OPERA I and OPERA II

The OPERA I (NCT01247324) and OPERA II (NCT01412333) trials in relapsing MS patients embodied two different phases. The initial, double-blind period (DBP) randomised 1,656 patients to receive ocrelizumab or interferon β-1a for a period of two years. The DBP was followed by the open-label extension (OLE) phase in which 1,325 patients either continued their ocrelizumab treatment or switched from interferon β-1a to ocrelizumab for an additional 3 years of treatment in the current analysis.

The investigators presented the 5-year data on the efficacy of maintaining or switching to ocrelizumab treatment on MRI-measured disease activity and brain atrophy, in the OLE phase of the Phase III OPERA I and OPERA II trials.

Overall, 88.6% of patients entering the OLE phase completed Year 3 of the OLE. The mean change in whole brain volume (WBV), from DBP baseline, was -1.874% at Year 5 in the continuous ocrelizumab group, compared with -2.154% in the interferon β-1a to ocrelizumab switch group (P=0.002).

The annualised change in WBV (cm³) remained low in the OLE for both groups, at less than 0.4% annually in the 5-year ocrelizumab group (-0.397% in Year 3, -0.32% in Year 4, and -0.354% in Year 5) and less than 0.45% in the switch group (-0.291% in Year 3, -0.437% in Year 4, and -0.359% in Year 5).

Loss in cortical grey matter volume (GMV) and white matter volume (WMV) was also significantly less with continuous ocrelizumab at Year 5. Patients who received ocrelizumab 2 years earlier had a mean change in cortical GMV of -2.018% by Year 5, versus -2.251% in those received it 2 years later (P=0.002). The mean change in WMV was -1.327% versus -1.620% by Year 5 respectively (P=0.004).

For MRI lesion activity, the rate of total T1 gadolinium-enhancing lesions had decreased from 0.491 per scan at Year 2 to 0.007 at Year 3 (OLE Year 1) in patients switched from interferon β-1a to ocrelizumab. The rate of total new/enlarging T2 lesions had decreased from 2.583 in Year 2 to 0.371 in OLE Year 1.