Real-World Effectiveness of Biologic Therapy in Allergic Bronchopulmonary Aspergillosis

Abstract

Background: Allergic bronchopulmonary aspergillosis (ABPA) is characterized by a severe hypersensitivity reaction to Aspergillus species. Current treatment relies on oral corticosteroids (OCS) and triazole antifungal therapy, but there is increasing evidence of the benefits of biologic therapies targeting type 2 inflammatory pathways.

Objective: To assess the real-world effectiveness of biologic therapies in patients with ABPA.

Methods: We performed a large retrospective single-center analysis of patients with ABPA as defined by the modified International Society for Human and Animal Mycology (ISHAM) criteria between 2014 and 2022. Baseline characteristics were recorded. Clinical outcomes were assessed at 12 months after commencement of a biologic including symptom scores, exacerbation frequency, corticosteroid use, and multidisciplinary team consensus of effectiveness.

Results: A total of 74 patients received a biologic, of whom 32% (n = 24) received anti-IgE therapy, 65% (n = 48) anti-IL5/5Rα therapy, and 3% (n = 2) anti-IL4-Rα therapy. Of the total, 65% (n = 48) patients were deemed to have a successful response at 12 months with a ≥50% reduction in OCS use and 35% (n = 26) stopped or changed biologic during the follow-up period because of failed clinical response (n = 21), side effects (n = 4), or medical comorbidities (n = 1). There was a significant reduction in the 6-item Asthma Control Questionnaire score (P < .0001), exacerbation rate over 12 months (P < .0001), and maintenance OCS use (P = .0173). Univariate analysis revealed that mucus plugging was associated with nonresponse to biologic therapy (P = .0189).

Conclusion: Biologic therapies are effective in a number of patients with ABPA. However, further prospective clinical trials are required to determine the effectiveness and which phenotypes likely to respond. These data nevertheless increase the evidence base for biologics in ABPA.

Keywords: Allergic bronchopulmonary aspergillosis; Asthma; Benralizumab; Biologics; Dupilumab; Mepolizumab; Omalizumab; Real world; Resiluzumab.