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

Gut. 2006 Nov;55(11):1568-74. doi: 10.1136/gut.2005.089854. Epub 2006 Apr 7.

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%).

Conclusion: 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.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / blood
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized
  • Child
  • Colitis, Ulcerative / drug therapy*
  • Colitis, Ulcerative / immunology
  • Daclizumab
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Humans
  • Immunoglobulin G / administration & dosage*
  • Immunoglobulin G / adverse effects
  • Immunoglobulin G / blood
  • Immunoglobulin G / therapeutic use
  • Immunosuppressive Agents / administration & dosage*
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / blood
  • Immunosuppressive Agents / therapeutic use
  • Lymphocyte Count
  • Male
  • Middle Aged
  • Mucous Membrane / immunology
  • Receptors, Interleukin-2 / blood
  • Receptors, Interleukin-2 / immunology*
  • Severity of Illness Index
  • T-Lymphocytes / immunology
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Immunoglobulin G
  • Immunosuppressive Agents
  • Receptors, Interleukin-2
  • Daclizumab