title: 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 rhuMAb-25 was well tolerated and only one patient (active group) was withdrawn because of a generalized urticarial rash after the first dose.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.
authors.affiliation: Centre de Pneumologie, Hôpital Laval, Sainte-Foy, Québec, Canada.
authors.forename: L P
authors.initials: LP
authors.lastname: Boulet
authors.forename: K R
authors.initials: KR
authors.lastname: Chapman
authors.forename: J
authors.initials: J
authors.lastname: Côté
authors.forename: S
authors.initials: S
authors.lastname: Kalra
authors.forename: R
authors.initials: R
authors.lastname: Bhagat
authors.forename: V A
authors.initials: VA
authors.lastname: Swystun
authors.forename: M
authors.initials: M
authors.lastname: Laviolette
authors.forename: L D
authors.initials: LD
authors.lastname: Cleland
authors.forename: F
authors.initials: F
authors.lastname: Deschesnes
authors.forename: J Q
authors.initials: JQ
authors.lastname: Su
authors.forename: A
authors.initials: A
authors.lastname: DeVault
authors.forename: R B
authors.initials: RB
authors.lastname: Fick
authors.forename: D W
authors.initials: DW
authors.lastname: Cockcroft
mesh_terms: D000328:Adult; D000485:Allergens / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000032:analysis / Q000627:therapeutic use*; D001249:Asthma / Q000276:immunology* / Q000628:therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000276:immunology* / Q000628:therapy*; D007073:Immunoglobulin E / Q000032:analysis / Q000276:immunology*; D008297:Male; D016210:Methacholine Chloride; D008875:Middle Aged
chemical_list: D000485:Allergens; D000911:Antibodies, Monoclonal; D016210:Methacholine Chloride; D007073:Immunoglobulin E