OPERA I/OPERA II results for ocrelizumab in RRMS


REPORT FROM ECTRIMS – BARCELONA, SPAIN – OCTOBER 7-10, 2015 – The much-anticipated results of the OPERA I and II studies of ocrelizumab in relapsing MS were presented on Friday and indicate that the anti-CD20 monoclonal antibody is highly effective compared to interferon-beta-1a s.c. (Hauser et al. ECTRIMS 2015; abstract 190).

OPERA I and II were concurrent phase III trials that randomized 1,656 subjects with relapsing MS to ocrelizumab 600 mg q24 weeks or IFNbeta-1a three times/week for 96 weeks. The primary endpoint was annualized relapse rate (ARR).

Ocrelizumab was dosed as two 300 mg infusions on days 1 and 15, followed by 600 mg infusions at 24-week intervals. Subjects also received low-dose (100 mg) methylprednisolone. Mean age of patients was 37 years; mean duration since MS symptom onset was 6-7 years; and mean EDSS score at baseline was 2.8. About 70% of patients were untreated in the two years prior to study entry; the treated subgroup had most commonly received an interferon. Most subjects had experienced >1 relapse in the preceding 12 months (mean 1.3) and 40% had >1 Gd+ lesions at baseline (mean 1.78-1.87 lesions) (Hauser et al. AAN 2015; abstract P07.201).

ARR was about 0.156 in the ocrelizumab group in both studies compared to 0.29 in the interferon groups, a reduction of 45-47%. The risk of 24-week confirmed disability progression was reduced 40% with ocrelizumab versus IFN. The number of Gd+ lesions was reduced 94-95%; and the number of new/enlarging T2 lesions was reduced 77%. The reduction in T2 lesions was >95% at later time points in the study. In an exploratory analysis, the rate of brain volume loss was reduced 23.5-23.8% with ocrelizumab in the two studies. About 47.5-47.9% in the ocrelizumab groups had no evidence of disease activity (NEDA), defined as no relapses, no confirmed disability progression and no Gd+ T1 or new/enlarging T2 lesions. This represented a 64-89% improvement over IFNbeta.

In a pooled analysis of safety data, the rate of serious adverse events was similar with IFN compared to ocrelizumab (8.7% vs. 6.9%). The rate of serious infections was 1.3% with ocrelizumab and 2.9% with IFN. No cases of opportunistic infection or progressive multifocal leukoencephalopathy (PML) were reported. The most common adverse event with ocrelizumab was infusion-related reactions (34%), which primarily occurred after the first infusion. Most infusion reactions were mild to moderate; there was one case of grade IV bronchospasm.

Dr. Hauser concluded that targeting CD20 B cells is an effective and well-tolerated approach for patients with relapsing MS.

Reviewer: Dr. Daniel Selchen, Head of Neurology, St. Michael’s Hospital, Toronto, Canada

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