Conventional Proton Pump Inhibitors Research Articles

Sintilimab-induced severe erosive hemorrhagic gastritis and pyloric obstruction: a case report and literature review.

Immune checkpoint inhibitors could restore immune surveillance to attack tumor through targeting CTLA-4, PD-1 or PD-L1, and have achieved huge success. However, immune-related adverse events (irAEs) have been attracting attention as their application is expanding. Gastritis is relatively rare as a subtype of irAEs, particularly severe gastritis. Guidelines on its clinical management still remain undefined due to limited data. Sintilimab is a PD-1 inhibitor approved in China. Here we offer a case of sintilimab-induced severe erosive hemorrhagic gastritis and pyloric obstruction. Conventional proton pump inhibitors and mucosal protective agents did not take effect, so glucocorticoid was chosen. This severe gastritis was successfully cured finally. Our report describing its clinical performances, endoscopic characteristics and treatments, could assist clinicians to better know this rare irAE.

Potassium-competitive acid blockers and acid-related disorders.

Potassium-competitive acid blockers (PCABs) represent a new class of compounds for the treatment of acid-related disorders. Recent FDA approval of the PCAB vonoprazan for erosive esophagitis has started an important new approach to acid-related disorders. Compared to conventional proton pump inhibitors (PPIs), PCABs provide more rapid, potent, and sustained suppression of gastric acid with faster and more durable symptom relief. Studies have demonstrated the efficacy of PCABs for erosive esophagitis, nonerosive reflux disease, and peptic ulcer disease including H. pylori. However, the PCAB vonoprazan was only approved in the US as part of combination therapy for eradication of H. pylori. Clinical trials have now demonstrated noninferiority of vonoprazan to lansoprazole for treatment of erosive esophagitis, particularly noting superiority of vonoprazan in patients with severe esophagitis resulting in FDA approval of vonoprazan for treatment of erosive esophagitis. Emerging data suggests a possible utility of vonoprazan for PPI-resistant gastroesophageal reflux disease (GERD) and on-demand therapy for nonerosive reflux disease. Vonoprazan is generally well tolerated but long-term safety data is not well established. The PCAB vonoprazan is a newly FDA approved treatment option for erosive esophagitis. Its possible role in PPI-resistant GERD and nonerosive reflux disease warrants further investigation.

Treatment of Helicobacter pylori with potassium competitive acid blockers: A systematic review and meta-analysis.

Helicobacter pylori (H. pylori) infects over half the global population, causing gastrointestinal diseases like dyspepsia, gastritis, duodenitis, peptic ulcers, G-MALT lymphoma, and gastric adenocarcinoma. Eradicating H. pylori is crucial for treating and preventing these conditions. While conventional proton pump inhibitor (PPI)-based triple therapy is effective, there's growing interest in longer acid suppression therapies. Potassium competitive acid blocker (P-CAB) triple and dual therapy are new regimens for H. pylori eradication. Initially used in Asian populations, vonoprazan (VPZ) has been recently Food and Drug Administration-approved for H. pylori eradication. To assess the efficacy of regimens containing P-CABs in eradicating H. pylori infection. This study, following PRISMA 2020 guidelines, conducted a systematic review and meta-analysis by searching MEDLINE and Scopus libraries for randomized clinical trials (RCTs) or observational studies with the following command: [("Helicobacter pylori" OR "H pylori") AND ("Treatment" OR "Therapy" OR "Eradication") AND ("Vonaprazan" OR "Potassium-Competitive Acid Blocker" OR "P-CAB" OR "PCAB" OR "Revaprazan" OR "Linaprazan" OR "Soraprazan" OR "Tegoprazan")]. Studies comparing the efficacy of P-CABs-based treatment to classical PPIs in eradicating H. pylori were included. Exclusion criteria included case reports, case series, unpublished trials, or conference abstracts. Data variables encompassed age, diagnosis method, sample sizes, study duration, intervention and control, and H. pylori eradication method were gathered by two independent reviewers. Meta-analysis was performed in R software, and forest plots were generated. A total of 256 references were initially retrieved through the search command. Ultimately, fifteen studies (7 RCTs, 7 retrospective observational studies, and 1 comparative unique study) were included, comparing P-CAB triple therapy to PPI triple therapy. The intention-to-treat analysis involved 8049 patients, with 4471 in the P-CAB intervention group and 3578 in the PPI control group across these studies. The analysis revealed a significant difference in H. pylori eradication between VPZ triple therapy and PPI triple therapy in both RCTs and observational studies [risk ratio (RR) = 1.17, 95% confidence interval (CI): 1.11-1.22, P < 0.0001] and (RR = 1.13, 95%CI: 1.09-1.17, P < 0.0001], respectively. However, no significant difference was found between tegoprazan (TPZ) triple therapy and PPI triple therapy in both RCTs and observational studies (RR = 1.04, 95%CI: 0.93-1.16, P = 0.5) and (RR = 1.03, 95%CI: 0.97-1.10, P = 0.3), respectively. VPZ-based triple therapy outperformed conventional PPI-based triple therapy in eradicating H. pylori, positioning it as a highly effective first-line regimen. Additionally, TPZ-based triple therapy was non-inferior to classical PPI triple therapy.

