Proton Pump Inhibitors

Purpose of the reviewAcid suppression with proton pump inhibitors (PPIs) represents the standard of care in the treatment of acid-related diseases. However, despite their effectiveness, PPIs display some intrinsic limitations, which underlie the unmet clinical needs that have been identified over the past decades. The aims of this review are to summarize the current status and future development of the new class of antisecretory drugs (potassium-competitive acid blockers, P-CABs) that have recently been introduced into medical practice.Recent findingsOver the past decades, clinical needs unmet by the current acid suppressants have been recognized, especially in the management of patients with GERD, Helicobacter pylori infection and NSAID-related peptic ulcer. The failure to address these needs is mainly due to their inability to achieve a consistent acid suppression in all patients and, particularly, to control nighttime acidity. It was then realized that an extended duration of acid suppression would exert additional benefits. The available data with P-CABs show that they are able to address these unmet clinical needs. Four different P-CABs (vonoprazan, tegoprazan, fexuprazan and keverprazan) are currently available. However, only two of them are approved outside Asia. Vonoprazan is available in North, Central and South America while tegoprazan is marketed only in Latin American countries. Two other compounds (namely linazapran glurate and zestaprazan) are presently under clinical development. While clinical trials on GERD have been performed with all P-CABs, only vonoprazan and tegoprazan have been investigated as components of Helicobacter pylori eradication regimens. The available data show that-in the above two clinical indications-P-CABs provide similar or better efficacy in comparison with PPIs. Their safety in the short-term overlaps that of PPIs, but data from long-term treatment are needed.

Proton pump inhibitors (PPIs) are among the most prescribed drugs worldwide owing to their proven efficacy in symptom control and mucosal healing for acid-related disorders including gastroesophageal reflux disease (GORD), peptic ulcer disease, Helicobacter pylori eradication, functional dyspepsia, and gastroprotection in high-risk patients. However, long-term use beyond approved indications is increasingly common and has raised safety concerns. Observational studies link chronic PPI use to a myriad of adverse outcomes such as enteric infections (e.g., Clostridioides difficile), nutrient deficiencies (magnesium, vitamin B12), osteoporotic fractures, chronic kidney disease, dementia, and gastric and colorectal cancer. While causality is not always established, these associations warrant cautious risk-benefit assessment in patients receiving prolonged therapy. Current guidelines advocate periodic review of ongoing PPI use and emphasise deprescribing where appropriate. Strategies include dose reduction, on-demand or intermittent use, and switching to H2-receptor antagonists, particularly in patients with non-erosive reflux disease or functional dyspepsia. Tools from the National Institute for Health and Clinical Excellence, American College of Gastroenterology, and the Canadian Deprescribing Network assist clinicians in identifying candidates for tapering or discontinuation. This narrative review focuses on the concept of "PPI stewardship" by providing an evidence-based overview of PPI indications, risks, and deprescribing strategies to promote appropriate, safer, and patient-centred use of acid-suppressive therapy.

BackgroundThis study aims to review the existing knowledge on the cost-effectiveness and item costs related to the diagnosis and treatment of gastroesophageal reflux disease (GERD) patients at different stages.MethodsThe study adhered to the PRISMA guidelines. The systematic search involved several steps: finding and identifying relevant articles, filtering them according to the set criteria, and examining the final number of selected articles to obtain the primary information. The number of articles published between 2013 and September 2024 in the Web of Science and PubMed databases was considered. The CHEERS checklist was used for the risk of bias assessment. Ultimately, 36 studies were included.ResultsRegarding the cost-effectiveness of GERD treatment, Proton pump inhibitors (PPIs) appeared to be the dominant solution for non-refractory patients. However, this might change with the adoption of the novel drug vonoprazan, which is more effective and cheaper. With advancements in emerging technologies, new diagnostic and screening approaches such as Endosheath, Cytosponge, and combined multichannel intraluminal impedance and pH monitoring catheters should be considered, with potential implications for optimal GERD management strategies.DiscussionThe new diagnostic methods are reliable, safe, and more comfortable than standard procedures. PPIs are commonly used as the first line of treatment for GERD. Surgery, such as magnetic sphincter augmentation or laparoscopic fundoplication, is only recommended for patients with treatment-resistant GERD or severe symptoms.OtherAdvances in emerging technologies for diagnostics and screening may lead to a shift in the entire GERD treatment model, offering less invasive options and potentially improving patients' quality of life.

BackgroundEosinophilic esophagitis (EoE) is a chronic allergic disorder driven by type 2 inflammation, characterized by eosinophilic infiltration and esophageal epithelial abnormalities, including barrier dysfunction, basal cell hyperplasia, epithelial thickening, and loss of differentiation. Although proton pump inhibitor (PPI) therapy is frequently employed in the management of EoE and is known to reduce esophageal eosinophilia, improve barrier function, and exert anti-inflammatory effects, the precise mechanism by which PPIs modulate type 2 inflammation and epithelial integrity remains incompletely understood.MethodsAir-liquid interface culture of esophageal epithelial cells was used to investigate the impact of the PPI omeprazole on barrier integrity in IL-13-treated cultures. Epithelial chemokine secretion was assessed following stimulation with IL-13 and omeprazole, and eosinophil migration from healthy human donors was evaluated using 3 μm pore-sized transwells. A co-culture system of epithelial cells and eosinophils was used to examine chemokine secretion, eosinophil adhesion, and activation marker expression.ResultsOmeprazole treatment of IL-13-treated air-liquid interface (ALI) cultures restored barrier integrity compared with IL-13-treated ALI cultures and resulted in 186 differentially expressed genes. Omeprazole treatment reduced STAT6 phosphorylation, downregulated calpain 14 expression, and upregulated desmoglein-1 in IL-13-treated ALI samples. IL-13 treatment induced upregulation of Eotaxin-3, CXCL10, and periostin, which were downregulated by omeprazole. Eosinophils co-cultured with human esophageal epithelial cells in the presence of omeprazole had diminished CD11b, CD18, and CD69 expression compared to those cultured with IL-13 alone, and less eotaxin-3, CXCL10, CCL2, and CCL4 were recovered from the co-culture media.ConclusionOmeprazole diminished the effects of IL-13 in both the epithelial air-liquid interface model and eosinophil-epithelial co-cultures, alleviating barrier dysfunction, chemokine expression, and the upregulation of eosinophil adhesion markers.