Risk of requiring a wheelchair in primary progressive multiple sclerosis: Data from the ORATORIO trial and the MSBase registry.

Background Reaching Expanded Disability Status Scale (EDSS) ≥7.0 represents the requirement for a wheelchair. Here we : (1) assess the effect of ocrelizumab on time to EDSS ≥7.0 over the ORATORIO (NCT01194570) double-blind and extended controlled periods (DBP+ECP); (2) quantify likely long-term benefits by extrapolating results; (3) 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 PPMS (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%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: -4.3-18.4]). In MSBase, the median time to 24-week confirmed EDSS ≥7.0 was 12.4 years. Conclusion 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.