received placebo (HR 0.75; 95%CI 0.59 to 0.98; p = 0.04). At 120 weeks, worsened performance on the timed 25-foot walk was observed in 38.9% of patients in the ocrelizumab group compared to 55.1% of patients who received placebo (p = 0.04). Between 0 and 120 weeks, the volume of T2 hyperintensities decreased by 3.4% in the ocrelizumab group and increased by 7.4% in patients who received placebo (p < 0.001). Between 24 and 120 weeks, brain volume loss was 0.90% in patients in the ocrelizumab group versus 1.09% in patients who received placebo (p = 0.02). The proportion of patients who had ≥1 infusion-related reaction was 39.9% in patients who received ocrelizumab and 25.5% in patients who received placebo. The proportion of patients who had any serious adverse event was 20.4% in patients who received ocrelizumab and 22.2% of patients who received placebo. The proportion of patients who had serious infections was 6.2% in patients who received ocrelizumab and 5.9% in patients who received placebo. The proportion of patients who developed neoplasms was 2.3% in patients who received ocrelizumab and 0.8% in patients who received placebo.

Image: PD

©2017 2 Minute Medicine, Inc. All rights reserved. No works may be reproduced without expressed written consent from 2 Minute Medicine, Inc. Inquire about licensing here. No article should be construed as medical advice and is not intended as such by the authors or by 2 Minute Medicine, Inc.