vonoprazan and Gastroesophageal-Reflux

This systematic review and network meta-analysis aimed to assess the relative efficacy of vonoprazan and proton pump inhibitors (PPIs) on early heartburn symptom resolution in patients with erosive esophagitis.. Limited available data directly compare the efficacy of vonoprazan, a first-in-class potassium-competitive acid blocker, with PPIs in erosive esophagitis.. We conducted a systematic literature review (in MEDLINE and CENTRAL) and subsequent network meta-analysis according to Cochrane and PRISMA guidelines. Double-blind, randomized controlled trials in adults with erosive esophagitis treated with vonoprazan or a PPI were included in the analysis. Primary outcomes were heartburn symptom resolution rate on Day 1 and Day 7. The study was performed with all available data, using a random effects model within a Bayesian framework.. Overall, 10 randomized controlled trials were included in the network meta-analysis. For heartburn resolution rate on Day 1 (9 of 10 trials), vonoprazan 20 mg once daily (QD) was superior to placebo (median odds ratio=16.75, 95% credible interval: 2.16-207.80). Point estimates numerically favored vonoprazan 20 mg QD over other comparators. For heartburn resolution rate on Day 7 (10 of 10 trials), vonoprazan 20 mg QD was superior to placebo and other comparators except rabeprazole 20 mg QD. Point estimates numerically favored vonoprazan 20 mg QD over rabeprazole 20 mg QD.. In this study, vonoprazan 20 mg QD was equally effective in heartburn resolution on Day 1, and equally or more effective on Day 7 versus PPIs in adults with erosive esophagitis.

Topics: Adult; Bayes Theorem; Esophagitis; Gastroesophageal Reflux; Heartburn; Humans; Network Meta-Analysis; Proton Pump Inhibitors; Pyrroles; Rabeprazole; Randomized Controlled Trials as Topic; Sulfonamides; Treatment Outcome

Gastroesophageal reflux disease (GERD) is a common disorder, and is typically treated with proton-pump inhibitors (PPIs) as the recommended first-line therapy. Recently, a new potassium-competitive acid blocker, vonoprazan, was launched in Japan. It is uncertain whether the standard dose of vonoprazan 20 mg is superior to that of PPIs for GERD, so a direct comparison of the therapeutic effects and adverse events between vonoprazan 20 mg and PPIs is needed.. MEDLINE, the Cochrane Central Register of Controlled Trials, and Embase were chosen as the literature sources. Randomized controlled trials for vonoprazan 20 mg and PPIs published in English were searched. Data from studies meeting the eligibility criteria were extracted individually by two researchers and compared to maintain consistency.. Fifty-six articles were identified in the databases, and one study was manually searched and added to the analysis, ultimately yielding six eligible studies. For the main analysis, the risk ratios (RR) of efficacy and adverse events between vonoprazan and PPIs were 1.06 (0.99-1.13) and 1.08 (0.96-1.22), respectively. Subgroup analysis for patients with severe esophagitis at baseline showed significantly higher results for vonoprazan than lansoprazole, with an RR of 1.14 (1.06-1.22).. Our findings suggest that vonoprazan is non-inferior to PPIs as therapy for patients with GERD. Subgroup analysis indicates that vonoprazan is more effective than PPIs for patients with severe erosive esophagitis. The safety outcomes for vonoprazan are similar to those for PPIs.

Topics: Gastroesophageal Reflux; Heartburn; Humans; Proton Pump Inhibitors; Pyrroles; Randomized Controlled Trials as Topic; Sulfonamides; Treatment Outcome

The introduction of acid inhibition in clinical practice has revolutionized the management of acid-related diseases, leading to the virtual abolition of elective surgery for ulcer disease and relegating antireflux surgery to patients with gastroesophageal reflux disease (GERD) not adequately managed by medical therapy. Proton pump inhibitors (PPIs) are the antisecretory drugs of choice for the treatment of reflux disease. However, these drugs still leave some unmet clinical needs in GERD. PPI-refractoriness is common, and persistent symptoms are observed in up to 40-55% of daily PPI users. Potassium-competitive acid blockers (P-CABs) clearly overcome many of the drawbacks and limitations of PPIs, achieving rapid, potent, and prolonged acid suppression, offering the opportunity to address many of the unmet needs. In recent years, it has been increasingly recognized that impaired mucosal integrity is involved in the pathogenesis of GERD. As a consequence, esophageal mucosal protection has emerged as a new, promising therapeutic avenue. When P-CABS are used as add-on medications to standard treatment, a growing body of evidence suggests a significant additional benefit, especially in the relief of symptoms not responding to PPI therapy. On the contrary, reflux inhibitors are considered a promise unfulfilled, and prokinetic agents should only be used on a case-by-case basis.

Topics: Cimetidine; Esomeprazole; Esophageal Mucosa; Gastroesophageal Reflux; Humans; Lansoprazole; Omeprazole; Proton Pump Inhibitors; Pyrroles; Sulfonamides

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, a new potassium-competitive acid blocker, vonoprazan, was launched in Japan. We aimed to evaluate the comparative efficacy of vonoprazan and other PPIs in healing GERD.. We used MEDLINE and the Cochrane Central Register of Controlled Trials to search the literature. Double-blind randomized controlled trials for PPIs and/or vonoprazan that were published in English or Japanese and assessed healing effects in adult GERD patients were included. To estimate the comparative efficacy of treatments, we performed a Bayesian network meta-analysis to assess the consistency assumption.. Of 4001 articles identified in the database, 42 studies were eligible. One study was hand-searched and added to the analysis. For the main analysis of healing effects at 8 weeks, odds ratios (ORs) of vonoprazan (20 mg daily) to esomeprazole (20 mg), rabeprazole (20 mg), lansoprazole (30 mg), and omeprazole (20 mg) were 2.29 (95% credible interval, 0.79-7.06), 3.94 (1.15-14.03), 2.40 (0.90-6.77), and 2.71 (0.98-7.90), respectively. Subgroup analysis for patients with severe esophagitis at baseline showed significantly higher ORs for vonoprazan versus most of the comparator PPIs.. This analysis shows that the GERD healing effect of vonoprazan is higher than that of rabeprazole (20 mg) but not higher than other PPIs. Subgroup analysis indicated that vonoprazan is more effective than most PPIs for patients with severe erosive esophagitis.