Vonoprazan versus Conventional Proton Pump Inhibitors Based Regimens in Helicobacter Pylori Eradication Therapy

Vonoprazan versus Conventional Proton Pump Inhibitors Based Regimens in Helicobacter Pylori Eradication Therapy

History and Pharmacological Mechanism of Gastric Acid-suppressive Drugs

Gastric acid-related disorders are commonly encountered in clinical practice. Acetylcholine, gastrin, and histamine are physiological agonists that stimulate acid secretion from parietal cells. Histamine plays a decisive role in the transformation of parietal cells into acid-secreting forms. The H&lt;sup&gt;+&lt;/sup&gt;, K&lt;sup&gt;+&lt;/sup&gt;- ATPase proton pump, which represents the final step of acid secretion, translocates from cytoplasmic tubulovesicles to secretory canaliculi upon parietal cell stimulation and facilitates exchange of intracellular H&lt;sup&gt;+&lt;/sup&gt; with extracellular K&lt;sup&gt;+&lt;/sup&gt; in a 1:1 ratio. Histamine-2 receptor antagonists and proton pump inhibitors (PPIs) are widely used in clinical practice, and potassium-competitive acid blockers (P-CABs) have gained attention in recent times. P-CABs address the unmet needs of patients who receive conventional PPIs and have broadened the spectrum of drug choices; however, further research is warranted to confirm long-term safety of these drugs. Comprehensive understanding of the mechanisms of actions, characteristics, advantages and disadvantages, and the adverse effect profile is essential for appropriate prescription of gastric acid-suppressive drugs. In this review, we provide a developing history and outline the pharmacological mechanisms underlying various gastric acid-suppressive drugs used in clinical settings.

Efficacy and safety of high-dose esomeprazole-amoxicillin dual therapy for Helicobacter pylori rescue treatment: a multicenter, prospective, randomized, controlled trial.

Background:High-dose dual therapy (HDDT) with proton pump inhibitors (PPIs) and amoxicillin has attracted widespread attention due to its favorable efficacy in eradicating Helicobacter pylori (H. pylori). This study aimed to compare the efficacy and safety of high-dose PPI–amoxicillin dual therapy and bismuth-containing quadruple therapy for H. pylori rescue treatment.Methods:This was a prospective, randomized, multicenter, non-inferiority trial. Patients recruited from eight centers who had failed previous treatment were randomly (1:1) allocated to two eradication groups: HDDT (esomeprazole 40 mg and amoxicillin 1000 mg three times daily; the HDDT group) and bismuth-containing quadruple therapy (esomeprazole 40 mg, bismuth potassium citrate 220 mg, and furazolidone 100 mg twice daily, combined with tetracycline 500 mg three times daily; the tetracycline, furazolidone, esomeprazole, and bismuth [TFEB] group) for 14 days. The primary endpoint was the H. pylori eradication rate. The secondary endpoints were adverse effects, symptom improvement rates, and patient compliance.Results:A total of 658 patients who met the criteria were enrolled in this study. The HDDT group achieved eradication rates of 75.4% (248/329), 81.0% (248/306), and 81.3% (248/305) asdetermined by the intention-to-treat (ITT), modified intention-to-treat (MITT), and per-protocol (PP) analyses, respectively. The eradication rates were similar to those in the TFEB group: 78.1% (257/329), 84.2% (257/305), and 85.1% (257/302). The lower 95% confidence interval boundary (−9.19% in the ITT analysis, − 9.21% in the MITT analysis, and −9.73% in the PP analysis) was greater than the predefined non-inferiority margin of −10%, establishing a non-inferiority of the HDDT group vs. the TFEB group. The incidence of adverse events in the HDDT group was significantly lower than that in the TFEB group (11.1% vs. 26.8%, P < 0.001). Symptom improvement rates and patients’ compliance were similar between the two groups.Conclusions:Fourteen-day HDDT is non-inferior to bismuth-containing quadruple therapy, with fewer adverse effects and good treatment compliance, suggesting HDDT as an alternative for H. pylori rescue treatment in the local region.Trial registration:Clinicaltrials.gov, NCT04678492.

