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Risk of requiring a wheelchair in primary progressive multiple sclerosis: Data from the ORATORIO trial and the MSBase registry
H. Butzkueven, T. Spelman, D. Horakova, S. Hughes, C. Solaro, G. Izquierdo, E. Kubala Havrdová, F. Grand'Maison, A. Prat, M. Girard, R. Hupperts, M. Onofrj, A. Lugaresi, B. Taylor, MSBase Study Group, G. Giovannoni, L. Kappos, SL. Hauser, X....
Language English Country Great Britain
Document type Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't
PubMed
33724638
DOI
10.1111/ene.14824
Knihovny.cz E-resources
- MeSH
- Multiple Sclerosis, Chronic Progressive * drug therapy MeSH
- Humans MeSH
- Disease Progression MeSH
- Registries MeSH
- Multiple Sclerosis * drug therapy MeSH
- Wheelchairs * MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Randomized Controlled Trial MeSH
BACKGROUND AND PURPOSE: Reaching Expanded Disability Status Scale (EDSS) ≥7.0 represents the requirement for a wheelchair. Here we (i) assess the effect of ocrelizumab on time to EDSS ≥7.0 over the ORATORIO (NCT01194570) double-blind and extended controlled periods (DBP+ECP), (ii) quantify likely long-term benefits by extrapolating results, and (iii) assess the plausibility of extrapolations using an independent real-world cohort (MSBase registry; ACTRN12605000455662). METHODS: Post hoc analyses assessing time to 24-week confirmed EDSS ≥7.0 in two cohorts of patients with primary progressive multiple sclerosis (baseline EDSS 3.0-6.5) were investigated in ORATORIO and MSBase. RESULTS: In the ORATORIO DBP+ECP, ocrelizumab reduced the risk of 24-week confirmed EDSS ≥7.0 (hazard ratio = 0.54, 95% confidence interval [CI]: 0.31-0.92; p = 0.022). Extrapolated median time to 24-week confirmed EDSS ≥7.0 was 12.1 and 19.2 years for placebo and ocrelizumab, respectively (7.1-year delay [95% CI: -4.3 to 18.4]). In MSBase, the median time to 24-week confirmed EDSS ≥7.0 was 12.4 years. CONCLUSIONS: Compared with placebo, ocrelizumab significantly delayed time to 24-week confirmed wheelchair requirement in ORATORIO. The plausibility of the extrapolated median time to reach this milestone in the placebo group was supported by observed real-world data from MSBase. Extrapolated benefits for ocrelizumab over placebo could represent a truly meaningful delay in loss of ambulation and independence.
Belfast Health and Social Care Trust Belfast UK
CHUM and Universite de Montreal Montreal Quebec Canada
CRRF Mons Luigi Novarese Moncrivello Italy
Department of Neurology Craigavon Area Hospital Craigavon UK
Department of Neuroscience Central Clinical School Monash University Melbourne Victoria Australia
Dipartimento di Scienze Biomediche e Neuromotorie Università di Bologna Bologna Italy
F Hoffmann La Roche Ltd Basel Switzerland
McGovern Medical School The University of Texas Health Science Center at Houston Houston Texas USA
Neuro Rive Sud Quebec City Quebec Canada
Queen Mary University of London London UK
Royal Hobart Hospital Hobart Tasmania Australia
University G d'Annunzio Chieti Italy
University of California San Francisco California USA
References provided by Crossref.org
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