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.
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.
Van Assche
G
G
Universitaire Ziekenhuizen Leuven, Inwendige Geneeskunde, UZ Gasthuisberg, Herestraat 49-B-3000, Leuven, Belgium. gert.vanassche@uz.kuleuven.ac.be
Sandborn
W J
WJ
Feagan
B G
BG
Salzberg
B A
BA
Silvers
D
D
Monroe
P S
PS
Pandak
W M
WM
Anderson
F H
FH
Valentine
J F
JF
Wild
G E
GE
Geenen
D J
DJ
Sprague
R
R
Targan
S R
SR
Rutgeerts
P
P
Vexler
V
V
Young
D
D
Shames
R S
RS
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
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D015375:Receptors, Interleukin-2; D000077561:Daclizumab