MP03-12 ASSOCIATION OF USE OF POTASSIUM COMPETITIVE ACID BLOCKERS AND EFFECTIVENESS OF PEMBROLIZUMAB IN PATIENTS WITH METASTATIC UROTHELIAL CARCINOMA

You have accessJournal of UrologyCME1 May 2022MP03-12 ASSOCIATION OF USE OF POTASSIUM COMPETITIVE ACID BLOCKERS AND EFFECTIVENESS OF PEMBROLIZUMAB IN PATIENTS WITH METASTATIC UROTHELIAL CARCINOMA Wataru Fukuokaya, Takahiro Kimura, Kazumasa Komura, Taizo Uchimoto, Kazuki Nishimura, Yu Oyama, Hirokazu Abe, Haruhito Azuma, Jun Miki, and Shin Egawa Wataru FukuokayaWataru Fukuokaya More articles by this author , Takahiro KimuraTakahiro Kimura More articles by this author , Kazumasa KomuraKazumasa Komura More articles by this author , Taizo UchimotoTaizo Uchimoto More articles by this author , Kazuki NishimuraKazuki Nishimura More articles by this author , Yu OyamaYu Oyama More articles by this author , Hirokazu AbeHirokazu Abe More articles by this author , Haruhito AzumaHaruhito Azuma More articles by this author , Jun MikiJun Miki More articles by this author , and Shin EgawaShin Egawa More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002515.12AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Evidence showed that proton pump inhibitor use was associated with worse survival of patients with metastatic urothelial carcinoma (UC) treated with pembrolizumab. Potassium competitive acid blocker (P-CAB) is a new class of acid blockers which has distinct advantages compared to other conventional proton pump inhibitors (PPI) in terms of the effectiveness for acid suppression. However, the impact of its use on the effectiveness of pembrolizumab in these patients is still unclear. We investigated the impact of P-CAB use on the effectiveness of pembrolizumab in patients with metastatic UC. METHODS: We retrospectively analyzed the records of 227 patients with metastatic UC treated with pembrolizumab. The primary outcome was overall survival (OS). Immune progression-free survival (iPFS) per immune response evaluation criteria in solid tumors were also compared. Multivariable Cox regression models were performed to evaluate the association between P-CAB use and these outcomes. RESULTS: Overall, 30 (13.2%) and 56 (24.7%) patients used P-CABs and PPIs, respectively. Median follow-up period of was 12.8 months (95% CI: 10.6 to 19.3). There were significant differences in baseline platelet count (median; P-CAB users vs. PPI users vs. non-users: 292.5 vs. 271 vs. 249 *1000/uL; P=0.047) and the use of concomitant analgesics (P-CAB users vs. PPI users vs. non-users: 22 [73.3%] vs. 28 [50.0%] vs. 38 [27.0%]; P <0.001). Multivariable Cox regression models showed that both P-CAB and PPI use were associated with worse OS (P-CAB, hazard ratio [HR]: 2.51, 95% confidence interval [CI]: 1.44 to 4.38, P=0.001; PPI, HR: 1.58, 95% CI: 0.96 to 2.61, P=0.072) and iPFS (P-CAB, HR: 1.79, 95% CI: 1.12 to 2.86, P=0.015; PPI, HR: 1.56, 95% CI: 1.07 to 2.28, P=0.021). CONCLUSIONS: Similar to PPI, P-CAB use was significantly associated with worse survival of patients with metastatic UC treated with pembrolizumab. Source of Funding: None © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e24 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Wataru Fukuokaya More articles by this author Takahiro Kimura More articles by this author Kazumasa Komura More articles by this author Taizo Uchimoto More articles by this author Kazuki Nishimura More articles by this author Yu Oyama More articles by this author Hirokazu Abe More articles by this author Haruhito Azuma More articles by this author Jun Miki More articles by this author Shin Egawa More articles by this author Expand All Advertisement PDF DownloadLoading ...

