B32-34 Exacerbation Reduction Following Dual Biologic Therapy in Severe Asthma: A Retrospective Case Series

Abstract Rationale A subset of patients with severe asthma (SA) remain inadequately controlled despite use of targeted biologic therapies. In these refractory cases, dual biologic therapy has emerged in clinical practice. However, there are no formal guidelines for routine dual-biologic use owing to limited evidence on safety, efficacy, and patient selection. We sought to characterize real-world dual biologic use, including patient profiles, treatment patterns, biomarker profiles, and change in exacerbation burden. Methods We conducted a retrospective analysis of a cohort of adult patients with moderate to severe asthma who received ≥3 months of overlapping biologic therapy for asthma and/or comorbid atopic conditions. Patients were identified via Electronic Health Record query, manual chart review, and from a cohort enrolled into the CHRONICLE registry at our site (NCT03373045). We captured demographics, comorbidities, concomitant asthma medications, biomarkers (blood eosinophil count (BEC), total Immunoglobulin E (IgE), fractional expired nitric oxide (FeNO)), spirometry (Forced Expiratory Volume in 1 second (FEV1) % predicted and liters, and asthma exacerbations rate. Exacerbations were identified for the 12 months pre and post dual-biologic initiation. Primary outcome was change in annualized asthma exacerbations rate (AAER) 12 months pre- vs post-initiation; paired t-tests and Wilcoxon signed-rank tests were used for analysis. Results Among 24 patients meeting inclusion criteria, the median age at dual biologic initiation (i.e., baseline) was 51 years (IQR: 44-56), 88% identified as White and 79% of patients were female. The median BEC was 1 cell/μL (n = 21), blood IgE was 58 IU/mL (n = 20), and FeNO was 31 ppb (n = 21). The median FEV₁ was 1.87 L and 64% (n = 20). All patients were on ICS-containing inhalers, and 46% were maintained on daily oral corticosteroids. The most common respiratory comorbidities included allergic rhinitis (n = 21), chronic rhinosinusitis (n = 17) and obstructive sleep apnea (n = 14). The most frequently prescribed dual biologic combinations were dupilumab/tezepelumab (n = 9), benralizumab/tezepelumab (n = 4), and dupilumab/benralizumab (n = 3). AAER declined following initiation of dual biologic therapy from 1.67 (±1.63) in the 12 months prior to baseline to 0.96 (±1.23) after one year of dual therapy, representing a 42.5% relative reduction. These reductions were statistically significant by both paired t-test (p = 0.0234) and Wilcoxon signed-rank test (p = 0.0276). Conclusions Dual-biologic therapy was associated with a reduction in exacerbations. These findings suggest potential clinical benefits of dual biologic therapy in SA with refractory disease on a single biologic. This abstract is funded by: None