Topics: Bayes Theorem; Esophagitis, Peptic; Gastroesophageal Reflux; Humans; Network Meta-Analysis; Patient Selection; Proton Pump Inhibitors; Pyrroles; Randomized Controlled Trials as Topic; Remission Induction; Severity of Illness Index; Sulfonamides; Time Factors; Treatment Outcome; Wound Healing

Long-term maintenance treatment of gastroesophageal reflux disease (GERD) is important to prevent relapse. Proton-pump inhibitors (PPIs) are used for both treatment and maintenance therapy of GERD. Recently, a potassium-competitive acid blocker vonoprazan was launched in Japan. We evaluated the comparative efficacy of vonoprazan and other PPIs for GERD maintenance.. A systematic literature search was performed using MEDLINE and Cochrane Central Register of Controlled Trials. Double-blind randomized controlled trials (RCTs) of PPIs, vonoprazan, and placebo for GERD maintenance published in English or Japanese were selected. Among them, studies conducted at the recommended dose and for the recommended use, and containing information on maintenance rate based on endoscopic assessment, were included. The comparative efficacies of treatments were estimated by performing a Bayesian network meta-analysis, which assessed the consistency assumption. Outcomes were number or rate of patients who maintained remission.. Of 4001 articles identified, 22 RCTs were eligible for analysis. One study published as an abstract was hand-searched and added. The consistency hypothesis was not rejected for the analysis. The odds ratio of vonoprazan 10 mg to each PPI was 13.92 (95% credible interval [CI] 1.70-114.21) to esomeprazole 10 mg; 5.75 (95% CI 0.59-51.57) to rabeprazole 10 mg; 3.74 (95% CI 0.70-19.99) to lansoprazole 15 mg; and 9.23 (95% CI 1.17-68.72) to omeprazole 10 mg.. The efficacy of vonoprazan in GERD maintenance treatment may be higher than that of some PPIs. However, a direct comparison of vonoprazan and PPIs is required to confirm these effects.

Topics: Gastroesophageal Reflux; Humans; Proton Pump Inhibitors; Pyrroles; Randomized Controlled Trials as Topic; Sulfonamides

Vonoprazan, a novel potassium-competitive acid blocking agent, is used in the management of gastroesophageal reflux disease (GERD). We aim to perform a systematic review and meta-analysis for the comparison of the effects of vonoprazan and proton pump inhibitors (PPIs) in GERD in randomized controlled trials (RCTs).. A systematic and comprehensive search will be performed using MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), Google Scholar, and clinical trial registries, for studies published up to September 2018. Only randomized clinical trials will be included. Primary outcomes of symptoms and esophageal erosion improvement in the intention-to-treat analysis, and secondary outcomes of symptoms and esophageal erosion improvement rate in the per protocol analysis, the comparative efficacy in terms of healing rate of esophageal erosion on endoscopy, the comparative efficacy in terms of improvement of esophageal impedance-pH study, adverse events, long-term safety, and the comparative efficacy in terms of CYP2C19 metabolite levels will be studied. The quality of included studies will be assessed using the modified risk of bias tool. Heterogeneity of estimates across studies as well as publication bias will be assessed. This systematic review and meta-analysis will be performed according to the protocol recommended by the Cochrane Collaboration and reported according to the preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines. All statistical analyses will be conducted using Stata SE version 15.0.. The results of this systematic review and meta-analysis will be published in a peer-reviewed journal.. To our knowledge, this systematic review and meta-analysis will be the first to evaluate existing research comparing Vonoprazan and PPIs in GERD. Our study will provide information about the effect of vonoprazan and PPIs in GERD in RCTs. The review will benefit patients, healthcare providers, and policymakers.

Topics: Cytochrome P-450 CYP2C19; Esophagus; Gastroesophageal Reflux; Humans; Proton Pump Inhibitors; Pyrroles; Randomized Controlled Trials as Topic; Sulfonamides; Systematic Reviews as Topic

Proton pump inhibitors (PPIs) display a number of limitations and unmet clinical needs that have prompted the development of novel drugs to improve the outcomes of acid-related diseases, including the eradication of H. pylori. In this context, a new synthesized potassium-competitive acid blocker (P-CAB), vonoprazan, showed higher suppression of gastric acid secretion. Areas covered: This review discusses the current knowledge regarding the efficacy of vonoprazan in the treatment of acid-related diseases, with a particular focus on its use in Helicobacter pylori eradication. Expert opinion: Vonoprazan showed some advantages over PPIs in terms of the pharmacokinetic and pharmacodynamic profile: fast onset of action without requiring acid activation and specific administration timing, more potent and prolonged inhibition of acid secretion, including a better nighttime acid control, and a less antisecretory variability. Recent evidence suggests that vonoprazan can be preferred to PPIs as maintenance therapy for reflux esophagitis and eradication of Helicobacter pylori owing to its stronger antisecretory effect. Moreover, vonoprazan displays favorable safety and tolerability profiles, even though long-term studies on the effects of vonoprazan are required.

Topics: Gastroesophageal Reflux; Helicobacter Infections; Helicobacter pylori; Humans; Proton Pump Inhibitors; Pyrroles; Sulfonamides; Treatment Outcome

This article aims to detail the major innovations occurred in Gastro-enterology in 2016, including the introduction of a new molecule, the vonoprazan, for the treatment of refractory gastroesophagal reflux disease (GERD) and a new way of eradication of H. pylori. The possibility to use an intermittent dose of PPI rather than continuously in severe gastric and duodenal ulcers after successful endoscopic hemostasis is also discussed as well as the withdrawal of corticosteroids in the treatment of autoimmune pancreatitis. The formulation of corticosteroids in the treatment of eosinophilic esophagitis, the interest of the chromo-endoscopy during colonoscopy highlighting small polyps (from 1 to 5 mm = « diminutive polyps ») and the introduction on the Swiss market for biosimilars in the treatment of inflammatory bowel disease (IBD) are also discussed.. Cet article a pour but de détailler les nouveautés majeures survenues en gastroentérologie pour 2016, notamment avec l’introduction d’une nouvelle molécule, le vonoprazan, destiné à la prise en charge du reflux gastro-œsophagien (RGO) réfractaire et des nouvelles modalités d’éradication d’

Topics: Biosimilar Pharmaceuticals; Disease Eradication; Drug Resistance, Bacterial; Duodenal Ulcer; Gastroenterology; Gastroesophageal Reflux; Helicobacter Infections; Helicobacter pylori; Humans; Pyrroles; Sulfonamides

Patients who continue to experience heartburn symptoms despite adequate-dose proton pump inhibitor therapy have unmet clinical needs. In this review, we focus on the most recent findings related to the mechanism of heartburn symptom generation, and on the treatment of gastroesophageal reflux disease-related and functional heartburn.. The immunological mechanism in the esophageal mucosa has been addressed as a potential mechanism of the onset of esophageal mucosa damage and the generation of heartburn symptoms. Peripheral or central hypersensitivity in viscera is a potentially unifying pathophysiological concept in functional heartburn. Vonoprazan, a novel and potent first-in-class potassium-competitive acid blocker, is expected to prove useful in the treatment of reflux disease.. New findings in the mechanisms of heartburn symptom generation are emerging, including the immunological mediation of esophageal mucosal damage and the development of visceral hypersensitivity in functional heartburn. In the future, we anticipate the emergence of new and specific therapeutic options based on these mechanisms, with less dependence on acid-suppressing agents.

Topics: Esophageal pH Monitoring; Esophagus; Gastric Acidity Determination; Gastroesophageal Reflux; Heartburn; Humans; Mucous Membrane; Proton Pump Inhibitors; Pyrroles; Sulfonamides; Treatment Outcome

Proton-pump inhibitors (PPIs) are cornerstone treatments for gastro-esophageal reflux disease (GERD); however, evidence suggests that most patients exhibit partial response to PPIs, suggesting the need for novel therapies that can provide an improved and sustained increase in gastric pH.. This study aimed to determine the effect of vonoprazan, a novel, orally active small-molecule potassium-competitive acid blocker, versus esomeprazole, a PPI, in preventing heartburn symptoms over a 4-week treatment period in patients with GERD and a partial response to esomeprazole treatment.. This randomized, double-blind, proof-of-concept, phase 2 clinical trial was conducted between 2016 and 2018 at 39 sites across Europe and designed to evaluate the efficacy and safety of vonoprazan 20 mg once daily (q.d.) and 40 mg q.d. versus esomeprazole 40 mg q.d. after 1:1:1 randomization of symptomatic patients with GERD and a partial response to a healing dose of esomeprazole.. No statistically significant difference in efficacy and safety was observed among treatment groups, and vonoprazan was well tolerated. The trial is registered with the National Board of Health (EudraCT: 2015-001154-14) database.

Topics: Double-Blind Method; Esomeprazole; Female; Gastroesophageal Reflux; Heartburn; Humans; Middle Aged; Proton Pump Inhibitors; Treatment Outcome

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.

Topics: Gastroesophageal Reflux; Heartburn; Humans; Proton Pump Inhibitors; Pyrroles; Sulfonamides; Treatment Outcome

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.

Topics: Gastroesophageal Reflux; Humans; Patient Preference; Proton Pump Inhibitors; Pyrroles; Randomized Controlled Trials as Topic; Treatment Outcome

Vonoprazan is a potassium competitive acid blocker used to treat erosive gastroesophageal reflux disease (GERD) with stronger, more stable acid-suppressing effects than proton pump inhibitors (PPIs). This study clarified the usefulness and superiority of vonoprazan administered every second day over PPIs in the maintenance therapy of erosive GERD.. This is a prospective, multicenter, open-label, two-period randomized cross-over study. Patients were randomized to either the vonoprazan-lansoprazole (VP-LZ) group, who were given vonoprazan 10 mg for the first 4 weeks and then lansoprazole 15 mg for the next 4 weeks both administered once every second day, or the lansoprazole-vonoprazan (LZ-VP) group, who were treated in reverse. GERD symptoms were compared using symptom diaries, the frequency scale for symptoms of GERD (FSSG), and the gastrointestinal symptom rating scale (GSRS).. We enrolled 122 patients between December 2017 and May 2019. Symptoms were well controlled in vonoprazan administration and lansoprazole administration were 93.6% and 82.1%, respectively, with a significant difference on McNemar's test (P = 0.003). During the second 4 weeks, 94.4% and 76.7% of patients in the VP-LZ and LZ-VP groups, respectively, were well controlled following for ≥ 6 consecutive days a week (P = 0.009). During the first 4 weeks, 96.7% and 80.0% of patients were well controlled with < 1 weekly in the VP-LZ and LZ-VP groups, respectively, during the first 4 weeks (P = 0.007). GERD symptoms, assessed via FSSG and GSRS, significantly decreased with vonoprazan administration once every second day.. Vonoprazan administered once every second day could be an effective alternative to PPIs in the maintenance treatment of erosive GERD (UMIN000030393).

Topics: Cross-Over Studies; Gastroesophageal Reflux; Humans; Prospective Studies; Proton Pump Inhibitors; Pyrroles; Sulfonamides; Treatment Outcome

To assess the efficacy and safety of vonoprazan on heartburn symptoms in patients with nonerosive reflux disease (NERD) (ClinicalTrials.gov: NCT02954848).. This phase 3, double-blind, placebo-controlled study included Japanese patients aged 20 years and older with grade N/M NERD and recurrent heartburn. Patients received placebo (n = 245) or vonoprazan 10 mg (n = 238) for 4 weeks. The primary efficacy outcome was frequency of heartburn experienced by patients during the treatment period (proportion of days without heartburn). Other outcomes included cumulative improvement rates of heartburn, proportion of patients with complete heartburn resolution in the fourth week of treatment, and safety.. Compared with placebo, the proportion of days without heartburn was not significantly higher in the vonoprazan group in the full analysis (primary end point, 72.55% vs 61.50%, vonoprazan vs placebo, P = 0.0643) but was significantly higher in the per-protocol-set sensitivity analysis (P = 0.0341). Early onset of response and significantly greater cumulative improvement rates of heartburn were observed in the vonoprazan group (P = 0.0003). In a post hoc analysis, a greater proportion of patients with complete heartburn resolution in the fourth week of treatment were reported in the vonoprazan group (P = 0.0023). Incidence of treatment-emergent adverse events was similar between treatment groups (23.5% vs 23.3%); most treatment-emergent adverse events were mild in severity.. Although vonoprazan 10 mg was not superior to placebo with respect to proportion of days without heartburn in Japanese patients with NERD, vonoprazan had a significantly higher cumulative rate of heartburn resolution and was well tolerated.

Topics: Dose-Response Relationship, Drug; Double-Blind Method; Endoscopy, Gastrointestinal; Female; Gastroesophageal Reflux; Heartburn; Humans; Male; Middle Aged; Pyrroles; Sulfonamides; Treatment Outcome

Proton pump inhibitors and vonoprazan (a potassium-competitive acid blocker) are recommended as first-line treatments for gastroesophageal reflux disease (GERD). However, few reports have investigated the onset of action of these agents for GERD symptom relief. The present study compared the symptom relief of esomeprazole with that of vonoprazan via monitoring self-reported GERD symptoms after treatment initiation.. This was a prospective, multicenter, randomized, open-label, parallel group, comparative clinical study between esomeprazole (20 mg/day) and vonoprazan (20 mg/day) administered for 4 weeks to patients with GERD symptoms. Patients who had scores ≥ 8 on the Gastroesophageal Reflux Disease Questionnaire (GerdQ) were defined as having GERD and enrolled in this study. Sixty patients were randomly assigned to either the esomeprazole group (n = 30) or the vonoprazan group (n = 30). Treatment response rates in each drug group were evaluated according to the GerdQ. The Frequency Scale for the Symptoms of GERD (FSSG) scores from the 1st day after treatment initiation and the Global Overall Symptom (GOS) scale scores during treatment were also evaluated.. At 4 weeks, the treatment response rates for symptom relief according to the GerdQ were 88.0% in the esomeprazole group and 81.8% in the vonoprazan group. The GOS scales, which reflect the impact of GERD symptoms, were similar for both groups. The FSSG scores decreased from the 1st to the 14th day in both groups.. There were no substantial differences in the symptom relief between the two groups at any time point in this short-term study.

Topics: Adult; Aged; Esomeprazole; Female; Gastroesophageal Reflux; Humans; Japan; Male; Middle Aged; Prospective Studies; Proton Pump Inhibitors; Pyrroles; Remission Induction; Self Report; Sulfonamides; Time Factors; Treatment Outcome

Proton pump inhibitors (PPIs) are widely used to treat gastro-oesophageal reflux disease (GORD). However, the onset of action is considered slow and PPIs cannot completely block acid secretion at night. A new potassium-competitive acid blocker (P-CAB) can rapidly block acid secretion. However, whether this P-CAB can relieve GORD symptoms quickly and adequately soon after starting treatment is unknown.. To determine how rapidly vonoprazan and lansoprazole provide heartburn relief.. Patients (n = 32) with endoscopically confirmed erosive oesophagitis who experienced heartburn at least once a week were randomised in a double-blind manner to receive either daily vonoprazan (20 mg) or lansoprazole (30 mg) before breakfast for 14 days. Day time and night time heartburn were assessed daily throughout the study using a five-point Likert scale. The primary endpoint was the first day of complete day and night heartburn relief for at least seven consecutive days. The ethics committees of the participating institutions approved the study protocol.. Heartburn was relieved sooner with vonoprazan than with lansoprazole (P < 0.05, log-rank test). Heartburn was completely relieved in 31.3% and 12.5% of patients on day 1 with vonoprazan and lansoprazole, respectively. Significantly more patients achieved complete nocturnal heartburn relief with vonoprazan than lansoprazole (P < 0.01). Both regimens were well tolerated.. Complete sustained heartburn relief was achieved sooner with vonoprazan than with lansoprazole during the first week of therapy. (UMIN000018776).

Topics: Adult; Aged; Double-Blind Method; Esophagitis; Female; Gastroesophageal Reflux; Heartburn; Humans; Lansoprazole; Male; Middle Aged; Proton Pump Inhibitors; Pyrroles; Sulfonamides

Vonoprazan, a novel potassium-competitive acid blocker, elicits potent acid inhibition and hypergastrinemia at a dose of 20 mg. Its recommended maintenance dose for gastro-esophageal reflux disease is 10 mg, which is sometimes insufficient for preventing nocturnal acid breakthrough (NAB). Concomitant use of a histamine 2 receptor antagonist (H. The aim of this study is to compare the levels of acid inhibition and serum gastrin attained by addition of lafutidine to vonoprazan 10 mg with levels after a dose increase of vonoprazan from 10 to 20 mg.. Thirteen healthy volunteers underwent 24-h intragastric pH monitoring and serum gastrin measurements on day 7 of three different regimens: vonoprazan 10 mg, vonoprazan 10 mg plus lafutidine 10 mg, and vonoprazan 20 mg.. Median pH 4 holding time ratios (range) by vonoprazan 10 mg, vonoprazan 10 mg plus lafutidine 10 mg, and vonoprazan 20 mg were 82% (47-88%), 88% (76-93%), and 99% (95-100%) while those at nighttime from 10 p.m. to 8 a.m. were 94% (29-100%), 100% (95-100%), and 100%, respectively. The incidences of NAB with vonoprazan 10 mg, vonoprazan plus lafutidine, and vonoprazan 20 mg were 38, 8, and 0%, respectively. Respective serum gastrin levels were 420 (173-508), 323 (196-521), and 504 (400-812) pg/ml.. Addition of lafutidine 10 mg to vonoprazan 10 mg achieved sufficient acid inhibition, especially at nighttime, without further increase of serum gastrin levels.

Topics: Acetamides; Adolescent; Adult; Cross-Over Studies; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Gastric Acid; Gastric Acidity Determination; Gastrins; Gastroesophageal Reflux; Healthy Volunteers; Histamine H2 Antagonists; Humans; Hydrogen-Ion Concentration; Male; Piperidines; Proton Pump Inhibitors; Pyridines; Pyrroles; Sulfonamides; Young Adult

To compare vonoprazan 10 and 20 mg. Rates of EE recurrence during the 24-wk maintenance period were 16.8%, 5.1%, and 2.0% with lansoprazole 15 mg, vonoprazan 10 mg, and vonoprazan 20 mg, respectively. Vonoprazan was shown to be non-inferior to lansoprazole 15 mg (. Our findings confirm the non-inferiority of vonoprazan 10 and 20 mg to lansoprazole 15 mg as maintenance therapy for patients with healed EE.

Topics: Adult; Aged; Biopsy; Double-Blind Method; Esophagitis, Peptic; Esophagoscopy; Esophagus; Female; Gastric Mucosa; Gastroesophageal Reflux; Heartburn; Humans; Incidence; Lansoprazole; Male; Middle Aged; Proton Pump Inhibitors; Pyrroles; Recurrence; Sulfonamides; Treatment Outcome

Approximately 20-40% of patients with gastroesophageal reflux disease (GERD) are refractory to proton pump inhibitor (PPI) treatment. The acid-inhibitory effect of vonoprazan, a novel potassium-competitive acid blocker (P-CAB), is significantly greater when compared to the effect of PPIs. We investigated the efficacy of vonoprazan treatment for PPI-refractory GERD and factors associated with P-CAB non-response.. We enrolled 277 GERD patients receiving continuous PPI therapy. Subjects completed a self-report questionnaire including the frequency scale for the symptoms of GERD (FSSG). Patients with PPI-refractory GERD received 20 mg of vonoprazan once daily for 8 weeks. After that, subjects completed the same questionnaire, and the results were used to identify P-CAB responders and non-responders.. Twenty-eight patients were identified as P-CAB responders and 26 were non-responders. Vonoprazan treatment significantly decreased scores of FSSG, nighttime symptom, and Athens Insomnia Scale. Multivariate analysis demonstrated co-existing functional dyspepsia (FD; OR 4.94) and the presence of sleep disturbances (OR 4.34) was associated with P-CAB non-response, whereas alcohol consumption was inversely associated.. Vonoprazan treatment might be appropriate as a promising new strategy for PPI-refractory GERD. Co-existing FD, sleep disturbances, and alcohol abstinence were significantly associated with P-CAB non-response. Other therapeutic options should be considered in patients with these factors.

Topics: Aged; Aged, 80 and over; Female; Gastroesophageal Reflux; Humans; Male; Middle Aged; Proton Pump Inhibitors; Pyrroles; Sleep Wake Disorders; Sulfonamides; Treatment Failure

The effects of vonoprazan, a new potassium-competitive acid blocker, on gastroesophageal reflux disease (GERD) symptom are not fully elucidated. The aim of this study is to determine the effect of vonoprazan on GERD and associated gastrointestinal symptoms. We retrospectively reviewed 88 Helicobacter pylori negative patients with GERD treated with vonoprazan 10 mg daily. Symptoms were evaluated using the Izumo scale, which reflects quality of life related to various abdominal symptoms. The rates of improvement and resolution of GERD symptoms were 86% (76/88) and 57% (50/88), respectively. Improvement and resolution in patients with erosive esophagitis was higher than in those with non-erosive reflux disease (91% vs 83%, p = 0.260 and 71% vs 47%, p = 0.025, respectively). We attempted to identify factors which predict the effects of vonoprazan. Multivariate analysis identified advanced age (≥60-year-old) (odds ratio [OR] 7.281, 95% confidence interval [CI] 2.056-25.776, p = 0.002), obesity (BMI ≥ 24) (OR 3.342, 95%CI 1.124-9.940, p = 0.030) and erosive esophagitis (OR 4.368, 95%CI 1.281-14.895, p = 0.018) as positive predictors of resolution of GERD symptoms. Alcohol use (OR 0.131, 95%CI 0.027-0.632, p = 0.011) and history of H. pylori eradication (OR 0.171, 95%CI 0.041-0.718, p = 0.015) were identified as negative predictors. Vonoprazan also improved epigastric pain (73%), postprandial distress (60%), constipation (58%) and diarrhea (52%) in patients with GERD. In conclusion, vonoprazan 10 mg daily is effective in improving GERD symptoms. Advanced age, obesity, erosive esophagitis, alcohol use and history of H. pylori eradication influence the resolution of GERD symptoms. Treatment with vonoprazan favorably affects gastrointestinal symptoms in patients with GERD.

