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

Louis Philippe Boulet, Kenneth R. Chapman, Johanne Côté, Sanjay Kalra, Rajesh Bhagat, Veronica A. Swystun, Michel Laviolette, Laura D. Cleland, Francine Deschesnes, John Q. Su, Arthur Devault, Robert B. Fick, Donald W. Cockcroft

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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 rhuMAb-25 was well tolerated and only one patient (active group) was withdrawn because of a generalized urticarial rash after the first dose.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 (Δ log PC15/0.3) respectively with rhuMAb-E25 and -0.3, +0.1, and -0.8 doubling doses with placebo (p0.002). 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.

Original languageEnglish (US)
Pages (from-to)1835-1840
Number of pages6
JournalAmerican journal of respiratory and critical care medicine
Volume155
Issue number6
DOIs
StatePublished - Jan 1 1997

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ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

Cite this

Boulet, L. P., Chapman, K. R., Côté, J., Kalra, S., Bhagat, R., Swystun, V. A., Laviolette, M., Cleland, L. D., Deschesnes, F., Su, J. Q., Devault, A., Fick, R. B., & Cockcroft, D. W. (1997). Inhibitory effects of an anti-IgE antibody E25 on allergen-induced early asthmatic response. American journal of respiratory and critical care medicine, 155(6), 1835-1840. https://doi.org/10.1164/ajrccm.155.6.9196083