To assess the effect of switching to or earlier initiation of ocrelizumab on 24-week confirmed disability progression (CDP), in the open-label extension (OLE) of ORATORIO (NCT01194570).

Efficacy and safety of ocrelizumab in primary progressive multiple sclerosis were demonstrated vs placebo in the Phase III ORATORIO study.

In the double-blind period (DBP), patients were randomized to ocrelizumab or placebo and followed for ≥120 weeks until a prespecified number of CDP events occurred. At completion of the DBP, patients remained on blinded treatment until the trial outcome was ascertained (extended controlled period; ECP). At OLE initiation, patients continued ocrelizumab (OCR-OCR) or switched from placebo to ocrelizumab (PBO-OCR). Time to onset of 24-week-CDP (increase from baseline Expanded Disability Status Scale [CDP-EDSS] score of ≥1 point if baseline EDSS≤5.5 or ≥0.5 points if baseline EDSS>5.5) and time-to-wheelchair confinement (EDSS≥7.0) were analyzed through Week 312.

Overall, 72% of patients entered the OLE. In the DBP, compared with placebo, ocrelizumab reduced the risk of 24-week-CDP by 25% (p=0.037). At Week 168 (12 weeks after the first patients entered the OLE), the proportion of patients with 24-week-CDP-EDSS in the PBO-OCR and OCR-OCR groups was 44.7% vs 33.3% (?=11.4%; p=0.005), respectively, and at Week 312 was 64.8% vs 51.7% (?13.1%; p=0.002). During the DBP+ECP+OLE, the risk of becoming wheelchair-confined was 42% lower (p=0.011) and the risk of 24-week-CDP was 28% lower (p=0.002) in the OCR-OCR group vs PBO-OCR. Results from 9-Hole Peg Test and Timed 25-Foot Walk will also be presented. The safety profile was generally consistent with the DBP.

After 6.5 study years (312 weeks), the proportion of patients with CDP-EDSS was lower in patients who initiated ocrelizumab earlier vs patients initially receiving placebo. Patients initiating ocrelizumab 3–5 study years earlier had significantly reduced risk of becoming wheelchair-confined vs patients switching from placebo.