In this study, we investigated the developmental and reproductive toxicity of YWS1903, a novel potassium-competitive acid blocker, in pregnant Sprague-Dawley rats.

YWS1903 was administered orally at doses of 0 (control), 20, 60, and 200 mg kg-1 from gestation days 6 to 17 (n = 24 per group). Concurrent toxicokinetic analysis was conducted to characterize the toxicokinetic profile and placental transfer of YWS1903.

Aside from hair loss at the highest dose, no significant maternal toxicity was observed up to 200 mg kg-1. Fetal assessments revealed reductions in body weight and crown-rump length at 200 mg kg-1, alongside increased skeletal malformations, but no visceral abnormalities were detected. Toxicokinetic linearity studies revealed that within the 20-200 mg kg-1 dose range, both Cmax and AUC0-t of YWS1903 exhibited disproportionate increases following initial and final administrations. In the high-dose group, the escalation in AUC0-t substantially exceeded the corresponding dose changes, suggesting potential saturation of metabolic pathways at higher exposure levels. YWS1903 was shown to cross the placenta, although fetal plasma concentrations were consistently lower than maternal levels, suggesting reduced direct fetal exposure.

The no observed adverse effect level was established at 60 mg kg-1, supporting the compound's safety at moderate doses. These findings provide valuable insights into YWS1903's developmental and reproductive safety profile and offer reference for its clinical application as a therapeutic agent for gastroesophageal reflux disease.

Potassium-competitive acid blockers (P-CABs) constitute a relatively new class of gastric acid-suppressing drugs. Among this class, vonoprazan is the first to have been approved in the United States. However, some P-CABs including vonoprazan, tegoprazan, and fexuprazan have been available in other countries since at least 2014. The first aim of this article is to review pharmacological differences between P-CABs that are currently approved or in development with proton pump inhibitors. The specific focus thereafter is on the likely role of P-CABs in the treatment of different manifestations of gastroesophageal reflux disease. Multiple clinical trials have compared P-CABs with proton pump inhibitors in erosive esophagitis. Additional trials have compared P-CABs with placebo in nonerosive reflux disease. Relevant results are reviewed, and inferences are drawn for their use in the United States. Finally, consideration is given to additional, potential uses of P-CABs in the broader spectrum of gastroesophageal reflux disease, and some suggestions are made for future research initiatives.

Potassium-competitive acid blockers (P-CABs) are a newer class of acid suppressants with convenient dosing and a rapid onset of action, while showing efficacy comparable to proton pump inhibitors (PPIs) in treating peptic symptoms of gastroesophageal reflux disease (GERD). This study aimed to assess the effect of P-CABs on GERD-related chronic cough.

This randomized, double-blind, active-controlled, exploratory trial evaluated adults with chronic cough (≥ 8 weeks) and a recent physician diagnosis of GERD or peptic symptoms (< 1 month). Participants were randomized (1:1) to receive either fexuprazan 40 mg or esomeprazole 40 mg (PPI) once daily for eight weeks, along with matched placebos. The primary endpoint was the change in Leicester Cough Questionnaire (LCQ) score from baseline. Secondary endpoints included changes in the cough severity Numerical Rating Scale (NRS) and Reflux Disease Questionnaire (RDQ) scores. Safety was evaluated through monitoring adverse events.

Of the 190 subjects recruited, 161 met the selection criteria and were randomized, and 146 completed the trial. The participants were predominantly female (74.3%, mean age 39 ± 12 years). After 8 weeks of treatment, cough-related quality of life improved significantly, with comparable LCQ scores change between the groups (fexuprazan: 4.9 ± 4.0 vs. esomeprazole: 5.3 ± 3.8, p = 0.558). Changes in cough severity NRS and RDQ scores were also similar between the groups. Adverse events were comparable and consisted mostly of mild symptoms.

These findings support the potential of P-CABs as a promising alternative to PPIs for patients with chronic cough requiring acid-suppressive therapy.

Effective acid suppression significantly enhances the eradication rate of Helicobacter pylori (H. pylori).

To assess the efficacy and safety of high-dose dual therapy (HDDT) utilizing various highly potent antisecretory medications, thereby providing additional clinical guidance for H. pylori eradication.

The study population comprised untreated H. pylori patients from three medical centers in central China. From February 10, 2024 to March 31, 2024, 439 subjects were randomly allocated to either the esomeprazole-amoxicillin (EA) or esomeprazole-amoxicillin-clarithromycin-bismuth (B-quadruple) group. Subsequently, from April 1, 2024 to May 10, 2024, 367 subjects were randomly assigned to either the vonoprazan-amoxicillin (VA) or vonoprazan-amoxicillin-clarithromycin (VAC) group. The study recorded treatment efficacy, adverse events, compliance, symptom alleviation, and associated costs.

EA-dual demonstrated non-inferiority to B-quadruple regimen in modified intention-to-treat (mITT) and per-protocol (PP) analyses (P < 0.025). However, the eradication rate of EA was lower than that of the B-quadruple group [70.59% vs 83.49%, 92.86% vs 98.38%, 93.94% vs 98.38%, intention-to-treat (ITT), mITT, PP respectively, P < 0.05]. In ITT, mITT, and PP analyses, VA-dual was non-inferior to VAC treatment (84.15% vs 83.15%, 96.25% vs 92.73%, 96.75% vs 93.75%, P < 0.025). No significant differences were observed in adverse events, compliance, and symptom relief between groups. VA exhibited the lowest cost. Antibiotic use within 2 years, poor compliance, and suburban residence were associated with reduced eradication efficacy (P < 0.05).

The HDDT based on vonoprazan demonstrated non-inferiority to the VAC triple regimen, suggesting its potential as a recommended first-line treatment for H. pylori eradication. While B-quadruple therapy showed better eradication rate than EA therapy, the latter proved non-inferior in mITT and PP analyses. Notably, antibiotic use within the preceding two years, adherence to treatment protocols, and patient residence emerged as critical factors influencing eradication success.

Gastric mucosal changes associated with long-term potassium-competitive acid blocker and proton pump inhibitor (PPI) therapy may raise concern. In contrast to that for PPIs, the evidence concerning the safety of long-term potassium-competitive acid blocker use is scant. Vonoprazan (VPZ) is a representative potassium-competitive acid blocker released in Japan in 2015. In order to shed some comparative light regarding the outcomes of gastric mucosal lesions associated with a long-term acid blockade, we have reviewed six representative gastric mucosal lesions: fundic gland polyps, gastric hyperplastic polyps, multiple white and flat elevated lesions, cobblestone-like gastric mucosal changes, gastric black spots, and stardust gastric mucosal changes. For these mucosal lesions, we have evaluated the association with the type of acid blockade, patient gender, Helicobacter pylori infection status, the degree of gastric atrophy, and serum gastrin levels. There is no concrete evidence to support a significant relationship between VPZ/PPI use and the development of neuroendocrine tumors. Current data also shows that the risk of gastric mucosal changes is similar for long-term VPZ and PPI use. Serum hypergastrinemia is not correlated with the development of some gastric mucosal lesions. Therefore, serum gastrin level is unhelpful for risk estimation and for decision-making relating to the cessation of these drugs in routine clinical practice. Given the confounding potential neoplastic risk relating to H. pylori infection, this should be eradicated before VPZ/PPI therapy is commenced. The evidence to date does not support the cessation of clinically appropriate VPZ/PPI therapy solely because of the presence of these associated gastric mucosal lesions.

