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Fung S. Vonoprazan: A Review in Erosive Esophagitis and Non-Erosive Gastro-Esophageal Reflux Disease. Drugs 2025:10.1007/s40265-025-02193-x. [PMID: 40388079 DOI: 10.1007/s40265-025-02193-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/17/2025] [Indexed: 05/20/2025]
Abstract
Vonoprazan (Voquezna®) is a potassium-competitive acid blocker (PCAB) with improved pharmacodynamic and pharmacokinetic properties compared with proton-pump inhibitors (PPIs) that allow for stronger control of gastric acid with once-daily oral administration and no requirement to be taken in relation to timing of meals for optimal efficacy. In the USA, vonoprazan has been approved as a first-in-class treatment for healing and maintenance of healing of erosive esophagitis, and for relief of heartburn in adult patients with erosive esophagitis and non-erosive gastro-esophageal reflux disease (GERD). In pivotal phase III trials, vonoprazan was non-inferior to the PPI lansoprazole in healing and superior to lansoprazole in maintenance of healing of erosive esophagitis, and was superior to placebo for treating heartburn in US patients with non-erosive GERD. Vonoprazan was generally well tolerated; the most common adverse events included abdominal pain, constipation, diarrhea, nausea, and dyspepsia. Vonoprazan is, therefore, a valuable addition to the therapies available for adults with erosive esophagitis and non-erosive GERD.
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Affiliation(s)
- Simon Fung
- Springer Nature, Private Bag 65901, Mairangi Bay, Auckland, 0754, New Zealand.
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2
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Hossa K, Małecka-Wojciesko E. Advances in Gastroesophageal Reflux Disease Management: Exploring the Role of Potassium-Competitive Acid Blockers and Novel Therapies. Pharmaceuticals (Basel) 2025; 18:699. [PMID: 40430518 PMCID: PMC12115254 DOI: 10.3390/ph18050699] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2025] [Revised: 04/29/2025] [Accepted: 05/06/2025] [Indexed: 05/29/2025] Open
Abstract
Gastroesophageal reflux disease (GERD) is a prevalent chronic gastrointestinal disorder that affects a substantial proportion of the global population. It is characterized by the extensive backward flow of stomach contents into the esophagus, leading to troublesome symptoms and potential complications. Proton pump inhibitors (PPIs) have long been the cornerstone of pharmacological treatment for GERD, effectively suppressing gastric acid secretion. However, a substantial subset of patients, referred to as PPI-refractory GERD, experience inadequate symptom control despite optimal PPI therapy. GERD significantly impacts patients' quality of life, affecting domains, such as vitality, pain, and physical functioning. Consequently, there is an urgent need for alternative therapeutic strategies and novel pharmacologic agents to provide more effective, long-term relief. Emerging treatment options include potassium-competitive acid blockers (PCABs) like vonoprazan, which offer more potent and sustained inhibition of gastric acid secretion compared to traditional PPIs. Additionally, prokinetic agents such as itopride have gained attention due to their potential to improve GERD symptoms by enhancing gastrointestinal motility and accelerating gastric emptying. This article reviews the mechanisms of action, clinical efficacy, and potential of these novel therapeutic approaches in improving patient outcomes in GERD management. With the growing prevalence of PPI resistance and side effects, a personalized, multifaceted approach to treatment is becoming increasingly necessary to optimize care for patients with GERD.
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Affiliation(s)
| | - Ewa Małecka-Wojciesko
- Department of Digestive Tract Diseases, Medical University of Lodz, 90-419 Lodz, Poland;
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3
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Zhu B, Chen L, Tao X, Zheng H, Li X, Wu Q, Long E, Lin H. Current research status and trends of potassium-competitive acid blockers in the treatment of acid-related diseases: a bibliometric analysis. Front Pharmacol 2025; 15:1477633. [PMID: 39840081 PMCID: PMC11747516 DOI: 10.3389/fphar.2024.1477633] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2024] [Accepted: 12/16/2024] [Indexed: 01/23/2025] Open
Abstract
Objective To explore the current research status and trends of potassium-competitive acid blockers (P-CABs) in the treatment of acid related diseases (ARDs) using bibliometric analysis. Materials and methods We collected publications related to P-CAB in the treatment of acid-related diseases in the Web of Science (WOS) Core Collection from the establishment of the database to 30 June 2024. We evaluated the publication volume and citation status over the years using the WOS platform, and visualized the authors, countries, institutions, keywords, and citations of the publications using CiteSpace and VOSviewer. Results This study included a total of 455 articles. The number of publications and citations related to research has been increasing year by year. The results show that the scholars with the highest number of publications mainly come from South Korea and Japan. Scholars such as Geun Seog Song, Bongtae Kim, and Nobuhiro Inatomi produced many works in related fields. The most popular drug in this field was vonoprazan, and research on this drug mainly focused on the effectiveness and safety evaluation of ARDs such as Helicobacter pylori infection, gastroesophageal reflux disease, peptic ulcers, etc. Researchers were concerned about the evaluation of treatment regimens and efficacy comparison between P-CABs and traditional proton pump inhibitors (PPIs) in the treatment of ARDs. At the same time, researchers are also closely monitoring the potential adverse reactions and long-term adverse outcomes of clinical application of P-CABs for ARDs. Conclusion The clinical application of P-CABs, represented by vonoprazan, in ARDs is receiving widespread attention from researchers. The exploration of the application of this type of drug in ARDs is constantly expanding, and it is a research field with great clinical value and research potential.
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Affiliation(s)
- Baoqiang Zhu
- Department of Pharmacy, The First People’s Hospital of Shuangliu District, West China (Airport) Hospital of Sichuan University, Chengdu, China
| | - Long Chen
- Department of Pharmacy, The First People’s Hospital of Shuangliu District, West China (Airport) Hospital of Sichuan University, Chengdu, China
| | - Xue Tao
- Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Academy of Medical Sciences and Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Hong Zheng
- Department of Pharmacy, The First People’s Hospital of Shuangliu District, West China (Airport) Hospital of Sichuan University, Chengdu, China
| | - Xia Li
- Department of Pharmacy, The First People’s Hospital of Shuangliu District, West China (Airport) Hospital of Sichuan University, Chengdu, China
| | - Qingfang Wu
- Department of Pharmacy, The First People’s Hospital of Shuangliu District, West China (Airport) Hospital of Sichuan University, Chengdu, China
| | - Enwu Long
- Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Academy of Medical Sciences and Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Haixia Lin
- Department of Pharmacy, The First People’s Hospital of Shuangliu District, West China (Airport) Hospital of Sichuan University, Chengdu, China
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Marabotto E, Calabrese F, Pasta A, Visaggi P, de Bortoli N, Mari A, Tolone S, Ghisa M, Bertin L, Savarino V, Savarino EV. Evaluating Vonoprazan for the treatment of erosive GERD and heartburn associated with GERD in adults. Expert Opin Pharmacother 2024; 25:2319-2325. [PMID: 39503620 DOI: 10.1080/14656566.2024.2427335] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2024] [Accepted: 11/05/2024] [Indexed: 11/12/2024]
Abstract
INTRODUCTION Gastroesophageal reflux disease (GERD) is a common debilitating chronic disease presenting in two main forms based on esophageal mucosal appearance, the erosive reflux disease (ERD) and the non-erosive reflux disease (NERD). Acid secretion is a key factor in the disease pathogenesis and management. Potent acid-suppressant drugs have been manufactured since the mid of 1970s, initially with histamine-H2-receptors antagonists, and later, inhibitors of the proton pump (H+-K+-ATPase).More recently, potassium-competitive acid blockers (p-CABs), particularlyVonoprazan, have been introduced. Vonoprazan has shown high efficacy and safety profiles and exhibits several advantages that allow to overcome shortcomings of proton pump inhibitors (PPIs). AREAS COVERED In this review, we provide an updated summary of Vonoprazan pharmacodynamics and its role in clinical practice for the management of erosive esophagitis and GERD-related heartburn. Moreover, we discuss characteristics of Vonoprazan that allow to bypass some limitations of the older PPIs. EXPERT OPINION Long-term safety and efficacy of Vonoprazan have already been demonstrated for the induction and maintenance of ERD, preventing nocturnal acid breakthrough, reducing reflux symptoms in non-responder to standard therapy. Ongoing and future studies are expected to further elucidate its long-term benefits and potential applications in other acid-related disorders.
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Affiliation(s)
- Elisa Marabotto
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy
- Gastroenterology Unit, Department of Internal Medicine, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Francesco Calabrese
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy
- Gastroenterology Unit, Department of Internal Medicine, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Andrea Pasta
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy
- Gastroenterology Unit, Department of Internal Medicine, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Pierfrancesco Visaggi
- Gastroenterology Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Nicola de Bortoli
- Gastroenterology Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Amir Mari
- Gastroenterology Unit, Nazareth Hospital EMMS, Azrieli Faculty of Medicine, Bar Ilan University, Ramat Gan, Israel
| | - Salvatore Tolone
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Matteo Ghisa
- Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy
- Gastroenterology Unit, Azienda Ospedale Università Padova, Padova, Italy
| | - Luisa Bertin
- Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy
- Gastroenterology Unit, Azienda Ospedale Università Padova, Padova, Italy
| | - Vincenzo Savarino
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy
- Gastroenterology Unit, Department of Internal Medicine, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Edoardo Vincenzo Savarino
- Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy
- Gastroenterology Unit, Azienda Ospedale Università Padova, Padova, Italy
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Simadibrata DM, Lesmana E, Lee YY. Experimental drugs for erosive esophagitis: what is in the clinical development pipeline? Expert Opin Investig Drugs 2024; 33:1009-1018. [PMID: 39152730 DOI: 10.1080/13543784.2024.2393868] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2023] [Revised: 08/05/2024] [Accepted: 08/14/2024] [Indexed: 08/19/2024]
Abstract
INTRODUCTION Proton pump inhibitor (PPI) has revolutionized the treatment of erosive esophagitis (EE) in the past few decades. However, roughly 30-40% of the patients, especially those with severe EE (Los Angeles Grade C/D), remain poorly responsive to this medication. Novel drugs have been formulated and/or repurposed to address this problem. AREAS COVERED This review highlights novel drugs that have been investigated for use in EE, such as mucosal protectants, prokinetics, transient lower esophageal sphincter relaxation (TLESR) reducers, novel PPIs, and the new potassium-competitive acid blocker (PCAB). Studies have demonstrated that PCAB has promising results (efficacy and safety) compared to PPI for the healing of EE, especially in severe diseases. EXPERT OPINION PCAB has gained interest in recent years, with pharmacokinetics and pharmacodynamics properties surpassing PPI. Although recent data on PCABs, which comprised mainly of Vonoprazan, have shown promising results, more randomized controlled trials for other PCAB drugs are needed to elucidate and confirm the superiority of this drug class to PPI, the current first-line treatment of EE.
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Affiliation(s)
- Daniel Martin Simadibrata
- Department of Medicine, MetroHealth Medical Center, Case Western Reserve University, Cleveland, OH, USA
- Medicine, Universitas Indonesia, Jakarta, Indonesia
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Elvira Lesmana
- Medicine, Universitas Indonesia, Jakarta, Indonesia
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Yeong Yeh Lee
- School of Medical Sciences, Universiti Sains Malaysia, Kota Bharu, Malaysia
- GI Function and Motility Unit, Hospital USM, Kota Bharu, Malaysia
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Ochiai Y, Ito S, Kikuchi D, Hoteya S. Long-term endoscopic change of gastric polyp associated with administration of vonoprazan. Clin J Gastroenterol 2024; 17:598-601. [PMID: 38575803 DOI: 10.1007/s12328-024-01961-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2023] [Accepted: 03/18/2024] [Indexed: 04/06/2024]
Abstract
Vonoprazan (VPZ) has been available in Japan since 2015. Endoscopic features of proton-pump inhibitor (PPI)-related gastric mucosal changes, including fundic gland and hyperplastic polyps, have been observed. However, the relationship between gastric polyps and VPZ remains unclear. A 65-year-old man with reflux esophagitis-associated symptoms refractory to PPI was referred to our hospital. VPZ (20 mg) was administered for 3 weeks, which proved effective. Afterward, VPZ dose was reduced to 10 mg; the reflux symptoms worsened, and 20 mg VPZ was restarted. Afterward, esophagogastroduodenoscopy (EGD) revealed a gradually enlarging gastric polyp in the cardia. After 5 years of VPZ administration, the patient developed a reddish polyp (approximately 10 mm) with a whitish substance in the cardia. Based on the clinical course, the polyp was considered to have enlarged because of the long-term VPZ administration. After being informed of the endoscopic findings, the patient decided to discontinue VPZ. One year after VPZ discontinuation, EGD revealed a shrunken polyp (5 mm). Long-term acid suppression causes hypergastrinemia, which may lead to gastric mucosal changes, including gastric polyps. There are few case reports of a decrease in the number and size of gastric polyps after VPZ discontinuation. Hence, some VPZ-induced endoscopic changes may be reversible.
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Affiliation(s)
- Yorinari Ochiai
- Department of Gastroenterology, Toranomon Hospital, Tokyo, 105-8470, Japan.
