Severe asthma with fungal sensitization (SAFS) is a complex clinical phenotype associated with poorly controlled type 2 inflammation and significant morbidity from both the disease itself and a high steroid burden.

To assess the effectiveness of biologic therapies targeting eosinophilic inflammation in SAFS.

We assessed the effectiveness of treatment with mepolizumab or benralizumab in patients with SAFS, and compared outcomes with patients with severe atopic asthma without fungal sensitization and patients with severe nonatopic asthma. Baseline clinical characteristics and clinical outcomes at 48 weeks were evaluated. A subgroup analysis was performed of patients who met the criteria for allergic bronchopulmonary aspergillosis (ABPA) rather than SAFS.

A total of 193 patients treated with mepolizumab (n = 63) or benralizumab (n = 130) were included. Patients with SAFS had higher baseline IgE level compared with patients with severe atopic asthma without fungal sensitization and severe nonatopic asthma (733 ± 837 IU/mL vs 338 ± 494 and 142 ± 171, respectively; both P < .001). There were no other significant baseline differences in clinical characteristics between groups. At 48 weeks, there were significant improvements in 6-item asthma control questionnaire score and exacerbation frequency, and reduction in maintenance oral corticosteroid dose across all groups (all P < .05). No significant between-group differences in outcomes were observed at 48 weeks. Patients with ABPA (n = 9) had a significant reduction in exacerbation frequency (P = .013) with treatment.

Treatment with eosinophil-targeting biologics led to improvements in exacerbation frequency, oral corticosteroid requirements, and patient-reported outcomes in patients with SAFS, with a reduction in exacerbations in the subgroup of patients with ABPA. These data highlight the potential clinical utility of targeting eosinophilic inflammation in SAFS and ABPA.