Proton Pump Inhibitor-based Therapy Research Articles

Ten-day vonoprazan-based versus fourteen-day proton pump inhibitor-based therapy for first-line Helicobacter pylori eradication in China: A meta-analysis of randomized controlled trials.

Background: A shorter treatment duration potentially offers the advantage of reducing adverse events (AEs) and enhancing patient compliance for Helicobacter pylori eradication. However, the difference in eradication rates between short-duration vonoprazan-based regimens and fourteen-day proton pump inhibitor (PPI)-based therapy remained unknown. Objective: This meta-analysis aimed to compare the efficacy and safety of ten-day vonoprazan-based regimens with fourteen-day conventional PPI-based therapy for H. pylori eradication. Methods: We performed a comprehensive literature search up to November 28, 2023, using PubMed. A random-effects model was applied to conduct a meta-analysis to determine the pooled Odds Ratio (OR) with 95% confidence intervals (CIs). Results: This meta-analysis included four randomized controlled clinical trials with 1560 patients. The H. pylori eradication rate of ten-day vonoprazan-based regimens was comparable to that of fourteen-day PPI-based therapy (88.7% vs 82.9%, OR 1.53, 95% CI [0.85-2.75], p = .16) in ITT analysis. The incidence of AEs in ten-day vonoprazan-based therapy was also similar to the control group (11.2% vs 17.6%, OR 0.66, 95% CI [0.33-1.31], p = .24). Conclusion: Current evidence suggests that the ten-day vonoprazan-based regimen is as effective as fourteen-day PPI-based therapy in eradicating H. pylori, with comparable AEs. However, additional research is required for confirmation.

Real-world outcomes associated with vonoprazan-based versus proton pump inhibitor-based therapy for Helicobacter pylori infection in Japan.

Japanese guidelines recommend triple therapy with vonoprazan or a proton pump inhibitor (PPI) in combination with antibiotics to treat Helicobacter pylori (H. pylori) infection. While studies have shown improved eradication rates and reduced costs with vonoprazan versus PPIs, there is little data describing healthcare resource use (HCRU) and treatment patterns. To compare patients treated with a vonoprazan-based or PPI-based regimen for H. pylori infection in Japan in terms of their characteristics, HCRU, healthcare costs, clinical outcomes, and treatment patterns. Retrospective matched cohort. We used data from the Japan Medical Data Center claims database (July 2014-January 2020) to identify adult patients with H. pylori infection and a first observed use of vonoprazan or a PPI in 2015 or later (index date). Patients prescribed a vonoprazan-based or a PPI-based regimen were matched 1:1 using propensity score matching. HCRU, healthcare costs, diagnostic tests, a proxy for H. pylori eradication (i.e. no triple therapy with amoxicillin in combination with metronidazole or clarithromycin >30 days after the index date), and second-line treatment were described during the 12-month follow-up period. Among 25,389 matched pairs, vonoprazan-treated patients had fewer all-cause and H. pylori-related inpatient stays and outpatient visits than PPI-treated patients, resulting in lower all-cause healthcare costs [185,378 Japanese yen (JPY) versus 230,876 JPY, p < 0.001]. Over 80% of patients received a post-treatment test for H. pylori. Fewer vonoprazan-treated than PPI-treated patients subsequently received an additional triple regimen for H. pylori infection (7.1% versus 20.0%, p < 0.001) or a prescription for vonoprazan or a PPI as monotherapy (12.4% versus 26.4%, p < 0.001) between 31 days and 12 months after the index date. Patients with H. pylori infection who were treated with vonoprazan-based therapy had lower rates of subsequent H. pylori treatment, lower overall and H. pylori-related HCRU, and lower healthcare costs than patients treated with PPI-based therapy.

Cost-effectiveness Analysis Comparing Vonoprazanbased Triple Therapy with Proton Pump Inhibitorbased Therapy in the Treatment of Helicobacter pylori Infection in Thailand

