title: Daclizumab HYP versus Interferon Beta-1a in Relapsing Multiple Sclerosis.
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.).
authors.affiliation: 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.).
authors.forename: Ludwig
authors.initials: L
authors.lastname: Kappos
authors.forename: Heinz
authors.initials: H
authors.lastname: Wiendl
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Selmaj
authors.forename: Douglas L
authors.initials: DL
authors.lastname: Arnold
authors.forename: Eva
authors.initials: E
authors.lastname: Havrdova
authors.forename: Alexey
authors.initials: A
authors.lastname: Boyko
authors.forename: Michael
authors.initials: M
authors.lastname: Kaufman
authors.forename: John
authors.initials: J
authors.lastname: Rose
authors.forename: Steven
authors.initials: S
authors.lastname: Greenberg
authors.forename: Marianne
authors.initials: M
authors.lastname: Sweetser
authors.forename: Katherine
authors.initials: K
authors.lastname: Riester
authors.forename: Gilmore
authors.initials: G
authors.lastname: O'Neill
authors.forename: Jacob
authors.initials: J
authors.lastname: Elkins
mesh_terms: D000276:Adjuvants, Immunologic / Q000009:adverse effects / Q000627:therapeutic use*; D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use*; D000077561:Daclizumab; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000009:adverse effects / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000009:adverse effects / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy*
chemical_list: D000276:Adjuvants, Immunologic; D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D016899:Interferon-beta; D000077561:Daclizumab; D000068556:Interferon beta-1a