Vonoprazan (Voquezna®) is a potassium-competitive acid blocker (PCAB) with improved pharmacodynamic and pharmacokinetic properties compared with proton-pump inhibitors (PPIs) that allow for stronger control of gastric acid with once-daily oral administration and no requirement to be taken in relation to timing of meals for optimal efficacy. In the USA, vonoprazan has been approved as a first-in-class treatment for healing and maintenance of healing of erosive esophagitis, and for relief of heartburn in adult patients with erosive esophagitis and non-erosive gastro-esophageal reflux disease (GERD). In pivotal phase III trials, vonoprazan was non-inferior to the PPI lansoprazole in healing and superior to lansoprazole in maintenance of healing of erosive esophagitis, and was superior to placebo for treating heartburn in US patients with non-erosive GERD. Vonoprazan was generally well tolerated; the most common adverse events included abdominal pain, constipation, diarrhea, nausea, and dyspepsia. Vonoprazan is, therefore, a valuable addition to the therapies available for adults with erosive esophagitis and non-erosive GERD.

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.

Concerns surrounding long-term proton pump inhibitor use have prompted the exploration of alternative treatments for reflux esophagitis (RE). We previously demonstrated that 24 weeks of on-demand treatment with vonoprazan, a potassium-competitive acid blocker, effectively managed mild RE (Los Angeles classification grade A/B) in more than 80% of patients. However, its long-term efficacy remains unknown. Therefore, the present study investigated sustained effectiveness.

We conducted a retrospective observational study on 30 participants with mild RE from our previous research. Participants with recurrent RE or symptom exacerbation were excluded and considered as treatment failure. Participants with the remission of RE and reflux symptoms under on-demand treatment until the clinic visit between October 2023 and February 2024 were regarded as treatment success. Predictors of treatment failure were analyzed.

During the observation period, 5 participants failed treatment due to symptom exacerbation and 6 due to recurrent RE. Five participants were excluded from analyses due to non-GERD causes. Fourteen participants (56.0%) successfully continued on-demand treatment for 91.5 months [89.3-92.8]. Age > 67 years significantly predicted treatment failure with a sensitivity of 72.7% and specificity of 85.7%. Although none of the patients with RE grade A had recurrent RE, it was not a significant difference.

Approximately 50% of patients with mild RE successfully continued on-demand treatment for more than 7 years. Age > 67 years was identified as a predictor of treatment failure. Prospective multi-center studies are warranted to validate these results.

X842 is a new type of gastric acid-suppressing agent with a rapid onset of action and a long duration of effect. We aim to investigate the efficacy and safety of different doses of X842 vs lansoprazole in the treatment of patients with erosive esophagitis (EE).

This phase 2 study included 90 patients with EE (Los Angeles grades A-D) who were randomized (1:1:1) to receive oral low-dose X842 (50 mg/d, n = 31), high-dose X842 (100 mg/d, n = 31), or lansoprazole (30 mg/d, n = 30) for 4 weeks. The main efficacy end point was the EE healing rate, which was the proportion of patients who achieved endoscopic healing after 4 weeks of treatment.

For intention-to-treat analysis, the EE healing rates at 4 weeks were 93.6% (29/31), 79.3% (23/29), and 80.0% (24/30) for the X842 50 mg, the X842 100 mg, and the lansoprazole 30 mg groups. For per-protocol analysis, the EE healing rates at 4 weeks were 93.6% (29/31), 80.8% (21/26), and 82.1% (23/28) in the 3 groups, respectively. The EE healing rate did not significantly differ among the 3 groups in either the intention-to-treat ( P = 0.2351) or per-protocol ( P = 0.3320) analysis. The incidence of drug-related treatment-emergent adverse events did not differ among groups. No severe drug-related treatment-emergent adverse events occurred in the X842 group.

Our findings confirmed that X842 had efficacy and a favorable safety profile similar to those of lansoprazole. Therefore, X842, a novel potassium-competitive acid blocker, is expected to become a promising therapeutic agent for EE.

Few prediction scores for Clostridioides difficile infection (CDI), a potentially life-threatening nosocomial diarrhea, combine high accuracy with simplicity. A simple prediction score for routine clinical practice is needed.

We conducted a retrospective cohort study of all inpatients aged ≥ 18 at a secondary care hospital in Japan. The derivation and validation cohorts consisted of patients from January 2016 to December 2020 and January 2021 to September 2022, respectively. Demographic and clinical data were retrieved using electronic medical records and an administrative database. The primary outcome was to derive and validate an accurate, simple prediction score for primary hospital-onset CDI. A derived prediction score by logistic regression analysis was calibrated and validated.

CDI developed in 102 of 25 517 and 25 of 6259 patients in the derived and validation cohorts (2.7 cases/10 000 patient-days). The derived model for predicting CDI, including antibiotic use, acid suppressant (proton pump inhibitors or vonoprazan) use, Charlson comorbidity index, and Barthel index, yielded c-statistics of 0.89 and 0.82 in the derivation and validation cohort. The model was well calibrated.

This simple prediction score enables early medical intervention and modification of treatment plans to reduce the risk of developing primary hospital-onset CDI.

Patients with erosive oesophagitis, and those with persistent symptomatic non-erosive gastro-oesophageal reflux disease, require long-term maintenance treatment with acid-suppressing agents.

To evaluate the safety of vonoprazan, a potassium-competitive acid blocker, in an integrated analysis of data from clinical trials in adults.

We included 14 clinical trials of vonoprazan conducted in multiple countries. Mean duration of exposure in person-years to vonoprazan (n = 5318) was 2068, to comparators lansoprazole (n = 1925) or esomeprazole (n = 86) was 751, and to placebo (n = 779) was 59. We report adverse events, serum gastrin, and liver enzyme levels as the main outcomes. Post-marketing safety data from December 26, 2014 (date of commercialisation in Japan) to December 25, 2023, are also provided.

Nasopharyngitis was the only adverse event reported by at least 5.0% of patients (6.94% vonoprazan, 5.07% proton pump inhibitor (PPI), 4.49% placebo). Incidence rates per 100 person-years for serious adverse events were 10.39 for vonoprazan, 10.65 for PPIs, and 1.69 for placebo. One patient each on vonoprazan and lansoprazole was diagnosed with gastric cancer. Mean serum gastrin levels were higher on vonoprazan than lansoprazole but normalised by 4 weeks after discontinuation. Elevated liver enzyme levels were infrequent and of low magnitude with no differences between vonoprazan and PPIs. There were four deaths; none was considered related to study drug.

