|
1
|
Armstrong D, Hungin AP, Kahrilas PJ, Sifrim D, Moayyedi P, Vaezi MF, Al‐Awadhi S, Anvari S, Bell R, Delaney B, Emura F, Gyawali CP, Katelaris P, Lazarescu A, Lee YY, Repici A, Roman S, Rooker CT, Savarino EV, Sinclair P, Sugano K, Yadlapati R, Yuan Y, Zerbib F, Sharma P. Management of Patients With Refractory Reflux-Like Symptoms Despite Proton Pump Inhibitor Therapy: Evidence-Based Consensus Statements. Aliment Pharmacol Ther 2025; 61:636-650. [PMID: 39740235 PMCID: PMC11754941 DOI: 10.1111/apt.18420] [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: 03/29/2024] [Revised: 04/16/2024] [Accepted: 11/18/2024] [Indexed: 01/02/2025]
Abstract
BACKGROUND Many patients diagnosed with gastro-oesophageal reflux disease (GERD) have persistent symptoms despite proton pump inhibitor (PPI) therapy. AIMS The aim of this consensus is to provide evidence-based statements to guide clinicians caring for patients with refractory reflux-like symptoms (rRLS) or refractory GERD. METHODS This consensus was developed by the International Working Group for the Classification of Oesophagitis. The steering committee developed specific PICO questions pertaining to the management of PPI rRLS. Methodologists conducted systematic reviews of the literature. The quality of evidence and strength of recommendations were rated using the GRADE approach. RESULTS Consensus was reached on 13 of 17 statements on diagnosis and management. For rRLS, suggested diagnostic strategies included endoscopy, ambulatory reflux testing and oesophageal manometry. The group did not reach consensus on the role of oesophageal biopsies or the use of reflux-symptom association in patients undergoing reflux testing. The group suggested against increasing the PPI dose in patients who had received 8 weeks of a twice-daily PPI. Adjunctive alginate or antacid therapy was suggested. There was no consensus on the role of adjunctive prokinetics. There was little role for adjunctive transient lower oesophageal sphincter relaxation (TLESR) inhibitors or bile acid sequestrants. Endoscopic or surgical anti-reflux procedures should not be performed in patients with rRLS in the absence of objectively confirmed GERD. CONCLUSIONS The management of rRLS should be personalised, based on shared decision-making regarding the role of diagnostic testing to confirm or rule out GERD as a basis for treatment optimisation. Anti-reflux procedures should not be performed without objective confirmation of GERD.
Collapse
Affiliation(s)
- David Armstrong
- Division of Gastroenterology & Farncombe Family Digestive Health Research InstituteMcMaster UniversityHamiltonOntarioCanada
| | - A. Pali Hungin
- Faculty of Medical SciencesNewcastle UniversityNewcastle upon TyneUK
| | - Peter J. Kahrilas
- Division of GastroenterologyNorthwestern UniversityChicagoIllinoisUSA
| | - Daniel Sifrim
- Barts and The London School of Medicine and DentistryQueen Mary University of LondonLondonUK
| | - Paul Moayyedi
- Division of Gastroenterology & Farncombe Family Digestive Health Research InstituteMcMaster UniversityHamiltonOntarioCanada
| | - Michael F. Vaezi
- Division of GastroenterologyVanderbilt University Medical CenterNashvilleTennesseeUSA
| | - Sameer Al‐Awadhi
- Department of GastroenterologyRashid Hospital, Dubai Academic Health CorporationDubaiUAE
| | - Sama Anvari
- Division of Gastroenterology & Farncombe Family Digestive Health Research InstituteMcMaster UniversityHamiltonOntarioCanada
| | - Reginald Bell
- Institute of Esophageal and Reflux SurgeryEnglewoodColoradoUSA
| | - Brendan Delaney
- Department of Surgery and CancerImperial College London, Saint Mary's CampusLondonUK
| | - Fabian Emura
- Digestive Health and Liver Diseases, Miller School of MedicineUniversity of MiamiMiamiFloridaUSA
- Gastroenterology Division, Universidad de La Sabana, ChiaCundinamarcaColombia
| | - C. Prakash Gyawali
- Division of GastroenterologyWashington University School of MedicineSt. LouisMissouriUSA
| | - Peter Katelaris
- Gastroenterology DepartmentConcord Hospital, University of SydneySydneyNew South WalesAustralia
| | - Adriana Lazarescu
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine and DentistryUniversity of AlbertaEdmontonAlbertaCanada
| | - Yeong Yeh Lee
- GI Function & Motility UnitHospital Universiti Sains MalaysiaKota BharuMalaysia
| | - Alessandro Repici
- Department of GastroenterologyIRCCS Istituto Clinico HumanitasRozzano (Milano)Italy
| | - Sabine Roman
- Division of Digestive PhysiologyCentre Hospitalier Universitaire de LyonLyonFrance
| | - Ceciel T. Rooker
- International Foundation for Functional Gastrointestinal Disorders (IFFGD)Mount PleasantSouth CarolinaUSA
| | | | | | - Kentaro Sugano
- Division of Gastroenterology, Department of MedicineJichi Medical UniversityTochigi‐kenJapan
| | - Rena Yadlapati
- Division of GastroenterologyUniversity of California San DiegoLa JollaCaliforniaUSA
| | - Yuhong Yuan
- Division of Gastroenterology & Farncombe Family Digestive Health Research InstituteMcMaster UniversityHamiltonOntarioCanada
| | - Frank Zerbib
- CHU de Bordeaux, Centre Médico‐Chirurgical Magellan, Hôpital Haut‐Levêque, Department of GastroenterologyUniversité de Bordeaux, INSERM CIC 1401BordeauxFrance
| | - Prateek Sharma
- Division of Gastroenterology and HepatologyUniversity of Kansas School of Medicine, and Kansas City VA Medical CenterKansas CityMissouriUSA
| | | |
Collapse
|
|
2
|
Nguyen T, Barnhill K, Zhornitskiy A, Yu KS, Fuller G, Makaroff K, Spiegel BMR, Gresham G, Almario CV. Comparing the efficacy of different proton pump inhibitor dosing regimens for the treatment of gastroesophageal reflux disease: a systematic review and meta-analysis. Dis Esophagus 2025; 38:doae109. [PMID: 39673371 DOI: 10.1093/dote/doae109] [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: 07/18/2024] [Revised: 11/05/2024] [Accepted: 11/14/2024] [Indexed: 12/16/2024]
Abstract
Several proton pump inhibitor (PPI) dosing regimens that vary by strength and frequency (once [Qday] or twice [BID] daily) are available to treat gastroesophageal reflux disease (GERD). We performed an updated systematic review and meta-analysis of randomized controlled trials (RCTs) assessing the impact of various PPI regimens on esophageal healing and GERD and heartburn symptoms. To identify relevant studies, we searched EMBASE and PubMed in January 2023, which yielded 1381 records. Eligible RCTs included those that enrolled adults diagnosed with GERD and compared different dosing regimens within the same PPI. The outcomes were esophageal healing and resolution of GERD and heartburn symptoms within 12 weeks (i.e. short-term) and > 12 weeks (i.e. long-term). Meta-analysis pooling of the odds ratios with 95% confidence intervals were estimated using the random-effects inverse-variance model. Overall, a total of 38 RCTs across 20 countries (N = 15,540 patients, mean age 50 years, 55% male) were included. Most PPI trials compared half standard dose Qday versus standard dose Qday or standard dose Qday versus double standard dose Qday. In general, when considering daily dosing, higher PPI strength significantly improved esophageal healing and relief of GERD symptoms both in the short- and long-term. Fewer trials compared Qday versus BID dosing; the impact of BID dosing on outcomes was inconsistent across the different PPI strength comparisons. In conclusion, this meta-analysis revealed that increasing PPI Qday dosages led to improved GERD outcomes. However, few studies compared Qday to BID dosing; as twice daily PPI usage is common in clinical practice, further studies are warranted to determine whether such dosing improves clinical outcomes.
Collapse
Affiliation(s)
- Tyra Nguyen
- Division of Population Sciences, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Katherine Barnhill
- Division of Population Sciences, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Alex Zhornitskiy
- Cedars-Sinai Center for Outcomes Research and Education (CS-CORE), Department of Medicine, Los Angeles, CA, USA
| | - Kyung Sang Yu
- Cedars-Sinai Center for Outcomes Research and Education (CS-CORE), Department of Medicine, Los Angeles, CA, USA
| | - Garth Fuller
- Cedars-Sinai Center for Outcomes Research and Education (CS-CORE), Department of Medicine, Los Angeles, CA, USA
| | - Katherine Makaroff
- Cedars-Sinai Center for Outcomes Research and Education (CS-CORE), Department of Medicine, Los Angeles, CA, USA
| | - Brennan M R Spiegel
- Cedars-Sinai Center for Outcomes Research and Education (CS-CORE), Department of Medicine, Los Angeles, CA, USA
- Karsh Division of Gastroenterology and Hepatology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Gillian Gresham
- Division of Population Sciences, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Christopher V Almario
- Cedars-Sinai Center for Outcomes Research and Education (CS-CORE), Department of Medicine, Los Angeles, CA, USA
- Karsh Division of Gastroenterology and Hepatology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| |
Collapse
|
|
3
|
S2k guideline Gastroesophageal reflux disease and eosinophilic esophagitis of the German Society of Gastroenterology, Digestive and Metabolic Diseases (DGVS). ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:1786-1852. [PMID: 39389106 DOI: 10.1055/a-2344-6282] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/12/2024]
|
|
4
|
Pan S, Thrift AP, Akhdar G, El-Serag HB. Gastric Cancer Risk in Patients with Long-Term Use of Proton Pump Inhibitors: A Systematic Review and Meta-Analysis of Observational and Interventional Studies. Dig Dis Sci 2023; 68:3732-3744. [PMID: 37432532 DOI: 10.1007/s10620-023-08018-9] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2023] [Accepted: 06/19/2023] [Indexed: 07/12/2023]
Abstract
BACKGROUND A growing number of studies that differ in design, quality, and results report an association between the use of proton pump inhibitors (PPIs) and the risk of gastric cancer (GC). We conducted a systematic review and meta-analysis, when possible, of observational and interventional studies examining PPI use and risk of GC. METHODS We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We identified studies fully published in English through January 2023 using MeSH and non-MeSH keywords. We used random effects models to calculate pooled risk estimates with 95% confidence interval (CI) between PPI use and overall GC, cardia GC, and non-cardia GC. We estimated heterogeneity (I2) among studies. We examined the effect of study design and quality, GC site, H. pylori infection, and PPI duration. We assessed quality using the Newcastle-Ottawa Quality Assessment Scale and Risk Of Bias In Non-randomized Studies of Interventions. RESULTS We identified 15 observational studies, of which 13 were included in the meta-analysis (six cohort and seven case-control). There was a modest 1.67-fold increase in overall GC risk (95% CI 1.39, 2.00) and no increase in cardia GC risk [odds ratio (OR) 1.12; 95% CI 0.80, 1.56] with PPI use. However, there was high heterogeneity (I2 = 61.3%, p = 0.004) among studies. All but one study had at least moderate risk of bias. In the six studies accounting for H. pylori, GC risk associated with PPI use increased slightly (OR 1.78; 95% CI 1.25, 2.52). Duration response was not reported consistently to allow pooled estimates. We identified only one interventional randomized controlled study that included GC as an outcome of interest, and it did not show increased GC risk. CONCLUSIONS The overall available evidence is not supportive of a meaningful change in GC risk, either cardia or non-cardia, with PPI use.
Collapse
Affiliation(s)
- Sharon Pan
- Texas A&M School of Medicine, Bryan, TX, USA
| | - Aaron P Thrift
- Section of Epidemiology and Population Sciences, Department of Medicine, Baylor College of Medicine, Houston, TX, USA
| | - Ghida Akhdar
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, TX, USA
| | - Hashem B El-Serag
- Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX, USA.
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, TX, USA.
