Omalizumab Protects against Allergen- Induced Bronchoconstriction in Allergic (Immunoglobulin E-Mediated) Asthma

• Published in: International archives of allergy and immunology Vol. 160; no. 1; pp. 102 - 110
• Main Authors: Zielen, Stefan, Lieb, Adrian, De La Motte, Stephan, Wagner, Frank, de Monchy, Jan, Fuhr, Rainard, Munzu, Clara, Koehne-Voss, Stephan, Rivière, Gilles-Jacques, Kaiser, Guenther, Erpenbeck, Veit J.
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland S. Karger AG 01.01.2013
• Subjects: Adolescent; Adult; Aged; Airway management; Allergies; Anti-Asthmatic Agents - administration & dosage; Anti-Asthmatic Agents - therapeutic use; Antibodies, Anti-Idiotypic - administration & dosage; Antibodies, Anti-Idiotypic - therapeutic use; Antibodies, Monoclonal, Humanized - administration & dosage; Antibodies, Monoclonal, Humanized - therapeutic use; Asthma; Asthma - drug therapy; Asthma - physiopathology; Asthma - prevention & control; Bronchial Provocation Tests; Bronchoconstriction - drug effects; Double-Blind Method; Drug therapy; Female; Forced Expiratory Volume - drug effects; Humans; Immunoglobulin E - blood; Immunoglobulin E - immunology; Immunoglobulins; Male; Middle Aged; Omalizumab; Original Paper; Treatment Outcome; Young Adult; Immunoglobulin E; Omalizumab; Allergic asthma; Bronchoconstriction; Allergen
• ISSN: 1018-2438; 1423-0097
• DOI: 10.1159/000339243

Background: Omalizumab has been shown to suppress responses to inhaled allergens in allergic asthma patients with pretreatment 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; body weight 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 before treatment and at weeks 8 and 16. The primary efficacy endpoint, the 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, and the exhaled fractional concentration of nitric oxide (FE NO ) was an exploratory endpoint. Results: Fifty patients were included in the study. 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 FE NO increases after ABP in both groups. Conclusions: Omalizumab blocked early asthmatic responses over a broad range of IgE/body weight combinations. Extending the dosing tables enables omalizumab to benefit a wider range of patients.