Reply

We appreciate Graham’s letter1 expressing interest in our American Gastroenterological Association clinical practice update (CPU) on integrating potassium-competitive acid blockers (PCABs) into clinical practice.2 Graham1 suggests that the advice and data regarding vonoprazan for treatment of Helicobacter pylori (HP) are misleading, and that we recommended vonoprazan-based triple therapy despite lack of high cure rates. He further mentions the high costs of vonoprazan as compared to generic proton pump inhibitors (PPIs) and suggests that only certain PPIs (esomeprazole, rabeprazole) should be used to treat HP, but he does conclude that dual therapy with optimized vonoprazan dosing will be superior to regimens containing these PPIs and will represent the future choice for HP treatment.

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Regarding the AGA Clinical Practice Update on Integrating Vonoprazan Into Clinical Practice

I recently read the American Gastroenterological Association clinical practice update on integrating potassium-competitive acid blockers into clinical practice.1 I believe the advice and data presented regarding the use of vonoprazan for the treatment of Helicobacter pylori infections are misleading. Vonoprazan triple therapy is recommended despite the US/European vonoprazan trial reporting that vonoprazan-based therapy failed to produce high, or even acceptable, cure rates in patients with both clarithromycin susceptible and resistant infections.

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AGA Clinical Practice Update on Screening and Surveillance in Individuals at Increased Risk for Gastric Cancer in the United States: Expert Review

Gastric cancer (GC) is a leading cause of preventable cancer and mortality in certain US populations. The most impactful way to reduce GC mortality is via primary prevention, namely Helicobacter pylori eradication, and secondary prevention, namely endoscopic screening and surveillance of precancerous conditions, such as gastric intestinal metaplasia (GIM). An emerging body of evidence supports the possible impact of these strategies on GC incidence and mortality in identifiable high-risk populations in the United States.

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Efficacy of susceptibility-guided quadruple therapy with antibiotic resistance using the string test coupled with quantitative PCR for Helicobacter pylori eradication: a protocol of a multicentre, open, randomised clinical trial

Introduction
Helicobacter pylori is a major health problem, with the high prevalence of H. pylori and the increasing antibiotic resistance rate in China. Antibiotic resistance is the main reason for the failure of H. pylori eradication. This study aims to evaluate the efficacy and safety of susceptibility-guided quadruple therapy with antibiotic resistance using the string test coupled with quantitative PCR (qPCR) for H. pylori eradication.

Methods and analysis
This is a multicentre, open, randomised clinical trial that will enroll 324 patients with H. pylori infection. Patients will be randomised to two groups for a 14-day treatment: Treatment group will be treated with proton pump inhibitor (PPI), bismuth with two different kinds of antibiotics susceptibly guided by string test coupled with qPCR, while control group will be treated empirically with PPI, bismuth with two different kinds of antibiotics. The types and dosages of bismuth, PPI and antibiotics administered in this trial are based on the 2022 Chinese Guidelines for the treatment of H. pylori infection and the Sixth Chinese National Consensus Report on the management of H. pylori infection. The primary endpoint is the eradication rate, while secondary endpoints include compliance, the incidence of adverse events and adverse drug reactions.

Ethics and dissemination
This study was approved by the ethics committee of the Third People’s Hospital of Zhengzhou (No. 2024-04-001-K02). The results will be published in the appropriate peer-reviewed journal.

Trial registration number
ChiCTR2400082768.

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Evolution of the use, effectiveness and safety of bismuth-containing quadruple therapy for Helicobacter pylori infection between 2013 and 2021: results from the European registry on H. pylori management (Hp-EuReg)

Background
Bismuth quadruple therapies (BQTs) including bismuth, a proton pump inhibitor (PPI) and two antibiotics have been shown to be highly effective for treating Helicobacter pylori infection even in areas of high bacterial antibiotic resistance.

Objective
To describe the time trends of use, effectiveness and safety of BQT in Europe using the European Registry on Helicobacter pylori Management (Hp-EuReg).

Design
Patients registered in the Hp-EuReg from 2013 to 2021 who had received BQT were included. The regimens prescribed, the number of eradication attempts, effectiveness, adherence and safety were analysed. The effectiveness was assessed by modified intention to treat (mITT). Time-trend and multivariate analyses were performed to determine variables that predicted treatment success.

Results
Of the 49 690 patients included in the Hp-EuReg, 15 582 (31%) had received BQT. BQT use increased from 8.6% of all treatments in 2013 to 39% in 2021. Single-capsule BQT—containing bismuth, metronidazole and tetracycline—plus a PPI (single-capsule BQT, ScBQT) was the most frequent treatment mode (43%). Schemes that obtained an effectiveness above 90% were the 10-day ScBQT and 14-day BQT using tetracycline plus metronidazole, or amoxicillin plus either clarithromycin or metronidazole. Only ScBQT achieved above 90% cure rates in all the geographical areas studied. Using the ScBQT scheme, adherence, the use of standard or high-dose PPIs, 14-day prescriptions and the use of BQT as first-line treatment were significantly associated with higher mITT effectiveness.

Conclusion
The use of BQT increased notably in Europe over the study period. A 10-day ScBQT was the scheme that most consistently achieved optimal effectiveness.

Trial registration number
NCT02328131.

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