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

• Published in: The Lancet (British edition) Vol. 349; no. 9051; pp. 521 - 524
• Main Authors: Stack, WA, Mann, SD, Roy, AJ, Heath, P, Sopwith, M, Freeman, J, Holmes, G, Long, R, Forbes, A, Kamm, MA, Hawkey, CJ
• Format: Journal Article
• Language: English
• Published: London Elsevier Ltd 22.02.1997; Lancet; Elsevier Limited
• Subjects: Adolescent; Adult; Aged; Antibodies - therapeutic use; Biological and medical sciences; C-Reactive Protein - analysis; Crohn Disease - therapy; Digestive system; Double-Blind Method; Drug therapy; Genetics; Glycoproteins - blood; Humans; Medical research; Medical sciences; Middle Aged; Neutralization; Pharmacology. Drug treatments; Placebos; Remission Induction; Tumor Necrosis Factor-alpha - immunology; Tumors; Human; Antibody; Cytokine; Biological activity; Inflammatory disease; Crohn disease; Randomization; Controlled environment study; Placebo; Double blind study; Digestive diseases; Intestinal disease; Clinical trial; Comparative study; Tumor necrosis factor α
• ISSN: 0140-6736; 1474-547X
• DOI: 10.1016/S0140-6736(97)80083-9

Tumour necrosis factor-α (TNFα) 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 TNFα, is effective in modifying disease activity in patients with moderately active Crohn's disease. 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). 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), 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 (Crohn's disease activity index ≤150) and three others had activity indices of 156 or lower. There were no significant changes in the placebo group. 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 TNFα is a potentially effective strategy in the management of Crohn's disease. The use of CDP571 in Crohn's disease requires further study.