| | - Shinji Ito
- Department of Pathology, Toranomon Hospital, Tokyo, Japan
| | - Daisuke Kikuchi
- Department of Gastroenterology, Toranomon Hospital, Tokyo, 105-8470, Japan
| | - Shu Hoteya
- Department of Gastroenterology, Toranomon Hospital, Tokyo, 105-8470, Japan
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7
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Zhang N, Han M, Zheng QW, Zhang MY, Zhi WL, Li JJ, Cui LX, Tian JL, Wang Y, Fang SQ. A scientometrics analysis and visualization of refractory gastroesophageal reflux disease. Front Pharmacol 2024; 15:1393526. [PMID: 39139634 PMCID: PMC11319146 DOI: 10.3389/fphar.2024.1393526] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2024] [Accepted: 07/18/2024] [Indexed: 08/15/2024] Open
Abstract
Background Refractory gastroesophageal reflux disease (refractory GERD) is a heterogeneous disease characterized by unresponsiveness or poor efficacy to proton-pump inhibitors (PPIs). This chronic disorder substantially weakens patients' mental wellbeing and quality of life, increasing the financial burden on society. Multiple articles have been reported in this area. However, literature involving scientometric analysis of refractory GERD is absent. Therefore, it is necessary to understand the evolution of research themes and the main hotspots of refractory GERD through bibliometric methods. Methods All documents related to refractory GERD based on the WOS Core Collection from January 2000 to November 2023 were selected for analysis. Citespace V 6.1 R6, VOSviewer V 1.6.20, and Scimago Graphica V 1.0.38 were used to perform bibliometric analysis. Results We collected a total of 241 research articles from 36 countries and 322 institutions, contributed by over 1,000 authors. Over the last 20 years, the number of articles in this field has increased year by year, and since 2011, the number of publications has increased dramatically, with 85.89% of the papers. These countries are led by the United States and Japan. GUT had the highest number of citations and DIGESTION had the highest number of publications. Research on standardized diagnosis and management, mechanisms, novel monitoring methods, and innovative drugs and procedures for refractory GERD are the main topics and hotspots in this field. This study also found that neuroimmune interaction is closely related to refractory GERD, which may be a new direction for future mechanism research. Conclusion Our study is the first bibliometric analysis of the global literature on refractory GERD. This research provides valuable insights for researchers, enabling them to quickly understand the research frontier and hot topics of this field.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | - Sheng-Quan Fang
- Department of Gastroenterology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
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Seo S, Jung HK, Gyawali CP, Lee HA, Lim HS, Jeong ES, Kim SE, Moon CM. Treatment Response With Potassium-competitive Acid Blockers Based on Clinical Phenotypes of Gastroesophageal Reflux Disease: A Systematic Literature Review and Meta-analysis. J Neurogastroenterol Motil 2024; 30:259-271. [PMID: 38972863 PMCID: PMC11238110 DOI: 10.5056/jnm24024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2024] [Revised: 03/30/2024] [Accepted: 04/10/2024] [Indexed: 07/09/2024] Open
Abstract
Background/Aims Gastroesophageal reflux disease (GERD) is typically managed based on the clinical phenotype. We evaluated the efficacy and safety of potassium-competitive acid blockers (PCABs) in patients with various clinical GERD phenotypes. Methods Core databases were searched for studies comparing PCABs and proton pump inhibitors (PPIs) in clinical GERD phenotypes of erosive reflux disease (ERD), non-erosive reflux disease (NERD), PPI-resistant GERD and night-time heartburn. Additional analysis was performed based on disease severity and drug dosage, and pooled efficacy was calculated. Results In 9 randomized controlled trials (RCTs) evaluating the initial treatment of ERD, the risk ratio for healing with PCABs versus PPIs was 1.09 (95% CI, 1.04-1.13) at 2 weeks and 1.03 (95% CI, 1.00-1.07) at 8 weeks, respectively. PCABs exhibited a significant increase in both initial and sustained healing of ERD compared to PPIs in RCTs, driven particularly in severe ERD (Los Angeles grade C/D). In 3 NERD RCTs, PCAB was superior to placebo in proportion of days without heartburn. Observational studies on PPI-resistant symptomatic GERD reported symptom frequency improvement in 86.3% of patients, while 90.7% showed improvement in PPIresistant ERD across 5 observational studies. Two RCTs for night-time heartburn had different endpoints, limiting meta-analysis. Pronounced hypergastrinemia was observed in patients treated with PCABs. Conclusions Compared to PPIs, PCABs have superior efficacy and faster therapeutic effect in the initial and maintenance therapy of ERD, particularly severe ERD. While PCABs may be an alternative treatment option in NERD and PPI-resistant GERD, findings were inconclusive in patients with night-time heartburn.
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Affiliation(s)
- Seungyeon Seo
- Department of Internal Medicine, College of Medicine, Ewha Womans University, Seoul, Korea
| | - Hye-Kyung Jung
- Department of Internal Medicine, College of Medicine, Ewha Womans University, Seoul, Korea
| | - C Prakash Gyawali
- Division of Gastroenterology, Washington University School of Medicine, St. Louis, MO, USA
| | - Hye Ah Lee
- Clinical Trial Center, Mokdong Hospital, Ewha Womans University, Seoul, Korea
| | - Hyung Seok Lim
- Department of Internal Medicine, College of Medicine, Ewha Womans University, Seoul, Korea
| | - Eui Sun Jeong
- Department of Internal Medicine, College of Medicine, Ewha Womans University, Seoul, Korea
| | - Seong Eun Kim
- Department of Internal Medicine, College of Medicine, Ewha Womans University, Seoul, Korea
| | - Chang Mo Moon
- Department of Internal Medicine, College of Medicine, Ewha Womans University, Seoul, Korea
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Xue C, Du Y, Yang H, Jin H, Zhao Y, Ren B, Dong Z. Evaluating vonoprazan and tegoprazan for gastroesophageal reflux disease treatment in Chinese Healthcare: an EVIDEM framework analysis. BMC Gastroenterol 2024; 24:208. [PMID: 38902604 PMCID: PMC11188247 DOI: 10.1186/s12876-024-03297-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2024] [Accepted: 06/14/2024] [Indexed: 06/22/2024] Open
Abstract
BACKGROUND In Chinese healthcare settings, drug selection decisions are predominantly influenced by the Pharmacy & Therapeutics Committee (PTC). This study evaluates two recently introduced potassium-competitive acid blockers, vonoprazan (VPZ) and tegoprazan (TPZ), utilizing the Evidence and Value: Impact on DEcisionMaking (EVIDEM) framework. METHODS The study employed the 10th edition of EVIDEM, which includes a core model with five domains and 13 criteria. Two independent expert panels were involved: the PTC expert panel, tasked with assigning weights using a 5-point scale, defining scoring indicators, examining the evidence matrix, scoring, and decision-making; and the evidence matrix expert panel, responsible for conducting a systematic literature review, creating the evidence matrix, and evaluating the value contributions of VPZ and TPZ. RESULTS The analysis estimated the value contributions of VPZ and TPZ to be 0.59 and 0.54, respectively. The domain of 'economic consequences of intervention' showed the most significant variation in value contribution between the two drugs, followed by 'comparative outcomes of intervention' and 'type of benefit of intervention'. CONCLUSION Employing the EVIDEM framework, VPZ's value contribution was found to be marginally superior to that of TPZ. The EVIDEM framework demonstrates potential for broader application in Chinese medical institutions.
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Affiliation(s)
- Chaojun Xue
- Hebei General Hospital, Shijiazhuang, Hebei Province, China
- Hebei Key Laboratory of Clinical Pharmacy, Shijiazhuang, Hebei Province, China
| | - Yuhan Du
- Hebei General Hospital, Shijiazhuang, Hebei Province, China
| | - Haotian Yang
- Hebei General Hospital, Shijiazhuang, Hebei Province, China
- Hebei Key Laboratory of Clinical Pharmacy, Shijiazhuang, Hebei Province, China
| | - Huixin Jin
- Hebei General Hospital, Shijiazhuang, Hebei Province, China
- Hebei Key Laboratory of Clinical Pharmacy, Shijiazhuang, Hebei Province, China
| | - Yue Zhao
- Hebei General Hospital, Shijiazhuang, Hebei Province, China
- Hebei Key Laboratory of Clinical Pharmacy, Shijiazhuang, Hebei Province, China
| | - Bingnan Ren
- Hebei General Hospital, Shijiazhuang, Hebei Province, China
- Hebei Key Laboratory of Clinical Pharmacy, Shijiazhuang, Hebei Province, China
| | - Zhanjun Dong
- Hebei General Hospital, Shijiazhuang, Hebei Province, China.
- Hebei Key Laboratory of Clinical Pharmacy, Shijiazhuang, Hebei Province, China.
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Bandyopadhyay S, Verma P, Samajdar SS, Das S. Vonoprazan causes symptomatic improvement in non-erosive gastroesophageal reflux disease: A systematic review and meta-analysis. Clin Res Hepatol Gastroenterol 2024; 48:102373. [PMID: 38719148 DOI: 10.1016/j.clinre.2024.102373] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2024] [Revised: 04/29/2024] [Accepted: 05/05/2024] [Indexed: 05/21/2024]
Abstract
OBJECTIVE To evaluate the efficacy and safety of vonoprazan therapy as compared to conventional proton pump inhibitors (PPIs) or no vonoprazan for non-erosive esophagitis. METHODS A thorough search was conducted across databases. The primary outcome was to determine the mean variance in the gastroesophageal reflux disease (GERD) score after vonoprazan treatment. Secondary outcomes comprised alterations in the scores for epigastric pain and post-prandial distress, the proportion of patients displaying improvement, and the occurrence of adverse events. Pooled mean differences and relative risks were determined utilizing random effects models. RESULTS A total of 1,944 articles were screened and nine of them were included. As compared to PPI or no vonoprazan therapy, vonoprazan treatment led to a significant reduction in the GERD score [mean difference: -3.88 (95 % CI: -5.48, -2.28), p < 0.01, i2=95 %]. As compared to PPI or no vonoprazan therapy, vonoprazan treatment led to a significant reduction in the epigastric pain score [mean difference: -3.02 (95 % CI: -5.41, -0.63), p = 0.01, i2=75 %] and post-prandial distress score [mean difference: -2.82 (95 % CI: -3.51, -2.12), p < 0.01, i2=0 %] (all moderate GRADE evidence). Vonoprazan therapy was found to be safe. CONCLUSION Treatment with vonoprazan could significantly improve symptoms in patients with non-erosive esophagitis or non-erosive GERD.
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Affiliation(s)
| | - Pooja Verma
- Department of Emergency Medicine, Himalayan Institute of Medical Sciences, Dehradun, India
| | - Shambo Samrat Samajdar
- Department of Clinical and Experimental Pharmacology, Calcutta School of Tropical Medicine, Kolkata, India
| | - Saibal Das
- Indian Council of Medical Research - Centre for Ageing and Mental Health, Kolkata, India; Department of Global Public Health, Karolinska Institutet, Stockholm, Sweden
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11
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Simadibrata DM, Lesmana E, Fass R. A systematic review and meta-analysis of the efficacy of vonoprazan for proton pump inhibitor-resistant gastroesophageal reflux disease. J Gastroenterol Hepatol 2024; 39:796-805. [PMID: 38263507 DOI: 10.1111/jgh.16475] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2023] [Accepted: 12/18/2023] [Indexed: 01/25/2024]
Abstract
BACKGROUND AND AIM Up to 40% of gastroesophageal reflux disease (GERD) patients experience inadequate symptom relief with a proton pump inhibitor (PPI), termed PPI-resistant or refractory GERD. Vonoprazan, a potassium-competitive acid blocker, has better efficacy than PPI in suppressing gastric acid secretion. This meta-analysis summarizes the efficacy and safety of vonoprazan for treating PPI-resistant GERD (both erosive esophagitis [EE] and non-erosive reflux disease [NERD]). METHODS Four electronic databases (Medline, Embase, SCOPUS, and CENTRAL) were searched for studies indexed until August 1, 2023. Both observational studies and clinical trials assessing the efficacy and safety of vonoprazan in PPI-resistant GERD were included. Efficacy outcomes included healing and maintenance rates of EE and improvement of the Frequency Scale for Symptoms of GERD (FSSG) scores. Serious adverse events (SAEs) were considered a safety outcome. The modified Newcastle-Ottawa Scale (NOS) was used to assess study quality. RESULTS Twelve studies were included in this meta-analysis. Healing rates of PPI-resistant EE with vonoprazan 20 mg were 91.7% (95% CI 86.8-94.8%) and 88.5% (95% CI 69.7-96.2%) at weeks 4 and 8, respectively. For healed PPI-resistant EE, the overall maintenance rates with vonoprazan 10 mg were 82.6% (95% 61.2-95.0%) at week 8, 86.0% (95% CI 72.1-94.7%) at week 24, and 93.8% (95% CI 69.8-99.8%) at week 48. FSSG scores were improved in 74.6% (95% CI 65.8-81.7%) and 51.9% (95% CI 37.8-65.7%) of patients at weeks 4 and 8. Overall, no SAE was reported. CONCLUSION Vonoprazan demonstrated high efficacy in the healing and maintenance of PPI-resistant EE and moderate efficacy for the improvement of FSSG score. Vonoprazan was well tolerated in PPI-resistant GERD patients.
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Affiliation(s)
- Daniel Martin Simadibrata
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
- Nuffield Department of Population Health, University of Oxford, Oxford, UK
| | - Elvira Lesmana
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
- Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
| | - Ronnie Fass
- Division of Gastroenterology and Hepatology, MetroHealth Medical System, Case Western Reserve University, Cleveland, OH, USA
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12
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Hoshino S, Momma E, Motomiya R, Tanabe T, Koeda M, Hoshikawa Y, Kawami N, Iwakiri K. Characteristics of proton pump inhibitor-resistant severe reflux esophagitis and efficacy of vonoprazan in elderly (older than 75 years) and non-elderly groups. JGH Open 2024; 8:e13023. [PMID: 38268954 PMCID: PMC10805484 DOI: 10.1002/jgh3.13023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2023] [Revised: 11/29/2023] [Accepted: 12/06/2023] [Indexed: 01/26/2024]
Abstract
Background and Aim Previous studies on age differences in proton pump inhibitor (PPI)-resistant reflux esophagitis (RE) have found that stenosis and bleeding complications were significantly more common in the elderly than in the non-elderly. We sought to examine differences between two groups of elderly (75 years or older) and non-elderly (<75 years) patients with (PPI)-resistant severe RE and also the efficacy of vonoprazan (VPZ) in these patients. Methods There were 14 patients in the elderly group and 15 in the non-elderly group. Information was obtained on patient background (sex, body mass index [BMI], gastric mucosal atrophy, and the presence of hernia and collagen disease), and all patients underwent the saliva secretion test and esophagogastroduodenoscopy (EGD). The saliva secretion test (amount of saliva secreted, salivary pH, and the acid-buffering capacity) was performed by chewing sugar-free gum for 3 min before EGD. The efficacy of VPZ in both groups was also assessed. Results Saliva secretion, sex, BMI, and the presence of gastric mucosal atrophy did not significantly differ between the two groups. The number of hernias larger than 4 cm was significantly higher in the elderly PPI-resistant group, and significantly more patients had collagen disease in the non-elderly group. The efficacy of VPZ was not significantly different between the two groups; however, 10 patients in the non-elderly group had collagen disease, and 4 did not achieve esophageal mucosal healing even with VPZ 20 mg. Conclusion The number of large hernias (>4 cm) was significantly higher in the elderly group, while significantly more non-elderly patients had collagen disease. In the non-elderly group with scleroderma, the efficacy of VPZ 20 mg may not be sufficient.
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Affiliation(s)
- Shintaro Hoshino
- Department of Gastroenterology, Nippon Medical SchoolGraduate School of MedicineBunkyo‐kuTokyoJapan
| | - Eri Momma
- Department of Gastroenterology, Nippon Medical SchoolGraduate School of MedicineBunkyo‐kuTokyoJapan
| | - Rina Motomiya
- Department of Gastroenterology, Nippon Medical SchoolGraduate School of MedicineBunkyo‐kuTokyoJapan
| | - Tomohide Tanabe
- Department of Gastroenterology, Nippon Medical SchoolGraduate School of MedicineBunkyo‐kuTokyoJapan
| | - Mai Koeda
- Department of Gastroenterology, Nippon Medical SchoolGraduate School of MedicineBunkyo‐kuTokyoJapan
| | - Yoshimasa Hoshikawa
- Department of Gastroenterology, Nippon Medical SchoolGraduate School of MedicineBunkyo‐kuTokyoJapan
| | - Noriyuki Kawami
- Department of Gastroenterology, Nippon Medical SchoolGraduate School of MedicineBunkyo‐kuTokyoJapan
| | - Katsuhiko Iwakiri
- Department of Gastroenterology, Nippon Medical SchoolGraduate School of MedicineBunkyo‐kuTokyoJapan
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13
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He J, Gao Y, Bai G, Wang J, Sun Y. Network meta-analysis of multiple doses of vonoprazan for the treatment of erosive esophagitis. J Comp Eff Res 2023; 12:e220165. [PMID: 37470274 PMCID: PMC10508317 DOI: 10.57264/cer-2022-0165] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2022] [Accepted: 07/04/2023] [Indexed: 07/21/2023] Open
Abstract
Aim: 20 mg of vonoprazan (VPZ20) is recommended in most countries to treat erosive esophagitis (EE). Whether other doses of vonoprazan, such as 5 mg (VPZ5), 10 mg (VPZ10), 20 mg (VPZ20), and 40 mg (VPZ40) are more effective is unknown. Materials & methods: Three databases were electronically searched to identify studies published before November 2021. Network meta-analysis was performed using STATA 14.0. Results: VPZ20 and VPZ40 were comparable to PPI, VPZ5 and VPZ10 in 4- and 8-week healing rates, and this was also detected in patients with refractory EE. All regimens resulted in similar treatment-emergent adverse events (TEAEs). However, VPZ40 ranked first for healing rate and TEAEs; however, VPZ20 ranked worst for TEAEs. Conclusion: Different doses of VPZ are comparable in efficacy and safety, but VPZ40 may be best in both effectiveness and safety.
