Phenotypic Clusters of Severe Asthma and Response to Dupilumab in Real-World Practice.

BACKGROUND: Severe asthma is a heterogeneous disease with variable clinical and inflammatory profiles that may influence responses to biological therapies. Identifying phenotypic clusters may help optimize patient selection and treatment outcomes. OBJECTIVE: To identify phenotypic clusters (PCs) of patients with severe asthma treated with dupilumab and to assess differences in treatment response across clusters over a 12-month period in a real-world setting. METHODS: This was a retrospective study involving 140 adult patients with severe, poorly controlled T2-asthma who received dupilumab as first-line biological therapy for at least 12 months. Agglomerative clustering was applied to baseline clinical, laboratory, and functional parameters to identify PCs. Treatment response was assessed at 1, 6, and 12 months using ACT, ACQ-5, AQLQ, lung function (pre-bronchodilator FEV1), T2-biomarkers, and exacerbation rates. RESULTS: Three phenotypic clusters were identified. PC1 (early-onset allergic asthma with high IgE and severe atopic dermatitis) and PC3 (late-onset mixed asthma with moderate IgE and persistent eosinophilia) showed rapid improvements in asthma control, lung function, and quality of life, with 71% and 75% of patients free from exacerbations, respectively. PC2 (predominantly non-allergic, late-onset, female-dominant, with CRSwNP and NSAID hypersensitivity) demonstrated slower but progressive improvement, with 61.2% remaining exacerbation-free after 12 months. CONCLUSION: This retrospective real-world study identified distinct phenotypic clusters of severe asthma with differential responses to dupilumab. Early identification of these phenotypes may help guide personalized asthma management.