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Strategy of proton pump inhibitor (PPI)-resistant gastroesophageal reflux disease (GERD) treatment. (A) Conventional strategy of PPI-resistant GERD treatment (an abridged edition of the Evidence-based Clinical Practice Guidelines for GERD 2015 published by the Japanese Society of Gastroenterology). 29 First choice is double dose PPI therapy. Switching to the other PPI is an option. Addition of prokinetics to PPI is effective in some cases. (B) The authors propose a new strategy of PPI-resistant GERD treatment. First choice is administration of potassium-competitive acid blocker (PCAB) standard dose. Addition of prokinetics to P-CAB may have an additional effect.
Source publication
Proton pump inhibitors are commonly utilized for the treatment of gastric acid-related diseases, such as gastroesophageal reflux disease, peptic ulcer disease, and Helicobacter pylori infection, and for the prevention of low-dose aspirin or nonsteroidal anti-inflammatory drug-induced peptic ulcers. Vonoprazan is a first-in-class potassium-competiti...
Contexts in source publication
Context 1
... tis (Fig. 1B), and 4-week treatment with vonoprazan and 8-week treatment with a PPI were recommended as initial therapies for mild erosive esophagitis and NERD (Fig. 1B). Conventionally, double dose PPI therapy, combination therapy of PPI and H2RA and the addition of a prokinetic agent to PPI were used for PPI- resistant reflux esophagitis (Fig. 2A). 37-40 Vonoprazan seems to be effective for PPI-resistant reflux esophagitis. 41 Twenty-four PPI- resistant reflux esophagitis patients were enrolled in this study and 58.3% had severe erosive esophagitis. In total, 87.5% of the whole patients and 85.7% of severe erosive esophagitis patients achieved endoscopic healing of erosive ...
Context 2
... rescue therapy may also be useful for PPI-resistant reflux esophagitis. 42 Shinozaki et al 43 reported that vonoprazan (10 mg/day; maintenance dose) treat- ment is also effective for PPI-resistant reflux esophagitis. Thus, we believe that the first choice for the treatment of PPI-resistant reflux esophagitis will be vonoprazan in the near future (Fig. 2B). There is no evidence of P-CAB plus prokinetic combination treatment for PPI-resistant reflux esophagitis until now. Further study is needed to additional effect of prokinetics on P-CAB based ...
Similar publications
Background
Vonoprazan, a novel acid-suppressive drug, is non-inferior to proton pump inhibitors (PPIs) for the management of gastric acid-related diseases. However, the safety of vonoprazan has not been systematically evaluated yet.
Objectives
To elucidate the incidence and type of adverse events (AEs) in patients taking vonoprazan.
Design
System...
Citations
... Esomeprazole (Nexium ® ; AstraZeneca, Gothenburg, Mölndal, Sweden) is a PPI whose healing effect was previously documented [26]. Fexuprazan (Fexuclue ® ; Daewoong Pharmaceutical Co., Ltd., Seoul, Korea) is a novel P-CAB [27][28][29][30][31][32][33][34]. According to a preclinical experiment comparing between fexuprazan and vonoprazan, the former was effective in inhibiting acid secretion in a dose-dependent manner and the degree of its inhibitory effect was equivalent to or higher than that of the latter [34]. ...
