Potassium-competitive Acid Blocker Research Articles

Efficacy and Safety of Vonoprazan and Amoxicillin Dual Therapy for Helicobacter pylori Eradication: A Systematic Review and Meta-Analysis

Introduction: Vonoprazan, a novel potassium-competitive acid blocker, has a strong acid suppression effect and potent efficacy in acid-associated diseases, including Helicobacter pylori eradication. We performed a systematic review and meta-analysis to investigate the efficacy and safety of vonoprazan/amoxicillin dual therapy for H. pylori eradication. Methods: We conducted a systematic literature search through PubMed, Web of Science, EMBASE, and the Cochrane Library up to June 2022, to identify randomized controlled trials and cohort studies comparing vonoprazan/amoxicillin dual therapy and triple therapies for H. pylori eradication. Primary outcomes were cure rates and relative efficacy. Secondary outcomes included adverse events, dropout rate, and subgroup analysis. Results: Five studies with 1,852 patients were included in the analysis. The cure rates of vonoprazan/amoxicillin dual therapy were 85.6% with 95% confidence interval (CI) of 79.7–91.5% and 88.5% (95% CI: 83.2–93.8%) in the intention-to-treat and per-protocol analyses. The efficacy of vonoprazan/amoxicillin dual therapy was not inferior to that of triple therapy with pooled risk ratio (RR) of 1.03 (95% CI: 0.97–1.10) and 1.02 (95% CI: 0.98–1.08) in intention-to-treat and per-protocol analyses; while it was significantly superior to the omeprazole or lansoprazole-based triple therapy (RR = 1.15, 95% CI: 1.05–1.25, p = 0.001). For clarithromycin-resistant strains, vonoprazan/amoxicillin dual therapy showed superiority to vonoprazan-based triple therapy (86.7% vs. 71.4%, RR = 1.20, 95% CI: 1.03–1.39, p = 0.02); however, vonoprazan/amoxicillin dual therapy was significant inferior to vonoprazan-based triple therapy for clarithromycin-sensitive strains (83.0% vs. 92.8%, RR = 0.90, 95% CI: 0.85–0.95, p = 0.0002). The adverse effects of vonoprazan/amoxicillin dual therapy were lower than those of triple therapy (21.2% vs. 26.5%, RR = 0.86, 95% CI: 0.73–1.01, p = 0.06), especially the incidence of diarrhea (p = 0.01). Conclusions: The efficacy of vonoprazan/amoxicillin dual therapy is noninferior to vonoprazan-based triple therapy but superior to the omeprazole or lansoprazole-based triple therapy and has less side effects. Patients with clarithromycin-resistant strains are particularly expected to benefit from vonoprazan/amoxicillin dual therapy.

Vonoprazan poses no additional risk of developing Clostridioides difficile infection compared to proton pump inhibitors.

The use of proton pump inhibitors (PPIs) has been repeatedly reported as a trigger of Clostridioides difficile infection (CDI), a leading cause of nosocomial diarrhea. However, only a few studies have reported on the association between vonoprazan, a novel potassium-competitive acid blocker providing potent acid suppression, and CDI, with no studies having been conducted in a clinical setting. We therefore evaluated the association between various classes of acid suppressants and CDI with special attention paid to differences in the magnitudes of association between PPIs and vonoprazan. A retrospective hospital-based cohort from a secondary-care hospital in Japan (n=25821) was collected, wherein eligible CDI cases were defined as hospital-onset cases (n=91). A multivariable adjusted logistic regression analysis for the entire cohort and propensity analyses for subgroups consisting of PPI and/or vonoprazan users at various doses (n=10306) were performed. The overall CDI incidence rate was 1.42/10000 patient-days, which was comparable with previous reports. A multivariable analysis showed that both PPIs and vonoprazan were positively associated with CDI (odds ratios [95% confidence intervals]: 3.15 [1.67-5.96] and 2.63 [1.01-6.88], respectively). In addition, matched subgroup analyses showed that PPIs and vonoprazan had equivalent magnitudes of association with CDI. We found that both PPIs and vonoprazan were associated with CDI, and the magnitude of the association was comparable. Because vonoprazan is widely available in Asian countries, further studies on the association of its usage with CDI are warranted.

