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.
Highlights
The advent of antisecretory drugs, such as H2-receptor antagonists (H2RAs) and proton pump inhibitors (PPIs), has revolutionized the management of acid-related diseases, leading to the virtual abolition of elective surgery for ulcer disease and relegating anti-reflux surgery to patients with reflux disease not adequately managed by medical therapy
potassiumcompetitive acid blockers (P-CABs) clearly overcome many of the drawbacks and limitations of the DRPPIs
Considering the difficulties encountered in attaining effective symptomatic control, at night, using currently available delayed-release PPIs (DR-PPIs) once daily, this new class of drugs achieves rapid, potent, and prolonged acid suppression and offers the chance of addressing many of the unmet clinical needs in gastroesophageal reflux disease (GERD) [4, 7, 8, 10], such as the need for fast and assured healing of severe reflux esophagitis and achieving rapid heartburn relief
Summary
The advent of antisecretory drugs, such as H2-receptor antagonists (H2RAs) and proton pump inhibitors (PPIs), has revolutionized the management of acid-related diseases, leading to the virtual abolition of elective surgery for ulcer disease and relegating anti-reflux surgery to patients with reflux disease not adequately managed by medical therapy. Two alternative formulations of existing drugs, instant release omeprazole (IRomeprazole) and modified-release dexlansoprazole (MRdexlansoprazole), have been introduced in some countries [11] These represent a measurable but small incremental advance in the pharmacological control of acid secretion over the DR-PPIs but fall short of achieving the ideal pharmacologic profile, considered desirable to control acidity in patients with more complex clinical problems [13]. A P-CAB offers a very rapid and greater elevation of intragastric pH than a DR-PPI, while maintaining a similar or greater degree of antisecretory effect, with a duration which is dependent on the drug half-life. This class of antisecretory compounds has attracted several Pharmaceutical Companies to this avenue of drug development.
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