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N Engl J Med. 2015 Oct 8;373(15):1418-28. doi: 10.1056/NEJMoa1501481.

Daclizumab HYP versus Interferon Beta-1a in Relapsing Multiple Sclerosis.

Author information

1
From the Neurologic Clinic and Policlinic, the Departments of Medicine, Clinical Research, and Biomedicine and Biomedical Engineering, University Hospital, Basel, Switzerland (L.K.); the Department of Neurology, University of Münster, Münster, Germany (H.W.); the Department of Neurology, Medical University of Lodz, Lodz, Poland (K.S.); NeuroRx Research and Montreal Neurological Institute, McGill University - both in Montreal (D.L.A.); the Department of Neurology, First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic (E.H.); the Department of Neurology and Neurosurgery, Russian National Research Medical University, and Moscow Multiple Sclerosis Center - both in Moscow (A.B.); Cole Neurological Institute, University of Tennessee, Knoxville (M.K.); the Department of Neurology and the Neurovirology Research Laboratory, University of Utah, and the Veterans Affairs Salt Lake City Health Care System - both in Salt Lake City (J.R.); AbbVie Biotherapeutics, Redwood City, CA (S.G.); and Biogen, Cambridge, MA (M.S., K.R., G.O., J.E.).

Abstract

BACKGROUND:

Daclizumab high-yield process (HYP) is a humanized monoclonal antibody that binds to CD25 (alpha subunit of the interleukin-2 receptor) and modulates interleukin-2 signaling. Abnormalities in interleukin-2 signaling have been implicated in the pathogenesis of multiple sclerosis and other autoimmune disorders.

METHODS:

We conducted a randomized, double-blind, active-controlled, phase 3 study involving 1841 patients with relapsing-remitting multiple sclerosis to compare daclizumab HYP, administered subcutaneously at a dose of 150 mg every 4 weeks, with interferon beta-1a, administered intramuscularly at a dose of 30 μg once weekly, for up to 144 weeks. The primary end point was the annualized relapse rate.

RESULTS:

The annualized relapse rate was lower with daclizumab HYP than with interferon beta-1a (0.22 vs. 0.39; 45% lower rate with daclizumab HYP; P<0.001). The number of new or newly enlarged hyperintense lesions on T2-weighted magnetic resonance imaging (MRI) over a period of 96 weeks was lower with daclizumab HYP than with interferon beta-1a (4.3 vs. 9.4; 54% lower number of lesions with daclizumab HYP; P<0.001). At week 144, the estimated incidence of disability progression confirmed at 12 weeks was 16% with daclizumab HYP and 20% with interferon beta-1a (P=0.16). Serious adverse events, excluding relapse of multiple sclerosis, were reported in 15% of the patients in the daclizumab HYP group and in 10% of those in the interferon beta-1a group. Infections were more common in the daclizumab HYP group than in the interferon beta-1a group (in 65% vs. 57% of the patients, including serious infection in 4% vs. 2%), as were cutaneous events such as rash or eczema (in 37% vs. 19%, including serious events in 2% vs. <1%) and elevations in liver aminotransferase levels that were more than 5 times the upper limit of the normal range (in 6% vs. 3%).

CONCLUSIONS:

Among patients with relapsing-remitting multiple sclerosis, daclizumab HYP showed efficacy superior to that of interferon beta-1a with regard to the annualized relapse rate and lesions, as assessed by means of MRI, but was not associated with a significantly lower risk of disability progression confirmed at 12 weeks. The rates of infection, rash, and abnormalities on liver-function testing were higher with daclizumab HYP than with interferon beta-1a. (Funded by Biogen and AbbVie Biotherapeutics; DECIDE ClinicalTrials.gov number, NCT01064401.).

PMID:
26444729
DOI:
10.1056/NEJMoa1501481
[Indexed for MEDLINE]
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