- Section of Gastroenterology, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX, USA.
| |
Collapse
|
|
5
|
Zheng Z, Lu Z, Song Y. Long-term proton pump inhibitors use and its association with premalignant gastric lesions: a systematic review and meta-analysis. Front Pharmacol 2023; 14:1244400. [PMID: 37693896 PMCID: PMC10492503 DOI: 10.3389/fphar.2023.1244400] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2023] [Accepted: 08/14/2023] [Indexed: 09/12/2023] Open
Abstract
Background: Long-term maintenance therapy with proton pump inhibitors (PPIs) is a common treatment strategy for acid-related gastrointestinal diseases. However, concerns have been raised about the potential increased risk of gastric cancer and related precancerous lesions with long-term PPI use. This systematic review and meta-analysis aimed to evaluate this potential risk. Methods: We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials for randomised controlled trials published before 1 March 2023, with no language restrictions. The primary endpoint was the occurrence and progression of gastric mucosal atrophy, intestinal metaplasia, Enterochromaffin-like (ECL) cell hyperplasia, gastric polyps, and gastric cancer during the trial and follow-up. Data were analysed using a random effects model. Results: Of the 4,868 identified studies, 10 met the inclusion criteria and were included in our analysis, comprising 27,283 participants. Compared with other treatments, PPI maintenance therapy for more than 6 months was associated with an increased risk of ECL cell hyperplasia (OR 3.01; 95% CI 1.29 to 7.04; p = 0.01). However, no significant increase was found in the risk of gastric mucosal atrophy (OR 1.01; 95% CI 0.55 to 1.85; p = 0.97), intestinal metaplasia (OR 1.14; 95% CI 0.49 to 2.68; p = 0.76), gastric polyps (OR 1.13; 95% CI 0.68 to 1.89; p = 0.64), or gastric cancer (OR 1.06; 95% CI 0.79 to 1.43; p = 0.71). Conclusion: This systematic review and meta-analysis does not support an increased risk of gastric cancer or related precancerous lesions with long-term PPI maintenance therapy. However, long-term PPI use should be monitored for potential complications such as ECL cell hyperplasia. Further studies are needed to confirm these findings and evaluate the safety of PPI maintenance therapy for acid-related gastrointestinal diseases. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, Identifier: PROSPERO (CRD42022379692).
Collapse
Affiliation(s)
- Zeyi Zheng
- School of Traditional Chinese Medicine, Inner Mongolia Medical University, Hohhot, Inner Mongolia, China
| | - Ziyu Lu
- School of Basic Medicine, Inner Mongolia Medical University, Hohhot, Inner Mongolia, China
| | - Yani Song
- School of Water Resources and Hydropower Engineering, Wuhan University, Wuhan, Hubei, China
| |
Collapse
|
|
6
|
S2k-Leitlinie Gastroösophageale Refluxkrankheit und eosinophile Ösophagitis der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) – März 2023 – AWMF-Registernummer: 021–013. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2023; 61:862-933. [PMID: 37494073 DOI: 10.1055/a-2060-1069] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/28/2023]
|
|
7
|
Yadlapati R, Hubscher E, Pelletier C, Jacob R, Brackley A, Shah S. Induction and maintenance of healing in erosive esophagitis in the United States. Expert Rev Gastroenterol Hepatol 2022; 16:967-980. [PMID: 36254610 DOI: 10.1080/17474124.2022.2134115] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
INTRODUCTION Erosive esophagitis (EE) occurs when refluxate from the stomach causes T-lymphocyte infiltration of the esophageal mucosa, resulting in mucosal breaks. Currently, therapy with proton-pump inhibitors (PPIs) is the standard treatment for EE in the United States, but few comprehensive reviews exist on the efficacy of PPIs in US populations. Here, we present the most contemporary, thorough analysis of PPI efficacy rates, and identify and characterize patient subgroups at risk for poor healing outcomes. AREAS COVERED We searched the literature to identify studies reporting rates of endoscopic healing and maintained healing of EE with PPI therapies in the US and found a paucity of recent evidence and real-world evidence. Twenty-two studies from 2009 and earlier were included in the final dataset. EXPERT OPINION Rates of EE healing with PPIs were highest after 8 weeks of treatment, with over 80% of patients in most treatment arms demonstrating endoscopic healing, compared to lower efficacy (<80%) at 4 weeks. Rates of maintained healing with PPIs at 6 and 12 months were mostly lower than 80%, although the data were limited. Symptomatic patients and those with severe EE were less likely to achieve healing. Obese patients experienced similar healing rates as non-obese patients.
Collapse
Affiliation(s)
- Rena Yadlapati
- Division of Gastroenterology, University of California San Diego, La Jolla, California, USA
| | | | - Corey Pelletier
- Health Economics and Outcomes Research, Phathom Pharmaceuticals, Florham Park, New Jersey, USA
| | - Rinu Jacob
- Health Economics and Outcomes Research, Phathom Pharmaceuticals, Florham Park, New Jersey, USA
| | - Allison Brackley
- Real-World Advanced Analytics, Cytel, Inc, Waltham, Massachusetts, USA
| | - Shailja Shah
- Division of Gastroenterology, University of California San Diego, La Jolla, California, USA
| |
Collapse
|
|
8
|
Liang SW, Wong MW, Yi CH, Liu TT, Lei WY, Hung JS, Lin L, Rogers BD, Chen CL. Current advances in the diagnosis and management of gastroesophageal reflux disease. Tzu Chi Med J 2022; 34:402-408. [PMID: 36578634 PMCID: PMC9791847 DOI: 10.4103/tcmj.tcmj_323_21] [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: 12/12/2021] [Revised: 01/10/2022] [Accepted: 02/23/2022] [Indexed: 12/31/2022] Open
Abstract
Gastroesophageal reflux disease (GERD) is very common and defined as troublesome symptoms owing to excessive acid reflux. The spectrum of GERD is broad, including not only erosive esophagitis and Barrett's esophagus but also nonerosive reflux disease (NERD), reflux hypersensitivity, and functional heartburn. Patients with reflux symptoms despite normal endoscopy remain common clinical presentation, can be heterogeneous overlapping with functional gastrointestinal disorders. Ambulatory esophageal pH monitoring with and without impedance helps the diagnosis of NERD. Metrics such as baseline impedance and postreflux swallow induced peristaltic wave enhance diagnostic accuracy in patients with inconclusive diagnoses. The major treatment of all manifestations of GERD is acid suppression with proton pump inhibitors, while other therapies, such as reflux-reducing agents and adjunctive medications, can be individualized where the response to traditional management is incomplete. GERD patients often need long-term treatment due to frequent relapses. Anti-reflux surgery can be effective too. Endoscopic therapies have some promising results, but long-term outcomes remain to be determined.
Collapse
Affiliation(s)
- Shu-Wei Liang
- Department of Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and Tzu Chi University, Hualien, Taiwan
| | - Ming-Wun Wong
- Department of Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and Tzu Chi University, Hualien, Taiwan,School of Post-Baccalaureate Chinese Medicine, Tzu Chi University, Hualien, Taiwan
| | - Chih-Hsun Yi
- Department of Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and Tzu Chi University, Hualien, Taiwan
| | - Tso-Tsai Liu
- Department of Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and Tzu Chi University, Hualien, Taiwan
| | - Wei-Yi Lei
- Department of Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and Tzu Chi University, Hualien, Taiwan
| | - Jui-Sheng Hung
- Department of Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and Tzu Chi University, Hualien, Taiwan
| | - Lin Lin
- Department of Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and Tzu Chi University, Hualien, Taiwan
| | - Benjamin D. Rogers
- Division of Gastroenterology, Hepatology and Nutrition, University of Louisville, Louisville, Kentucky, USA,Division of Gastroenterology, Washington University School of Medicine, St Louis, Missouri, USA
| | - Chien-Lin Chen
- Department of Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and Tzu Chi University, Hualien, Taiwan,Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan,Address for correspondence: Dr. Chien-Lin Chen, Department of Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, 707, Section 3, Chung-Yang Road, Hualien, Taiwan. E-mail:
| |
Collapse
|
|
9
|
Dash SK, Acharjya SK, Chakraborty A, Sahoo M, Tripathy S, Tripathy B, Deo R. Application of Analytical Tools and Techniques for Estimation of a Proton Pump Inhibitor (Esomeprazole Magnesium Trihydrate): A Comprehensive Review. CURR PHARM ANAL 2022. [DOI: 10.2174/1573412918666220426110831] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Objective:
The application of various sophisticated analytical tools and techniques is essential for estimating an active pharmaceutical ingredient present in either biofluids or pharmaceutical dosage forms. Reporting the multiple analytical methods used to quantify esomeprazole magnesium trihydrate, a proton pump inhibitor, is the ultimate goal of this review article.
Evidence acquisition:
This article deals with a detailed discussion of different reported analytical procedures along with their pros and cons and their relevant criteria for quantifying the drug. Various analytical techniques like UV-Visible spectrophotometry, HPLC, HPTLC, hyphenated techniques, etc., are developed to assess the esomeprazole magnesium trihydrate in bulk materials, different pharmaceutical formulations, and biological matrices.
Conclusion:
Literature survey confirmed that the hyphenated techniques and chromatographic techniques are best tools for biological matrices. Spectroscopic methods like UV and visible techniques are widely used for pharmaceutical matrices. All of the reported methods are accurate, precise, cost-effective, and sensitive.
Collapse
Affiliation(s)
- Sanat Kumar Dash
- Department of Pharmaceutical Analysis and Quality Assurance, Roland Institute of Pharmaceutical Sciences, Berhampur, India
| | - Sasmita Kumari Acharjya
- Department of Pharmaceutical Analysis and Quality Assurance, Roland Institute of Pharmaceutical Sciences, Berhampur, India
| | - Atyurmila Chakraborty
- Department of Pharmaceutical Analysis and Quality Assurance, Roland Institute of Pharmaceutical Sciences, Berhampur, India
| | - Mitali Sahoo
- Department of Pharmaceutical Analysis and Quality Assurance, Roland Institute of Pharmaceutical Sciences, Berhampur, India
| | - Satyanarayan Tripathy
- Department of Pharmaceutical Analysis and Quality Assurance, Roland Institute of Pharmaceutical Sciences, Berhampur, India
| | - Bimala Tripathy
- Department of Pharmaceutical Analysis and Quality Assurance, Roland Institute of Pharmaceutical Sciences, Berhampur, India
| | - Ramanath Deo
- Department of Pharmaceutical Analysis and Quality Assurance, Roland Institute of Pharmaceutical Sciences, Berhampur, India
| |
Collapse
|
|
10
|
Rosenberg V, Tzadok R, Chodick G, Kariv R. Proton pump inhibitors long term use-trends and patterns over 15 years of a large health maintenance organization. Pharmacoepidemiol Drug Saf 2021; 30:1576-1587. [PMID: 34453456 DOI: 10.1002/pds.5352] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2021] [Revised: 08/05/2021] [Accepted: 08/25/2021] [Indexed: 11/09/2022]
Abstract
BACKGROUND Proton pump inhibitors (PPI) are used for a variety of indications. Despite reported associations with undesirable effects, their long-term use is on the rise, while appropriate indications, dose, and treatment duration may deviate from guideline recommendations. OBJECTIVES Primary to examine the annual patterns of PPI use. Secondary- to assess indications for initiating PPI treatment, long-term use, and factors associated with long-term use in a large Israeli health maintenance organization. METHODS A historical cohort study of 528 420 eligible PPI users during 2000-2015, analyzed PPI use using defined daily doses and the proportion of patients covered method. Data on indications for treatment initiation, clinical and socio-demographic parameters were captured as well. A multivariable logistic-regression model was used to identify factors associated with long-term use of PPI. RESULTS The annual incidence rates of patients initiating PPI treatment were relatively constant, ranging between 2.4% and 3.1% of the adult population, with a monotonic increase in annual consumption and prevalence (reaching 12.7% in 2015). Reflux, functional symptoms, and Helicobacter pylori eradication were the most common indications for initiating PPI therapy. However, 27% of patients had no recorded indication for treatment. Fifteen percent of patients used PPI for over 6 months, especially in older age groups. CONCLUSIONS Utilization of PPI increases steadily, mainly due to chronic use. Prolonged consumption is associated with specific clinical indications and older age. Health organizations should encourage awareness of appropriate use among physicians, specifically in the elderly, patients with reflux, and those with functional disorders.
