Randomised controlled trial of CDP571 antibody to tumour necrosis factor-α in Crohnʹs disease

Background Tumour necrosis factor-α (TNFα) is thought to have a central role in the pathogenesis of Crohnʹs disease. We tested the hypothesis that CDP571, a genetically engineered human antibody to TNFα, is effective in modifying disease activity in patients with moderately active Crohnʹs disease. Methods In this double-blind, placebo-controlled study, 31 patients were randomly assigned to CDP571 (n=21) or placebo (n=10). The primary endpoint was change in Crohnʹs disease activity index 2 weeks after a single infusion of CDP571 (5 mg/kg), or human albumin as placebo. One patient who attended no follow-up assessments was excluded from the analyses (CDP571 group). Findings The median Crohnʹs disease activity index fell from 263 (IQR 186·5–323·5) at baseline to 167 (137·5–294·0) at 2 weeks in the CDP571-treated patients (p=0·0003); the change in the placebo group (253 [240–334] to 247 [183–256]) was not significant. In the treated group, there were also significant differences between baseline and 2 weeks in Harvey-Bradshaw score (p=0·0005), key symptom score (p=0·049), α1-glycoprotein concentration (p=0·012), and erythrocyte sedimentation rate (p=0·01); concentrations of C-reactive protein fell, but not significantly (p=0·067). Six patients achieved remission (Crohnʹs disease activity index ≤150) and three others had activity indices of 156 or lower. There were no significant changes in the placebo group. Interpretation A single 5 mg/kg infusion of CDP571 reduced disease activity in Crohnʹs disease at 2 weeks. These data suggest that antibody neutralisation of TNFα is a potentially effective strategy in the management of Crohnʹs disease. The use of CDP571 in Crohnʹs disease requires further study.