Abstract Rationale Biologic therapies have transformed the management of moderate-to-severe asthma in many ways. Dupilumab and tezepelumab, targeting interleukin (IL)-4/IL-13 and thymic stromal lymphopoietin (TSLP), respectively, are two of the major biologic therapies that are FDA-approved. Dupilumab is approved for moderate-to-severe asthma in patients six years and older with an eosinophilic or oral corticosteroid-dependent phenotype, while tezepelumab is approved for severe asthma in patients 12 years and older regardless of phenotype or biomarker status. However, comparative real-world effectiveness data are limited, particularly regarding acute care utilization, and no direct head-to-head randomized controlled trials have compared tezepelumab to dupilumab. Methods We performed a retrospective cohort study using the TriNetX research network, which provides de-identified electronic medical records from over 100 healthcare institutions. Patients aged 18 years of age and older, within one year of asthma diagnosis, receiving inhaled corticosteroids (ICS), and who initiated dupilumab or tezepelumab between January 1, 2022, and January 1, 2025, were included. Propensity score matching (1:1) was conducted, balancing baseline demographics, body mass index (BMI), eosinophil count, forced expiratory volume in one second (FEV₁), smoking status, comorbidities, and medication use, resulting in 2,207 matched patients per group. Outcomes included emergency department (ED) visits, inpatient admissions, intensive care unit (ICU) admissions, and asthma exacerbations. Cox proportional hazards models estimated hazard ratios (HR) and 95% confidence intervals (CI). All-cause mortality was excluded due to low event frequency (10 per group). All outcomes were defined as events occurring between 1 day and 1 year after the index date. Results Compared to tezepelumab, dupilumab was associated with a higher risk of ED visits (HR 1.269; 95% CI 1.082-1.488; p = 0.003) and ICU admissions (HR 1.704; 95% CI 1.110-2.617; p = 0.014). No significant differences were observed in inpatient admissions (HR 1.138; 95% CI 0.913-1.419; p = 0.25) or asthma exacerbations (HR 0.935; 95% CI 0.834-1.049; p = 0.251) Table 1. Conclusion In this real-world matched cohort of adults with asthma receiving ICS, tezepelumab was associated with lower ED and ICU utilization compared with dupilumab, while no significant differences were seen for inpatient admissions or exacerbations. There are no direct randomized trials comparing these agents, and indirect evidence suggests both reduce exacerbations versus placebo but may differ by outcome or phenotype. Given the lack of direct comparative data and potential residual confounding in observational analyses, these findings should be considered hypothesis-generating and confirmed in prospective studies. This abstract is funded by: None
Lee et al. (Fri,) studied this question.