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Randomized Controlled Trial
. 2023 May;29(6):741-747.
doi: 10.1177/13524585231162586. Epub 2023 May 6.

Ocrelizumab-treated patients with relapsing multiple sclerosis show volume loss rates similar to healthy aging

Shannon Kolind  1 , Laura Gaetano  2 , Haz-Edine Assemlal  3 , Corrado Bernasconi  2 , Ulrike Bonati  2 , Colm Elliott  3 , Niels Hagenbuch  2 , Stefano Magon  2 , Douglas L Arnold  4 , Anthony Traboulsee  1
Affiliations
Randomized Controlled Trial

Ocrelizumab-treated patients with relapsing multiple sclerosis show volume loss rates similar to healthy aging

Shannon Kolind et al. Mult Scler. 2023 May.

Abstract

Background: Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system characterized by two major and interconnected hallmarks: inflammation and progressive neurodegeneration.

Objective: The aim of this work was to compare neurodegenerative processes, in the form of global and regional brain volume loss rates, in healthy controls (HCs) and in patients with relapsing MS (RMS) treated with ocrelizumab, which suppresses acute inflammation.

Methods: Whole brain, white matter, cortical gray matter, thalamic, and cerebellar volume loss rates were assessed in 44 HCs that were part of a substudy in the OPERA II randomized controlled trial (NCT01412333) and 59 patients with RMS enrolled in the same substudy as well as age- and sex-matched patients in OPERA I (NCT01247324) and II. Volume loss rates were computed using random coefficients models over a period of 2 years.

Results: Ocrelizumab-treated patients showed global and regional brain volume loss rates that were approaching that of HCs.

Conclusion: These findings are consistent with an important role of inflammation on overall tissue loss and the role of ocrelizumab in reducing this phenomenon.

Keywords: Relapsing multiple sclerosis; brain volume loss; ocrelizumab.

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Conflict of interest statement

The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: S.K. reports grants and consulting fees from Roche; grants and consulting fees from Sanofi-Genzyme; consulting fees from Novartis; and grants from Biogen. L.G. was an employee of and shareholder in F. Hoffmann-La Roche Ltd. at the time of the project. She is now an employee of Novartis AG. H-E.A. is an employee of NeuroRx Research. C.B. is a contractor for F. Hoffmann-La Roche Ltd. U.B. is an employee of and shareholder in F. Hoffmann-La Roche Ltd. C.E. is an employee of NeuroRx Research and has received speaker honoraria from EMD Serono. N.H. is an employee of and shareholder in F. Hoffmann-La Roche Ltd. S.M. is an employee of and shareholder in F. Hoffmann-La Roche Ltd. D.L.A. reports consulting fees from Albert Charitable Trust, Alexion Pharma, Biogen, Celgene, Frequency Therapeutics, Genentech, Med-Ex Learning, Merck, Novartis, Population Council, Receptos, Roche, and Sanofi-Aventis; grants from Biogen, Immunotec, and Novartis; and an equity interest in NeuroRx ‘Research’?. A.T. reports grants and personal fees from Roche; grants and personal fees from Sanofi-Genzyme; personal fees from Novartis; and personal fees from EMD Serono outside the submitted work.

Figures

Figure 1.
Figure 1.
Annualized percentage changes [mean (SD)] in WB, WM, CGM, THAL, and CBL volume in ocrelizumab-treated patients with RMS, interferon-treated patients with RMS, and healthy controls. Annualized percentage changes were derived using each subject’s individual volume loss rate calculated by the mixed-effects models (random intercepts, random slopes). Three comparisons with HCs were carried out: the first with ocrelizumab-treated patients who participated in the original substudy (“Same site OCR-treated patients with RMS vs HCs”) using data at Week 48, Week 96, and OLE Week 46; the second with age- and sex-matched ocrelizumab-treated patients who participated in the larger OPERA I/II trial (“Matched OCR-treated patients with RMS versus HCs”) using data at Week 48, Week 96, and OLE Week 46; the third with age- and sex-matched interferon-treated patients who participated in the larger OPERA I/II trial (“Matched IFN-treated patients with RMS versus HCs”) using data at baseline, Week 48, and Week 96. CBL: cerebellum; CGM: cortical gray matter; HC: healthy control; IFN: interferon β-1a; OCR: ocrelizumab; OLE: open-label extension; RMS: relapsing multiple sclerosis; SD: standard deviation; THAL: thalamus; WB: whole brain; WM: white matter.
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