This meta-analysis aims to compare the efficacy and safety of vonoprazan-amoxicillin (VA) dual therapy in comparison to bismuth-containing quadruple therapy (BQT) for patients with Helicobacter pylori (H. pylori) infection.

Four databases (PubMed, Embase, Web of Science, and Cochrane Library) were searched published from establishment of database to June 1, 2024, for articles studying VA dual therapy compared to BQT for patients with H. pylori infection. Meta-analyses of eradication rates, adverse events, compliance and cost were preformed.

A total of 17 studies were included for meta-analysis. Compared with BQT, VA increased the incidence of H. pylori eradication rate, with significant difference under the ITT analysis (86.9% vs. 80.4%, RR = 1.07, 95% CI: 1.01-1.12, p = 0.01) but there no significant difference under the PP analysis (90.7% vs. 86.5%, RR = 1.03, 95% CI: 0.99-1.08, p = 0.13). Besides, VA significantly increased compliance (RR = 1.03, 95% CI: 1.01-1.05, p < 0.01) and decreased the occurrence of total adverse events (27.0% vs. 11.5%, RR = 0.43, 95% CI: 0.37-0.51, p < 0.01). Furthermore, VA has lower cost compared to BQT.

Our findings indicated that VA dual therapy provided a higher eradication rate, enhanced compliance, decreased adverse events, and lowered cost relative to BQT for patients with H. pylori infection.

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024576738, identifier CRD42024576738 (PROSPERO).

Vonoprazan and amoxicillin (VA) dual therapy as a mainstream Helicobacter pylori regimen has gained momentum worldwide, but the optimum dosages remain unclear. We aimed to compare the efficacy and safety of VA dual therapy with 2 g amoxicillin or 3 g amoxicillin, and to assess the short-term effects of therapy on the gut microbiota and antibiotic resistome.

We conducted an open-label, non-inferiority randomised controlled trial at 12 centres in China. Individuals infected with H pylori, aged 18-70 years, and without previous eradication therapy were recruited. Participants were randomly assigned at a 1:1 ratio (block size of six) to receive vonoprazan (20 mg twice a day) with either low-dose amoxicillin (1 g twice a day; LVA therapy) or high-dose amoxicillin (1 g three times a day; HVA therapy) for 14 days. Gastric biopsies were collected before treatment for detection of antibiotic resistance. Stool samples were collected at baseline, week 2, and week 8-10 for shotgun metagenomic sequencing. The primary outcome was the eradication rate of H pylori, assessed by 13C urea breath test, in both intention-to-treat and per-protocol analyses. Secondary outcomes were adverse events, adherence, antibiotic resistance, and alterations to the gut microbiota and antibiotic resistome. The margin used to establish non-inferiority was -0·10. The trial was registered with ClinicalTrials.gov, NCT05649709.

Between Feb 13, 2023, and Jan 25, 2024, 504 patients (204 [40%] male and 300 [60%] female; mean age 43 years [SD 13]) were randomly assigned to LVA therapy or HVA therapy (n=252 in each group). No infections were resistant to amoxicillin. The H pylori eradication rate was 85·3% (215 of 252; 95% CI 80·4 to 89·2) in the LVA group and 86·5% (218 of 252; 81·7 to 90·2) in the HVA group in the intention-to-treat analysis (p=0·70) and 88·8% (213 of 240; 84·1 to 92·2) and 92·4% (218 of 236; 88·3 to 95·1), respectively, in the per-protocol analysis (p=0·18). The efficacy of LVA was non-inferior to HVA in the intention-to-treat analysis (risk difference -1·2%, 95% CI -7·3 to 4·9, p=0·0022) and the per-protocol analysis (-3·6%, -9·0 to 1·7, p=0·0085). 31 (12%) patients in the LVA group and 43 (17%) patients in the HVA group reported adverse events. Adherence to therapy was 97% in the LVA group and 96% in the HVA group. The diversity of gut microbiota decreased after treatment but was restored to baseline at week 8-10 in both groups. The abundance of beta-lactam-related resistance genes was increased at week 2 after treatment, and was restored to pretreatment level at week 8-10 for the LVA group but not the HVA group.

LVA dual therapy was effective and non-inferior to HVA dual therapy as first-line treatment of H pylori infection and showed a non-lasting effect on the abundance of beta-lactam-related resistance genes. High amoxicillin dosage (eg, 3 g per day) is not required to achieve high cure rates with vonoprazan dual therapy.

National Natural Science Foundation of China, Project for Academic and Technical Leaders of Major Disciplines in Jiangxi Province, and Key Research and Development Program of Jiangxi Province.

Owing to the high prevalence of antibiotic resistance in Helicobacter pylori (H. pylori) in China, bismuth-containing quadruple therapies have been recommended for H. pylori eradication. This study compared the efficacy and safety of quadruple regimens containing vonoprazan vs. esomeprazole for H. pylori eradication in a patient population in China.

This was a phase 3, multicenter, randomized, double-blind study. Patients with confirmed H. pylori infection were randomized 1:1 to receive quadruple therapy for 14 days: amoxicillin 1000 mg and clarithromycin 500 mg after meals, bismuth potassium citrate 600 mg before meals, plus either vonoprazan 20 mg or esomeprazole 20 mg before meals, all twice daily. The primary outcome was the eradication rate of H. pylori, evaluated using a 13C urea breath test at 4 weeks after treatment. The non-inferiority margin was at 10%.

The study included 510 patients, 506 of whom completed the follow-up assessment. The primary analysis revealed eradication rates of 86.8% (210/242) and 86.7% (208/240) for vonoprazan and esomeprazole therapy, respectively (treatment difference: 0.1%; 95% confidence interval [CI]: -5.95, 6.17; non-inferiority P = 0.0009). Per-protocol analysis showed eradication rates of 87.4% for vonoprazan and 86.3% for esomeprazole (treatment difference: 1.2%; 95% CI: -5.03, 7.36; non-inferiority P = 0.0004). Vonoprazan and esomeprazole were well tolerated, with similar safety profiles.

Vonoprazan was found to be well-tolerated and non-inferior to esomeprazole for eradicating H. pylori in patients from China.

ClinicalTrials.gov, NCT04198363.

To explore the current research status and trends of potassium-competitive acid blockers (P-CABs) in the treatment of acid related diseases (ARDs) using bibliometric analysis.

We collected publications related to P-CAB in the treatment of acid-related diseases in the Web of Science (WOS) Core Collection from the establishment of the database to 30 June 2024. We evaluated the publication volume and citation status over the years using the WOS platform, and visualized the authors, countries, institutions, keywords, and citations of the publications using CiteSpace and VOSviewer.

