Clinical outcomes in severe asthma patients switching biologic therapies: A real-world cohort analysis

Background : Severe asthma is a heterogeneous condition in which biologic therapies targeting type 2 inflammation have substantially improved disease control. However, a proportion of patients fail to achieve a sustained response, necessitating biologic switching in routine clinical practice. Objective : Evaluate real-world patterns, clinical outcomes, and determinants of biologic switching in patients with severe asthma. Methods : This 15-year ambispective cohort study evaluated patients with severe asthma treated with biologic therapies between 2009 and 2025. Patients were classified as never-switchers or switchers. Clinical outcomes, exacerbation burden, oral corticosteroid use, lung function, and inflammatory biomarkers were assessed at baseline, 4/6 months, and 12 months. Comparative analyses were performed across cohorts. Results : Among 345 included patients, 116 (33.6%) underwent biologic switching. Inadequate clinical efficacy was the predominant reason for switching, frequently accompanied by persistent upper-airway comorbidities. Clinical improvement was observed following both initial biologic initiation and subsequent switching; however, patients requiring switching exhibited a higher residual disease burden and rarely achieved the level of disease control observed in stable patients. Early response at 4/6 months was informative for longer-term outcomes, and switching was safe. Conclusion : In real-world practice, biologic switching represents a common and clinically meaningful strategy in severe asthma. Early treatment response may assist in identifying patients requiring timely reassessment and individualized therapeutic optimization.