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Affiliation(s)
- Jie He
- Gastrology/Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200000, China
| | - Yuanyuan Gao
- Apartment of Mental disease/Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200000, Shanghai, China
| | - Ge Bai
- Oncology/Shanxi University of Traditional Chinese Medicine, Taiyuan, Shanxi, 030000, China
| | - Jie Wang
- Gastrology/Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200000, China
| | - Yongshun Sun
- Gastrology/Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200000, China
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14
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Choi YJ. [Treatment of Acid-related Diseases Using Potassium-competitive Acid Blockers]. THE KOREAN JOURNAL OF GASTROENTEROLOGY = TAEHAN SOHWAGI HAKHOE CHI 2022; 80:247-253. [PMID: 36567437 DOI: 10.4166/kjg.2022.143] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/06/2022] [Revised: 12/16/2022] [Accepted: 12/17/2022] [Indexed: 12/27/2022]
Abstract
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.
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Affiliation(s)
- Yoon Jin Choi
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
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15
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Tsuboi K, Hoshino M, Omura N, Yamamoto SR, Akimoto S, Masuda T, Sakashita Y, Fukushima N, Takeuchi H, Yano F, Eto K. The pathological conditions and surgical outcomes depending on the degree of hernia in the intra-thoracic stomach. Esophagus 2022:10.1007/s10388-022-00979-6. [PMID: 36562858 DOI: 10.1007/s10388-022-00979-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2022] [Accepted: 12/16/2022] [Indexed: 12/24/2022]
Abstract
BACKGROUND In recent years, the number of patients requiring surgery for intra-thoracic stomach (ITS) has been increasing due to the effects of obesity and gibbus due to aging. The aim of this study is to assess the effects of the degree of hernia on the pathological conditions and surgical outcomes in ITS patients. METHODS ITS was defined as cases in which over 50% of the stomach had deviated into the mediastinum by esophagogastric fluoroscopy and/or computed tomography, with 65 patients who underwent laparoscopic surgery as the initial surgery included. We compared the pathological conditions and surgical outcomes by dividing the subjects into 3 groups: Group A: 50%- < 75%; Group B: 75%- < 100%; and Group C: 100% (upside-down stomach), depending on the degree of deviation into the mediastinum of the stomach. RESULTS The breakdown of patients was 33 in Group A, 21 in Group B, and 11 in Group C. Regarding the preoperative pathological conditions, Group C had a high body mass index (BMI) and a low score for factor V according to upper gastrointestinal endoscopy (p = 0.0109, p = 0.0062, respectively). While the surgical results indicated that the operation time was extended depending on the degree of hernia (p = 0.0051), there was no marked difference in other surgical outcomes or the postoperative course among the three groups, with a high degree of satisfaction. CONCLUSIONS In the case of ITS, although the operation time was extended depending on the degree of the hernia, the surgical outcomes were the same, and overall good results were obtained.
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Affiliation(s)
- Kazuto Tsuboi
- Department of Surgery, Fuji City General Hospital, 50, Takashima-Cho, Fuji, Shizuoka, 417-8567, Japan. .,Department of Surgery, The Jikei University School of Medicine, Tokyo, Japan.
| | - Masato Hoshino
- Department of Surgery, The Jikei University School of Medicine, Tokyo, Japan
| | - Nobuo Omura
- Department of Surgery, Nishisaitama-Chuo National Hospital, Saitama, Japan.,Department of Surgery, The Jikei University School of Medicine, Tokyo, Japan
| | - Se-Ryung Yamamoto
- Department of Surgery, The Jikei University School of Medicine, Tokyo, Japan
| | - Shunsuke Akimoto
- Department of Surgery, The Jikei University School of Medicine, Tokyo, Japan
| | - Takahiro Masuda
- Department of Surgery, The Jikei University School of Medicine, Tokyo, Japan
| | - Yuki Sakashita
- Department of Surgery, The Jikei University School of Medicine, Tokyo, Japan
| | - Naoko Fukushima
- Department of Surgery, The Jikei University School of Medicine, Tokyo, Japan
| | - Hideyuki Takeuchi
- Department of Surgery, The Jikei University School of Medicine, Tokyo, Japan
| | - Fumiaki Yano
- Department of Surgery, The Jikei University School of Medicine, Tokyo, Japan
| | - Ken Eto
- Department of Surgery, The Jikei University School of Medicine, Tokyo, Japan
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16
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Lee KN, Lee OY, Chun HJ, Kim JI, Kim SK, Lee SW, Park KS, Lee KL, Choi SC, Jang JY, Kim GH, Sung IK, Park MI, Kwon JG, Kim N, Kim JJ, Lee ST, Kim HS, Kim KB, Lee YC, Choi MG, Lee JS, Jung HY, Lee KJ, Kim JH, Chung H. Randomized controlled trial to evaluate the efficacy and safety of fexuprazan compared with esomeprazole in erosive esophagitis. World J Gastroenterol 2022; 28:6294-6309. [PMID: 36504556 PMCID: PMC9730436 DOI: 10.3748/wjg.v28.i44.6294] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2022] [Revised: 10/17/2022] [Accepted: 11/09/2022] [Indexed: 11/24/2022] Open
Abstract
BACKGROUND 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. AIM To compare fexuprazan to esomeprazole and establish its efficacy and safety in patients with erosive esophagitis (EE). METHODS 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. RESULTS 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. CONCLUSION 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.
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Affiliation(s)
- Kang Nyeong Lee
- Department of Internal Medicine, Hanyang University College of Medicine, Seoul 04763, South Korea
| | - Oh Young Lee
- Department of Internal Medicine, Hanyang University College of Medicine, Seoul 04763, South Korea
| | - Hoon Jai Chun
- Department of Internal Medicine, Korea University Anam Hospital, Seoul 02841, South Korea
| | - Jin Il Kim
- Department of Internal Medicine, The Catholic University of Korea, Yeouido ST. Mary’s Hospital, Seoul 07260, South Korea
| | - Sung Kook Kim
- Department of Internal Medicine, Kyungpook National University Hospital, Daegu 41944, South Korea
| | - Sang Woo Lee
- Department of Internal Medicine, Korea University Ansan Hospital, Ansan-si 15355, South Korea
| | - Kyung Sik Park
- Department of Internal Medicine, Keimyung University Dongsan Hospital, Daegu 42601, South Korea
| | - Kook Lae Lee
- Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul 07061, South Korea
| | - Suck Chei Choi
- Department of Internal Medicine, Wonkwang University Hospital, Iksan 54538, South Korea
| | - Jae-Young Jang
- Department of Internal Medicine, KyungHee University Medical Center, Seoul 02447, South Korea
| | - Gwang Ha Kim
- Department of Internal Medicine, Pusan National University School of Medicine and Biomedical Research Institute, Pusan National University Hospital, Busan 47241, South Korea
| | - In-kyung Sung
- Department of Internal Medicine, KKonkuk University Medical Center, Seoul 05030, South Korea
| | - Moo In Park
- Department of Internal Medicine, Kosin University Gaspel Hospital, Busan 49267, South Korea
| | - Joong Goo Kwon
- Department of Internal Medicine, Daegu Catholic University Medical Center, Daegu 42471, South Korea
| | - Nayoung Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam-si 13620, Gyeonggi-do, South Korea
| | - Jae Jun Kim
- Department of Internal Medicine, Samsung Medical Center, Seoul 06351, South Korea
| | - Soo Teik Lee
- Department of Internal Medicine, Chonbuk National University Hospital, Jeonju-si 54907, South Korea
| | - Hyun Soo Kim
- Department of Internal Medicine, Chonnam National University Hospital, Gwangju 61469, South Korea
| | - Ki Bae Kim
- Department of Internal medicine, Chungbuk National University School of Medicine, Cheong Ju 28644, South Korea
| | - Yong Chan Lee
- Department of Internal Medicine, Severance Hospital, Seoul 03722, South Korea
| | - Myung-Gyu Choi
- Department of Internal Medicine, The Catholic University of Korea, Seoul ST. Mary’s Hospital, Seoul 06591, South Korea
| | - Joon Seong Lee
- Digestive Disease Center, Soonchunhyang University College of Medicine, Seoul 04401, South Korea
| | - Hwoon-Yong Jung
- Department of Internal Medicine, Asan Medical Center, Seoul 05505, South Korea
| | - Kwang Jae Lee
- Department of Gastroenterology, Ajou University School of Medicine, Suwon 16499, South Korea
| | - Jie-Hyun Kim
- Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, South Korea
| | - Hyunsoo Chung
- Department of Internal Medicine, Seoul National University Hospital, Seoul 03080, South Korea
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17
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Zhang M, Xiao Y, Chen M. The role of vonoprazan in patients with erosive esophagitis. Therap Adv Gastroenterol 2022; 15:17562848221122623. [PMID: 36117573 PMCID: PMC9478709 DOI: 10.1177/17562848221122623] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2022] [Accepted: 08/01/2022] [Indexed: 02/04/2023] Open
Abstract
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.
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Affiliation(s)
- Mengyu Zhang
- Department of Gastroenterology, The First
Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong
Province, China
| | - Yinglian Xiao
- Department of Gastroenterology, The First
Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong
Province, China
| | - Minhu Chen
- Department of Gastroenterology, The First
Affiliated Hospital of Sun Yat-sen University, 58 Zhongshan II Road,
Guangzhou, Guangdong Province 510080, China
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18
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Higuchi T, Yamade M, Takahashi S, Tamura S, Tani S, Kagami T, Uotani T, Hamaya Y, Iwaizumi M, Osawa S, Sugimoto K, Furuta T. Influence of daily versus alternate-day dosing of vonoprazan on intragastric pH, serum gastrin, and the antiplatelet function of clopidogrel : Influence of alternate-day dosing of vonoprazan. Eur J Clin Pharmacol 2022; 78:955-963. [PMID: 35445847 DOI: 10.1007/s00228-022-03313-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2021] [Accepted: 03/11/2022] [Indexed: 11/03/2022]
Abstract
BACKGROUND Vonoprazan, a potassium-competitive acid blocker, inhibits gastric acid secretion and attenuates the antiplatelet function of clopidogrel more potently than esomeprazole. We investigated whether alternate-day dosing of vonoprazan might avoid this interaction with clopidogrel while providing sufficient gastric acid inhibition. METHODS Following 24 h of pH monitoring (control regimen), 12 healthy volunteers received three regimens (clopidogrel-only regimen: clopidogrel 75 mg daily [q.d.]; vonoprazan alternate-day regimen: vonoprazan 10 mg every other day [q.o.d.] + clopidogrel 75 mg q.d.; vonoprazan daily regimen: vonoprazan 10 mg q.d. + clopidogrel 75 mg q.d.) for 14 days in a randomized open-label crossover manner. Intragastric pH monitoring was performed for 24 h on day 13 in the clopidogrel-only and vonoprazan q.d. regimens and for 48 h on days 13 and 14 in the vonoprazan q.o.d. regimen. Serum gastrin and inhibition of platelet aggregation (IPA) were measured before the commencement of pH monitoring in each regimen. RESULTS Twelve volunteers completed the study. Equivalent median IPA values in the q.o.d. and q.d. regimens were measured (21.8% and 25%, respectively) and were significantly lower than that with the clopidogrel-only regimen (40.8%). The median pH4 holding time ratio for the vonoprazan q.o.d. regimen (49.7%) was superior to that of the clopidogrel-only regimen (18.4%), but was significantly inferior to that of the vonoprazan q.d. regimen (77.0%; p < 0.01). CONCLUSION Alternate-day administration of vonoprazan could not prevent the interaction between vonoprazan and clopidogrel, and acid inhibition was inferior to that with vonoprazan daily administration. Alternate-day administration of vonoprazan thus appears to be of questionable clinical utility.
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Affiliation(s)
- Tomohiro Higuchi
- First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Mihoko Yamade
- First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Satoru Takahashi
- First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Satoshi Tamura
- First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
- Department of Endoscopic and Photodynamic Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Shinya Tani
- First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Takuma Kagami
- Department of Gastroenterology, Seirei Hamamatsu General Hospital, Hamamatsu, Japan
| | - Takahiro Uotani
- Department of Gastroenterology, Japanese Red Cross Shizuoka Hospital, Shizuoka, Japan
| | - Yasushi Hamaya
- First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Moriya Iwaizumi
- Department of Clinical Laboratory Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Satoshi Osawa
- Department of Endoscopic and Photodynamic Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Ken Sugimoto
- First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Takahisa Furuta
- Center for Clinical Research, Hamamatsu University School of Medicine, Hamamatsu, Japan.
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Savarino V, Antonioli L, Fornai M, Marabotto E, Demarzo MG, Zingone F, Ghisa M, Barberio B, Zentilin P, Ribolsi M, Savarino E. An update of pharmacology, efficacy, and safety of vonoprazan in acid-related disorders. Expert Rev Gastroenterol Hepatol 2022; 16:401-410. [PMID: 34550866 DOI: 10.1080/17474124.2021.1984878] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
INTRODUCTION Patients with acid-related disorders (ARDs) of the upper digestive tract remain highly prevalent and need to be continuously investigated to improve their management. AREAS COVERED This review provides a summary of the most recent advancements in the treatment of ARDs with particular focus on the new drugs available to overcome the unmet needs of traditional therapies. EXPERT OPINION Proton pump inhibitors remain the best therapy in treating ARDs, but a consistent proportion of these patients continues to present mucosal lesions or to experience symptoms despite treatment. These cases pertain mainly to the most severe forms of erosive esophagitis or to non-erosive reflux disease. Also, the increasing rate of patients with H. pylori infection not responding to eradication therapy represents a difficult clinical condition. The recent advent of a new class of antisecretory drugs, such as the potassium competitive acid blockers and, among them the most studied vonoprazan, which are characterized by a better pharmacological profile than PPIs (rapid onset of action, longer lasting acid suppression, control of nocturnal acidity), has the potential to overcome the above-mentioned unmet needs. More research should be done to assess their efficacy in Western populations and their safety in patients treated in the long term.