Vonoprazan was well tolerated. Its safety profile from both clinical trial and post-marketing data were consistent and comparable to that of its PPI comparators with respect to treatment-emergent adverse events.

Many patients diagnosed with gastro-oesophageal reflux disease (GERD) have persistent symptoms despite proton pump inhibitor (PPI) therapy.

The aim of this consensus is to provide evidence-based statements to guide clinicians caring for patients with refractory reflux-like symptoms (rRLS) or refractory GERD.

This consensus was developed by the International Working Group for the Classification of Oesophagitis. The steering committee developed specific PICO questions pertaining to the management of PPI rRLS. Methodologists conducted systematic reviews of the literature. The quality of evidence and strength of recommendations were rated using the GRADE approach.

Consensus was reached on 13 of 17 statements on diagnosis and management. For rRLS, suggested diagnostic strategies included endoscopy, ambulatory reflux testing and oesophageal manometry. The group did not reach consensus on the role of oesophageal biopsies or the use of reflux-symptom association in patients undergoing reflux testing. The group suggested against increasing the PPI dose in patients who had received 8 weeks of a twice-daily PPI. Adjunctive alginate or antacid therapy was suggested. There was no consensus on the role of adjunctive prokinetics. There was little role for adjunctive transient lower oesophageal sphincter relaxation (TLESR) inhibitors or bile acid sequestrants. Endoscopic or surgical anti-reflux procedures should not be performed in patients with rRLS in the absence of objectively confirmed GERD.

The management of rRLS should be personalised, based on shared decision-making regarding the role of diagnostic testing to confirm or rule out GERD as a basis for treatment optimisation. Anti-reflux procedures should not be performed without objective confirmation of GERD.

Zastaprazan is a potent potassium-competitive acid blocker developed to treat gastroesophageal reflux disease. The aim of this study was to evaluate the efficacy and safety of zastaprazan compared with esomeprazole in patient with erosive esophagitis (EE).

A phase III, multicenter, randomized, double-blind, noninferiority clinical study was conducted with 300 subjects with confirmed EE. Subjects were randomized to receive zastaprazan 20 mg or esomeprazole 40 mg once daily up to 8 weeks. The primary end point was the cumulative proportion of subject with healed EE confirmed by endoscopy at week 8. The secondary end points included the healing rate at week 4, symptom response, and quality of life assessment. Safety profiles and serum gastrin levels were also assessed.

In the full analysis set, the cumulative healing rate at week 8 were 97.92% (141/144) for zastaprazan and 94.93% (131/138) ( P = 0.178) for esomeprazole. The healing rate at week 4 in the zastaprazan group was higher than the esomeprazole group (95.14% [137/144] vs 87.68% [121/138]; P = 0.026). There was no significant difference between groups in healing rates (the per-protocol set) at week 8 and week 4, symptom responses, quality of life assessments, and safety profiles. In addition, serum gastrin levels increased during treatment in both groups, with a significant difference between the 2 groups ( P = 0.047), but both decreased after treatment.

An 8-week therapy of zastaprazan 20 mg is noninferior to esomeprazole 40 mg in subjects with predominantly low-grade EE. The healing rate at week 4 appears to be higher for zastaprazan than esomeprazole.

The aim is to examine the Reflux Symptom Score-12 (RSS-12) and assess the effectiveness of vonoprazan fumarate in managing laryngopharyngeal reflux disease (LPRD) among the Chinese population.

A total of 140 patients with LPRD who were treated at our otorhinolaryngology outpatient clinic were included. The patients were randomly divided into the vonoprazan treatment group and the esomeprazole treatment group. The outcome indicators were the pretreatment and post treatment values of the Reflux Symptom Index (RSI), RSS-12, and reflux finding score.

The mean pretreatment RSS-12 and RSI values were 55.79 ± 11.94 and 18.67 ± 3.60 in the vonoprazan treatment group and 54.91 ± 11.95 and 18.44 ± 3.66 in the esomeprazole treatment group, respectively. Furthermore, both groups showed a significant decrease in the RSI and RSS-12 values after 4, 8, and 12 weeks of acid suppression therapy. In particular, 12 weeks of treatment led to a good treatment response in 91.4% and 87.1% of the patients in the vonoprazan treatment and esomeprazole treatment groups, respectively, based on their RSI values, and a favorable treatment response in 82.9% and 77.1% of those in the vonoprazan treatment and esomeprazole treatment groups, respectively, according to their RSS-12 values. More importantly, after 4 and 8 weeks of acid-suppressive therapy, the relative baseline change in RSS-12 scores in the vonoprazan treatment group was considerably larger than that in the omeprazole treatment group.

Compared to proton pump inhibitors (PPIs), vonoprazan fumarate has demonstrated superior early therapeutic efficacy, resulting in a notable improvement in laryngopharyngeal reflux symptoms at the start of treatment. When we extended acid-suppressive medication for 12 weeks, we saw a treatment effect comparable to that of PPIs.

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.

Effective suppression of gastric acid secretion promotes healing of erosive esophagitis. Treatment guidelines recommend proton pump inhibitors (PPIs) and histamine H2-receptor antagonists (H2RAs). Emerging evidence also supports potassium-competitive acid blockers (P-CABs). The aim was to construct a mathematical model to examine the relationship between pH holding time ratios (HTRs) and erosive esophagitis healing rates with H2RAs, PPIs and P-CABs. By literature search, we identified studies of H2RAs, PPIs or P-CABs that reported mean pH >4 HTRs at steady state (days 5-8) and erosive esophagitis healing rates after 4 and/or 8 weeks. We aggregated treatments by drug class and developed a non-linear, mixed-effects model to explore the relationship between pH >4 HTRs and healing rates. The pH dataset included 82 studies (4297 participants; 201 dosage arms); healing rate data came from 103 studies (43,417 patients; 196 treatment arms). P-CABs achieved the longest periods with intragastric pH >4, and the highest healing rates after 4 and 8 weeks. The predicted probabilities of achieving ≥90% healing rates at 8 weeks were 74.1% for P-CABs, 17.3% for PPIs and 0% for H2RAs. P-CABs provide the longest duration with intragastric pH >4 and, accordingly, the highest healing rates of erosive esophagitis.

