Project Abstract Eosinophilic Esophagitis (EoE) is a chronic immune mediated inflammatory disease of the esophagus that has emerged as a common cause of swallowing difficulty in children and adults leading to increased health care utilization and negatively impacting quality of life. With rapidly increasing prevalence, clinical phenotypes have emerged including a fibrostenotic phenotype (FS-EoE) defined by characteristic endoscopic appearance, significant esophageal stiffness and narrowing. This phenotype has had lower treatment response and increased symptom burden. Management guidelines do not yet provide a paradigm that consider symptom severity or the presence of fibrostenosis and do not yet incorporate newly approved biologics for EoE. With the recent approval of biologics targeting pathways implicated in the propagation of inflammation and fibrotic remodeling, comparative studies that inform patients and providers alike on the effectiveness of alternate treatment strategies are needed. The purpose of this small R01 proposal is to establish pilot data on the comparative effectiveness and feasibility of a randomized clinical trial of dupilumab versus swallowed topical corticosteroid, fluticasone, in the treatment of FS-EoE. This trial proposes the use of a novel and innovative outcome measure of treatment response, distensibility as measured by EndoFLIP, for its ability to measure changes in esophageal narrowing and association with patient reported symptoms. Biospecimens collected during the course of this trial, including esophageal mucosal biopsies and a state-of-the-art Esophageal String Test, will be used to establish a biorepository linked to trial outcome data to explore next step mechanistic questions related to treatment response and esophageal remodeling in EoE. Results from this proposed study will lay the foundation for a definitive multicenter comparative therapeutic trial for the management of FS-EoE.