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 Medicine and Melbourne Brain Centre The Royal Melbourne Hospital University of Melbourne Melbourne Victoria Australia

Department of Neurology and Center of Clinical Neuroscience 1st Faculty of Medicine Charles University and General University Hospital Prague Czech Republic

Department of Neurology and Center of Clinical Neuroscience General University Hospital and Charles University Prague Czech Republic

Department of Neurology Craigavon Area Hospital Craigavon UK

Department of Neurology Neuroimmunology Centre d'Esclerosi Múltiple de Catalunya Hospital Universitari Vall d'Hebron Barcelona Spain

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

IRCCS Istituto delle Scienze Neurologiche di Bologna UOSI Riabilitazione Sclerosi Multipla Bologna Italy

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

Research Center for Clinical Neuroimmunology and Neuroscience and MS Center University Hospital Basel and University of Basel Basel Switzerland

Royal Hobart Hospital Hobart Tasmania Australia

University G d'Annunzio Chieti Italy

University of California San Francisco California USA

Vithas Nisa Hospital Seville Spain

Zuyderland Ziekenhuis Sittard The Netherlands

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ClinicalTrials.gov
NCT01194570

ANZCTR
ACTRN12605000455662