title: Randomised controlled trial of CDP571 antibody to tumour necrosis factor-alpha in Crohn's disease.
abstract: 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).
  
  
  RESULTS
  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), 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 < or = 150) and three others had activity indices of 156 or lower. There were no significant changes in the placebo group.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Gastroenterology, University Hospital, Nottingham, UK.
authors.forename: W A
authors.initials: WA
authors.lastname: Stack
authors.forename: S D
authors.initials: SD
authors.lastname: Mann
authors.forename: A J
authors.initials: AJ
authors.lastname: Roy
authors.forename: P
authors.initials: P
authors.lastname: Heath
authors.forename: M
authors.initials: M
authors.lastname: Sopwith
authors.forename: J
authors.initials: J
authors.lastname: Freeman
authors.forename: G
authors.initials: G
authors.lastname: Holmes
authors.forename: R
authors.initials: R
authors.lastname: Long
authors.forename: A
authors.initials: A
authors.lastname: Forbes
authors.forename: M A
authors.initials: MA
authors.lastname: Kamm
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000906:Antibodies / Q000627:therapeutic use*; D002097:C-Reactive Protein / Q000032:analysis; D003424:Crohn Disease / Q000628:therapy*; D004311:Double-Blind Method; D006023:Glycoproteins / Q000097:blood; D006801:Humans; D008875:Middle Aged; D010919:Placebos; D012074:Remission Induction; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
chemical_list: D000906:Antibodies; D006023:Glycoproteins; D010919:Placebos; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein