To assess the efficacy of switching to or maintaining ocrelizumab therapy on 48-week confirmed disability progression (CDP) in the open-label extension (OLE) of the pooled OPERA I and OPERA II Phase III trials in relapsing multiple sclerosis (RMS).

In the double-blind period (DBP) of the pooled OPERA I and OPERA II trials (NCT01247324; NCT01412333), the risks of 12- and 24-week CDP were both reduced by 40% for ocrelizumab versus interferon (IFN) β1a (p<0.001 and p=0.003, respectively). These benefits were maintained through 3 years of the OLE. Longer time periods to CDP have not been assessed to date.

At the start of the OLE, patients continued ocrelizumab therapy or were switched from IFNβ1a to ocrelizumab (IFN-OCR). Time to onset of 48-week CDP (CDP48) was analyzed for the 2-year DBP and over 3 years of the OLE.

Overall, 80% of patients entered the OLE and 89% of these completed OLE Year 3. In the DBP, ocrelizumab reduced the risk of CDP48 by 57% (p<0.001) versus IFNβ1a. The proportion of patients with CDP48 was lower with continuous ocrelizumab versus IFN-OCR at OLE Years 1, 2 and 3 (6.5% vs 11.7%, Δ=5.2% [p<0.001]; 9.4% vs 14.1%, Δ=4.7% [p=0.007]; and 10.4% vs 15.7%, Δ=5.4% [p=0.004]).

The benefits of ocrelizumab on CDP48 observed in the 2-year DBP were greater than for 12- and 24-week CDP, potentially due to a higher specificity for permanent disability accumulation. The benefit was maintained after 3 years’ ocrelizumab treatment in the OLE. After 5 years of follow-up, the CDP48 benefits accrued in those initiating ocrelizumab 2 years earlier were maintained versus those switching from IFNβ1a to ocrelizumab at OLE baseline. These results support previous analyses of the sustained effect of ocrelizumab on the reduction of risk of disability progression in patients with RMS.