Abstract Introduction Tezepelumab targets thymic stromal lymphopoietin and was shown in pivotal trials to cut exacerbations across biomarker strata, including patients with low eosinophils and very low IgE. Hypersensitivity occurred infrequently in trials, but the product label warns that anaphylaxis can occur and may be delayed in onset. Dupilumab, which blocks IL-4/IL-13 signaling, also reduces exacerbations and improves control, though there are no head-to-head data pitting it against tezepelumab. Bronchial thermoplasty (BT) can help a subset of patients with severe asthma, but responses are heterogeneous. Since SARS-CoV-2, many clinicians also recognize a post-COVID phenotype with heightened airway reactivity that complicates treatment choices. Case Presentation A 43-year-old woman with severe, refractory asthma—well until a confirmed COVID-19 infection in 2020—required six subsequent intubations. She underwent three BT sessions (last 10/2024) with little symptomatic relief. Tezepelumab was started as an outpatient. After the second injection she noted mild facial swelling; after the fourth, she developed marked facial edema and dyspnea requiring multiple intramuscular epinephrine doses and hospital observation in 2023. Tezepelumab was stopped and dupilumab initiated the same year. She recently re-presented with dyspnea without an identifiable trigger. Chest radiograph was clear; respiratory pathogen panel and pneumonia work-up were negative. Eosinophils were 0% and total IgE 3 IU/mL. Prior PFTs (08/2024) showed FEV1 88% predicted, FEV1/FVC 90%, normal DLCO. Echocardiogram (05/2025) showed LVEF 55-60% with grade I diastolic dysfunction. She was intubated, sedated (ketamine, midazolam, propofol), treated with IV methylprednisolone, then extubated, transitioned to oral prednisone, and resumed dupilumab on discharge. Discussion/Clinical Importance This case highlights a clinically significant, temporally associated anaphylaxis to tezepelumab—consistent with post-marketing safety warnings—despite the absence of anaphylaxis in registration trials. The patient’s low-eosinophil/low-IgE, post-COVID phenotype underscores the need for vigilant monitoring for delayed hypersensitivity, prompt de-challenge, and mechanism-guided switching to an alternative biologic (dupilumab) when appropriate. Given heterogeneous BT response and the lack of head-to-head tezepelumab-dupilumab data, individualized algorithms that integrate airway biology, prior procedures, and safety signals are warranted. This abstract is funded by: none
Basta et al. (Fri,) studied this question.