A randomized, placebo-controlled trial using anti-IgE to treat allergic bronchopulmonary aspergillosis

Abstract

Background: Allergic bronchopulmonary aspergillosis (ABPA) often presents with persistently uncontrolled asthma despite the use of corticosteroids and antifungal therapy. A humanised anti-IgE monoclonal antibody (Omalizumab) is currently used to treat severe asthma, however ABPA patients are generally excluded from therapy with this drug, due to their very high serum IgE levels. Aim: To assess the clinical and immunological effects of anti-IgE in ABPA in a randomized, placebo-controlled trial. Methods: Patients with chronic ABPA were randomised to 4-months treatment with anti-IgE (750mg monthly) or placebo followed by a 3-month wash-out period in a cross-over design. The primary outcome was number of exacerbations. Secondary clinical outcomes included lung function, FEV1, FeNO, quality of life scores and symptoms. Immunological parameters measured included in vitro basophil activation to Aspergillus fumigatus extract and basophil FceR1 and surface-bound IgE levels determined by flow cytometry. Results: The cohort consisted of Thirteen patients with mean total IgE 2314± 2125IU/ml. A reduction in exacerbation frequency was observed in the active treatment phase compared to the placebo period (2 vs 12 events, p=0.048). Mean FeNO decreased from 30.5 to 17.1 ppb during treatment (p=0.03). Basophil sensitivity to Aspergillus fumigatus and surface-bound IgE and FceR1 levels decreased significantly after treatment with anti-IgE but not placebo. Conclusion: Anti-IgE (Omalizumab) can be used safely to treat ABPA, despite high serum IgE levels. Clinical improvement was accompanied by decreased basophil reactivity to Aspergillus fumigatus and FceR1 and surface-bound IgE levels.