Inhibitory effects of an anti-IgE antibody E25 on allergen-induced early asthmatic response.

Abstract

Inhaled allergens, acting through IgE-dependent mechanisms, are important triggers of asthma symptoms and inducers of airway hyperresponsiveness and airway inflammation. The effect of anti-IgE recombinant humanized monoclonal antibody-E25 (rhuMAb-E25) on the provocation concentration of allergen causing a 15% fall in FEV1 (allergen PC15) during the allergen-induced early asthmatic response (EAR) was assessed in a multicenter, randomized, double-blind, parallel group study. Ten of 11 allergic asthmatic subjects randomized to receive intravenous rhuMAb-E25, 2 mg/kg on study day 0 and 1 mg/kg on Days 7, 14, 28, 42, 56, and 70 completed the study; nine received intravenous placebo. The allergen PC15 was measured on Days -1, 27, 55, and 77 and methacholine PC20 on Days -2, 42, and 76. rhuMAb-25 was well tolerated and only one patient (active group) was withdrawn because of a generalized urticarial rash after the first dose. Compared with baseline values (Day -1), the median allergen PC15 on Days 27, 55, and 77 were increased by 2.3, 2.2, and 2.7 doubling doses (delta log PC15/0.3) respectively with rhuMAb-E25 and -0.3, +0.1, and -0.8 doubling doses with placebo (p < or = 0.002). Methacholine PC20 improved slightly after rhuMAb-E25, this change becoming statistically significant on Day 76 (p < 0.05); no change was observed in the placebo group. Mean serum-free IgE fell by 89% after rhuMAb-E25 while there was no significant change after placebo. The inhibitory effects of rhuMAb-E25 on allergen-induced EAR suggest that it may be an effective, novel antiallergic treatment for asthma.

The Effect of Omalizumab on Eosinophilic Inflammation of the Respiratory Tract in Patients with Allergic Asthma

“…Neutralization of free IgE by omalizumab and its effect on the expression and function of FceRI are reflected in clinical phenomena, such as inhibition of early [26,27] and late phase of allergic reaction [28,29] and also a decrease in the severity of chronic allergic inflammation.…”

“…Boulet et al [26] conducted omalizumab therapy in patients with allergic asthma. They observed that on day 27 they had to administer a bigger than a double dose of allergen concentration in inhaled provocation in order to decrease FEV 1 ( forced expiratory volume in 1 second) by 15% (PC15 for the allergen) in the early phase of asthmatic reaction to the allergen.…”

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

“…Results: Anti-IgE treatment significantly decreased IgE serum levels and reduced the early allergic response, as demonstrated by a significantly smaller reduction in FEV1 and a significant increase in median allergen PC15 after allergen challenge on days 27, 55, and 77 (57). A similar effect was observed for the late-phase response to allergen, assessed 2-7 h after allergen provocation (58).…”

“…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.…”

Le récepteur de forte affinité pour l’IgE : leçons d’une analyse structurale

“…L'efficacité de cet anticorps a été testée au cours d'études cliniques chez des patients asthmatiques dont l'atteinte était modérée ou sévère, et chez des patients atteints de rhinite allergique. Chez les patients ayant un asthme modéré, le traitement a réduit certaines des réponses précoces et tardives observées lors d'un test de provocation par les allergènes [31,32]. Chez des patients dont l'asthme modéré ou sévère nécessitait le recours à la corticothérapie, trois études chez des adultes [33][34][35] et une étude chez des enfants [34] ont été pratiquées.…”