Collapse
Affiliation(s)
- Vered Rosenberg
- Kahn-Sagol-Maccabi Research and Innovation Institute, Maccabi Healthcare Services, Tel Aviv, Israel
| | - Roie Tzadok
- Department of Internal Medicine H, Sourasky Medical Center, Tel Aviv, Israel
| | - Gabriel Chodick
- Kahn-Sagol-Maccabi Research and Innovation Institute, Maccabi Healthcare Services, Tel Aviv, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Revital Kariv
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.,Department of Gastroenterology, Sourasky Medical Center, Tel Aviv, Israel
| |
Collapse
|
|
11
|
Goh K, Lee Y, Leelakusolvong S, Makmun D, Maneerattanaporn M, Quach DT, Raja Ali RA, Sollano JD, Tran VH, Wong RK. Consensus statements and recommendations on the management of mild-to-moderate gastroesophageal reflux disease in the Southeast Asian region. JGH Open 2021; 5:855-863. [PMID: 34386592 PMCID: PMC8341192 DOI: 10.1002/jgh3.12602] [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: 05/13/2021] [Revised: 06/11/2021] [Accepted: 06/14/2021] [Indexed: 02/05/2023]
Abstract
This paper reports the proceedings from the first consensus meeting on the management of mild-to-moderate gastroesophageal reflux disease (GERD) in the Southeast Asian (SEA) region. Seventeen statements were drawn up by a steering committee that focused on epidemiology, mechanism of action, diagnostic investigations, and treatment. Voting on the recommendations used the Delphi method with two rounds of voting among the 10 panel members. The consensus panel agreed that GERD is mostly a mild disease in the SEA region with predominantly non-erosive reflux disease (NERD). Complicated GERD and Barrett's esophagus are infrequently seen. The panel recommended endoscopy in patients with alarm or refractory symptoms but cautioned that the incidence of gastric cancer is higher in SEA. pH and impedance measurements were not recommended for routine assessment. The acid pocket is recognized as an important pathogenic factor in GERD. Lifestyle measures such as weight reduction, avoidance of smoking, reduction of alcohol intake, and elevation of the head of the bed were recommended but strict avoidance of specific foods or drinks was not. Alginates was recommended as the first-line treatment for patients with mild-to-moderate GERD while recognizing that proton-pump inhibitors (PPIs) remained the mainstay of treatment of GERD. The use of alginates was also recommended as adjunctive therapy when GERD symptoms were only partially responsive to PPIs.
Collapse
Affiliation(s)
- Khean‐Lee Goh
- Department of MedicineUniversity of MalayaKuala LumpurMalaysia
| | - Yeong‐Yeh Lee
- Department of Medicine, School of Medical SciencesUniversiti Sains MalaysiaKota BharuMalaysia
| | - Somchai Leelakusolvong
- Division of Gastroenterology, Faculty of Medicine, Siriraj HospitalMahidol UniversityBangkokThailand
| | - Dadang Makmun
- Division of Gastroenterology, Department of Internal MedicineFaculty of Medicine Universitas Indonesia/Cipto Mangunkusumo National General HospitalJakartaIndonesia
| | - Monthira Maneerattanaporn
- Division of Gastroenterology, Faculty of Medicine, Siriraj HospitalMahidol UniversityBangkokThailand
| | - Duc Trong Quach
- Department of Internal MedicineUniversity of Medicine and PharmacyHo Chi Minh CityVietnam
| | - Raja Affendi Raja Ali
- Gastroenterology Unit, Department of Medicine and Gut Research Group, Faculty of MedicineUniversiti Kebangsaan MalaysiaBangiMalaysia
| | - Jose D Sollano
- Department of GastroenterologyUniversity of Santo TomasManilaPhilippines
| | - Van Huy Tran
- Department of Gastroenterology, Hue University of Medicine and PharmacyHue UniversityHue CityVietnam
| | - Reuben Kong‐Min Wong
- Department of Medicine, Faculty of MedicineNational University of SingaporeSingapore
| |
Collapse
|
|
12
|
Hou M, Hu H, Jin C, Yu X. Efficacy and Safety of Esomeprazole for the Treatment of Reflux Symptoms in Patients with Gastroesophageal Reflux Disease: A Systematic Review and Meta-Analysis. IRANIAN JOURNAL OF PUBLIC HEALTH 2020; 49:2264-2274. [PMID: 34178733 PMCID: PMC8215048 DOI: 10.18502/ijph.v49i12.4807] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
Background: We investigated the efficacy of esomeprazole for the treatment of gastroesophageal reflux disease (GERD) in a meta-analysis of clinical trials results. Methods: Medline, Embase, PubMed and Web of Science databases were systematically searched for suitable studies, and double-blind, randomized controlled trials (RCTs) were involved. A meta-analysis of RCTs was performed to analyze the efficacy of esomeprazole on clinical outcomes that associated with the severity of GERD. Results: A total of 8 clinical trials were selected in our meta-analysis (N=4495, patients with GERD). Esomeprazole treatment yielded a significant improvement in clinical signs and symptoms of GERD compared to placebo group. Funnel plot and Egger test showed there was no significant bias in the publication. Cochrane collaboration tool and Jadad scale were used to indicate that all 8 RCTs were of high quality. The results of Galbraith radial plot showed that no study was the major source of heterogeneity. Esomeprazole treatment significantly decreased the relapse rates more than that of placebo group (RR = 0.729; 95% CI: 0.670 to 0.794; P<0.001). It seems to be lower rates of heartburn (RR = 0.747; 95%CI: 0.665–0.839; P <0.001) and epigastric pain (RR = 0.795; 95%CI: 0.679–0.932; P =0.005) in esomeprazole-treated group compared with the placebo group. Moreover, serious adverse events was less likely to happen after esomeprazole therapy (RR = 1.406, 95% CI: 1.030–1.918; P =0.032). Conclusion: Compared with the control group, esomeprazole is a promising therapeutic agent that improves the management of patients with GERD.
Collapse
Affiliation(s)
- Mingxing Hou
- Department of Gastroenterology Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia, 010058, China
| | - Haiqing Hu
- Department of Gastroenterology and Hepatology Chinese PLA General Hospital, Beijing, 100853, China
| | - Chunlu Jin
- Department of Gastroenterology and Hepatology Chinese PLA General Hospital, Beijing, 100853, China
| | - Xuemei Yu
- Department of Gastroenterology and Hepatology Chinese PLA General Hospital, Beijing, 100853, China
| |
Collapse
|
|
13
|
Why differences between New York and New Delhi matter in approach to gastroesophageal reflux disease. Indian J Gastroenterol 2019; 38:371-377. [PMID: 31768894 DOI: 10.1007/s12664-019-00987-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
|
|
14
|
Miwa H, Igarashi A, Teng L, Uda A, Deguchi H, Tango T. Systematic review with network meta-analysis: indirect comparison of the efficacy of vonoprazan and proton-pump inhibitors for maintenance treatment of gastroesophageal reflux disease. J Gastroenterol 2019; 54:718-729. [PMID: 30919071 PMCID: PMC6647489 DOI: 10.1007/s00535-019-01572-y] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2018] [Accepted: 03/14/2019] [Indexed: 02/08/2023]
Abstract
BACKGROUND Long-term maintenance treatment of gastroesophageal reflux disease (GERD) is important to prevent relapse. Proton-pump inhibitors (PPIs) are used for both treatment and maintenance therapy of GERD. Recently, a potassium-competitive acid blocker vonoprazan was launched in Japan. We evaluated the comparative efficacy of vonoprazan and other PPIs for GERD maintenance. METHODS A systematic literature search was performed using MEDLINE and Cochrane Central Register of Controlled Trials. Double-blind randomized controlled trials (RCTs) of PPIs, vonoprazan, and placebo for GERD maintenance published in English or Japanese were selected. Among them, studies conducted at the recommended dose and for the recommended use, and containing information on maintenance rate based on endoscopic assessment, were included. The comparative efficacies of treatments were estimated by performing a Bayesian network meta-analysis, which assessed the consistency assumption. Outcomes were number or rate of patients who maintained remission. RESULTS Of 4001 articles identified, 22 RCTs were eligible for analysis. One study published as an abstract was hand-searched and added. The consistency hypothesis was not rejected for the analysis. The odds ratio of vonoprazan 10 mg to each PPI was 13.92 (95% credible interval [CI] 1.70-114.21) to esomeprazole 10 mg; 5.75 (95% CI 0.59-51.57) to rabeprazole 10 mg; 3.74 (95% CI 0.70-19.99) to lansoprazole 15 mg; and 9.23 (95% CI 1.17-68.72) to omeprazole 10 mg. CONCLUSIONS The efficacy of vonoprazan in GERD maintenance treatment may be higher than that of some PPIs. However, a direct comparison of vonoprazan and PPIs is required to confirm these effects.
Collapse
Affiliation(s)
- Hiroto Miwa
- Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa, Nishinomiya, Hyogo, 663-8501, Japan.
| | - Ataru Igarashi
- Department of Health Economics and Outcomes Research, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo, 113-0033, Japan
| | - Lida Teng
- Department of Health Economics and Outcomes Research, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo, 113-0033, Japan
| | - Akihito Uda
- Japan Medical Affairs, Takeda Pharmaceutical Company Ltd, 1-1, Nihonbashi-honcho 2-chome, Chuo-ku, Tokyo, 103-8668, Japan
| | - Hisato Deguchi
- Japan Medical Affairs, Takeda Pharmaceutical Company Ltd, 1-1, Doshomachi 4-chome, Chuo-ku, Osaka, 541-0054, Japan
| | - Toshiro Tango
- Center for Medical Statistics, 2-9-6 Higashi Shimbashi, Minato-ku, Tokyo, 105-0021, Japan
| |
Collapse
|
|
15
|
Sobrino-Cossío S, Teramoto-Matsubara O, Mateos-Pérez G, Abdo-Francis JM, Tawil J, Olguín-Ramírez C, Orozco-Gamiz A, Galvis-García ES. In search of the grail: A race for acid suppression. REVISTA DE GASTROENTEROLOGIA DE MEXICO (ENGLISH) 2019; 84:344-356. [PMID: 31239096 DOI: 10.1016/j.rgmx.2019.04.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/26/2019] [Revised: 03/26/2019] [Accepted: 04/30/2019] [Indexed: 06/09/2023]
Abstract
Proton pump inhibitors are the reference standards for the treatment of acid-related diseases. Acid suppression in gastroesophageal reflux disease is associated with a high rate of mucosal cicatrization, but symptom response differs among endoscopic phenotypes. Extraesophageal manifestations have a good clinical response in patients that present with abnormal acid exposure (diagnostic test) in the esophagus. Proton pump inhibitors have shown their effectiveness for reducing symptom intensity in nighttime reflux and sleep disorders, improving quality of life and work productivity. That can sometimes be achieved through dose modifications by splitting or increasing the dose, or through galenic formulation. Proton pump inhibitors are not exempt from controversial aspects related to associated adverse events. Technological development is directed at improving proton pump inhibitor performance through increasing the half-life, maximum concentration, and area under the curve of the plasma concentrations through galenic formulation, as well as creating safer and more tolerable drugs. The present review is focused on the mechanisms of action, pharmacokinetic properties, and technological advances for increasing the pharmacologic performance of a proton pump inhibitor.
Collapse
Affiliation(s)
- S Sobrino-Cossío
- Hospital Ángeles del Pedregal, Ciudad de México, México; Gástrica, Centro Avanzado en Endoscopia y Estudios Funcionales, Ciudad de México, México.
| | - O Teramoto-Matsubara
- Gástrica, Centro Avanzado en Endoscopia y Estudios Funcionales, Ciudad de México, México; Centro Médico ABC, Ciudad de México, México
| | - G Mateos-Pérez
- Hospital Ángeles del Pedregal, Ciudad de México, México; Hospital Ángeles Acoxpa, Ciudad de México, México
| | - J M Abdo-Francis
- Gástrica, Centro Avanzado en Endoscopia y Estudios Funcionales, Ciudad de México, México; Hospital Ángeles Acoxpa, Ciudad de México, México
| | - J Tawil
- Departamento de Trastornos Funcionales Digestivos, Gedyt-Gastroenterología Diagnóstica y Terapéutica, Buenos Aires, Argentina
| | - C Olguín-Ramírez
- Gástrica, Centro Avanzado en Endoscopia y Estudios Funcionales, Ciudad de México, México
| | - A Orozco-Gamiz
- Gastrolab Laboratorio de Fisiología Gastrointestinal, Guadalajara, Jalisco, México
| | - E S Galvis-García
- Gástrica, Centro Avanzado en Endoscopia y Estudios Funcionales, Ciudad de México, México; Hospital General de México «Dr. Eduardo Liceaga», Ciudad de México, México
| |
Collapse
|
|
16
|
Sobrino-Cossío S, Teramoto-Matsubara O, Mateos-Pérez G, Abdo-Francis J, Tawil J, Olguín-Ramírez C, Orozco-Gamiz A, Galvis-García E. In search of the grail: A race for acid suppression. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO (ENGLISH EDITION) 2019. [DOI: 10.1016/j.rgmxen.2019.04.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
|
|
17
|
Lin WL, Muo CS, Lin WC, Hsieh YW, Kao CH. Association of Increased Risk of Pneumonia and Using Proton Pump Inhibitors in Patients With Type II Diabetes Mellitus. Dose Response 2019; 17:1559325819843383. [PMID: 31080379 PMCID: PMC6498779 DOI: 10.1177/1559325819843383] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2018] [Revised: 02/24/2019] [Accepted: 03/20/2019] [Indexed: 12/15/2022] Open
Abstract
Background: This study explored the possible association between the use of proton pump inhibitors (PPIs) and the increased incidence of pneumonia in patients with type 2 diabetes mellitus (T2DM). Methods: We selected 4940 patients with T2DM of whom 988 and 3952 were enrolled in PPI and propensity score-matched control cohorts, respectively. All patients were followed from the index date until admission with pneumonia, withdrawal from the National Health Insurance program or the end of 2013. The PPIs associated with risk of incident pneumonia were examined. Furthermore, we assessed the risk of pneumonia according to annual defined daily doses in the PPI cohort. Results: After a 14-year follow-up, the cumulative incidence of pneumonia in the PPI users was 11.4% higher than that in the controls (30.3% vs 18.9%). Compared to the controls, the PPI users had a 1.70-fold higher risk of pneumonia in the Cox proportional hazards model after adjustment for matched pairs. The risk of pneumonia increased with the annual PPI defined daily dose. Conclusion: The results of this population-based retrospective cohort study suggest that PPI use increased the risk of pneumonia in patients with T2DM. The effects were more prominent in patients administered higher doses of PPIs.
