Marked Clinical and Functional Response to Tezepelumab After Failure of Anti-Interleukin-5 (Anti-IL-5) Therapy in Severe Asthma

Biologics targeting type 2 inflammation, including anti-interleukin-5 (anti-IL-5) antibodies, have improved outcomes in severe asthma, but some patients remain symptomatic with apparently persistent severe airflow limitation. We report an 86-year-old woman with long-standing severe asthma who initially had high blood eosinophil counts and serum immunoglobulin E (IgE) levels. She responded to mepolizumab for years, while airflow limitation persisted. She developed an exacerbation seven years after mepolizumab initiation despite ongoing mepolizumab and inhaled triple therapy, while type 2 biomarkers normalized. She continued to experience dyspnea with triggers such as cold air and pollen. After switching from mepolizumab to tezepelumab, her symptoms rapidly resolved; forced expiratory volume in one second (FEV₁) increased from 0.64 L (45.7% predicted) to 1.45 L (103% predicted) within two months, and the concave flow-volume loop became almost normal. This case suggests that chronic airflow limitation in severe asthma is not always irreversible and that switching to tezepelumab may induce dramatic functional recovery even after anti-IL-5 therapy.