Tag Archives: CYP2C19

Optimizing PPI Therapy for Eosinophilic Esophagitis with CYP2C19 Genotyping

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P Bose et al. American Journal of Gastroenterology. DOI: 10.14309/ajg.0000000000004117 Dose May Matter: CYP2C19 Genotype and Proton-Pump Inhibitor Response in Pediatric Eosinophilic Esophagitis

Methods: A cohort study of pooled data from 2 tertiary-care pediatric centers (Riley Children’s Health,Indianapolis, IN, and Children’s Hospital of Philadelphia, Philadelphia, PA) was conducted. N=131, mean age 8.5 yrs. Individuals with certain CYP2C19 polymorphisms were classified as normal (NMs), intermediate/slow(IMs), and rapid metabolizers (RMs) of PPIs based on the presence of normal function (*1), loss-of-function (*2), or gain-of-function (*17) alleles. PPI choice and dosing:

Key findings:

  • PPI response occurred in 22.1% of subjects (29/131)
  • Overall, IMs had the highest proportion of PPI response at 33.3% (10/30), followed by NM of 21.7% (13/60) and RM of 14.6% (6/41) (P 5 0.205).
  • No ultra-rapid metabolizers had a response.

Discussion: “Atypical dosing for PPI use in EoE may be related to mechanisms of action apart from gastric acid suppression, such as inhibiting eosinophil migration or restoring esophageal mucosal barrier integrity, which have been previously proposed.”

There may have been a selection bias in this population. The methods section does not detail these cohorts precisely. It is unclear if all patients in these centers undergo CYP2C19 genotype testing. In most centers, CYP2C19 genotype testing is uncommon and may be more likely in those who have not responded to therapy.

My take:

  1. CYP2C19 genotype testing may help determine whether PPI therapy is likely to work for a patient with EoE and influence the dosage selected. This is not a new concept. It was noted at a NASPGHAN meeting in 2017.
  2. In those with unfavorable CYP2C19 genotype, either an alternative therapy or a PPI that is not metabolized with CYP2C19 (eg. rabeprazole) should be considered.

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Here’s Why CYP2C19 Testing May Be Helpful For Refractory Reflux

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Recent pediatric Rome V recommendations suggested the use of CYP2C19 testing in patients with reflux that was not responding to time-limited therapy (link: Rome V Pediatric Upper Gastrointestinal Disorders of Gut-Brain Interaction (Part 1)). The following retrospective study of adults (n=421) at an academic medical center provides a strong rationale.

L Creech et al. Clin Gastroenterol Hepatol 2026; 24: 1550-1557. Open Access! High Prevalence of CYP2C19 Rapid and Ultrarapid Metabolism Among Patients With Gastroesophageal Reflux Disease

Key finding:

  • 44% (n=184) of patients presenting to gastroenterology clinic with gastroesophageal reflux disease who underwent CYP2C19 genotyping were found to be rapid metabolizers (RMs) (38%) or ultrarapid metabolizers (6%)
  • The prevalence of Barrett’s esophagus/erosive esophagitis was higher among ultrarapid metabolizers (24%; n = 5/21) than among normal metabolizers (7%; n = 12/165; odds ratio, 3.5)
  • Among the 184 RMs, 79% (n = 146) had a change in management due to CYP testing results: 65% (n = 120) changed their medication (89 patients were switched to rabeprazole), 22% (n = 41) continued PPI therapy, and 14% (n = 26) increased their PPI dose

Discussion points:

Prevalence of CYP RMs in Other Studies:

  • “Ionovo et al studied over 2 million patients who underwent genetic testing using 23andMe and found that the rate of RMs (∗1/∗17) in the general population was 26.0%, and the rate of URMs (∗17/∗17) was 4.4%.25“
  • “Fricke-Galindo et al analyzed data from 138 studies of over 52,000 healthy volunteers from around the world.26 The highest rates of combined RMs and URMs were reported in the Middle Eastern populations (36%), followed by European (28.6%), African (16.8%), and Asian populations (3.4%).26 The prevalence was 26.7% in the United States.”
  • “Among GI clinical practice guidelines, the 2025 American Society for Gastrointestinal Endoscopy (ASGE) guideline was the first to suggest routine incorporation of CYP testing into the management of patients with GERD.30“
  • “PCABs offer a viable alternative to PPIs in patients who are RMs and should be considered accordingly. PCABs are also not dependent on preprandial dosing and thus are easier for patients to take. However, the cost of PCABs continues to be a limiting factor.”
  • Testing cost: “A typical out-of-pocket price of $250 to $400 and is covered by some insurance.39“
  • Limitations: The study population has a selection bias compared to the general population. Patients referred to a GI clinic are more likely to have treatment-refractory GERD and thus have higher rates of RMs.

My take: In patients with established GERD who are not responding to treatment, CYP testing may be helpful. This is probably true for patients with EoE as well. In patients with GERD who are RMs, options include changing to rabeprazole, higher doses, or possible use of PCABs.

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