Tezepelumab effectiveness in Aspirin-Exacerbated Respiratory Disease: a real-world multicenter study

Aspirin-exacerbated respiratory disease (AERD) is a severe asthma phenotype characterized by chronic rhinosinusitis with nasal polyps and hypersensitivity to non-steroidal anti-inflammatory drugs, and is associated with a high disease burden. Real-world evidence on the effectiveness of tezepelumab in AERD remains limited.

To evaluate the effectiveness of tezepelumab in patients with severe asthma and AERD in routine clinical practice and to compare outcomes with those of patients without AERD.

This multicenter retrospective real-world study included patients with severe uncontrolled asthma treated with tezepelumab 210 mg every 4 weeks for 12 months. Clinical, functional, and inflammatory parameters were assessed at baseline, 6 months, and 12 months. Outcomes included severe exacerbations, emergency department visits, oral corticosteroid (OCS) exposure, asthma control, lung function, and clinical remission. Sensitivity analyses using Firth penalized logistic regression were performed to account for sparse-data bias.

Among 157 patients, 23 (14.6%) had AERD. After 12 months, tezepelumab was associated with a 70% reduction in severe exacerbations, a 76% reduction in emergency department visits, and a 55% reduction in cumulative OCS exposure in patients with AERD. Compared with patients without AERD, those with AERD had lower severe exacerbation rates (incidence rate ratio [IRR] 0.74, 95% confidence interval [CI] 0.57-0.97; p=0.028) and greater reductions in OCS exposure (IRR 0.74, 95% CI 0.71-0.77; p<0.001). Asthma control improved significantly, whereas lung function changes were modest and did not reach statistical significance. Sensitivity analyses yielded consistent but imprecise estimates with wide confidence intervals.

Tezepelumab was associated with clinically meaningful improvements in patients with severe asthma and AERD. Although patients with AERD showed a trend toward greater clinical benefit than those without AERD, the sensitivity analyses precluded definitive conclusions regarding a differential treatment effect. These findings support further prospective studies to clarify whether AERD identifies a phenotype with enhanced responsiveness to upstream TSLP blockade.