Characterisation of degradation products of tegoprazan by LC-MS and GC-MS

Tegoprazan is a novel orally active potassium-competitive acid blocker (P-CAB), capable of binding to the K+ binding site of H+/K+-ATPase in a reversible way to inhibit gastric acid secretion. Tegoprazan has been approved for treating acid-related diseases. In this study, stress testings of tegoprazan were performed under various conditions, including hydrolysis (acidic, alkaline, and neutral), oxidation, photolysis, and thermal stress. Tegoprazan showed instability in acidic, alkaline, and oxidative conditions. Eight degradation products (DPs) were identified. The DPs were characterized by LC-HRMS, LC-MSn, or GC-Q-TOF-MS. Meanwhile, DP-1, DP-2 and DP-3 were successfully synthesized and confirmed by NMR. The degradation pathway of tegoprazan was summarized. To the best of our knowledge, this is the first study on the forced degradation of tegoprazan.

Prediction of the Drug-Drug Interaction Potential between Tegoprazan and Amoxicillin/Clarithromycin Using the Physiologically Based Pharmacokinetic and Pharmacodynamic Model.

Tegoprazan is a novel potassium-competitive acid blocker. This study investigated the effect of drug-drug interaction on the pharmacokinetics and pharmacodynamics of tegoprazan co-administered with amoxicillin and clarithromycin, the first-line therapy for the eradication of Helicobacter pylori, using physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) modeling. The previously reported tegoprazan PBPK/PD model was modified and applied. The clarithromycin PBPK model was developed based on the model provided by the SimCYP® compound library. The amoxicillin model was constructed using the middle-out approach. All of the observed concentration-time profiles were covered well by the predicted profiles with the 5th and 95th percentiles. The mean ratios of predicted to observed PK parameters, including the area under the curve (AUC), maximum plasma drug concentration (Cmax), and clearance, were within the 30% intervals for the developed models. Two-fold ratios of predicted fold-changes of Cmax and AUC from time 0 to 24 h to observed data were satisfied. The predicted PD endpoints, including median intragastric pH and percentage holding rate at pH above 4 or 6 on day 1 and day 7, were close to the corresponding observed data. This investigation allows evaluation of the effects of CYP3A4 perpetrators on tegoprazan PK and PD changes, thus providing clinicians with the rationale for co-administration dosing adjustment.

Pharmacodynamic and Pharmacokinetic Drug Interactions between Fexuprazan, a Novel Potassium-Competitive Inhibitor, and Aspirin, in Healthy Subjects

Acid-reducing agents are commonly used for the prevention of aspirin-induced gastrointestinal complications such as peptic ulcers. As a novel potassium-competitive acid blocker, fexuprazan is expected to prevent aspirin-induced gastrointestinal complications. This randomized, open-label study aimed to evaluate the pharmacodynamic and pharmacokinetic interactions between aspirin and fexuprazan in healthy Koreans. Subjects randomized to the aspirin group received 500 mg aspirin in combination with 80 mg fexuprazan. For the fexuprazan group, fexuprazan 80 mg was administered alone and then in combination with aspirin 500 mg. Platelet aggregation inhibited by aspirin and the pharmacokinetic parameters of aspirin and fexuprazan were compared between monotherapy and combination therapy. A total of 22 subjects completed the study. The platelet aggregation-inhibitory activity and systemic exposure to aspirin were not significantly affected by fexuprazan coadministration. The systemic exposure of fexuprazan was decreased up to 20% by aspirin coadministration, which was not regarded as clinically meaningful considering the previously reported exposure-response relationship. In conclusion, there were no clinically relevant pharmacodynamic or pharmacokinetic interactions between aspirin and fexuprazan. This finding suggests the potential of fexuprazan for the prevention of aspirin-induced gastrointestinal complications, serving as a baseline for optimizing its therapeutic application with aspirin.

Discovery of novel potassium-competitive acid blockers: Protonated form of ligand-receptor complex system.

Potassium-competitive acid blockers (P-CABs) are acid-suppressing drugs targeting the gastric proton pump (H+,K+-ATPase). They are able to mediate the electro-neutral exchange of H+ and K+ coupled with ATP hydrolysis. Because the conditions of both the cytoplasmic side (pH ∼7) and extracytoplasmic side (pH ∼1) of the target H+,K+-ATPase is are quite different, putting into consideration the moderate protonated forms of both the target protein and the P-CABs is important for system modeling. The three different protonated forms of the receptor models were evaluated with experimental data using docking and molecular dynamics. Here, we utilized the in-silico approaches to discover possible inhibitors against H+,K+-ATPase. Candidate substances were screened from the ChEMBL, Enamine, and Mcule databases. The high-throughput virtual screening (HTVS) was performed to screen for potent compounds. Molecular dynamics (MD) simulations were carried out among high docking scored candidates to validate the stability and binding affinity. These findings show that the proper modeling of the target-ligand complex is important for screening potent compounds, especially in extreme environments.

The effect of potassium-competitive acid blocker tegoprazan on gastric cancer cells.

385 Background: Proton pump inhibitors (PPI) and potassium-competitive acid blocker (P-CAB) are both effective gastric acid secretion blockers. PPI was reported to inhibit proliferation and induce apoptosis of gastric cancer. However, no study on the effect of Tegoprazan, a novel P-CAB, on gastric cancer have been attempted. Methods: In this study, the anti-cancer effect of tegoprazan in gastric cancer cell line AGS and MKN74 were analyzed with esomeprazole (PPI) as a control. After treatment with tegoprazan and esomeprazole, AGS cells were analyzed with with RNA sequencing and Ingenuity Pathway Analysis (IPA). MTT assays, AnnexinV-FITC/PI staining, flow cytometry and western blot were used for subsequent analysis. The wound-healing assay, matrigel chamber assays, colony forming assay, and western blot of epithelial-mesenchymal transition (EMT) markers were used for analysis of oncogenic and migratory ability. Results: In RNA sequencing and subsequent IPA analysis, tegoprazan significantly increased the pathways involved in cell death of gastric cancer cell compared to esomeprazole. MTT assays proved that tegoprazan inhibits proliferation of AGS and MKN74 cells in dose-dependent manner. AnnexinV-FITC/PI staining and western blot demonstrated that tegoprazan stimulates apoptosis of gastric cancer cells. PI staining and flow cytometry confirmed that tegoprazan blocks G1/S phase entry, finally leading to cell cycle arrest. Moreover, wound-healing assay, matrigel chamber assays, colony forming assay, and western blot of epithelial-mesenchymal transition (EMT) markers indicated that tegoprazan inhibits cell migration, invasion, colony formation, and EMT. To determine key molecule of anti-cancer effect of tegoprazan, upstream regulator analysis in IPA was done and cMYC has strong effect on G1/S phase entry, through PI3K/AKT/GSK3β signaling pathway in this experiment. In this study, the experimental results for tegoprazan showed significant changes compared to esomeprazole. Conclusions: Our findings showed that tegoprazan has more evident anti-cancer effect than esomeprazole. cMYC could be a key molecule for anti-cancer effect through PI3K/AKT/GSK3β signaling pathway by tegoprazan in gastric cancer.

Comparison of hepatotoxicity of tegoprazan, a novel potassium-competitive acid blocker, with proton pump inhibitors using real-world data: A nationwide cohort study.

Proton pump inhibitors (PPIs) are acid suppressants that are frequently prescribed in many countries to reduce heartburn. A potassium-competitive acid blocker (P-CAB; tegoprazan) was launched relatively recently that also inhibits gastric acid secretion. This study aimed to compare the hepatotoxicity of the six existing PPIs with P-CAB. This retrospective cohort study was conducted between January 2019 and December 2020 and included data from the total population of 50 million inhabitants in Korea. Propensity score (PS) matching was performed using 10 variables, and the differences in hepatotoxicity between P-CAB and the six PPIs were compared in a similar distribution. The primary endpoint was hepatotoxicity which included toxic liver disease, hepatitis, hepatic failure, liver transplantation, and other liver diseases. The risk ratios (RR) of tegoprazan vs. the six PPIs (dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole, and rabeprazole) were all significant [RR: 0.70 (95% CI: 0.69-0.72), 0.81 (95% CI: 0.79-0.83), 0.61 (95% CI: 0.59-0.63), 1.17 (95% CI: 1.13-1.20), 0.61 (95% CI: 0.59-0.62), and 0.73 (95% CI: 0.71-0.75), respectively]. The risk ratio of tegoprazan vs. the six existing PPIs was 0.73 (95% CI: 0.72-0.75). The hazard ratios (HRs) of hepatotoxicity of the six PPIs to tegoprazan showed significantly higher values apart from omeprazole (HR: dexlansoprazole, 1.13; esomeprazole, 1.04; lansoprazole, 1.25; omeprazole, 0.77; pantoprazole, 1.26; rabeprazole, 1.15, respectively, and the six existing PPIs, 1.10). Using a large-scale data cohort analysis consisting of 50 million Koreans, tegoprazan did not induce higher hepatotoxicity compared with the six conventional PPIs.

Development of a Physiologically Based Pharmacokinetic Model for Tegoprazan: Application for the Prediction of Drug–Drug Interactions with CYP3A4 Perpetrators

Tegoprazan is a novel potassium-competitive acid blocker (P-CAB) developed by CJ Healthcare (Korea) for the treatment of gastroesophageal reflux disease and helicobacter pylori infections. Tegoprazan is mainly metabolized by cytochrome P450 (CYP) 3A4. Considering the therapeutic indications, tegoprazan is likely to be administered in combination with various drugs. Therefore, the investigation of drug-drug interactions (DDI) between tegoprazan and CYP3A4 perpetrators is imperative. In the present study, we first aimed to develop a physiologically based pharmacokinetic (PK) model for tegoprazan and its major metabolite, M1, using PK-Sim®. This model was applied to predict the DDI between tegoprazan and CYP3A4 perpetrators. Clarithromycin, a potent inhibitor of CYP3A4, and rifampicin, a strong inducer of CYP3A4, were selected as case studies. Our results show that clarithromycin significantly increased the exposure of tegoprazan. The area under the concentration-time curve (AUC) and Cmax of tegoprazan in the steady state increased up to 4.54- and 2.05-fold, respectively, when tegoprazan (50 mg, twice daily) was coadministered with clarithromycin (500 mg, three times daily). Rifampicin significantly reduced the exposure of tegoprazan. The AUC and Cmax of tegoprazan were reduced by 5.71- and 3.51-fold when tegoprazan was coadministered with rifampicin (600 mg, once daily). Due to the high DDI potential, the comedication of tegoprazan with CYP3A4 perpetrators should be controlled. The dosage adjustment for each individual is suggested.

How widespread and convenient H. pylori susceptibility testing will result in pharmacological opportunities

ABSTRACT Introduction Until recently, antimicrobial therapy for Helicobacter pylori infections was almost universally empirical and based on a combination of expert opinion and local effectiveness. However, the new requirement that all therapeutic regimens reliably achieve high cure rates, the introduction of potassium competitive acid blockers and the availability of susceptibility testing many pharmacological opportunities particularly since all current therapies will require optimization. The ability to rapidly and inexpensively obtain H. pylori susceptibility data using stool samples makes obtaining susceptibility data practical and allows using susceptibility-based therapy routinely for both treatment-naïve patient and treatment failures. Areas covered We searched the literature from 1990 to current to identify studies reporting the effect of susceptibility testing on H. pylori treatment. This review examines how widespread and convenient H. pylori susceptibility testing will result in pharmacological opportunities. . Many pharmacological opportunities will emanate from a renewal of efforts to develop, propagate, confirm, and update best practices based on local and regional susceptibility/resistance patterns. Expert opinion The ability to evaluate treatment decisions and outcomes in susceptible infections and reliably achieve high cure rates should foster precise tailoring of pharmacologic therapy and should achieve the goals of high cure rates while preventing antimicrobial misuse and extending the useful life of current antibiotics.

Size-reduced fexuprazan 20 mg demonstrated the optimal bioavailability and bioequivalence with the reference formulation.

Fexuprazan (DWP14012), a potassium-competitive acid blocker, is a medical formulation prescribed to inhibit the secretion of gastric acid. The present study encompasses a comparative evaluation of pharmacokinetic (PK) analysis between the previous (reference) and size-reduced (test) formulation of fexuprazan 20 mg in healthy subjects. The study employed a randomized, open-label, single-dose, 2-sequence, 2-period, crossover design with a 7-day wash-out between periods. A total of 24 subjects were enrolled in this randomized study. During each period, the 21 subjects received either the test or reference formulation. Blood samples were collected at multiple time point ranging from 0 (pre-dose) to 48 hours post-dosing for PK analysis. The calculated PK parameters were considered bioequivalent when the 90% confidence intervals (CIs) of the geometric mean ratios (GMRs) were within the bioequivalence limit of 0.8-1.25. Safety and tolerability were included in the evaluation. A total of 20 subjects completed the study. Point estimates (90% CIs) of the GMRs were 1.1014 (0.9892-1.2265) for the maximum plasma concentration and 1.0530 (0.9611-1.1536) for the area under the plasma concentration-time curve from zero to the time of the last quantifiable concentration, between the test and reference formulations. The reference and size-reduced test formulations of fexuprazan were well tolerated with no reports of serious adverse events. In conclusion, size-reduced and previous formulations of fexuprazan 20 mg were bioequivalent with regard to PKs, safety and tolerability.

Rescue therapy for refractory Helicobacter pylori infection: current status and future concepts.

Helicobacter pylori infection is an important issue worldwide, and several guidelines have been published for clinicians to achieve successful eradication. However, there are still some patients who remain infected with H. pylori after treatment. Clinicians should identify the reasons that caused treatment failure and find strategies to manage them. We have searched and organized the literature and developed methods to overcome factors that contribute to prior treatment failure, such as poor compliance, inadequate intragastric acid suppression, and antibiotic resistance. To improve compliance, telemedicine or smartphone applications might play a role in the modern world by increasing doctor-patient relationships, while concomitant probiotics could be administered to reduce adverse effects and enhance adherence. For better acid suppression, high-potency and high-dose proton-pump inhibitors or potassium-competitive acid blockers have preferable efficacy. To overcome antibiotic resistance, susceptibility tests either by culture or by genotyping are the most commonly used methods and have been suggested for antibiotic selection before rescue therapy, but empirical therapy according to detailed medical history could be an alternative. Eradication with a longer treatment period (14 days) has a better outcome than shorter period (7 or 10 days). Ultimately, clinicians should select antibiotics based on the patient's history of drug allergy, previous antibiotic exposure, local antibiotic resistance, available medications, and cost. In addition, identifying patients with a high risk of cancer and shared decision-making are also essential for those who have experienced eradication failure.

Update on the second-line treatment of Helicobacter pylori infection: a narrative review.

A standard bismuth quadruple therapy, a fluoroquinolone-containing triple (or quadruple) therapy or a proton pump inhibitor (PPI)-amoxicillin high-dose dual therapy has been recommended as a second-line treatment for Helicobacter pylori infection by the Maastricht VI/Florence Consensus Report. The major shortcoming of levofloxacin-amoxicillin triple therapy is low cure rate for eradicating levofloxacin-resistant strains. With the rising prevalence of levofloxacin-resistant strains, levofloxacin-amoxicillin triple therapy cannot reliably achieve a high eradication rate for second-line treatment of H. pylori infection in most countries now. The present article aims to review current second-line eradication regimens with a per-protocol eradication rate exceeding 85% in most geographic areas. Recently, a novel tetracycline-levofloxacin quadruple therapy consisting of a PPI, bismuth, tetracycline, and levofloxacin for rescue treatment of H. pylori infection has been developed. The new therapy achieved a higher per-protocol eradication rate than levofloxacin-amoxicillin triple treatment in a randomized controlled trial (98% versus 69%). Additionally, the tetracycline-levofloxacin quadruple therapy also exhibits a higher eradication rate than amoxicillin-levofloxacin quadruple therapy. High-dose dual PPI-amoxicillin therapy is another novel second-line treatment for H. pylori infection. The new therapy can achieve an eradication rate of 89% by per-protocol analysis for the second-line treatment in Taiwan. Recently, levofloxacin-based sequential quadruple therapy and potassium-competitive acid blocker have also been applied in the second-line treatment of H. pylori infection. A meta-analysis revealed that a vonoprazan-based regimen has significant superiority over a PPI-based regimen for second-line H. pylori eradication therapy. In conclusion, the eradication rate of levofloxacin-amoxicillin triple therapy is suboptimal in the second-line treatment of H. pylori infection now. Currently, a standard bismuth quadruple therapy (tetracycline-metronidazole quadruple therapy), a tetracycline-levofloxacin quadruple therapy, an amoxicillin-levofloxacin quadruple therapy, a levofloxacin-based sequential quadruple therapy or a high-dose PPI-amoxicillin dual therapy is recommended for the second-line treatment of H. pylori infection.

The Efficacy of Potassium Competitive Acid Blocker-based First-line Triple Therapy on Helicobacter pylori Eradication as Compared to Proton Pump Inhibitor-based Treatment: A Systematic Review and Meta-analysis

Although randomized controlled trials (RCTs) comparing potassium competitive acid blockers (PCABs) and proton-pump inhibitors (PPIs) have been previously conducted, systematic reviews are lacking. In this systematic review and meta-analysis, we searched the CENTRAL, EMBASE, MEDLINE, KMBASE, and KoreaMed databases for relevant RCTs up to October 3, 2020. We assessed the Helicobacter pylori eradication rate of PCAB-based first-line triple therapy and compared it with that of PPI-based therapy. In all five of the included studies comprising a total of 1542 patients, the intervention used was vonoprazan (VPZ)-based therapy, and there were no studies on tegoprazan (TPZ)-based therapy. The pooled risk ratios (RRs) for the eradication rate of VPZ-based therapy as compared to those of PPI-based therapies was 1.17 (95% confidence interval (CI): 1.10–1.26, P<0.00001 for overall effect, I2=41%, P=0.15 for heterogeneity). The RR of VPZ-based therapy compared to that of PPI-based for clarithromycin (CAM)-resistant strains was 1.29 (95% CI: 1.12– 1.48, P<0.0003 for overall effect, I2=0%, P=0.78 for heterogeneity). VPZ-based first-line triple therapy shows a significant H. pylori eradication rate compared to that of the PPI-based. Notably, VPZ-based therapy shows a better eradication rate than that PPI-based therapy, even in patients with CAM-resistant strains.

Effects of Tegoprazan Versus Esomeprazole on Nighttime Heartburn and Sleep Quality in Gastroesophageal Reflux Disease: A Multicenter Double-blind Randomized Controlled Trial.

Patients with gastroesophageal reflux disease (GERD) frequently experience nighttime heartburn and sleep disturbance. Tegoprazan is a new potassium-competitive acid blocker that can rapidly block acid secretion. This study aims to evaluate the efficacy of tegoprazan compared with esomeprazole in relieving nighttime heartburn and sleep disturbances. Patients with erosive esophagitis, nighttime heartburn, and sleep disturbances were randomized to receive tegoprazan 50 mg or esomeprazole 40 mg for 2 weeks. The primary endpoint was time to first nighttime heartburn-free interval. The percentage of nighttime heartburn-free days was also compared between the 2 groups. A total of 46 patients were enrolled in this study. Time to the first nighttime heartburn-free interval was shorter with tegoprazan than with esomeprazole but the difference was not statistically significant (1.5 days vs 3 days, P = 0.151). The percentage of nighttime heartburn-free days was higher in the tegoprazan group but the difference was insignificant (57.8% vs 43.1%, P = 0.107). Adverse events occurred in 2 patients. They were mild in severity. Tegoprazan may induce faster relief of nighttime heartburn symptoms and may improve sleep disorders associated with nighttime heartburn. Further large-scale studies are required to validate our findings.

Prescription changes in patients with gastrointestinal disorders after withdrawal of ranitidine: a nationwide population-based cohort study

Objective Ranitidine products contain unacceptable levels of N-nitrosodimethylamine. This study aimed to investigate changes in the treatment regimen and their influencing factors after the ranitidine recall. Methods This retrospective study used data from nationwide Korean claims from 2019. Patients with gastrointestinal disorders treated with ranitidine for at least a month on 25 September 2019, were selected for this study. Other histamine-2 receptor antagonists (H2RAs), proton pump inhibitors (PPIs), potassium-competitive acid blockers (PCABs), and prostaglandin E1 analogs were administered as alternatives to ranitidine. Kaplan–Meier survival and Cox proportional hazards regression analyses were performed to gauge the time until switching to alternative drugs and assess the influencing factors. Results In total, 7502 patients were included in this study, among which 5164 (68.8%) switched from ranitidine to an alternative drug. The most prescribed alternative drugs were H2RAs, followed by PPIs, PCABs, and prostaglandin E1 analogs. Increasing age; Medical Aid insurance (MedAid); and a history of hypertension, diabetes mellitus, asthma, and osteoarthritis were associated with a higher probability of switching treatments. Patients with concomitant gastroesophageal reflux disease and peptic ulcers were more likely to switch to alternative drugs than patients with gastritis. Conclusions Approximately two-thirds of patients with gastrointestinal disorders switched from ranitidine to alternative drugs within 3 months after ranitidine withdrawal. The Cox regression analysis showed that age (>55 years); insurance type (MedAid); comorbidities, such as hypertension, diabetes mellitus, asthma, and osteoarthritis, and gastrointestinal disorder severity influenced the switch from ranitidine to alternative drugs.

Treatment of Acid-related Diseases Using Potassium-competitive Acid Blockers

Proton pump inhibitors (PPIs) have several limitations to their efficacy including insufficient acid suppression, slow onset of action, and variable efficacy among patients due to CYP2C19 metabolism. Potassium-competitive acid blockers inhibit H+-K+-ATPase in a reversible and K+-competitive manner, are novel acid suppressive drugs with rapid onset of action, meal independence, and prolonged control of intragastric acidity compared to PPIs. Potassium-competitive acid blockers exhibited non-inferior therapeutic efficacies on reflux esophagitis, gastric ulcers, and Helicobacter pylori eradication. The review is focused on the unmet needs across the acid-related diseases and recent updates on clinical studies using vonoprazan and tegoprazan.

Efficacy and Tolerability of 14-Day Tegoprazan- versus Rabeprazole-Based Triple Therapy for Eradication of Helicobacter pylori: A Real-World Evidence Study.

Tegoprazan, a new, fast, and strong potassium-competitive acid blocker, has been approved for the treatment of gastric acid-related diseases in Korea. However, real-world clinical data regarding this drug are scarce. We aimed to compare the Helicobacter pylori eradication rates of tegoprazan- and rabeprazole-based triple therapy. We retrospectively reviewed data from patients who received first-line treatment for H. pylori infection using tegoprazan- or rabeprazole-based triple therapy for 2 weeks (50 mg tegoprazan or 20 mg rabeprazole+1,000 mg amoxicillin+500 mg clarithromycin twice daily). The primary endpoint was the eradication rate as determined by intention-to-treat analysis. Of the 677 patients included in our study, 344 and 333 received tegoprazan-based and rabeprazole-based triple therapy, respectively. The eradication rate from intention-to-treat analysis was 76.7% (95% confidence interval [CI], 72.1% to 81.0%) for tegoprazan-based triple therapy and 75.4% (95% CI, 70.5% to 79.8%) for rabeprazole-based triple therapy. There was no significant difference in the eradication rates between the two groups (p>0.999). Per-protocol analysis also revealed no significant difference between the eradication rates of the two groups (tegoprazan 83.4% [95% CI, 79.0% to 87.2%] vs rabeprazole 83.5% [79.0% to 87.4%], p>0.999). Furthermore, there was no significant difference in adverse event rates between the two groups (tegoprazan, 27.6%; rabeprazole, 25.8%; p=0.604). The eradication rate of tegoprazan-based triple therapy was similar to that of rabeprazole-based triple therapy. Further studies on the dose-escalation effect of tegoprazan for H. pylori eradication and the efficacy of tegoprazan in regimens other than conventional triple therapy are needed.

