vonoprazan and Heartburn

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

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

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 (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

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

Acid suppression improves dyspepsia symptoms but the efficacy of vonoprazan for functional dyspepsia remains unclear. The aim of this study is to evaluate the effectiveness of vonoprazan therapy for functional dyspepsia without heartburn.. Patients receiving vonoprazan 10 mg once daily or acotiamide 100 mg three times daily for more than one month were included and retrospectively reviewed. Functional dyspepsia was diagnosed based on the ROME IV criteria. Patients with heartburn were excluded. Eighty-five patients were divided into vonoprazan (n=48) and acotiamide (n=37) groups.. There were no significant differences at baseline between the vonoprazan and acotiamide groups. The functional dyspepsia score significantly improved in both groups (p<0.001). The degree of score reduction (55% vs 59%, p=0.559) and the resolution rates (21% vs 30%, p=0.345) were similar. Epigastric pain and postprandial distress scores were significantly improved in both groups, and the degree of improvement of each score was similar. Constipation and diarrhea scores were significantly improved in both groups, and the degree of improvement similar.. These preliminary results suggest that vonoprazan is effective for the treatment of functional dyspepsia without heartburn in the short-term, with results similar to acotiamide therapy.

Topics: Dyspepsia; Heartburn; Humans; Retrospective Studies