Topics: Endoscopy; Female; Gastroesophageal Reflux; Humans; Male; Middle Aged; Pyrroles; Sulfonamides

The global prevalence of GERD is substantially increasing each year, and GERD is a chronic disease that reduces the quality of life of patients. The efficacy of conventional drugs is diverse, and most require long-term or lifetime administration; thus, the development of more effective therapeutic agents is needed. Herein, a more effective treatment for GERD was tested. We investigated whether JP-1366 affected gastric H+/K+-ATPase activity and used the Na+/K+-ATPase assay to confirm the selectivity of H+/K+-ATPase inhibition. To clarify the mechanism of enzyme inhibition, JP-1366 and TAK-438 were analyzed by Lineweaver-Burk. Also, we investigated the effects of JP-1366 in various models involving reflux esophagitis. We found that JP-1366 mediates strong, selective, and dose-dependent inhibition of H+/K+-ATPase. We found that JP-1366 significantly suppressed gastric acid secretion in histamine-treated pylorus-ligated rats in a dose-dependent manner. Additionally, we confirmed that JP-1366 inhibited histamine-stimulated gastric acid secretion in the HPD model. JP-1366 exhibited a more than 2-fold higher inhibitory effect on esophageal injury than TAK-438 in GERD lesions and had a more potent inhibitory effect in indomethacin- or aspirin-induced gastric ulcer rat models than TAK-438. Additionally, JP-1366 inhibited gastric ulcers. These results support the possibility that JP-1366 is a good candidate drug for treating acid-related diseases.

Topics: Adenosine Triphosphatases; Animals; Gastric Acid; Gastroesophageal Reflux; Histamine; Potassium; Proton Pump Inhibitors; Quality of Life; Rats

Topics: Gastroesophageal Reflux; Humans; Proton Pump Inhibitors; Pyrroles; Sulfonamides

Topics: Gastroesophageal Reflux; Humans; Proton Pump Inhibitors; Pyrroles; Sulfonamides

Vonoprazan, a potassium-competitive acid blocker, is under investigation in the United States and Europe for the treatment of erosive esophagitis and Helicobacter pylori infection. Population pharmacokinetic (popPK) analysis allows the identification of factors that could affect drug exposure in population subgroups. Here, we report a popPK model based on pooled data sets of available pharmacokinetic (PK) studies in healthy volunteers and patients with gastroesophageal reflux disease, including erosive esophagitis, from Asia and Europe. This model was used to evaluate the impact of different covariates, including race and disease status, on vonoprazan exposure. We analyzed PK data from 746 patients and 410 healthy volunteers from 15 clinical trials using a nonlinear mixed-effects approach to develop the popPK model. Model development focused on characterizing and quantifying the effects of clinical covariates of race (Asian vs non-Asian) and disease status (gastroesophageal reflux disease vs healthy volunteers) on vonoprazan exposure. Identified clinical covariates included fed/fasting status, race, sex, disease status, weight, serum creatinine, and age. The impact of variations in these clinical covariates on exposure to vonoprazan was smaller than the effect of halving or doubling the dose. PK parameters were similar in Asian and non-Asian populations. Variations in weight, age, and race are not predicted to have a clinically relevant impact on vonoprazan exposure or safety and require no changes in vonoprazan dosing. The limited impact of race on exposure suggests that efficacy and safety data for vonoprazan in Asian populations are translatable to non-Asian populations.

Topics: Esophagitis; Gastroesophageal Reflux; Helicobacter Infections; Helicobacter pylori; Humans; Proton Pump Inhibitors; Pyrroles; Sulfonamides

The newly developed vonoprazan (a potassium-competitive acid blocker) has a greater ability to suppress gastric acid production than convention proton pump inhibitors (PPIs). The objective of the present study was to determine how vonoprazan influences the pathogenesis of refractory gastroesophageal reflux disease (GERD) in clinical practice.. Between March 2013 and November 2018, a total of 73 refractory GERD patients (34 in the conventional PPI group versus 39 in the vonoprazan group) were enrolled in this retrospective study. We then compared the underlying disease conditions between the 2 groups, examined by high-resolution manometry and multichannel intraluminal impedance/pH (MII-pH) monitoring.. There was a significant difference in the proportion of underlying disease conditions, including erosive esophagitis, non-erosive reflux disease, reflux hypersensitivity, functional heartburn and oesophageal motility disorder (EMD), between the conventional PPI (6, 14, 23, 40 and 17% respectively) and vonoprazan groups (0, 0, 10, 49, and 41% respectively; p < 0.01). No cases of acid-related GERD were observed in the vonoprazan group. When the EMD patients were excluded, the lower oesophageal acid exposure time of the vonoprazan group (0.1% [0.0-0.5%], n = 23) was significantly lower than that of the conventional PPI group (0.35% [0.1-3.9%], n = 28; p < 0.05), and the gastric pH <4 holding time of the vonoprazan group (7.7% [0.7-34.5%]) was also significantly lower than that of the conventional PPI group (61.6% [49.4-74.3%], p < 0.01).. Vonoprazan serves as a diagnostic tool to exclude acid-related GERD.

Topics: Esophageal pH Monitoring; Gastroesophageal Reflux; Humans; Proton Pump Inhibitors; Pyrroles; Retrospective Studies; Sulfonamides; Treatment Outcome

Weakly acidic reflux has been reported to be the major cause of symptoms in patients with proton pump inhibitor (PPI)-refractory nonerosive reflux disease (NERD) undergoing PPI treatment. We previously reported that reflux at pH 4-5 was the main factor that induced symptoms in such patients. The present study aimed to elucidate the symptom-ameliorating effect of vonoprazan (VPZ) by evaluating the change in the pH value of the refluxate using multichannel intraluminal impedance and pH (MII-pH) monitoring.. We retrospectively evaluated the records of MII-pH monitoring in 29 symptom index (SI) and/or symptom association probability (SAP)-positive patients with PPI-refractory NERD. After switching to VPZ 20 mg/day, we performed MII-pH monitoring again. We assessed the change in the score of the frequency scale for the symptoms of gastroesophageal reflux disease (FSSG), the pH value of the refluxate, and the percent times of intragastric pH <4 or <5 before and after switching. We divided the patients into the following 2 groups according to the FSSG score after switching: effective and noneffective groups.. Among of the 29 SI/SAP-positive patients, 16 underwent switching to VPZ. Furthermore, of these 16 patients, 10 underwent MII-pH monitoring again after switching. The FSSG score decreased, the pH value of the refluxate increased, and the percent times of intragastric pH <4 or <5 reduced after switching when compared with the findings before switching. In the effective group, both the proportion of reflux at pH <4 and that of reflux at pH 4-5 decreased while taking VPZ when compared with the findings while taking double-dose PPI. In the noneffective group, the proportion of reflux at pH <4 decreased but that of reflux at pH 4-5 increased and that of reflux at pH <5 did not change overall while taking VPZ. In addition, the percent times of intragastric pH <5 values were low in the effective group.. Symptom suppression appears to be inadequate in patients with persistent reflux at pH 4-5 even with VPZ 20 mg/day. Strong acid suppressive therapy with VPZ to increase the pH value of the refluxate to ≥5 is useful for symptom improvement.