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Affiliation(s)
- Vincenzo Savarino
- Division of Gastroenterology, Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - Luca Antonioli
- Division of Gastroenterology, Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - Matteo Fornai
- Division of Gastroenterology, Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - Elisa Marabotto
- Division of Gastroenterology, Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - Maria Giulia Demarzo
- Division of Gastroenterology, Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - Fabiana Zingone
- Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Matteo Ghisa
- Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Brigida Barberio
- Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Patrizia Zentilin
- Division of Gastroenterology, Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - Mentore Ribolsi
- Gastroenterology Unit, Departmental Faculty of Medicine and Surgery, Università Campus Bio-Medico Di Roma, Rome, Italy
| | - Edoardo Savarino
- Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
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20
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Determinants of reflux perception in patients with non-erosive reflux disease who have reflux-related symptoms on potassium-competitive acid blocker therapy. Esophagus 2022; 19:367-373. [PMID: 34655001 DOI: 10.1007/s10388-021-00889-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2021] [Accepted: 10/09/2021] [Indexed: 02/03/2023]
Abstract
BACKGROUND This study investigated potential determinants of reflux perception in patients with non-erosive reflux disease (NERD) who had reflux-related symptoms on potassium-competitive acid blocker (P-CAB) therapy. METHODS This study included 23 patients with reflux-related symptoms despite P-CAB therapy. Esophageal impedance-pH monitoring was performed on P-CAB and the following potential determinants of reflux perception were investigated: reflux nadir pH value; change in pH (baseline-nadir); bolus clearance time; reflux extent; proportions of acid, weakly acidic, and weakly alkaline reflux episodes; and proportions of liquid and mixed reflux episodes. RESULTS Overall, ≥ 90% of all and symptomatic reflux episodes were weakly acidic reflux and 63% of symptomatic reflux episodes were reflux episodes with pH ≥ 5. There were no significant differences regarding potential determinants between symptomatic and asymptomatic reflux episodes. However, the proportion of symptomatic reflux episodes was significantly greater with pH < 5 (13.8%) than with pH ≥ 5 (9.5%) (P = 0.0431). In reflux episodes with pH < 5, the proportion of symptomatic reflux episodes was significantly greater in proximal sites (20.6%) than in distal sites (10.6%) (P = 0.0178). Conversely, in reflux episodes with pH ≥ 5, there was no significant difference regarding reflux perception according to reflux extent (proximal: 9.6% vs. distal: 9.0%, P = 0.9337). CONCLUSIONS In patients with P-CAB-resistant NERD, reflux symptoms were mainly caused by reflux episodes with pH ≥ 5 on P-CAB therapy. The proportions of symptomatic reflux episodes among reflux sites differed according to reflux pH value; thus, the mechanisms of reflux perception may differ according to reflux pH value.
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21
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Matsuda S, Kato M, Sakakibara Y, Hamada H, Sasaki Y, Mori H, Hirai Y, Inoue S, Toyokawa T, Kagaya T, Kuwai T, Esaka N, Yamashita H, Watanabe N, Matsumoto M, Fujii H, Demura M, Kubo K, Mabe K, Harada N. A study for every second day administration of vonoprazan for maintenance treatment of erosive GERD (ESD von GERD): a multicenter randomized cross-over study. J Gastroenterol 2022; 57:133-143. [PMID: 35092498 DOI: 10.1007/s00535-022-01850-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Accepted: 01/08/2022] [Indexed: 02/04/2023]
Abstract
BACKGROUND Vonoprazan is a potassium competitive acid blocker used to treat erosive gastroesophageal reflux disease (GERD) with stronger, more stable acid-suppressing effects than proton pump inhibitors (PPIs). This study clarified the usefulness and superiority of vonoprazan administered every second day over PPIs in the maintenance therapy of erosive GERD. METHODS This is a prospective, multicenter, open-label, two-period randomized cross-over study. Patients were randomized to either the vonoprazan-lansoprazole (VP-LZ) group, who were given vonoprazan 10 mg for the first 4 weeks and then lansoprazole 15 mg for the next 4 weeks both administered once every second day, or the lansoprazole-vonoprazan (LZ-VP) group, who were treated in reverse. GERD symptoms were compared using symptom diaries, the frequency scale for symptoms of GERD (FSSG), and the gastrointestinal symptom rating scale (GSRS). RESULTS We enrolled 122 patients between December 2017 and May 2019. Symptoms were well controlled in vonoprazan administration and lansoprazole administration were 93.6% and 82.1%, respectively, with a significant difference on McNemar's test (P = 0.003). During the second 4 weeks, 94.4% and 76.7% of patients in the VP-LZ and LZ-VP groups, respectively, were well controlled following for ≥ 6 consecutive days a week (P = 0.009). During the first 4 weeks, 96.7% and 80.0% of patients were well controlled with < 1 weekly in the VP-LZ and LZ-VP groups, respectively, during the first 4 weeks (P = 0.007). GERD symptoms, assessed via FSSG and GSRS, significantly decreased with vonoprazan administration once every second day. CONCLUSIONS Vonoprazan administered once every second day could be an effective alternative to PPIs in the maintenance treatment of erosive GERD (UMIN000030393).
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Affiliation(s)
- Soichiro Matsuda
- Department of Gastroenterology, National Hospital Organization Hakodate National Hospital, 18-16, Kawahara-chou, Hakodate, Hokkaido, 041-8512, Japan
| | - Mototsugu Kato
- Department of Gastroenterology, National Hospital Organization Hakodate National Hospital, 18-16, Kawahara-chou, Hakodate, Hokkaido, 041-8512, Japan.
| | - Yuko Sakakibara
- Department of Gastroenterology, National Hospital Organization Osaka National Hospital, Osaka, Japan
| | - Hiroshige Hamada
- Department of Gastroenterology, National Hospital Organization Higashihiroshima Medical Center, Hiroshima, Japan
| | - Yoshihiro Sasaki
- Department of Gastroenterology, National Hospital Organization Disaster Medical Center, Tokyo, Japan
| | - Hideki Mori
- Department of Gastroenterology, National Hospital Organization Tokyo Medical Center, Tokyo, Japan
| | - Yuichiro Hirai
- Department of Gastroenterology, National Hospital Organization Tokyo Medical Center, Tokyo, Japan
| | - Shuji Inoue
- Department of Gastroenterology, National Hospital Organization Kochi National Hospital, Kochi, Japan
| | - Tatsuya Toyokawa
- Department of Gastroenterology, National Hospital Organization Fukuyama Medical Center, Hiroshima, Japan
| | - Takashi Kagaya
- Department of Gastroenterology, National Hospital Organization Kanazawa Medical Center, Ishikawa, Japan
| | - Toshio Kuwai
- Department of Gastroenterology, National Hospital Organization Kure Medical Center, Hiroshima, Japan
| | - Naoki Esaka
- Department of Gastroenterology, National Hospital Organization Kyoto Medical Center, Kyoto, Japan
| | - Haruhiro Yamashita
- Department of Gastroenterology, National Hospital Organization Okayama Medical Center, Okayama, Japan
| | - Noriko Watanabe
- Department of Gastroenterology, National Hospital Organization Mie Chou Medical Center, Mie, Japan
| | - Mio Matsumoto
- Department of Gastroenterology, National Hospital Organization Hokkaido Medical Center, Hokkaido, Japan
| | - Hiroyuki Fujii
- Department of Gastroenterology, National Hospital Organization Fukuokahigashi Medical Center, Fukuoka, Japan
| | - Mamiko Demura
- Department of Clinical Research, National Hospital Organization Hakodate National Hospital, Hokkaido, Japan
| | - Kimitoshi Kubo
- Department of Gastroenterology, National Hospital Organization Hakodate National Hospital, 18-16, Kawahara-chou, Hakodate, Hokkaido, 041-8512, Japan
| | - Katsuhiro Mabe
- Department of Gastroenterology, National Hospital Organization Hakodate National Hospital, 18-16, Kawahara-chou, Hakodate, Hokkaido, 041-8512, Japan
| | - Naohiko Harada
- Department of Gastroenterology, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan
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22
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Shirai Y, Kawami N, Iwakiri K, Kuwana M. Use of vonoprazan, a novel potassium-competitive acid blocker, for the treatment of proton pump inhibitor-refractory reflux esophagitis in patients with systemic sclerosis. JOURNAL OF SCLERODERMA AND RELATED DISORDERS 2022; 7:57-61. [PMID: 35386943 PMCID: PMC8922677 DOI: 10.1177/23971983211021747] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Accepted: 05/09/2021] [Indexed: 02/03/2023]
Abstract
Objective 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. Methods 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. Results 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. Conclusion Vonoprazan is a potential treatment option for treating proton pump inhibitor-refractory reflux esophagitis in systemic sclerosis patients.
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Affiliation(s)
- Yuichiro Shirai
- Department of Allergy and Rheumatology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan
| | - Noriyuki Kawami
- Department of Gastroenterology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan
| | - Katsuhiko Iwakiri
- Department of Gastroenterology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan
| | - Masataka Kuwana
- Department of Allergy and Rheumatology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan
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23
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Shinozaki S, Osawa H, Hayashi Y, Miura Y, Yano T, Lefor AK, Yamamoto H. Predictors and timing for the development of symptomatic gastroesophageal reflux disease after successful Helicobactor pylori eradication therapy. Scand J Gastroenterol 2022; 57:16-21. [PMID: 34547219 DOI: 10.1080/00365521.2021.1975310] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND Helicobacter pylori (H. pylori) eradication success increases the incidence of erosive esophagitis by normalization of gastric acid secretion. The aim of this study is to clarify predictors and timing for the development of symptomatic gastroesophageal reflux disease (GERD) after successful H. pylori eradication based on long-term follow-up. METHODS From April 2014 to October 2020, 330 patients with H. pylori infections treated with a standard triple-drug regimen were enrolled, and their records retrospectively reviewed. Development of symptomatic GERD was defined as requiring proton pump inhibitor or vonoprazan therapy to treat symptoms. RESULTS The mean follow-up period was 2.8 years, and symptomatic GERD developed in 41 (12%) patients during the study period. Overall rates of GERD-symptom free patients at 6 months, 1, and 2 years after eradication were 97%, 93%, and 89%, respectively. We evaluated predictors for the development of symptomatic GERD using a Cox proportional hazards regression model. In multivariate analysis, being a current smoker, having functional dyspepsia, hiatal hernia, and severe gastric atrophy were identified as significant predictive factors. The GERD domain score in the Izumo scale was significantly decreased 1 month after vonoprazan therapy consistent with effective treatment of symptomatic GERD. CONCLUSIONS The rate of development of symptomatic GERD after successful H. pylori eradication is low over long-term follow-up and is easily controlled by vonoprazan therapy. However, patients with smoking habits, functional dyspepsia, hiatal hernia, or severe gastric atrophy should be followed carefully after eradication.
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Affiliation(s)
- Satoshi Shinozaki
- Shinozaki Medical Clinic, Utsunomiya, Japan.,Department of Medicine, Division of Gastroenterology, Jichi Medical University, Shimotsuke, Japan
| | - Hiroyuki Osawa
- Department of Medicine, Division of Gastroenterology, Jichi Medical University, Shimotsuke, Japan
| | - Yoshikazu Hayashi
- Department of Medicine, Division of Gastroenterology, Jichi Medical University, Shimotsuke, Japan
| | - Yoshimasa Miura
- Department of Medicine, Division of Gastroenterology, Jichi Medical University, Shimotsuke, Japan
| | - Tomonori Yano
- Department of Medicine, Division of Gastroenterology, Jichi Medical University, Shimotsuke, Japan
| | | | - Hironori Yamamoto
- Department of Medicine, Division of Gastroenterology, Jichi Medical University, Shimotsuke, Japan
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24
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Xu WT, Xu XB, Ren TS, Qi XS. Vonoprazan for treatment of gastroesophageal reflux disease: Research advances. Shijie Huaren Xiaohua Zazhi 2021; 29:1248-1253. [DOI: 10.11569/wcjd.v29.i21.1248] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Affiliation(s)
- Wen-Tao Xu
- Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang 110840, Liaoning Province, China,Postgraduate College, Shenyang Pharmaceutical University, Shenyang 110016, Liaoning Province, China
| | - Xiang-Bo Xu
- Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang 110840, Liaoning Province, China,Postgraduate College, Shenyang Pharmaceutical University, Shenyang 110016, Liaoning Province, China
| | - Tian-Shu Ren
- Department of Pharmacy, General Hospital of Northern Theater Command, Shenyang 110840, Liaoning Province, China
| | - Xing-Shun Qi
- Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang 110840, Liaoning Province, China,Postgraduate College, Shenyang Pharmaceutical University, Shenyang 110016, Liaoning Province, China
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25
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Ochiai Y, Iizuka T, Hoshihara Y, Suzuki Y, Hayasaka J, Nomura K, Tanaka M, Odagiri H, Yamashita S, Matsui A, Kikuchi D, Ueno M, Udagawa H, Hoteya S. Efficacy of Vonoprazan for Refractory Reflux Esophagitis after Esophagectomy. Dig Dis 2021; 39:569-576. [PMID: 33567428 PMCID: PMC8686710 DOI: 10.1159/000515146] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2020] [Accepted: 01/27/2021] [Indexed: 02/02/2023]
Abstract
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.
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Affiliation(s)
- Yorinari Ochiai
- Department of Gastroenterology, Toranomon Hospital, Tokyo, Japan,*Yorinari Ochiai,
| | - Toshiro Iizuka
- Department of Gastroenterology, Toranomon Hospital, Tokyo, Japan
| | - Yoshio Hoshihara
- Department of Gastroenterology, Toranomon Hospital, Tokyo, Japan,Department of Gastroenterology, Nippon Medical School, Tokyo, Japan
| | - Yugo Suzuki
- Department of Gastroenterology, Toranomon Hospital, Tokyo, Japan
| | | | - Kosuke Nomura
- Department of Gastroenterology, Toranomon Hospital, Tokyo, Japan
| | - Masami Tanaka
- Department of Gastroenterology, Toranomon Hospital, Tokyo, Japan
| | - Hiroyuki Odagiri
- Department of Gastroenterology, Toranomon Hospital, Tokyo, Japan
| | | | - Akira Matsui
- Department of Gastroenterology, Toranomon Hospital, Tokyo, Japan
| | - Daisuke Kikuchi
- Department of Gastroenterology, Toranomon Hospital, Tokyo, Japan
| | - Masaki Ueno
- Department of Gastrointestinal Surgery, Toranomon Hospital, Tokyo, Japan
| | - Harushi Udagawa
- Department of Gastrointestinal Surgery, Toranomon Hospital, Tokyo, Japan
| | - Shu Hoteya
- Department of Gastroenterology, Toranomon Hospital, Tokyo, Japan
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26
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Yoon S, Oh E, Park MS, Jang SB, Byun HM, Park H, Kim H, Kim CO. Comparison of the pharmacokinetics and pharmacodynamics of YH4808 in healthy subjects for defining an appropriate dosing regimen. Transl Clin Pharmacol 2021; 29:150-159. [PMID: 34621707 PMCID: PMC8492394 DOI: 10.12793/tcp.2021.29.e15] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2021] [Revised: 09/09/2021] [Accepted: 09/13/2021] [Indexed: 11/19/2022] Open
Abstract
YH4808 is a novel potassium-competitive acid blocker developed for gastric acid-related disorders. Previous studies indicate its potential to improve symptoms of gastric acid-related disorders. The current study was aimed to find the optimal regimen of YH4808 for night time pH control. This study was performed in two parts. Each was a randomized, open-label, active-controlled, multiple-doses, two-treatment, two-period crossover study conducted in 20 healthy Korean volunteers. Subjects were randomly assigned to one of the four groups. The three groups received different dosage regimens of YH4808 (100 mg twice a day, 200 mg once a day, or 200 mg twice a day), and the fourth group received esomeprazole 40 mg twice a day. The pharmacokinetic parameters demonstrated that the systemic exposure of YH4808 increased in a dose-proportional manner. The difference in the proportion of time above pH 4 over 24 h from the baseline was the greatest in the group receiving YH4808 200 mg twice a day. The values of the area under the effect curve at night time (12 A.M.–7 A.M.) were higher in all YH4808 groups than in the esomeprazole group. However, the differences among the YH4808 groups were not statistically significant (p > 0.05). YH4808 exhibited potential for better pH control during the night in comparison to esomeprazole. The optimal regimen for night time pH control among all the YH4808 regimens was 200 mg twice a day.