Collapse
Affiliation(s)
- Wen-Ling Lin
- Graduate Institute of Pharmacy, China Medical University, Taichung.,Department of Pharmacy, China Medical University Hospital, Taichung
| | - Chin-Shin Muo
- Management Office for Health Data, China Medical University Hospital, Taichung.,College of Medicine, China Medical University, Taichung
| | - Wen-Chuan Lin
- Graduate Institute of Pharmacy, China Medical University, Taichung
| | - Yow-Wen Hsieh
- Graduate Institute of Pharmacy, China Medical University, Taichung.,Department of Pharmacy, China Medical University Hospital, Taichung
| | - Chia-Hung Kao
- Graduate Institute of Biomedical Sciences and School of Medicine, College of Medicine, China Medical University, Taichung.,Department of Nuclear Medicine and PET Center, China Medical University Hospital, Taichung.,Department of Bioinformatics and Medical Engineering, Asia University, Taichung
| |
Collapse
|
|
18
|
Chiang HH, Wu DC, Hsu PI, Kuo CH, Tai WC, Yang SC, Wu KL, Yao CC, Tsai CE, Liang CM, Wang YK, Wang JW, Huang CF, Chuah SK. Clinical efficacy of 60-mg dexlansoprazole and 40-mg esomeprazole after 24 weeks for the on-demand treatment of gastroesophageal reflux disease grades A and B: a prospective randomized trial. Drug Des Devel Ther 2019; 13:1347-1356. [PMID: 31118571 PMCID: PMC6499145 DOI: 10.2147/dddt.s193559] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2018] [Accepted: 03/12/2019] [Indexed: 12/22/2022] Open
Abstract
Purpose: Research comparing the clinical efficacy of dexlansoprazole and esomeprazole has been limited. This study aims to compare the clinical efficacy of single doses of dexlansoprazole (modified-release 60 mg) and esomeprazole (40 mg) after 24-week follow-up in patients with mild erosive esophagitis. Methods: We enrolled 86 adult GERD subjects, randomized in a 1:1 ratio to two sequence groups defining the order in which they received single doses of dexlansoprazole (n=43) and esomeprazole (n=43) for 8 weeks as initial treatment. Patients displaying complete symptom resolution (CSR) by the end of initial treatment (8 weeks) were switched to on-demand therapy until the end of 24 weeks. Follow-up endoscopy was performed either at the end of 24 weeks or when severe reflux symptoms occurred. Five patients were lost to follow-up, leaving 81 patients (dexlansoprazole, n=41; esomeprazole, n=40) in the per-protocol analysis. Results: The GERDQ scores at 4-, 8-, 12-, 16-, 20-, and 24-week posttreatment were less than the baseline score. The CSR, rate of symptom relapse, days to symptom resolution, sustained healing rate of erosive esophagitis, treatment failure rate, and the number of tablets taken in 24 weeks were similar in both groups. The esomeprazole group had more days with reflux symptoms than the dexlansoprazole group (37.3±37.8 vs 53.9±54.2; P=0.008). In the dexlansoprazole group, patients exhibited persistent improvement in the GERDQ score during the on-demand period (week 8 vs week 24; P<0.001) but not in the esomeprazole group (week 8 vs week 24; P=0.846). Conclusions: This study suggests that the symptom relief effect for GERD after 24 weeks was similar for dexlansoprazole and esomeprazole. Dexlansoprazole exhibited fewer days with reflux symptoms in the 24-week study period, with better persistent improvement in the GERDQ score in the on-demand period. (ClinicalTrials. gov number: NCT03128736).
Collapse
Affiliation(s)
- Hung-Hsien Chiang
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Deng-Chyang Wu
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital and Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Pin-I Hsu
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, National Yang-Ming University, Kaohsiung, Taiwan
| | - Chao-Hung Kuo
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital and Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Wei-Chen Tai
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Shih-Cheng Yang
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Keng-Liang Wu
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chih-Chien Yao
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Cheng-En Tsai
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chih-Ming Liang
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Yao-Kuang Wang
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital and Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Jiunn-Wei Wang
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital and Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chih-Fang Huang
- Division of Family Physicians, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Seng-Kee Chuah
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - on behalf of the Taiwan Acid-Related Disease Study Group
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital and Kaohsiung Medical University, Kaohsiung, Taiwan
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, National Yang-Ming University, Kaohsiung, Taiwan
- Division of Family Physicians, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| |
Collapse
|
|
19
|
Gyawali CP, Fass R. Management of Gastroesophageal Reflux Disease. Gastroenterology 2018; 154:302-318. [PMID: 28827081 DOI: 10.1053/j.gastro.2017.07.049] [Citation(s) in RCA: 196] [Impact Index Per Article: 28.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2017] [Revised: 07/29/2017] [Accepted: 07/31/2017] [Indexed: 02/06/2023]
Abstract
Management of gastroesophageal reflux disease (GERD) commonly starts with an empiric trial of proton pump inhibitor (PPI) therapy and complementary lifestyle measures, for patients without alarm symptoms. Optimization of therapy (improving compliance and timing of PPI doses), or increasing PPI dosage to twice daily in select circumstances, can reduce persistent symptoms. Patients with continued symptoms can be evaluated with endoscopy and tests of esophageal physiology, to better determine their disease phenotype and optimize treatment. Laparoscopic fundoplication, magnetic sphincter augmentation, and endoscopic therapies can benefit patients with well-characterized GERD. Patients with functional diseases that overlap with or mimic GERD can also be treated with neuromodulators (primarily antidepressants), or psychological interventions (psychotherapy, hypnotherapy, cognitive and behavioral therapy). Future approaches to treatment of GERD include potassium-competitive acid blockers, reflux-reducing agents, bile acid binders, injection of inert substances into the esophagogastric junction, and electrical stimulation of the lower esophageal sphincter.
Collapse
Affiliation(s)
- C Prakash Gyawali
- Division of Gastroenterology, Washington University School of Medicine, St. Louis, Missouri
| | - Ronnie Fass
- Division of Gastroenterology and Hepatology, Esophageal and Swallowing Center, Case Western Reserve University, MetroHealth Medical Center, Cleveland, Ohio.
| |
Collapse
|
|
20
|
Uchiyama T, Higurashi T, Kuriyama H, Kondo Y, Hata Y, Nakajima A. Oral esomeprazole vs injectable omeprazole for the prevention of hemorrhage after endoscopic submucosal dissection. World J Gastrointest Endosc 2017; 9:514-520. [PMID: 29085562 PMCID: PMC5648994 DOI: 10.4253/wjge.v9.i10.514] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2017] [Revised: 05/19/2017] [Accepted: 07/17/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To evaluate the effectiveness of oral esomeprazole (EPZ) vs injectable omeprazole (OPZ) therapy to prevent hemorrhage after endoscopic submucosal dissection (ESD).
METHODS A case-control study was conducted using a quasi-randomized analysis with propensity score matching. A total of 258 patients were enrolled in this study. Patients were treated with either oral EPZ or injectable OPZ. The endpoint was the incidence of hemorrhage after ESD.
RESULTS Data of 71 subjects treated with oral EPZ and 172 subjects treated with injectable OPZ were analyzed. Analysis of 65 matched samples revealed no difference in the incidence of hemorrhage after ESD between the oral EPZ and injectable OPZ groups (OR = 0.89, 95%CI: 0.35-2.27, P ≥ 0.99).
CONCLUSION We conclude that oral EPZ therapy is a useful alternative to injectable PPI therapy for the prevention of hemorrhage after ESD.
Collapse
Affiliation(s)
- Takashi Uchiyama
- Department of Gastroenterology and Hepatology, Yokohama City University School of Medicine, Yokohama city, Kanagawa Prefecture 236-0042, Japan
- Department of Gastroenterology, Chigasaki Municipal Hospital, Chigasaki city, Kanagawa Prefecture 235-0042, Japan
| | - Takuma Higurashi
- Department of Gastroenterology and Hepatology, Yokohama City University School of Medicine, Yokohama city, Kanagawa Prefecture 236-0042, Japan
| | - Hitoshi Kuriyama
- Department of Gastroenterology, Chigasaki Municipal Hospital, Chigasaki city, Kanagawa Prefecture 235-0042, Japan
| | - Yoshinobu Kondo
- Department of Endocrinology and Metabolism, Chigasaki Municipal Hospital, Chigasaki city, Kanagawa Prefecture 235-0042, Japan
| | - Yasuo Hata
- Department of Gastroenterology, Chigasaki Municipal Hospital, Chigasaki city, Kanagawa Prefecture 235-0042, Japan
| | - Atsushi Nakajima
- Department of Gastroenterology and Hepatology, Yokohama City University School of Medicine, Yokohama city, Kanagawa Prefecture 236-0042, Japan
| |
Collapse
|
|
21
|
Abstract
PURPOSE OF REVIEW Proton pump inhibitor (PPI) use in gastroesophageal reflux disease (GERD) has been redefined, in light of recent advances highlighting GERD phenotypes that respond to PPIs, and fresh revelations of potential risks of long-term PPI therapy. RECENT FINDINGS Erosive esophagitis predicts excellent response to PPI therapy, but non-erosive reflux disease (NERD) with abnormal reflux parameters on ambulatory reflux monitoring also demonstrates a similar response. In contrast, response is suboptimal in the absence of abnormal reflux parameters. In this setting, if an alternate appropriate indication for PPI therapy does not coexist, risks may outweigh benefits of PPI therapy. Adverse events from long-term PPI therapy continue to be reported, most based on association rather than cause-and-effect. Appropriate indications need to be established before embarking on long-term PPI therapy. Future research will define true risks of long-term PPI therapy, and develop alternate management options for acid peptic diseases.
Collapse
Affiliation(s)
- C Prakash Gyawali
- Division of Gastroenterology, Washington University School of Medicine, 660 S. Euclid Ave, Campus Box 8124, St. Louis, MO, 63110, USA.
| |
Collapse
|
|
22
|
Savarino E, Zentilin P, Marabotto E, Bodini G, Della Coletta M, Frazzoni M, de Bortoli N, Martinucci I, Tolone S, Pellegatta G, Savarino V. A review of pharmacotherapy for treating gastroesophageal reflux disease (GERD). Expert Opin Pharmacother 2017; 18:1333-1343. [PMID: 28754071 DOI: 10.1080/14656566.2017.1361407] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Medical therapy of gastroesophageal reflux disease (GERD) is based on the use of proton pump inhibitors (PPIs) as first choice treatment. Despite their effectiveness, about 20-30% of patients report an inadequate response and alternative drugs are required. Areas covered: This review provides an overview of current pharmacotherapy for treating GERD by showing the results of PPIs, reflux inhibitors, antidepressants and mucosa protective medications. Expert opinion: Medical therapy of GERD does not definitely cure the disease, because even PPIs are not able to change the key factors responsible for it. However, they remain the mainstay of medical treatment, allowing us to alleviate symptoms, heal esophagitis and prevent complications in the majority of cases. Nevertheless, many patients do not respond, because acid does not play any pathogenetic role. Prokinetics and reflux inhibitors have the potential to control motor abnormalities, but the results of clinical trials are inconsistent. Antidepressant drugs are effective in specific subgroups of NERD patients with visceral hypersensitivity, but larger, controlled clinical studies are necessary. Protective drugs or medical devices have been recently adopted to reinforce mucosal resistance and preliminary trials have confirmed their efficacy either combined with or as add-on medication to PPIs in refractory patients.
