Introduction

Eosinophilic esophagitis (EoE), a chronic, progressive, type 2 inflammatory disease. Dupilumab is a fully human monoclonal antibody that blocks interleukin (IL)-4 and IL-13, key drivers of type 2 inflammation.

Aims & Methods

The aim of this analysis was to assess the impact of dupilumab on caregiver-reported EoE symptoms in children aged 1 to <12 years with active EoE in the placebo-controlled Part A of the Phase 3 EoE KIDS trial (NCT04394351). This analysis was conducted in children randomized to dupilumab higher-exposure or placebo. The Pediatric Eosinophilic Esophagitis Symptom Score (PEESS) version 2.0 (caregiver version) comprises 20 items (items scored 0–4; higher scores indicate greater burden) assessing frequency (11 questions) and severity (9 questions) of symptoms and adaptive behaviors, containing 4 subdomains: dysphagia, nausea/vomiting, gastroesophageal reflux disease, and pain. PEESSv2.0 was evaluated at baseline and Week 16 in EoE KIDS; total, frequency, severity, domain (all scored 0–100), and individual item scores were compared in patients treated with dupilumab higher-exposure or placebo. Reported p-values are nominal.

Results

Baseline characteristics were similar in dupilumab higher-exposure (n=37) and placebo (n=34) groups; baseline mean PEESSv2.0 total scores were 38.0 and 38.3, respectively. At Week 16, PEESSv2.0 total was reduced with dupilumab higher-exposure vs placebo (least squares [LS] mean change [95% confidence interval (CI)] -19.86 [-24.98, -14.74] vs -11.83 [-17.61, -6.05]; LS mean difference [95% CI] -8.03 [-15.39, -0.67], p<0.05). At Week 16, all domain subscores were at least numerically reduced with dupilumab higher-exposure vs placebo with nominal significance observed in LS mean scores for frequency (-22.47 vs -11.88 [p<0.01]), dysphagia (-23.38 vs -13.76 [p<0.05]), and nausea/vomiting (-29.08 vs -15.30 [p<0.05]) domains.

Conclusion

Dupilumab higher-exposure led to improvement in PEESSv2.0 total score vs placebo at Week 16 in EoE KIDS. Frequency, dysphagia, and nausea/vomiting domains were improved with nominal significance, though all domains were improved numerically with dupilumab vs placebo.

Disclosure

Rothenberg ME: Allakos, AstraZeneca, BMS, Celldex, ClostraBio, EnZen Therapeutics, GSK, Guidepoint, Pfizer, PulmOne, Regeneron Pharmaceuticals Inc., Revolo Biotherapeutics, Sanofi, Santa Ana Bio, Serpin Pharma, Spoon Guru, and Uniquitybio – consultant; Allakos, Celldex, ClostraBio, EnZen Therapeutics, PulmOne, Santa Ana Bio, Serpin Pharma, Spoon Guru, and Uniquitybio – equity interest; Receives royalties from Mapi Research Trust (for PEESSv2), Teva Pharmaceuticals (for reslizumab), and UpToDate; and is the inventor of patents owned by Cincinnati Children’s Hospital.
Oliva S: Celgene/Receptos/BMS, Medtronic, Ocean Pharma, Sanofi/Regeneron – advisory board; Medtronic, Sanofi/Regeneron – speaker fees.
Ashok D: Sanofi – speaker fees.
Xia C, Durrani S, Radwan A, Thomas R: Regeneron Pharmaceuticals Inc. – employees and shareholders.
Pela T, Jacob-Nara J, Tilton ST: Sanofi – employee, may hold stock and/or stock options in the company.