Antifungals plus steroids show no added benefit for ABPA in CF study

Adding antifungal therapy to oral corticosteroids was not associated with additional benefits for people with cystic fibrosis (CF) being treated for allergic bronchopulmonary aspergillosis (ABPA), a large U.S. real-world study found.

ABPA is a lung condition in which the immune system overreacts to the fungus Aspergillus fumigatus, causing allergic inflammation in the airways.

The study included about 3,000 people with CF who had been newly diagnosed with ABPA. Among those initially treated with oral corticosteroids alone, lung function showed a more favorable trend after treatment began than during the previous year. However, neither antifungal treatment alone nor antifungals combined with corticosteroids showed significantly better lung function outcomes than corticosteroids alone. The three approaches also showed no significant differences in the time to a pulmonary exacerbation — a sudden worsening of lung symptoms — or to an ABPA relapse.

The study, “Comparing the real-world effectiveness of oral corticosteroids and antifungals for the treatment of allergic bronchopulmonary aspergillosis in cystic fibrosis,” was published in the journal Chest.

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Steroids remain first-line treatment for ABPA in CF

ABPA affects an estimated 5%-10% of people with CF and can cause increased cough and mucus production, wheezing, and declining lung function.

Oral corticosteroids, such as prednisone or prednisolone, are recommended as the first-line treatment for ABPA. Antifungal medications, which aim to reduce the amount of fungus in the airways, are also commonly used alone or alongside corticosteroids. However, there is limited evidence supporting their use in people with CF.

Researchers at the University of Pennsylvania used data from the Cystic Fibrosis Foundation Patient Registry to examine how ABPA is treated in people with CF and what factors are linked to antifungal use. They also compared lung function, pulmonary exacerbations, and ABPA relapse among patients who initially received corticosteroids alone, antifungals alone, or both treatments.

The analysis included 3,096 people with CF, ages 6 and older, who were diagnosed with ABPA between 2006 and 2022. Their median age was 19.3 years, and 47.7% were female.

Overall, 2,301 patients (74.3%) received oral corticosteroids, antifungals, or both. Of these, 49.6% initially received corticosteroids alone, 30.2% received antifungals alone, and 20.2% received both treatments.

The percentage of newly diagnosed patients who received corticosteroids, antifungals, or both during their diagnosis year fell from 58.3% in 2006 to 39.5% in 2022.

Study finds no added benefit from combination therapy

The researchers noted that the decline was sharper after 2019 and may partly reflect the growing use of CFTR modulators, particularly Trikafta. Antifungal treatment was started sooner in people who had more pulmonary exacerbations during the previous year, received care at larger CF centers, or were taking oral corticosteroids. Older age, CFTR modulator use, and CF-related liver disease were linked to starting antifungal treatment later.

Among patients initially treated with corticosteroids alone, the monthly trend in lung function improved by 0.24 percentage points after treatment began, compared with the previous year. Lung function was measured using forced expiratory volume in one second as a percent of predicted (FEV1pp), which compares how much air a person can forcefully exhale in one second with the amount expected for someone like them. No significant change in this trend was observed with antifungal therapy alone or with combination treatment.

There were also no significant differences between the three initial treatments in the time until patients experienced a pulmonary exacerbation. The study defined these as episodes of worsening lung symptoms that required hospitalization or intravenous (IV) treatment at home. Among patients who stopped treatment and remained off therapy for at least six months, the initial treatment choice also was not associated with how long it took before treatment was restarted for an ABPA relapse.

The researchers noted that the study could not establish cause and effect. They also could not determine corticosteroid doses or antifungal drug levels from the registry.

Overall, while the combination of oral corticosteroids with antifungal therapy “is commonly used as initial ABPA treatment in the U.S., we observed no significant differences in improvements in lung function, time to pulmonary exacerbation, or time to first clinical relapse compared with [oral corticosteroids alone],” the researchers concluded.