CDP571, a humanised monoclonal antibody to tumour necrosis factor alpha, for moderate to severe Crohn's disease: a randomised, double blind, placebo controlled trial.
BACKGROUND
Targeting tumour necrosis factor alpha (TNF-alpha) has demonstrated efficacy in Crohn's disease.


OBJECTIVE
To evaluate CDP571, a humanised antibody to TNF-alpha, for treating active Crohn's disease.


METHODS
A total of 396 patients with moderate to severe Crohn's disease.


METHODS
In a 28 week, randomised, double blind, placebo controlled trial, patients received intravenous CDP571 (10 mg/kg) or placebo every eight weeks to week 24. The primary outcome measure was clinical response (a decrease in the Crohn's disease activity index (CDAI) to > or =100 points or remission (CDAI score < or =150 points)) at week 28. A secondary outcome measure was clinical response (using the same definition) at week 2.


RESULTS
Clinical response occurred at week 28 in 80/263 (30.4%) CDP571 patients and 31/132 (23.5%) placebo patients (p = 0.102). Clinical response at week 2 occurred in 90/263 (34.2%) CDP571 patients and 28/132 (21.2%) placebo patients (p = 0.011). Post hoc exploratory subgroup analysis of 159 patients with baseline C reactive protein (CRP) > or =10 mg/l demonstrated significant differences between CDP571 and placebo in clinical response rates at weeks 2 (CDP571, 50/101 (49.5%); placebo, 9/58 (15.5%); p<0.001) and 28 (CDP571, 29/101 (28.7%); placebo, 7/58 (12.1%); p = 0.018). Adverse events occurred at similar frequencies in both treatment groups.


CONCLUSIONS
CDP571 is modestly effective for short but not long term treatment of unselected patients with moderate to severe Crohn's disease. The clinical relevance of this short term effect is unclear. Post hoc analysis suggests both short and long term efficacy of CDP571 in patients with elevated baseline CRP (> or =10 mg/l). CDP571 is well tolerated.
Sandborn
W J
WJ
Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. sandborn.william@mayo.edu
Feagan
B G
BG
Radford-Smith
G
G
Kovacs
A
A
Enns
R
R
Innes
A
A
Patel
J
J
D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D002097:C-Reactive Protein / Q000378:metabolism; D003424:Crohn Disease / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D005765:Gastrointestinal Agents / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000276:immunology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000911:Antibodies, Monoclonal; D005765:Gastrointestinal Agents; D014409:Tumor Necrosis Factor-alpha; C402162:CDP 571; D002097:C-Reactive Protein