The role of vonoprazan in patients with erosive esophagitis.

Acid suppression is the primary therapy for erosive esophagitis (EE). Although proton pump inhibitors (PPIs) are considered as the first-line medication for EE, 10–20% of patients with Los Angeles C and D grade EE do not gain complete mucosal healing and symptom control despite 8-week double-dose PPI treatment. Vonoprazan is a novel potassium-competitive acid blocker (P-CAB), which blocks the H+, K+-adenosine triphosphatase enzymes in a K+-competitive and reversible manner. Vonoprazan exhibits different pharmacological and pharmacokinetic profiles from conventional PPIs, and has a rapid, potent and sustained acid inhibitory effect. In this review, we summarized and discussed current evidence regarding the role of vonoprazan in terms of mucosal healing, maintaining remission and symptom relief for the management of EE, including the initial and maintenance treatment of EE, as well as for PPI-resistant EE patients. Safety concerns and cost-effectiveness analysis of vonoprazan were also mentioned in the article. As a potent and well-tolerated acid blocker, vonoprazan has the potential to become a novel option for the management of EE.

The influence of pretreatment with PPI on Helicobacter pylori eradication: A systematic review and meta-analysis.

Background:In this meta-analysis, we aimed to comprehensively investigate the impact of pretreatment with proton pump inhibitor (PPI) on Helicobacter pylori (H. pylori) eradication and provide novel inspiration to clinical practice.Methods:Relevant studies were selected through PubMed, Embase, and Cochrane Library from inception to March 2021. Two reviewers performed the selection independently. The primary outcome of the meta-analysis was the eradication rate. A modified Jadad scale was used to evaluate literature quality quantitatively.Results:Ten studies were included in this research. The results showed no significant difference between PPI pretreatment and standard treatment on eradication of H. pylori [relative risk (RR): 1.17, 95% confidence interval (95% CI): 0.0.73–1.88]. There was no significant difference between the PPI pretreatment group and the standard therapy group for conventional triple therapy, PPI and amoxicillin and clarithromycin (RR: 1.29, 95% CI: 0.60–2.77). Similar results were obtained in the therapy strategy of PPI and amoxicillin and metronidazole (RR: 3.01, 95% CI: 0.62–14.74). Interestingly, for the therapy regimen of PPI and clarithromycin and metronidazole, PPI pretreatment indicated superiority on H. pylori eradication rate (RR: 0.48, 95% CI: 0.23–0.97, P < .05).Conclusion:PPI pretreatment did not affect the H. pylori eradication rates, regardless of the various types of bacteriostatic antibiotic, except the therapy regimen of PPI and clarithromycin and metronidazole.

Drug-Drug Interaction between Tacrolimus and Vonoprazan in Kidney Transplant Recipients.