This study included a total of 455 articles. The number of publications and citations related to research has been increasing year by year. The results show that the scholars with the highest number of publications mainly come from South Korea and Japan. Scholars such as Geun Seog Song, Bongtae Kim, and Nobuhiro Inatomi produced many works in related fields. The most popular drug in this field was vonoprazan, and research on this drug mainly focused on the effectiveness and safety evaluation of ARDs such as Helicobacter pylori infection, gastroesophageal reflux disease, peptic ulcers, etc. Researchers were concerned about the evaluation of treatment regimens and efficacy comparison between P-CABs and traditional proton pump inhibitors (PPIs) in the treatment of ARDs. At the same time, researchers are also closely monitoring the potential adverse reactions and long-term adverse outcomes of clinical application of P-CABs for ARDs.

The clinical application of P-CABs, represented by vonoprazan, in ARDs is receiving widespread attention from researchers. The exploration of the application of this type of drug in ARDs is constantly expanding, and it is a research field with great clinical value and research potential.

Vonoprazan is a novel potassium-competitive acid blocker (P-CAB) that offers several advantages, such as fast onset time and strong acid inhibition, in the treatment of Helicobacter pylori infection. This study aims to evaluate the efficacy, adverse reactions, and compliance of the 14-day vonoprazan-amoxicillin dual therapy versus drug sensitivity-based individualized therapy in the retreatment of H. pylori infection.

This multicenter, open-label, randomized, controlled non-inferiority study enrolled 240 adult patients who previously failed anti-H. pylori treatment. These patients were randomly assigned to receive the 14-day vonoprazan-amoxicillin dual therapy or drug sensitivity-based individualized therapy. The primary outcome was the eradication rate, and the secondary outcomes mainly included adverse events, patient compliance, antibiotic resistance rates, and risk factors that affected the eradication rate.

The intention-to-treat (ITT) and per-protocol (PP) analyses revealed that the eradication rates for the vonoprazan-amoxicillin dual therapy and drug sensitivity-based individualized therapy were comparably high, with rates of 87.50% and 83.33%, respectively. Furthermore, the vonoprazan-amoxicillin dual therapy fulfilled the criteria for the non-inferiority test, when compared to individualized therapy. The incidence of adverse reactions was significantly lower in the vonoprazan-amoxicillin dual therapy group. Both groups showed similarly good compliance and comparable rates of antibiotic resistance. The previous treatment with a clarithromycin-containing regimen was identified as an independent risk factor for clarithromycin resistance.

The 14-day vonoprazan-amoxicillin dual therapy exhibits high eradication rates and low incidence of adverse reactions in retreated patients, indicating its effectiveness and safety as a rescue regimen for patients with H. pylori infection.

Proton pump inhibitors (PPIs) are the first-line treatment for gastroesophageal reflux disease (GERD). However, due to their intrinsic limitations, there are still unmet clinical needs that have fostered the development of potassium-competitive acid blockers (P-CABs). Currently, four different drugs (vonoprazan, tegoprazan, fexuprazan, and keverprazan) are marketed in some Asian countries, whereas only vonoprazan and tegoprazan are available in Western countries (USA and Brazil or Mexico, respectively).

This review summarizes the current knowledge on P-CABs acute and long-term safety in GERD treatment compared to that of PPIs. Full-text articles and abstracts were searched in PubMed.

P-CABs proved to address some of the unmet clinical needs in GERD, with a favorable risk-benefit ratio compared to conventional PPIs. Preclinical and clinical findings have highlighted P-CAB safety to be superimposable, to that of PPIs, in short-term treatments, although further studies are warranted to monitor their effects in long-term therapy. From an epidemiological point of view, the paucity of rigorous data for many variables (e.g. age, ethnicity, drug interactions, comorbidities, genetic polymorphisms, interindividual susceptibility, and gut dysbiosis) deserves a worldwide framework of continuous pre/post-marketing pharmacovigilance programs to reduce potential confounding factors and accurately link acute and chronic P-CAB therapy to adverse outcomes.

The efficacy of the 14-day esomeprazole-amoxicillin (EA) dual therapy in eradicating Helicobacter pylori (H. pylori) has been widely discussed previously. Vonoprazan, a novel potassium-competitive acid blocker, presents rapid, potent, and long-lasting acid inhibitory effects compared to esomeprazole. However, there is currently a scarcity of direct comparisons between the 10-day vonoprazan-amoxicillin (VA) and the 14-day EA dual therapy for H. pylori eradication.

This study aimed to compare the efficacy and safety of the 10-day VA and the 14-day EA dual therapy for H. pylori first-line eradication.

This study was a prospective, multicenter, open-label, randomized controlled trial.

The study was conducted at 10 hospitals in China. In total, 570 newly diagnosed H. pylori-infected patients were recruited from April 2023 to February 2024. These patients were randomly assigned to either the 10-day VA group (vonoprazan 20 mg twice daily + amoxicillin 1000 mg three times daily) or the 14-day EA group (esomeprazole 20 mg four times daily + amoxicillin 750 mg four times daily). The primary outcome was the eradication rate, with secondary outcomes including adverse events and compliance.

The 10-day VA regimen outperformed the 14-day EA regimen in terms of eradication rates in intention-to-treat (ITT) analysis (85.4% vs 76.7%, p = 0.008), modified ITT analysis (90.7% vs 84.8%, p = 0.036), and per-protocol (PP) analysis (91.1% versus 85.5%, p = 0.047). The non-inferiority p-values in all three analyses were less than 0.001. No statistically significant difference was observed in the incidence of adverse events between the two groups (9.1% vs 11.7%, p = 0.308). The 10-day VA regimen demonstrated higher compliance compared to the 14-day EA regimen (p = 0.006).

The 10-day VA dual therapy showed a satisfactory eradication rate of 91.1% (PP analysis), demonstrating good safety and better compliance compared to the 14-day EA dual therapy as the first-line eradication.

This trial was registered in the Chinese Clinical Trial Registry (registration number: ChiCTR2300070475) on April 12, 2023.

Aging is a multifactorial biological process characterized by a decline in physiological function and increasing susceptibility to various diseases, including malignancies and gastrointestinal disorders. Helicobacter pylori (H. pylori) infection is highly prevalent among older adults, particularly those in institutionalized settings, contributing to conditions such as atrophic gastritis, peptic ulcer disease, and gastric carcinoma. This review examines the intricate interplay between aging, gastrointestinal changes, and H. pylori pathogenesis. The age-associated decline in immune function, known as immunosenescence, exacerbates the challenges of managing H. pylori infection. Comorbidities and polypharmacy further increase the risk of adverse outcomes in older adults. Current clinical guidelines inadequately address the specific needs of the geriatric population, who are disproportionately affected by antibiotic resistance, heightened side effects, and diagnostic complexities. This review focuses on recent advancements in understanding H. pylori infection among older adults, including epidemiology, diagnostics, therapeutic strategies, and age-related gastric changes. Diagnostic approaches must consider the physiological changes that accompany aging, and treatment regimens need to be carefully tailored to balance efficacy and tolerability. Emerging strategies, such as novel eradication regimens and adjunctive probiotic therapies, show promise for improving treatment outcomes. However, significant knowledge gaps persist regarding the impact of aging on H. pylori pathogenesis and treatment efficacy. A multidisciplinary approach involving gastroenterologists, geriatricians, and other specialists is crucial to providing comprehensive care for this vulnerable population. Future research should focus on refining diagnostic and therapeutic protocols to bridge these gaps, ultimately enhancing clinical outcomes and reducing the burden of H. pylori-associated diseases in the aging population.

