P 1 Effect of ocrelizumab on magnetic resonance imaging markers of neurodegeneration in patients with relapsing multiple sclerosis – analysis of the phase III, double-blind, double-dummy, interferon beta-1a- controlled OPERA I and OPERA II studies. Issue 10 (October 2017)

• Record Type: Journal Article
• Authors: Ziemssen, T.; Arnold, D.L.; Bar-Or, A.; Comi, G.; Hartung, H.P.; Hauser, S.L.; Kappos, L.; Lublin, F.; Selmaj, K.; Traboulsee, A.; Masterman, D.; Chin, P.; Garren, H.; Wolinsky, J.S.
• Is Part Of: Clinical neurophysiology. Volume 128:Issue 10(2017:Oct.)
• Page Start: e326
• Publication Date: 2017-10
• Subjects: Neurophysiology -- Periodicals; Electroencephalography -- Periodicals; Electromyography -- Periodicals; Neurology -- Periodicals; 612.8
• DOI: 10.1016/j.clinph.2017.06.080
• Languages: English
• ISSNs: 1388-2457

Abstract

Abstract : Background: Ocrelizumab (OCR) is a humanised monoclonal antibody that selectively targets CD20+B cells. The pathogenesis of multiple sclerosis (MS), including neurodegeneration, is thought to be influenced by B cells. Volumetric magnetic resonance imaging (MRI) measurements can be used to assess neurodegeneration. Objective: To evaluate the effect of OCR vs interferon beta-1a (IFN β -1a) on brain MRI markers of neurodegeneration in patients with relapsing MS enrolled in two identical Phase III, randomised, double-blind, double-dummy trials (OPERA I and OPERA II). Methods: In OPERA I and OPERA II, patients were randomised (1:1) to receive OCR 600 mg via intravenous infusion every 24 weeks or subcutaneous IFN β -1a 44 μ g three-times weekly over 96 weeks. MRI endpoints thought to be related to neurodegeneration included the change in whole brain volume, change in cortical grey matter volume and change in cerebral white matter volume. Results: Compared with IFN β -1a, OCR reduced the rate of whole brain volume loss from baseline to Week 96 by 23.5% ( p < 0.0001) and 23.8% ( p = 0.0001), and from Week 24 to Week 96 by 22.8% ( p = 0.0042) and 14.9% ( p = 0.0900) in OPERA I and OPERA II, respectively. OCR-treated patients showed a smaller mean percentage of cortical grey matter volume loss compared with IFN β -1a from baseline to Week 96, with a mean difference of 0.273% ( p = 0.0005) in OPERA I and 0.516% ( p < 0.0001) in OPERA II. In OPERA I, OCR- treated patients also showed a smaller mean percentage volume loss of cerebral white matter compared with IFN β -1a from baseline to Week 96, with a mean difference of 0.261% ( p = 0.0024); in OPERA II, there was no difference ( p = 0.2748) in cerebral white matter volume loss in patients treated with OCR compared with IFN β -1a from baseline to Week 96. Conclusion: The rate of neurodegeneration as measured by whole brain, cortical grey and cerebral white matter volume loss on MRI was reduced by OCR compared with IFN β -1a in patients with relapsing MS over 96 weeks. This study is sponsored by F. Hoffmann-La Roche Ltd.