Background: Fexuprazan (Fexuclue®; Daewoong Pharmaceutical Co., Ltd., Seoul, Korea) is a novel potassium-competitive acid blocker (P-CAB). This multi-center, randomized, double-blind, active-controlled, parallel-group, therapeutic confirmatory, phase III study was conducted to assess its efficacy and safety compared with esomeprazole (Nexium®; AstraZeneca, Gothenburg, Mölndal, Sweden) in Korean patients with erosive esophagitis (EE). Methods: This study evaluated patients diagnosed with EE at a total of 25 institutions in Korea between 13 December 2018 and 7 August 2019. After voluntarily submitting a written informed consent form, the patients were evaluated using a screening test and then randomized to either of the two treatment arms. The proportion of the patients who achieved the complete recovery of mucosal breaks at 4 and 8 weeks, the proportion of those who achieved the complete recovery of heartburn at 3 and 7 days and 8 weeks, and changes in the GERD–Health-Related Quality of Life Questionnaire (GERD-HRQL) scores at 4 and 8 weeks from baseline served as efficacy outcome measures. The incidence of treatment-emergent adverse events (TEAEs) and adverse drug reactions (ADRs) and the serum gastrin levels served as safety outcome measures. Results: The study population comprised a total of 231 patients (n = 231) with EE, including 152 men (65.80%) and 79 women (34.20%); their mean age was 54.37 ± 12.66 years old. There were no significant differences in the efficacy and safety outcome measures between the two treatment arms (p > 0.05). Conclusions: It can be concluded that the efficacy and safety of Fexuclue® are not inferior to those of esomeprazole in Korean patients with EE.
... The impact of the CYP2C19 genotype on the PK and PD characteristics of PPIs varies depending on the contribution of this enzyme to the metabolism of each PPI drug [75]. In first-generation PPIs (omeprazole, lansoprazole, and pantoprazole), CYP2C19 is responsible for more than 80% of their metabolism [81], making these drugs more susceptible to the impact of CYP2C19 genetic variations. The metabolism of the second-generation PPI esomeprazole is less reliant on CYP2C19 compared to omeprazole [82], and is therefore less affected by genetic variations in this enzyme. ...
Proton-pump inhibitors (PPIs) are the most administered first-line treatment for eosinophilic esophagitis (EoE). However, only around half of EoE patients respond histologically to a double dosage of PPI. In addition, 70% of responders maintain EoE in remission after tapering the PPI dose. In order to avoid endoscopy with biopsies—the only accurate method of assessing PPI response—efforts have been made to identify PPI responder patients. The clinical or endoscopic features and biomarkers evaluated so far, however, have not proven to be sufficient in predicting PPI response. Although new approaches based on omics technologies have uncovered promising biomarkers, the specialized and complex procedures required are difficult to implement in clinical settings. Alternatively, PPI pharmacogenetics based on identifying variations in CYP2C19 and STAT6 genes have shown promising results in EoE, and could easily be performed in most laboratories. Other genetic variations have also been associated with PPI response and may explain those cases not related to CYP2C19 or STAT6. Here, we provide an overview of PPI treatment in EoE and evidence of how genetic variations in CYP2C19 and other genes could affect PPI effectiveness, and also discuss studies evaluating the role of pharmacogenetics in predicting PPI response in patients with EoE.
... The better efficacy of vonoprazan vs. lansoprazole could be attributed to the unique pharmacological characteristics of PCABs in achieving better acid suppression. 21,22 Several advantages of PCABs include the stability of the prodrug under acidic conditions, higher affinity towards gastric parietal cells, and its ability to remain pharmacologically active even under neutral conditions. In contrast, PPI such as lansoprazole 15 mg requires an acidic condition to achieve its pharmacologically active state and is also notably less acid-stable, which could significantly reduce its duration of efficacy. ...
Introduction
Proton pump inhibitor (PPI) is the mainstay therapy for the maintenance of healed erosive esophagitis (EE). It is unknown whether potassium‐competitive acid blockers (PCABs) are more efficacious and safer than PPIs.
Methods
Only randomized controlled trials (RCTs) comparing PCABs to PPIs in the maintenance of healing rates of endoscopically proven healed EE and indexed in MEDLINE, EMBASE, and CENTRAL until 3 February 2024, were included. A fixed‐effects model meta‐analysis was performed to pool primary efficacy outcome (maintenance of healing rates at week 24) and safety data (any treatment‐emergent adverse event or TEAE). The risk of bias was assessed using Cochrane's Risk of Bias 2 (RoB2) tool.