The purpose of this American Gastroenterological Association (AGA) Institute Clinical Practice Update (CPU) is to summarize the available evidence and offer expert Best Practice Advice on the integration of potassium-competitive acid blockers (P-CABs) in the clinical management of foregut disorders, specifically including gastroesophageal reflux disease, Helicobacter pylori infection, and peptic ulcer disease.

This expert review was commissioned and approved by the AGA Institute Governing Board and CPU Committee to provide timely guidance on a topic of high clinical importance to the AGA membership. This CPU expert review underwent internal peer review by the CPU Committee and external peer review through the standard procedures of Gastroenterology. These Best Practice Advice statements were developed based on review of the published literature and expert consensus opinion. Because formal systematic reviews were not performed, these Best Practice Advice statements do not carry formal ratings of the quality of evidence or strength of the presented considerations. Best Practice Advice Statements BEST PRACTICE ADVICE 1: Based on nonclinical factors (including cost, greater obstacles to obtaining medication, and fewer long-term safety data), clinicians should generally not use P-CABs as initial therapy for acid-related conditions in which clinical superiority has not been shown. BEST PRACTICE ADVICE 2: Based on current costs in the United States, even modest clinical superiority of P-CABs over double-dose proton pump inhibitors (PPIs) may not make P-CABs cost-effective as first-line therapy. BEST PRACTICE ADVICE 3: Clinicians should generally not use P-CABs as first-line therapy for patients with uninvestigated heartburn symptoms or nonerosive reflux disease. Clinicians may use P-CABs in selected patients with documented acid-related reflux who fail therapy with twice-daily PPIs. BEST PRACTICE ADVICE 4: Although there is currently insufficient evidence for clinicians to use P-CABs as first-line on-demand therapy for patients with heartburn symptoms who have previously responded to antisecretory therapy, their rapid onset of acid inhibition raises the possibility of their utility in this population. BEST PRACTICE ADVICE 5: Clinicians should generally not use P-CABs as first-line therapy in patients with milder erosive esophagitis (EE) (Los Angeles classification of erosive esophagitis grade A/B EE). Clinicians may use P-CABs in selected patients with documented acid-related reflux who fail therapy with twice-daily PPIs. BEST PRACTICE ADVICE 6: Clinicians may use P-CABs as a therapeutic option for the healing and maintenance of healing in patients with more severe EE (Los Angeles classification of erosive esophagitis grade C/D EE). However, given the markedly higher costs of the P-CAB presently available in the United States and the lack of randomized comparisons with double-dose PPIs, it is not clear that the benefits in endoscopic outcomes over standard-dose PPIs justify the routine use of P-CABs as first-line therapy. BEST PRACTICE ADVICE 7: Clinicians should use P-CABs in place of PPIs in eradication regimens for most patients with H pylori infection. BEST PRACTICE ADVICE 8: Clinicians should generally not use P-CABs as first-line therapy in the treatment or prophylaxis of peptic ulcer disease. BEST PRACTICE ADVICE 9: Although there is currently insufficient evidence for clinicians to use P-CABs as first-line therapy in patients with bleeding gastroduodenal ulcers and high-risk stigmata, their rapid and potent acid inhibition raises the possibility of their utility in this population.

Acid 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.

Over 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.

Factors that determine clinical responses to vonoprazan remain unknown. This study aimed to characterize plasma vonoprazan and CYP3A activity using its endogenous marker and genetic variants in patients with digestive system disorders. Fifty-three patients who were receiving vonoprazan for at least 3 days were enrolled. Blood samples for determination of plasma vonoprazan and its metabolite (ODA-VP) were obtained. Plasma 4β-hydroxycholesterol (4β-OHC), CYP3A5 and ABCB1 genotypes, and plasma gastrin were determined. CYP3A recognition for vonoprazan was evaluated using recombinant CYP3A proteins. Plasma vonoprazan levels exhibited a large interindividual variation. The absolute plasma concentration of vonoprazan was correlated with its dose-normalized value, and had a positive correlation with the inverse value of its metabolic ratio. A negative correlation was observed between plasma vonoprazan and 4β-OHC levels. The metabolic ratio of vonoprazan was positively correlated with the plasma 4β-OHC level. Genetic variants of CYP3A5 and ABCB1 were not associated with the plasma concentration of vonoprazan and its metabolic ratio. Possible saturated metabolism of vonoprazan to its major metabolite was observed at a therapeutic dose. Although the CYP3A5 genotype did not alter plasma vonoprazan, CYP3A activity based on plasma 4β-OHC partially explained the variation in plasma vonoprazan in patients with digestive system disorders.

Gastroesophageal reflux disease (GERD) is a chronic disease of the esophagus characterized by the regurgitation of stomach contents into the esophagus, causing troublesome symptoms and/or complications. Among patients with GERD, around 30% of patients have visible mucosal damage, while 70% have normal esophageal mucosa. Accordingly, the optimal pharmacological treatment of GERD should address different disease manifestations, including symptoms, the mucosal damage when present, and possible chronic complications, including strictures, Barrett's esophagus, and esophageal adenocarcinoma.

Available medical treatments for GERD include proton pump inhibitors (PPIs), potassium-competitive acid blockers (PCABs), histamine receptor antagonists (H2-RAs), prokinetics, and mucosal protectants, such as alginates, hyaluronic acid/chondroitin-sulfate, and poliprotect. Each compound has its own advantages and disadvantages, and knowledge of expected benefits and tips for their use is paramount for the success of treatment. In addition, the appropriateness of indications for initiating treatment is also crucial to achieve positive results when managing GERD patients.

PPIs, PCABs, H2-RAs, prokinetics, and mucosal protectants can all be used in patients with GERD, but careful assessment of patients' characteristics as well as advantages and disadvantages of each therapeutic compound is essential to ensure successful treatment of GERD.

We compared efficacy of vonoprazan-dual or triple therapies and bismuth-quadruple therapy for treatment-naive Helicobacter pylori (HP) infection in Southern China, where primary resistance rates of clarithromycin and levofloxacin are >30%.

This was an investigator-initiated, three-arm, randomized clinical trial in Southern China. Between March 2022 and August 2023, treatment-naïve HP-infected adults were randomly assigned to receive one of three 14-day regimens (1:1:1 ratio): vonoprazan-dual (VA-dual; vonoprazan 20 mg twice daily and amoxicillin 1 g thrice daily), vonoprazan-triple (VAC-triple; vonoprazan 20 mg/amoxicillin 1 g/clarithromycin 500 mg twice daily), or bismuth-quadruple therapy containing bismuth, esomeprazole, tetracycline, and metronidazole. Primary outcome was noninferiority in HP eradication, evaluated by UBT 4-6 weeks post-treatment by intention-to-treat (ITT) and per-protocol (PP) analysis (based on subjects who completed 14-day treatment and rechecked UBT). Bonferroni-adjusted p-value of <0.017 was used to determine statistical significance.

