Acid Suppressant Therapy: a Step Forward with Potassium-Competitive Acid Blockers

Abstract

Purpose of the reviewThe introduction of H2-receptor antagonists (H2RAs) and proton pump inhibitors (PPIs) into clinical practice has been a real breakthrough in the treatment of acid-related diseases. PPIs are now the standard of care for the treatment of gastroesophageal reflux disease (GERD), peptic ulcer disease (PUD), Helicobacter pylori infection, NSAID-associated gastroduodenal lesions, and upper gastrointestinal bleeding (UGIB). However, despite their effectiveness, PPIs display some intrinsic limitations, which underlie the unmet clinical needs that have been identified over the past decades.Recent findingsTo address these needs, new long-acting compounds (such as tenatoprazole and AGN 201904-Z) and new PPI formulations, including instant release omeprazole (IR-omeprazole) and dexlansoprazole modified release (MR), have been developed. However, a major advance has been the development of the potassium-competitive acid blockers (P-CABs), which block the K+,H+-ATPase potassium channel, are food independent, are reversible, have a rapid onset of action, and maintain a prolonged and consistent elevation of intragastric pH. Vonoprazan and tegoprazan are the two marketed P-CABs while two other compounds (namely fexuprazan and X842) are under active development. Available for almost 6 years now, a considerable experience has been accumulated with vonoprazan, the efficacy and safety of which are detailed in this paper, together with the preliminary results of the other members of this new pharmacologic class.SummaryBased on the available evidence, erosive reflux disease, H. pylori infection, and secondary prevention of NSAID gastropathy can be considered established indications for vonoprazan and are being explored for tegoprazan and fexuprazan. In the treatment of severe (LA C & D) reflux esophagitis and H. pylori eradication, vonoprazan proved to be superior to PPIs. Other uses of P-CABs are being evaluated, but clinical data are not yet sufficient to allow a definitive answer on its efficacy and possible superiority over the current standard of care (i.e., PPIs). The most notable indication of upper GI (non-variceal) bleeding, where vonoprazan would prove superior to PPIs, has not yet been explored. The safety of P-CABs in the short-term overlaps that of PPIs, but data from long-term treatment are needed.