Optimizing proton-pump inhibitor therapy in paediatric eosinophilic esophagitis through CYP2C19 pharmacogenetic testing

Sierra Scodellaro; Kristen A Bortolin; Margaret A Marcon; Ruud H J Verstegen; Susana Da Silva; Shinya Ito; Tamorah Lewis; Nicola L Jones; Iris Cohn; Jessie M Hulst

doi:10.1093/jcag/gwaf003

Optimizing proton-pump inhibitor therapy in paediatric eosinophilic esophagitis through CYP2C19 pharmacogenetic testing

J Can Assoc Gastroenterol. 2025 Mar 13;8(3):89-96. doi: 10.1093/jcag/gwaf003. eCollection 2025 Jun.

Authors

Sierra Scodellaro¹, Kristen A Bortolin², Margaret A Marcon^{2

3}, Ruud H J Verstegen^{1

3

4}, Susana Da Silva⁵, Shinya Ito^{1

3}, Tamorah Lewis^{1

3}, Nicola L Jones^{2

3}, Iris Cohn^{1

3}, Jessie M Hulst^{2

3

6}

Affiliations

¹ Department of Paediatrics, Division of Clinical Pharmacology and Toxicology, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada.
² Department of Paediatrics, Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada.
³ Department of Paediatrics, University of Toronto, Toronto, ON M5G 1X8, Canada.
⁴ Department of Paediatrics, Division of Rheumatology, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada.
⁵ Temerty Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada.
⁶ Department of Nutritional Sciences, University of Toronto, Toronto, ON M5S 1A8, Canada.

Abstract

Background: Eosinophilic esophagitis (EoE) is a chronic inflammatory disorder which can respond to proton-pump inhibitors (PPIs). Genetic variation in the CYP2C19 metabolism gene influences PPI efficacy and adverse effects. Pharmacogenetic testing (PGx) can predict PPI response by analyzing genetic variation, particularly identifying patients categorized as CYP2C19 rapid or ultra-rapid metabolizers who might benefit from PPI dosage increases or changes to pharmacotherapy. Although PGx clinical practice guidelines have been established for PPI use, routine clinical implementation has been slow.

Methods: We conducted a non-interventional prospective cohort study of patients followed by a paediatric EoE clinic between 2020 and 2023. Eligible patients underwent CYP2C19 PGx testing, with results correlated to PPI use and histological outcomes assessed via endoscopic biopsies.

Results: Sixty-nine patients underwent PGx testing; 20 (29%) and 5 (7%) were determined to be rapid and ultra-rapid metabolizers, respectively. PGx-based management changes were made in 44 (64%) patients. Forty-three (62%) patients completed reassessment endoscopy, of which 21 (49%) demonstrated histological remission; 17 (40%) of these patients achieved remission after PGx-guided drug changes.

Conclusions: This study demonstrates that PPI non-response in patients with EoE may partly be due to inadequate PPI dosing in those with rapid or ultra-rapid CYP2C19 metabolizer status. Identifying CYP2C19 metabolizer status in pediatric patients with EoE for first-generation PPIs leads to therapeutic management changes and can improve histological remission rates. Clinicians treating EoE patients should consider routine PGx testing in combination with monitoring clinical factors to guide individualized PPI therapy and optimize dosing.

Keywords: CYP2C19; eosinophilic esophagitis (EoE); pharmacogenetics (PGx); precision medicine; second-generation proton-pump inhibitors (PPIs).