A total of 298 subjects (mean age: 35.7 ± 8.4 years; male: 134 [45.0%]; VC-dual: 100, VAC-triple: 98, bismuth-quadruple: 100) were enrolled, and 292 (98.0%) had UBT rechecked. ITT analysis showed that both VA-dual (eradication rate of 96.0%) and VAC-triple therapies (95.9%) were noninferior to bismuth-quadruple therapy (92.0%) (difference: 4.0%, 95% CI: -2.9% to 11.5%, p < 0.001; and 3.9%, 95% CI: -3.1% to 11.5%, p < 0.001, respectively). PP analysis also revealed noninferiority (96.7% or 96.7% vs. 97.4%, with difference: -2.9% and -2.9%, p = 0.009 and 0.010, respectively). The frequency of adverse events was 39.0%, 56.1%, and 71.0% in VA-dual, VAC-triple, and bismuth-quadruple therapies, respectively.

VA-dual and VA-triple therapies are highly effective and noninferior to bismuth-quadruple therapy in Southern China. Given the lower adverse effects and fewer antibiotic use, VA-dual therapy is the preferred first-line treatment for HP infection.

Chinese Clinical Trial Registry (No. ChiCTR2200056375). Registered on February 4, 2022, https://www.chictr.org.cn/showproj.aspx?proj=14131.

Peptic ulcer disease (PUD) and postprocedural artificial ulcers are common ulcer disease. For them, proton pump inhibitor (PPI) and potassium-competitive acid blocker (P-CAB) are commonly used in clinical practice. PPI requires acid, time, and multiple doses, but P-CAB has fewer limitations. We compared the efficacy, safety, and prevention of PPI and P-CAB in PUD or artificial ulcer.

We searched PubMed, ClinicalTrials.gov , Embase, Cochrane Library, and Web of Science databases for all studies. All eligible randomized controlled trials up to August 5, 2023, were included. Healing rates, shrinking rates, treatment-emergent adverse events rates, and recurrence rates were measured. Risk of bias, sensitivity analyses, and heterogeneity were also performed.

Twenty researches that were selected from 926 screening studies and in total 6,551 participants were included. The risk ratio (RR) of healing rate with P-CABs vs PPIs of PUD at 4 weeks was RR 1.01 (95% confidence interval 0.98-1.04). In addition, the healing rate distinction of artificial peptic ulcer was RR 1.04 (0.89-1.22), and the shrinking rate was mean difference 0.10 (-1.30-1.51). The result of treatment-emergent adverse event rate of PUD was RR 1.11 (0.91-1.35), and the delayed bleeding rate of artificial ulcer was RR 0.35 (0.16-0.80). The RR for recurrence rate of drug-related ulcers was 0.45 (0.25-0.81).

P-CAB is noninferior in healing artificial ulcer and PUD, also the incidence of treatment-emergent adverse events. But, there may be a statistical advantage in holding back delayed bleeding and preventing drug-induced ulcers. More standardized experiments are needed for further applications and more precise conclusions.

High-dose dual therapy (HDDT) using proton-pump inhibitors (PPI) and amoxicillin attracted attention for its simplicity and lower adverse event profile. Besides, vonoprazan is not available worldwide. This real-world study aims to compare the efficacy of esomeprazole-based and rabeprazole-based HDDT regimens and to identify clinical factors influencing outcomes.

A retrospective study enrolled 346 Helicobacter pylori-infected naïve patients from January 2016 to August 2023. Patients were assigned to either a 14-day esomeprazole-based HDDT (EA-14; esomeprazole 40 mg t.i.d. and amoxicillin 750 mg q.i.d. for 14 days, n = 173) or a 14-day rabeprazole-based HDDT (RA-14; rabeprazole 20 mg and amoxicillin 750 mg q.i.d. for 14 days, n = 173).

Five patients from the EA-14 group and 10 from the RA-14 group were lost to follow-up, resulting in 168 and 163 patients for the per-protocol (PP) analysis, respectively. Eradication rates for the EA-14 and RA-14 groups were 90.2% and 80.9% (P = 0.014) in intention-to-treat (ITT) analysis; and 92.9% and 85.9% (P = 0.039) in PP analysis. Adverse event rates were similar between the two groups (11.9% vs 11.7%, P = 0.944). In multiple logistic regression analysis, age≧60 was associated with eradication failure (P = 0.046) and a trend of significance for smoking (P = 0.060) in the EA-14 group but not in the RA-14 group. A trend of significance was also observed for eradication regimens (EA-14 vs RA-14) (P = 0.071). The antibiotic resistance rates were amoxicillin (2.3%), clarithromycin (14.7%), metronidazole (40.3%), and dual resistance to clarithromycin and metronidazole (7.0%).

Esomeprazole-based HDDT achieved over 90% eradication rates but rabeprazole-based HDDT, which failed.

Refractory gastroesophageal reflux disease (refractory GERD) is a heterogeneous disease characterized by unresponsiveness or poor efficacy to proton-pump inhibitors (PPIs). This chronic disorder substantially weakens patients' mental wellbeing and quality of life, increasing the financial burden on society. Multiple articles have been reported in this area. However, literature involving scientometric analysis of refractory GERD is absent. Therefore, it is necessary to understand the evolution of research themes and the main hotspots of refractory GERD through bibliometric methods.

All documents related to refractory GERD based on the WOS Core Collection from January 2000 to November 2023 were selected for analysis. Citespace V 6.1 R6, VOSviewer V 1.6.20, and Scimago Graphica V 1.0.38 were used to perform bibliometric analysis.

We collected a total of 241 research articles from 36 countries and 322 institutions, contributed by over 1,000 authors. Over the last 20 years, the number of articles in this field has increased year by year, and since 2011, the number of publications has increased dramatically, with 85.89% of the papers. These countries are led by the United States and Japan. GUT had the highest number of citations and DIGESTION had the highest number of publications. Research on standardized diagnosis and management, mechanisms, novel monitoring methods, and innovative drugs and procedures for refractory GERD are the main topics and hotspots in this field. This study also found that neuroimmune interaction is closely related to refractory GERD, which may be a new direction for future mechanism research.

Our study is the first bibliometric analysis of the global literature on refractory GERD. This research provides valuable insights for researchers, enabling them to quickly understand the research frontier and hot topics of this field.

The situation of Helicobacter pylori eradication therapy has been changing over time, owing to increases in antimicrobial-resistant strains, lifestyle improvements, and changes in indications for eradication. In Japan, eradication therapy is now available to all H. pylori-positive patients under the medical insurance system, and the potassium-competitive acid blocker vonoprazan has been used for eradication from 2015. Recently, with the aging of society, opportunities to provide eradication to elderly patients are increasing, but the current status and effectiveness of eradication in elderly patients remains unclear. Therefore, we aimed to investigate the trends of H. pylori eradication in a metropolitan area to determine the factors associated with successful H. pylori eradication in elderly patients older than 80 years.

Trends in the eradication rates of patients who received first- or second-line eradication at 20 hospitals in the Tokyo metropolitan area from 2013 to 2023 were investigated.