Topics: Esophageal pH Monitoring; Gastroesophageal Reflux; Humans; Potassium; Proton Pump Inhibitors; Pyrroles; Retrospective Studies; Sulfonamides

Topics: Esophagitis; Gastroesophageal Reflux; Humans; Proton Pump Inhibitors; Pyrroles; Sulfonamides

Behavioral disorders, such as supragastric belching (SGB) and rumination syndrome (RS), which may be treated by cognitive behavioral therapy, are common in patients with reflux symptoms refractory to proton pump inhibitors (PPI). Vonoprazan (VPZ) has been used as a new type of acid inhibitor in Japan since 2015. We herein investigated the prevalence of behavioral disorders in patients with VPZ-refractory reflux symptoms and attempted to identify predictive factors.. We retrospectively analyzed esophagogastroduodenograms, high-resolution manometry, and 24-h multiluminal impedance pH-metry (MIIpH) in patients with VPZ-refractory reflux symptoms (heartburn or regurgitation) receiving 20 mg VPZ who underwent these tests at our hospital between January 2015 and April 2020. Patients were divided as follows: non-erosive reflux disease with pathological esophageal acid exposure (NERD), functional heartburn (FH), reflux hypersensitivity (RH), excessive (> 13 per day) SGB, and possible RS based on MIIpH parameters.. Among 49 patients, 6 (12.2%) had SGB, 4 (8.2%) possible RS, 29 (59.2%) FH, 9 (18.4%) RH, and 1 (2%) NERD. Possible RS patients had more postprandial non-acid reflux events than FH patients (p < 0.05). The multivariate logistic regression analysis did not identify any predictive factors with statistical significance.. More than 20% patients with VPZ-refractory reflux symptoms had behavioral disorders. The use of HRM and MIIpH may be clinically relevant for a better diagnosis and more specific treatment.

Topics: Aged; Female; Gastroesophageal Reflux; Humans; Japan; Logistic Models; Male; Mental Disorders; Middle Aged; Prevalence; Proton Pump Inhibitors; Pyrroles; Retrospective Studies; Sulfonamides

To date, no cases of vonoprazan-associated gastric mucosal redness have been reported, and its endoscopic and pathological features remain largely unclear. We report four cases of vonoprazan-associated gastric mucosal redness. In all cases, esophagogastroduodenoscopy (EGD) demonstrated linear or spotty redness that newly appeared in the greater curvature of the middle gastric body after the initiation of vonoprazan, which disappeared after its discontinuation. A tissue biopsy taken from the gastric mucosa with redness revealed inflammatory cell infiltration, parietal cell protrusions (PCPs), and oxyntic gland dilatation. To our knowledge, this is the first report describing the endoscopic and pathological features of vonoprazan-associated gastric mucosal redness.

Topics: Aged; Aged, 80 and over; Endoscopy, Digestive System; Female; Gastric Mucosa; Gastroesophageal Reflux; Humans; Inflammation; Male; Proton Pump Inhibitors; Pyrroles; Sulfonamides; Treatment Outcome

Proton pump inhibitors (PPIs) have been the first line treatment for gastroesophageal reflux disease (GERD). The aim of this study was to evaluate the efficacy of vonoprazan (VPZ), a potassium-competitive acid blocker for reflux esophagitis (RE), nonerosive reflux disease (NERD), and PPI-resistant GERD patients.An open-label, single-center, observational study in our hospital was performed from August 2016 to August 2017. All patients diagnosed with GERD were asked to self-report a questionnaire of frequency scale for the symptoms of GERD (FSSG) and rate their degree of satisfaction with the treatment of GERD during outpatient visit. A total of 200 (RE 47, NERD 49, PPI-resistant GERD 104) patients were included in the present study. The primary endpoint was the change of FSSG and the proportion of degree of satisfaction with the treatment at the end of the initial therapy. A percentage of improvement (improvement rate) and resolution (resolution rate) at the end of the initial therapy were evaluated. Secondary endpoint included the proportion of patients with symptomatic relapse in the 24-week maintenance phase.FSSG and the degree of satisfaction were significantly improved after the initial therapy in every group. Improvement and resolution rate after the initial therapy were 83.0% and 67.0% in RE, 66.7% and 60.4% in NERD, and 76.0% and 60.4% in PPI-resistant group. There was no significance between after the initial therapy and 24 weeks in improvement and resolution rate. Thirty-two of the total 48 patients did not take VPZ at 24 weeks. Total FSSG score in each group was 1.67 ± 1.97, 2.71 ± 4.91, and 4.0 ± 4.93. The nonrelapse rate at 24 weeks in each group was 66.7%, 60.0%, and 50.0%. The resolution rate at 24 weeks in each group was 38.9%, 45.0%, and 30.0%.The VPZ therapy is effective for initial and maintenance therapy and improves heartburn and patient's satisfaction significantly in all 3 groups. Among patients who stopped taking VPZ during the maintenance period, 42.0% of RE and NERD group and 30% of PPI-resistant group experience complete remission from GERD at 24 weeks by introduction of VPZ.

Topics: Aged; Female; Gastroesophageal Reflux; Humans; Male; Proton Pump Inhibitors; Pyrroles; Severity of Illness Index; Sulfonamides; Surveys and Questionnaires; Treatment Outcome

We evaluated the efficacy of vonoprazan (VPZ), a novel potassium-competitive acid blocker, in patients with proton pump inhibitor (PPI)-refractory gastroesophageal reflux disease (GERD), exhibiting continued pathological esophageal acid exposure (EAE).. Despite ≥8 weeks of appropriate PPI therapy, patients with -persistent reflux symptoms and pathological EAE times (EAETs ≥4%) were invited to switch to VPZ treatment. After an 8-week-course of once-daily VPZ (20 mg), multichannel intraluminal impedance-pH (MII-pH) monitoring was repeated to compare gastric acid exposure times (GAETs), EAETs, and other reflux parameters relative to the baseline values. Before each MII-pH study, reflux symptom severities were scored using the Gastrointestinal Symptom Rating Scale; erosive esophagitis and fasting plasma gastrin levels were also assessed.. From among the 124 patients undergoing MII-pH monitoring, 13 patients (median age, 69 years; females, 64%) were monitored at baseline (while on PPI therapy) and after VPZ therapy. The median GAET associated with VPZ treatment (23.8%) was less than that for PPI treatment (41.1%; p = 0.01), including both daytime and nighttime measurements. VPZ therapy resulted in better median EAET values (4.5%) than did PPI therapy (10.6%) during the 24-h monitoring period (p = 0.055). EAE normalization was achieved in 46% of VPZ-treated patients and was associated with complete gastric acid suppression (p = 0.005). After switching to VPZ, reflux symptoms (p < 0.01) and erosive esophagitis (p = 0.01) improved.. In patients with PPI-refractory GERD, VPZ provides more potent gastric acid suppression, more effective EAE control, enhanced symptom improvement, and better esophagitis healing than PPIs.

Topics: Aged; Aged, 80 and over; Drug Substitution; Esophageal pH Monitoring; Esophagitis, Peptic; Female; Gastroesophageal Reflux; Humans; Male; Middle Aged; Proton Pump Inhibitors; Pyrroles; Retrospective Studies; Sulfonamides; Treatment Outcome

Gastroesophageal reflux disease (GERD) can be treated using a vonoprazan-first strategy (first-line treatment with vonoprazan), or esomeprazole-first/rabeprazole-first strategies (first-line treatment with proton-pump inhibitors [PPIs], esomeprazole/rabeprazole, followed by a switch to vonoprazan). This cost-utility analysis used long-term simulation modeling to evaluate the cost-effectiveness of a vonoprazan-first strategy compared with the esomeprazole-first and rabeprazole-first strategies.. A Markov simulation model was developed to evaluate the cost-effectiveness of vonoprazan-first, esomeprazole-first, and rabeprazole-first strategies, comprising healing and maintenance therapies, over 5 years (4-week cycles). Healing therapy began with the administration of a normal dose of drug per real-world practice. If patients were not healed endoscopically, either a longer duration of healing therapy was provided (vonoprazan), the dose was increased (rabeprazole), or patients were switched to vonoprazan (immediately for esomeprazole, and after dose-escalation for rabeprazole, respectively). Healed patients received maintenance (lower/same dose as healing therapy). Recurrence resulted in re-challenge with healing therapy. Transition probabilities were derived from the results of indirect comparisons (network meta-analysis) and costs calculated from the Japanese payer perspective. Outcomes were defined as quality-adjusted life years (QALYs), with utilities based on published values.. Expected costs of the vonoprazan-, esomeprazole-, and rabeprazole-first strategies were ¥36,194, ¥76,719, and ¥41,105, respectively, over 5 years. QALY gains for vonoprazan-first strategy versus the esomeprazole- and rabeprazole-first strategies were 0.014 and 0.003, respectively. Both estimated incremental cost-effectiveness ratios were dominant and robust to two sensitivity analyses.. Vonoprazan-first strategy increased QALYs and appeared to be cost-effective for GERD patients compared with the esomeprazole- or rabeprazole-first strategies.

Topics: Computer Simulation; Cost-Benefit Analysis; Esomeprazole; Gastroesophageal Reflux; Humans; Japan; Markov Chains; Proton Pump Inhibitors; Pyrroles; Quality-Adjusted Life Years; Rabeprazole; Recurrence; Sulfonamides; Time Factors; Treatment Outcome

Topics: Celiac Disease; Clostridioides difficile; Colorectal Neoplasms; Endoscopy, Digestive System; Enterocolitis, Pseudomembranous; Foodborne Diseases; Gastroesophageal Reflux; Gastrointestinal Diseases; Humans; Pancreatic Intraductal Neoplasms; Pancreatitis; Proton Pump Inhibitors; Pyrimidinones; Pyrroles; Sulfonamides; Tetrahydroisoquinolines

To evaluate the efficacy of on-demand therapy using 20-mg vonoprazan for non-erosive reflux disease.. On-demand therapy by taking one 20-mg tablet of vonoprazan only when reflux symptoms occurred was performed for 8 weeks by 30 patients (11 men, mean age: 67.8) with non-erosive reflux disease who responded well to maintenance therapy using proton pump inhibitor and answered "very satisfied" or "satisfied" to an overall satisfaction survey (5-grade scale). The degree of overall satisfaction with the treatment, score of symptoms, and fasting gastrin levels before breakfast was examined before and after on-demand therapy. The number of vonoprazan tablets taken and the frequency (regular, temporary, rare) of its administration were also investigated.. All patients completed 8-week on-demand therapy with 20-mg vonoprazan. Comparisons of patient satisfaction levels before and after therapy revealed no significant differences in the number of patients who were very satisfied and satisfied with the therapy. Furthermore, there were no significant differences in score of symptoms or gastrin levels before and after therapy. During 8-week on-demand therapy, patients took 11 tablets (median) (7.0-18.0 tablets: 25-75 percentiles), and 30.0% of patients (n = 9) took vonoprazan on a regular basis (at least 2 tablets a week).. On-demand therapy with 20-mg vonoprazan exerted equivalent effects to continuous PPI maintenance therapy for patients with non-erosive reflux disease.

Topics: Aged; Drug Administration Schedule; Female; Gastrins; Gastroesophageal Reflux; Humans; Male; Middle Aged; Patient Satisfaction; Prospective Studies; Proton Pump Inhibitors; Pyrroles; Sulfonamides; Treatment Outcome

Objective Gastroesophageal reflux disease (GERD) is a highly prevalent disorder that negatively affects patients' quality of life and reduces their work productivity. The medical expenses associated with the treatment of GERD are the highest among all digestive diseases. Current guidelines recommend the administration of a standard dose of proton pump inhibitor (PPI) for eight weeks as an initial GERD treatment. However, there is growing concern regarding the safety of PPI treatment. Recently, a novel potassium-competitive acid blocker (P-CAB), vonoprazan (VPZ), was approved for the treatment of reflux esophagitis in Japan and may provide clinical benefits in GERD treatment. This study was conducted to evaluate the cost-effectiveness of a P-CAB, VPZ vs. a PPI, lansoprazole (LPZ), for the acute medical treatment of reflux esophagitis. Methods A clinical decision analysis was performed using a Markov chain approach to compare VPZ to LPZ in the acute treatment of reflux esophagitis in Japan. Results The P-CAB strategy was superior to the PPI strategy in terms of cost-effectiveness (direct cost per patient to achieve clinical success) and the number of days for which medication was required. Sensitivity analyses revealed that this superiority was robust within the plausible range of probabilities. This remained true even when the healing rates in cases of mild esophagitis were applied. Conclusion The P-CAB strategy was consistently superior to the conventional PPI strategy using the original LPZ in terms of cost-effectiveness and the number of days for which medication was required. Thus, VPZ appears to be the drug of choice for the acute medical treatment of reflux esophagitis.