Collapse
Affiliation(s)
- Edoardo Savarino
- a Gastrointestinal Unit, Department of Surgery, Oncology and Gastroenterology , University of Padua , Padua , Italy
| | - Patrizia Zentilin
- b Gastrointestinal Unit, Department of Internal Medicine and Medical Specialties , University of Genoa , Genoa , Italy
| | - Elisa Marabotto
- b Gastrointestinal Unit, Department of Internal Medicine and Medical Specialties , University of Genoa , Genoa , Italy
| | - Giorgia Bodini
- b Gastrointestinal Unit, Department of Internal Medicine and Medical Specialties , University of Genoa , Genoa , Italy
| | - Marco Della Coletta
- a Gastrointestinal Unit, Department of Surgery, Oncology and Gastroenterology , University of Padua , Padua , Italy
| | - Marzio Frazzoni
- c Digestive Pathophysiology Unit , Baggiovara Hospital , Modena , Italy
| | - Nicola de Bortoli
- d Department of Translational Research and New Technology in Medicine and Surgery , University of Pisa , Pisa , Italy
| | - Irene Martinucci
- d Department of Translational Research and New Technology in Medicine and Surgery , University of Pisa , Pisa , Italy
| | - Salvatore Tolone
- e General and Bariatric Surgery Unit, Department of Surgery , Second University of Napoli , Napoli , Italy
| | - Gaia Pellegatta
- b Gastrointestinal Unit, Department of Internal Medicine and Medical Specialties , University of Genoa , Genoa , Italy
| | - Vincenzo Savarino
- b Gastrointestinal Unit, Department of Internal Medicine and Medical Specialties , University of Genoa , Genoa , Italy
| |
Collapse
|
|
23
|
Boghossian TA, Rashid FJ, Thompson W, Welch V, Moayyedi P, Rojas‐Fernandez C, Pottie K, Farrell B. Deprescribing versus continuation of chronic proton pump inhibitor use in adults. Cochrane Database Syst Rev 2017; 3:CD011969. [PMID: 28301676 PMCID: PMC6464703 DOI: 10.1002/14651858.cd011969.pub2] [Citation(s) in RCA: 69] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
BACKGROUND Proton pump inhibitors (PPIs) are a class of medications that reduce acid secretion and are used for treating many conditions such as gastroesophageal reflux disease (GERD), dyspepsia, reflux esophagitis, peptic ulcer disease, and hypersecretory conditions (e.g. Zollinger-Ellison syndrome), and as part of the eradication therapy for Helicobacter pylori bacteria. However, approximately 25% to 70% of people are prescribed a PPI inappropriately. Chronic PPI use without reassessment contributes to polypharmacy and puts people at risk of experiencing drug interactions and adverse events (e.g. Clostridium difficile infection, pneumonia, hypomagnesaemia, and fractures). OBJECTIVES To determine the effects (benefits and harms) associated with deprescribing long-term PPI therapy in adults, compared to chronic daily use (28 days or greater). SEARCH METHODS We searched the following databases: Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 10), MEDLINE, Embase, clinicaltrials.gov, and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP). The last date of search was November 2016. We handsearched the reference lists of relevant studies. We screened 2357 articles (2317 identified through search strategy, 40 through other resources). Of these articles, we assessed 89 for eligibility. SELECTION CRITERIA We included randomized controlled trials (RCTs) and quasi-randomized trials comparing at least one deprescribing modality (e.g. stopping PPI or reducing PPI) with a control consisting of no change in continuous daily PPI use in adult chronic users. Outcomes of interest were: change in gastrointestinal (GI) symptoms, drug burden/PPI use, cost/resource use, negative and positive drug withdrawal events, and participant satisfaction. DATA COLLECTION AND ANALYSIS Two review authors independently reviewed and extracted data and completed the risk of bias assessment. A third review author independently confirmed risk of bias assessment. We used Review Manager 5 software for data analysis. We contacted study authors if there was missing information. MAIN RESULTS The review included six trials (n = 1758). Trial participants were aged 48 to 57 years, except for one trial that had a mean age of 73 years. All participants were from the outpatient setting and had either nonerosive reflux disease or milder grades of esophagitis (LA grade A or B). Five trials investigated on-demand deprescribing and one trial examined abrupt discontinuation. There was low quality evidence that on-demand use of PPI may increase risk of 'lack of symptom control' compared with continuous PPI use (risk ratio (RR) 1.71, 95% confidence interval (CI) 1.31 to 2.21), thereby favoring continuous PPI use (five trials, n = 1653). There was a clinically significant reduction in 'drug burden', measured as PPI pill use per week with on-demand therapy (mean difference (MD) -3.79, 95% CI -4.73 to -2.84), favoring deprescribing based on moderate quality evidence (four trials, n = 1152). There was also low quality evidence that on-demand PPI use may be associated with reduced participant satisfaction compared with continuous PPI use. None of the included studies reported cost/resource use or positive drug withdrawal effects. AUTHORS' CONCLUSIONS In people with mild GERD, on-demand deprescribing may lead to an increase in GI symptoms (e.g. dyspepsia, regurgitation) and probably a reduction in pill burden. There was a decline in participant satisfaction, although heterogeneity was high. There were insufficient data to make a conclusion regarding long-term benefits and harms of PPI discontinuation, although two trials (one on-demand trial and one abrupt discontinuation trial) reported endoscopic findings in their intervention groups at study end.
Collapse
Affiliation(s)
- Taline A Boghossian
- The Ottawa HospitalDepartment of Pharmacy501 Smyth RoadOttawaONCanadaK1H 8L6
| | - Farah Joy Rashid
- The Ottawa HospitalDepartment of Pharmacy501 Smyth RoadOttawaONCanadaK1H 8L6
| | - Wade Thompson
- University of OttawaBruyère Research Institute43 rue Bruyere StRoom 730DOttawaONCanadaK1N 5C8
| | - Vivian Welch
- University of OttawaBruyère Research Institute43 rue Bruyere StRoom 730DOttawaONCanadaK1N 5C8
| | - Paul Moayyedi
- McMaster UniversityDepartment of Medicine, Division of Gastroenterology1200 Main Street WestRoom 4W8EHamiltonONCanadaL8N 3Z5
| | - Carlos Rojas‐Fernandez
- University of WaterlooSchool of Pharmacy10 Victoria St S.Room 7004KitchenerONCanadaN2G 1C5
| | - Kevin Pottie
- University of OttawaBruyère Research Institute43 rue Bruyere StRoom 730DOttawaONCanadaK1N 5C8
- University of OttawaFamily Medicine75 Bruyere StOttawaONCanadaK1N 5C8
| | - Barbara Farrell
- University of OttawaBruyère Research Institute43 rue Bruyere StRoom 730DOttawaONCanadaK1N 5C8
- University of WaterlooSchool of Pharmacy10 Victoria St S.Room 7004KitchenerONCanadaN2G 1C5
- University of OttawaFamily Medicine75 Bruyere StOttawaONCanadaK1N 5C8
| | | |
Collapse
|
|
24
|
Abstract
OBJECTIVE To assess the impact of Roux-en-Y gastric bypass (GBP) on gastroesophageal reflux disease (GERD) in morbidly obese patients. BACKGROUND Recently, authors have reported that early results of GBP can control GERD. However, longer follow-ups based on objective parameters for GERD are missing. METHODS Fifty-three patients [15 men (28%), 39 years old (range, 18-59), body mass index = 46 ± 7.7 kg/m2] were consecutively evaluated for GERD irrespectively of related symptoms, before the operation (E1) and at 6 (E2) and 39 ± 7 months postoperatively (E3). The end points were (1) esophageal syndromes based on the Montreal Consensus and (2) an esophageal acid exposure assessment. RESULTS Body mass index dropped from 46 ± 7.7 kg/m2 at E1 to 30 ± 5.2 kg/m2 at E3. Typical reflux syndrome displayed a significant decrease from 31 (58%) at E1 to 8 (15%) at E2 and 5 (9%) at E3. Statistically significant differences occurred between E1 and both postoperative evaluations (P < 0.001). Reflux esophagitis was detected in 24 (45%), 17 (32%), and 10 patients (19%) at E1, E2, and E3, respectively (P = 0.002). The incidence of GERD decreased in 34 (64%) and 21 (40%) patients at E1 and E2, respectively, and then in 12 (23%) patients at E3. DeMeester scores reduced from 28.6 (E1) to 9.4 (E2) and 1.2 (E3) (P < 0.001). CONCLUSIONS For most morbidly obese patients, in addition to causing significant weight loss, GBP reduces GERD symptoms, improves reflux esophagitis, and decreases esophageal acid exposure for longer than 3 years.
Collapse
|
|
25
|
Safety and Tolerability of Esomeprazole in Children With Gastroesophageal Reflux Disease. J Pediatr Gastroenterol Nutr 2015; 60 Suppl 1:S16-23. [PMID: 26121345 DOI: 10.1097/mpg.0b013e318176b2cb] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
OBJECTIVES To evaluate safety, tolerability, and symptom improvement with once-daily esomeprazole in children with endoscopically proven gastroesophageal reflux disease (GERD). PATIENTS AND METHODS In this 8-week, multicenter, randomized, uncontrolled, double-blind study, children ages 1 to 11 years were stratified by weight to receive esomeprazole 5 or 10 mg (children < 20 kg) or 10 or 20 mg (children ≥ 20 kg) once daily. Safety and tolerability was assessed by evaluating adverse events (AEs; both treatment- and non-treatment-related AEs) and changes from baseline in medical history, physical examinations, and clinical laboratory tests. Investigators scored symptom severity every 2 weeks using the Physician's Global Assessment (PGA). Patients' parents rated GERD symptoms of heartburn, acid regurgitation, and epigastric pain (none to severe, 0-3) at baseline (based on past 72 hours) and daily (from past 24 hours). RESULTS Of 109 patients randomized, 108 had safety data. AEs were experienced by 68.0% and 65.2% of children < 20 kg receiving esomeprazole 5 and 10 mg, respectively, and 83.9% and 82.8% of children ≥ 20 kg receiving esomeprazole 10 and 20 mg, respectively, regardless of causality. Overall, only 9.3% of patients reported 13 treatment-related AEs; the most common were diarrhea (2.8% [3/108]), headache (1.9% [2/108]), and somnolence (1.9% [2/108]). Vomiting, a serious AE in 2 patients, was not judged by the investigator to be related to treatment. At the final visit, PGA scores improved significantly from baseline (P < 0.001). Of 58 patients with moderate to severe baseline PGA symptom scores, 91.4% had lower scores by the final visit. GERD symptom scores were significantly improved from baseline to the final week of the study in all of the treatment groups (P < 0.01) CONCLUSIONS: In children ages 1 to 11 years with endoscopically proven GERD, esomeprazole (at daily doses of 5, 10, or 20 mg) was generally well tolerated. The frequency and severity of GERD-related symptoms were significantly reduced during the active treatment period.
Collapse
|
|
26
|
Tolia V, Gilger MA, Barker PN, Illueca M. Healing of Erosive Esophagitis and Improvement of Symptoms of Gastroesophageal Reflux Disease After Esomeprazole Treatment in Children 12 to 36 Months Old. J Pediatr Gastroenterol Nutr 2015; 60 Suppl 1:S31-6. [PMID: 26121348 DOI: 10.1097/mpg.0b013e3181ddcf11] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
OBJECTIVES The aim of the study was to evaluate erosive esophagitis healing and symptom improvement with once-daily esomeprazole in children ages 12 to 36 months with endoscopically or histologically proven gastroesophageal reflux disease (GERD). PATIENTS AND METHODS Data from children ages 12 to 36 months were included in a post-hoc analysis of an 8-week, multicenter, randomized, and double-blind by dose strata study of patients ages 1 to 11 years with endoscopically or histologically confirmed GERD. Children were randomized to receive esomeprazole 5 or 10 mg once daily. Patients underwent endoscopy and, if required, mucosal biopsy at baseline. Patients who had erosive esophagitis (graded using the Los Angeles classification system) at baseline underwent a follow-up endoscopy at final study visit to assess healing of erosive esophagitis. Investigators scored severity of GERD symptoms at baseline and every 2 weeks using the Physician Global Assessment. RESULTS Thirty-one of 109 primary study patients ages 12 to 36 months were included in the post hoc analysis. At baseline, 15 patients (48.4%) had erosive esophagitis, underwent follow-up endoscopy, and were healed after 8 weeks of esomeprazole treatment. Of the 19 patients with moderate-to-severe baseline Physician Global Assessment symptom scores, 84.2% had lower scores by the final visit. Following esomeprazole treatment, GERD symptoms were significantly improved from baseline to final visit (P ≤ 0.0018). CONCLUSIONS Esomeprazole 5 or 10 mg may be used to successfully treat erosive esophagitis and symptoms of GERD in children as young as 1 year. Moreover, although not yet validated in pediatric patients, the Los Angeles classification system was useful in grading erosive esophagitis in children ages 12 to 36 months.