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 management of acid-based disorders was transformed in the 1980s with the advent of proton pump inhibitors (PPIs), which target the hydrogen-potassium adenosine triphosphatase (proton pump) of the parietal cell. Potassium-competitive acid blockers (P-CABs), a newer class of medications, act at the same proton pump through a novel mechanism resulting in profound and sustained acid suppression. Although trials in Asian populations over the past decades have highlighted the potential benefit of P-CABs, clinical trials in Western populations have been initiated more recently. These trials evaluated vonoprazan in patients with Helicobacter pylori infection, erosive esophagitis, and heartburn with nonerosive reflux disease and have demonstrated promising results, culminating in US Food and Drug Administration approval for these indications. Adverse event profiles between PPIs and P-CABs appear comparable thus far, although additional long-term data on P-CABs are needed. While navigating the evolving landscape of acid suppression, it is crucial to identify which patients and diseases are poised to derive the most benefit from this emerging therapeutic option. This article seeks to highlight important pharmacologic properties of PPIs and P-CABs, understand the current literature with a focus on clinical trials in Western populations, and explore potential scenarios for integrating P-CABs into therapeutic regimens.

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.

Potassium-competitive acid blockers have emerged as a promising treatment of acid-related disorders. However, the optimal dosage for maximizing their efficacy remains unclear. The aim of this network meta-analysis was to compare the efficacy and safety of various dosages of potassium-competitive acid blockers and proton-pump inhibitors for treating acid-related disorders.

We searched PubMed, Embase, Cochrane Library, and Web of Science from inception to July 16, 2023. Data extraction was performed independently by 2 authors. The Cochrane Risk of Bias in Randomized Trials tool (RoB 2.0) was used for bias assessment. The efficacy and safety were compared using the odds ratio with 95% confidence intervals.

Twelve articles were included in the present meta-analysis. For gastric/duodenal ulcers, keverprazan 30 mg (K30) exhibited the highest surface under the cumulative ranking (SUCRA) value (92.8%) for healing rate. In terms of total adverse events, lansoprazole 30 mg (L30) exhibited the lowest SUCRA value (25.3%) in the treatment of gastric/duodenal ulcers. For the healing rate in erosive esophagitis, the maximum SUCRA value of vonoprazan 40 mg (V40) was 90.7% in the first subgroup (erosive esophagitis using vonoprazan, keverprazan, and lansoprazole) and the maximum SUCRA value of T50 was 72.1% in the second subgroup (erosive esophagitis using tegoprazan, fexuprazan, and esomeprazole). For the total adverse events in erosive esophagitis, L15 exhibited the lowest SUCRA value (12.2%) in the first group and E40 exhibited the lowest SUCRA value (24.4%) in the second group.

K30 may be the most effective dosage for increasing the healing rate of gastric/duodenal ulcers. For erosive esophagitis, V40 and T50 may be the preferred dosages.

This meta-analysis aimed to investigate the efficacy and safety of potassium-competitive acid blockers (P-CABs) and proton pump inhibitors (PPIs) in treating erosive esophagitis (EE).

PubMed, Embase, Cochrane Library, and Web of Science were systematically searched using predefined search terms up to January 2024. Relevant randomized controlled trials were included. The outcoming were the EE healing rate and treatment-related adverse events incidence.

Nine randomized controlled trials involving 4012 patients were included. Patients receiving P-CAB exhibited a significantly better overall healing rate compared with PPI at week 2 [risk ratio (RR) = 1.06], but no statistical difference was observed at week 4 and week 8. Subgroup analysis revealed that P-CAB demonstrated a higher healing rate for patients with Los Angeles (LA) grade C/D, regardless of the assessment at week 2 (RR = 1.17), week 4 (RR = 1.10), or week 8 (RR = 1.08). However, no significant difference was found between PPI and P-CAB for patients with LA grade A/B at week 2, week 4, or week 8. Furthermore, patients treated with P-CAB had lower recurrence rates during maintenance therapy compared with PPI (RR = 0.79). In terms of safety, P-CAB was associated with a lower incidence of headache compared with PPI (RR = 0.32), with no statistical difference found in any treatment-related adverse events between the two groups.

P-CAB was found to be safe and effective for EE treatment compared with PPI, particularly in 2-week short-term treatment, severe EE (LA grade C/D) treatment, or maintenance therapy. Limitations such as potential heterogeneity among included trials should be considered in the interpretation of these findings.

Peptic ulcer bleeding is the most common cause of upper gastrointestinal bleeding, which has a high mortality risk. The standard therapy for acute peptic ulcer bleeding combines medication administration and endoscopic therapies. Both pharmacologic and endoscopic therapies have developed continuously in the past few decades. Proton pump inhibitors (PPIs) already reached a high efficacy in ulcer healing and have been widely used in the past few decades. Endoscopic hemostasis, which includes local epinephrine injection, heater probe coagulation, use of hemostatic clips, and/or band ligation, is highly effective with an overall hemostatic success rate of 85%-90%. However, 10%-20% of patients could not be cured by the current standard combination treatment. Recurrent ulcer bleeding, despite an initial successful hemostasis, is also a big problem for longer hospitalization stays, higher mortality, and higher complication rates, especially for malignant ulcer bleeding. How to manage all types of peptic ulcer bleeding and how to prevent early recurrent peptic ulcer bleeding remain unresolved clinical problems. Recently, several novel medications and endoscopic methods have been developed. Potassium competitive acid blockers have shown a stronger and longer acid suppression than PPI. Hemostatic powder spray and hemostatic gel emulsion are novel hemostatic weapons with emerging evidence, which are potential missing pieces of the puzzle. This literature review will go through the development of endoscopic hemostasis to the prospects of novel endoscopic treatments.

Gastroesophageal reflux disease (GERD) is typically managed based on the clinical phenotype. We evaluated the efficacy and safety of potassium-competitive acid blockers (PCABs) in patients with various clinical GERD phenotypes.

Core databases were searched for studies comparing PCABs and proton pump inhibitors (PPIs) in clinical GERD phenotypes of erosive reflux disease (ERD), non-erosive reflux disease (NERD), PPI-resistant GERD and night-time heartburn. Additional analysis was performed based on disease severity and drug dosage, and pooled efficacy was calculated.

