Clinical efficacy and immunologic effects of omalizumab in allergic bronchopulmonary aspergillosis

J Allergy Clin Immunol Pract. 2015 Mar-Apr;3(2):192-9. doi: 10.1016/j.jaip.2014.12.008. Epub 2015 Jan 29.

Abstract

Background: Allergic bronchopulmonary aspergillosis (ABPA) often presents with persistently uncontrolled asthma despite the use of corticosteroids and antifungal therapy. Omalizumab is a humanized anti-IgE monoclonal antibody currently used to treat severe asthma.

Objective: The aim was to assess the clinical and immunologic effects of omalizumab in ABPA in a randomized, placebo-controlled trial.

Methods: Patients with chronic ABPA were randomized to 4-month treatment with omalizumab (750 mg monthly) or placebo followed by a 3-month washout period in a cross-over design. The main endpoint was number of exacerbations. Other clinical endpoints included lung function, exhaled nitric oxide (FeNO), quality of life and symptoms. In vitro basophil activation to Aspergillus fumigatus extract and basophil FcεR1 and surface-bound IgE levels were assessed by flow cytometry.

Results: Thirteen patients were recruited with mean total IgE 2314 ± 2125 IU/mL. Exacerbations occurred less frequently during the active treatment phase compared with the placebo period (2 vs 12 events, P = .048). Mean FeNO decreased from 30.5 to 17.1 ppb during omalizumab treatment (P = .03). Basophil sensitivity to A. fumigatus and surface-bound IgE and FcεR1 levels decreased significantly after omalizumab but not after placebo.

Conclusion: Omalizumab can be used safely to treat ABPA, despite high serum IgE levels. Clinical improvement was accompanied by decreased basophil reactivity to A. fumigatus and FcεR1 and surface-bound IgE levels.

Keywords: Allergic bronchopulmonary aspergillosis; Basophils; Clinical trial; Omalizumab.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Anti-Allergic Agents / pharmacology
  • Anti-Allergic Agents / therapeutic use*
  • Antigens, Fungal / immunology
  • Aspergillosis, Allergic Bronchopulmonary / blood
  • Aspergillosis, Allergic Bronchopulmonary / drug therapy*
  • Aspergillosis, Allergic Bronchopulmonary / immunology
  • Aspergillosis, Allergic Bronchopulmonary / physiopathology
  • Aspergillus fumigatus / immunology
  • Basophils / drug effects
  • Basophils / immunology
  • Cross-Over Studies
  • Female
  • Forced Expiratory Volume
  • Humans
  • Immunoglobulin E / blood
  • Male
  • Middle Aged
  • Nitric Oxide / metabolism
  • Omalizumab / pharmacology
  • Omalizumab / therapeutic use*
  • Quality of Life
  • Receptors, IgE / immunology
  • Treatment Outcome

Substances

  • Anti-Allergic Agents
  • Antigens, Fungal
  • Receptors, IgE
  • Omalizumab
  • Nitric Oxide
  • Immunoglobulin E