Information sourced from NEJM Journal Watch:
Ocrelizumab Demonstrates Superiority to Interferon in Relapsing Multiple Sclerosis
Compared with high-dose interferon, relapses were reduced by 47%, disability by 40%, and new lesions after 3 months by >95%.
For this multicenter, randomized, double-blind, placebo-controlled, manufacturer-sponsored, phase III study of the investigational drug ocrelizumab (see also NEJM JW Neurol Mar 2017 and N Engl J Med 2017; 376:280), investigators recruited 1656 patients with relapsing multiple sclerosis (MS) and recent disease activity. Two independent but similar trials (OPERA I and OPERA II) were pooled for analysis. Patients received either ocrelizumab (two 300-mg doses separated by 2 weeks, followed by one 600-mg dose every 6 months) or thrice-weekly interferon β-1a (IFN).
During the 96-week trial period, the annualized relapse rate was reduced by 47% with ocrelizumab versus IFN. Confirmed disability worsening was reduced by 40%. No evidence of disease activity was observed in 48% of the ocrelizumab group versus in 25% to 29% of those on IFN. Gadolinium-enhancing lesions were reduced by 94%. Between weeks 24 and 48, new and active lesions were reduced by 95%, increasing to 98% by week 96.
Ocrelizumab was associated with a small increased rate of upper respiratory tract infections and nasopharyngitis but no difference in serious infections. No participant experienced an opportunistic infection during this 96-week trial. Infusion reactions were more common with ocrelizumab than with IFN (34% vs. 10%), usually mild or moderate and occurring with the first dose; one infusion reaction, with no reported complications, led to a patient’s study withdrawal. Neoplasms occurred in four ocrelizumab recipients (2 breast carcinoma, 1 renal cell carcinoma, 1 melanoma) and two IFN recipients (mantle cell lymphoma and squamous cell chest carcinoma).
Ocrelizumab is highly effective for relapsing MS and has a convenient semiannual dosing schedule. The results are surprising, because B cells were previously thought less important than T cells, and IFN has direct effects on reducing blood–brain barrier breakdown and new lesion formation by MRI. Early safety appears favorable, but long-term studies and postmarketing surveillance are necessary. Pending FDA approval, this appears to be a promising option for patients needing to switch treatment owing to disease activity and for patients presenting with more concerning prognostic features.
Robert T. Naismith, MD reviewing Hauser SL et al. N Engl J Med 2017 Jan 19.
Dr. Naismith has received honoraria for consulting with Genentech, manufacturer of ocrelizumab.
Hauser SL et al. Ocrelizumab versus interferon beta-1a in relapsing multiple sclerosis. N Engl J Med 2017 Jan 19; 376:221.
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