The eradication rates in the per-protocol analysis were 82.3% (95% confidence interval [CI]: 81.2%-83.2%) for the first-line treatment (n = 6481), and 87.9% (86.9%-88.9%) for the second-line treatment (n = 4899). Multivariate analysis showed that independent factors for successful eradication in the first-line treatment were an age of older than 80 years (OR: 0.606; 95% CI: 0.448-0.822), peptic ulcers (vs. atrophic gastritis: 3.817; 3.286-4.433), and vonoprazan (vs. proton pump inhibiters (PPIs), 3.817; 3.286-4.433), and an age of older than 80 years (0.503; 0.362-0.699) and vonoprazan (1.386; 1.153-1.667) in the second-line treatment.

After 2015, the eradication rate of both first- and second-line therapies were maintained at a higher level than before 2015, owing to the use of vonoprazan. As the H. pylori eradication rate in patients older than 80 years was low, an effective strategy for these patients needs to be developed in the future.

The effect of preprandial or postprandial administration of amoxicillin on the efficacy of vonoprazan-amoxicillin dual therapy (VA-dual therapy) for Helicobacter pylori treatment has not been studied. It is also unclear whether amoxicillin dosing four times daily is more effective than three times daily. We aimed to investigate the effect of different amoxicillin administration regimens on the efficacy of VA-dual therapy.

H. pylori-infected subjects were randomly assigned to three groups in a 1:1:1 ratio to receive a 14-day dual therapy consisting of vonoprazan 20 mg twice daily + amoxicillin 1000 mg three times daily before meals (BM-TID) or 1000 mg three times daily after meals (AM-TID) or 750 mg four times daily after meals (AM-QID). H. pylori eradication rates, adverse events rates, compliance, and antibiotic resistance were compared.

Between May 2021 to April 2023, 327 subjects were enrolled. The eradication rates of BM-TID, AM-TID, and AM-QID dual therapy were 88.1%, 89.9%, and 93.6% in intention-to-treat (ITT) analysis, 90.6%, 94.2%, and 99.0% in modified ITT (MITT) analysis, and 90.4%, 94.1%, and 99.0% in per-protocol (PP) analysis. Although there was non-inferiority between BM-TID and AM-TID, as well as between AM-TID and AM-QID, AM-QID was significantly more effective than BM-TID. There were no significant differences in adverse event rates, compliance, and antibiotic resistance among the three groups.

Postprandial administration and the increased frequency of administration of amoxicillin may contribute to a better efficacy of VA-dual therapy, especially for rescue therapy. All VA-dual therapy in our study could achieve good efficacy for first-line treatment.

clinicaltrials.gov: NCT05901051.

In Chinese healthcare settings, drug selection decisions are predominantly influenced by the Pharmacy & Therapeutics Committee (PTC). This study evaluates two recently introduced potassium-competitive acid blockers, vonoprazan (VPZ) and tegoprazan (TPZ), utilizing the Evidence and Value: Impact on DEcisionMaking (EVIDEM) framework.

The study employed the 10th edition of EVIDEM, which includes a core model with five domains and 13 criteria. Two independent expert panels were involved: the PTC expert panel, tasked with assigning weights using a 5-point scale, defining scoring indicators, examining the evidence matrix, scoring, and decision-making; and the evidence matrix expert panel, responsible for conducting a systematic literature review, creating the evidence matrix, and evaluating the value contributions of VPZ and TPZ.

The analysis estimated the value contributions of VPZ and TPZ to be 0.59 and 0.54, respectively. The domain of 'economic consequences of intervention' showed the most significant variation in value contribution between the two drugs, followed by 'comparative outcomes of intervention' and 'type of benefit of intervention'.

Employing the EVIDEM framework, VPZ's value contribution was found to be marginally superior to that of TPZ. The EVIDEM framework demonstrates potential for broader application in Chinese medical institutions.

A liquid chromatography-tandem mass spectrometry method with vonoprazan fumarate-d4 as a stable isotope-labeled internal standard was developed and validated aiming at quantification of vonoprazan fumarate in human plasma for a bioequivalence study. Chromatographic separation was achieved by acetonitrile one-step protein precipitation using a gradient elution of 0.1% formic acid aqueous solution and acetonitrile with a run time of 3.65 min. Detection was carried out on a tandem mass spectrometer in multiple reaction monitoring mode via a positive electrospray ionization interface. The multiple reaction monitoring mode of precursor-product ion transitions for vonoprazan fumarate and vonoprazan fumarate-d4 were m/z 346.0 → 315.1 and 350.0 → 316.0, respectively. The linear range was 0.150-60.000 ng/ml. This method was fully validated with acceptable results in terms of selectivity, carryover, lower limit of quantification, calibration curve, accuracy, precision, dilution effect, matrix effect, stability, recovery and incurred sample reanalysis. A successful application of this method was realized in the bioequivalence study of vonoprazan fumarate tablet (20 mg) among healthy Chinese volunteers.

To evaluate the efficacy and safety of vonoprazan therapy as compared to conventional proton pump inhibitors (PPIs) or no vonoprazan for non-erosive esophagitis.

A thorough search was conducted across databases. The primary outcome was to determine the mean variance in the gastroesophageal reflux disease (GERD) score after vonoprazan treatment. Secondary outcomes comprised alterations in the scores for epigastric pain and post-prandial distress, the proportion of patients displaying improvement, and the occurrence of adverse events. Pooled mean differences and relative risks were determined utilizing random effects models.

A total of 1,944 articles were screened and nine of them were included. As compared to PPI or no vonoprazan therapy, vonoprazan treatment led to a significant reduction in the GERD score [mean difference: -3.88 (95 % CI: -5.48, -2.28), p < 0.01, i2=95 %]. As compared to PPI or no vonoprazan therapy, vonoprazan treatment led to a significant reduction in the epigastric pain score [mean difference: -3.02 (95 % CI: -5.41, -0.63), p = 0.01, i2=75 %] and post-prandial distress score [mean difference: -2.82 (95 % CI: -3.51, -2.12), p < 0.01, i2=0 %] (all moderate GRADE evidence). Vonoprazan therapy was found to be safe.

Treatment with vonoprazan could significantly improve symptoms in patients with non-erosive esophagitis or non-erosive GERD.

The vonoprazan (VPZ)-amoxicillin (AMO) dual therapy (VA) demonstrates a satisfactory eradication rate for Helicobacter pylori (H. pylori ). However, the optimal dosage of AMO in this regimen remains uncertain. The objective of this study is to investigate the efficacy of different doses of AMO in the VA regimen for first-line treatment of H. pylori infection.

A total of 192 treatment-naive H. pylori -infected patients were randomly assigned to one of three groups: low-dose VA (LD-VA: VPZ 20 mg b.i.d + AMO 750 mg t.i.d), moderate-dose VA (MD-VA:VPZ 20 mg b.i.d + AMO 1000 mg t.i.d), and high-dose VA (HD-VA: VPZ 20 mg b.i.d + AMO 1250 mg t.i.d). All groups received 14 days of treatment. The study evaluated and compared the eradication rates, adverse events (AEs), and patient compliance among the three groups.