Kidney transplant recipients with tacrolimus-based immunosuppressive therapy are often treated with proton-pump inhibitors (PPIs) to prevent gastric ulcer complications. Vonoprazan, a potassium-competitive acid blocker, is a novel PPI possessing different metabolic pathways from conventional PPIs (e.g., omeprazole, lansoprazole and rabeprazole). However, no data are available on the change in blood concentration of tacrolimus after switching rabeprazole, a conventional PPI, to vonoprazan coadministration in the initial period of post-transplantation. This is a retrospective study of 18 kidney transplant recipients. The blood concentration and the concentration to dose (C/D) ratio of tacrolimus were compared before and after switching from rabeprazole to vonoprazan. Impacts of CYP2C19 and CYP3A5 genetic polymorphisms on the drug–drug interaction were also examined. The median (range) trough concentration of tacrolimus was significantly increased from 5.2 (3.6–7.4) to 8.1 (6.1–11.7) ng/mL (p < 0.0005) after switching from rabeprazole to vonoprazan. The C/D ratio of tacrolimus was also significantly increased from 38.1 (16.5–138.1) to 48.9 (26.2–207.2) (p < 0.0005). The percent changes of tacrolimus concentrations and C/D were 65.8% and 41.8%, respectively. CYP2C19 and CYP3A5 genetic polymorphisms did not affect the change in concentration and C/D ratio of tacrolimus. The present study indicates that vonoprazan coadministration increases the tacrolimus concentration regardless of CYP2C19 or CYP3A5 genetic polymorphisms. Thus, frequent monitoring of blood tacrolimus concentration is required when vonoprazan is introduced as an intensive gastric acid blocker in the early phase of post-transplantation.

Non-acid reflux and sleep apnea: the importance of drug induced sleep endoscopy

BackgroundWe present the first case of a patient with obstructive sleep apnea syndrome (OSA), where drug induced sleep endoscopy was helpful to suspect a non-acid reflux disease and showed an improvement in a swollen epiglottis after treatment. Patient ameliorated significantly his disease only with medical therapy.Case presentationA 54-year-old man without significant anatomical findings with obstructive sleep apnea syndrome and non-acid gastroesophageal reflux disease (GERD) disease whose Apnea- hypopnea index (AHI) was significantly reduced with the intake of 500 mg of sodium alginate twice a day for 6 months. Conventional digestive tests such as esophagoscopy and simple- and double-channel 24-h pH-metry suggested mild GERD. Conventional proton-pump inhibitor treatment with pantoprazole (40 mg daily) was started without any improvement in his sleep. Multichannel intraluminal 24-h impedanciometry indicated the presence of severe pathological GER of gaseous origin. The patient’s AHI decreased from 25.3 at baseline to 8 after treatment with sodium alginate. A drug-induced sleep endoscopy study showed the changes before and after this treatment and was helpful for the diagnosis.ConclusionsThus, medical treatment can be a therapeutic option in some patients with OSA. Multichannel 24-h impedanciometry should be performed when nonacid GERD is suspected.

Use of vonoprazan, a novel potassium-competitive acid blocker, for the treatment of proton pump inhibitor-refractory reflux esophagitis in patients with systemic sclerosis.

Proton pump inhibitor-refractory reflux esophagitis is one of the intractable conditions of systemic sclerosis for which new treatments are required. Vonoprazan is a novel potassium-competitive acid blocker and has been shown to have several advantages over conventional proton pump inhibitors, including a long duration of gastric acid suppression. To investigate the efficacy of vonoprazan for treating proton pump inhibitor-refractory reflux esophagitis in patients with systemic sclerosis, 10 patients with proton pump inhibitor-refractory reflux esophagitis who were switched to vonoprazan were selected from our systemic sclerosis database. Reflux esophagitis was evaluated by endoscopy, and gastroesophageal reflux disease-related symptoms were assessed by the frequency scale for the symptoms of gastroesophageal reflux disease questionnaire before and after switching from proton pump inhibitor to vonoprazan at an average interval of 3.5 [2-5.5] months. After switching patients to vonoprazan, the endoscopic findings of reflux esophagitis were significantly improved (p = .033), and six patients (60%) achieved mucosal healing. The total frequency scale for the symptoms of gastroesophageal reflux disease score was also significantly decreased (p = .043), mainly by improving the acid reflux score. Vonoprazan was well tolerated and was continued for 15.5 [11.25-23.75] months in all patients. Vonoprazan is a potential treatment option for treating proton pump inhibitor-refractory reflux esophagitis in systemic sclerosis patients.

