The effects of a monoclonal antibody directed against tumor necrosis factor-alpha in asthma.
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.
Erin
Edward M
EM
National Heart and Lung Institute, Imperial College, London, UK.
Leaker
Brian R
BR
Nicholson
Grant C
GC
Tan
Andrew J
AJ
Green
Linda M
LM
Neighbour
Helen
H
Zacharasiewicz
Angela S
AS
Turner
Jackie
J
Barnathan
Elliot S
ES
Kon
Onn Min
OM
Barnes
Peter J
PJ
Hansel
Trevor T
TT
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
D000911:Antibodies, Monoclonal; D016207:Cytokines; D007155:Immunologic Factors; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab