RANDOMIZED CONTROLLED TRIAL OF CDP571 ANTIBODY TO TUMOR-NECROSIS-FACTOR-ALPHA IN CROHNS-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 mo derately 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 asses sments was excluded from the analyses (CDP571 group). Findings The med ian 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 patient s (p=0.0003); the change in the placebo group (253 [240-334] to 247 [1 83-256]) was not significant. In the treated group, there were also si gnificant differences between baseline and 2 weeks in Harvey-Bradshaw score (p=0.0005), hey symptom score (p=0.049), alpha 1-glycoprotein co ncentration (p=0.012), and erythrocyte sedimentation rate (p=0.01); co ncentrations of C-reactive protein fell, but not significantly (p=0.06 7). Six patients achieved remission (Crohn's disease activity index le ss than or equal to 150) and three others had activity indices of 156 or lower. There were no significant changes in the placebo group. Inte rpretation A single 5 mg/kg infusion of CDP571 reduced disease activit y in Crohn's disease at 2 weeks. These data suggest that antibody neut ralisation of TNF alpha is a potentially effective strategy in the man agement of Crohn's disease. The use of CDP571 in Crohn's disease requi res further study.