Efficacy of Vonoprazan for Refractory Reflux Esophagitis after Esophagectomy

Background: Refractory reflux esophagitis (RRE), unresponsive to conventional proton-pump inhibitors (PPIs), is a complication in esophagectomy with gastric pull-up. Vonoprazan (VPZ), a novel potassium-competitive acid blocker, has been available in Japan since 2015. Here, we investigated the efficacy of VPZ on PPI-resistant RRE after esophagectomy with gastric pull-up. Methods: This was a single-center retrospective study. We used the revised Los Angeles (r-LA) classification based on the Los Angeles classification and the modified Los Angeles classification to evaluate abnormal forms of mucosal breaks such as lateral spreading consistently. Patients who underwent esophagectomy with gastric pull-up and had RRE grade B–D as per the r-LA classification, despite using standard-dose PPIs or double dose of rabeprazole, were included. Sixteen patients who switched to VPZ (20 mg/day) and 14 patients who continued PPIs were assigned to the VPZ and PPI groups, respectively. Endoscopic observations were reviewed by 3 endoscopists using the r-LA classification to ensure consistent diagnosis, while the treatment arm and patient information were blinded to evaluators. We defined mucosal breaks that improved by at least one grade after treatment as improved mucosa and recovery to grade M or N as mucosal healing. Results: The percentage of patients with improved mucosa in the VPZ and PPI groups was 81.3 and 14.3%, respectively (p < 0.001). The rate of mucosal healing was 68.8 and 7.1%, respectively (p = 0.001). Conclusion: VPZ significantly improved PPI-resistant RRE after esophagectomy with gastric pull-up.

Use of vonoprazan for management of systemic sclerosis-related gastroesophageal reflux disease.

Gastroesophageal reflux disease (GERD) in systemic sclerosis (SSc) can significantly reduce a patient's quality of life. GERD in SSc is occasionally resistant to conventional anti-acid treatment. Vonoprazan is an H+/K+-ATPase blocker that is approved in Japan for treatment of GERD. The aim of the present study was to evaluate the efficacy of vonoprazan in SSc-related GERD. The frequency scale for symptoms of GERD (FSSG) scores were collected before and after vonoprazan treatment in 15 SSc patients with GERD. Additionally, endoscopic esophagogastroduodenoscopy was performed in select patients. Conventional proton pump inhibitors or histamine-2 receptor antagonists had been previously administered in 93% (14/15) of the patients. Although the baseline esophagogastroduodenoscopy examination did not show severe erosion in the majority of patients, the mean total FSSG score before vonoprazan treatment was notably high (25.2±10.7) compared to a normal score of <8. After vonoprazan treatment, the FSSG score decreased to 9.6±7.0. The mean improvement rate of the total FSSG, acid reflux and dysmotility scores were 60.8±21.2% (P=0.0004), 67.3±24.8% (P<0.0001) and 55.4±26.0% (P=0.0022), respectively. These results suggest that vonoprazan may be a potentially effective treatment for GERD in patients with SSc.

Tu1503 ENDOSCOPIC AND HISTOLOGICAL CHARACTERISTICS OF NEW GASTRIC FINDINGS THAT APPEARED WITH STRONG ACID SECRETION SUPPRESSOR (P-CAB).

