Abstract Introduction Allergic bronchopulmonary aspergillosis (ABPA) is caused by an exaggerated allergic response to Aspergillus fumigatus exposure and is a common complication in people with cystic fibrosis (CF) leading to decreased lung function and frequent pulmonary exacerbations. ABPA is driven by a T-helper type 2 (Th2) cell mediated immune response leading to IL-4, IL-5, IL-13 cytokine release. This response in CF may be due to dysfunction of the CF transmembrane conductance regulator (CFTR) protein leading to altered Th2 regulation. Standard treatment involves systemic glucocorticoids with antifungal agents used as adjuncts. Recurrence of ABPA after discontinuation of therapy is common, however, and can be complicated by multiple side effects. Dupilumab, a monoclonal antibody which interrupts the IL-4 and IL-13 pathways, has been used successfully in the treatment of asthma-associated ABPA, though there are currently no published reports of its use in CF-associated ABPA in children. Here, we present the use of dupilumab as treatment for ABPA in three pediatric patients with CF. Case series Three patients with CF with varying CFTR mutations and ages ranging from 14-18 years presented with persistent cough and shortness of breath, elevated total serum IgE levels, eosinophilia, presence of Aspergillus-specific antibodies, as well as radiographic changes including worsening bronchiectasis. They were diagnosed with ABPA at ages 3-8 years. All three children were treated with multiple courses of systemic steroids and antifungal medications, but continued to have recurrent exacerbations with worsening lung function with persistently elevated IgE. Dupilumab was initiated at ages 13-17 years, with subsequent reduction of IgE and detection of Aspergillus-specific antibodies, and discontinuation of steroid and antifungal therapies. Stopping steroids was particularly beneficial as one patient had undergone liver transplant and another had CF-related diabetes. One of the patients, who was the only child eligible for highly effective modulator therapy (HEMT), met criteria for remission from ABPA based on recently published guidelines. However, clinical outcomes varied, with some patients experiencing limited improvement in lung function, continued challenges with pulmonary exacerbations, and coexisting infections like nontuberculous mycobacteria (NTM). Discussion There were no adverse events associated with the use of dupilumab in our pediatric patients with CF-associated ABPA. Dupilumab shows promise as a potential treatment for refractory cases of ABPA or in those who cannot tolerate glucocorticoid therapy. Further studies are needed to better understand the efficacy and safety in the treatment of ABPA in children with CF. This abstract is funded by: KIM24B0, BARNES25H0, 1K23HL169902, GIBSON23Q0
Kim et al. (Fri,) studied this question.