Comparative Risk of Respiratory Virus Infections Among Patients with Asthma Treated with Biologic Therapies

BACKGROUND: Respiratory virus infections are a major cause of morbidity in asthma. Although biologic therapies targeting type 2 inflammation are widely used for severe asthma, their comparative effects on respiratory virus infection risk remain unclear. METHODS: We conducted a retrospective cohort study using the TriNetX US Collaborative Network, including adults with asthma who newly initiated benralizumab, omalizumab, dupilumab, or mepolizumab. Using an active comparator, new-user design with 1:1 propensity score matching, we compared benralizumab with each biologic. The primary outcome was a composite of respiratory virus infections (COVID-19, influenza, RSV infection, and viral pneumonia) over three years. Hazard ratios (HRs) were estimated using Cox proportional hazards models. RESULTS: After matching, 5,663 benralizumab-omalizumab pairs, 7,075 benralizumab-dupilumab pairs, and 6,492 benralizumab-mepolizumab pairs were included. Benralizumab was associated with a higher risk of composite respiratory virus infection than omalizumab (HR 1.49, 95% CI 1.33-1.66), dupilumab (HR 1.24, 95% CI 1.11-1.39), and mepolizumab (HR 1.24, 95% CI 1.12-1.38; all p < 0.001). Risks of COVID-19 and influenza were consistently higher with benralizumab across all comparisons. Viral pneumonia risk was higher versus dupilumab (HR 1.59, 95% CI 1.18-2.14) but not versus omalizumab or mepolizumab. RSV infection risk did not differ significantly. CONCLUSIONS: Benralizumab was associated with a higher risk of respiratory virus infections than omalizumab, dupilumab, and mepolizumab. These findings suggest that profound eosinophil depletion may impair antiviral host defense and should be considered when selecting biologic therapy for patients at increased risk of respiratory viral infections.