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 allergi c 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, 2 1 men, FEV1 > 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 Ig E 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 atte nuating the early phase responses to allergen at both times during treatmen t. Although aerosolized E25 was generally well tolerated, one subject recei ving aerosolized E25 10 mg daily was found to have serum IgG and IgA antibo dies to E25. We conclude that aerosol administration of an anti-IgE monoclo nal antibody does not inhibit the airway responses to inhaled allergen in a llergic 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 ef fector cells to neutralize IgE arising from local airway and pulmonary sour ces and IgE arising from the vascular space. Additionally, the aerosol rout e of delivery of monoclonal antibodies may be more immunogenic than the par enteral route.