Real-World Infectious Outcomes with Dupilumab Compared with Proton Pump Inhibitors and Topical Steroids in Eosinophilic Esophagitis: A Multi-cohort Propensity Matched Analysis

BACKGROUND: Dupilumab is increasingly used for the treatment of eosinophilic esophagitis (EoE), yet its infectious safety profile in real-world clinical practice remains incompletely defined. Given the immunomodulatory effects of IL-4/IL-13 pathway inhibition, understanding infection risk relative to conventional therapies, such as proton pump inhibitors (PPIs) and swallowed TCS, is clinically important. METHODS: Using the TriNetX Research USA network, we conducted three retrospective propensity-matched cohort analyses among adults with EoE initiating (1) dupilumab vs. PPIs, (2) dupilumab vs. topical steroids, (3) dupilumab vs. combined PPI/topical steroid therapy, and (4) dupilumab vs. no treatment. Patients receiving other systemic immunosuppressive biologics were excluded. One-to-one matching was adjusted for demographics and comorbidities associated with infection risk. Infectious outcomes ≥ 30 days post-index were noted. Relative risks and Kaplan-Meier analyses were performed. RESULTS: After propensity matching, cohorts included 3053 pairs (dupilumab v. PPI), 2143 pairs (dupilumab v. topical steroids), 3973 pairs (dupilumab v. combined therapy), and 2329 pairs (dupilumab vs. no treatment). Infection rates were similar between dupilumab and PPIs or topical steroids alone across all outcomes. Compared with combined PPI/topical steroid therapy, dupilumab was associated with lower rates of COVID-19 (10.3 vs. 12.6%; RR 0.82, p = 0.001), pneumonia (1.9 vs 2.7%; RR 0.69, p = 0.011), and influenza (1.6 vs 2.3%; RR 0.71, p = 0.034). Herpes zoster, cellulitis, or urinary tract infection had similar rates. CONCLUSIONS: In large real-world matched cohorts, dupilumab was not associated with increased infectious risk compared with standard EoE therapies. These findings provide reassurance regarding the infectious safety of dupilumab in routine clinical practice.