https://orcid.org/0009-0008-5944-8877
![Sample our Medicine, Dentistry, Nursing & Allied Health journals, sign in here to start your FREE access for 14 days]({"type":"image" , "src" : "/sda/5944/TOC-Subject-Sample-2021-Medicine-Dentistry-Nursing-Allied-Health.jpg"})
ABSTRACT
Gastroesophageal reflux disease (GERD) and Helicobacter pylori (H. pylori) infection are different disease states that are united by the core role of acid suppression in their management. In GERD, proton pump inhibitors (PPIs) have long been standard therapy based on abundant positive clinical trial data supporting their efficacy and safety. In H. pylori, PPIs are also a critical element of therapy in combination with 1 or more antibiotics to achieve and maintain a pH that maximizes the efficacy of therapy. Despite the considerable clinical success and widespread use of PPIs, room remains for agents with differentiated pharmacokinetic and pharmacodynamic profiles. The potassium-competitive acid blockers (PCABs) are mechanistically distinct from PPIs but are acid-stable and do not require activation of the proton pump by coadministration of food. In pharmacodynamic studies, these agents have shown greater durations of acid suppression above the critical threshold of pH 4 (for GERD) and pH 6 (for H. pylori), which have been shown to optimize therapeutic efficacy in these settings. These results have translated in clinical studies to similar and, in some cases, improved outcomes relative to PPIs in these disease states. This review summarizes current knowledge on the physiology of acid secretion, pathophysiology and management of GERD and H. pylori, and key characteristics and clinical trial data for PPIs and PCABs.
Abbreviations
| ATP | = | adenosine triphosphate |
| CYP | = | cytochrome |
| EE | = | erosive esophagitis |
| GERD | = | gastroesophageal reflux disease |
| KCNQ1 | = | potassium voltage-gated channel subfamily Q member 1 |
| NERD | = | non-erosive reflux disease |
| PCAB | = | potassium-competitive acid blocker |
| PPI | = | proton pump inhibitor |
Declaration of financial/other relationships
CM Antequera has participated in an advisory board for Phathom Pharmaceuticals, Inc. K Orleck has received payment/honoraria from AbbVie, Janssen, Salix, BMS, Lilly, Ardelyx and consulting fees from AbbVie, Lilly, Janssen, Ardelyx. WL Wright has participated in an advisory board for Phathom Pharmaceuticals, Inc. R Jacob and A Kenneally are employees of Phathom Pharmaceuticals, Inc. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. A reviewer on this manuscript has disclosed receiving honoraria from Takeda Pharmaceuticals. Another reviewer on this manuscript has disclosed being on the Takeda Brazilian Board. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.
Acknowledgments
Editorial assistance was provided under the direction of the authors by John Ferguson and Medical Leverage, a communications company. All authors participated in the drafting of this manuscript and are responsible for its content.
Author contributions
Carol Antequera: conceptualization, visualization, writing – review & editing; Kimberly Orleck: conceptualization, visualization, writing – review & editing; Rinu Jacob: conceptualization, project administration, supervision, visualization, writing – review & editing; Amy Kenneally: conceptualization, supervision, visualization, writing – review & editing; Wendy L. Wright: conceptualization, visualization, writing – review & editing.