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Affiliation(s)
- Sukyong Yoon
- Department of Clinical Pharmacology, Severance Hospital, Yonsei University College of Medicine, Seoul 03722, Korea.,Department of Pharmacology, Yonsei University College of Medicine, Seoul 03722, Korea
| | - EunSil Oh
- Department of Clinical Pharmacology, Severance Hospital, Yonsei University College of Medicine, Seoul 03722, Korea
| | - Min Soo Park
- Department of Clinical Pharmacology, Severance Hospital, Yonsei University College of Medicine, Seoul 03722, Korea.,Department of Pediatrics, Yonsei University College of Medicine, Seoul 03722, Korea
| | - Seong Bok Jang
- Clinical Development Department, Yuhan Corporation, Seoul 06927, Korea
| | - Hae Mi Byun
- Clinical Development Department, Yuhan Corporation, Seoul 06927, Korea
| | - Hyeonsoo Park
- Department of Clinical Pharmacology, Severance Hospital, Yonsei University College of Medicine, Seoul 03722, Korea.,Department of Pharmacology, Yonsei University College of Medicine, Seoul 03722, Korea
| | - Heeyoung Kim
- Department of Clinical Pharmacology, Severance Hospital, Yonsei University College of Medicine, Seoul 03722, Korea.,Department of Pharmacology, Yonsei University College of Medicine, Seoul 03722, Korea
| | - Choon Ok Kim
- Department of Clinical Pharmacology, Severance Hospital, Yonsei University College of Medicine, Seoul 03722, Korea
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27
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Voulgaris TA, Karamanolis GP. Esophageal manifestation in patients with scleroderma. World J Clin Cases 2021; 9:5408-5419. [PMID: 34307594 PMCID: PMC8281422 DOI: 10.12998/wjcc.v9.i20.5408] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2021] [Revised: 04/22/2021] [Accepted: 05/10/2021] [Indexed: 02/06/2023] Open
Abstract
The esophagus is the most commonly affected part of the gastrointestinal system in patients with systemic sclerosis (SSc). Esophageal involvement may lead to a significant reduction in patient quality of life. The exact pathophysiology is complex and not yet fully elucidated. Ultimately, esophageal smooth muscle becomes atrophied and replaced by fibrous tissue leading to severe motility disturbance of the distal esophagus. Symptoms are mainly attributed to gastroesophageal reflux disease and to esophageal dysmotility. Compelling evidence has correlated esophageal involvement to the severity of pulmonary disease. No formed guidelines exist about the diagnostic modalities used to assess esophageal disease in patients with SSc, though upper gastrointestinal endoscopy is the first and most important modality used as it can reveal alterations commonly observed in patients with SSc. Further exploration can be made by high resolution manometry and pH-impedance study. Proton pump inhibitors remain the mainstay of treatment, while prokinetic agents are commonly used as add-on therapy in patients with symptoms attributed to gastroesophageal reflux disease not responding to standard therapy as well as to motility disturbances. Gastroesophageal reflux disease symptoms in patients with SSc are frequently difficult to manage, and new therapeutic modalities are emerging. The role of surgical treatment is restricted and should only be preserved for resistant cases.
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Affiliation(s)
- Theodoros A Voulgaris
- Department of Gastroenterology and Hepatology, Laiko General Hospital, National and Kapodistian University of Athens, Athens 11527, Greece
| | - Georgios P Karamanolis
- Department of Gastroenterology and Hepatology, Laiko General Hospital, National and Kapodistian University of Athens, Athens 11527, Greece
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28
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Xiao YL, Zhou LY, Hou XH, Li YQ, Zou DW, Chen MH. Chinese expert consensus on gastroesophageal reflux disease in 2020. J Dig Dis 2021; 22:376-389. [PMID: 34105263 DOI: 10.1111/1751-2980.13028] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2021] [Accepted: 06/07/2021] [Indexed: 12/11/2022]
Affiliation(s)
- Ying Lian Xiao
- Department of Gastroenterology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China
| | - Li Ya Zhou
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
| | - Xiao Hua Hou
- Department of Gastroenterology, Union Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei Province, China
| | - Yan Qing Li
- Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong Province, China
| | - Duo Wu Zou
- Department of Gastroenterology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Min Hu Chen
- Department of Gastroenterology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China
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29
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Tanabe T, Koeda M, Kitasako Y, Momma E, Hoshikawa Y, Hoshino S, Kawami N, Kaise M, Iwakiri K. Stimulated saliva secretion is reduced in proton pump inhibitor-resistant severe reflux esophagitis patients. Esophagus 2021; 18:676-683. [PMID: 33590389 DOI: 10.1007/s10388-021-00825-1] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2020] [Accepted: 02/05/2021] [Indexed: 02/03/2023]
Abstract
BACKGROUND Salivary secretion in patients with proton-pump inhibitor (PPI)-resistant severe reflux esophagitis has not been examined. In this study, saliva secretion and salivary epidermal growth factor (EGF) in patients with PPI-resistant severe reflux esophagitis were investigated. METHODS We recruited 22 PPI-resistant and 22 PPI-responsive severe reflux esophagitis patients who were not infected with Helicobacter pylori. Saliva secretion testing and esophageal manometry using high-resolution manometry were performed. Saliva secretion was assessed as follows: each patient chewed sugar-free gum for 3 min prior to endoscopy and the amount and pH of saliva as well as the pH of saliva after acid loading as an index of the acid-buffering capacity were measured. The salivary EGF concentration was assessed by ELISA. RESULTS The amount of saliva secreted was significantly lower in the PPI-resistant group than in the PPI-responsive group, with medians (25th-75th percentile) of 3.7 (2.2-6.8) and 4.9 (4.0-7.8) mL, respectively (p = 0.029). Salivary pH was significantly lower in the PPI-resistant group [6.9 (6.7-7.2)] than in the PPI-responsive group [7.2 (7.1-7.4), p = 0.001]. Salivary pH after acid loading was significantly lower in the PPI-resistant group [5.6 (5.3-5.9)] than in the PPI-responsive group [6.4 (6.1-6.5), p = 0.002]. The salivary EGF concentration was significantly higher in the PPI-resistant group [3211.5 (1865.0-4121.5)] than in the PPI-responsive group [1816.0 (1123.5-2792.3), p = 0.041]. No significant differences were observed in the proportion of esophageal motility abnormalities. CONCLUSION Stimulated saliva secretion was reduced in PPI-resistant severe reflux esophagitis patients.
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Affiliation(s)
- Tomohide Tanabe
- Department of Gastroenterology, Nippon Medical School, Graduate School of Medicine, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan
| | - Mai Koeda
- Department of Gastroenterology, Nippon Medical School, Graduate School of Medicine, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan
| | - Yuichi Kitasako
- Cariology and Operative Dentistry, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, Japan.,Dental Clinic, Ministry of Foreign Affairs, 2-2-1, Kasumigaseki, Chiyoda-ku, Tokyo, Japan
| | - Eri Momma
- Department of Gastroenterology, Nippon Medical School, Graduate School of Medicine, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan
| | - Yoshimasa Hoshikawa
- Department of Gastroenterology, Nippon Medical School, Graduate School of Medicine, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan
| | - Shintaro Hoshino
- Department of Gastroenterology, Nippon Medical School, Graduate School of Medicine, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan
| | - Noriyuki Kawami
- Department of Gastroenterology, Nippon Medical School, Graduate School of Medicine, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan
| | - Mitsuru Kaise
- Department of Gastroenterology, Nippon Medical School, Graduate School of Medicine, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan
| | - Katsuhiko Iwakiri
- Department of Gastroenterology, Nippon Medical School, Graduate School of Medicine, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan.
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30
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Okanobu H, Kohno T, Mouri R, Hatsushika Y, Yamashita Y, Miyaki E, Fukuhara T, Okazaki A, Sakano A, Urabe A, Takaki S, Mori N, Tsuji K, Ochi H, Furukawa Y. Efficacy of vonoprazan 10 mg compared with 20 mg for the initial treatment in patients with erosive esophagitis: a randomized pilot study. Esophagus 2021; 18:669-675. [PMID: 33221955 DOI: 10.1007/s10388-020-00798-7] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2020] [Accepted: 11/04/2020] [Indexed: 02/03/2023]
Abstract
BACKGROUND The study aimed to investigate the efficacy of vonoprazan 10 mg compared with 20 mg in patients with erosive esophagitis. METHOD Seventy-three patients with erosive esophagitis were randomly divided into two groups either vonoprazan 20 mg (n = 37) or 10 mg (n = 36). They were administered each dose for 4 weeks as the initial treatment followed by maintenance treatment with 10 mg for 8 weeks. The primary endpoints were mucosal healing rate and symptom relief at 4 weeks. The secondary endpoint was symptom relief at 12 weeks after the maintenance treatment. Mucosal healing was assessed endoscopically, and symptom relief was assessed using the FSSG score. RESULTS At 4 weeks, the endoscopic healing rates of the 20 mg and 10 mg groups were 94.6% and 94.4%, respectively. The FSSG scores of the 20 mg and 10 mg groups were significantly decreased in both treatment groups from 13 (4-39) to 4 (0-25) and 14 (4-40) to 3 (0-29), respectively. At 12 weeks, the scores further decreased to 2 (0-13) and 2 (0-26), respectively. The vonoprazan 10 mg group showed a similar therapeutic effect to the 20 mg group in mucosal healing at 4 weeks and in symptom relief throughout the study period. When stratified by esophagitis grading, these findings were still demonstrated in grade A/B patients but not in grade C/D patients. CONCLUSION Our findings suggest that initial treatment with vonoprazan 10 mg might be useful especially in patients with mild erosive esophagitis. Large controlled studies are warranted to confirm our investigation.
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Affiliation(s)
- Hideharu Okanobu
- Department of Gastroenterology, Hiroshima Red Cross Hospital and Atomic-Bomb, Survivors Hospital, 1-9-6, Sendamachi, Naka-ku, Hiroshima, 730-8619, Japan.
| | - Tomohiko Kohno
- Department of Gastroenterology, Hiroshima Red Cross Hospital and Atomic-Bomb, Survivors Hospital, 1-9-6, Sendamachi, Naka-ku, Hiroshima, 730-8619, Japan
| | - Ritsuo Mouri
- Department of Gastroenterology, Hiroshima Red Cross Hospital and Atomic-Bomb, Survivors Hospital, 1-9-6, Sendamachi, Naka-ku, Hiroshima, 730-8619, Japan
| | - Yoshiki Hatsushika
- Department of Gastroenterology, Hiroshima Red Cross Hospital and Atomic-Bomb, Survivors Hospital, 1-9-6, Sendamachi, Naka-ku, Hiroshima, 730-8619, Japan
| | - Yumiko Yamashita
- Department of Gastroenterology, Hiroshima Red Cross Hospital and Atomic-Bomb, Survivors Hospital, 1-9-6, Sendamachi, Naka-ku, Hiroshima, 730-8619, Japan
| | - Eisuke Miyaki
- Department of Gastroenterology, Hiroshima Red Cross Hospital and Atomic-Bomb, Survivors Hospital, 1-9-6, Sendamachi, Naka-ku, Hiroshima, 730-8619, Japan
| | - Takayuki Fukuhara
- Department of Gastroenterology, Hiroshima Red Cross Hospital and Atomic-Bomb, Survivors Hospital, 1-9-6, Sendamachi, Naka-ku, Hiroshima, 730-8619, Japan
| | - Akihito Okazaki
- Department of Gastroenterology, Hiroshima Red Cross Hospital and Atomic-Bomb, Survivors Hospital, 1-9-6, Sendamachi, Naka-ku, Hiroshima, 730-8619, Japan
| | - Ayaka Sakano
- Department of Medical Checkup Center, Hiroshima Red Cross Hospital and Atomic-Bomb Survivors Hospital, 1-9-6, Sendamachi, Naka-ku, Hiroshima, 730-8619, Japan
| | - Ayako Urabe
- Department of Medical Checkup Center, Hiroshima Red Cross Hospital and Atomic-Bomb Survivors Hospital, 1-9-6, Sendamachi, Naka-ku, Hiroshima, 730-8619, Japan
| | - Shintaro Takaki
- Department of Gastroenterology, Hiroshima Red Cross Hospital and Atomic-Bomb, Survivors Hospital, 1-9-6, Sendamachi, Naka-ku, Hiroshima, 730-8619, Japan
| | - Nami Mori
- Department of Gastroenterology, Hiroshima Red Cross Hospital and Atomic-Bomb, Survivors Hospital, 1-9-6, Sendamachi, Naka-ku, Hiroshima, 730-8619, Japan
| | - Keiji Tsuji
- Department of Gastroenterology, Hiroshima Red Cross Hospital and Atomic-Bomb, Survivors Hospital, 1-9-6, Sendamachi, Naka-ku, Hiroshima, 730-8619, Japan
| | - Hidenori Ochi
- Department of Medical Checkup Center, Hiroshima Red Cross Hospital and Atomic-Bomb Survivors Hospital, 1-9-6, Sendamachi, Naka-ku, Hiroshima, 730-8619, Japan
| | - Yoshinari Furukawa
- Department of Gastroenterology, Hiroshima Red Cross Hospital and Atomic-Bomb, Survivors Hospital, 1-9-6, Sendamachi, Naka-ku, Hiroshima, 730-8619, Japan
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Savarino V, Marabotto E, Zentilin P, Demarzo MG, de Bortoli N, Savarino E. Pharmacological Management of Gastro-Esophageal Reflux Disease: An Update of the State-of-the-Art. Drug Des Devel Ther 2021; 15:1609-1621. [PMID: 33907381 PMCID: PMC8064680 DOI: 10.2147/dddt.s306371] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2021] [Accepted: 04/06/2021] [Indexed: 12/12/2022] Open
Abstract
Gastro-esophageal reflux disease (GERD) is a highly prevalent, chronic disorder, whose knowledge remains limited and the management of these patients changes continuously. This review provides a summary of the most recent advancements in the pathogenesis of this disease and the new drugs introduced into the market to overcome some of the unmet needs of traditional therapies. Nowadays, the most fruitful diagnostic examinations are 24-hour impedance-pH monitoring, which allows us to separate true NERD from esophageal functional disorders and high-resolution manometry, which helps to exclude the existence of motility disorders sharing the same symptoms of GERD. Proton pump inhibitors (PPIs) remain the first-choice therapy in the treatment of GERD, but a consistent proportion of these patients continue to experience symptoms despite their intake. These cases pertain mainly to the subpopulation with non-erosive reflux disease (NERD) and represent very challenging clinical situations, because it is mandatory to understand the reasons for PPI failure. The management of these difficult patients requires necessarily to test them and avoid the use of empiric treatments that are often unsuccessful, costly and potentially dangerous. Recently, several new drugs have been used to increase the defensive properties of this mucosa with promising results in randomized clinical trials.
