title: Omalizumab protects against allergen- induced bronchoconstriction in allergic (immunoglobulin E-mediated) asthma.
abstract: 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.
authors.affiliation: Department of Pediatric Allergy, Pneumology and Cystic Fibrosis, University Children's Hospital, J.W. Goethe University, Frankfurt, Germany. Stefan.Zielen@kgu.de
authors.forename: Stefan
authors.initials: S
authors.lastname: Zielen
authors.forename: Adrian
authors.initials: A
authors.lastname: Lieb
authors.forename: Stephan
authors.initials: S
authors.lastname: De La Motte
authors.forename: Frank
authors.initials: F
authors.lastname: Wagner
authors.forename: Jan
authors.initials: J
authors.lastname: de Monchy
authors.forename: Rainard
authors.initials: R
authors.lastname: Fuhr
authors.forename: Clara
authors.initials: C
authors.lastname: Munzu
authors.forename: Stephan
authors.initials: S
authors.lastname: Koehne-Voss
authors.forename: Gilles-Jacques
authors.initials: GJ
authors.lastname: Rivière
authors.forename: Guenther
authors.initials: G
authors.lastname: Kaiser
authors.forename: Veit J
authors.initials: VJ
authors.lastname: Erpenbeck
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000888:Antibodies, Anti-Idiotypic / Q000008:administration & dosage / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control; D001985:Bronchial Provocation Tests; D016084:Bronchoconstriction / Q000187:drug effects; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D008297:Male; D008875:Middle Aged; D000069444:Omalizumab; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D018927:Anti-Asthmatic Agents; D000888:Antibodies, Anti-Idiotypic; D061067:Antibodies, Monoclonal, Humanized; D000069444:Omalizumab; D007073:Immunoglobulin E