BACKGROUND: Standard treatments for eosinophilic esophagitis (EoE) may present adherence, tolerance, and efficacy challenges. Dupilumab 300 mg weekly is approved for the treatment of EoE in patients ≥ 1 year old, weighing ≥ 15 kg. This analysis aimed to evaluate dupilumab efficacy in patients from the LIBERTY EoE TREET trial (NCT03633617), with prior history of different EoE interventions. RESEARCH DESIGN AND METHODS: This analysis included patients from Parts B/B - C of LIBERTY EoE TREET. Dupilumab efficacy was analyzed according to prior swallowed budesonide or fluticasone use and in those patients with previously trialed food elimination diet, esophageal dilation, or baseline proton pump inhibitor use, as stratified by prior swallowed topical corticosteroid (STC) use or STC inadequate response/intolerance/contraindication. RESULTS: Dupilumab improved the proportion of patients achieving peak intraepithelial eosinophil count ≤ 6 eosinophils/high-power field, absolute change in Dysphagia Symptom Questionnaire score, and other histologic, symptomatic, and endoscopic endpoints vs. placebo at Week (W) 24, irrespective of prior swallowed budesonide/fluticasone use. Improvements were maintained at W52. Similar results were observed across the other subgroups. CONCLUSION: Dupilumab was efficacious in patients with EoE irrespective of prior treatments/interventions. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov identifier is NCT03633617.