In 9 randomized controlled trials (RCTs) evaluating the initial treatment of ERD, the risk ratio for healing with PCABs versus PPIs was 1.09 (95% CI, 1.04-1.13) at 2 weeks and 1.03 (95% CI, 1.00-1.07) at 8 weeks, respectively. PCABs exhibited a significant increase in both initial and sustained healing of ERD compared to PPIs in RCTs, driven particularly in severe ERD (Los Angeles grade C/D). In 3 NERD RCTs, PCAB was superior to placebo in proportion of days without heartburn. Observational studies on PPI-resistant symptomatic GERD reported symptom frequency improvement in 86.3% of patients, while 90.7% showed improvement in PPIresistant ERD across 5 observational studies. Two RCTs for night-time heartburn had different endpoints, limiting meta-analysis. Pronounced hypergastrinemia was observed in patients treated with PCABs.

Compared to PPIs, PCABs have superior efficacy and faster therapeutic effect in the initial and maintenance therapy of ERD, particularly severe ERD. While PCABs may be an alternative treatment option in NERD and PPI-resistant GERD, findings were inconclusive in patients with night-time heartburn.

This meta-analysis evaluated the efficacy and safety of potassium-competitive acid blockers (PCABs) compared to proton pump inhibitors (PPIs) in treating gastroesophageal reflux disease (GERD). A comprehensive literature search was conducted across multiple databases, and 11 randomized controlled trials comparing PCABs with PPIs were included. The primary outcome was the healing of erosive esophagitis (EE), with secondary outcomes, including relief of heartburn symptoms and adverse events. The analysis included 11 studies and a pooled sample of 4,108 GERD patients. Results showed that PCABs were significantly more effective in healing EE compared to PPIs (OR: 1.67, 95% CI: 1.24-2.24, p<0.01). PCABs also demonstrated a higher rate of complete resolution of heartburn symptoms, although this difference did not reach statistical significance (OR: 1.43, 95% CI: 0.98-2.09, p=0.06). In terms of safety, there was no significant difference in adverse events between PCABs and PPIs (OR: 0.91, 95% CI: 0.79-1.04, p=0.18), including serious adverse events. The superior efficacy of PCABs can be attributed to their unique pharmacological properties, which allow for more rapid and potent acid suppression compared to PPIs. However, the long-term safety profile of PCABs, particularly newer agents, requires further investigation. The study was limited by the predominance of vonoprazan among the PCABs studied and the focus on patients with EE rather than non-erosive reflux disease. In conclusion, this meta-analysis suggests that PCABs are more effective than PPIs in treating GERD, particularly in healing EE, while maintaining a comparable safety profile. Future research should focus on evaluating a wider range of PCABs, assessing their efficacy in non-erosive reflux disease, and investigating their long-term safety in GERD management.

Gastroesophageal reflux disease (GERD) is a common disease caused by reflux of gastric contents to the esophagus. Proton-pump inhibitors (PPIs) are recommended as a first-line therapy to treat GERD. Recently, the potassium-competitive acid inhibitors have been increasingly in use in clinical practice. We aimed to evaluate the efficacy and safety of P-CABs in GERD.

We searched PubMed, the Cochrane Library, EMBASE and Web Of Science for publications regarding randomized controlled trials comparing potassium-competitive acid inhibitors to PPI monotherapy or Placebo with respect to efficacy and safety in GERD (until April 2023). The primary outcome was an absence or global symptom improvement and the incidence of adverse events in GERD. The quality of the included literature was assessed using the bias assessment tool recommended in the Cochrane Systematic Assessor's Handbook 5.1.0. We use RevMan 5.3 software for Meta-analysis, sensitivity analysis and publication bias analysis.

Of the 991 screened studies, 14 studies including 4868 participants were analyzed. The ORs for the healing rates of GERD with P-CABs versus PPI/Placebo were 2.10 (95% confidence interval [CI] 1.53-2.88), additionally, 1.09 (95% CI 1.05-1.14), 1.03 (95% CI 1.00-1.06) and 1.03 (95% CI 0.99-1.06) in Weeks 2, 4, and 8, respectively. The effectiveness rate of the experimental group was significantly higher than that of the control group (RR 1.73; 95% CI 1.27-2.36). The overall OR of Incidence of adverse events with P-CABs versus PPI/Placebo was 1.08 (95% CI 0.88-1.12). Overall, the risk of bias was low to some concerns. Furthermore, sensitivity analyses confirmed the robustness of the study's conclusion.

Our findings suggest that potassium-competitive acid inhibitors is non-inferior to PPIs as therapy for patients with GERD. The safety outcomes for potassium-competitive acid inhibitors are similar to those for PPIs.

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.

Proton-pump inhibitors (PPIs) and potassium-competitive acid blockers (P-CABs) are recommended for erosive esophagitis (EE), with good safety and tolerance. However, it is unclear which is the best treatment option for EE.

This study aimed to evaluate the comparative efficacy of P-CABs and PPIs for healing EE patients, seeking an appropriate treatment choice in the 4- or 8-week treatment and standard or double dose.

A systematic review and network meta-analysis.

Relevant databases were searched to collect randomized controlled trials of PPIs and P-CABs in the treatment of EE up to 31 May 2023. Studies on standard or double-dose PPIs or P-CABs which were published in English and assessed 4- or 8-week healing effects in EE were included. A network meta-analysis was performed to evaluate the efficacy of the treatments under the frequentist framework. Sensitivity and subgroup analyses of patients with different baseline EE were also conducted.

In all, 34 studies involving 25,054 patients and 9 PPIs, 6 P-CABs, or placebo treatment interventions were included. The pooled 4-week healing rate was significantly statistically lower than the pooled 8-week healing rate for most treatments. Besides, the higher healing rate of double-dose treatment than standard-dose treatment was not observed in the initial treatment of most drugs. The main analysis only included studies conducted for both patients with and without severe EE at baseline, and the proportion of severe EE included in the study was >10%, Keverprazan 20 mg qd ranked best with a surface under the cumulative ranking curve (SUCRA) value of 84.7, followed by Ilaprazole 10 mg qd with a SUCRA value of 82.0, for the healing rate at 8 weeks. Sensitivity analysis showed that the results were robust. Subgroup analysis showed that most P-CABs had higher healing rates than PPIs, particularly for patients with severe EE. And the healing rate of Keverprazan 20 mg qd at 8 weeks ranked best in the subgroup without or with severe EE at baseline.