Results
Four RCTs with a total of 2554 patients were eligible for inclusion. All trials were of low risk of bias. Compared to lansoprazole 15 mg, the maintenance rates of healed EE at week 24 were significantly higher with vonoprazan 10 mg (RR 1.13; 95% CI 1.07–1.19) and vonoprazan 20 mg (RR 1.15; 95% CI 1.10–1.21). Likewise, compared to lansoprazole 15 mg, any TEAEs were significantly greater with vonoprazan 20 mg (RR 1.10; 95% CI 1.01–1.20) but not vonoprazan 10 mg.
Conclusion
Vonoprazan 10 and 20 mg were superior to lansoprazole 15 mg in the maintenance of the healing of EE. Any TEAEs were greater with vonoprazan 20 mg.
... So, they provide a fast onset of action, delivering their full effect from the very first dose. P-CABs also have a longer plasma half-life compared to PPIs, making them effective in inhibiting nocturnal gastric acid (Sakurai et al., 2015;Mori and Suzuki, 2019). Additionally, the blood drug concentration of P-CABs was not significantly influenced by CYP2C19 gene polymorphism, it makes efficacy monitoring more convenient (Kagami et al., 2016). ...
Background: Lansoprazole, a proton-pump inhibitor (PPI), is the primary therapy for peptic ulcers (PU). Potassium competitive acid blockers (P-CAB) offer an alternative for acid suppression. However, the efficacy and safety of P-CABs versus lansoprazole in the management of PU has not been evaluated.
Methods: Five databases were searched for randomized clinical trials in English until 31 August 2023. Data extraction provided outcome counts for ulcer healing, recurrent NSAID-related ulcer, and adverse events. The pooled effect, presented as rate difference (RD), was stratified by ulcer location, follow-up time, and the types of P-CAB, along with their corresponding 95% confidence intervals (95% CI).
Results: The pooled healing rates of peptic ulcers were 95.3% (1,100/1,154) and 95.0% (945/995) for P-CABs and lansoprazole, respectively (RD: 0.4%, 95% CI: −1.4%–2.3%). The lower bounds of the 95% CI fell within the predefined non-inferiority margin of −6%. In subgroup analyses base on ulcer location, and follow-up time also demonstrated non-inferiority. The drug-related treatment-emergent adverse events (TEAEs) did not differ significantly among groups (RR: 0.997, 95% CI: 0.949–1.046, p = 0.893). However, P-CAB treatment was associated with an increased risk of the serious adverse events compared to lansoprazole (RR: 1.325, 95% CI: 1.005–1.747, p = 0.046).
Conclusion: P-CABs demonstrated non-inferiority to lansoprazole in the management of peptic ulcer. The safety and tolerability profile are comparable, with similar TEAEs rates. However, P-CABs appear to have a higher risk of serious adverse events.
Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=458361 Identifier: PROSPERO (No. CRD42023458361).
... Вонопразан с 2020 года включён в анатомотерапевтическо-химическую классификация (АТХ), в группу «A02BC ИПП», и ему присвоен код A02BC08, а двум комбинациям вонопразана с антимикробными средствами включены в группу «А0BD Комбинации препаратов для эрадикации Helicobacter pylori». Во время проведённых в Японии исследований было установлено, что в рамках тройной эрадикационной терапии первой линии вонопразан обеспечивает лучшую частоту эрадикации НР (около 98%) чем лансопра-зол (примерно 76%) у больных язвенной болезнью желудка и двенадцатиперстной кишки [8]. Аналогично, вонопразан продемонстрировал лучшую частоту эрадикации в комплексе с теми же антибиотиками в рамках терапии второй линии [9]. ...
