title: A pilot study on the use of the humanized anti-interleukin-2 receptor antibody daclizumab in active ulcerative colitis.
abstract: OBJECTIVE
  Medical therapy of refractory ulcerative colitis (UC) is associated with long-term side effects of cyclosporine and steroids. Because cyclosporine acts by inhibiting interleukin-2 (IL-2) production, we studied the efficacy and safety of humanized anti-IL2 receptor (CD25) antibodies daclizumab for refractory UC in an open label pilot study.
  
  
  METHODS
  Ten patients with chronically active UC received daclizumab, 1 mg/kg i.v. twice with a 4-wk interval. Clinical, endoscopic, and histological evaluation was scored at regular intervals. CD25 immunohistochemistry was followed in mucosal biopsies. The primary study endpoint was clinical improvement at wk 8.
  
  
  RESULTS
  Nine of 10 patients completed the study. The median clinical activity score decreased from a median of 8 (95% CI = 7.2-9.2) at baseline to 3.5 (95% CI = 1.4-4.9) at wk 8 (p < 0.005). Endoscopic scores were significantly decreased at wk 8 (wk 0: 8, 95% CI = 6.3-8.5; wk 8: 5.0, 95% CI = 2.6-6.3; p < 0.01). Mucosal biopsies showed a significant decrease in CD25+ cells, and there was a trend toward lower histology scores at wk 8. Quality of life as assessed by the Inflammatory Bowel Disease Questionnaire increased after therapy (baseline: 131, 95% CI = 119-178; wk 8: 169; 95% CI = 124-216, p < 0.05). Nausea was most frequently reported as an adverse event, but always in patients that were concomitantly started on azathioprine.
  
  
  CONCLUSIONS
  The anti-IL-2R antibody daclizumab was safe and well tolerated in acute UC. Patients experienced clinical benefit along with signs of endoscopic improvement, but further controlled trials are needed to determine the therapeutic benefit of this compound.
authors.affiliation: Department of Gastroenterology, University of Leuven, Belgium.
authors.forename: Gert
authors.initials: G
authors.lastname: Van Assche
authors.forename: Ignace
authors.initials: I
authors.lastname: Dalle
authors.forename: Maja
authors.initials: M
authors.lastname: Noman
authors.forename: Isolde
authors.initials: I
authors.lastname: Aerden
authors.forename: Caroline
authors.initials: C
authors.lastname: Swijsen
authors.forename: Katrien
authors.initials: K
authors.lastname: Asnong
authors.forename: Bart
authors.initials: B
authors.lastname: Maes
authors.forename: Jan
authors.initials: J
authors.lastname: Ceuppens
authors.forename: Karel
authors.initials: K
authors.lastname: Geboes
authors.forename: Paul
authors.initials: P
authors.lastname: Rutgeerts
mesh_terms: D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D003093:Colitis, Ulcerative / Q000188:drug therapy*; D000077561:Daclizumab; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000009:adverse effects / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D000077561:Daclizumab