Effectiveness of tezepelumab in severe asthma: A multicenter real-world study.

Abstract

Severe asthma is a complex, heterogeneous disease that remains a major therapeutic challenge. Despite several biologics targeting type 2 (T2) inflammation, some patients remain uncontrolled, highlighting the need for upstream interventions. Tezepelumab, a monoclonal antibody against thymic stromal lymphopoietin (TSLP), has shown broad efficacy in randomized trials regardless of eosinophilic status or biomarker levels. We conducted a prospective, multicenter, observational study to assess real-world effectiveness and safety of tezepelumab in severe asthma. Thirty patients were enrolled at two tertiary centers in Italy between September 2023 and December 2024. Inclusion criteria were a severe asthma diagnosis per ERS and GINA 2024 guidelines and inadequate control despite maximal inhaled therapy. Tezepelumab was given at 210 mg every 4 weeks. Clinical, functional, and biomarker data were collected at baseline, 1 month, and 6 months. After six months, patients showed significant improvement in Asthma Control Test (ACT) score, with marked reductions in oral glucocorticoid use and exacerbation rate. Sinonasal symptoms improved over time. Blood eosinophils and FeNO decreased significantly, while total IgE remained unchanged. Lung function improved in both FEV₁/FVC ratio and FEF_25-75, suggesting benefit on airflow limitation and small airway function. No serious adverse events occurred. Improvements were consistent in both T2-high and T2-low subgroups. This real-world study confirms tezepelumab's clinical effectiveness and safety in severe asthma. Benefits across inflammatory phenotypes support TSLP blockade as a broad-spectrum therapeutic approach. Larger, longer-term studies are warranted to confirm results and identify response predictors.