Laryngopharyngeal Lesion Appeared in a Patient With Eosinophilic Esophagitis

Question: A 52-year-old woman with eosinophilic esophagitis (EoE) stable on the potassium-competitive acid blocker vonoprazan (VPZ) was presented with a cobblestone-like lesion lying between the hypopharynx and the aryepiglottic fold (Figure A). The lesion was found on esophagogastroduodenoscopy (EGD) performed to examine her newly developed mild hemoptysis. The pharynx and larynx were intact 4 months earlier (Figure B). Chest radiography and sputum test for tuberculosis were negative. Her medical condition included dyslipidemia and urticaria. She did not drink alcohol or smoke cigarettes. For further assessment, she was referred to an otorhinolaryngologist, and subsequently the lesion was biopsied with the use of laryngoscopy under general anesthesia. Histologic evaluation found nuclear enlargement with spongiosis in the epithelium cells (Figure C) and remarkable infiltration of inflammatory cells in the subepithelial layer (Figure D). There was insignificant eosinophilia in the biopsies. p53 immunohistochemical staining showed a few positive epithelial cells (Figure E). In addition, enhanced computed tomography found no lymphadenopathy in the neck. On the basis of the findings, the lesion was diagnosed as possible low-grade dysplasia. From then on, she had been closely monitored, in which both the pharyngo-laryngeal lesion and EoE had not changed for 1 year until both conditions exacerbated with newly developed hoarseness. Esophageal biopsy showed increase in intraepithelial eosinophil counts up to 46 per high-power field (Figure F). For deterioration of EoE, topical corticosteroid (200 μg oral fluticasone twice per day) was added to VPZ. Her symptoms gradually improved, and 2 months later a follow-up EGD found significant improvement in not only EoE but also the pharyngo-laryngeal lesion (Figure G). This unexpected response to the treatment led to histologic reassessment of the lesion.

Randomized controlled trial to evaluate the efficacy and safety of fexuprazan compared with esomeprazole in erosive esophagitis

Fexuprazan, a novel potassium-competitive acid blocker, reversibly suppresses the K+/H+-ATPase enzyme in proton pumps within gastric parietal cells. Fexuprazan's suppression of gastric acid was maintained in healthy individuals for 24 h in a dose-dependent manner. To compare fexuprazan to esomeprazole and establish its efficacy and safety in patients with erosive esophagitis (EE). Korean adult patients with endoscopically confirmed EE were randomized 1:1 to receive fexuprazan 40 mg or esomeprazole 40 mg once daily for eight weeks. The primary endpoint was the proportion of patients with healed EE confirmed by endoscopy at week 8. The secondary endpoints included the healing rate of EE at week 4, symptom response, and quality of life assessment. Safety profiles and serum gastrin levels were compared between the groups. Of the 263 randomized, 218 completed the study per protocol (fexuprazan 40 mg, n = 107; esomeprazole 40 mg, n = 111). Fexuprazan was non-inferior to esomeprazole regarding the healing rate at week 8 [99.1% (106/107) vs 99.1% (110/111)]. There were no between-group differences in the EE healing rate at week 4 [90.3% (93/103) vs 88.5% (92/104)], symptom responses, and quality of life assessments. Additionally, serum gastrin levels at weeks 4 and 8 and drug-related side effects did not significantly differ between the groups. Fexuprazan 40 mg is non-inferior to esomeprazole 40 mg in EE healing at week 8. We suggest that fexuprazan is an alternative promising treatment option to PPIs for patients with EE.