Effect of aerosolized anti-IgE (E25) on airway responses to inhaled allergen in asthmatic subjects.
Intravenous administration of a humanized monoclonal antibody of IgE (E25) attenuates the early and late phase response to inhaled allergen in allergic asthmatic subjects. To test whether direct delivery of E25 to the airway might have the same effect, we conducted a randomized, double-blind, three group study in 33 subjects with mild allergic asthma (20 to 46 yr of age, 21 men, FEV(1) > 70% predicted). The airway responses to aerosolized allergen were determined at baseline, after 2 and 8 wk of once daily treatment with aerosolized placebo (n = 11), aerosolized E25 1 mg (n = 12), or aerosolized E25 10 mg (n = 10), and after 4 wk of treatment withdrawal. We found that E25 was detectable in the serum during aerosol treatment, although serum IgE did not change significantly in any of the three groups during treatment. In addition, both doses of E25 were no more effective than placebo in attenuating the early phase responses to allergen at both times during treatment. Although aerosolized E25 was generally well tolerated, one subject receiving aerosolized E25 10 mg daily was found to have serum IgG and IgA antibodies to E25. We conclude that aerosol administration of an anti-IgE monoclonal antibody does not inhibit the airway responses to inhaled allergen in allergic asthmatic subjects. We speculate that the observed lack of efficacy may be due to the inability of aerosol route of delivery to result in high enough concentrations of E25 in the tissue compartments surrounding IgE effector cells to neutralize IgE arising from local airway and pulmonary sources and IgE arising from the vascular space. Additionally, the aerosol route of delivery of monoclonal antibodies may be more immunogenic than the parenteral route.
Fahy
J V
JV
The Cardiovascular Research Institute and the Department of Medicine, University of California, San Francisco, California, USA. jfahy@itsa.ucsf.edu
Cockcroft
D W
DW
Boulet
L P
LP
Wong
H H
HH
Deschesnes
F
F
Davis
E E
EE
Ruppel
J
J
Su
J Q
JQ
Adelman
D C
DC
D000280:Administration, Inhalation; D000328:Adult; D000336:Aerosols; D000485:Allergens / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D019540:Area Under Curve; D001249:Asthma / Q000276:immunology / Q000503:physiopathology / Q000628:therapy*; D001985:Bronchial Provocation Tests; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000503:physiopathology / Q000628:therapy; D006969:Hypersensitivity, Immediate / Q000503:physiopathology / Q000628:therapy; D007073:Immunoglobulin E / Q000276:immunology*; D008168:Lung / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D012129:Respiratory Function Tests; D018709:Statistics, Nonparametric
D000336:Aerosols; D000485:Allergens; D000911:Antibodies, Monoclonal; D007073:Immunoglobulin E