Five-year efficacy outcomes of ocrelizumab in relapsing multiple sclerosis: A propensity-matched comparison of the OPERA studies with other disease-modifying therapies in real-world lines of treatments
- PMID: 39290861
- PMCID: PMC11406495
- DOI: 10.1177/11795735241260563
Five-year efficacy outcomes of ocrelizumab in relapsing multiple sclerosis: A propensity-matched comparison of the OPERA studies with other disease-modifying therapies in real-world lines of treatments
Abstract
Background: Clinical trials comparing the efficacy of ocrelizumab (OCR) with other disease-modifying therapies (DMTs) other than interferon (IFN) β-1a in relapsing multiple sclerosis (RMS) are lacking.
Objectives: To compare the treatment effect of OCR vs six DMTs' (IFN β-1a, glatiramer acetate, fingolimod, dimethyl fumarate, teriflunomide, natalizumab) treatment pathways used in clinical practice by combining clinical trial and real-world data.
Methods: Patient-level data from OPERA trials and open-label extension phase, and from the German NeuroTransData (NTD) MS registry, were used to build 1:1 propensity score-matched (PSM) cohorts controlling for seven baseline covariates, including brain imaging activity. Efficacy outcomes were time to first relapse and time to 24-week confirmed disability progression over 5.5 years of follow-up. Intention-to-treat analysis using all outcome data irrespective of treatment switch was applied.
Results: The analyses included 611 OPERA patients and 7141 NTD patients. We built 12 paired-matched cohorts (six for each outcome, two for each DMT) to compare efficacy of OCR in OPERA with each DMT treatment pathway in NTD. Post-matching, baseline covariates and PS were well balanced (standardized mean difference <.2 for all cohorts). Over 5.5 years, patients treated with OCR showed a statistically significant reduction in the risk of relapse (hazard ratios [HRs] .30 to .54) and disability progression (HRs .51 to .67) compared with all index therapies and their treatment switching pathways in NTD. Treatment switch and/or discontinuation occurred frequently in NTD cohorts.
Conclusion: OCR demonstrates superiority in controlling relapses and disability progression in RMS compared with real-world treatment pathways over a 5.5-year period. These analyses suggest that high-efficacy DMTs and high treatment persistence are critical to achieve greatest clinical benefit in RMS.
Registration: OPERA I (NCT01247324), OPERA II (NCT01412333).
Keywords: Multiple sclerosis; comparative effectiveness research; ocrelizumab; real-world data; treatment pathways.
© The Author(s) 2024.
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: F. Hoffmann-La Roche Ltd., Basel, Switzerland, provided financial support for the study and publication of this manuscript. Writing and editorial support was provided by Articulate Science, UK. E Muros-Le Rouzic is an employee of and shareholder in F. Hoffmann-La Roche Ltd. Y Heer was an employee of PricewaterhouseCoopers and contracted to perform statistical projects for NeuroTransData at the time of this analysis. S Yiu is an employee of Roche Products Ltd. V Tozzi is an employee of PricewaterhouseCoopers and contracted to perform statistical projects for NeuroTransData at the time of this analysis. S Braune has received honoraria from Kassenärztliche Vereinigung Bayerns and health maintenance organizations for patient care; and from Biogen, Merck, NeuroTransData, Novartis, and Roche for consulting, project management, clinical studies, and lectures; he also received honoraria and expense compensation as a board member of NeuroTransData. P van Hövell was an employee of PricewaterhouseCoopers and contracted to perform statistical projects for NeuroTransData at the time of this analysis. A Bergmann has received consultancy fees from advisory board, speaker, and other activities for NeuroTransData; project management and clinical studies for and travel expenses from Novartis and Servier. C Bernasconi is a consultant for F. Hoffmann-La Roche Ltd. F Model was an employee of and shareholder in F. Hoffmann-La Roche Ltd. at the time of this analysis and is now an employee of Denali Therapeutics. L Craveiro is an employee of and shareholder in F. Hoffmann-La Roche Ltd.
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