Efficacy and Safety of Dupilumab Treatment for Adult Allergic Bronchopulmonary Aspergillosis: A Real‐World Analysis of 16 Cases in China

Allergic Bronchopulmonary Aspergillosis (ABPA) is a chronic inflammatory disease resulting from hypersensitivity to Aspergillus fumigatus, often leading to persistent airway inflammation, bronchial damage and a decline in lung function. It is primarily observed in individuals with asthma and cystic fibrosis (CF). Conventional treatment strategies typically include systemic corticosteroids to control inflammation alongside antifungal therapy to manage fungal colonisation [1, 2]. However, prolonged corticosteroid use is associated with significant risks. In response to these concerns, dupilumab, a biologic agent targeting the IL-4 and IL-13 signalling pathways, has emerged as a promising therapeutic option. Dupilumab has demonstrated efficacy in treating asthma and atopic dermatitis, particularly by reducing inflammation and corticosteroid use. In addition, dupilumab has been investigated in case reports for ABPA and has shown potential as a steroid-sparing therapy, further supporting its use in clinical practice [3, 4]. Our study aimed to evaluate the efficacy and safety of dupilumab in the treatment of ABPA in a real-world clinical setting. We conducted a retrospective observational study using real-world data from a tertiary care hospital in China, involving 16 adult patients diagnosed with ABPA who received dupilumab from March 2022 to December 2024. The inclusion criteria were adults aged 18–65 years with a confirmed ABPA diagnosis, elevated IgE levels, positive A. fumigatus-specific allergen tests, characteristic chest radiographs and a minimum treatment duration of 24 weeks with dupilumab, which ensured that the long-term outcomes of dupilumab treatment could be evaluated [5]. Patients who had experienced inadequate responses to conventional therapies, such as corticosteroids and antifungal treatments, were also included. All patients received an initial dose of 600 mg of dupilumab, followed by 300 mg every 2 weeks, alongside their ongoing corticosteroid and antifungal therapy. The treatment duration was 24 weeks. Primary outcomes were improvements in FEV1, annual exacerbation rates and symptoms. Secondary outcomes included changes in serum IgE, eosinophil counts, FeNO levels and safety. Patients had a mean age of 47.4 ± 11.8 years, with 75% having asthma-associated ABPA. Common comorbidities were allergic rhinitis (62.5%) and chronic rhinosinusitis (25%) (Table S1). Mean baseline FEV1 was 58.7% ± 14.8% predicted, IgE was 1250.5 ± 317.6 kU/L, and A. fumigatus-specific IgE was 75.2 ± 20.5 kUA/L (Table S1). At 12 weeks, 75% of patients showed a 16.7% improvement in FEV1, with two showing minimal improvement due to irreversible lung damage. At 24 weeks, FEV1 improved by 24.7% (p < 0.05), exacerbation rates decreased by 82.6% (p < 0.01), and IgE levels fell by 69.6% (p < 0.05). Eosinophil counts and FeNO levels declined by 51.9% and 43.6%, respectively (both p < 0.05) (Table 1). Symptoms improved in 87.5% of patients within 4–6 weeks. Dupilumab was well tolerated, with mild injection site reactions, conjunctivitis and upper respiratory tract infections observed. No serious adverse events or infections were reported, and no patients discontinued treatment due to adverse events. However, with the advent of biological therapies, ABPA now has more promising treatment options. Omalizumab and benralizumab, for example, have also shown potential in ABPA treatment by targeting IgE and IL-5, respectively, providing additional therapeutic avenues [6-8]. Despite these advancements, the number of large-scale case series specifically reporting on dupilumab for ABPA remains limited. Most current evidence is based on individual case reports or small cohort studies, and further research is needed to establish dupilumab's role in the broader treatment landscape for ABPA. Our study provides real-world evidence that dupilumab is a highly effective and well-tolerated treatment for ABPA, leading to clinical improvements in symptom control, lung function (FEV1) and a steroid-sparing effect. These findings suggest that dupilumab can serve as a viable alternative to long-term corticosteroid therapy, especially in steroid-dependent patients or those with frequent exacerbations. The reductions in serum IgE levels, A. fumigatus (m3) SIgE levels, eosinophil counts and FeNO levels further support the anti-inflammatory effects of dupilumab treatment. This study has several limitations. Its retrospective design relies on pre-existing data, limiting causal inferences and completeness. The small sample size (n = 16) reduces statistical power and generalisability. The 24-week follow-up is insufficient for evaluating long-term outcomes or late-onset adverse events. Additionally, patient heterogeneity, including comorbidities like asthma and bronchiectasis, may have influenced outcomes. Lastly, the absence of a control group prevents direct comparisons with other therapies. Future larger, controlled studies with extended follow-ups are needed to confirm these findings. Our real-world analysis highlights the efficacy and safety of dupilumab as a steroid-sparing treatment for ABPA, offering significant improvements in lung function, symptom control and a reduction in corticosteroid use. These findings suggest that dupilumab could be a key therapy for managing ABPA, particularly for patients who are dependent on steroids or have frequent exacerbations. Xu Li and Peng Jin were involved in the conception and design of the study, data collection, analysis, and interpretation. Xu Li and Peng Jin were also responsible for drafting the manuscript. Peng Jin contributed to the critical revision of the manuscript for important intellectual content. All authors participated in the data collection and performed the statistical analysis. Yanfei Li and Lili Zhi assisted with the interpretation of the results and provided supervision throughout the study. Lili Zhi also contributed to the manuscript revision and was responsible for the overall guidance of the study. All authors read and approved the final manuscript. This study was approved by the Institutional Review Board (IRB). The written consent form was obtained from all patients in this study. The authors declare no conflicts of interest. The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.