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. 2024 Sep 13:16:11795735241260563.
doi: 10.1177/11795735241260563. eCollection 2024.

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

Erwan Muros-Le Rouzic  1 , Yanic Heer  2 , Sean Yiu  3 , Viola Tozzi  2 , Stefan Braune  4 , Philip van Hövell  2 , Arnfin Bergmann  4 , Corrado Bernasconi  1 , Fabian Model  1 , Licinio Craveiro  1 ; NTD study group
Affiliations

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

Erwan Muros-Le Rouzic et al. J Cent Nerv Syst Dis. .

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.

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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: 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.

Figures

Figure 1.
Figure 1.
Love plots for absolute standardized differences after PSM for matching factors defined for relapse and 24W-CDP outcomes. 24W-CDP, 24-week confirmed disability progression; DMF, dimethyl fumarate; EDSS, Expanded Disability Status Scale; FTY, fingolimod; GA, glatiramer acetate; Gd+, gadolinium-enhancing; IFN β-1a, interferon β-1a; NTD, NeuroTransData registry; NTZ, natalizumab; OCR, ocrelizumab; PSM, propensity score-matched; TERI, teriflunomide.
Figure 2.
Figure 2.
Time to first relapse in patients receiving OCR in OPERA vs patients receiving each index therapy in the NTD-matched cohorts over 288 weeks. CI, confidence interval; DMF, dimethyl fumarate; FTY, fingolimod; GA, glatiramer acetate; HR, hazard ratio; IFN β-1a, interferon β-1a; NTD, NeuroTransData registry; NTZ, natalizumab; OCR, ocrelizumab; TERI, teriflunomide.
Figure 3.
Figure 3.
Time to discontinuation of each index therapy in the NTD-matched cohorts for time to first relapse outcome over 288 weeks. DMF, dimethyl fumarate; FTY, fingolimod; GA, glatiramer acetate; IFN β-1a, interferon β-1a; NTD, NeuroTransData registry; NTZ, natalizumab; TERI, teriflunomide.
Figure 4.
Figure 4.
Time to 24W-CDP relapse in patients receiving OCR in OPERA vs patients receiving each index therapy in the NTD-matched cohorts over 288 weeks. 24W-CDP, 24-week confirmed disability progression; CI, confidence interval; DMF, dimethyl fumarate; FTY, fingolimod; GA, glatiramer acetate; HR, hazard ratio; IFN β-1a, interferon β-1a; NTD, NeuroTransData registry; NTZ, natalizumab; OCR, ocrelizumab; TERI, teriflunomide.
Figure 5.
Figure 5.
Time to discontinuation of each index therapy in the NTD-matched cohorts for time to 24W-CDP outcome over 288 weeks. 24W-CDP, 24-week confirmed disability progression; DMF, dimethyl fumarate; FTY, fingolimod; GA, glatiramer acetate; IFN β-1a, interferon β-1a; NTD, NeuroTransData registry; NTZ, natalizumab; TERI, teriflunomide.
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