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Alimentary Pharmacology & Therapeutics Sep 2009No randomized controlled trial (RCT) has compared all European-licensed standard- and double-dose PPIs for the healing of severe erosive oesophagitis. (Comparative Study)
Comparative Study Review
Systematic review: standard- and double-dose proton pump inhibitors for the healing of severe erosive oesophagitis -- a mixed treatment comparison of randomized controlled trials.
BACKGROUND
No randomized controlled trial (RCT) has compared all European-licensed standard- and double-dose PPIs for the healing of severe erosive oesophagitis.
AIM
To compare the effectiveness of licensed doses of PPIs for healing severe erosive oesophagitis (i.e. esomeprazole 40 mg, lansoprazole 30 mg, omeprazole 20 mg and 40 mg, pantoprazole 40 mg and rabeprazole 20 mg).
METHODS
Systematic review of CENTRAL, EMBASE and MEDLINE for RCTs in patients with erosive oesophagitis (completed October 2008). Endoscopically verified healing rates at 4 and 8 weeks were extracted and re-calculated if not analysed by intention-to-treat. A mixed treatment comparison was used to combine direct treatment comparisons with indirect trial evidence while maintaining randomization. Odds ratios (OR) are reported compared to omeprazole 20 mg.
RESULTS
A total of 3021 papers were identified in the literature search; 12 were of sufficient quality to be included in the analysis. Insufficient data were available to included rabeprazole. Esomeprazole 40 mg was found to provide significantly higher healing rates at 4 weeks [OR 1.84, 95% Credible Interval (95% CrI): 1.50 to 2.22] and 8 weeks (OR 1.91, 95% CrI: 1.13 to 2.88). No other PPI investigated had significantly higher healing rates than omeprazole 20 mg.
CONCLUSION
Esomeprazole 40 mg consistently demonstrates higher healing rates compared with licensed standard- and double-dose PPIs.
Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Anti-Ulcer Agents; Dose-Response Relationship, Drug; Esomeprazole; Esophagitis; Humans; Lansoprazole; Omeprazole; Proton Pump Inhibitors; Rabeprazole; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 19558609
DOI: 10.1111/j.1365-2036.2009.04077.x -
Journal of Investigational Allergology... 2009To evaluate pediatric studies of the effect on asthma symptoms of treatment with proton pump inhibitors (PPI) used to treat gastroesophageal reflux disease (GERD). (Review)
Review
OBJECTIVE
To evaluate pediatric studies of the effect on asthma symptoms of treatment with proton pump inhibitors (PPI) used to treat gastroesophageal reflux disease (GERD).
METHODS
We entered the MeSH terms "gastroesophageal reflux AND asthma AND children" in the PubMed tool Clinical Queries, selecting "therapy" and "broad, sensitive search." The search ended on April 14, 2008. We included only clinical trials performed in pediatric patients.
RESULTS
Four studies were considered to be relevant, although only 1 was a randomized, double-blind, placebo-controlled trial. The 3 nonrandomized trials showed that PPIs benefited patients with asthma. The randomized, double-blind, placebo-controlled trial found that omeprazole did not improve asthma symptoms. An improved (although not statistically significant) score was observed in the quality of life questionnaire in children with a reflux index greater than 10% and in those with more severe asthma treated with omeprazole compared with the placebo group.
CONCLUSIONS
Scant data in these studies mean that we cannot make solid recommendations. However, in specific cases, we think that treatment of asthma symptoms with a PPI is valid as long as at least 2 conditions are satisfied: asthma must not respond to standard treatment, and 1 instrumental parameter of GERD severity must be satisfied, that is, a reflux index greater than or equal to 10 must be present.
Topics: Asthma; Child; Gastroesophageal Reflux; Humans; Omeprazole; Proton Pump Inhibitors; Randomized Controlled Trials as Topic
PubMed: 19274922
DOI: No ID Found -
Canadian Journal of Gastroenterology =... Sep 2008Proton pump inhibitors (PPIs) have become the mainstay of treatment for and prevention of many serious gastrointestinal diseases. Laboratory and clinical evidence... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Proton pump inhibitors (PPIs) have become the mainstay of treatment for and prevention of many serious gastrointestinal diseases. Laboratory and clinical evidence suggests that the increase in gastric pH caused by PPIs may be linked to increased bacterial colonization of the stomach and may predispose patients to an increased risk for respiratory infections.
OBJECTIVE
To examine the association between PPI treatment and respiratory infections.
METHODS
A literature search was conducted using PubMed, MEDLINE and Cochrane databases of randomized, placebo-controlled trials evaluating the efficacy of PPIs. Studies that listed and quantified the specific adverse events of 'respiratory infection' or 'upper respiratory infection' (or equivalent), and compared their rates between PPIs and placebo were included. The chi(2) analysis was used to calculate the significance of association in individual studies and a meta-analysis of the selected studies was performed.
