Abstract Rationale Biologic therapies targeting type-2 inflammation have revolutionized the management of severe eosinophilic asthma (SEA). However, long-term real-world comparative data between anti-IL-5 receptor (benralizumab) and anti-IL-4Rα (dupilumab) agents remain scarce, particularly regarding acute respiratory failure (ARF) and cardiovascular outcomes. This study compared the real-world effectiveness and safety of benralizumab and dupilumab in adults with SEA and persistent eosinophilia. Methods A retrospective, federated electronic health record analysis was conducted using the TriNetX Research Network, encompassing 110 healthcare organizations. Adults aged ≥18 years with severe persistent asthma and eosinophilia were included. Cohorts were defined by exposure to either dupilumab or benralizumab, excluding prior or concurrent mepolizumab or other biologics. Propensity-score matching (1:1) was performed across demographic, comorbidity, and laboratory covariates. Outcomes included acute respiratory failure (ARF), major adverse cardiovascular events (MACE), all-cause mortality, and ocular adverse events (conjunctivitis or keratitis). Risk estimates, hazard ratios (HR), and Kaplan-Meier survival analyses were calculated. Results Before matching, 3,243 dupilumab and 1,123 benralizumab users were identified. After 1:1 propensity matching, 1,096 patients per cohort were retained with balanced covariates (standardized mean differences 0.1). The median follow-up duration was approximately 2.4 years (713 vs 659 days). The incidence of ARF was 5.7% among dupilumab and 7.0% among benralizumab users (risk difference -1.4%, p = 0.19; HR 0.77, 95% CI 0.55-1.07). MACE occurred in 6.6% and 6.9% of patients, respectively (risk difference -0.4%, p = 0.73; HR 0.91, 95% CI 0.66-1.25). All-cause mortality was 2.0% for dupilumab and 2.6% for benralizumab (risk difference -0.5%, p = 0.39; HR 0.75, 95% CI 0.43-1.30), while ocular events occurred in 6.8% versus 5.9% (risk difference 0.8%, p = 0.43; HR 1.11, 95% CI 0.79-1.54). Kaplan-Meier analyses showed no significant difference in event-free survival for any endpoint (log-rank p 0.1). Adverse events were infrequent and predominantly mild, with no new safety signals observed. Conclusions In this large multicenter real-world analysis of adults with severe eosinophilic asthma, benralizumab and dupilumab demonstrated comparable long-term safety profiles, including similar risks of acute respiratory failure, cardiovascular events, ocular complications, and mortality. These findings support class-level safety equivalence among biologics targeting the type-2 inflammatory pathway and reinforce individualized selection based on comorbid phenotype and therapeutic response rather than safety differentials. This abstract is funded by: None
Prasad et al. (Fri,) studied this question.
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