Collapse
Affiliation(s)
- Vasundkara Tolia
- *Providence Hospital, Southfield, MI †Baylor College of Medicine, Houston, TX ‡AstraZeneca LP, Wilmington, DE
| | | | | | | |
Collapse
|
|
27
|
Song H, Zhu J, Lu D. Long-term proton pump inhibitor (PPI) use and the development of gastric pre-malignant lesions. Cochrane Database Syst Rev 2014; 2014:CD010623. [PMID: 25464111 PMCID: PMC10843246 DOI: 10.1002/14651858.cd010623.pub2] [Citation(s) in RCA: 53] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND Proton pump inhibitors (PPIs) are the most effective drugs to reduce gastric acid secretion. PPIs are one of the most commonly prescribed classes of medications worldwide. Apart from short-term application, maintenance therapy with PPIs is recommended and increasingly used in certain diseases, such as Zollinger-Ellison syndrome and gastro-oesophageal reflux disease, especially for people with erosive oesophagitis or Barrett's oesophagus. Although PPIs are generally safe, their efficacy and safety of long-term use remains unclear. The question of whether the long-term use of PPIs could promote the development of gastric pre-malignant lesions has been widely investigated, but results are inconsistent. Limited insight on this problem leads to a dilemma in decision making for long-term PPI prescription. OBJECTIVES To compare the development or progression of gastric pre-malignant lesions, such as atrophic gastritis, intestinal metaplasia, enterochromaffin-like (ECL) cell hyperplasia, and dysplasia, in people taking long-term (six months or greater) PPI maintenance therapy. SEARCH METHODS We searched the following databases (from inception to 6 August 2013): the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and CINAHL. In addition, we searched the reference lists of included trials and contacted experts in the field. SELECTION CRITERIA We searched for randomised controlled trials (RCTs) in adults (aged 18 years or greater) concerning the effects of long-term (six months or greater) PPI use on gastric mucosa changes, confirmed by endoscopy or biopsy sampling (or both). DATA COLLECTION AND ANALYSIS Two review authors independently performed selection of eligible trials, assessment of trial quality, and data extraction. We calculated odds ratios (OR) for analysis of dichotomous data and mean differences for continuous data, with 95% confidence intervals (CI). MAIN RESULTS We included seven trials (1789 participants). Four studies had high risk of bias and the risk of bias in the other three trials was unclear. In addition, it was difficult to assess possible reporting bias. We pooled 1070 participants from four RCTs to evaluate corporal atrophy development revealing an insignificantly increased OR of 1.50 (95% CI 0.59 to 3.80; P value = 0.39; low-quality evidence) for long-term PPI users relative to non-PPI users. In five eligible trials, corporal intestinal metaplasia was assessed among 1408 participants, also with uncertain results (OR 1.46; 95% CI 0.43 to 5.03; P value = 0.55; low-quality evidence). However, by pooling data of 1705 participants from six RCTs, our meta-analysis showed that participants with PPI maintenance treatment were more likely to experience either diffuse (simple) (OR 5.01; 95% CI 1.54 to 16.26; P value = 0.007; very-low-quality evidence) or linear/micronodular (focal) ECL hyperplasia (OR 3.98; 95% CI 1.31 to 12.16; P value = 0.02; low-quality evidence) than controls. No participant showed any dysplastic or neoplastic change in any included studies. AUTHORS' CONCLUSIONS There is presently no clear evidence that the long-term use of PPIs can cause or accelerate the progression of corpus gastric atrophy or intestinal metaplasia, although results were imprecise. People with PPI maintenance treatment may have a higher possibility of experiencing either diffuse (simple) or linear/micronodular (focal) ECL cell hyperplasia. However, the clinical importance of this outcome is currently uncertain.
Collapse
Affiliation(s)
- Huan Song
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Box 281, Stockholm, SE- 17177, Sweden.
| | | | | |
Collapse
|
|
28
|
Goirand F, Le Ray I, Bardou M. Pharmacokinetic evaluation of esomeprazole for the treatment of gastroesophageal reflux disease. Expert Opin Drug Metab Toxicol 2014; 10:1301-11. [PMID: 25019289 DOI: 10.1517/17425255.2014.939627] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
INTRODUCTION Proton pump inhibitors (PPIs) are widely used for the treatment of acid-related diseases such as gastroesophageal reflux disease (GERD). They are recommended by the American College of Gastroenterology for healing erosive esophagitis (EO) and as long-term treatment in patients with healed EO. The available PPIs differ somewhat in their pharmacokinetics and clinical properties, but whether these differences are of clinical relevance is a matter of debate. Some safety concerns have been raised with the use of PPIs, mostly an increased incidence of infectious diseases such as community-acquired pneumonia or Clostridium difficile diarrhea. AREAS COVERED This article explores the results of clinical studies on the pharmacokinetics and pharmacodynamics of esomeprazole , as well as on its clinical efficacy to manage patients with GERD. EXPERT OPINION GERD is a public health concern as its worldwide incidence and associated complications are increasing alongside the exponentially increasing problem of obesity. PPIs are the first pharmacological option because of their efficacy and overall positive risk-to-benefit ratio. Improved efficacy with the use of stereospecific isomers of PPIs, such as esomeprazole, has not yet been convincingly demonstrated. Nevertheless, because of individual experience with former treatment, some patients may report better symptom control when treated with a specific PPI rather than with others.
Collapse
Affiliation(s)
- Françoise Goirand
- CRI U866, INSERM (Institut National de la Santé et de la Recherche Médicale) , Dijon , France
| | | | | |
Collapse
|
|
29
|
Re: proton pump inhibitors and risk for recurrent Clostridium difficile infection among inpatients. Am J Gastroenterol 2014; 109:601-2. [PMID: 24698870 DOI: 10.1038/ajg.2013.481] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
|
|
30
|
Mejia A, Kraft WK. Acid peptic diseases: pharmacological approach to treatment. Expert Rev Clin Pharmacol 2014; 2:295-314. [PMID: 21822447 DOI: 10.1586/ecp.09.8] [Citation(s) in RCA: 68] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
Acid peptic disorders are the result of distinctive, but overlapping pathogenic mechanisms leading to either excessive acid secretion or diminished mucosal defense. They are common entities present in daily clinical practice that, owing to their chronicity, represent a significant cost to healthcare. Key elements in the success of controlling these entities have been the development of potent and safe drugs based on physiological targets. The histamine-2 receptor antagonists revolutionized the treatment of acid peptic disorders owing to their safety and efficacy profile. The proton-pump inhibitors (PPIs) represent a further therapeutic advance due to more potent inhibition of acid secretion. Ample data from clinical trials and observational experience have confirmed the utility of these agents in the treatment of acid peptic diseases, with differential efficacy and safety characteristics between and within drug classes. Paradigms in their speed and duration of action have underscored the need for new chemical entities that, from a single dose, would provide reliable duration of acid control, particularly at night. Moreover, PPIs reduce, but do not eliminate, the risk of ulcers in patients taking NSAIDs, reflecting untargeted physiopathologic pathways and a breach in the ability to sustain an intragastric pH of more than 4. This review provides an assessment of the current understanding of the physiology of acid production, a discussion of medications targeting gastric acid production and a review of efficacy in specific acid peptic diseases, as well as current challenges and future directions in the treatment of acid-mediated diseases.
Collapse
Affiliation(s)
- Alex Mejia
- Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, 1170 Main Building, 132 South 10th Street, Philadelphia, PA 19107-5244, USA, Tel.: +1 203 243 7501
| | | |
Collapse
|
|
31
|
Wu MS, Tan SC, Xiong T. Indirect comparison of randomised controlled trials: comparative efficacy of dexlansoprazole vs. esomeprazole in the treatment of gastro-oesophageal reflux disease. Aliment Pharmacol Ther 2013; 38:190-201. [PMID: 23718547 DOI: 10.1111/apt.12349] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2013] [Revised: 04/16/2013] [Accepted: 05/07/2013] [Indexed: 12/24/2022]
Abstract
BACKGROUND Dexlansoprazole is a new proton pump inhibitor (PPI) with a dual delayed-release system. Both dexlansoprazole and esomeprazole are an enantiomer of lansoprazole and omeprazole respectively. However, there is no head-to-head trial data or indirect comparison analyses between dexlansoprazole and esomeprazole. AIM To compare the efficacy of dexlansoprazole with esomeprazole in healing erosive oesophagitis (EO), the maintenance of healed EO and the treatment of non-erosive reflux disease (NERD). METHODS Randomised Controlled Trials (RCTs) comparing dexlansoprazole or esomeprazole with either placebo or another PPI were systematically reviewed. Random-effect meta-analyses and adjusted indirect comparisons were conducted to compare the treatment effect of dexlansoprazole and esomeprazole using a common comparator. The relative risk (RR) and 95% confidence interval (CI) were calculated. RESULTS The indirect comparisons revealed significant differences in symptom control of heartburn in patients with NERD at 4 weeks. Dexlansoprazole 30 mg was more effective than esomeprazole 20 mg or 40 mg (RR: 2.01, 95% CI: 1.15-3.51; RR: 2.17, 95% CI: 1.39-3.38). However, there were no statistically significant differences between the two drugs in EO healing and maintenance of healed EO. Comparison of symptom control in healed EO was not able to be made due to different definitions used in the RCTs. CONCLUSIONS Adjusted indirect comparisons based on currently available RCT data suggested significantly better treatment effect in symptom control of heartburn in patients with NERD for dexlansoprazole against esomeprazole. No statistically significant differences were found in other EO outcomes. However, these study findings need to be interpreted with caution due to small number of studies and other limitations.
Collapse
Affiliation(s)
- M S Wu
- Department of Internal Medicine, Taiwan National University, Taipei, Taiwan
| | | | | |
Collapse
|
|
32
|
Valutazione economica della terapia di mantenimento al bisogno con esomeprazolo nella malattia da reflusso gastroesofageo. ACTA ACUST UNITED AC 2013. [DOI: 10.1007/bf03320536] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
|
|
33
|
Gastroesophageal reflux disease: drug therapy. Rev Assoc Med Bras (1992) 2011. [DOI: 10.1016/s0104-4230(11)70124-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
|
|
34
|
|
|
35
|
Attwood SE, Galmiche JP. A debate on the roles of antireflux surgery and long term acid suppression in the management of gastro-oesophageal reflux disease. Frontline Gastroenterol 2011; 2:206-211. [PMID: 28839611 PMCID: PMC5517238 DOI: 10.1136/fg.2010.003962] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/08/2011] [Indexed: 02/04/2023] Open
Affiliation(s)
- Stephen E Attwood
- Department of Surgery, Northumbria Healthcare NHS Trust, North Tyneside General Hospital, North Shields, UK
| | - Jean Paul Galmiche
- Department of Gastroenterology, IMAD, CHU Hôtel Dieu, Nantes Cedex, France
| |
Collapse
|
|
36
|
Compare D, Pica L, Rocco A, De Giorgi F, Cuomo R, Sarnelli G, Romano M, Nardone G. Effects of long-term PPI treatment on producing bowel symptoms and SIBO. Eur J Clin Invest 2011; 41:380-6. [PMID: 21128930 DOI: 10.1111/j.1365-2362.2010.02419.x] [Citation(s) in RCA: 86] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Gastroesophageal reflux disease (GERD), including erosive reflux disease and non-erosive reflux disease (NERD), is a chronic disease with a significant negative effect on quality of life. State-of-the-art treatment involves proton pump inhibitors (PPIs). However, relapse of symptoms occurs in the majority of the patients who require recurrent or continuous therapy. Although PPIs are well tolerated, little information is available about gastrointestinal side effects. AIM To evaluate the effects of long-term PPI treatment on development of bowel symptoms and/or small intestinal bacterial overgrowth (SIBO). METHODS Patients with NERD not complaining of bowel symptoms were selected by upper endoscopy, 24-h pH-metry and a structured questionnaire concerning severity and frequency of bloating, flatulence, abdominal pain, diarrhoea and constipation. Patients were treated with esomeprazole 20 mg bid for 6 months. Prior to and after 8 weeks and 6 months of therapy, patients received the structured questionnaire and underwent evaluation of SIBO by glucose hydrogen breath test (GHBT). RESULTS Forty-two patients with NERD were selected out of 554 eligible patients. After 8 weeks of PPI treatment, patients complained of bloating, flatulence, abdominal pain and diarrhoea in 43%, 17%, 7% and 2%, respectively. After 6 months, the incidence of bowel symptoms further increased and GHBT was found positive in 11/42 (26%) patients. By a post hoc analysis, a significant (P < 0·05) percentage of patients (8/42) met Rome III criteria for irritable bowel syndrome. CONCLUSIONS Prolonged PPI treatment may produce bowel symptoms and SIBO; therefore, the strategy of step-down or on-demand PPI therapy should be encouraged in GERD.
