INHIBITORY EFFECTS OF AN ANTI-IGE ANTIBODY E25 ON ALLERGEN-INDUCED EARLY ASTHMATIC RESPONSE

Inhaled allergens, acting through IgE-dependent mechanisms, are import ant triggers of asthma symptoms and inducers of airway hyperresponsive ness and airway inflammation. The effect of anti-IgE recombinant human ized monoclonal antibody-E25 (rhuMAb-E25) on the provocation concentra tion of allergen causing a 15% fall in FEV1 (allergen PC15) during the allergen-induced early asthmatic response (EAR) was assessed in a mul ticenter, randomized, double-blind, parallel group study. Ten of 11 al lergic 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 D ays-2, 42, and 76. rhuMAb-25 was well tolerated and only one patient ( active group) was withdrawn because of a generalized urticarial rash a fter the first dose.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 a nd -0.3, +0.1, and -0.8 doubling doses with placebo (p less than or eq ual to 0.002). Methacholine PC20 improved slightly after rhuMAb-E25, t his 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 plac ebo. The inhibitory effects of rhuMAb-E25 on allergen-induced EAR sugg est that it may be an effective, novel antiallergic treatment for asth ma.