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Affiliation(s)
- Vincenzo Savarino
- Department of Internal Medicine (DIMI), University of Genoa, Genoa, Italy
| | - Elisa Marabotto
- Department of Internal Medicine (DIMI), University of Genoa, Genoa, Italy
| | - Patrizia Zentilin
- Department of Internal Medicine (DIMI), University of Genoa, Genoa, Italy
| | | | - Nicola de Bortoli
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Edoardo Savarino
- Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy
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Kikuchi H, Fukuda S, Koike T, Shimodaira Y, Watanabe K, Saito M, Nakagawa K, Hatta W, Masamune A, Iijima K. Association of residual gastric acid secretion with persistent symptoms in gastroesophageal reflux disease patients receiving standard-dose proton pump inhibitor therapy. Esophagus 2021; 18:380-387. [PMID: 32737802 DOI: 10.1007/s10388-020-00765-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2020] [Accepted: 07/24/2020] [Indexed: 02/03/2023]
Abstract
BACKGROUND Although a third of gastroesophageal reflux disease (GERD) patients are refractory to proton pump inhibitor (PPI) therapy, the underlying mechanism of the refractoriness remains unclear. We compared the level of gastric acid suppression during PPI treatment between responders and non-responders by directly measuring gastric acid secretion in GERD patients taking PPIs. METHODS Seventy-five consecutive patients receiving standard-dose PPI therapy for GERD were prospectively recruited, irrespective of persistent GERD symptoms. They were asked about their GERD symptoms using a validated questionnaire, and simultaneously underwent both a routine endoscopic examination and a gastric acid secretory testing using an endoscopic gastrin test. Associations between residual gastric acid secretion during PPI treatment and persistent GERD symptoms were analyzed by a logistic regression analysis. RESULTS Overall, 26 of 75 (34.7%) patients were judged to be positive for persistent GERD symptoms. The patients with and without persistent symptoms showed similar gastric acid secretion levels (1.3 [1.3] mEq/10 min vs. 1.4 [2.0] mEq/10 min). Sufficient gastric acid suppression, defined as < 0.6, was not significantly associated with persistent GERD symptoms (odds ratio 1.1, 95% confidence interval 0.40-3.5). CONCLUSIONS This study provided solid evidence to support that the gastric acid suppression level during PPI treatment does not differ between patients with and without persistent GERD symptoms. The insignificant role of residual gastric acid in the persistent GERD symptoms suggests that the use of medications other than those that enhance gastric acid inhibitory effects would be an essential approach for the management of PPI-refractory GERD.
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Affiliation(s)
- H Kikuchi
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Sendai, 980-8574, Japan
| | - S Fukuda
- Department of Gastroenterology, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita, Akita, 010-8543, Japan
| | - T Koike
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Sendai, 980-8574, Japan
| | - Y Shimodaira
- Department of Gastroenterology, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita, Akita, 010-8543, Japan
| | - K Watanabe
- Department of Gastroenterology, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita, Akita, 010-8543, Japan
| | - M Saito
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Sendai, 980-8574, Japan
| | - K Nakagawa
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Sendai, 980-8574, Japan
| | - W Hatta
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Sendai, 980-8574, Japan
| | - A Masamune
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Sendai, 980-8574, Japan
| | - K Iijima
- Department of Gastroenterology, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita, Akita, 010-8543, Japan.
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Shinozaki S, Osawa H, Hayashi Y, Miura Y, Lefor AK, Yamamoto H. Long-term vonoprazan therapy is effective for controlling symptomatic proton pump inhibitor-resistant gastroesophageal reflux disease. Biomed Rep 2021; 14:32. [PMID: 33585034 PMCID: PMC7873583 DOI: 10.3892/br.2021.1408] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2020] [Accepted: 01/19/2021] [Indexed: 12/12/2022] Open
Abstract
Vonoprazan, a novel potassium-competitive acid blocker, results in greater inhibition of gastric acid secretion than proton pump inhibitors (PPI). The aim of this study was to assess the long-term outcomes of patients with PPI-resistant gastroesophageal reflux disease (GERD) treated with vonoprazan. The medical records of patients with symptomatic GERD treated with vonoprazan for 1 year were retrospectively reviewed. Changes in abdominal symptoms were assessed using the Izumo scale, a self-reported questionnaire which is useful in evaluating the symptoms of GERD, epigastric pain, postprandial distress, constipation and diarrhea, and is commonly used in routine clinical practice. A total of 30 patients were included and stratified into a non-erosive (n=22) and erosive group (n=8). At baseline, postprandial distress symptoms were significantly greater in the non-erosive group compared with the erosive group (P=0.013). Even with vonoprazan therapy, symptoms of GERD in the non-erosive group were refractory compared with the erosive group, and required additional treatment in a larger proportion of patients (45 vs. 13%). GERD symptoms in the non-erosive group significantly improved from baseline and remained better after 1 year of vonoprazan therapy, similar to the erosive group. In addition, vonoprazan improved epigastric pain and postprandial distress symptoms in the non-erosive group, and 1 year of vonoprazan therapy did not aggravate constipation or diarrhea. In conclusion, 1 year of vonoprazan therapy improves GERD symptoms in patients with PPI-resistant GERD.
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Affiliation(s)
- Satoshi Shinozaki
- Shinozaki Medical Clinic, Utsunomiya, Tochigi 321-3223, Japan
- Department of Medicine, Division of Gastroenterology, Jichi Medical University, Shimotsuke, Tochigi 329-0498, Japan
| | - Hiroyuki Osawa
- Department of Medicine, Division of Gastroenterology, Jichi Medical University, Shimotsuke, Tochigi 329-0498, Japan
| | - Yoshikazu Hayashi
- Department of Medicine, Division of Gastroenterology, Jichi Medical University, Shimotsuke, Tochigi 329-0498, Japan
| | - Yoshimasa Miura
- Department of Medicine, Division of Gastroenterology, Jichi Medical University, Shimotsuke, Tochigi 329-0498, Japan
| | - Alan Kawarai Lefor
- Department of Surgery, Jichi Medical University, Shimotsuke, Tochigi 329-0498, Japan
| | - Hironori Yamamoto
- Department of Medicine, Division of Gastroenterology, Jichi Medical University, Shimotsuke, Tochigi 329-0498, Japan
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34
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Hoshikawa Y, Hoshino S, Kawami N, Iwakiri K. Prevalence of behavioral disorders in patients with vonoprazan-refractory reflux symptoms. J Gastroenterol 2021; 56:117-124. [PMID: 33247348 DOI: 10.1007/s00535-020-01751-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2020] [Accepted: 11/12/2020] [Indexed: 02/04/2023]
Abstract
BACKGROUND Behavioral disorders, such as supragastric belching (SGB) and rumination syndrome (RS), which may be treated by cognitive behavioral therapy, are common in patients with reflux symptoms refractory to proton pump inhibitors (PPI). Vonoprazan (VPZ) has been used as a new type of acid inhibitor in Japan since 2015. We herein investigated the prevalence of behavioral disorders in patients with VPZ-refractory reflux symptoms and attempted to identify predictive factors. METHODS We retrospectively analyzed esophagogastroduodenograms, high-resolution manometry, and 24-h multiluminal impedance pH-metry (MIIpH) in patients with VPZ-refractory reflux symptoms (heartburn or regurgitation) receiving 20 mg VPZ who underwent these tests at our hospital between January 2015 and April 2020. Patients were divided as follows: non-erosive reflux disease with pathological esophageal acid exposure (NERD), functional heartburn (FH), reflux hypersensitivity (RH), excessive (> 13 per day) SGB, and possible RS based on MIIpH parameters. RESULTS Among 49 patients, 6 (12.2%) had SGB, 4 (8.2%) possible RS, 29 (59.2%) FH, 9 (18.4%) RH, and 1 (2%) NERD. Possible RS patients had more postprandial non-acid reflux events than FH patients (p < 0.05). The multivariate logistic regression analysis did not identify any predictive factors with statistical significance. CONCLUSION More than 20% patients with VPZ-refractory reflux symptoms had behavioral disorders. The use of HRM and MIIpH may be clinically relevant for a better diagnosis and more specific treatment.
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Affiliation(s)
- Yoshimasa Hoshikawa
- Department of Gastroenterology, Nippon Medical School, Graduate School of Medicine, 1-1-5, Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan
| | - Shintaro Hoshino
- Department of Gastroenterology, Nippon Medical School, Graduate School of Medicine, 1-1-5, Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan
| | - Noriyuki Kawami
- Department of Gastroenterology, Nippon Medical School, Graduate School of Medicine, 1-1-5, Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan
| | - Katsuhiko Iwakiri
- Department of Gastroenterology, Nippon Medical School, Graduate School of Medicine, 1-1-5, Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan.
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35
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Tabuchi M, Minami H, Akazawa Y, Ashida M, Hara T, Ichinose K, Kitayama M, Hashiguchi K, Matsushima K, Yamaguchi N, Takeshima F, Kondo H, Kawakami A, Nakao K. Use of vonoprazan for management of systemic sclerosis-related gastroesophageal reflux disease. Biomed Rep 2020; 14:25. [PMID: 33408859 PMCID: PMC7780750 DOI: 10.3892/br.2020.1401] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2020] [Accepted: 11/13/2020] [Indexed: 12/13/2022] Open
Abstract
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.
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Affiliation(s)
- Maiko Tabuchi
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Science, Nagasaki 852-8501, Japan
| | - Hitomi Minami
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Science, Nagasaki 852-8501, Japan
| | - Yuko Akazawa
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Science, Nagasaki 852-8501, Japan.,Department of Pathology, Nagasaki University Graduate School of Biomedical Science, Nagasaki 852-8501, Japan
| | - Miwa Ashida
- Department of Dermatology, Nagasaki University Graduate School of Biomedical Science, Nagasaki 852-8501, Japan
| | - Toshihide Hara
- Department of Dermatology, Japan Community Healthcare Organization, Isahaya General Hospital, Isahaya, Nagasaki 854-8501, Japan
| | - Kunihiro Ichinose
- Department of Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical Science, Nagasaki 852-8501, Japan
| | - Moto Kitayama
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Science, Nagasaki 852-8501, Japan
| | - Keiichi Hashiguchi
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Science, Nagasaki 852-8501, Japan
| | - Kayoko Matsushima
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Science, Nagasaki 852-8501, Japan
| | - Naoyuki Yamaguchi
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Science, Nagasaki 852-8501, Japan
| | - Fuminao Takeshima
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Science, Nagasaki 852-8501, Japan
| | - Hisayoshi Kondo
- Division of Scientific Data Registry, Atomic Bomb Disease and Hibakusya Medicine Unit, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki 852-8523, Japan
| | - Atsushi Kawakami
- Department of Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical Science, Nagasaki 852-8501, Japan
| | - Kazuhiko Nakao
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Science, Nagasaki 852-8501, Japan
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36
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Scarpignato C, Hongo M, Wu JCY, Lottrup C, Lazarescu A, Stein E, Hunt RH. Pharmacologic treatment of GERD: Where we are now, and where are we going? Ann N Y Acad Sci 2020; 1482:193-212. [PMID: 32935346 DOI: 10.1111/nyas.14473] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2020] [Revised: 07/20/2020] [Accepted: 07/30/2020] [Indexed: 02/06/2023]
Abstract
The introduction of acid inhibition in clinical practice has revolutionized the management of acid-related diseases, leading to the virtual abolition of elective surgery for ulcer disease and relegating antireflux surgery to patients with gastroesophageal reflux disease (GERD) not adequately managed by medical therapy. Proton pump inhibitors (PPIs) are the antisecretory drugs of choice for the treatment of reflux disease. However, these drugs still leave some unmet clinical needs in GERD. PPI-refractoriness is common, and persistent symptoms are observed in up to 40-55% of daily PPI users. Potassium-competitive acid blockers (P-CABs) clearly overcome many of the drawbacks and limitations of PPIs, achieving rapid, potent, and prolonged acid suppression, offering the opportunity to address many of the unmet needs. In recent years, it has been increasingly recognized that impaired mucosal integrity is involved in the pathogenesis of GERD. As a consequence, esophageal mucosal protection has emerged as a new, promising therapeutic avenue. When P-CABS are used as add-on medications to standard treatment, a growing body of evidence suggests a significant additional benefit, especially in the relief of symptoms not responding to PPI therapy. On the contrary, reflux inhibitors are considered a promise unfulfilled, and prokinetic agents should only be used on a case-by-case basis.
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Affiliation(s)
- Carmelo Scarpignato
- Department of Health Sciences, United Campus of Malta, Msida, Malta.,Faculty of Medicine, Chinese University of Hong Kong, Shatin, Hong Kong
| | - Michio Hongo
- Department of Comprehensive Medicine, Tohoku University, Sendai, Miyagi, Japan
| | - Justin C Y Wu
- Department of Medicine and Therapeutics, Prince of Wales Hospital, Shatin, Hong Kong, China
| | - Christian Lottrup
- Department of Medicine, Aalborg University Hospital, Hobro, Denmark.,Mech-Sense, Department of Gastroenterology & Hepatology, Aalborg University Hospital, Aalborg, Denmak
| | - Adriana Lazarescu
- Division of Gastroenterology, University of Alberta, Edmonton, Alberta, Canada
| | - Ellen Stein
- Division of Gastroenterology and Hepatology, Johns Hopkins University, Baltimore, Maryland
| | - Richard H Hunt
- Division of Gastroenterology and Farncombe Family Digestive Health Research Institute, Department of Medicine, McMaster University, Hamilton, Ontario, Canada
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37
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Chapelle N, Ben Ghezala I, Barkun A, Bardou M. The pharmacotherapeutic management of gastroesophageal reflux disease (GERD). Expert Opin Pharmacother 2020; 22:219-227. [PMID: 32893683 DOI: 10.1080/14656566.2020.1817385] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
INTRODUCTION Gastroesophageal reflux disease (GERD) is a very common worldwide condition, affecting about 15-20% of the whole population, and representing a major burden for health-care systems. Because of its frequency, health physicians - family doctors as well as specialists - should be aware of the different pharmacotherapeutic approaches in managing GERD, according to disease severity. AREAS COVERED Authors summarize the pharmacological management of GERD in adults, present the different pharmaceutical classes, and review the evidence on efficacy for each treatment according to the most common clinical scenarios: non-erosive gastroesophageal reflux disease (NERD), erosive esophagitis (EE), and proton-pump inhibitor (PPI) refractory GERD. They also provide an overview of treatments under development. EXPERT OPINION To date, PPIs remain the most effective treatment option for both NERD and EE. However, Potassium-Competitive Acid blockers (PCAB) may be considered, with at least similar efficacy in Asian populations. Preliminary data suggest that PCABs could be superior to classic PPIs in patients with severe EE, and may also be of particular interest in the management of PPI-refractory GERD patients. Their definitive role in GERD management, however, still remains to be determined based on properly designed and conducted randomized clinical trials.
