D1.128 - Use of Tezepelumab in four Patients with Allergic Bronchopulmonary Aspergillosis and severe uncontrolled Asthma: A Case Series

Allergic bronchopulmonary aspergillosis (ABPA) is an immunoallergic disorder caused by hypersensitivity to Aspergillus fumigatus, mainly affecting patients with asthma. It is associated with recurrent exacerbations, bronchiectasis, lung function impairment, and prolonged systemic corticosteroid exposure. Treatment options are limited in patients refractory to standard therapy and currently available biologics. Given its upstream mechanism of action, inhibition of thymic stromal lymphopoietin (TSLP) with Tezepelumab may improve disease control in ABPA. 

We present a descriptive Case series of four patients with severe asthma and ABPA who showed inadequate response to previous treatments, including oral corticosteroids, antifungal therapy, and biologics targeting IgE, IL-5, and IL-4/13. Tezepelumab was administered at 210 mg subcutaneously every four weeks. Clinical outcomes, lung function (FEV₁), asthma control (ACT), exacerbation rate, emergency department visits, oral corticosteroid use, and inflammatory biomarkers were assessed at baseline and after one year of treatment.

Our Case series included three women and one man with a median age of 65 years old, all with long-standing ABPA (median time since diagnosis: 7.5 years) and recurrent exacerbations (2 - 3/ year) despite biologic treatments with Omalizumab, Dupilumab, Omalizumab + Dupilumab, or Benralizumab. After one year of Tezepelumab treatment, severe exacerbations were completely eliminated in three patients and reduced to one mild episode in the remaining patient. No emergency department visits or hospitalizations occurred during the follow-up period. Both patients who needed chronic oral corticosteroids previously were able to discontinue them. All ACT scores were >/=19 points, accompanied by stabilization or improvement in FEV1. Blood eosinophils and serum total IgE were remarkably reduced (median reduction of 785 cells/ul and 974 kU/L, respectively). No clinically relevant adverse events were observed.

Tezepelumab was associated with meaningful clinical improvement, reduction of exacerbations, oral corticosteroid sparing and decrease in inflammatory parameters in patients with uncontrolled ABPA despite biological treatment. These findings support TSLP inhibition as a promising therapeutic strategy in this difficult-to-treat population and warrant confirmation in larger prospective studies.