Topics: Adult; Cost-Benefit Analysis; Drug Administration Schedule; Female; Gastroesophageal Reflux; Gastrointestinal Agents; Humans; Japan; Lansoprazole; Markov Chains; Pyrroles; Quality of Life; Sulfonamides

Objective Clinically, patients with proton pomp inhibitor (PPI)-resistant gastroesophageal reflux disease (GERD) are very challenging to treat. The aim of this study was to determine the rates of symptom relief and adverse events among PPI-resistant GERD patients that changed their therapy from a PPI to vonoprazan. Methods Patients with severe gastroesophageal reflux symptoms (total GERD-Q score ≥8) without endoscopic findings of mucosal breaks who changed their medication from a PPI to vonoprazan during a 12-week period from 2015 to 2016 at 2 hospitals were selected. The primary outcome was the self-reported relief of gastroesophageal reflux symptoms. The odds ratio (OR) for the improvement of symptoms was calculated based on an exact binomial distribution using a matched-pair analysis. The secondary outcome was the GERD-Q score and adverse events. Results Twenty-six patients (6 men) with a mean age of 67.5 years were analyzed. After the therapy was changed from a PPI to vonoprazan, 18 patients (69.2%) reported an improvement, 6 (23.1%) reported no change, and 2 (7.7%) reported an exacerbation of symptoms. A change in therapy was significantly associated with improved self-reported symptoms (OR 9.0, p<0.001). The mean total GERD-Q score during vonoprazan treatment was significantly lower than that during PPI therapy (11.96 vs. 8.92). There were no significant differences in the incidence of adverse events between the therapies. Conclusion Changing the medication from a PPI to vonoprazan was significantly associated with an improvement in gastroesophageal reflux symptoms. Vonoprazan is one of the most promising treatment options for patients with PPI-resistant GERD.

Topics: Adult; Aged; Female; Gastroesophageal Reflux; Humans; Male; Middle Aged; Odds Ratio; Proton Pump Inhibitors; Pyrroles; Retrospective Studies; Self Report; Sulfonamides; Treatment Outcome

Topics: Clinical Trials as Topic; Esophagitis, Peptic; Gastric Acid; Gastroesophageal Reflux; H(+)-K(+)-Exchanging ATPase; Half-Life; Humans; Inhibitory Concentration 50; Japan; Potassium; Prevalence; Proton Pump Inhibitors; Pyrroles; Sulfonamides; Treatment Outcome

The novel potassium-competitive acid blocker, vonoprazan, provides rapid and effective acid suppression. The aim of this study is to evaluate the long-term outcomes of patients with symptomatic gastroesophageal reflux disease (GERD) treated with vonoprazan.. This retrospective cohort study included 55 patients with symptomatic GERD treated with vonoprazan who have been followed for more than one year. The effectiveness of vonoprazan on gastrointestinal symptoms was evaluated using the Izumo scale, a self-reported questionnaire reflecting quality of life related to various abdominal symptoms.. These 55 patients with symptomatic GERD had non-erosive reflux disease (n = 30) or erosive esophagitis (n = 25). Vonoprazan (10 mg) for one month improved GERD symptoms in 89% (responders) and the improvement was maintained at one year in 82% without additional treatment. One-year maintenance therapy resulted in sustained resolution of GERD symptoms in 47%. Of the 49 responders, nine patients had relapse of GERD symptoms and dose escalation of vonoprazan improved the symptoms in six patients. Postprandial distress and the presence of erosive esophagitis before starting vonoprazan were identified as significant negative and positive predictors of sustained resolution of GERD symptoms for one year, respectively. Epigastric pain, postprandial distress, constipation and diarrhea were significantly improved at one-month and maintained at one year. After one-year of treatment, the endoscopic healing rate of erosive esophagitis was 95%.. One-year treatment with vonoprazan significantly improves GERD symptoms and endoscopic healing of erosive esophagitis is satisfactory. The long-term use of vonoprazan is effective and useful to control GERD.

Topics: Aged; Endoscopy, Gastrointestinal; Esophagitis, Peptic; Female; Gastroesophageal Reflux; Humans; Japan; Logistic Models; Male; Middle Aged; Multivariate Analysis; Proton Pump Inhibitors; Pyrroles; Quality of Life; Recurrence; Retrospective Studies; Severity of Illness Index; Sulfonamides; Surveys and Questionnaires; Wound Healing

Topics: Adult; Biopsy; Endoscopy, Gastrointestinal; Gastric Mucosa; Gastroesophageal Reflux; Humans; Male; Parietal Cells, Gastric; Proton Pump Inhibitors; Pyrroles; Sulfonamides

A potent, rapid acting potassium-competitive acid blocker, vonoprazan, is introduced for clinical use in Japan. A number of phase III clinical trials comparing the efficacy of vonoprazan with lansoprazole, showed non-inferior or superior effectiveness in a spectrum of acid-related diseases. In particular, vonoprazan was superior to regular dose of lansoprazole in healing severe gastroesophageal reflux diseases (Los Angeles grade C and D). A triple therapy regimen with vonoprazan, amoxicillin and clarithromycin for 7 days also showed an excellent eradication rate exceeding 90%. The adverse events across these trials were comparable with the standard dose of lansoprazole. As a consequence of profound acid suppression, serum gastrin during vonoprazan therapy rose to much higher levels than those during lansoprazole therapy, pointing to a requirement for the assurance of long-term safety of vonoprazan.

Topics: Clinical Trials as Topic; Gastric Acid; Gastroesophageal Reflux; Humans; Potassium Channel Blockers; Proton Pump Inhibitors; Pyrroles; Sulfonamides

Inhibition of the gastric H,K-ATPase by the potassium-competitive acid blocker (P-CAB) 1-[5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl]-N-methylmethanamine (TAK-438), is strictly K(+)-competitive with a K(i) of 10 nM at pH 7. In contrast to previous P-CABs, this structure has a point positive charge (pK(a) 9.06) allowing for greater accumulation in parietal cells compared with previous P-CABs [e.g., (8-benzyloxy-2-methyl-imidazo(1,2-a)pyridin-3-yl)acetonitrile (SCH28080), pK(a) 5.6]. The dissociation rate of the compound from the isolated ATPase is slower than other P-CABs, with the t(1/2) being 7.5 h in 20 mM KCl at pH 7. The stoichiometry of binding of TAK-438 to the H,K-ATPase is 2.2 nmol/mg in the presence of Mg-ATP, vanadate, or MgP(i). However, TAK-438 also binds enzyme at 1.3 nmol/mg in the absence of Mg(2+). Modeling of the H,K-ATPase to the homologous Na,K-ATPase predicts a close approach and hydrogen bonding between the positively charged N-methylamino group and the negatively charged Glu795 in the K(+)-binding site in contrast to the planar diffuse positive charge of previous P-CABs. This probably accounts for the slow dissociation and high affinity. The model also predicts hydrogen bonding between the hydroxyl of Tyr799 and the oxygens of the sulfonyl group of TAK-438. A Tyr799Phe mutation resulted in a 3-fold increase of the dissociation rate, showing that this hydrogen bonding also contributes to the slow dissociation rate. Hence, this K(+)-competitive inhibitor of the gastric H,K-ATPase should provide longer-lasting inhibition of gastric acid secretion compared with previous drugs of this class.

Topics: Acridine Orange; Animals; Fluorescent Dyes; Gastroesophageal Reflux; H(+)-K(+)-Exchanging ATPase; HEK293 Cells; Humans; Models, Molecular; Molecular Targeted Therapy; Phosphorylation; Protein Binding; Proton Pump Inhibitors; Pyrroles; Software; Stereoisomerism; Stomach; Sulfonamides; Swine