This study showed that an 8-week treatment seemed more effective than the 4-week treatment for healing EE patients. The healing effect of Keverprazan (20 mg qd) ranked best in 8-week treatment, for both severe and non-severe EE patients.

The study protocol was registered with INPLASY (registration number INPLASY2023120053).

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.

Healing rates of severe erosive esophagitis (EE; Los Angeles [LA] Grade C/D) in patients treated with a proton pump inhibitor (PPI) is suboptimal (~60-70%). Vonoprazan, a potassium-competitive acid blocker, is suggested to have better healing rates in patients with severe EE. This meta-analysis compares the efficacy and safety of vonoprazan 20 mg versus lansoprazole 30 mg daily in healing EE, specifically in those with LA Grade C/D.

We searched MEDLINE, Embase, and CENTRAL on May 24, 2023. Studies that randomized EE patients to vonoprazan 20 mg daily or lansoprazole 30 mg daily and compared healing rates were included. The risk of bias was assessed using Cochrane's Risk of Bias 2 tool. The fixed-effect model was used to obtain the pooled efficacy and safety outcomes. Subgroup analysis was done to compare healing rates in mild (LA Grade A/B) versus severe EE and based on study location.

Four randomized controlled trials (RCTs) with low risks of bias comprising 2208 participants were included. Vonoprazan 20 mg was superior to lansoprazole 30 mg daily in healing severe EE at all weeks (Week 2 RR 1.294 [95% CI 1.169-1.433], Week 4 1.160 [1.059-1.270], and Week 8 1.175 [95% CI 1.107-1.247]), but was similar for mild EE at all weeks (P-interaction < 0.01). Vonoprazan 20 mg was more efficacious than lansoprazole 30 mg at Week 8 in Western versus Asian studies (P-interaction < 0.01). Any, serious, and drug-related treatment-emergent adverse events were comparable between groups.

Vonoprazan 20 mg is superior to lansoprazole 30 mg for healing severe EE but not mild EE. Vonoprazan 20 mg daily has a similar safety profile to lansoprazole 30 mg daily.

Although proton pump inhibitors (PPIs) or potassium-competitive acid blocker (PCAB) are useful in peptic ulcer prevention, their efficacy in preventing other gastrointestinal bleeding remains unclear. This study aimed to identify the status of gastrointestinal bleeding in the modern era when PPIs are widely used.

This study included patients who underwent percutaneous coronary intervention (PCI) between 2018 and 2019 at two high-volume centers. Patients were categorized based on whether they experienced gastrointestinal bleeding within 2 years of PCI into groups A (patients who experienced gastrointestinal bleeding within 2 years after PCI) and B (patients who did not experience gastrointestinal bleeding).

Groups A and B included 21 (4.1%) and 494 (95.9%) patients, respectively (a total of 515 patients). Age at the initial PCI (77.8±2.4 and 72.0±0.5 years in groups A and B, respectively; p = 0.02), weight (53.8±3.2 and 61.8±0.7 kg in groups A and B, respectively; p = 0.01), and concomitant warfarin use (14.3% and 2.0% in groups A and B, respectively; p = 0.0005) were significantly different between the groups. The high bleeding risk rate (90.5% and 47.6% in groups A and B, respectively; p = 0.0001) was significantly different between the groups. A total of 95.9% of patients were taking PPIs or PCAB without significant differences between the groups. However, only one patient, who was taking steroids, had a gastric ulcer during PCAB treatment.

Acid-related upper gastrointestinal bleeding is largely controlled by PPIs in post-PCI patients. Furthermore, the risk factors for non-acid-related bleeding include older age, lower weight, and concomitant warfarin use.

Los Angeles grade C/D esophagitis is a severe manifestation of gastroesophageal reflux disease that require active treatment and close follow-up. Potassium competitive acid blockers (P-CAB) are promising alternatives to proton pump inhibitors (PPI). We aimed to compare the efficacy and safety of P-CAB and PPI in healing grade C/D esophagitis to aid clinical decision-making.

A systematic literature search was performed using PubMed, MEDLINE, and Cochrane Central Register of Controlled Trials. Randomized controlled trials were eligible for inclusion if efficacy of P-CAB and PPI in healing grade C/D esophagitis was reported. Pooled risk ratios and risk difference with 95% credible intervals were used to summarize estimated effect of each comparison. The benefit of treatments was ranked using the surface under the cumulative probability ranking score.

Of 5,876 articles identified in the database, 24 studies were eligible. Studies included incorporated 3 P-CAB (vonoprazan, tegoprazan, and keverprazan) and 6 PPI (lansoprazole, esomeprazole, omeprazole, rabeprazole extended-release (ER), pantoprazole, and dexlansoprazole). Based on the failure to achieve mucosal healing, 20 mg of vonoprazan q.d. ranked the first among PPI in initial and maintained healing of grade C/D esophagitis (surface under the cumulative probability ranking score = 0.89 and 0.87, respectively). Vonoprazan had similar risk of incurring adverse events, severe adverse events, and withdrawal to drug when compared with PPI. For those who attempted lower maintenance treatment dose, 10 mg of vonoprazan q.d. was a reasonable choice, considering its moderate efficacy and safety.

Vonoprazan has considerable efficacy in initial and maintained healing of grade C/D esophagitis compared with PPI, with moderate short-term and long-term safety.

