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

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

Sierra Scodellaro  1 , Kristen A Bortolin  2 , Margaret A Marcon  2   3 , Ruud H J Verstegen  1   3   4 , Susana Da Silva  5 , Shinya Ito  1   3 , Tamorah Lewis  1   3 , Nicola L Jones  2   3 , Iris Cohn  1   3 , Jessie M Hulst  2   3   6
Affiliations

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

Sierra Scodellaro et al. J Can Assoc Gastroenterol. .

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).

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Conflict of interest statement

Conflict of interest disclosure forms (ICMJE) have been collected for all co-authors and can be accessed as supplementary material here.

Figures

Graphical Abstract
Graphical Abstract
Figure 1.
Figure 1.
Proposed clinical management algorithm for newly diagnosed treatment naïve paediatric EoE patients or known EoE patients with active disease on non-PPI therapy based on CYP2C19 metabolizer status. Abbreviations: IM, intermediate metabolizer; NM, normal metabolizer; PM, poor metabolizer; PPI, proton-pump inhibitor; RM, rapid metabolizer; UM, ultra-rapid metabolizer. First-generation PPI includes lansoprazole, and omeprazole. Second-generation PPI (excluding dexlansoprazole) refers to rabeprazole and esomeprazole. *Histological remission = peak eosinophil count < 15/hpf in oesophageal biopsies and improvement in symptoms confirmed by endoscopy. **Histological improvement = change from diffuse to localized disease or a reduction in eosinophil count of at least 50% in oesophageal biopsies at 1 or more levels, while maintaining a peak count > 15/hpf.
Figure 2.
Figure 2.
Proposed clinical management algorithm for paediatric EoE patients with active disease on first-generation PPI therapy based on CYP2C19 metabolizer status. Abbreviations: IM, intermediate metabolizer; NM, normal metabolizer; PM, poor metabolizer; PPI, proton-pump inhibitor; RM, rapid metabolizer; UM, ultra-rapid metabolizer. First-generation PPI includes lansoprazole and omeprazole. Second-generation PPI (excluding dexlansoprazole) refers to rabeprazole and esomeprazole.*Histological remission = peak eosinophil count < 15/hpf in oesophageal biopsies and improvement in symptoms confirmed by endoscopy. **Histological improvement = change from diffuse to localized disease or a reduction in eosinophil count of at least 50% in oesophageal biopsies at 1 or more levels, while maintaining a peak count > 15/hpf.
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