Randomised controlled trial of CDP571 antibody to tumour necrosis factor-alpha in Crohn's disease

Background Tumour necrosis factor-alpha (TNF alpha) is thought to have a central role in the pathogenesis of Crohn's disease. We tested the hypothesis that CDP571, a genetically engineered human antibody to TNF alpha, is effective in modifying disease activity in patients with moderately active Crohn's 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 Crohn's 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 Crohn's 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), hey symptom score (p=0.049), alpha 1-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 (Crohn's disease activity index less than or equal to 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 Crohn's disease at 2 weeks. These data suggest that antibody neutralisation of TNF alpha is a potentially effective strategy in the management of Crohn's disease. The use of CDP571 in Crohn's disease requires further study.