Potent Acid Suppression with PPIs and P-CABs: What’s New?

Acid suppression treatment has revolutionized the management of the acid-related disorders since the introduction of the H₂-receptor antagonists (H₂-RAs) and the proton pump inhibitors (PPIs). However, there has been increasing identification of needs for improvement in antisecretory therapy, especially in gastroesophageal reflux disease (GERD), the eradication of Helicobacter pylori (H. pylori), protection from aspirin (ASA) and non-steroidal inflammatory drug (NSAID) injury and the management of upper gastrointestinal (UGI) bleeding. There have also been increasing publications addressing safety concerns of antisecretory drugs.

The needs have been identified as shortcomings of the pharmacology of the delayed release-PPIs (DR-PPIs), which have short plasma half-lives, required to be given before a meal and show poor control of nocturnal acid secretion. New-generation PPIs have been developed, including dexlansoprazole modified release (MR), instant release omeprazole (IR-omeprazole), while metered release preparations such as Durasec™ or novel molecules such as tenatoprazole have also been developed and achieve superior control of intragastric pH especially at night. The major advance has been the development of the potassium channel acid blocking drugs, which block the K⁺,H⁺-ATPase K⁺ channel, are food independent, reversible, have a rapid onset of action, and maintain a prolonged and consistent elevation of intragastric pH. Vonoprazan, the first P-CAB, has so far been introduced only into a small number of Asian countries. Safety issues have been extensively addressed in numerous publications. This review sets the needs, individual new drug classes and key individual new treatments into clinical context.

Acid suppression treatment is reviewed including the pharmacology, the unmet clinical needs across the acid-related disorders, the place of new drug treatments, and where superiority exists. The safety of antisecretory drugs is broadly summarized with reference to several recent comprehensive reviews and set within the clinical context of patient management, particularly those on long-term treatment who are the greatest risk of some adverse events.