Objective: Helicobacter pylori (H. pylori) infection is one of the leading causes of gastrointestinal diseases such as dyspepsia, peptic ulcers. Thailand has a 45.9% prevalence of the infection and an increasing rate of resistance to clarithromycin, leading to standard treatments being less successful. Vonoprazan represents a novel drug offering a new treatment regimen. Although vonoprazan has been available in Thailand since 2019, its cost-effectiveness has not been studied previously.Materials and Methods: This study analysed the cost-effectiveness of vonoprazan-based triple therapy compared with PPI-based therapy, in treating clarithromycin resistant H. pylori, by using the markov model from a societal perspective.Results: The total cost of vonoprazan-based triple therapy, levofloxacin-PPI based triple therapy and concomitant-PPI therapy were 784,932.08 baht, 783,863.65 baht and 783,874.55 baht respectively. The quality-adjusted life years (QALYs) of vonoprazan-based triple therapy, levofloxacin-PPI based triple therapy and concomitant-PPI therapy were 25.1118 years, 25.1147 years and 25.1054 years respectively. The cost-effectiveness ratio (CER) of vonoprazanbased triple therapy, levofloxacin-PPI based triple therapy and concomitant-PPI therapy were 31,257.50 baht/ QALYs, 31,211.35 baht/QALYs and 31,223.34 baht per QALYs respectively.Conclusion: Therefore, levofloxacin-PPI based triple therapy was found to be the most cost-effective regimen and the dominant strategy compared with concomitant-PPI or vonoprazan-based triple therapy. It provided higher QALYs and lower treatment costs. Levofloxacin-PPI based triple therapy should be the first choice of an alternative strategy in treating clarithromycin-resistant H. pylori. The results of this study can be used by policymakers to help inform their decisions.

CYP2C19 Polymorphisms in Indonesia: Comparison among Ethnicities and the Association with Clinical Outcomes.

Simple SummaryCYP2C19 is known as an enzyme primarily responsible for metabolizing various drugs, such as proton pump inhibitor, antiplatelet, anti-epileptic, and anticoagulant. CYP2C19 is known to be polymorphic and can result in the clinical efficacy of drugs. To examine the prevalence and the distribution of the CYP2C19 genetic polymorphisms in Indonesia, we performed polymerase chain reaction-restriction fragment length polymorphism to the genomic DNA of Indonesian participants. In addition, we also analyzed the distribution of CYP2C19 polymorphisms among ethnicities and clinical outcomes. We found that the prevalence of intermediate metabolizers were the highest in Indonesia, followed by rapid metabolizers and poor metabolizers, respectively. The distribution of metabolizer groups were different between ethnic groups in Indonesia. Therefore, dosage adjustment should be considered when administering drugs-affected by CYP2C19 in Indonesia. The results presented in this study showed the distribution of CYP2C19 variant alleles at the population level in Indonesia and might be used as a consideration for providing personalized treatment in clinical practice.CYP2C19 polymorphisms are important factors for proton pump inhibitor-based therapy. We examined the CYP2C19 genotypes and analyzed the distribution among ethnicities and clinical outcomes in Indonesia. We employed the polymerase chain reaction-restriction fragment length polymorphism method to determine the CYP2C19 genotypes and evaluated inflammation severity with the updated Sydney system. For CYP2C19*2, 46.4% were the homozygous wild-type allele, 14.5% were the homozygous mutated allele, and 39.2% were the heterozygous allele. For CYP2C19*3, 88.6% were the homozygous wild-type allele, 2.4% were the homozygous mutated allele, and 9.0% were the heterozygous allele. Overall, the prevalence of rapid, intermediate, and poor metabolizers in Indonesia was 38.5, 41.6, and 19.9%, respectively. In the poor metabolizer group, the frequency of allele *2 (78.8%) was higher than the frequency of allele *3 (21.2%). The Papuan had a significantly higher likelihood of possessing poor metabolizers than the Balinese (OR 11.0; P = 0.002). The prevalence of poor metabolizers was lower compared with the rapid and intermediate metabolizers among patients with gastritis and gastroesophageal reflux disease. Intermediate metabolizers had the highest prevalence, followed by rapid metabolizers and poor metabolizers. Dosage adjustment should therefore be considered when administering proton pump inhibitor-based therapy in Indonesia.

Efficacy of Low Dose Proton Pump Inhibitor-Based Therapy to Eradicate Helicobacter pylori in Patients with Subtotal Gastrectomy.