Objective The use of a proton pump inhibitor (PPI) reduces rebleeding and mortality in patients with upper gastrointestinal bleeding (UGIB). Vonoprazan is a novel oral agent with strong and sustained acid-inhibitory activity. We clarified the effect of vonoprazan compared with oral PPIs in such patients. Methods We analyzed the Diagnosis Procedure Combination database. The primary outcome was rebleeding, and secondary outcomes were in-hospital mortality and in-hospital mortality after rebleeding. Propensity score matching was performed to balance the comparison groups, and logistic regression analyses were used to compare the outcomes between vonoprazan and oral PPIs. Patients Patients on vonoprazan or oral PPIs who underwent endoscopic hemostasis for UGIB between 2014 and 2019 were included. Results We enrolled 78,964 patients, of whom 27,101 and 51,863 were prescribed vonoprazan and a PPI, respectively. After propensity score matching, the rebleeding rate of vonoprazan did not significantly differ from that of oral PPIs [6.4% vs. 6.1%; odds ratio (OR), 1.05; 95% confidence interval (CI), 0.98-1.13]; similarly, the in-hospital mortality rate (1.4% vs. 1.5%; OR, 0.91; 95% CI, 0.79-1.05) and in-hospital mortality after rebleeding (0.3% vs. 0.2%; OR, 1.09; 95% CI, 0.78-1.54) also did not significantly differ between the groups. The acquired findings were robust across dose-restricted analyses and several sensitivity analyses. Conclusion Rebleeding and in-hospital mortality risks in patients on vonoprazan were similar to those in patients on oral PPIs. Considering the higher cost of vonoprazan, oral PPIs might be an optimal oral agent as an acid-suppressive therapy in such patients.

Gastroesophageal Reflux Disease (GERD) is a prevalent condition in Brazil, affecting 12% to 20% of the urban population, with significant implications for patient quality of life and potential for complications.

This paper focuses on the recent update of the Brazilian guidelines for GERD, a necessary revision due to advancements in knowledge and practice since the last publication over a decade ago. The update pays particular attention to the role and safety of proton pump inhibitors (PPIs), acknowledging the growing concerns about their long-term use, adverse events, and overprescription.

The methodology of the guideline update involved an extensive literature review in multiple languages (English, French, Italian, Spanish, and Portuguese), drawing from major databases such as Medline, Embase, and SciELO-Lilacs.

This comprehensive approach resulted in a carefully curated selection of studies, systematic reviews, and meta-analyses, specifically focusing on PPIs and other therapeutic strategies for GERD. The updated guidelines are presented in a user-friendly question-and-answer format, adhering to the PICO system (Population, Intervention, Comparison, Outcomes) for clarity and ease of interpretation. The recommendations are supported by robust scientific evidence and expert opinions, enhancing their practical applicability in clinical settings. To ensure the reliability and clarity of the recommendations, the GRADE system (Grading of Recommendations Assessment, Development, and Evaluation) was employed. This system categorizes the strength of recommendations as strong, weak, or conditional and classifies evidence quality as high, moderate, low, or very low. These classifications provide insight into the confidence level of each recommendation and the likelihood of future research impacting these guidelines.

The primary aim of these updated guidelines is to offer practical, evidence-based advice for the management of GERD in Brazil, ensuring that healthcare professionals are equipped with the latest knowledge and tools to deliver optimal patient care.

•Gastrointestinal specialists rely heavily on guidelines to manage digestive pathologies effectively. The Brazilian clinical guideline for therapeutic management of gastroesophageal reflux disease (GERD) is an invaluable tool for these specialists.

•It critically analyzes practical aspects of therapy through 12 questions covering a wide range of topics, from behavioral measures to surgical and endoscopic indications.

•The recommendations in this guideline are justified using the GRADE system (Grading of Recommendations Assessment, Development, and Evaluation), and experienced experts provide comments and suggestions at the end of each question.

Acid inhibitors have been considered in treating gastroesophageal reflux-related cough (GERC). Compared to proton pump inhibitors (PPIs), potassium-competitive acid blockers (P-CABs) have more potent and durable effects on anti-acid secretion. However, whether vonoprazan and esomeprazole have different therapeutic effects on GERC remains unknown. Patients diagnosed with GERC were enrolled in our study and randomly treated with vonoprazan (20 mg, once daily, P-CAB) or esomeprazole (20 mg, twice daily, PPI) for two months. A prokinetic agent was also administered. Patients were followed up once a month. Cough severity visual analogue scale (VAS) was measured as the primary outcome, while cough symptom score (CSS) and scores for cough-related quality-of-life or reflux-related symptoms were the secondary endpoints. A total of 50 patients completed the study, with 25 patients in each group. P-CAB and PPI groups showed similar decreases in cough severity VAS and CSS scores after the 2-month treatment (all P < 0.001). For quality-of-life, the Leicester Cough Questionnaire (LCQ) score increased significantly from baseline in both groups, but the P-CAB group had greater improvement and a higher LCQ score in month 2 (all P ≤ 0.05). For reflux-related symptoms, the Hull Airway Reflux Questionnaire (HARQ) score declined substantially over time in the P-CAB group, while the reflux symptom index (RSI) score decreased in both groups. The P-CAB group tended to have a lower HARQ (P = 0.051) and RSI (P = 0.069) scores in month 2. In conclusion, vonoprazan may be comparable to esomeprazole in cough symptom relief in GERC during the 2-month treatment period, but possibly provides better gains on classic reflux symptoms and quality-of-life. The long-term efficacy of P-CABs on GERC may be worth further exploration. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR2200067089.

To investigate the risk of acute kidney injury (AKI) in patients with cancer following the initiation of proton pump inhibitors (PPIs) and potassium-competitive acid blocker (PCAB), considering sex and anti-cancer drug use. We conducted a self-controlled case-series study using the Japan Medical Data Center claims data from 12422 patients with cancer who were prescribed PPIs or PCAB between January 2017 and December 2019. Considering the timing of PPI or PCAB, control period (days -120 to -1), risk period 1 (days 0 to +30), and risk period 2 (days +31 to +365) were defined. To assess the incidence rate ratio (IRR) and 95% confidence interval (CI) as the risk ratio, we adjusted for anti-cancer drugs to assess the risk of AKI. Additionally, we also examined sex differences to identify the risk of AKI. AKI was observed in risk period 1 [2.05 (1.12-3.72), p = 0.0192], but a slight reduction was noted in risk period 2 [0.60 (0.36-1.00), p = 0.0481]. A sex-specific increase in the risk of AKI was observed only in males during risk period 1 [2.18 (1.10-4.32), p = 0.0260], with a reduction in risk period 2 [0.48 (0.26-0.89), p = 0.0200]. We identified an increased risk of AKI in patients with cancer starting PPIs or PCAB particularly in males within 30 d after PPI or PCAB initiation, emphasizing the need for vigilant monitoring and management of AKI in this patient population.