Collapse
Affiliation(s)
- Debora Compare
- Department of Clinical and Experimental Medicine, Gastroenterology Unit, University of Naples Federico II, Naples, Italy
| | | | | | | | | | | | | | | |
Collapse
|
|
37
|
Dabholkar AH, Han C, Paris MM, Perez MC, Atkinson SN, Peura DA. The 12-month safety profile of dexlansoprazole, a proton pump inhibitor with a dual delayed release formulation, in patients with gastro-oesophageal reflux disease. Aliment Pharmacol Ther 2011; 33:366-77. [PMID: 21118280 DOI: 10.1111/j.1365-2036.2010.04519.x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Dexlansoprazole MR is a Dual Delayed Release formulation of dexlansoprazole, an enantiomer of lansoprazole, designed to extend the duration of acid suppression. AIM To assess the 12-month safety of dexlansoprazole MR in patients with symptomatic gastro-oesophageal reflux disease (GERD). METHODS In this randomised open-label study, patients received dexlansoprazole MR 60 or 90 mg once-daily for 12 months. Safety was evaluated at months 1, 3, 6, 9 and 12/final visit through physical examinations, laboratory evaluations, endoscopies, gastric biopsies, fasting serum gastrin values and adverse events (AEs). RESULTS Of 591 patients receiving dexlansoprazole MR 60 and 90 mg, 71% and 65%, respectively, experienced ≥1 treatment-emergent AE; the most frequent AE was upper respiratory infection (14% and 13% in the 60- and 90-mg groups). Thirty patients experienced ≥1 serious AE; a majority of serious AEs were unrelated to study drug. No clinically meaningful change in any clinical laboratory parameters was noted. As expected, serum gastrin values rose with dexlansoprazole therapy; increases were not dose related. No clinically concerning trends were identified in gastric pathology results; no endocrine cell hyperplasia, adenocarcinoma, or lymphoma were observed. CONCLUSIONS Twelve-month treatment with dexlansoprazole MR 60 and 90 mg was well tolerated by GERD patients in this study (Clinicaltrials.gov identifier NCT00255190).
Collapse
Affiliation(s)
- A H Dabholkar
- Takeda Global Research & Development Center, Inc., Deerfield, IL 60015, USA.
| | | | | | | | | | | |
Collapse
|
|
38
|
Bruley des Varannes S, Coron E, Galmiche JP. Short and long-term PPI treatment for GERD. Do we need more-potent anti-secretory drugs? Best Pract Res Clin Gastroenterol 2010; 24:905-21. [PMID: 21126703 DOI: 10.1016/j.bpg.2010.09.004] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2010] [Revised: 09/17/2010] [Accepted: 09/20/2010] [Indexed: 02/06/2023]
Abstract
Because the reflux of the acidic gastric content into the esophagus plays a major role in the pathogenesis of symptoms of GERD and lesions of erosive esophagitis, acid suppression with a proton pump inhibitor (PPI) is currently the mainstay of anti-reflux therapy. There is a strong correlation between the degree of acid suppression provided by a given drug and its efficacy. The superiority of PPIs over other drugs (antacids, prokinetics and H(2)-receptor antagonists) has now been established beyond doubt, both for short- and long-term treatment. However, there are still some unmet therapeutic needs in GERD; hence, patients with non-erosive reflux disease (NERD) are less responsive to PPIs than those with erosive esophagitis. Moreover, the efficacy of PPIs in patients with atypical symptoms is frequently limited to the relief of associated heartburn or regurgitation. With respect to safety, although most studies on short- and long-term PPI use have provided reassuring data, recent reports have drawn attention to potential side effects or drug-drug interference. Better healing rates in the most severe forms of esophagitis, or a faster onset of symptom relief, may require optimization of acid suppressive therapy with regard to the daily course of acid secretion, especially during the night. Different pharmacological approaches can be considered, with the ultimate goals of achieving faster, stronger and more-sustained acid inhibition. How a better pharmacological profile may translate into clinical benefit should now be tested in appropriate, controlled studies.
Collapse
|
|
39
|
Yang YX, Metz DC. Safety of proton pump inhibitor exposure. Gastroenterology 2010; 139:1115-27. [PMID: 20727892 DOI: 10.1053/j.gastro.2010.08.023] [Citation(s) in RCA: 156] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2010] [Revised: 08/16/2010] [Accepted: 08/16/2010] [Indexed: 12/12/2022]
Abstract
Proton pump (H(+)/K(+)-adenosine triphosphatase) inhibitors (PPIs) are widely used to treat patients with acid-related disorders because they are generally perceived to be safe and effective. However, as with any pharmacologic agent, they have the potential for side effects. Many studies have examined the side effects of long-term or short-term PPI exposure. We review the mechanism of action of PPIs, focusing on recently released products that might have greater risks of adverse effects than older products because of increased potency and/or duration of action. We summarize the data available on the putative adverse effects of PPI therapy and propose guidelines for clinicians who prescribe these agents to limit the potential for adverse outcomes in users of these effective therapeutic agents.
Collapse
Affiliation(s)
- Yu-Xiao Yang
- Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
| | | |
Collapse
|
|
40
|
Chiba N, Fennerty MB. Gastroesophageal Reflux Disease. EVIDENCE‐BASED GASTROENTEROLOGY AND HEPATOLOGY 2010:17-61. [DOI: 10.1002/9781444314403.ch2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
|
|
41
|
Johnson DA, Katz PO, Levine D, Röhss K, Astrand M, Junghard O, Nagy P. Prevention of relapse of healed reflux esophagitis is related to the duration of intragastric pH > 4. J Clin Gastroenterol 2010; 44:475-478. [PMID: 20502348 DOI: 10.1097/mcg.0b013e3181dd9c5b] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
Proton pump inhibitors (PPIs) are the preferred treatment for maintenance of healed reflux esophagitis (RE). However, little is known regarding the relationship between prevention of RE relapse and degree of gastric acid suppression. The aim of this review was to examine this relationship in further detail. Data from four comparative studies on maintenance PPI therapy for prevention of relapse of RE were combined with data from two pharmacodynamic studies of duration of intragastric pH >4 during the 24-hour period on day 5 of PPI dosing in healthy subjects. A log-linear model was fitted to the data using the method of maximum likelihood. Variability in relapse rates and pH data was taken into account using a binomial and normal likelihood function, respectively. Pharmacodynamic studies resulted in a wide range of acid-suppressive effect, and based on corresponding maintenance of RE healing rates with different PPIs and doses, an inverse (non-linear) statistically significant relationship between percentage of time with pH >4 and maintenance of RE healing was identified (P<0.001). These findings indicate that long-term maintenance of healed RE is related to the extent of acid suppression in a 24-hour period.
Collapse
|
|
42
|
Morgner-Miehlke A, Petersen K, Miehlke S, Labenz J. Esomeprazole: potent acid suppression in the treatment of acid-related disorders. Expert Rev Clin Immunol 2010; 1:511-27. [PMID: 20477595 DOI: 10.1586/1744666x.1.4.511] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Esomeprazole (S-omeprazole), an enantiomer of the racemate omeprazole, is the first proton pump inhibitor to be developed as an isomer. This confers improved pharmacokinetics and pharmacodynamics compared with the racemate R/S-omeprazole. The difference in the pharmacokinetics of esomeprazole compared with omeprazole and the R-isomer is due to reductions in total body clearance and first-pass metabolism in the liver. Pharmacodynamic studies showed that esomeprazole 40 mg provides greater intragastric acid control than respective doses of all the other proton pump inhibitors on the market. Several well-designed clinical trials, employing both endoscopic and symptomatic response criteria, have compared the efficacy of esomeprazole with that of other proton pump inhibitors in the management of gastroesophageal reflux disease patients, and in the eradication of Helicobacter pylori. In addition, the efficacy of esomeprazole for the healing and prevention of nonsteroidal anti-inflammatory drug-associated dyspeptic symptoms and ulcers has been established. The aim of this review is to provide an overview of the pharmacokinetics, pharmacodynamics and consequent clinical importance of esomeprazole in the treatment of acid-related disorders.
Collapse
Affiliation(s)
- A Morgner-Miehlke
- Medical Department I, Gastroenterology, University Hospital, Fetscherstrasse 74, 01307 Dresden, Germany.
| | | | | | | |
Collapse
|
|
43
|
Donnellan C, Preston C, Moayyedi P, Sharma N. WITHDRAWN: Medical treatments for the maintenance therapy of reflux oesophagitis and endoscopic negative reflux disease. Cochrane Database Syst Rev 2010:CD003245. [PMID: 20166065 DOI: 10.1002/14651858.cd003245.pub3] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Abstract
BACKGROUND Gastro-oesophageal reflux disease (GORD) - reflux of stomach contents +/- bile into the oesophagus causing symptoms such as heartburn and acid reflux - is a common relapsing and remitting disease which often requires long-term maintenance therapy. Patients with GORD may have oesophagitis (inflammation of the oesophagus) or a normal endoscopy (endoscopy negative reflux disease or ENRD). OBJECTIVES To assess the effects of continuous maintenance therapy in adults with GORD (both ENRD and healed oesophagitis). SEARCH STRATEGY We searched Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 2, 2003), MEDLINE (1966 to 2003), EMBASE (1980 to 2003), CINAHL (1982-2003), and the National Research Register (Issue 2, 2003) and reference lists of articles. We also contacted manufacturers and researchers in the field. SELECTION CRITERIA Randomised controlled studies comparing PPIs, H2RAs, prokinetics, sucralfate and combinations either in comparison to another treatment regimen or to placebo in adults with reflux oesophagitis and ENRD. DATA COLLECTION AND ANALYSIS One author extracted data from included trials and a second author carried out an unblinded check. Two authors independently assessed trial quality. Study authors were contacted for additional information. MAIN RESULTS Maintenance of patients with healed oesophagitis: For a healing dose of PPI (generally the standard dose given by the manufacturer) versus placebo, the relative risk (RR) for oesophagitis relapse was 0.26 (95% confidence interval (CI) 0.19 to 0.36); versus H2RAs the RR was 0.36 (95% CI 0.28 to 0.46) and versus maintenance PPIs the RR was 0.63 (95% CI 0.55 to 0.73). However overall adverse effects were also more common and headaches were more common when comparing healing PPIs to H2RAs.For a maintenance dose of PPI (half of the standard dose) versus placebo, the RR for oesophagitis relapse was 0.46 (95% CI 0.38 to 0.57) and versus H2RAs the RR was 0.57 (95% CI 0.47 to 0.69). Overall adverse effects were more common.H2RAs were of marginal help but beneficial for symptomatic relief. Prokinetics and sucralfate were also more effective than placebo.For ENRD patients: Limited data with one RCT showed benefit for omeprazole 10 mg once daily over placebo (RR 0.4; 95% CI 0.29 to 0.53). AUTHORS' CONCLUSIONS The findings in this review support the long-term treatment of oesophagitis to prevent relapse, both endoscopically and symptomatically. Healing doses of PPIs are more effective than all other therapies, although there is an increase in overall adverse effects compared to placebo, and headache occurrence compared to H2RAs. H2RAs prevent relapse more effectively than placebo, demonstrating a role for PPI-intolerant patients. Prokinetics and sucralfate both show benefit over placebo, but the former is no longer licenced. There is only limited data for ENRD.
Collapse
Affiliation(s)
- Clare Donnellan
- Gastroenterology, University of Leeds, Room 190A, B Floor, Clarendon Wing, LGI, Leeds, West Yorkshire, UK, LS1 3EX
| | | | | | | |
Collapse
|
|
44
|
Liakakos T, Karamanolis G, Patapis P, Misiakos EP. Gastroesophageal reflux disease: medical or surgical treatment? Gastroenterol Res Pract 2009; 2009:371580. [PMID: 20069112 PMCID: PMC2804043 DOI: 10.1155/2009/371580] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2009] [Revised: 10/14/2009] [Accepted: 10/26/2009] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Gastroesophageal reflux disease is a common condition with increasing prevalence worldwide. The disease encompasses a broad spectrum of clinical symptoms and disorders from simple heartburn without esophagitis to erosive esophagitis with severe complications, such as esophageal strictures and intestinal metaplasia. Diagnosis is based mainly on ambulatory esophageal pH testing and endoscopy. There has been a long-standing debate about the best treatment approach for this troublesome disease. METHODS AND RESULTS Medical treatment with PPIs has an excellent efficacy in reversing the symptoms of GERD, but they should be taken for life, and long-term side effects do exist. However, patients who desire a permanent cure and have severe complications or cannot tolerate long-term treatment with PPIs are candidates for surgical treatment. Laparoscopic antireflux surgery achieves a significant symptom control, increased patient satisfaction, and complete withdrawal of antireflux medications, in the majority of patients. CONCLUSION Surgical treatment should be reserved mainly for young patients seeking permanent results. However, the choice of the treatment schedule should be individualized for every patient. It is up to the patient, the physician and the surgeon to decide the best treatment option for individual cases.
