Association of CYP2C19 Phenotype on Historical Medication Prescribing for Gastroesophageal Reflux Disease

Introduction: While consensus guidelines exist for phenotype-guided proton pump inhibitor (PPI) dosing in Helicobacter pylori infection, the impact in gastroesophageal reflux disease (GERD) treatment in a real-world setting is unknown. The study aims were to determine whether CYP2C19 rapid metabolizers (RMs) and ultrarapid metabolizers (UMs) have higher PPI doses and more treatment failures than normal metabolizers (NMs) in the treatment of GERD. Methods: In this retrospective chart review, adults with pharmacogenetic (PGx) testing results at the study center and treated with PPI therapy for GERD were included for enrollment into 1 of 3 cohorts: CYP2C19 UM, RM, and NM. Pertinent baseline characteristics collected were age, body mass index, tobacco, and alcohol history. The primary outcome was the comparison of total daily omeprazole equivalents (OEs) of the highest prescribed PPI dose. Secondary outcomes included incidence of upper gastrointestinal bleed (UGIB) and historical trials of PPIs, histamine-2 blockers, antacids, sucralfate, and prokinetics. Continuous outcomes were compared with one-way analysis of variance, and nominal outcomes were compared with a χ 2 in RStudio. Results: There were 48 UM, 298 RM, and 432 NM that met study inclusion. Baseline characteristics were similar across cohorts. Mean total OE did not differ between groups: UM 41.6 mg, RM 40.1 mg, NM 38.5 mg ( P = 0.52). There were no differences seen among individual gastric agents or mean total number of historical gastric medications trialed: UM 2.5, RM 2.4, NM 2.3 ( P = 0.17) medications. The incidence of UGIB was not statistically different between cohorts: UM 12.5%, RM 12.8%, NM 9.3% ( P = 0.13). Conclusion and Relevance: There was no association between CYP2C19 phenotype and historical medication prescribing for GERD.