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

Background: Allergic bronchopulmonary aspergillosis (ABPA) is a disease resulting from an overactive type 2 response to 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.