Real-world efficacy of anti-IL-5 treatment in patients with allergic bronchopulmonary aspergillosis

Abstract

Despite standard treatment with systemic corticosteroids and/or antifungal triazoles, a substantial proportion of patients with allergic bronchopulmonary aspergillosis (ABPA) experience frequent relapses and require long-term treatment despite unfavorable adverse effects. We investigated the efficacy and safety of anti-interleukin (IL)-5/IL-5 receptor α chain (Rα) monoclonal antibodies (mAbs) in patients with ABPA complicated by asthma. ABPA cases treated with anti-IL-5/IL-5Rα mAbs were collected from 132 medical institutes in 2018 and published case reports in Japan. Clinical outcomes, laboratory and physiological data, and radiographic findings during 32 weeks before and after treatment were retrospectively evaluated. We analyzed 29 cases of ABPA: 20 treated with mepolizumab and nine with benralizumab. Treatment with anti-IL-5/IL-5Rα mAbs reduced the frequency of exacerbations (p = 0.03), decreased the dose of oral corticosteroids (p < 0.01), and improved pulmonary function (p = 0.01). Mucus plugs in the bronchi shrank or diminished in 18 patients (82%). Despite the clinical/radiographical improvement, serum levels of total IgE, the key biomarker for the pharmacological response in ABPA, were unchanged. Anti-IL-5/IL-5Rα mAbs that directly target eosinophils are promising candidates for the treatment of patients with ABPA, especially those with mucus plugs in the bronchi.

Figure 1

Clinical outcomes of patients. Number of exacerbations within 32 weeks (A, n = 29), percent forced expiratory volume in one second (FEV₁) of predicted values (B, n = 25), and dose of oral prednisolone (C, n = 15) before and after initiating treatment with mepolizumab or benralizumab in patients with allergic bronchopulmonary aspergillosis complicated by asthma. Treatment with mepolizumab or benralizumab significantly reduced exacerbation rate and oral corticosteroid dose, and improved pulmonary functions.

Figure 2

Biomarkers. Peripheral blood eosinophil counts (A, n = 29), serum IgE levels (B, n = 28), and fraction of exhaled nitric oxide (F_ENO) (C, n = 20) before and after initiating treatment with mepolizumab or benralizumab in patients with allergic bronchopulmonary aspergillosis complicated by asthma. Peripheral blood eosinophil counts were decreased significantly after treatment with mepolizumab or benralizumab, whereas there was no significant change in the serum IgE levels or F_ENO.