The article presents data on the results of a comparative study of the clinical and antihelicobacteric efficacy of two schemes of eradication therapy in 60 patients with HP-associated chronic gastritis. The main group of patients received eradication therapy consisting of vonoprazane, amoxicillin, clarithromycin and bismuth tricalium decitrate for 10 days. In the second group of patients with chronic gastritis, esomeprazole was used as an antisecretory drug against the background of similar therapy. The results of the study showed that in the first group of patients, the dynamics of acid suppression under the influence of vonoprasane was significantly higher compared to esomeprazole. Also, in the main group of patients, the rate of eradication of HP infection was 93%, whereas in the group of patients taking esomeprazole, this indicator was 80%.
... Complaints such as heartburn or tightness at night, as well as decreased success of helicobacter pylori eradication, have not been overcome by PPI. 1,2 Potassium competitive acid blockers (P-CAB) are a new class that works differently from proton pump inhibitors (PPIs) by H+/K+-ATPase inhibition. P-CAB has many advantages, including not requiring an acidic atmosphere, faster onset of gastric acid production suppression, more stability in suppressing stomach acid in the long term, and resistance to cytochrome P (CYP)2C19 polymorphism. ...
Proton pump inhibitors (PPIs) are the main therapy for stomach acid disorders to date. The disadvantage of PPI is the difficulty of controlling symptoms at night, such as tightness, chest pain, and coughing cough. Potassium competitive acid blockers (P-CAB) are a new class in the management of stomach acid disorders. Potassium competitive acid blockers work by a different mechanism, which binds non-covalently to H+/K+-ATPase. This mechanism results in a faster, stronger, and long-lasting suppression effect of gastric acid production. Besides being able to cure gastric complaints at night, P-CAB increases the success of Helicobacter pylori eradication. The safety of the use of this P_CAB drug, according to research is quite mild and acceptable. Currently, examples of P-CAB groups on the market are vonoprazan and tegoprazan. This narrative review is intended to provide further insight into this potassium competitive acid blocker (P-CAB) class of drugs.
... We did not study tegoprazan compared to proton pump inhibitors which makes this a limitation to our study. Mori et al. [25] reported that proton pump inhibitors are commonly used to treat gastric acid-related diseases, peptic ulcer disease, and low-dose aspirin or nonsteroidal anti-inflammatory drug-induced peptic ulcers. However, vonoprazan, a first-in-class potassiumcompetitive acid blocker, has unique benefits over other traditional proton pump inhibitors due to its strong acid suppression capabilities. ...
... However, vonoprazan, a first-in-class potassiumcompetitive acid blocker, has unique benefits over other traditional proton pump inhibitors due to its strong acid suppression capabilities. As a result, vonoprazan is an effective treatment for gastroesophageal reflux disease and Helicobacter pylori infection [25]. We did not study vonoprazan compared to proton pump inhibitors which makes this a limitation to our study. ...
Aim
To compare the efficacy and safety of Lansoprazole plus Levosulpiride over esomeprazole.
Methodology
This randomized control trial recruited 1000 participants having symptomatic gastroesophageal reflux disease (GERD) and erosive esophagitis and they were blindly randomized into two groups in 1:1 ratio with appropriate concealment. Group 1 was given lansoprazole plus Levosulpiride combination twice daily whereas group 2 was prescribed only esomeprazole twice daily. The primary efficacy endpoint was healing of erosive esophagitis and GERD at week 49. Secondary assessments included improvement in quality of life. Participants’ quality of life was assessed before starting the treatment and post treatment using short form health survey questionnaire (SF-36).
Results
Lansoprazole plus levosulpiride group had significantly lower rates of positive post-intervention GERD and erosive esophagitis status, and higher rates of sustained resolution of heartburn compared to the esomeprazole alone group. However, the lansoprazole plus levosulpiride group also had a higher risk of nausea.
Conclusion
Lansoprazole plus levosulpiride is a more effective and safe treatment for GERD than Esomeprazole alone. Participants in the Lansoprazole plus levosulpiride group showed a significantly higher rate of sustained resolution of GERD, lower rates of post-intervention GERD and erosive esophagitis status and a higher incidence of nausea compared to the Esomeprazole alone group. Although quality of life worsened in both groups, adverse effects did not significantly differ. These findings strongly support the use of Lansoprazole plus levosulpiride as a preferred treatment option for GERD and erosive esophagitis, which could have significant clinical implications for managing this common condition.
