Scientific Poster Session II: Late-Breaking Original Research

Late Breaking Original Research
  Sunday, November 12, 2023
  12:45 PM–02:15 PM

Abstract

Introduction: Patient risk factors for PPI-associated AEs beyond PPI dose and therapy duration have not been well defined but could help personalize treatment decisions to reduce AE risk. Genetic variation in CYP2C19 is a known contributor of variation in PPI exposure and response, especially for 1^st generation PPIs. Patients with decreased CYP2C19 activity have significantly higher PPI exposure and greater acid suppression but it remains unclear if this contributes to AE risk.

Research Question or Hypothesis: Decreased CYP2C19 activity will increase PPI-associated AEs.

Study Design: Retrospective review

Methods: Patients who received at least 30 consecutive days of PPI with biorepository genetic data were included. New diagnoses of bone fracture(BF), hypomagnesemia(HM), pneumonia(PNA), and Clostridioides difficile infection(CDI) during or within 14 days of PPI use were extracted. CYP2C19 activity was defined as increased, normal, or decreased based on genotype in accordance with CPIC guidelines. PPI agent and total daily dose were captured and classified by generation and intensity. AEs were evaluated across CYP2C19 activity, PPI generation, and dose intensity via Chi-squared test. Cumulative days of PPI were compared between patients with and without AE.

Results: We included 12625 patients; 92% received a 1^st generation PPI and 38.8% had normal CYP2C19 activity. AEs occurred in 4.4% of patients. CYP2C19 activity was not associated with BF, HM, or PNA. CDI rates were highest in patients with decreased CYP2C19 activity, especially when considering only 1^st generation PPIs (OR:1.5;95%CI:1.1-2.1). High intensity PPI increased risk of pneumonia (OR:3.9;95%CI:2.0-7.6), CDI (OR:1.7;95%CI:1.2-2.5), and HM (OR:1.9;95%CI:1.3-2.7). Patients with AEs had higher median cumulative days of therapy (1216(529-2234) vs. 610(245-1458);p<0.01).

Conclusion: CYP2C19 genotype may help identify patients with higher CDI risk when receiving 1^st generation PPI therapy. PPI discontinuation or using a 2^nd generation PPI could be evaluated in future trials as potential strategies to reduce risk of developing CDI.

Presenting Author

Amy Pasternak PharmD
University of Michigan College of Pharmacy

Authors

Gregory Eschenauer PharmD
University of Michigan College of Pharmacy

Krishna Rao MD, MS
University of Michigan Medical School