Download PDF
CC BY-NC-ND 4.0 · Endosc Int Open 2021; 09(06): E843-E847
DOI: 10.1055/a-1401-9853
Innovation forum

CYP2C19 genotype variability in patients with refractory gastroesophageal reflux after per-oral endoscopic myotomy (POEM)

Yaseen B. Perbtani
1   Department of Internal Medicine, University of Florida, Gainesville, Florida, United States
,
Donevan R. Westerveld
2   Division of Gastroenterology and Hepatology, University of Florida, Gainesville, Florida, United States
,
Dennis J. Yang
1   Department of Internal Medicine, University of Florida, Gainesville, Florida, United States
,
Peter V. Draganov
1   Department of Internal Medicine, University of Florida, Gainesville, Florida, United States
› Author Affiliations
› Further Information
Also available at
   Permissions and Reprints

Abstract

Background and study aims Symptomatic gastroesophageal reflux is a recognized potential adverse event following peroral endoscopic myotomy (POEM). Proton pump inhibitors (PPIs) are an effective first-line therapy; although their efficacy can be affected by genotype cytochrome P450 2C19 (CYP2C19) variability leading to enhanced clearance of PPIs. The aim of our study was to evaluate the incidence of CYP2C19 genotype variability in POEM patients with refractory gastroesophageal reflux symptoms.

Patients and methods This was a single-center, prospective, cohort study of consecutive POEM cases during a 7-year study period (2013–2020). Reflux symptoms were assessed with the validated gastroesophageal reflux disease questionnaire (GerdQ) and objective pH testing after POEM. CYP2C19 genotype testing was obtained in all patients with refractory gastroesophageal reflux disease (GERD) symptoms, defined as an abnormal pH study and GerdQ score ≥ 8 while on PPIs twice daily.

Results POEM was performed in 325 consecutive patients (48.3 % female; mean age 57 years) during the study period. Twenty patients (6.8 %) had PPI-refractory, post-POEM gastroesophageal reflux based on their GerdQ score (median 9, range 8–11) and abnormal pH studies. CYP2C19 genotype testing identified 55 % (11/20) of these patients as being rapid metabolizers. Out of these, 9 (82 %) had improvement in clinical GERD symptoms after changing to a PPI less affected by CYP2C19 pharmacogenetics.

Conclusions Post-POEM, PPI-refractory GERD is rare. As shown in this study, rapid metabolizers commonly respond by changing to a PPI less affected by CYP2C19 pharmacogenetics, thereby reducing the risk of long-term consequences from GERD and unnecessary anti-reflux surgery.



Publication History

Received: 10 October 2020

Accepted: 15 February 2021

Article published online:
27 May 2021

© 2021. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Inoue H, Minami H, Kobayashi Y. et al. Peroral endoscopic myotomy (POEM) for esophageal achalasia. Endoscopy 2010; 42: 265-271
    Article in Thieme ConnectPubMedGoogle Scholar
  • 2 Inoue H, Shiwaku H, Kobayashi Y. et al. Statement for gastroesophageal reflux disease after peroral endoscopic myotomy from an international multicenter experience. Esophagus 2020; 17: 3-10
    CrossrefPubMedGoogle Scholar
  • 3 Repici A, Fuccio L, Maselli R. et al. GERD after per-oral endoscopic myotomy as compared with Heller's myotomy with fundoplication: a systematic review with meta-analysis. Gastrointest Endosc 2018; 87: 934-943.e918
    CrossrefPubMedGoogle Scholar
  • 4 Subramanian CR, Triadafilopoulos G. Refractory gastroesophageal reflux disease. Gastroenterol Rep 2015; 3: 41-53
    CrossrefPubMedGoogle Scholar
  • 5 Andersson T, Holmberg J, Röhss K. et al. Pharmacokinetics and effect on caffeine metabolism of the proton pump inhibitors, omeprazole, lansoprazole, and pantoprazole. Br J Clin Pharmacol 1998; 45: 369-375
    CrossrefPubMedGoogle Scholar
  • 6 El Rouby N, Lima JJ, Johnson JA. Proton pump inhibitors: from CYP2C19 pharmacogenetics to precision medicine. Expert Opin Drug Metab Toxicol 2018; 14: 447-460
    CrossrefPubMedGoogle Scholar
  • 7 Furuta T, Sugimoto M, Kodaira C. et al. CYP2C19 genotype is associated with symptomatic recurrence of GERD during maintenance therapy with low-dose lansoprazole. Eur J Clin Pharmacol 2009; 65: 693-698
    CrossrefPubMedGoogle Scholar
  • 8 Kahrilas PJ, Bredenoord AJ, Fox M. et al. The Chicago Classification of esophageal motility disorders, v3.0. Neurogastroenterol Motil 2015; 27: 160-174
    CrossrefPubMedGoogle Scholar
  • 9 Jones R, Junghard O, Dent J. et al. Development of the GerdQ, a tool for the diagnosis and management of gastro-oesophageal reflux disease in primary care. Aliment Pharmacol Ther 2009; 30: 1030-1038
    CrossrefPubMedGoogle Scholar
  • 10 Scott SA, Sangkuhl K, Gardner EE. et al. Clinical Pharmacogenetics Implementation Consortium guidelines for cytochrome P450-2C19 (CYP2C19) genotype and clopidogrel therapy. Clin Pharmacol Ther 2011; 90: 328-332
    CrossrefPubMedGoogle Scholar
  • 11 Furuta T, Shirai N, Watanabe F. et al. Effect of cytochrome P4502C19 genotypic differences on cure rates for gastroesophageal reflux disease by lansoprazole. Clin Pharmacol Ther 2002; 72: 453-460
    CrossrefPubMedGoogle Scholar
  • 12 Ichikawa H, Sugimoto M, Sugimoto K. et al. Rapid metabolizer genotype of CYP2C19 is a risk factor of being refractory to proton pump inhibitor therapy for reflux esophagitis. J Gastroenterol Hepatol 2016; 31: 716-726
    CrossrefPubMedGoogle Scholar
  • 13 Jones EL, Meara MP, Schwartz JS. et al. Gastroesophageal reflux symptoms do not correlate with objective pH testing after peroral endoscopic myotomy. Surg Endosc 2016; 30: 947-952
    CrossrefPubMedGoogle Scholar