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Affiliation(s)
- Nicolas Chapelle
- Institut des Maladies de l'Appareil Digestif, Service de Gastroentérologie, Oncologie Digestive et Assistance Nutritionnelle , Nantes, France
| | - Ines Ben Ghezala
- Centre d'Investigations Cliniques CIC1432, CHU de Dijon , Dijon, France
| | - Alan Barkun
- Gastroenterology Department, McGill University , Montreal, Canada
| | - Marc Bardou
- Centre d'Investigations Cliniques CIC1432, CHU de Dijon , Dijon, France.,Gastroenterology Department, CHU de Dijon , Dijon, France
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38
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Delshad SD, Almario CV, Chey WD, Spiegel BM. Prevalence of Gastroesophageal Reflux Disease and Proton Pump Inhibitor-Refractory Symptoms. Gastroenterology 2020; 158:1250-1261.e2. [PMID: 31866243 PMCID: PMC7103516 DOI: 10.1053/j.gastro.2019.12.014] [Citation(s) in RCA: 144] [Impact Index Per Article: 28.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2019] [Revised: 12/06/2019] [Accepted: 12/10/2019] [Indexed: 12/14/2022]
Abstract
BACKGROUND & AIMS There are few data on the prevalence of gastroesophageal reflux disease (GERD) in the United States. We performed a population-based study to determine the prevalence of GERD symptoms and persistent GERD symptoms despite use of proton pump inhibitors (PPIs). METHODS We conducted the National Gastrointestinal Survey in 2015 using MyGiHealth, an app that guides participants through National Institutes of Health gastrointestinal Patient-Reported Outcomes Measurement Information System surveys. Primary outcomes were prevalence of GERD symptoms in the past and persistence of GERD symptoms (heartburn or regurgitation 2 or more days in past week) among participants taking PPIs. Population weights were applied to the data and multivariable regression was used to adjust for confounding. RESULTS Among 71,812 participants, 32,878 (44.1%) reported having had GERD symptoms in the past and 23,039 (30.9%) reported having GERD symptoms in the past week. We also found that 35.1% of those who had experienced GERD symptoms were currently on therapy (55.2% on PPIs, 24.3% on histamine-2 receptor blockers, and 24.4% on antacids). Among 3229 participants taking daily PPIs, 54.1% had persistent GERD symptoms. Younger individuals, women, Latino individuals, and participants with irritable bowel syndrome or Crohn's disease were more likely to have continued symptoms, even when taking PPIs. CONCLUSIONS Using a population-based survey, we found GERD symptoms to be common: 2 of 5 participants have had GERD symptoms in the past and 1 of 3 had symptoms in the past week. We also found that half of PPI users have persistent symptoms. Given the significant effect of GERD on quality of life, further research and development of new therapies are needed for patients with PPI-refractory GERD symptoms.
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Affiliation(s)
- Sean D. Delshad
- Cedars-Sinai Center for Outcomes Research and Education (CS-CORE), Los Angeles, CA,Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA
| | - Christopher V. Almario
- Cedars-Sinai Center for Outcomes Research and Education (CS-CORE), Los Angeles, CA,Division of Digestive and Liver Diseases, Cedars-Sinai Medical Center, Los Angeles, CA,Division of Health Services Research, Cedars-Sinai Medical Center, Los Angeles, CA,Division of Informatics, Cedars-Sinai Medical Center, Los Angeles, CA
| | - William D. Chey
- Division of Gastroenterology, Michigan Medicine, Ann Arbor, MI
| | - Brennan M.R. Spiegel
- Cedars-Sinai Center for Outcomes Research and Education (CS-CORE), Los Angeles, CA,Division of Digestive and Liver Diseases, Cedars-Sinai Medical Center, Los Angeles, CA,Division of Health Services Research, Cedars-Sinai Medical Center, Los Angeles, CA
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Shibli F, Kitayama Y, Fass R. Novel Therapies for Gastroesophageal Reflux Disease: Beyond Proton Pump Inhibitors. Curr Gastroenterol Rep 2020; 22:16. [PMID: 32185589 DOI: 10.1007/s11894-020-0753-y] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/10/2023]
Abstract
PURPOSE OF REVIEW Despite the many areas of unmet needs in gastroesophageal reflux disease (GERD), proton pump inhibitors (PPIs) remain the cornerstone of medical therapy. However, since their introduction, the therapeutic limitations of PPIs in GERD management have been increasingly recognized. RECENT FINDINGS In this review we discuss the new medical, endoscopic, and surgical therapeutic modalities that have been developed over the last decade. They include the potassium-competitive acid blockers (P-CABs) which provide a rapid onset, prolonged, and profound acid suppression, mucosal protectants which promote the physiological protective barrier of the esophageal mucosa, new prokinetics and neuromodulators. There are growing numbers of novel therapeutic endoscopic techniques that are under investigation or were recently introduced into the market, further expanding our therapeutic armamentarium for GERD. The development of diverse therapeutic modalities for GERD, despite the availability of PPIs, suggests that there are many areas of unmet need in GERD that will continue and drive future exploration for novel therapies.
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Affiliation(s)
- Fahmi Shibli
- The Esophageal and Swallowing Center, Division of Gastroenterology and Hepatology, MetroHealth Medical Center, Case Western Reserve University, 2500 MetroHealth Drive, Cleveland, OH, 44109, USA
| | - Yoshitaka Kitayama
- The Esophageal and Swallowing Center, Division of Gastroenterology and Hepatology, MetroHealth Medical Center, Case Western Reserve University, 2500 MetroHealth Drive, Cleveland, OH, 44109, USA
| | - Ronnie Fass
- The Esophageal and Swallowing Center, Division of Gastroenterology and Hepatology, MetroHealth Medical Center, Case Western Reserve University, 2500 MetroHealth Drive, Cleveland, OH, 44109, USA.
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Gotoh Y, Ishibashi E, Honda S, Nakaya T, Noguchi C, Kagawa K, Murakami K. Efficacy of vonoprazan for initial and maintenance therapy in reflux esophagitis, nonerosive esophagitis, and proton pump inhibitor-resistant gastroesophageal reflux disease. Medicine (Baltimore) 2020; 99:e19520. [PMID: 32176102 PMCID: PMC7440130 DOI: 10.1097/md.0000000000019520] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
Proton pump inhibitors (PPIs) have been the first line treatment for gastroesophageal reflux disease (GERD). The aim of this study was to evaluate the efficacy of vonoprazan (VPZ), a potassium-competitive acid blocker for reflux esophagitis (RE), nonerosive reflux disease (NERD), and PPI-resistant GERD patients.An open-label, single-center, observational study in our hospital was performed from August 2016 to August 2017. All patients diagnosed with GERD were asked to self-report a questionnaire of frequency scale for the symptoms of GERD (FSSG) and rate their degree of satisfaction with the treatment of GERD during outpatient visit. A total of 200 (RE 47, NERD 49, PPI-resistant GERD 104) patients were included in the present study. The primary endpoint was the change of FSSG and the proportion of degree of satisfaction with the treatment at the end of the initial therapy. A percentage of improvement (improvement rate) and resolution (resolution rate) at the end of the initial therapy were evaluated. Secondary endpoint included the proportion of patients with symptomatic relapse in the 24-week maintenance phase.FSSG and the degree of satisfaction were significantly improved after the initial therapy in every group. Improvement and resolution rate after the initial therapy were 83.0% and 67.0% in RE, 66.7% and 60.4% in NERD, and 76.0% and 60.4% in PPI-resistant group. There was no significance between after the initial therapy and 24 weeks in improvement and resolution rate. Thirty-two of the total 48 patients did not take VPZ at 24 weeks. Total FSSG score in each group was 1.67 ± 1.97, 2.71 ± 4.91, and 4.0 ± 4.93. The nonrelapse rate at 24 weeks in each group was 66.7%, 60.0%, and 50.0%. The resolution rate at 24 weeks in each group was 38.9%, 45.0%, and 30.0%.The VPZ therapy is effective for initial and maintenance therapy and improves heartburn and patient's satisfaction significantly in all 3 groups. Among patients who stopped taking VPZ during the maintenance period, 42.0% of RE and NERD group and 30% of PPI-resistant group experience complete remission from GERD at 24 weeks by introduction of VPZ.
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Affiliation(s)
- Yasuhiko Gotoh
- Department of Gastroenterology, Shin Beppu Hospital, Beppu
| | | | | | | | | | - Koichi Kagawa
- Department of Gastroenterology, Shin Beppu Hospital, Beppu
| | - Kazunari Murakami
- Department of Gastroenterology, Oita University Hospital, Yufu, Oita, Japan
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Takeuchi T, Furuta T, Fujiwara Y, Sugimoto M, Kasugai K, Kusano M, Okada H, Suzuki T, Higuchi T, Kagami T, Uotani T, Yamade M, Sawada A, Tanaka F, Harada S, Ota K, Kojima Y, Murata M, Tamura Y, Funaki Y, Kawamura O, Okamoto Y, Fujimoto K, Higuchi K. Randomised trial of acid inhibition by vonoprazan 10/20 mg once daily vs rabeprazole 10/20 mg twice daily in healthy Japanese volunteers (SAMURAI pH study). Aliment Pharmacol Ther 2020; 51:534-543. [PMID: 31990424 DOI: 10.1111/apt.15641] [Citation(s) in RCA: 40] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2019] [Revised: 09/10/2019] [Accepted: 01/05/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND Vonoprazan (V), a potassium-competitive acid blocker, has a more durable acid-inhibitory effect as compared with standard-dose proton pump inhibitors (PPIs) but has not been compared with 2-4 times higher daily PPI doses administered in two divided doses. AIMS To evaluate the acid-inhibitory effect of V 10/20 mg once-daily (OD; V10/V20) vs rabeprazole (R) 10/20 mg twice-daily (BID; R20/R40) in healthy Japanese volunteers. METHODS This multicentre, randomised, open-label, two-period, crossover study compared V10 or V20 vs R20, or V20 vs R40 using three cohorts of 10 healthy Japanese adults. Within each cohort, subjects were randomised to receive V or R for 7 days and, following a washout period ≥7 days, the other treatment for 7 days. On day 6 of each period, 24-hours multichannel gastric impedance-pH monitoring was performed. Percent times pH ≥ 3, ≥4 and ≥5 (pH 3, 4 and 5 holding time ratios [HTRs]) in 24 hours were evaluated as primary pharmacodynamic endpoints. RESULTS Acid-inhibitory effect (24-hours pH 3 HTR) of V20 was greater than those of R20 (91.0% vs 65.3%; P = .0049) and R40 (98.5% vs 85.9%; P = .0073). Similar results were obtained for 24-hours pH 4 and 5 HTRs. V20 also achieved greater nocturnal pH 4 (91.5% vs 73.2%; P = .0319) and 5 HTRs (78.8% vs 62.2%; P = .0325) as compared with R40. One subject (20%) developed diarrhoea while receiving R40 which was considered treatment-related. CONCLUSIONS Compared with 2-4 times the standard daily dose of R, V20 exerts a more potent and durable acid-inhibitory effect. Trial identifier: UMIN000022198 (www.umin.ac.jp/ctr/index.htm).
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Affiliation(s)
| | - Takahisa Furuta
- Center for Clinical Research, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Yasuhiro Fujiwara
- Department of Gastroenterology, Osaka City University Graduate School of Medicine School of Medicine, Osaka, Japan
| | - Mitsushige Sugimoto
- Division of Digestive Endoscopy, Shiga University of Medical Science Hospital, Otsu, Japan
| | - Kunio Kasugai
- Department of Gastroenterology, Aichi Medical University, Aichi, Japan
| | - Motoyasu Kusano
- Department of Endoscopy and Endoscopic Surgery, Gunma University Hospital, Meabashi, Japan
| | - Hiroyuki Okada
- Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Okayama, Japan
| | - Takahiro Suzuki
- First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Tomohiro Higuchi
- First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Takuma Kagami
- First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Takahiro Uotani
- First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Mihoko Yamade
- First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Akinari Sawada
- Department of Gastroenterology, Osaka City University Graduate School of Medicine School of Medicine, Osaka, Japan
| | - Fumio Tanaka
- Department of Gastroenterology, Osaka City University Graduate School of Medicine School of Medicine, Osaka, Japan
| | - Satoshi Harada
- Second Department of Internal Medicine, Osaka Medical College, Takatsuki, Japan
| | - Kazuhiro Ota
- Second Department of Internal Medicine, Osaka Medical College, Takatsuki, Japan
| | - Yuichi Kojima
- Endoscopic Center, Osaka Medical College Hospital, Takatsuki, Japan
| | - Masaki Murata
- Division of Digestive Endoscopy, Shiga University of Medical Science Hospital, Otsu, Japan
| | - Yasuhiro Tamura
- Department of Gastroenterology, Aichi Medical University, Aichi, Japan
| | - Yasushi Funaki
- Department of Gastroenterology, Aichi Medical University, Aichi, Japan
| | - Osamu Kawamura
- Department of Endoscopy and Endoscopic Surgery, Gunma University Hospital, Meabashi, Japan
| | - Yuki Okamoto
- Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Okayama, Japan
| | - Kazuma Fujimoto
- Department of Internal Medicine, Saga Medical School, Saga, Japan
| | - Kazuhide Higuchi
- Second Department of Internal Medicine, Osaka Medical College, Takatsuki, Japan
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Risk of hemorrhage and stricture significantly increases in elderly patients with proton pump inhibitor (PPI)-resistant reflux esophagitis. Esophagus 2020; 17:87-91. [PMID: 31679094 DOI: 10.1007/s10388-019-00702-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2019] [Accepted: 10/27/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND To examine the clinical characteristics, including complications, of patients older than 75 years of age with proton pump inhibitor-resistant reflux esophagitis. METHODS Patients who were resistant to standard-dose proton pump inhibitors were enrolled in the present study. Eligible patients (n = 26) were divided into those who were older (n = 11) and younger (n = 15) than 75 years of age. Clinical characteristics including complications (hemorrhage and stricture), body mass index, the severity of reflux esophagitis, Helicobactor pylori infection, gastric mucosal atrophy, hiatal hernia, kyphosis, and the use of antithrombotic agents were examined. The efficacy of 20 mg vonoprazan for proton pump inhibitor-resistant reflux esophagitis was also investigated. RESULTS The severity of reflux esophagitis was significantly higher in the elderly group than in the non-elderly group. No other significant differences were observed between the groups. The proportion of patients with hemorrhage was significantly larger in the elderly group than in the non-elderly group. Similarly, the proportion of patients with stricture was significantly larger in the elderly group than in the non-elderly group. Nine out of 10 patients in the elderly group and all patients in the non-elderly group achieved healing after the 4-week administration of 20 mg vonoprazan. No significant differences were observed in healing rates between the groups. CONCLUSION Among patients with proton pump inhibitor-resistant reflux esophagitis, the rates of severe reflux esophagitis and complications (hemorrhage and/or stricture) were significantly higher in elderly patients than in non-elderly patients. Regardless of age, 20 mg vonoprazan was effective for proton pump inhibitor-resistant reflux esophagitis.
