학술논문
Risk of requiring a wheelchair in primary progressive multiple sclerosis: Data from the ORATORIO trial and the MSBase registry
Document Type
article
Author
Butzkueven, Helmut; Spelman, Tim; Horakova, Dana; Hughes, Stella; Solaro, Claudio; Izquierdo, Guillermo; Havrdová, Eva Kubala; Grand'Maison, Francois; Prat, Alexandre; Girard, Marc; Hupperts, Raymond; Onofrj, Marco; Lugaresi, Alessandra; Taylor, Bruce; Group, the MSBase Study; Giovannoni, Gavin; Kappos, Ludwig; Hauser, Stephen L; Montalban, Xavier; Craveiro, Licinio; Freitas, Rita; Model, Fabian; Overell, James; Rouzic, Erwan Muros‐Le; Sauter, Annette; Wang, Qing; Wormser, David; Wolinsky, Jerry S
Source
European Journal of Neurology. 29(4)
Subject
Language
Abstract
Background and purposeReaching 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).MethodsPost 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.ResultsIn 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.ConclusionsCompared 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.