Intravenous CDP870, a PEGylated Fab' fragment of a humanized antitumour necrosis factor antibody, in patients with moderate-to-severe Crohn's disease: an exploratory study.
BACKGROUND
CDP870 is a PEGylated Fab' fragment of a humanized monoclonal antibody that neutralizes tumour necrosis factor-alpha.


OBJECTIVE
To evaluate the safety and efficacy of a single intravenous dose of CDP870 or placebo over a 12-week period in patients with moderate-to-severe Crohn's disease.


METHODS
Ninety-two adult patients with Crohn's disease (Crohn's Disease Activity Index: 220-450 points) were randomized to receive CDP870 [1.25 (n = 2), 5 (n =26), 10 (n = 17) or 20 mg/kg (n = 23)] or placebo (n = 24). Crohn's Disease Activity Index scores were determined at weeks 0, 2, 4, 8 and 12. The primary end-point was the percentage of patients achieving clinical response [i.e. a decrease in Crohn's Disease Activity Index score > or = 100 points or remission (Crohn's Disease Activity Index score: < or =150 points)] at week 4 in the intent-to-treat population.


RESULTS
The percentage of patients achieving the primary end-point was comparable across all treatment groups (56.0%, 60.0%, 58.8% and 47.8% for placebo, CDP870 5, 10 and 20 mg/kg, respectively). The remission rate at week 2 was 47.1% with CDP870 10 mg/kg vs. 16.0% for placebo (P = 0.041). All treatments were well-tolerated: adverse events, reported by 43 patients treated with CDP870 and 15 patients treated with placebo, were mainly mild-to-moderate in intensity. There were no infusion reactions.


CONCLUSIONS
A single intravenous dose of CDP870 was well-tolerated by patients with Crohn's disease. While no statistically significant difference in clinical response rates between CDP870 and placebo was observed, clinical benefit in terms of remission was demonstrated.
Winter
T A
TA
Department of Internal Medicine, University of Kentucky, KY 40536-0298, USA. winter@uky.edu
Wright
J
J
Ghosh
S
S
Jahnsen
J
J
Innes
A
A
Round
P
P
D000293:Adolescent; D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D061067:Antibodies, Monoclonal, Humanized; D000068582:Certolizumab Pegol; D003424:Crohn Disease / Q000188:drug therapy*; D006801:Humans; D007140:Immunoglobulin Fab Fragments; D007262:Infusions, Intravenous; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D016896:Treatment Outcome
D000893:Anti-Inflammatory Agents; D061067:Antibodies, Monoclonal, Humanized; D007140:Immunoglobulin Fab Fragments; D011092:Polyethylene Glycols; D000068582:Certolizumab Pegol