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Yokoya Y, Igarashi A, Uda A, Deguchi H, Takeuchi T, Higuchi K. Cost-utility analysis of a 'vonoprazan-first' strategy versus 'esomeprazole- or rabeprazole-first' strategy in GERD. J Gastroenterol 2019; 54:1083-1095. [PMID: 31396703 DOI: 10.1007/s00535-019-01609-2] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2019] [Accepted: 07/31/2019] [Indexed: 02/04/2023]
Abstract
BACKGROUND Gastroesophageal reflux disease (GERD) can be treated using a vonoprazan-first strategy (first-line treatment with vonoprazan), or esomeprazole-first/rabeprazole-first strategies (first-line treatment with proton-pump inhibitors [PPIs], esomeprazole/rabeprazole, followed by a switch to vonoprazan). This cost-utility analysis used long-term simulation modeling to evaluate the cost-effectiveness of a vonoprazan-first strategy compared with the esomeprazole-first and rabeprazole-first strategies. METHODS A Markov simulation model was developed to evaluate the cost-effectiveness of vonoprazan-first, esomeprazole-first, and rabeprazole-first strategies, comprising healing and maintenance therapies, over 5 years (4-week cycles). Healing therapy began with the administration of a normal dose of drug per real-world practice. If patients were not healed endoscopically, either a longer duration of healing therapy was provided (vonoprazan), the dose was increased (rabeprazole), or patients were switched to vonoprazan (immediately for esomeprazole, and after dose-escalation for rabeprazole, respectively). Healed patients received maintenance (lower/same dose as healing therapy). Recurrence resulted in re-challenge with healing therapy. Transition probabilities were derived from the results of indirect comparisons (network meta-analysis) and costs calculated from the Japanese payer perspective. Outcomes were defined as quality-adjusted life years (QALYs), with utilities based on published values. RESULTS Expected costs of the vonoprazan-, esomeprazole-, and rabeprazole-first strategies were ¥36,194, ¥76,719, and ¥41,105, respectively, over 5 years. QALY gains for vonoprazan-first strategy versus the esomeprazole- and rabeprazole-first strategies were 0.014 and 0.003, respectively. Both estimated incremental cost-effectiveness ratios were dominant and robust to two sensitivity analyses. CONCLUSIONS Vonoprazan-first strategy increased QALYs and appeared to be cost-effective for GERD patients compared with the esomeprazole- or rabeprazole-first strategies.
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Affiliation(s)
- Yuta Yokoya
- Second Department of Internal Medicine, Osaka Medical College, 2-7 Digaku-cho, Takatsuki, Japan
| | - Ataru Igarashi
- Unit of Public Health and Preventive Medicine, School of Medicine, Yokohama City University, Yokohama, Japan
- Department of Health Economics and Outcomes Research, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan
| | - Akihito Uda
- Japan Medical Affairs, Takeda Pharmaceutical Company Limited, Tokyo, Japan
| | - Hisato Deguchi
- Japan Medical Affairs, Takeda Pharmaceutical Company Limited, Tokyo, Japan
| | - Toshihisa Takeuchi
- Second Department of Internal Medicine, Osaka Medical College, 2-7 Digaku-cho, Takatsuki, Japan.
| | - Kazuhide Higuchi
- Second Department of Internal Medicine, Osaka Medical College, 2-7 Digaku-cho, Takatsuki, Japan
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Sugawara K, Koizumi S, Horikawa Y, Mimori N, Tsuji T, Ishii H, Fujimori S, Onochi K, Watanabe H, Iijima K. Is the new potent acid-inhibitory drug vonoprazan effective for healing idiopathic peptic ulcers? A multicenter observational study in Akita Prefecture, Japan. J Gastroenterol 2019; 54:963-971. [PMID: 31037448 DOI: 10.1007/s00535-019-01587-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2019] [Accepted: 04/22/2019] [Indexed: 02/04/2023]
Abstract
BACKGROUND The incidence of peptic ulcers unrelated to H. pylori infection and non-steroidal anti-inflammatory drugs (NSAIDs), termed idiopathic peptic ulcers (IPUs), has increased worldwide. We recently reported that IPUs were refractory to proton pump inhibitor (PPI) treatment. Vonoprazan, which was recently developed in Japan, has shown a more potent acid-inhibitory effect than ordinary PPIs. In the present study, we compared the healing rates among peptic ulcers of different etiologies following treatment with vonoprazan. METHOD A multicenter observational study was performed at six participating hospitals in Akita Prefecture, Japan. Consecutive patients who had endoscopically confirmed gastro-duodenal ulcers were enrolled between August 2016 and March 2018. For each patient, the Helicobacter pylori infection status and NSAID use, including aspirin, were checked, and 20 mg vonoprazan was administered for 6 weeks for duodenal ulcers and 8 weeks for gastric ulcers. The healing status was checked by endoscopy at the end of vonoprazan treatment. Patients were divided into four subgroups according to the H. pylori status and NSAID usage. RESULTS The proportion of IPUs was 18.2%. A total of 162 patients completed the study protocol. The healing rate of IPUs was marginally lower than that of simple H. pylori-associated ulcers (81.2% vs. 93.5%, P = 0.05). Similarly, the healing rate of NSAID-related ulcers, irrespective of concomitant H. pylori infection, was significantly lower than that of simple H. pylori-associated ulcers. CONCLUSIONS Six- or 8-week vonoprazan treatment still seems to be insufficient for healing IPUs. Longer-term vonoprazan or another treatment option may be required to heal potentially refractory peptic ulcers.
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Affiliation(s)
- Kae Sugawara
- Department of Gastroenterology, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita, Akita, 010-8543, Japan
| | - Shigeto Koizumi
- Department of Gastroenterology, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita, Akita, 010-8543, Japan
| | - Yohei Horikawa
- Department of Gastroenterology, Hiraka General Hospital, Yokote, Japan
| | - Nobuya Mimori
- Department of Gastroenterology, Hiraka General Hospital, Yokote, Japan
| | - Tsuyotoshi Tsuji
- Department of Gastroenterology, Akita City Hospital, Akita, Japan
| | - Hajime Ishii
- Department of Gastroenterology, Akita City Hospital, Akita, Japan
| | - Shusei Fujimori
- Department of Gastroenterology, Yokote Municipal Hospital, Yokote, Japan
| | - Kengo Onochi
- Department of Gastroenterology, Omagari Kosei Medical Center, Daisen, Japan
| | - Hiroyuki Watanabe
- Department of Gastroenterology, Akita Kousei Medical Center, Akita, Japan
| | - Katsunori Iijima
- Department of Gastroenterology, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita, Akita, 010-8543, Japan.
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Efficacy of long-term maintenance therapy with 10-mg vonoprazan for proton pump inhibitor-resistant reflux esophagitis. Esophagus 2019; 16:377-381. [PMID: 31119492 DOI: 10.1007/s10388-019-00676-x] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2019] [Accepted: 05/14/2019] [Indexed: 02/03/2023]
Abstract
BACKGROUND To investigate the efficacy of long-term (52 weeks) maintenance therapy by 10-mg vonoprazan administration for proton pump inhibitor-resistant reflux esophagitis continued from the preceding study. METHODS Sixteen patients with proton pump inhibitor-resistant reflux esophagitis (mean age 70.9 years, eight males) in whom endoscopic healing was achieved by 20-mg vonoprazan administration for 4 weeks and maintenance of remission was maintained by 10-mg vonoprazan administration for 8 weeks were enrolled. Endoscopy was performed at 52 weeks after the initiation of maintenance therapy with 10-mg vonoprazan to evaluate whether there was any recurrence of reflux esophagitis. Changes in the gastric mucosa were investigated at 52 weeks. Symptoms were assessed using the frequency scale for the symptoms of gastroesophageal reflux disease and the fast gastrin level at 8 and 52 weeks following the maintenance therapy. RESULTS Endoscopic remission was maintained at 52 weeks in 15 (93.8%) of the 16 patients with proton pump inhibitor-resistant reflux esophagitis. One patient relapsed with grade C of reflux esophagitis. There were no significant differences in the symptom score at 8 and 52 weeks, nor the gastrin level at 8 and 52 weeks. There was no change in the stomach on endoscopy at 52 weeks. CONCLUSION Long-term maintenance therapy by 10-mg vonoprazan administration is very effective for proton pump inhibitor-resistant reflux esophagitis patients in whom endoscopic healing was maintained by 8 weeks maintenance therapy with 10-mg vonoprazan administration.
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The potential role of potassium-competitive acid blockers in the treatment of gastroesophageal reflux disease. Curr Opin Gastroenterol 2019; 35:344-355. [PMID: 31045597 DOI: 10.1097/mog.0000000000000543] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
PURPOSE OF REVIEW Gastroesophageal reflux disease (GERD) is primarily a motor disorder, but its pathogenesis is multifactorial. Although gastric acid secretion is usually normal in GERD patients, treatment with proton pump inhibitors (PPIs) has become the standard of care, despite increasing awareness of their shortcomings. In this article, a new class of antisecretory drugs (namely potassium-competitive acid blockers, P-CABs), developed to overcome these limitations, is discussed. RECENT FINDINGS P-CABs block the K exchange channel of the proton pump, resulting in rapid, competitive, reversible inhibition of acid secretion. These drugs offer a more rapid elevation of intragastric pH than PPIs, while maintaining similar antisecretory effect, the duration of which is dependent on half-life and can be prolonged with extended release formulations. Thus, P-CABs offer advances in the treatment of GERD including rapid heartburn relief, faster and more reliable healing of severe grades of erosive esophagitis, as a consequence of better control of nighttime acid secretion than PPIs. SUMMARY P-CABs overcome many of the drawbacks of PPIs. The unique antisecretory effects of vonoprazan might be especially useful in the long-term treatment of patients with Barrett's esophagus.
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Hoshikawa Y, Kawami N, Hoshino S, Tanabe T, Umezawa M, Kaise M, Iwakiri K. Efficacy of on-demand therapy using 20-mg vonoprazan for non-erosive reflux disease. Esophagus 2019; 16:201-206. [PMID: 30600486 DOI: 10.1007/s10388-018-00654-9] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2018] [Accepted: 12/21/2018] [Indexed: 02/03/2023]
Abstract
BACKGROUND To evaluate the efficacy of on-demand therapy using 20-mg vonoprazan for non-erosive reflux disease. METHODS On-demand therapy by taking one 20-mg tablet of vonoprazan only when reflux symptoms occurred was performed for 8 weeks by 30 patients (11 men, mean age: 67.8) with non-erosive reflux disease who responded well to maintenance therapy using proton pump inhibitor and answered "very satisfied" or "satisfied" to an overall satisfaction survey (5-grade scale). The degree of overall satisfaction with the treatment, score of symptoms, and fasting gastrin levels before breakfast was examined before and after on-demand therapy. The number of vonoprazan tablets taken and the frequency (regular, temporary, rare) of its administration were also investigated. RESULTS All patients completed 8-week on-demand therapy with 20-mg vonoprazan. Comparisons of patient satisfaction levels before and after therapy revealed no significant differences in the number of patients who were very satisfied and satisfied with the therapy. Furthermore, there were no significant differences in score of symptoms or gastrin levels before and after therapy. During 8-week on-demand therapy, patients took 11 tablets (median) (7.0-18.0 tablets: 25-75 percentiles), and 30.0% of patients (n = 9) took vonoprazan on a regular basis (at least 2 tablets a week). CONCLUSION On-demand therapy with 20-mg vonoprazan exerted equivalent effects to continuous PPI maintenance therapy for patients with non-erosive reflux disease.
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Affiliation(s)
- Yoshimasa Hoshikawa
- Department of Gastroenterology, Nippon Medical School, Graduate School of Medicine, 1-1-5, Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan
| | - Noriyuki Kawami
- Department of Gastroenterology, Nippon Medical School, Graduate School of Medicine, 1-1-5, Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan
| | - Shintaro Hoshino
- Department of Gastroenterology, Nippon Medical School, Graduate School of Medicine, 1-1-5, Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan
| | - Tomohide Tanabe
- Department of Gastroenterology, Nippon Medical School, Graduate School of Medicine, 1-1-5, Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan
| | - Mariko Umezawa
- Department of Gastroenterology, Nippon Medical School, Graduate School of Medicine, 1-1-5, Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan
| | - Mitsuru Kaise
- Department of Gastroenterology, Nippon Medical School, Graduate School of Medicine, 1-1-5, Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan
| | - Katsuhiko Iwakiri
- Department of Gastroenterology, Nippon Medical School, Graduate School of Medicine, 1-1-5, Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan.
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Mori H, Suzuki H. Role of Acid Suppression in Acid-related Diseases: Proton Pump Inhibitor and Potassium-competitive Acid Blocker. J Neurogastroenterol Motil 2019; 25:6-14. [PMID: 30504527 PMCID: PMC6326200 DOI: 10.5056/jnm18139] [Citation(s) in RCA: 60] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2018] [Revised: 09/27/2018] [Accepted: 10/25/2018] [Indexed: 12/11/2022] Open
Abstract
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-competitive acid blocker, which has distinct advantages compared to other conventional proton pump inhibitors in terms of the efficacy for acid suppression. Due to its strong gastric acid suppression capabilities, vonoprazan serves as an effective drug for the treatment of gastroesophageal reflux disease and H. pylori infection.
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Affiliation(s)
- Hideki Mori
- Department of Gastroenterology, National Hospital Organization Tokyo Medical Center, Tokyo,
Japan
| | - Hidekazu Suzuki
- Fellowship Training Center and Medical Education Center, Keio University School of Medicine, Tokyo,
Japan
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Kawami N, Hoshino S, Hoshikawa Y, Takenouchi N, Umezawa M, Hanada Y, Kaise M, Iwakiri K. Pathogenesis of Potassium-Competitive Acid Blocker-Resistant Non-Erosive Reflux Disease. Digestion 2019; 98:194-200. [PMID: 29870976 DOI: 10.1159/000488530] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2018] [Accepted: 03/16/2018] [Indexed: 02/04/2023]
Abstract
BACKGROUND The present study examined the pathogenesis of potassium-competitive acid blocker (P-CAB)-resistant non-erosive reflux disease (NERD). METHODS Forty-three patients with NERD, who had persistent reflux symptoms despite the administration of P-CAB, were included in this study. After excluding eosinophilic esophagitis and primary esophageal motility disorders, esophageal impedance-pH monitoring was performed. In symptom index (SI)-positive patients, the mechanism of SI-positivity and percent time with intragastric pH > 4 and with esophageal pH < 4 were investigated according to the presence or absence of Helicobacter pylori infection. RESULTS One (2.3%) of 43 patients had a primary esophageal motility disorder (Jackhammer esophagus). Eighteen (41.9%) and 3 (7%) patients were SI-positive for liquid and gas-only reflux, respectively, and the remaining 21 patients who were SI-negative (48.8%) had functional heartburn. All patients SI-positive for liquid reflux were SI-positive for weakly acidic reflux. Gastric acid was sufficiently suppressed by P-CAB, regardless of the presence or absence of H. pylori infection. CONCLUSIONS The pathogenesis of -P-CAB-resistant NERD was elucidated in 51% of patients. Symptoms in all patients SI-positive for liquid reflux were related to weakly acidic reflux, and symptoms related to acid reflux may be ruled out by the administration of P-CAB.
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