title: The effects of a monoclonal antibody directed against tumor necrosis factor-alpha in asthma.
abstract: BACKGROUND
  Neutralization of tumor necrosis factor-alpha (TNF-alpha) is an effective antiinflammatory therapy for several chronic inflammatory diseases.
  
  
  OBJECTIVE
  We undertook a double-blind, placebo-controlled, parallel-group design study in 38 patients with moderate asthma treated with inhaled corticosteroids but symptomatic during a run-in phase. Infliximab (5 mg/kg) or placebo was administered by intravenous infusion at Weeks 0, 2, and 6. We assessed clinical response by monitoring lung function, symptoms, and inhaled beta(2)-agonist usage using hand-held electronic devices.
  
  
  RESULTS
  The primary endpoint, change in morning PEF at Days 50-56 compared with the last 7 d of the run-in, was not significantly different on treatment. However, infliximab was associated with a decrease in mean diurnal variation of PEF at Week 8 (p = 0.02; 95% confidence interval [CI], -8.1 to -0.72). Furthermore, there was a decrease in the number of patients with exacerbations of asthma (p = 0.01; 95% CI, 4.4 to 52.7) and an increased probability of freedom from exacerbation with time (p = 0.03) in patients on infliximab (n = 14) compared with placebo (n = 18). In addition, infliximab decreased levels of TNF-alpha (p = 0.01) and other cytokines in sputum supernatants. There were no serious adverse events related to the study agent.
  
  
  CONCLUSIONS
  Treatment with infliximab was well tolerated and caused a decrease in the number of patients with exacerbations in symptomatic moderate asthma. The promising preliminary findings underscore the need to evaluate therapy directed against TNF-alpha in larger trials enrolling patients with more severe asthma.
authors.affiliation: National Heart and Lung Institute, Imperial College, London, UK.
authors.forename: Edward M
authors.initials: EM
authors.lastname: Erin
authors.forename: Brian R
authors.initials: BR
authors.lastname: Leaker
authors.forename: Grant C
authors.initials: GC
authors.lastname: Nicholson
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Tan
authors.forename: Linda M
authors.initials: LM
authors.lastname: Green
authors.forename: Helen
authors.initials: H
authors.lastname: Neighbour
authors.forename: Angela S
authors.initials: AS
authors.lastname: Zacharasiewicz
authors.forename: Jackie
authors.initials: J
authors.lastname: Turner
authors.forename: Elliot S
authors.initials: ES
authors.lastname: Barnathan
authors.forename: Onn Min
authors.initials: OM
authors.lastname: Kon
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Barnes
authors.forename: Trevor T
authors.initials: TT
authors.lastname: Hansel
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology; D016207:Cytokines / Q000032:analysis; D004311:Double-Blind Method; D004804:Eosinophils / Q000276:immunology; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology / Q000627:therapeutic use*; D000069285:Infliximab; D008297:Male; D010366:Peak Expiratory Flow Rate / Q000187:drug effects; D012129:Respiratory Function Tests; D013183:Sputum / Q000737:chemistry; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D016207:Cytokines; D007155:Immunologic Factors; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab