Introduction
Eosinophilic esophagitis (EoE) is a chronic, progressive, type 2 inflammatory disease of the esophagus. Dupilumab, a fully human monoclonal antibody that blocks interleukin-4 and interleukin-13, significantly improved histologic and endoscopic outcomes versus placebo in Parts A and B of the EoE KIDS study in pediatric (1–11 years) patients with EoE (NCT04394351).
Aims & Methods
The aim of this analysis was to assess safety and efficacy of long-term dupilumab in the Part C open-label extension (OLE). Patients completing Week (W)52 in Part B were eligible for Part C, where they received the weight-tiered, open-label dupilumab regimen later approved by the FDA (similar to the Part A and B higher-exposure regimen). Part C ended early with FDA approval of dupilumab for pediatric patients with EoE; efficacy data to the last prespecified assessment at W100 are reported.
Results
102 patients enrolled in Part A, 98 in Part B, and 61 in Part C. At W100, the proportions of patients achieving peak esophageal intraepithelial eosinophil counts of ≤6 and <15 eosinophils/high-power field (eos/hpf) were similar/improved vs those observed with higher-exposure dupilumab through W52 of Part B: 70.7% vs 62.9% and 92.7% vs 85.7%, respectively. Additionally, mean (standard deviation) changes from Part A baseline at W100 were similar to those with higher-exposure dupilumab through W52 of Part B in EoE-Histologic Scoring System grade and stage scores (-0.85 [0.39] vs -0.97 [0.39], and -0.85 [0.36] vs -0.89 [0.32], respectively) and EoE-Endoscopic Reference Score (-5.34 [2.54] vs -4.77 [3.08]). Overall, 53/61 (86.9%) patients reported mild or moderate adverse events (AEs) and 3/61 (4.9%) reported serious AEs (none deemed related to dupilumab). The most common treatment-related AE during Part C was injection site reaction.
Conclusion
Dupilumab had a consistent, acceptable safety profile and maintained histologic and endoscopic efficacy in pediatric patients with EoE to W100. Future analyses will evaluate symptoms.
Disclosure
Chehade M: Adare Pharma Solutions/Ellodi, Allakos, AstraZeneca, BMS, Nexstone Immunology, Phathom, Recludix Pharma, Regeneron Pharmaceuticals Inc., Sanofi, Shire/Takeda ‒ consultant; Adare Pharma Solutions/Ellodi, Allakos, AstraZeneca, Celgene/BMS, Danone, Regeneron Pharmaceuticals Inc., Shire/Takeda ‒ research funding. Dellon ES: Abbvie, Adare/Ellodi, Akesobio, Alfasigma, ALK, Allakos, Amgen, Apollo, Aqilion, Arena/Pfizer, Aslan, AstraZeneca, Avir, Biocryst, Bryn, Calypso, Celgene/Receptos/BMS, Celldex, EsoCap, Eupraxia, Dr. Falk Pharma, Ferring, GI Reviewers, GSK, Holoclara, Invea, Knightpoint, LucidDx, Morphic, Nexstone Immunology/Uniquity, Nutricia, Parexel/Calyx, Phathom, Regeneron, Revolo, Robarts/Alimentiv, Sanofi, Shire/Takeda, Target RWE, Upstream Bio – consultant; Allakos, Aqilion, Holoclara, Invea – educational grant. Adare/Ellodi, Allakos, Arena/Pfizer, AstraZeneca, Celldex, Eupraxia, Ferring, GSK, Meritage, Miraca, Nutricia, Celgene/Receptos/BMS, Regeneron, Revolo, Sanofi, Shire/Takeda – research funding; Allakos, Aqilion, Holoclara, Invea – educational grant. Pesek RD: Regeneron Pharmaceuticals Inc. ‒ advisory board. Collins MH: Alimentiv, Allakos, Arena, AstraZeneca, BMS, Calypso, EsoCap, GSK, Regeneron Pharmaceuticals Inc., Shire – consultant. Ashok D: Alexion Pharma, LaunchitDTx, Mirum Pharma ‒ consulting fees. Sanofi ‒ speaker fees. Liu R, Xia C: Regeneron Pharmaceuticals Inc. – employees and shareholders. Louisias M: Sanofi – employees, may hold stock and/or stock options in the company.