Eradication rates for LD-VA, MD-VA, and HD-VA were 76.6% (49/64), 79.7% (51/64), and 84.4% (54/64), respectively, as determined by intention-to-treat analysis; 90.6% (48/53), 94.3% (50/53), and 98.1% (53/54) according to per-protocol analysis; 89.1% (49/55), 94.4% (51/54), and 96.4% (54/56) with modified intention-to-treat analysis (all P  > 0.05). Although not statistically significant, numerically higher eradication rates were observed with the higher dose AMO VA regimen. There were no statistically significant differences in the incidence of AEs and compliance among the three VA regimens.

Fourteen-day VA regimens with AMO doses exceeding 2 g/day demonstrated satisfactory eradication rates. HD-VA therapy is potentially the most effective regimen. Large-sample clinical trials are required to further validate these findings.

Potassium-competitive acid blockers (PCABs) represent a new class of compounds for the treatment of acid-related disorders. Recent FDA approval of the PCAB vonoprazan for erosive esophagitis has started an important new approach to acid-related disorders.

Compared to conventional proton pump inhibitors (PPIs), PCABs provide more rapid, potent, and sustained suppression of gastric acid with faster and more durable symptom relief. Studies have demonstrated the efficacy of PCABs for erosive esophagitis, nonerosive reflux disease, and peptic ulcer disease including H. pylori. However, the PCAB vonoprazan was only approved in the US as part of combination therapy for eradication of H. pylori. Clinical trials have now demonstrated noninferiority of vonoprazan to lansoprazole for treatment of erosive esophagitis, particularly noting superiority of vonoprazan in patients with severe esophagitis resulting in FDA approval of vonoprazan for treatment of erosive esophagitis. Emerging data suggests a possible utility of vonoprazan for PPI-resistant gastroesophageal reflux disease (GERD) and on-demand therapy for nonerosive reflux disease. Vonoprazan is generally well tolerated but long-term safety data is not well established.

The PCAB vonoprazan is a newly FDA approved treatment option for erosive esophagitis. Its possible role in PPI-resistant GERD and nonerosive reflux disease warrants further investigation.

Erosive esophagitis (EE) is a gastroesophageal reflux disease characterized by mucosal breaks in the esophagus. Proton pump inhibitors are widely used as maintenance therapy for EE, but many patients still relapse. In this trial, we evaluated the noninferiority of vonoprazan vs. lansoprazole as maintenance therapy in patients with healed EE.

We performed a double-blind, double-dummy, multicenter, phase 3 clinical trial among non-Japanese Asian adults with endoscopically confirmed healed EE from April 2015 to February 2019. Patients from China, South Korea, and Malaysia were randomized to vonoprazan 10 mg or 20 mg once daily or lansoprazole 15 mg once daily for 24 weeks. The primary endpoint was endoscopically confirmed EE recurrence rate over 24 weeks with a noninferiority margin of 10% using a two-sided 95% confidence interval (CI). Treatment-emergent adverse events (TEAEs) were recorded.

Among 703 patients, EE recurrence was observed in 24/181 (13.3%) and 21/171 (12.3%) patients receiving vonoprazan 10 mg or 20 mg, respectively, and 47/184 (25.5%) patients receiving lansoprazole (differences: -12.3% [95% CI, -20.3% to -4.3%] and -13.3% [95% CI, -21.3% to -5.3%], respectively), meeting the primary endpoint of noninferiority to lansoprazole in preventing EE recurrence at 24 weeks. Evidence of superiority (upper bound of 95% CI <0%) was also observed. At 12 weeks, endoscopically confirmed EE recurrence was observed in 5/18, 2/20, and 7/20 of patients receiving vonoprazan 10 mg, vonoprazan 20 mg, and lansoprazole, respectively. TEAEs were experienced by 66.8% (157/235), 69.0% (156/226), and 65.3% (158/242) of patients receiving vonoprazan 10 mg, vonoprazan 20 mg, and lansoprazole, respectively. The most common TEAE was upper respiratory tract infection in 12.8% (30/235) and 12.8% (29/226) patients in vonoprazan 10 mg and 20 mg groups, respectively and 8.7% (21/242) patients in lansoprazole group.

Vonoprazan maintenance therapy was well-tolerated and noninferior to lansoprazole for preventing EE recurrence in Asian patients with healed EE.

https://clinicaltrials.gov; NCT02388737.

The efficacy and optimal dose of the new acid-suppressant vonoprazan (VPZ) for quadruple therapy remain uncertain. This study aimed to compare the efficacy and safety of 20 mg VPZ daily (VOD) and 20 mg VPZ twice daily (VTD) with a proton pump inhibitor (PPI) twice daily in quadruple therapy.

We retrospectively analyzed the data of 954 patients treated with quadruple therapy to eradicate Helicobacter pylori. Eradication rates and adverse events were compared between the VOD and VTD groups, and between the VOD and PPI groups. Multivariate analysis was conducted to identify the predictors of eradication failure.

Eradication was successful in 875 (91.7%) of the 954 patients. The total, initial, and rescue eradication rates in the VOD group were 92.1%, 93.3%, and 77.8%, respectively. In both the crude and multivariate analyses, the VOD group showed eradication rates comparable to those of the VTD and PPI groups (all P > 0.05). Age > 60 years (odds ratio [OR] = 2.165, P = 0.012) and use of rescue therapy (OR = 3.496, P < 0.001) were independent risk factors for eradication failure, whereas VPZ at a low dosing frequency of 20 mg daily was not. A total of 787 patients (82.5%) were followed up (mean follow-up time, 6.7 ± 2.0 months). Compared with the VOD group, the VTD group was more likely to experience adverse events (OR = 2.073, P = 0.035).

VPZ at a low dose of 20 mg daily is an effective and safe component of the quadruple therapy for H.pylori eradication.

Helicobacter pylori (H. pylori) infection is the most prevalent type of bacterial infection. Current guidelines from different regions of the world neglect specific African conditions and requirements. The African Helicobacter and Microbiota Study Group (AHMSG), founded in 2022, aimed to create an Africa-specific consensus report reflecting Africa-specific issues.

Eighteen experts from nine African countries and two European delegates supported by nine African collaborators from eight other countries prepared statements on the most important African issues in four working groups: (1) epidemiology, (2) diagnosis, (3) indications and prevention, and (4) treatment. Limited resources, restricted access to medical systems, and underdeveloped diagnostic facilities differ from those of other regions. The results of the individual working groups were presented for the final consensus voting, which included all board members.

There is a need for further studies on H. pylori prevalence in Africa, with diagnosis hinged on specific African situation. Treatment of H. pylori in the African setting should be based on accessibility and reimbursement, while indication and prevention should be defined in specific African countries.

Both vonoprazan and proton pump inhibitors (PPIs) are currently used to treat artificial ulcers after gastric endoscopic submucosal dissection. However, evidence-based medicine proving the efficacy of vonoprazan is still lacking. Therefore, this meta-analysis aimed to compare the efficacy of vonoprazan and PPIs for the treatment of artificial ulcers after gastric endoscopic submucosal dissection.

