The goal of this clinical trial is to [primary purpose: e.g., learn if intervention or health behavior can treat, prevent, diagnose etc.] in [describe participant population/primary condition; could include any of the following: sex/gender, age groups, healthy volunteers]. The main question[s] it aims to answer [is/are]:

Does dupilumab or swallowed topical fluticasone improve the diameter of the esophagus more? Does dupilumab or swallowed topical fluticasone reduce inflammation in the esophagus more? Are comparative effective clinical trials feasible in this patient population?

Researchers will compare dupilumab 300 mg weekly compared to swallowed fluticasone to see if there is a difference in treatment response.

Participants will be asked to:

• Be randomized to either dupilumab sq weekly or swallowed topical fluticasone twice daily.
• Participate in 8 study visits over 52 weeks
• Complete questionnaires
• Have an endoscopy with biopsies and EndoFLIP measurements.
• Swallow an Esophageal String Test

Inclusion Criteria:

• Seen at CHCO for clinical care.
• Age 12 - 25 years old inclusive
• Weight ≥40 kg at the time of screening visit
• Confirmed EoE as diagnosed by biopsy with eosinophils ≥15 eosinophils/hpf in at least 2 esophageal regions at screening endoscopy
• Report of an average of at least 2 episodes of dysphagia per week in the 4 weeks prior to screening.
• Evidence of fibrostenotic features at time of screening endoscopy (grade 2 or 3 esophageal rings, stricture, delayed passage of barium tablet on fluoroscopy, and/or distensibility ≤15mm)

Exclusion Criteria:

• Esophageal dilation performed at index endoscopy
• Patients with stricture undergoing dilation at index endoscopy may be rescreened if they meet all other eligibility criteria.
• Patients with acute food impaction will not be enrolled at their therapeutic endoscopy but are eligible for enrollment subsequently if they meet all other eligibility criteria.
• Eligible patients on current STCs can be enrolled but need to be on stable dosing less than or equal to 440 mcg two times daily fluticasone equivalent for 3 months prior to enrollment.
• Patients who have received dupilumab in the past 12 months for any indication are excluded.
• Diet restrictions and PPI use must stay unchanged in the 8 weeks prior to index endoscopy and through the study period.
• Patients with a fasting morning cortisol <5 within 2 months of screening will not be enrolled. If repeat cortisol levels are normal, patients can be reconsented.
• Known other esophageal disease or esophageal injury (e.g. achalasia, tracheoesophageal fistula, congenital stricture, caustic injury, history of esophageal surgery), inflammatory bowel disease, liver disease, connective tissue disorder, or bleeding disorder.
• Patients with a known gelatin allergy will be excluded from EST collection.