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.
NEJM Journal Watch is produced by NEJM Group, a division of the Massachusetts Medical Society. Copyright ©2017 Massachusetts Medical Society. All rights reserved.
The above message comes from NEJM Journal Watch, who is solely responsible for its content.
You have received this email because you requested follow-up information to an Epocrates DocAlert® message. For more information about Epocrates, please click here.
For questions, feedback, or suggestions regarding Epocrates DocAlert® messages, please contact the Medical Information Team at email@example.com.