Helicobacter pylori eradication is crucial in the treatment of peptic ulcers caused by H. pylori infection, a disease highly prevalent in Asia. We present a pooled analysis of two randomized, double-blind, double-dummy, phase 3 studies evaluating the efficacy and safety of vonoprazan-based bismuth-containing quadruple therapy for H. pylori eradication. Patients aged ≥18 years with endoscopically confirmed duodenal or gastric ulcers were randomized 1 : 1 to receive vonoprazan 20 mg or lansoprazole 30 mg once daily for up to 6 (duodenal ulcers) or 8 weeks (gastric ulcers). H. pylori-positive patients received vonoprazan- or lansoprazole-based bismuth-containing quadruple therapy for the first 2 weeks. H. pylori eradication was determined using the carbon-13 urea breath test at a follow-up visit 4 weeks post-treatment. The H. pylori eradication rate was 90.6% with vonoprazan vs. 85.2% with lansoprazole (difference: 5.4%; 95% confidence interval (CI): -0.1, 10.8). H. pylori eradication rates were 7.1% (95% CI: 1.4, 12.8) and 12.6% (95% CI: 3.9, 22.0) higher in patients aged <65 years and current smokers, respectively, with vonoprazan vs. lansoprazole. In the Chinese subpopulation, the H. pylori eradication rate was 92.0% with vonoprazan vs. 86.0% with lansoprazole (difference: 6.1%; 95% CI: 0.5, 11.7). Treatment-emergent adverse events occurred in 72.7 vs. 62.6% of H. pylori-positive patients at baseline in the vonoprazan vs. lansoprazole arm. H. pylori eradication with vonoprazan-based quadruple therapy was noninferior to lansoprazole-based quadruple therapy and exceeded 90%, a clinically relevant threshold for determining the efficacy of H. pylori eradication regimens (ClinicalTrials.gov identifier: NCT03050359; NCT03050307).

Vonoprazan results in more potent acid suppression for gastroesophageal reflux disease (GERD) than proton pump inhibitors. It has only been approved for treating erosive esophagitis in China, but 30-40% of GERD patients cannot achieve the goal of treatment with vonoprazan 20 mg daily. This study aims to investigate whether vonoprazan could relieve the symptoms of Chinese patients with non-erosive reflux disease (NERD) and whether increased dosage or different times of dosing could increase the response rate of GERD.

This study is a pragmatic, open-label, crossover-cluster, randomized controlled trial with patient preference arms. Two thousand eight hundred eighty patients with GERD from 48 hospitals in China will be enrolled. These hospitals will be divided into a compulsory randomization cluster (24 hospitals) and a patient preference cluster (24 hospitals). Patients in the compulsory randomization cluster will be randomized to three regimens according to the crossover-cluster randomization. Patients in the patient preference cluster may choose to receive any regimen if they have a preference; otherwise, patients will be randomly assigned. The three treatment regimens will last 4 weeks, including (1) vonoprazan 20 mg p.o. after breakfast, (2) vonoprazan 20 mg p.o. after dinner, and (3) vonoprazan 20 mg p.o. after breakfast and after dinner. Patients will attend a baseline visit, a 4-week e-diary, a fourth-week visit, and a sixth-month visit online. The primary outcome is the symptom relief rate of all patients after 4-week therapy. Secondary outcomes include the healing rate of EE patients, the severity of symptoms, compliance with the therapy at the fourth-week follow-up visit, recurrent symptoms, and the frequency of self-conscious doctor visits at the sixth-month follow-up visit.

This trial will explore the effectiveness of different regimens of vonoprazan that will be implemented with GERD patients in China. The randomization with patient preferences considered and the crossover-cluster component may improve the robustness and extrapolation of study conclusions.

https://www.chictr.org.cn ChiCTR2300069857. Registered on 28 March 2023.

February 18, 2023, Version 2.

Non-erosive reflux disease (NERD) symptoms are often episodic, making on-demand treatment an attractive treatment approach.

We compared the efficacy and safety of on-demand vonoprazan versus placebo in patients with NERD.

Patients with NERD, defined as heartburn for ≥6 months and for ≥4/7 consecutive days with normal endoscopy, received once-daily vonoprazan 20 mg during a 4-week run-in period. Patients without heartburn during the last 7 days and with ≥80% study drug and diary compliance were randomised 1:1:1:1 to vonoprazan 10, 20, 40 mg or placebo on-demand for 6 weeks. The primary endpoint was the percentage of evaluable heartburn episodes completely relieved within 3 h of on-demand dosing and sustained for 24 h.

Of 458 patients in the run-in period, 207 entered the on-demand period. In the vonoprazan 10 mg group, 56.0% (201/359) of evaluable heartburn episodes met the criteria for complete and sustained relief; 60.6% (198/327) in the 20 mg group; and 70.0% (226/323) in the 40 mg group, compared with 27.3% (101/370) in the placebo group (p < 0.0001 versus placebo for each vonoprazan group). By 1 h post-dose, vonoprazan was associated with complete relief of significantly more heartburn episodes compared with placebo. No serious treatment-emergent adverse events were reported.

On-demand vonoprazan may be a potential alternative to continued daily acid suppression therapy for the relief of episodic heartburn in patients with NERD.

gov: NCT04799158.

Proton-pump inhibitors (PPIs) are the mainstay of treatment in erosive esophagitis (EE). An alternative to PPIs in EE is Vonoprazan, a potassium competitive acid blocker. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing vonoprazan to lansoprazole.

Multiple databases searched through November 2022. Meta-analysis was performed to assess endoscopic healing at two, four and eight weeks, including for patients with severe EE (Los Angeles C/D). Serious adverse events (SAE) leading to drug discontinuation were assessed. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology.

Four RCTs with 2208 patients were included in the final analysis. Vonoprazan 20 mg once-daily was compared to lansoprazole 30 mg once-daily dosing. Among all patients, at two and eight weeks post-treatment, vonoprazan resulted in significantly higher rates of endoscopic healing as compared to lansoprazole, risk ratios (RR) 1.1, p<0.001 and RR 1.04, p=0.03. The same effect was not observed at four weeks, RR 1.03 (CI 0.99-1.06, I2=0%) following therapy. Among patients with severe EE, vonoprazan resulted in higher rates of endoscopic healing at two weeks, RR 1.3 (1.2-1.4, I2=47%), p=<0.001, at four weeks, RR 1.2 (1.1-1.3, I2=36%), p=<0.001 and at eight weeks post-treatment, RR 1.1 (CI 1.03-1.3, I2=79%), p=0.009. We found no significant difference in the overall pooled rate of SAE and pooled rate of adverse events leading to drug discontinuation. Finally, the overall certainty of evidence for our main summary estimates was rated as high (grade A).

