title: Daclizumab high-yield process in relapsing-remitting multiple sclerosis (SELECT): a randomised, double-blind, placebo-controlled trial.
abstract: BACKGROUND
  Daclizumab, a humanised monoclonal antibody, modulates interleukin-2 signalling by blocking the α subunit (CD25) of the interleukin-2 receptor. We assessed whether daclizumab high-yield process (HYP) would be effective when given as monotherapy for a 1 year treatment period in patients with relapsing-remitting multiple sclerosis.
  
  
  METHODS
  We did a randomised, double-blind, placebo-controlled trial at 76 centres in the Czech Republic, Germany, Hungary, India, Poland, Russia, Ukraine, Turkey, and the UK between Feb 15, 2008, and May 14, 2010. Patients aged 18-55 years with relapsing-remitting multiple sclerosis were randomly assigned (1:1:1), via a central interactive voice response system, to subcutaneous injections of daclizumab HYP 150 mg or 300 mg, or placebo, every 4 weeks for 52 weeks. Patients and study personnel were masked to treatment assignment, except for the site pharmacist who prepared the study drug for injection, but had no interaction with the patient. The primary endpoint was annualised relapse rate. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00390221.
  
  
  RESULTS
  204 patients were assigned to receive placebo, 208 to daclizumab HYP 150 mg, and 209 to daclizumab HYP 300 mg, of whom 188 (92%), 192 (92%), and 197 (94%), respectively, completed follow-up to week 52. The annualised relapse rate was lower for patients given daclizumab HYP 150 mg (0·21, 95% CI 0·16-0·29; 54% reduction, 95% CI 33-68%; p<0·0001) or 300 mg (0·23, 0·17-0·31, 50% reduction, 28-65%; p=0·00015) than for those given placebo (0·46, 0·37-0·57). More patients were relapse free in the daclizumab HYP 150 mg (81%) and 300 mg (80%) groups than in the placebo group (64%; p<0·0001 in the 150 mg group and p=0·0003 in the 300 mg group). 12 (6%) patients in the placebo group, 15 (7%) of those in the daclizumab 150 mg group, and 19 (9%) in the 300 mg group had serious adverse events excluding multiple sclerosis relapse. One patient given daclizumab HYP 150 mg who was recovering from a serious rash died because of local complication of a psoas abscess.
  
  
  CONCLUSIONS
  Subcutaneous daclizumab HYP administered every 4 weeks led to clinically important effects on multiple sclerosis disease activity during 1 year of treatment. Our findings support the potential for daclizumab HYP to offer an additional treatment option for relapsing-remitting disease.
  
  
  BACKGROUND
  Biogen Idec and AbbVie Biotherapeutics Inc.
authors.affiliation: St Josef-Hospital, Ruhr-University Bochum, Bochum, Germany. ralf.gold@ruhr-uni-bochum.de
authors.forename: Ralf
authors.initials: R
authors.lastname: Gold
authors.forename: Gavin
authors.initials: G
authors.lastname: Giovannoni
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Selmaj
authors.forename: Eva
authors.initials: E
authors.lastname: Havrdova
authors.forename: Xavier
authors.initials: X
authors.lastname: Montalban
authors.forename: Ernst-Wilhelm
authors.initials: EW
authors.lastname: Radue
authors.forename: Dusan
authors.initials: D
authors.lastname: Stefoski
authors.forename: Randy
authors.initials: R
authors.lastname: Robinson
authors.forename: Katherine
authors.initials: K
authors.lastname: Riester
authors.forename: Jitesh
authors.initials: J
authors.lastname: Rana
authors.forename: Jacob
authors.initials: J
authors.lastname: Elkins
authors.forename: Gilmore
authors.initials: G
authors.lastname: O'Neill
mesh_terms: D000293:Adolescent; D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000009:adverse effects; D000077561:Daclizumab; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005060:Europe; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage* / Q000009:adverse effects; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000175:diagnosis* / Q000188:drug therapy*; D011788:Quality of Life; D012016:Reference Values; D018570:Risk Assessment; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G; C000598527:daclizumab HYP; D000077561:Daclizumab