title: Daclizumab, a humanised monoclonal antibody to the interleukin 2 receptor (CD25), for the treatment of moderately to severely active ulcerative colitis: a randomised, double blind, placebo controlled, dose ranging trial.
abstract: BACKGROUND
  An uncontrolled pilot study demonstrated that daclizumab, a humanised monoclonal antibody to the interleukin 2 receptor (CD25), might be effective for the treatment of active ulcerative colitis.
  
  
  METHODS
  A randomised, double blind, placebo controlled trial was conducted to evaluate the efficacy of daclizumab induction therapy in patients with active ulcerative colitis. A total of 159 patients with moderate ulcerative colitis were randomised to receive induction therapy with daclizumab 1 mg/kg intravenously at weeks 0 and 4, or 2 mg/kg intravenously at weeks 0, 2, 4, and 6, or placebo. The primary end point was induction of remission at week 8. Remission was defined as a Mayo score of 0 on both endoscopy and rectal bleeding components and a score of 0 or 1 on stool frequency and physician's global assessment components. Response was defined as a decrease from baseline in the Mayo score of at least 3 points.
  
  
  RESULTS
  Two per cent of patients receiving daclizumab 1 mg/kg (p = 0.11 v placebo) and 7% of patients receiving 2 mg/kg (p = 0.73) were in remission at week 8, compared with 10% of those who received placebo. Response occurred at week 8 in 25% of patients receiving daclizumab 1 mg/kg (p = 0.04) and in 33% of patients receiving 2 mg/kg (p = 0.30) versus 44% of those receiving placebo. Daclizumab was well tolerated. The most frequently reported adverse events in daclizumab treated patients compared with placebo treated patients were nasopharyngitis (14.6%) and pyrexia (10.7%).
  
  
  CONCLUSIONS
  Patients with moderate ulcerative colitis who are treated with daclizumab are not more likely to be in remission or response at eight weeks than patients treated with placebo.
authors.affiliation: Universitaire Ziekenhuizen Leuven, Inwendige Geneeskunde, UZ Gasthuisberg, Herestraat 49-B-3000, Leuven, Belgium. gert.vanassche@uz.kuleuven.ac.be
authors.forename: G
authors.initials: G
authors.lastname: Van Assche
authors.forename: W J
authors.initials: WJ
authors.lastname: Sandborn
authors.forename: B G
authors.initials: BG
authors.lastname: Feagan
authors.forename: B A
authors.initials: BA
authors.lastname: Salzberg
authors.forename: D
authors.initials: D
authors.lastname: Silvers
authors.forename: P S
authors.initials: PS
authors.lastname: Monroe
authors.forename: W M
authors.initials: WM
authors.lastname: Pandak
authors.forename: F H
authors.initials: FH
authors.lastname: Anderson
authors.forename: J F
authors.initials: JF
authors.lastname: Valentine
authors.forename: G E
authors.initials: GE
authors.lastname: Wild
authors.forename: D J
authors.initials: DJ
authors.lastname: Geenen
authors.forename: R
authors.initials: R
authors.lastname: Sprague
authors.forename: S R
authors.initials: SR
authors.lastname: Targan
authors.forename: P
authors.initials: P
authors.lastname: Rutgeerts
authors.forename: V
authors.initials: V
authors.lastname: Vexler
authors.forename: D
authors.initials: D
authors.lastname: Young
authors.forename: R S
authors.initials: RS
authors.lastname: Shames
mesh_terms: D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D002648:Child; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000276:immunology; D000077561:Daclizumab; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D009092:Mucous Membrane / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000097:blood / Q000276:immunology*; D012720:Severity of Illness Index; D013601:T-Lymphocytes / Q000276:immunology; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D015375:Receptors, Interleukin-2; D000077561:Daclizumab