Tezepelumab in severe asthma with pulmonary mucus plugs and eosinophilic chronic rhinosinusitis after dupilumab intolerance and suboptimal mepolizumab response: A case report

Background: Tezepelumab, a monoclonal antibody targeting thymic stromal lymphopoietin (TSLP), has demonstrated efficacy in the treatment of severe asthma and chronic rhinosinusitis with nasal polyps. However, real-world evidence remains limited, particularly for patients with eosinophilic chronic rhinosinusitis (ECRS) who exhibit inadequate or unfavorable responses to other biologics. Case presentation: We report the case of a woman with severe asthma complicated by ECRS, who exhibited divergent clinical responses to multiple biologic agents. Treatment with dupilumab initially improved both asthma and sinonasal symptoms, but was discontinued because of persistent marked peripheral eosinophilia and the development of pulmonary ground-glass opacities. Subsequent therapy with mepolizumab led to improvement in eosinophilia and partial resolution of radiologic abnormalities; however, asthma control deteriorated, and chest computed tomography revealed atelectasis and mucus plugs, accompanied by worsening of ECRS. Tezepelumab was subsequently introduced, resulting in marked improvement in asthma control, resolution of pulmonary mucus plugs, and improvement in sinonasal symptoms and radiologic findings. Conclusion: This case highlights the heterogeneous therapeutic responses to biologics targeting different inflammatory pathways in patients with severe asthma and ECRS. Upstream inhibition of TSLP with tezepelumab provided comprehensive control of both pulmonary and sinonasal disease, indicating that tezepelumab may be an effective therapeutic option for selected patients with complex type 2 airway inflammation.