Since the number of H.pylori-infected persons decreases rapidly, it is expected that acid-related diseases will continue to increase in Japan. The need for gastric acid secretion suppressors is expected to increase in the future. There are several known gastric findings associated with the use of conventional proton pump inhibitors (PPIs). However, there are no reports of gastric findings associated with the use of potassium competitive acid blocker (P-CAB) a more potent gastric acid secretion suppressor. This time we found a new gastric finding associated with the use of P-CAB. This gastric finding is white granular findings with slight elevation similar the White Glove Appearance (WGA) which is known as gastric cancer cases. Since we named this finding White Granule with Small Elevation (WGSE), we introduce WGSE of this finding with endoscopic and histological analysis. <Case 1> A 57-year-old woman was given esomeprazole (EPZ) 20 mg / day and steroid for eosinophilic gastroenteritis. When esomeprazole was changed to Vonoprazan (VPZ) 20 mg / day because erosive gastritis was apparent by endoscopy, WGSE was observed in the gastric fundic gland area. WGSE worsened with continuing VPZ and the dose was reduced to 10 mg / day. Then WGSE gradually decreased and finally disappeared when medicine was changed to famotidine 40 mg / day. <Case 2> A 75-year-old woman was started on VPZ 20 mg for severe reflux esophagitis and maintenance therapy was performed at 10 mg / day. WGSE was observed in the gastric fundic gland area. The change to EPZ 20mg / day is being considered if symptoms are stable in the future. The WGSE histological findings were so similar the WGA observed in gastric cancer cases. Its characteristic finding showed a cystic dilated duct with accumulated gastric secretions. It could be detected WGSE under only continuous P-CAB use, not observed when using PPI. In addition, WGSE decreased with tapering of P–CAB. WGSE were completely disappeared with the change to H2 receptor antagonist. Therefore, we consider that WGSE is to be a specific change with continued use of P-CAB. Previous reports have said that WGA is sometimes observed in autoimmune gastritis with hypergastrinemia, so we have been believed that hypergastrinemia due to strong gastric acid suppression is the most important cause of WGSE. The highest serum gastrin levels of our cases were 1,750 pg/ml and 4,500 pg/ml, those were markedly high level. Although hypergastrinemia occurs with continued PPI use too, no WGSE has been reported. In other words, it is thought to be a gastric finding peculiar to continued use of P-CAB with severe hypergastrinemia. When using P-CAB in the future, it is necessary to pay attention to the appearance of WGSE. Our study found WGSE, the first stomach finding that was especially apparent when using P-CAB.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Clinical Characterization of Vonoprazan-Refractory Gastroesophageal Reflux Disease

Introduction: 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. Methods: 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. Results: 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). Conclusions: Vonoprazan serves as a diagnostic tool to exclude acid-related GERD.

P6405Potential for drug-drug interaction between vonoprazan and prasugrel on antiplatelet effect assessed by VerifyNow P2Y12 assay in patients with coronary artery disease

Abstract Background Vonoprazan is a potassium-competitive acid blocker increasingly used in Japan to prevent gastrointestinal bleeding in patients under dual antiplatelet therapy (DAPT) after coronary stents implantation. Since cytochrome P450 (CYP) 3A4 is involved in the primary metabolism of vonoprazan and prasugurel, there is a possibility that CYP-mediated drug-drug interaction between them can attenuate the antiplatelet function of prasugrel. Purpose The aim of this study was to investigate whether antiplatelet effect of prasugrel could be attenuated upon coadministration with vonoprazan compared to conventional proton pump inhibitors (PPIs). Method We evaluated 72 patients (57 males, 67±11 years) with coronary artery disease who were taking either vonoprazan (n=35) or PPIs (n=37) in combination with DAPT (aspirin and prasugrel) after drug-eluting stents implantation. PPIs included 21 esomeprazole, 8 lansoprazole, and 8 rabeprazole. Antiplatelet effects of prasugrel were assessed using VerifyNow P2Y12 assay. Primary measurements were P2Y12 reaction units (PRU) and P2Y12 percent inhibition. High on-treatment platelet reactivity (HPR) on prasugrel was defined as PRU &gt;208. Administration period of vonoprazan or PPIs in combination with DAPT ≤7 days was defined as early administration period. Results Median administration period of vonoprazan or PPIs in combination with DAPT was 127 days. There were no significant differences in baseline clinical characteristics between patients with vonoprazan and PPIs. In the analysis for all subjects, patients with vonoprazan showed similar PRU (166±50 vs. 167±64, p=0.93) and percent inhibition (36±18 vs. 38±23, p=0.66) compared to those with PPIs. No significant differences were observed in the prevalence of HPR between patients with vonoprazan and PPIs (17 vs. 30%, p=0.27). In the analysis for patients in early administration period [vonoprazan (n=14) vs. PPIs (n=10)], there were no significant differences in PRU (166±47 vs. 186±82, p=0.45), percent inhibition (33±17 vs. 30±26, p=0.73), and prevalence of HPR (14 vs. 50%, p=0.085) between patients with vonoprazan and PPIs. In addition, the analysis for patients over early administration period [vonoprazan (n=21) vs. PPIs (n=27)] showed that PRU (166±55 vs. 160±57, p=0.73), percent inhibition (37±19 vs. 41±21, p=0.57), and prevalence of HPR (19 vs. 22%, p=1.00) were comparable between patients with vonoprazan and PPIs. Conclusion Compared to PPIs, vonoprazan did not exhibit significant inhibitory effects on the antiplatelet activity of prasugrel assessed by VerifyNow assay. These findings suggest that there are possibly no clinically harmful drug-drug interactions between vonoprazan and prasugrel.

