Anti–IL-4Ra therapy is superior to other biologic classes in treating allergic bronchopulmonary aspergillosis

Abstract

Background

Allergic bronchopulmonary aspergillosis (ABPA) is a disease resulting from an overactive type 2 response to Aspergillus. Initial studies suggest that asthma biologics can effectively treat ABPA, but it is unclear which biologic class is superior.

Objective

We sought to compare the effectiveness of asthma biologics in the treatment of ABPA.

Methods

We performed a retrospective analysis of patients with ABPA treated with asthma biologics, and measured outcomes of respiratory exacerbations, daily oral corticosteroids, and antifungals. We assessed these variables while individuals were treated with 1 of 3 biologic classes: anti-IgE, anti–IL-5/IL-5 receptor alpha (IL-5Ra), anti–IL-4 receptor alpha (IL-4Ra).

Results

A total of 21 patients were included in our analysis. Anti–IL-4Ra was associated with a significantly lower number of exacerbations and oral corticosteroid use compared with anti-IgE or anti–IL-5/IL-5Ra therapies. Anti–IL-4Ra also had significantly lower antifungal use than anti-IgE, and there was a trend toward lower antifungal use when compared with anti–IL-5/IL-5Ra. In a subgroup of 10 patients treated with 2 or more biologics sequentially, we found that 8 of them achieved clinical control on anti–IL-4Ra therapy after failing anti-IgE and/or anti–IL-5/IL-5Ra therapies.

Conclusions

Dupilumab blocks the IL-4Ra, resulting in the downstream inhibition of both IL-4 and IL-13 effector pathways. Dupilumab may benefit patients with ABPA by inhibiting the generation of airway mucus (IL-13), and by reducing local B-cell differentiation into IgE antibody–secreting cells (IL-4). On the basis of our findings and with the known molecular mechanisms of dupilumab, we believe that anti–IL-4Rα–targeted therapy may be more effective than anti-IgE or anti–IL-5/IL-5Rα therapies to treat ABPA.