CDP571, a humanized monoclonal antibody to tumour necrosis factor-alpha, for steroid-dependent Crohn's disease: a randomized, double-blind, placebo-controlled trial.
BACKGROUND
More than 50% of patients with Crohn's disease become either steroid resistant or dependent. Accordingly, development of new treatments for steroid-dependent Crohn's disease is a research priority.


OBJECTIVE
To evaluate CDP571, a humanized antibody to tumour necrosis factor-alpha, for the treatment of steroid-dependent Crohn's disease.


METHODS
Patients with steroid-dependent Crohn's disease (n = 271) were enrolled in a 36-week, double-blind, placebo-controlled trial. Steroid dependence was defined as use of prednisolone or prednisone (15-40 mg/day) or budesonide (9 mg/day) for > or =8 weeks, a previous failed attempt to decrease or discontinue steroids within 8 weeks of screening, and a Crohn's Disease Activity Index score of < or =150 points. Patients were randomized to receive intravenous CDP571 10 mg/kg or placebo 8-weekly through to week 32. Steroids were then tapered using a defined schedule. The primary efficacy endpoint was the percentage of patients with steroid sparing, defined as discontinuation of steroid therapy without a disease flare (Crohn's Disease Activity Index score > or =220 points) at week 36.


RESULTS
Steroid sparing occurred in 53 of 181 (29.3%) CDP571 patients and 33 of 90 (36.7%) placebo patients (P = 0.24). Adverse events occurred at similar frequencies in both treatment groups.


CONCLUSIONS
CDP571 was ineffective for sparing steroids in patients with steroid-dependent Crohn's disease. CDP571 was well tolerated.
Feagan
B G
BG
University of Western Ontario, London, ON, Canada. bfeagan@robarts.ca
Sandborn
W J
WJ
Lichtenstein
G
G
Radford-Smith
G
G
Patel
J
J
Innes
A
A
D000328:Adult; D000888:Antibodies, Anti-Idiotypic / Q000097:blood; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D002097:C-Reactive Protein / Q000032:analysis; D003424:Crohn Disease / Q000188:drug therapy*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005765:Gastrointestinal Agents / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D013256:Steroids / Q000008:administration & dosage; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000276:immunology
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D005765:Gastrointestinal Agents; D013256:Steroids; D014409:Tumor Necrosis Factor-alpha; C402162:CDP 571; D002097:C-Reactive Protein