A Triple-Drug Blister-Packaged Drug with Vonoprazan Improves First-Line Eradication of Helicobacter pylori in Elderly Patients: A Retrospective Propensity Score-Matched Cohort Study

Background: A blister-packaged drug might be useful to enhance the eradication of Helicobacter pylori. We investigated the effect of a blister-packaged drug for H. pylori eradication. Methods: We treated 1,758 patients with H. pylori infections and evaluated the successful eradication rate in patients who underwent first-line eradication between January 2013 and May 2018. Treatments included a conventional proton pump inhibitor (PPI) blister-packaged drug containing lansoprazole or rabeprazole with clarithromycin (CAM) and amoxicillin (AC), vonoprazan (VPZ) with CAM and AC in a separate tablet, or a VPZ blister-packaged drug (VONOSAP) containing VPZ with CAM and AC, with all drugs given twice daily for 7 days. Results: Finally, we evaluated 1,263 patients (conventional PPI: n = 644, VPZ: n = 326, and VONOSAP: n = 293). The overall successful eradication rates were 71.9% in the conventional PPI group, 90.2% in the VPZ group, and 92.2% in the VONOSAP group. There was a significantly lower eradication rate in the PPI group than in the VPZ and VONOSAP (p < 0.00001, p < 0.0001) groups, but there was no significant difference between the VPZ and VONOSAP groups (p = 0.4006). We enrolled a total of 256 age- and gender-matched patients in the VPZ and VONOSAP groups, and both groups had successful eradication rates of approximately 90% (89.8 vs. 90.4%, respectively, p = 0.7641). After analyzing the subgroup of patients older than 75 years, there was a significant treatment benefit of VONOSAP but not of VPZ in elderly patients (EPs). Conclusion: Triple-drug blister-packaged drugs including VPZ may improve the first-line eradication of H. pylori in EPs.

Vonoprazan versus Lansoprazole for the Initial Treatment of Reflux Esophagitis: A Cost-effectiveness Analysis in Japan.

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.

Vonoprazan and Helicobacter pylori Treatment: A Lesson From Japan or a Limited Geographic Phenomenon?

Within a short time after the discovery of Helicobacter pylori, its critical role in many gastroduodenal disorders became evident. Many in vitro and in vivo data have proven that infection should be treated in order to avoid lasting colonization which may lead to problematic gastroduodenal diseases. Probiotics, preventive and therapeutic vaccines and antibiotic therapy are the main options proposed to cure these disorders. 25 years ago, triple therapy including a traditional proton pump inhibitor (PPI) and two antibiotics (amoxicillin and clarithromycin or metronidazole) was defined as the best therapy formulation for the H. pylori infection. With the strongly decreased effectiveness of this scheme, many empirical therapeutic regimens have been developed. However, the prevalence of resistance is increasing worldwide and reveals important geographic differences and even the most recent and effective regimens show some critical points. Therefore, efficacy of vonoprazan-based therapy in regions with low rate of clarithromycin resistance may be limited. In this review, we attempt to open a new window to overcome the problem of antibiotic resistance to H. pylori. In fact, we focused our attention on the possibility that conventional PPI may be replaced by vonoprazan, thus giving rise to the beginning of a new era characterized by an improved therapeutic option for H. pylori infection. Therefore, we hypothesize that switching to vonoprazan as a novel acid blocker for H. pylori treatment might allow an unexpected reassessment of the triple therapy, at least in regions with low rate of clarithromycin resistance. Nevertheless, this optimistic view of the problem could be disproved by the possible failure of vonoprazan based therapeutic regimens outside of Japan in geographic areas characterized by different rates of antibiotic resistances.