Comparing the real-world effectiveness of oral corticosteroids and antifungals for the treatment of allergic bronchopulmonary aspergillosis in cystic fibrosis

BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA) is a complication of cystic fibrosis (CF) that often requires treatment. Oral corticosteroids (OCS) are the first-line therapy; however, antifungals alone or in combination with OCS are commonly used despite limited data supporting their role. RESEARCH QUESTION: What factors are associated with antifungal treatment initiation for ABPA in people with CF? Do antifungals, with or without OCS, improve respiratory outcomes compared to OCS alone? STUDY DESIGN AND METHODS: We conducted a retrospective cohort study of people with CF with first diagnosis of ABPA from 2006 to 2022. Factors associated with antifungal initiation following ABPA diagnosis were evaluated using a Cox proportional hazards (PH) model. We used an inverse probability of treatment weighting (IPTW) generalized estimating equations (GEE) model to evaluate changes in lung function before and after initiation of first treatment (OCS, antifungals, or combination treatment). IPTW Cox PH models were used to evaluate associations between the first treatment type and time to first pulmonary exacerbation and ABPA clinical relapse. RESULTS: Among 3,096 people with CF and incident ABPA, 74.3% received OCS and/or antifungals. Older age, CFTR modulator use, and CF liver disease were associated with longer time to antifungal initiation, while prior pulmonary exacerbations, larger care center size, and OCS use were associated with earlier initiation. OCS monotherapy was associated with an increase in forced expiratory volume in one second percent predicted slope of 0.24 (95% CI 0.09-0.38, p<0.01) after treatment initiation. No significant differences were observed between combination therapy or antifungal monotherapy compared to OCS alone in changes in lung function decline, time to pulmonary exacerbations or time to clinical relapse. INTERPRETATION: Combination OCS/antifungal therapy was not associated with greater improvements in lung function or reduced risk of pulmonary exacerbations or clinical relapse compared to OCS monotherapy.