Biologic therapies targeting type 2 inflammation in NSAID-exacerbated respiratory disease

Nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (N-ERD) is an inflammatory airway disease characterized by adult-onset asthma, chronic rhinosinusitis with nasal polyps and hypersensitivity reactions to cyclooxygenase-1 (COX-1) inhibitors. The disease is driven by dysregulated eicosanoid metabolism and sustained type 2 inflammation affecting both the upper and lower airways, resulting in severe disease and limited response to conventional therapies. In recent years, biologic agents targeting key inflammatory pathways have substantially expanded therapeutic options for patients with N-ERD. In this review, we summarize current evidence on the efficacy and mechanisms of action of approved biologic therapies, including omalizumab, anti-IL-5/IL-5Rα agents (mepolizumab, reslizumab, depemokimab, benralizumab), dupilumab and tezepelumab, with a particular focus on their effects on sinonasal disease, asthma control, aspirin tolerance, and patient-reported outcomes. Current evidence suggests that dupilumab provides the most consistent multi-domain clinical benefit, particularly in patients with refractory disease phenotypes. We further discuss emerging concepts of personalized and integrated treatment strategies combining biologics, endoscopic sinus surgery, and aspirin desensitization. Finally, we highlight unmet needs, potential biomarkers and future research directions aimed at optimizing treatment selection and improving long-term disease control in N-ERD.