Proton pump inhibitor (PPI)-based therapy is standard to eradicate Helicobacter pylori (H. pylori). Gastric acidity is lowered after gastrectomy because of bile reflux and impaired mechanism of acid secretion. Therefore, low-dose PPI may be effective for H. pylori eradication in the remnant stomach after gastrectomy. In this study, we compared the efficacy of low-dose PPI with standard double-dose PPI to eradicate H. pylori in patients who underwent subtotal gastrectomy. A total of 145 patients who were treated for eradication after gastrectomy was analyzed. They were treated with PPI-based triple regimen (PPI, clarithromycin and amoxicillin) for 14 days. We compared the eradication rate in the low-dose PPI group (lansoprazole 15 mg once daily) with that in the standard double-dose PPI group (lansoprazole 30 mg twice daily). The H. pylori eradication rate was 79.1% in the low-dose PPI group and 85.3% in the standard double-dose group; the difference was not significant statistically (p = 0.357). In the multivariate analysis, low-dose PPI (odds ratio (OR) = 1.79, 95% confidence interval (CI), 0.68–4.69) was not associated with eradication failure, while Billroth II anastomosis (OR = 4.45, 85% CI, 1.23–16.2) was significantly associated with eradication failure. Low-dose PPI-based triple regimen was as effective as standard double-dose PPI-based regimen for H. pylori eradication in patients with subtotal gastrectomy. Further study is needed to confirm the effect of low-dose PPI on H. pylori eradication in patients with gastrectomy.

Effect of Age on Effectiveness of Vonoprazan in Triple Therapy for Helicobacter pylori Eradication.

Objective We evaluated the efficacy of vonoprazan-based eradication therapy for Helicobacter pylori (H. pylori), including the effects of age, gender, and grade of atrophy in comparison to proton pump inhibitor-based therapy. Method We retrospectively reviewed the records of 1,172 patients who received first-line triple therapy with amoxicillin, clarithromycin, and vonoprazan or a proton pump inhibitor (PPI) for H. pylori eradication, as well as 157 patients treated with second-line therapy consisting of amoxicillin, metronidazole, and vonoprazan or a PPI. Results The eradication rate of all cases treated with first-line triple therapy was 86.9% (1,019/1,172), while that in those treated with vonoprazan-based therapy was 92.5% (384/415). Our analysis showed that the use of vonoprazan resulted in a significantly improved success rate of first-line eradication therapy in comparison to proton pump inhibitor-based therapy [odds ratio (OR), 2.36; 95% confidence interval (CI) 1.55 to 3.56]. The superiority of vonoprazan was remarkable in non-elderly patients, while its effect was unclear in elderly patients. When used as second-line eradication therapy, the advantage of vonoprazan over PPI administration was not clear. Conclusion The inclusion of vonoprazan increased the success rate of first-line eradication therapy; however, the advantage was reduced with aging and remained unclear in elderly patients.

Vonoprazan-based triple therapy is non-inferior to susceptibility-guided proton pump inhibitor-based triple therapy for Helicobacter pylori eradication

BackgroundAll Helicobacter pylori-infected patients are recommended for eradication with an appropriate regimen in each geographic area. The choice of the therapy is somewhat dependent on the antimicrobial susceptibility. The rate of clarithromycin resistance has been increasing and is associated with failure; thus, susceptibility testing is recommended before triple therapy with clarithromycin. However, antimicrobial susceptibility testing is not yet clinically available and an alternative newly developed acid inhibitor vonoprazan is used for triple therapy in Japan. The aim of this study was to determine whether vonoprazan-based triple therapy is plausible treatment in H. pylori eradication.MethodsA retrospective observational study of H. pylori eradication was conducted in a single institute. The patients who requested antimicrobial susceptibility testing were treated with susceptibility-guided proton pump inhibitor-based triple therapy in International University of Health and Welfare Hospital from 2013 to 2016. Other patients were treated with empirical treatment with a proton pump inhibitor. From 2015 to 2016, vonoprazan-based triple treatment (vonoprazan, 20 mg; amoxicillin, 750 mg; and clarithromycin, 200 or 400 mg, b.i.d.) was conducted, and its effectiveness was compared with susceptibility-guided proton pump inhibitor-based triple therapy. We also investigated the improvement in eradication rate when antimicrobial susceptibility testing was performed, and compared the outcomes of vonoprazan-based and proton pump inhibitor-based empirical therapy.ResultsA total of 1355 patients who received first-line eradication treatment were enrolled in the present study. The eradication rates of the empirical proton pump inhibitor-based therapy and the vonoprazan-based therapy group in a per-protocol analysis were 86.3% (95% CI 83.8–88.8) and 97.4% (95% CI 95.7–99.1), respectively. In 212 patients who received antimicrobial susceptibility testing, the rate of clarithromycin resistant was 23.5% and the eradication rate in susceptibility-guided treatment was 95.7% (95% CI 92.9–98.4). The difference between susceptibility-guided and vonoprazan-based therapy was − 1.7% (95% CI − 4.9 to 1.5%), and the non-inferiority of vonoprazan-based triple therapy was confirmed.ConclusionsVonoprazan-based triple therapy was effective as susceptibility-guided triple therapy for H. pylori eradication. An empirical triple therapy with vonoprazan is preferable even in area with high rates of clarithromycin-resistance.Trial registration The study was retrospectively registered in University Hospital Medical Information Network (UMIN000032351)