Collapse
Affiliation(s)
- Theodore Liakakos
- Department of Surgery, University of Athens School of Medicine, Attikon University Hospital, Rimini 1, Chaidari, Athens 124 62, Greece
| | - George Karamanolis
- Department of Internal Medicine, Gastroenterology Unit, University of Athens School of Medicine, Attikon University Hospital, Rimini 1, Chaidari, Athens 124 62, Greece
| | - Paul Patapis
- Department of Surgery, University of Athens School of Medicine, Attikon University Hospital, Rimini 1, Chaidari, Athens 124 62, Greece
| | - Evangelos P. Misiakos
- Department of Surgery, University of Athens School of Medicine, Attikon University Hospital, Rimini 1, Chaidari, Athens 124 62, Greece
| |
Collapse
|
|
45
|
Saccar CL. The pharmacology of esomeprazole and its role in gastric acid related diseases. Expert Opin Drug Metab Toxicol 2009; 5:1113-24. [PMID: 19606942 DOI: 10.1517/17425250903124363] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Esomeprazole (S-isomer of omeprazole) demonstrates a better pharmacokinetic/pharmacodynamic profile than the racemic product omeprazole. Esomeprazole's pharmacological activity of gastric acid secretion is through proton pump inhibition. The pharmacokinetic properties provide for an enhanced pharmacological effect. Esomeprazole is rapidly absorbed and the extent of absorption is higher resulting in higher systemic absorption of esomeprazole (bioavailability), which coupled with reduced clearance results in greater systemic exposure. This pharmacodynamic profile then provides for a prolongation of inhibition of gastric acid output and correlates well with its more beneficial therapeutic efficacy over omeprazole and some of the other proton-pump inhibitors. It has been well proven as an effective agent in the treatment of gastro-esophagitis reflux disease, (reflux esophagitis and non-erosive reflux disease), NSAID-induced gastric-intestinal symptoms and ulcers, Helicobacter pylori infection and Zollinger-Ellison syndrome. Esomeprazole has a good tolerability profile and a low potential for drug interaction.
Collapse
|
|
46
|
Gunasekaran T, Tolia V, Colletti RB, Gold BD, Traxler B, Illueca M, Crawley JA. Effects of esomeprazole treatment for gastroesophageal reflux disease on quality of life in 12- to 17-year-old adolescents: an international health outcomes study. BMC Gastroenterol 2009; 9:84. [PMID: 19922626 PMCID: PMC2784471 DOI: 10.1186/1471-230x-9-84] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2009] [Accepted: 11/18/2009] [Indexed: 12/15/2022] Open
Abstract
Background Although gastroesophageal reflux disease (GERD) is common in adolescents, the burden of GERD on health-related quality of life (HRQOL) in adolescents has not been previously evaluated. Therefore, the objective of the study was to examine the effect of GERD on HRQOL in adolescents. Methods This international, 31-site, 8-week safety study randomized adolescents, aged 12 to 17 years inclusive, with GERD to receive esomeprazole 20 or 40 mg once daily. The Quality of Life in Reflux and Dyspepsia questionnaire (QOLRAD), previously validated in adults, consists of 25 questions grouped into 5 domains: emotional distress, sleep disturbance, food/drink problems, physical/social functioning, and vitality. The QOLRAD was administered at the baseline and week-8 (final) visits. Results Of the 149 patients randomized, 134 completed the QOLRAD at baseline and final visits and were eligible for analysis of their HRQOL data. Baseline QOLRAD scores indicated GERD had a negative effect on the HRQOL of these adolescents, especially in the domains of vitality and emotional distress, and problems with food/drink. At the final visit, mean scores for all 5 QOLRAD domains improved significantly (P < .0001); change of scores (ie, delta) for all domains met or exceeded the adult QOLRAD minimal clinically significant difference standard of 0.5 units. Conclusion GERD had a negative effect on QOL in adolescents. After esomeprazole treatment, statistically and clinically significant improvements occurred in all domains of the QOLRAD for these adolescents. Trial Registration D9614C00098; ClinicalTrials.gov Identifier NCT00241501
Collapse
|
|
47
|
Howden CW, Larsen LM, Perez MC, Palmer R, Atkinson SN. Clinical trial: efficacy and safety of dexlansoprazole MR 60 and 90 mg in healed erosive oesophagitis - maintenance of healing and symptom relief. Aliment Pharmacol Ther 2009; 30:895-907. [PMID: 19681809 DOI: 10.1111/j.1365-2036.2009.04119.x] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Dexlansoprazole MR, a modified-release formulation of dexlansoprazole, an enantiomer of lansoprazole, effectively heals erosive oesophagitis. AIM To assess dexlansoprazole MR in maintaining healed erosive oesophagitis. METHODS Patients (n = 451) with erosive oesophagitis healed in either of two dexlansoprazole MR healing trials randomly received dexlansoprazole MR 60 or 90 mg or placebo once daily in this double-blind trial. The percentage of patients who maintained healing at month 6 was analysed using life table and crude rate methods. Secondary endpoints were percentages of nights and of 24-h days without heartburn based on daily diaries. RESULTS Dexlansoprazole MR 60 and 90 mg were superior to placebo for maintaining healing (P < 0.0025). Maintenance rates were 87% and 82% for the 60 and 90 mg doses, respectively, vs. 26% for placebo (life table), and 66% and 65% vs. 14%, respectively (crude rate). Both doses were superior to placebo for the percentage of 24-h heartburn-free days (60 mg, 96%; 90 mg, 94%; placebo, 19%) and nights (98%, 97%, and 50%, respectively). Diarrhoea, flatulence, gastritis (symptoms) and abdominal pain occurred more frequently with dexlansoprazole MR than placebo, but were not dose-related. CONCLUSION Dexlansoprazole MR effectively maintained healed erosive oesophagitis and symptom relief compared with placebo, and was well tolerated.
Collapse
Affiliation(s)
- C W Howden
- Division of Gastroenterology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | | | | | | | | |
Collapse
|
|
48
|
Furuta T, Sugimoto M, Kodaira C, Nishino M, Yamade M, Ikuma M, Shirai N, Watanabe H, Umemura K, Kimura M, Hishida A. CYP2C19 genotype is associated with symptomatic recurrence of GERD during maintenance therapy with low-dose lansoprazole. Eur J Clin Pharmacol 2009; 65:693-698. [PMID: 19259653 DOI: 10.1007/s00228-009-0628-5] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2008] [Accepted: 01/28/2009] [Indexed: 12/19/2022]
Abstract
BACKGROUND/AIMS Maintenance therapy of gastroesophageal reflux disease (GERD) is usually performed with a low dose of a proton-pump inhibitor (PPI). Because PPIs are metabolized by CYP2C19 in the liver, we investigated whether a patient's CYP2C19 genotype was associated with symptomatic recurrence of GERD during maintenance therapy with a low dose of a PPI. METHODS We enrolled 124 patients with erosive GERD whose esophageal mucosal breaks were endoscopically proven to be cured after treatment with lansoprazole 30 mg/day for 8 weeks. When reflux symptoms occurred less than once per week, the dose of lansoprazole was decreased to 15 mg/day, but if symptoms then occurred more than once per week, it was restored to 30 mg/day. CYP2C19 genotypes were classified as rapid metabolizer (RM), intermediate metabolizer (IM) or poor metabolizer (PM). RESULTS In 18 of 54 RMs, 28 of 56 IMs, and 8 of 14 PMs, the maintenance dose of lansoprazole was decreased to 15 mg/day, but in 16 (88.9%), 22 (78.6%), and 4 (50%), respectively, there was symptomatic recurrence of GERD and the dose was restored to 30 mg/day. The hazard ratios of symptomatic recurrence of GERD in IMs and PMs compared with RMs were 0.40 (95%CI: 0.19-0.87, P = 0.021) and 0.19 (95%CI: 0.05-0.69, P = 0.011). CONCLUSION When the dose of lansoprazole is decreased, the RM genotype of CYP2C19 appears to be a risk factor for symptomatic recurrence of GERD. The CYP2C19 genotyping test would be useful for determining the optimal dose of a PPI for maintenance therapy of GERD.
Collapse
Affiliation(s)
- Takahisa Furuta
- Center for Clinical Research, Hamamatsu University School of Medicine, 1-20-1, Handayama, Higashi-Ku, Hamamatsu, 431-3192, Japan.
| | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
49
|
Peura DA, Freston JW, Haber MM, Kovacs TO, Hunt B, Atkinson S. Lansoprazole for long-term maintenance therapy of erosive esophagitis: double-blind comparison with ranitidine. Dig Dis Sci 2009; 54:955-63. [PMID: 18726153 DOI: 10.1007/s10620-008-0466-9] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2008] [Accepted: 07/16/2008] [Indexed: 01/11/2023]
Abstract
In a study evaluating the efficacy and safety of lansoprazole to prevent the relapse of erosive esophagitis (EE), 206 of 241 patients (85%) healed after open-label treatment with lansoprazole 30 mg once daily for 8 weeks and received double-blind maintenance treatment with lansoprazole 15 mg once daily or ranitidine 150 mg twice daily for up to 1 year. At 1 year, 67% of lansoprazole-treated and 13% of ranitidine-treated patients remained healed (P<0.001). Lansoprazole-treated patients experienced significantly greater symptom relief (P<0.001), and, if asymptomatic at entry into the maintenance phase, remained asymptomatic for significantly longer than ranitidine-treated patients (P<0.001). Symptom status correlated with healing (P=0.001), supporting the symptom-directed management of EE. Both treatments were well tolerated and no unexpected events occurred. Daily therapy with lansoprazole to prevent the relapse of EE is effective, well tolerated, and superior to ranitidine in the maintenance of healing and symptom relief.
Collapse
Affiliation(s)
- David A Peura
- University of Virginia Health System, Charlottesville, VA 22908-0708, USA.
| | | | | | | | | | | |
Collapse
|
|
50
|
Metz DC, Howden CW, Perez MC, Larsen L, O'Neil J, Atkinson SN. Clinical trial: dexlansoprazole MR, a proton pump inhibitor with dual delayed-release technology, effectively controls symptoms and prevents relapse in patients with healed erosive oesophagitis. Aliment Pharmacol Ther 2009; 29:742-54. [PMID: 19210298 DOI: 10.1111/j.1365-2036.2009.03954.x] [Citation(s) in RCA: 50] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Dexlansoprazole MR heals all grades of erosive oesophagitis (EO). AIM To assess efficacy and safety of dexlansoprazole MR in maintaining healed EO and heartburn relief. METHODS In this randomized, double-blind trial, 445 patients with healed EO received dexlansoprazole MR 30 mg or 60 mg or placebo once daily for 6 months. This trial assessed maintenance of endoscopic healing (primary endpoint) and continued symptom relief based on daily diaries (secondary endpoints). RESULTS Dexlansoprazole MR 30 mg and 60 mg were superior to placebo for maintaining healed EO (P < 0.0025; Hochberg's). By life-table analysis, maintenance rates were 75%, 83% and 27% for dexlansoprazole MR 30 mg, 60 mg and placebo respectively. Crude maintenance rates were 66% for both dexlansoprazole MR doses and 14% for placebo. Dexlansoprazole MR controlled heartburn (medians of 91-96% for 24-h heartburn-free days, 96-99% for heartburn-free nights). The only more common adverse event occurring at a significantly higher rate in dexlansoprazole MR groups than placebo when analysed per patient-months of exposure was upper respiratory tract infection. CONCLUSIONS Dexlansoprazole MR effectively maintained EO healing and symptom relief; most patients were heartburn-free for >90% of days. Both doses were well tolerated.
Collapse
Affiliation(s)
- D C Metz
- University of Pennsylvania School of Medicine, Division of Gastroenterology, Philadelphia, PA, USA
| | | | | | | | | | | |
Collapse
|