To the Editor We read with interest the article “Successful Treatment with Benralizumab for Allergic Bronchopulmonary Aspergillosis that Developed after Disastrous Heavy Rainfall in Western Japan” wherein the authors have used benralizumab as a first-line treatment for allergic bronchopulmonary aspergillosis (ABPA) (1). While glucocorticoids are the first-line treatment for ABPA, they were not given in the index case due to a fear of adverse effects related to glucocorticoids.
In cases with a contraindication for glucocorticoids, an attractive option in treating acute-stage ABPA is antifungal triazoles. In patients with ABPA, Aspergillus DNA can be detected in the sputum in almost 80% of all patients (2). In two different randomized controlled trials, we have previously demonstrated itraconazole and voriconazole to be as effective as glucocorticoids in the management of treatment-naïve ABPA (3,4). An added advantage with antifungal triazoles is that by reducing the fungal burden secondary to fungal colonization in the airways, the drug can also decrease the chance of future exacerbations.
Anti-Th2 therapies such as benralizumab certainly have a role to play in the management of ABPA. However, the evidence for anti-Th2 biological agents is in the form of case reports and case series, and even that mostly for refractory cases (5). Currently, anti-Th2 therapies, in general, should be reserved for use in the following situations, namely:
1) When there is a contraindication for both glucocorticoids and antifungal triazoles.
2) When ABPA is refractory to treatment with both glucocorticoids and antifungal triazoles.
3) When uncontrolled asthma persists despite glucocorticoids.
4) In patients encountering adverse effects with glucocorticoids and antifungal triazoles.
As a result, we believe that the upfront use of benralizumab was not warranted in the index case. More evidence is required before anti-Th2 therapies should be used as an alternative to glucocorticoids or triazoles in the management of ABPA.
The authors state that they have no Conflict of Interest (COI).
References
- 1.Matsuura H, Fujiwara K, Omori H, et al. Successful treatment with benralizumab for allergic bronchopulmonary aspergillosis that developed after disastrous heavy rainfall in Western Japan. Intern Med 60: 1443-1450, 2021. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Denning DW, Park S, Lass-Florl C, et al. High-frequency triazole resistance found in nonculturable Aspergillus fumigatus from lungs of patients with chronic fungal disease. Clin Infect Dis 52: 1123-1129, 2011. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Dhooria S, Sehgal IS, Muthu V, Agarwal R. Treatment of allergic bronchopulmonary aspergillosis: from evidence to practice. Future Microbiol 15: 365-376, 2020. [DOI] [PubMed] [Google Scholar]
- 4.Agarwal R, Dhooria S, Sehgal IS, et al. A randomised trial of voriconazole and prednisolone monotherapy in acute-stage allergic bronchopulmonary aspergillosis complicating asthma. Eur Respir J 52: 1801159, 2018. [DOI] [PubMed] [Google Scholar]
- 5.Eraso IC, Sangiovanni S, Morales EI, Fernández-Trujillo L. Use of monoclonal antibodies for allergic bronchopulmonary aspergillosis in patients with asthma and cystic fibrosis: literature review. Ther Adv Respir Dis 14: 1753466620961648, 2020. [DOI] [PMC free article] [PubMed] [Google Scholar]