The PubMed, EMBASE and Cochrane Library databases were searched up to September 2023 for related randomized controlled trials (RCTs). RCTs that compared the efficacy of vonoprazan and PPIs in treating artificial gastric ulcers after gastric endoscopic submucosal dissection were included. Two independent reviewers screened the included studies, extracted the data and assessed the risk of bias. The following outcomes were extracted for comparison: ulcer healing rate, ulcer shrinkage rate, delayed postoperative bleeding rate, and ulcer perforation rate.

Nine randomized controlled trials involving 926 patients were included. The pooled results showed that vonoprazan had a significantly lower rate of delayed postoperative bleeding than did PPIs (RR = 0.46; 95% CI = 0.23-0.91; P = 0.03). No significant differences were found in terms of ulcer healing, shrinkage rates, or ulcer perforation rates between vonoprazan and PPIs.

Compared with PPIs, vonoprazan is superior at reducing delayed postoperative bleeding after endoscopic submucosal dissection. However, further studies are needed to prove the efficacy of vonoprazan.

Identifier CRD42024509227.

Yu et al's study in the World Journal of Gastroenterology (2023) introduced a novel regimen of Vonoprazan-amoxicillin dual therapy combined with Saccharomyces boulardii (S. boulardii) for the rescue therapy against Helicobacter pylori (H. pylori), a pathogen responsible for peptic ulcers and gastric cancer. Vonoprazan is a potassium-competitive acid blocker renowned for its rapid and long-lasting acid suppression, which is minimally affected by mealtime. Compared to proton pump inhibitors, which bind irreversibly to cysteine residues in the H+/K+-ATPase pump, Vonoprazan competes with the K+ ions, prevents the ions from binding to the pump and blocks acid secretion. Concerns with increasing antibiotic resistance, effects on the gut microbiota, patient compliance, and side effects have led to the advent of a dual regimen for H. pylori. Previous studies suggested that S. boulardii plays a role in stabilizing the gut barrier which improves H. pylori eradication rate. With an acceptable safety profile, the dual-adjunct regimen was effective regardless of prior treatment failure and antibiotic resistance profile, thereby strengthening the applicability in clinical settings. Nonetheless, S. boulardii comes in various formulations and dosages, warranting further exploration into the optimal dosage for supplementation in rescue therapy. Additionally, larger, randomized, double-blinded controlled trials are warranted to confirm these promising results.

Vonoprazan holds significant research promise for Helicobacter pylori eradication, with the goal of determining the most effective drug regimen. In this study, H. pylori patients (426) were enrolled and randomized into 3 groups: an EA14 group (20 mg of esomeprazole qid and 1000 mg of amoxicillin tid for 14 days), a VA14 group (20 mg of vonoprazan bid and 750 mg of amoxicillin qid for 14 days), and a VA10 group (20 mg of vonoprazan bid and 1000 mg of amoxicillin tid for 10 days). Key outcomes encompassed the H. pylori eradication rate, patient adverse effects, and compliance. In the EA14, VA14, and VA10 groups, H. pylori eradication rates were 89.4%, 90.1%, and 88.7% in intention-to-treat analysis, and 94.2%, 94.4%, and 94.6% in per-protocol analysis, respectively. Adverse events incidences were 14.8%, 12.7%, and 5.6%, while compliance rates were 88.7%, 90.9%, and 95.8%, respectively. Notably, the VA10 regimen demonstrated comparable H. pylori eradication rates, adverse effect incidences, and compliance levels to the EA14 and VA14 regimens.

Acid-suppressive drugs (ASDs) are widely used in many gastric acid-associated diseases. Nocturnal acid breakthrough has been a common problem of many ASDs, such as proton-pump inhibitors (PPIs) and H2 -receptor antagonists (H2RAs). Potassium-competitive acid blockers (P-CABs) are expected to solve this continuing conundrum. This article examined major ASDs and compared them with placebo in terms of nocturnal acid-inhibitory effects, using a network meta-analysis of randomized controlled trials (RCTs).

To compare the effectiveness of major ASDs, a Bayesian network meta-analysis (NMA) was applied to process data extracted from RCTs. The plausible ranking for each regimen and some subgroups were assessed by surface under the cumulative ranking curves (SUCRA).

Fifty-five RCTs were conducted with 2015 participants. In terms of nocturnal acid-inhibitory effects, the overall results showed that tegoprazan (SUCRA 91.8%) and vonoprazan (SUCRA 91.0%) had the best performance, followed by new PPIs (including tenatoprazole and ilaprazole) (SUCRA 76.6%), additional H2RAs once at bedtime (AHB) (SUCRA 61.3%), isomer PPIs (including esomeprazole and dexlansoprazole) (SUCRA 38.6%), revaprazan (SUCRA 34.7%), traditional PPIs (including omeprazole, rabeprazole, pantoprazole, lansoprazole) (SUCRA 32.6%), H2RAs (SUCRA 23.1%), and placebo (SUCRA 0.3%). In some subgroups, the nocturnal acid-inhibitory effect of vonoprazan or tegoprazan was better than most of the other regimens, even new PPIs and AHB.

This is the first study to compare the effect of ASDs on inhibiting nocturnal acid breakthrough. Overall, in terms of nocturnal acid-inhibitory effect, vonoprazan and tegoprazan had an advantage against other regimens including H2RAs, isomer PPIs, traditional PPIs, AHB, and new PPIs. Even in some subgroups, such as language classification (English), types of study design (crossover-RCT), age (≤40 years), BMI (18.5-24.9 kg/m2 ), continent (Asia and North America), disease status (health), the duration of therapy (2 weeks), and time of administration (at daytime or at night-time), the nocturnal acid-inhibitory effect of vonoprazan or tegoprazan were better than most regimens, even AHB and new PPIs.

Background: Lansoprazole, a proton-pump inhibitor (PPI), is the primary therapy for peptic ulcers (PU). Potassium competitive acid blockers (P-CAB) offer an alternative for acid suppression. However, the efficacy and safety of P-CABs versus lansoprazole in the management of PU has not been evaluated. Methods: Five databases were searched for randomized clinical trials in English until 31 August 2023. Data extraction provided outcome counts for ulcer healing, recurrent NSAID-related ulcer, and adverse events. The pooled effect, presented as rate difference (RD), was stratified by ulcer location, follow-up time, and the types of P-CAB, along with their corresponding 95% confidence intervals (95% CI). Results: The pooled healing rates of peptic ulcers were 95.3% (1,100/1,154) and 95.0% (945/995) for P-CABs and lansoprazole, respectively (RD: 0.4%, 95% CI: -1.4%-2.3%). The lower bounds of the 95% CI fell within the predefined non-inferiority margin of -6%. In subgroup analyses base on ulcer location, and follow-up time also demonstrated non-inferiority. The drug-related treatment-emergent adverse events (TEAEs) did not differ significantly among groups (RR: 0.997, 95% CI: 0.949-1.046, p = 0.893). However, P-CAB treatment was associated with an increased risk of the serious adverse events compared to lansoprazole (RR: 1.325, 95% CI: 1.005-1.747, p = 0.046). Conclusion: P-CABs demonstrated non-inferiority to lansoprazole in the management of peptic ulcer. The safety and tolerability profile are comparable, with similar TEAEs rates. However, P-CABs appear to have a higher risk of serious adverse events. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=458361 Identifier: PROSPERO (No. CRD42023458361).