The effect of an anti-IgE monoclonal antibody on the early- and late-phase responses to allergen inhalation in asthmatic subjects.

Abstract

A humanized murine monoclonal antibody directed to the Fc epsilonR1-binding domain of human IgE (rhuMAb-E25) has been shown to inhibit the binding of IgE to mast cells without provoking mast cell activation. To examine the effects of neutralizing IgE on allergic airway responses, we assessed the effects of 9 wk of treatment with rhuMAb-E25 in a parallel group, randomized, double-blind, placebo-controlled study of 19 allergic asthmatic subjects. We found that treatment with rhuMAb-E25 reduced serum IgE, increased the dose of allergen needed to provoke an early asthmatic response, reduced the mean maximal fall in FEV1 during the early response (30 +/- 10% at baseline to 18.8 +/- 8%, versus 33 +/- 8% at baseline to 34 +/- 4% after placebo; p = 0.01), and reduced the mean maximal fall in FEV1 during the late response (24 +/- 20% at baseline to 9 +/- 10% versus 20 +/- 17% at baseline to 18 +/- 17% after placebo; p = 0.047). We conclude that an anti-IgE monoclonal antibody, which inhibits binding of IgE to its receptor, suppresses the early- and late-phase responses to inhaled allergen in allergic asthmatic subjects. Targeting IgE with rhuMAb-E25 might be a useful treatment for allergic asthma.

From IgE to Anti‐IgE: Where do we stand?

“…A similar effect was observed for the late-phase response to allergen, assessed 2-7 h after allergen provocation (58). Interestingly, anti-IgE treatment significantly reduced the rise in sputum eosinophils following allergen challenge, an inflammatory reaction linked to the development of the late asthmatic response.…”

“…Two studies were performed in patients with mild asthma to test the ability of anti-IgE to inhibit early and late-phase allergic responses after bronchial challenge with allergen (57,58). Study design: Randomized, double-blind, placebo-controlled, parallel-group study.…”

Randomized Trial of Omalizumab (Anti-IgE) for Asthma in Inner-City Children

“…[3][4][5][6][7][8][9] Anti-IgE treatment reduces exacerbations, symptoms and, in some patients, the dose of inhaled glucocorticoids needed to maintain disease control. [4][5][6][7][8][9] Because of the increased morbidity associated with a high prevalence of allergic sensitization and the heavy burden of allergen exposure among inner-city residents, 10,11 this population in particular may benefit from an IgE-targeted treatment. We hypothesized that the addition of omalizumab would improve disease control by reducing symptoms and exacerbations in inner-city children, adolescents, and young adults with persistent asthma.…”

House dust mite-specific IgE antibodies in induced sputum are associated with sputum eosinophilia in mite-sensitive asthmatics

“…17 Treatment with anti-IgE monoclonal antibody in allergic asthmatic patients suppressed the earlyand late-phase responses to inhaled allergen. 18 In the mouse model, administration of the anti-IgE monoclonal antibody before allergen challenge inhibited the recruitment of eosinophils into the lungs and the production of IL-4 and IL-5. 19 These reports are consistent with our in vivo study results demonstrating significant association between sputum eosinophilia and allergen-specific IgE antibodies in induced sputum from atopic asthmatic patients.…”