1Queen Mary University of London, London, United Kingdom, 2McGill University, 3NeuroRx Research, Montreal, QC, Canada, 4University Hospital of Strasbourg, Strasbourg, France,5Technische Universität München, 6Munich Cluster for Systems Neurology (SyNergy), Munich, Germany, 7Hospital Vall d’Hebron University, Barcelona, Spain, 8University of Miami, Miami, FL, United States, 9F. Hoffmann-La Roche Ltd., Basel, Switzerland, 10Genentech, Inc., South San Francisco, CA,11University of Texas Health Science Center at Houston, Houston, TX, United StatesBackground: Data from Phase III trials suggest that selective B-cell targeting may be a potential therapeutic approach in relapsing and primary progressive multiple sclerosis (PPMS). Ocrelizumab (OCR), a humanised monoclonal antibody that selectively targets CD20+ B cells, has shown superior efficacy compared with placebo (PBO) in the Phase III ORATORIO study in patients with PPMS, in which the primary endpoint was 12-week confirmed disability progression (CDP). To address limitations in using the Expanded Disability Status Scale to define clinical disability progression, a composite measure of CDP (cCDP), which also includes measures of upper extremity function and ambulation speed, was used to assess the effect of OCR in patients with PPMS.
Objective: To assess the effect of OCR on 12- and 24-week cCDP in patients with PPMS.
Methods: Patients were randomised (2:1) to receive OCR 600mg as two 300mg intravenous infusions 14 days apart or matching PBO every 24 weeks for ≥120 weeks until an overall prespecified number of CDP events occurred. cCDP was defined as time to first onset of either CDP, ≥20% worsening on the timed 25-foot walk (T25FW) test or ≥20% worsening on the 9-hole peg test (9HPT) sustained for ≥12 or ≥24 weeks. In this exploratory analysis of 12- and 24-week cCDP among the ORATORIO intention-to-treat population, 244 PBO- and 488 OCR-treated patients were evaluable.
Results: Compared with PBO, OCR significantly reduced the risk of 12- and 24-week CDP by 24% (hazard ratio [HR] [95% confidence interval (CI)]: 0.76 [0.59-0.98]; p=0.0321) and 25% (HR [95% CI]: 0.75 [0.58-0.98]; p=0.0365), respectively. OCR vs PBO reduced the risk of 12- and 24-week cCDP by 26% (HR [95% CI]: 0.74 [0.61-0.89]; p=0.0014) and 29% (HR [95% CI]: 0.71 [0.58-0.87]; p=0.0008), respectively. Compared with PBO, OCR also consistently and significantly reduced the risk of 12- and 24-week confirmed ≥20% worsening on T25FW by 25% (HR [95% CI]: 0.75 [0.61-0.92]; p=0.0053) and 27% (HR [95% CI]: 0.73 [0.59-0.91]; p=0.0055), respectively, and the risk of 12- and 24-week confirmed ≥20% worsening on 9HPT by 44% (HR [95% CI]: 0.56 [0.41-0.78]; p=0.0004) and 45% (HR [95% CI]: 0.55 [0.38-0.77]; p=0.0006), respectively.
Conclusions: In ORATORIO, OCR treatment showed consistent benefit on disability progression, ambulation and upper limb function, as demonstrated by significant reduction in the risk of cCDP in patients with PPMS.
Sponsored by F. Hoffmann-La Roche Ltd.
COI ProfG multiple