... P-CABs like vonoprazan and tegoprazan are prominent examples. Vonoprazan is effective in treating GERD and H. pylori infection and shows rapid onset and an extended half-life [63][64][65]. Intermittent use of P-CABs is preferred in managing reflux esophagitis [66]. Acid suppression is the primary therapy for erosive esophagitis (EE). ...
Gastroesophageal Reflux Disease (GERD) is a chronic ailment that results from the backward flow of stomach acid into the esophagus, causing heartburn and acid regurgitation. This review explores nanotechnology as a novel treatment approach for GERD. Chitosan nanoparticles (CSNPs) offer several advantages, including biocompatibility, biodegradability, and targeted drug delivery capabilities. CSNPs have been extensively studied due to their ability to encapsulate and release medications in a controlled manner. Different nanoparticle (NP) delivery systems, including gels, microspheres, and coatings, have been developed to enhance drug retention, drug targeting, and controlled release in the esophagus. These nanoparticles can target specific molecular pathways associated with acid regulation, esophageal tissue protection, and inflammation modulation. However , the optimization of nanoparticle formulations faces challenges, including ensuring stability, scalability, and regulatory compliance. The future may see CSNPs combined with other treatments like proton pump inhibitors (PPIs) or mucosal protectants for a synergistic therapeutic approach. Thus, CSNPs provide exciting opportunities for novel GERD treatment strategies.
... Like PPIs, PCABs target the H + /K + ATPase transporter located on the luminal membrane of parietal cells to inhibit gastric acid production [27]. Whereas PPIs inhibit the H + /K + ATPase enzyme system itself, PCABs competitively block the K + binding site of the gastric H + /K + -ATPase [28]. ...
Purpose of Review
Refractory GERD (rGERD) is a common condition with a significant and costly impact on patients and healthcare systems alike. As such, it is imperative to understand the tools available to diagnose and treat rGERD.
Recent Findings
In this review, the modalities used to diagnose rGERD are discussed in detail, including esophagogastroduodenoscopy (EGD) and ambulatory reflux monitoring (the “gold standard”). The adjunctive role of high-resolution esophageal manometry (HREM) is also addressed. A comprehensive discussion of the various treatment options is provided, including lifestyle modifications, pharmacotherapy, endoscopic therapies, and surgical options. Promising emerging therapies are explored. Management of concomitant functional esophageal disorders is also discussed.
Summary
We review the current diagnostic and management algorithms for the management of rGERD and provide insight into emerging therapies.
... В настоящее время эта группа представлена главным образом препаратами вонопразан (В) и тегопразан (Т) (а также их комбинациями с антибиотиками в рамках эрадикационной терапии), кроме того, ряд аналогов проходит различные фазы клинических испытаний. Первый препарат этой группы ревопразан не продемонстрировал преимуществ перед ИПП и практически не используется [2], а информация о недавно полученном фексупразане сводится пока к единичным сообщениям [3]. ...
Purpose. To summarize the estimates of the effect of the use of potassium-competitive proton pump inhibitors in pharmacotherapy algorithms for patients with peptic ulcer disease, GERD on treatment outcomes. Material and methods. The most large-scale (as a rule) publications of the last five years devoted to the problem under consideration are analyzed. The search was carried out by keywords in the Pubmed information database (ncbi.nlm.nih.gov). Findings. Potassium-competitive acid blockers (P-CABs), in comparison with «traditional» drugs of this class (proton pump inhibitors), have advantages from a clinical and pharmacoeconomic point of view both in peptic ulcer disease (in particular, as part of eradication therapy) and in gastro-esophageal reflux disease. Confirmation of these data in the conditions of use of K-CCB in patients of the Russian Federation seems appropriate.