Based on limited number of published non-inferiority RCTs, our analysis demonstrates that among patients with EE, vonoprazan 20 mg once-daily dosing achieves comparable and in those with severe EE, higher endoscopic healing rates as compared to lansoprazole 30 mg once-daily dosing. Both drugs have a comparable safety profile.

Aim: 20 mg of vonoprazan (VPZ20) is recommended in most countries to treat erosive esophagitis (EE). Whether other doses of vonoprazan, such as 5 mg (VPZ5), 10 mg (VPZ10), 20 mg (VPZ20), and 40 mg (VPZ40) are more effective is unknown. Materials & methods: Three databases were electronically searched to identify studies published before November 2021. Network meta-analysis was performed using STATA 14.0. Results: VPZ20 and VPZ40 were comparable to PPI, VPZ5 and VPZ10 in 4- and 8-week healing rates, and this was also detected in patients with refractory EE. All regimens resulted in similar treatment-emergent adverse events (TEAEs). However, VPZ40 ranked first for healing rate and TEAEs; however, VPZ20 ranked worst for TEAEs. Conclusion: Different doses of VPZ are comparable in efficacy and safety, but VPZ40 may be best in both effectiveness and safety.

VISION is a randomised, phase 4, open-label, parallel-group, multicentre study conducted in 33 centres in Japan. The aim of this study was to assess the long-term safety of vonoprazan for maintenance treatment of healed erosive oesophagitis versus lansoprazole.

Patients with endoscopically diagnosed erosive oesophagitis were randomised 2:1 to once-daily vonoprazan 20 mg or lansoprazole 30 mg, for a 4- to 8-week healing phase. Patients with endoscopically confirmed healing entered a 260-week maintenance phase with a once-daily starting dose of vonoprazan 10 mg or lansoprazole 15 mg. Primary endpoint was change in gastric mucosal histopathology.

Of 208 patients (vonoprazan, n = 139; lansoprazole, n = 69) entering the healing phase, 202 entered the maintenance phase (vonoprazan, n = 135; lansoprazole, n = 67). At 3 years, 109 vonoprazan-treated and 58 lansoprazole-treated patients remained on treatment. Histopathological evaluation of gastric mucosa showed that hyperplasia of parietal, foveolar and G cells was more common with vonoprazan than lansoprazole at week 156 of the maintenance phase. There was no marked increase in the occurrence of parietal, foveolar and G cell hyperplasia among patients in the vonoprazan group from week 48 to week 156. Histopathological evaluation of the gastric mucosa also showed no neoplastic changes in either group. No new safety issues were identified.

In this interim analysis of VISION, no new safety concerns were identified in Japanese patients with healed erosive oesophagitis receiving vonoprazan or lansoprazole as maintenance treatment for 3 years. (CT.gov identifier: NCT02679508; JapicCTI-163153; Japan Registry of Clinical Trials: jRCTs031180040).

Vonoprazan, a novel acid-suppressive drug, is non-inferior to proton pump inhibitors (PPIs) for the management of gastric acid-related diseases. However, the safety of vonoprazan has not been systematically evaluated yet.

To elucidate the incidence and type of adverse events (AEs) in patients taking vonoprazan.

Systematic review and meta-analysis.

PubMed, EMBASE, and Cochrane Library databases were searched for all studies reporting the safety of vonoprazan. The incidences of any AEs, drug-related AEs, serious AEs, AEs leading to drug discontinuation, and common AEs were pooled. Odds ratios (ORs) were calculated to compare the incidence of AEs between patients taking vonoprazan and PPIs.

Seventy-seven studies were included. The pooled incidences of any AEs, drug-related AEs, serious AEs, and AEs leading to drug discontinuation were 20, 7, 1, and 1%, respectively. The incidences of any AEs (OR = 0.96, p = 0.66), drug-related AEs (OR = 1.10, p = 0.44), serious AEs (OR = 1.14, p = 0.36), and AEs leading to drug discontinuation (OR = 1.09, p = 0.55) were not significantly different between patients taking vonoprazan and PPIs. In subgroup analyses, patients with peptic ulcer disease (PUD) had higher incidences of any AEs, serious AEs, and AEs leading to drug discontinuation than those with gastroesophageal reflux disease (GERD), Helicobacter pylori (H. pylori) infection, and artificial ulcer after gastric endoscopic submucosal dissection (ESD), but patients with H. pylori infection had a higher incidence of drug-related AEs than those with PUD, GERD, and artificial ulcer after gastric ESD. The incidence of AEs was higher in patients taking long-term use of vonoprazan than those taking short-term use of vonoprazan.

Vonoprazan is well tolerated and shows similar safety compared to PPIs. The safety of vonoprazan may be primarily influenced by its indications and duration.

PROSPERO CRD42022314982.

The use of proton pump inhibitors (PPIs) has been repeatedly reported as a trigger of Clostridioides difficile infection (CDI), a leading cause of nosocomial diarrhea. However, only a few studies have reported on the association between vonoprazan, a novel potassium-competitive acid blocker providing potent acid suppression, and CDI, with no studies having been conducted in a clinical setting. We therefore evaluated the association between various classes of acid suppressants and CDI with special attention paid to differences in the magnitudes of association between PPIs and vonoprazan.

A retrospective hospital-based cohort from a secondary-care hospital in Japan (n = 25 821) was collected, wherein eligible CDI cases were defined as hospital-onset cases (n = 91). A multivariable adjusted logistic regression analysis for the entire cohort and propensity analyses for subgroups consisting of PPI and/or vonoprazan users at various doses (n = 10 306) were performed.

The overall CDI incidence rate was 1.42/10 000 patient-days, which was comparable with previous reports. A multivariable analysis showed that both PPIs and vonoprazan were positively associated with CDI (odds ratios [95% confidence intervals]: 3.15 [1.67-5.96] and 2.63 [1.01-6.88], respectively). In addition, matched subgroup analyses showed that PPIs and vonoprazan had equivalent magnitudes of association with CDI.