Potent Potassium-competitive Acid Blockers: A New Era for the Treatment of Acid-related Diseases

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Abstract

Conventional proton pump inhibitors (PPIs) are used as a first-line therapy to treat acid-related diseases worldwide. However, they have a number of limitations including slow onset of action, influence by cytochrome P450 polymorphisms, unsatisfactory effects at night, and instability in acidic conditions. Alternative formulations of conventional PPIs have been developed to overcome these problems; however, these drugs have only introduced small advantages for controlling acid secretion compared to conventional PPIs. Potassium-competitive acid blockers (P-CABs) were developed and have beneficial effects including rapid, long-lasting, and reversible inhibition of the gastric hydrogen potassium ATPase, the proton pump of the stomach. Vonoprazan was recently innovated as a novel, orally active P-CAB. It is currently indicated for the treatment of gastric and duodenal ulcers, reflux esophagitis, and prevention of low-dose aspirin- or nonsteroidal anti-inflammatory drug-related gastric and duodenal ulcer recurrence in Japan. Vonoprazan does not require enteric coating as it is acid-stable, and it can be taken without food because it is quickly absorbed. Vonoprazan accumulates in parietal cells under both acidic and neutral conditions. It does not require an acidic environment for activation, has long-term stability at the site of action, and has satisfactory safety and tolerability. Thus, vonoprazan may address the unmet medical need for the treatment of acid-related diseases.

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Epidemiology of gastro-oesophageal reflux disease: a systematic review.

J. Dent, H B El-Serag, M.-A. Wallander … (2005)

A systematic review of the epidemiology of gastro-oesophageal reflux disease (GORD) has been performed, applying strict criteria for quality of studies and the disease definition used. The prevalence and incidence of GORD was estimated from 15 studies which defined GORD as at least weekly heartburn and/or acid regurgitation and met criteria concerning sample size, response rate, and recall period. Data on factors associated with GORD were also evaluated. An approximate prevalence of 10-20% was identified for GORD, defined by at least weekly heartburn and/or acid regurgitation in the Western world while in Asia this was lower, at less than 5%. The incidence in the Western world was approximately 5 per 1000 person years. A number of potential risk factors (for example, an immediate family history and obesity) and comorbidities (for example, respiratory diseases and chest pain) associated with GORD were identified. Data reported in this systematic review can be interpreted with confidence as reflecting the epidemiology of "true" GORD. The disease is more common in the Western world than in Asia, and the low rate of incidence relative to prevalence reflects its chronicity. The small number of studies eligible for inclusion in this review highlights the need for global consensus on a symptom based definition of GORD.

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Helicobacter pylori treatment in the era of increasing antibiotic resistance.

David Graham, Lori Fischbach (2010)

With few exceptions, the most commonly recommended triple Helicobacter pylori regimen (proton pump inhibitor (PPI), amoxicillin and clarithromycin) now provides unacceptably low treatment success. A review of worldwide results suggests that successful eradication using a triple regimen is not consistently observed in any population. Clinicians should use 'only use what works locally' and ignore consensus statements and society guidelines if they are not consistent with local results. Clinical trials should be result based, with the goal of identifying regimens with >90-95% success. New treatments should be only be compared with the currently locally effective treatment (>90%) or a historical untreated control (which has been shown to reliably yield 0% eradication); trials using placebos or treatments known to be inferior are with rare exceptions unethical. If a highly effective regimen is not available locally, we recommend trying a 14 day concomitant quadruple treatment regimen containing a PPI, amoxicillin, clarithromycin and a nitroimidazole; 10 day sequential treatment (PPI plus amoxicillin for 5 days followed by a PPI, clarithromycin and a nitroimidazole for 5 days); or 14 day bismuth-containing quadruple treatments. Treatments needing further evaluation include those containing furazolidone or nitazoxanide, hybrids of sequential-concomitant therapies and amoxicillin-PPI dual therapy with PPI doses such that they maintain intragastric pH >6.

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Vonoprazan, a novel potassium-competitive acid blocker, as a component of first-line and second-line triple therapy for Helicobacter pylori eradication: a phase III, randomised, double-blind study

Kazunari Murakami, Yuuichi Sakurai, Madoka Shiino … (2016)

Objective The objective of this study was to assess the efficacy, safety and tolerability of vonoprazan, a novel potassium-competitive acid blocker, as a component of Helicobacter pylori eradication therapy. Design A randomised, double-blind, multicentre, parallel-group study was conducted to verify the non-inferiority of vonoprazan 20 mg to lansoprazole 30 mg as part of first-line triple therapy (with amoxicillin 750 mg and clarithromycin 200 or 400 mg) in H pylori-positive patients with gastric or duodenal ulcer history. The first 50 patients failing first-line therapy with good compliance also received second-line vonoprazan-based triple therapy (with amoxicillin 750 mg and metronidazole 250 mg) as an open-label treatment. Results Of the 650 subjects randomly allocated to either first-line triple therapy, 641 subjects completed first-line therapy and 50 subjects completed second-line therapy. The first-line eradication rate (primary end point) was 92.6% (95% CI 89.2% to 95.2%) with vonoprazan versus 75.9% (95% CI 70.9% to 80.5%) with lansoprazole, with the difference being 16.7% (95% CI 11.2% to 22.1%) in favour of vonoprazan, thus confirming the non-inferiority of vonoprazan (p<0.0001). The second-line eradication rate (secondary end point) was also high (98.0%; 95% CI 89.4% to 99.9%) in those who received second-line therapy (n=50). Both first-line triple therapies were well tolerated with no notable differences. Second-line triple therapy was also well tolerated. Conclusion Vonoprazan is effective as part of first-line triple therapy and as part of second-line triple therapy in H pylori-positive patients with a history of gastric or duodenal ulcer. Trial registration number NCT01505127.

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Author and article information

Journal

Journal ID (nlm-ta): J Neurogastroenterol Motil

Journal ID (iso-abbrev): J Neurogastroenterol Motil

Title: Journal of Neurogastroenterology and Motility

Publisher: Korean Society of Neurogastroenterology and Motility

ISSN (Print): 2093-0879

ISSN (Electronic): 2093-0887

Publication date (Print): July 2018

Publication date (Electronic): 01 July 2018

Volume: 24

Issue: 3

Pages: 334-344

Affiliations

Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan

Author notes

[* ]Correspondence: Tadayuki Oshima, MD, PhD, Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan, Tel: +81-798-45-6662, Fax: +81-798-45-6661, E-mail: t-oshima@ 123456hyo-med.ac.jp

Article

Publisher ID: jnm-24-334

DOI: 10.5056/jnm18029

PMC ID: 6034668

PubMed ID: 29739175

SO-VID: 9fac293b-bea2-4f03-943d-df604a5dd3cd

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This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

History

Date received : 22 January 2018

Date revision received : 03 April 2018

Date accepted : 17 April 2018

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Potent Potassium-competitive Acid Blockers: A New Era for the Treatment of Acid-related Diseases

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Most cited references 104

Epidemiology of gastro-oesophageal reflux disease: a systematic review.

Helicobacter pylori treatment in the era of increasing antibiotic resistance.

Vonoprazan, a novel potassium-competitive acid blocker, as a component of first-line and second-line triple therapy for Helicobacter pylori eradication: a phase III, randomised, double-blind study

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