Real-World Phenotypic Profiles and Longitudinal Lung Function Outcomes in Severe Asthma Treated with Biologic...

Background: Biologic therapies have transformed severe asthma management, but real-world evidence comparing phenotypes, lung function trajectories, and persistence across biologic classes remains limited. Objective: To characterize a real-world cohort of biologic-treated severe asthma patients, focusing on baseline phenotypes, longitudinal post-bronchodilator spirometry (including a spirometric surrogate suggestive of small airways involvement), and discontinuation/switching patterns. Methods: In this retrospective observational study at a tertiary referral center, adults with severe asthma treated with benralizumab, mepolizumab, omalizumab, or tezepelumab were included. Demographic, clinical, biomarker, and functional data were collected at baseline and follow-up. Post-bronchodilator FEV₁ and FEF25-75 (% predicted) were assessed at baseline, 6 months, 12 months, and 24-36 months when available. Longitudinal outcomes were analyzed using multivariable linear mixed-effects models; discontinuation and switching were recorded. Results: Eighty-seven patients were included (benralizumab n = 13, omalizumab n = 10, mepolizumab n = 30, tezepelumab n = 34), representing 10.9% of the clinic's population. Most had long-standing disease, elevated body mass index, and a T2-high profile. Baseline characteristics were generally similar across groups, with expected differences in total IgE (p = 0.007) and blood eosinophils (p < 0.001). The primary endpoint (FEV₁ % predicted change from baseline to 12 months) showed adjusted mean changes of +12.46 (95% CI +1.63 to +19.29; p = 0.020) with benralizumab, +15.82 (+8.35 to +23.64; p < 0.001) with mepolizumab, +16.65 (+1.58 to +31.71; p < 0.001) with omalizumab, and +15.69 (+6.52 to +24.87; p = 0.030) with tezepelumab; trajectories differed by biologic class (time × biologic p = 0.019). Although the interaction term indicated heterogeneous temporal patterns, these adjusted findings should be interpreted as associative in the context of biomarker-driven treatment selection and not as evidence of comparative superiority of any biologic class. Discontinuation occurred in 15/87 (17.2%), with switching most commonly due to inadequate control. Conclusions: Real-world severe asthma patients demonstrate heterogeneous phenotypes and spirometric trajectories on biologics. Integrating biomarkers with longitudinal lung function monitoring, including small-airway spirometric surrogates, supports individualized management.