Format

Send to

Choose Destination
Neurology. 2019 Sep 4. pii: 10.1212/WNL.0000000000008189. doi: 10.1212/WNL.0000000000008189. [Epub ahead of print]

Onset of clinical and MRI efficacy of ocrelizumab in relapsing multiple sclerosis.

Author information

1
From the Department of Radiology and Nuclear Medicine (F.B.), VU University Medical Centre, Amsterdam, the Netherlands; UCL Institutes of Healthcare Engineering and Neurology (F.B.), London, UK; Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research, Biomedicine and Biomedical Engineering (L.K.), University Hospital Basel, University of Basel, Switzerland; Department of Neurology (J.S.W.), McGovern Medical School, UTHealth, Houston, TX; Department of Radiology (D.K.B.L.), University of British Columbia, Vancouver, Canada; Department of Neurology and Center for Neuroinflammation and Experimental Therapeutics (A.B.-O.), University of Pennsylvania, Philadelphia; Department of Neurology, Medical Faculty (H.-P.H.), Heinrich-Heine University Düsseldorf, Germany; F. Hoffmann-La Roche Ltd. (S.B., A.S., J.N., H.K.), Basel, Switzerland; Genentech, Inc. (J.H., L.J.), South San Francisco; and Department of Neurology (S.L.H.), University of California, San Francisco. During completion of the work related to this article, S. Belachew was an employee of F. Hoffmann-La Roche Ltd.; his current affiliation is Biogen, Cambridge, MA. f.barkhof@vumc.nl.
2
From the Department of Radiology and Nuclear Medicine (F.B.), VU University Medical Centre, Amsterdam, the Netherlands; UCL Institutes of Healthcare Engineering and Neurology (F.B.), London, UK; Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research, Biomedicine and Biomedical Engineering (L.K.), University Hospital Basel, University of Basel, Switzerland; Department of Neurology (J.S.W.), McGovern Medical School, UTHealth, Houston, TX; Department of Radiology (D.K.B.L.), University of British Columbia, Vancouver, Canada; Department of Neurology and Center for Neuroinflammation and Experimental Therapeutics (A.B.-O.), University of Pennsylvania, Philadelphia; Department of Neurology, Medical Faculty (H.-P.H.), Heinrich-Heine University Düsseldorf, Germany; F. Hoffmann-La Roche Ltd. (S.B., A.S., J.N., H.K.), Basel, Switzerland; Genentech, Inc. (J.H., L.J.), South San Francisco; and Department of Neurology (S.L.H.), University of California, San Francisco. During completion of the work related to this article, S. Belachew was an employee of F. Hoffmann-La Roche Ltd.; his current affiliation is Biogen, Cambridge, MA.

Abstract

OBJECTIVE:

To assess the onset of ocrelizumab efficacy on brain 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 (A Study of Ocrelizumab in Comparison With Interferon Beta-1a [Rebif] in Participants With Relapsing Multiple Sclerosis) 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.

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center