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Randomized Controlled Trial
. 2022 Apr;29(4):1238-1242.
doi: 10.1111/ene.14823. Epub 2021 May 5.

Risk of requiring a walking aid after 6.5 years of ocrelizumab treatment in patients with relapsing multiple sclerosis: Data from the OPERA I and OPERA II trials

Gavin Giovannoni  1 , Ludwig Kappos  2 , Jerome de Seze  3 , Stephen L Hauser  4 , James Overell  5 , Harold Koendgen  5 , Marianna Manfrini  5 , Qing Wang  5 , Jerry S Wolinsky  6
Affiliations
Randomized Controlled Trial

Risk of requiring a walking aid after 6.5 years of ocrelizumab treatment in patients with relapsing multiple sclerosis: Data from the OPERA I and OPERA II trials

Gavin Giovannoni et al. Eur J Neurol. 2022 Apr.

Abstract

Background and purpose: Requiring a walking aid is a fundamental milestone in multiple sclerosis (MS), represented by an Expanded Disability Status Scale (EDSS) score ≥6.0. In the present study, we assess the effect of ocrelizumab (OCR) on time to EDSS score ≥6.0 in relapsing MS.

Methods: Time to EDSS score ≥6.0 confirmed for ≥24 and ≥48 weeks was assessed over the course of 6.5 years (336 weeks) in the double-blind period (DBP) and open-label extension (OLE) period of the OPERA I (NCT01247324) and OPERA II (NCT01412333) studies.

Results: Time to reach EDSS score ≥6.0 was significantly delayed in those initially randomized to OCR versus interferon. Over 6.5 years, the risk of requiring a walking aid confirmed for ≥24 weeks was 34% lower among those who initiated OCR earlier versus delayed treatment (average hazard ratio [HR] DBP + OLE 0.66, 95% confidence interval [CI] 0.45-0.95; p = 0.024); the risk of requiring a walking aid confirmed for ≥48 weeks was 46% lower (average HR DBP+OLE 0.54, 95% CI 0.35-0.83; p = 0.004).

Conclusion: The reduced risk of requiring a walking aid in earlier initiators of OCR demonstrates the long-term implications of earlier highly effective treatment.

Keywords: disease progression; interferon beta 1a; multiple sclerosis; ocrelizumab; walking stick.

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Conflict of interest statement

G. Giovannoni has received personal compensation for serving as a consultant for F. Hoffmann‐La Roche Ltd, AbbVie, Actelion, Atara Biotherapeutics, Biogen, Celgene, Sanofi Genzyme, Genentech, Inc., GlaxoSmithKline, Merck Serono, Novartis and Teva, has received personal compensation from Elsevier for serving as an editor on MSARDs, and has received financial support for research activities from F. Hoffmann‐La Roche Ltd, Biogen, Merck, Merck Serono, Novartis, Sanofi Genzyme and Takeda. L. Kappos's institution (University Hospital Basel) received in the last 3 years and used exclusively for research support at the Department: steering committee, advisory board, consultancy fees and support of educational activities from Actelion, Allergan, Almirall, Baxalta, Bayer, Biogen, Celgene/Receptos, CSL‐Behring, Desitin, Excemed, Eisai, Genzyme, Japan Tobacco, Merck, Minoryx, Novartis, Pfizer, F. Hoffmann‐La Roche Ltd, Sanofi Aventis, Santhera and Teva, and license fees for Neurostatus‐UHB products. The Research of the MS Center in Basel has been supported by grants from Bayer, Biogen, Novartis, the Swiss MS Society, the Swiss National Research Foundation, Innosuisse, the European Union and Roche Research Foundations. J. de Seze has received consultancy fees and served as an expert for advisory boards for Alexion, Allergan, Almirall, Bayer, Biogen, Chugai, CSL Behring, F. Hoffmann‐La Roche Ltd, Genzyme, LFB, Merck, Novartis, Sanofi and Teva. S. L. Hauser serves on the board of trustees for Neurona and on scientific advisory boards for Alector, Annexon, Bionure and Molecular Stethoscope, and has received travel reimbursement and writing assistance from F. Hoffmann‐La Roche Ltd and Novartis for CD20‐related meetings and presentations. J. Overell is currently an employee and shareholder of F. Hoffmann‐La Roche Ltd. During his previous employment he received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Teva, Biogen, Celgene, EMD Serono, MedDay, Novartis, Roche, Sanofi Genzyme, WebMD Global and Allergan. His research and department were supported by grants from Sanofi Genzyme, Biogen, Novartis, and Roche. H. Koendgen is an employee and shareholder of F. Hoffmann‐La Roche Ltd. M. Manfrini is an employee and shareholder of F. Hoffmann‐La Roche Ltd. Q. Wang is an employee of F. Hoffmann‐La Roche Ltd. J. S. Wolinsky has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Acorda Therapeutics, Actelion, Alkermes, Brainstorm Cell Therapeutics, Celgene, EMD Serono, GeNeuro, GW Pharma Ltd, MedDay Pharmaceuticals, NervGen Pharma Corp, Novartis, Otsuka, PTC Therapeutics, Roche/Genentech and Sanofi Genzyme; royalties are received for out‐licensed monoclonal antibodies through UTHealth from Millipore Corporation.

Figures

FIGURE 1
FIGURE 1
(a) Time to walking aid (EDSS score ≥6.0) confirmed for ≥24 weeks in the OLE. (b) Time to walking aid (EDSS score ≥6.0) confirmed for ≥48 weeks in the OLE. Hazard ratios were estimated by Cox regression stratified by study, geographical region (United States vs. ROW), and baseline EDSS score (<4.0 vs. ≥4.0). Comparison of the survival distributions used the log‐rank test. Patients with a post‐baseline EDSS score ≥6 sustained for ≥24 or ≥48 weeks were considered as having an event. Patients with an EDSS score ≥6 at the time of treatment discontinuation with no further EDSS score were censored. Patients with missing baseline EDSS score were excluded from the analysis. CDP, confirmed disability progression; DBP, double‐blind period; HR, hazard ratio; IFN, interferon; OCR, ocrelizumab; OLE, open‐label extension; ROW, rest of world
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