Zielen, S, Lieb, A, De La Motte, D, Wagner, F, De Monchy, J, Fuhr, R, Munzu, Clara, Koehne-Voss, Stephan, Riviere, G, Kaiser, Guenther and Erpenbeck, Veit (2012) Omalizumab protects against allergen-induced bronchoconstriction in allergic (IgE-mediated) asthma. International archives of allergy and immunology, 160 (1). pp. 102-110. ISSN 1018-2438

Abstract

Background: Omalizumab has been shown to suppress responses to inhaled allergens in allergic asthma patients with pre-treatment immunoglobulin E (IgE) ≤700 IU/ml. To extend current dosing tables, we evaluated the potential of high omalizumab doses to block allergen-induced bronchoconstriction in patients with higher IgE levels.

Methods: Asthmatic adults (18–65 years; bodyweight 40–150 kg) were divided into groups according to screening IgE (Group 1: 30–300 IU/ml; Group 2: 700–2,000 IU/ml) and randomized 2:1 to omalizumab/placebo every 2 or 4 weeks for 12–14 weeks. Allergen bronchoprovocation (ABP) testing was performed at pre-treatment and weeks 8 and 16. The primary efficacy endpoint, early phase allergic response (EAR), was defined as the maximum percentage drop in forced expiratory volume in 1 s during the first 30 min after ABP. Serum free IgE was determined as a pharmacodynamic endpoint; exhaled fractional concentration of nitric oxide (FENO) was an exploratory endpoint.

Results: Fifty patients were included. Omalizumab improved EAR; at week 8 EAR was 23.1% for placebo, 9.3% in Group 1 (p = 0.018 versus placebo) and 5.6% in Group 2 (p < 0.001). At week 16, EAR was 20%, 11.8% (p = 0.087) and 5.1% (p < 0.001), respectively. Free IgE decreased in Groups 1 and 2 and remained <50 ng/ml in all patients during weeks 6–16. Omalizumab completely suppressed FENO increases after ABP in both groups.

Conclusions: Omalizumab blocked early asthmatic responses over a broad range of IgE–bodyweight combinations. Extending the dosing tables enables omalizumab to benefit a wider range of patients.

Item Type:	Article
Date Deposited:	13 Oct 2015 13:14
Last Modified:	13 Oct 2015 13:14
URI:	https://oak.novartis.com/id/eprint/6120