Levofloxacin and proton pump inhibitor‐based triple therapy versus standard triple first‐line therapy for Helicobacter pylori eradication

Standard triple therapy for Helicobacter pylori infection fails in up to one quarter of patients. Levofloxacin-based triple therapy may be more efficacious. The aim of this paper was to compare levofloxacin and proton pump inhibitor-based triple therapy with standard triple therapy for H. pylori infection. PubMed, Embase, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, Google Scholar, and Ovid were systematically searched to identify randomized controlled trials comparing levofloxacin and proton pump inhibitor-based therapy with standard triple therapy in treatment-naive patients with H. pylori infection until August 2013. Ten randomized controlled trials involving 2676 patients (1357 in the levofloxacin group and 1319 in the control group) met the inclusion criteria. The pooled odds ratio by intention-to-treat analysis and by per protocol analysis in the levofloxacin regimen versus standard regimen was 1.28 [95% confidence interval (CI): 0.88-1.85] and 1.23 (95% CI: 0.82-1.84) by the random effects model, respectively. There was no statistical significance of the incidence of total side effects between the groups, but levofloxacin-based therapy was associated with a significant reduction in the incidence of taste disturbance compared with standard third therapy. Levofloxacin-based therapy was as safe and effective as triple therapy for H. pylori infection and could be considered as an additional treatment option. However, more rigorous research is required to accurately assess the role of levofloxacin in eradicating H. pylori infection.

CYP2C19 genotypes in the pharmacokinetics/pharmacodynamics of proton pump inhibitor-based therapy of Helicobacter pylori infection

Importance of the field: Proton pump inhibitors (PPIs) are potent gastric acid inhibitors. Therapies with a PPI and antibiotics are used to cure Helicobacter pylori (H. pylori) infection, which is closely related to many gastrointestinal diseases. Most PPIs are mainly metabolized by cytochrome 2C19 (CYP2C19). The genetic polymorphisms of CYP2C19 may lead to the differences in pharmacokinetics (PK), pharmacodynamics (PD) and clinical efficacy of PPIs.Areas covered in this review: The roles of PPIs on the eradication of H. pylori are summarized. The impact f CYP2C19 polymorphism on the PK and PD of PPIs is addressed and related to the present status of therapy for H. pylori infection. The opinions on the strategy of PPIs-based therapies of H. pylori infection are provided.What the reader will gain: Update the factors that may influence the PPIs-based therapies of H. pylori infection.Take home message: The eradication rates of H. pylori infection are significantly different between patients who are CYP2C19 extensive metabolizers and poor metabolizers, partly because of the differences in the PK and PD of PPIs. Nonetheless, the differences can be improved by adjusting the regimens of PPIs and using antibiotics that have less H. pylori-resistance.

Influence of anti-Helicobacter triple-therapy with metronidazole, omeprazole and clarithromycin on intestinal microflora.

Proton pump inhibitor-based therapy including two antibiotics is the treatment of choice for Helicobacter pylori infection. Oral antibiotic treatment can lead to intestinal overgrowth of potentially pathogenic bacteria. To investigate the intestinal microflora before and at different times after H. pylori treatment with omeprazole, clarithromycin and metronidazole. Bacterial growth in faecal samples from 51 patients infected with H. pylori was determined qualitatively and quantitatively. During the same period of time, stool samples from 27 H. pylori-negative controls were taken and investigated at the same intervals. The microflora of H. pylori-infected patients was different from that in H. pylori negative controls. It was characterized by a high concentration of lactobacilli, mainly Lactobacillus acidophilus. Immediately after therapy there was an increased colonization with yeasts, while the growth of lactobacilli and other species was inhibited. Clostridium difficile was cultured from three cases, but without clinical manifestations of pseudomembranous colitis. After 4 weeks of therapy, the microflora returned to normal and was not different from that of the H. pylori-negative control group. In H. pylori-positive patients the intestinal flora is characterized by an increase in growth of acid-tolerant L. acidophilus. Eradication therapy exerts only a short-term influence on intestinal flora, whereas in the long term, the intestinal microflora is restored to a pattern similar to that of the control group.