Clinical Efficacy of Biologics and ATAD in NSAID-Exacerbated Respiratory Disease: A Phenotype-Based Comparative Study

The emergence of biologics has challenged the traditional role of aspirin therapy after desensitization (ATAD) in treating nonsteroidal anti-inflammatory drug-exacerbated respiratory disease, raising the million-dollar question: "Which treatment is right for which patient?" However, comparative efficacy data and phenotype-based strategies remain scarce.

To compare the efficacy of omalizumab, mepolizumab, benralizumab, ATAD, and their combinations in nonsteroidal anti-inflammatory drug-exacerbated respiratory disease, and to propose phenotype-based treatment recommendations.

This retrospective study included 70 adult patients diagnosed with nonsteroidal anti-inflammatory drug-exacerbated respiratory disease who had received treatment for at least 6 months. Outcomes included Asthma Control Test score, Sino-Nasal Outcome Test score, smell/taste score, blood eosinophils, oral corticosteroid use, and emergency department visits. Phenotypes were identified via hierarchical clustering using Factor Analysis for Mixed Data and Ward's method.

Sex (Cramér's V = 0.10), age (eta squared = 0.005), and body mass index (epsilon squared = 0.001) were similar across treatment groups. Improvements were observed in Sino-Nasal Outcome Test score (effect size [ES] = 2.0), eosinophils (ES = 1.6), Asthma Control Test score (ES = -2.1), oral corticosteroid use (ES = 1.0), loss of smell or taste score (ES = 0.7), and emergency department visits (ES = 0.3) in the ATAD + biologic group; Sino-Nasal Outcome Test score (ES = 1.76), Asthma Control Test score (ES = 2.31), and oral corticosteroid use (ES = 0.86) in the omalizumab group; eosinophils (ES = 2.81) and emergency department visits (ES = 0.69) in the benralizumab group; and loss of smell or taste score (ES = 0.88) in the mepolizumab group. Among the 3 phenotype groups identified through hierarchical clustering, cluster 1 benefited most from ATAD + biologic, cluster 2 from biologics, and cluster 3 from ATAD.

Each treatment demonstrated specific benefits, but combination therapy provided the most comprehensive clinical outcomes. Phenotype-guided strategies may optimize therapeutic decisions: ATAD for mild, biologics for moderate, and combination therapy for severe phenotypes.