title: Omalizumab rapidly decreases nasal allergic response and FcepsilonRI on basophils.
abstract: BACKGROUND
  Omalizumab is a monoclonal anti-IgE antibody that is effective for the treatment of allergic respiratory disorders; however, its onset of action is unknown.
  
  
  OBJECTIVE
  This study was designed to determine the onset of action of omalizumab through the use of a challenge model to determine time-dependent inhibition of ragweed-induced changes in nasal volume as well as correlate the kinetics of omalizumab-induced decreases in serum free IgE and FcepsilonRI receptors on basophils.
  
  
  METHODS
  We conducted a 6-week, randomized, double-blind, placebo-controlled study of 24 rhinitic patients with ragweed allergy. After PD(30) ragweed nasal allergen challenge, patients received either omalizumab, approximately 0.016 mg/kg per IgE (IU/mL), or placebo at days 0 and 28 and were rechallenged with ragweed PD(30) dose biweekly. FcepsilonRI expression on blood basophils was determined by flow cytometry at baseline and 7, 14, 28, and 42 days after treatment. IgE levels were measured at baseline and on days 3, 28, and 42.
  
  
  RESULTS
  Mean IgE levels decreased by 96% (P <.001) from baseline within 3 days in the omalizumab group. Baseline 30% ragweed-induced nasal volume response was decreased to 20.4% at 7 to 14 days (P <.001) and 12.2% at 35 to 42 days (P <.001) for the omalizumab group. There was a median decrease in basophil FcepsilonRI expression of 73% (P <.001) in the omalizumab group, with maximum inhibition occurring within 14 days of treatment. No significant changes in IgE levels, nasal allergen challenge responses, or basophil FcepsilonRI expression were observed throughout the study in the placebo group.
  
  
  CONCLUSIONS
  Our study showed that the onset of action by omalizumab in blunting ragweed-induced nasal responses is within 2 weeks, and this response was associated with 2 putative mechanisms of action: decreased serum free IgE and decreased FcepsilonRI receptor expression on immune effector cells.
authors.affiliation: Division of Allergy/Immunology, Department of Medicine, Creighton University, Omaha, Neb, USA.
authors.forename: Henry
authors.initials: H
authors.lastname: Lin
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Boesel
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Griffith
authors.forename: Calman
authors.initials: C
authors.lastname: Prussin
authors.forename: Barbara
authors.initials: B
authors.lastname: Foster
authors.forename: F A
authors.initials: FA
authors.lastname: Romero
authors.forename: Robert
authors.initials: R
authors.lastname: Townley
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Casale
mesh_terms: D000328:Adult; D031164:Ambrosia / Q000009:adverse effects / Q000276:immunology; D018926:Anti-Allergic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D001491:Basophils / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009299:Nasal Provocation Tests; D000069444:Omalizumab; D017455:Receptors, IgE / Q000187:drug effects / Q000378:metabolism; D006255:Rhinitis, Allergic, Seasonal / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D018926:Anti-Allergic Agents; D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D017455:Receptors, IgE; D000069444:Omalizumab; D007073:Immunoglobulin E