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Optimizing proton-pump inhibitor therapy in paediatric eosinophilic esophagitis through CYP2C19 pharmacogenetic
Sierra Scodellaro1, Kristen A Bortolin2, Margaret A Marcon2,3
1Department of Paediatrics, Division of Clinical Pharmacology and Toxicology, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada.
Insights
Pharmacogenetic testing for CYP2C19 metabolizer status in eosinophilic esophagitis (EoE) patients can guide proton-pump inhibitor (PPI) therapy. Identifying rapid or ultra-rapid metabolizers helps optimize PPI dosing, improving treatment outcomes and remission rates.
Area of Science:
- Gastroenterology
- Pharmacogenomics
- Pediatric Medicine
Background:
- Eosinophilic esophagitis (EoE) is a chronic inflammatory condition managed with proton-pump inhibitors (PPIs).
- Genetic variations in CYP2C19 influence PPI efficacy and side effects.
- Pharmacogenetic (PGx) testing can predict PPI response, but clinical implementation is slow.
Purpose of the Study:
- To investigate the impact of CYP2C19 pharmacogenetic testing on PPI management in pediatric EoE patients.
- To correlate PGx results with PPI efficacy and histological outcomes in EoE.
Main Methods:
- A prospective cohort study of pediatric EoE patients was conducted.
- Patients underwent CYP2C19 PGx testing.
- PPI use and histological outcomes via endoscopic biopsies were assessed.
Main Results:
- 29% of 69 patients were rapid metabolizers and 7% were ultra-rapid metabolizers.
- PGx-guided management changes were made in 64% of patients.
- 49% of patients achieved histological remission, with 40% of those responding to PGx-guided therapy.
Conclusions:
- Inadequate PPI dosing due to rapid/ultra-rapid CYP2C19 metabolism may contribute to non-response in EoE.
- Identifying CYP2C19 status in pediatric EoE patients guides therapeutic changes and improves remission rates.
- Routine PGx testing should be considered for individualized PPI therapy in EoE.
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.
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