RESULTS
Of 7457 studies initially identified and 70 relevant randomized, controlled trials (RCTs) selected, seven studies met the inclusion criteria. A total of 16 comparisons for chi(2) analysis were possible given the multiple dosage arms used in several studies. PPIs included in the studies were esomeprazole, rabeprazole, pantoprazole and omeprazole. More than one-half of the studies showed a trend toward an association between PPI use and respiratory infections, although the majority of the studies failed to show a significant correlation. A single study using high-dose esomeprazole (40 mg) showed a significant association -4.3% rate of respiratory infections in the active group compared with 0% in the placebo group (P<0.05). Meta-analysis showed a trend toward an association between PPIs and respiratory infections, although it failed to reach significance (OR 1.42, 95% CI 0.86 to 2.35; P=0.17).
CONCLUSION
Although a trend was evident in both a chi(2) analysis of individual studies and a meta-analysis, the present review and meta-analysis failed to show a conclusive association between PPIs and respiratory infections. Very few RCTs actively sought out respiratory infections, which excluded the majority of RCTs identified. A well-structured, placebo-controlled prospective study would be needed to determine whether a true association between PPIs and respiratory infections exists.
Topics: Clinical Trials as Topic; Community-Acquired Infections; Humans; Proton Pump Inhibitors; Respiratory Tract Infections
PubMed: 18818790
DOI: 10.1155/2008/821385 -
Alimentary Pharmacology & Therapeutics Oct 2008The evidence on whether high-dose proton pump inhibitors (PPIs) increase cure rates of Helicobacter pylori treatment has not been previously assessed. (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
The evidence on whether high-dose proton pump inhibitors (PPIs) increase cure rates of Helicobacter pylori treatment has not been previously assessed.
AIM
To evaluate the evidence on the usefulness of high-dose PPI in standard triple therapy by performing a systematic review and a meta-analysis.
METHODS
A systematic search was performed in multiple databases and in the abstracts submitted to the Digestive Diseases Week, the European Helicobacter Study Group congress and the United European Gastroenterology Week. Randomized trials comparing a standard dose of a PPI with high-dose PPI both twice a day in triple therapy combining a PPI plus clarithromycin and either amoxicillin or metronidazole were selected. Relative risk (RR) and 95% confidence intervals (95% CIs) for all comparisons were calculated using Review Manager.
RESULTS
Six studies fulfilled the inclusion criteria. All used triple therapy for 7 days. A mean intention-to-treat cure rate of 82% was achieved with high-dose PPI and one of 74% with standard dose (RR: 1.09; 95% CI: 1.01-1.17). Subgroup analysis showed that the maximum increase was observed when the PPI compared were omeprazole 20 mg or pantoprazole 40 mg vs. esomeprazole 40 mg.
CONCLUSION
High-dose PPI seems more effective than standard-dose for curing H. pylori infection in 7-day triple therapy.
Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Drug Administration Schedule; Esomeprazole; Helicobacter Infections; Helicobacter pylori; Humans; Omeprazole; Pantoprazole; Proton Pump Inhibitors
PubMed: 18644011
DOI: 10.1111/j.1365-2036.2008.03807.x -
Health Technology Assessment... Apr 2008To review the clinical effectiveness and cost-effectiveness of cyclooxygenase-2 (COX-2) selective non-steroidal anti-inflammatory drugs (NSAIDs) (etodolac, meloxicam,... (Meta-Analysis)
Meta-Analysis Review
Cyclooxygenase-2 selective non-steroidal anti-inflammatory drugs (etodolac, meloxicam, celecoxib, rofecoxib, etoricoxib, valdecoxib and lumiracoxib) for osteoarthritis and rheumatoid arthritis: a systematic review and economic evaluation.
OBJECTIVES
To review the clinical effectiveness and cost-effectiveness of cyclooxygenase-2 (COX-2) selective non-steroidal anti-inflammatory drugs (NSAIDs) (etodolac, meloxicam, celecoxib, rofecoxib, etoricoxib, valdecoxib and lumiracoxib) for osteoarthritis (OA) and rheumatoid arthritis (RA).
DATA SOURCES
Electronic databases were searched up to November 2003. Industry submissions to the National Institute for Health and Clinical Excellence (NICE) in 2003 were also reviewed.
REVIEW METHODS
Systematic reviews of randomised controlled trials (RCTs) and a model-based economic evaluation were undertaken. Meta-analyses were undertaken for each COX-2 selective NSAID compared with placebo and non-selective NSAIDs. The model was designed to run in two forms: the 'full Assessment Group Model (AGM)', which includes an initial drug switching cycle, and the 'simpler AGM', where there is no initial cycle and no opportunity for the patient to switch NSAID.
RESULTS
Compared with non-selective NSAIDs, the COX-2 selective NSAIDs were found to be equally as efficacious as the non-selective NSAIDs (although meloxicam was found to be of inferior or equivalent efficacy) and also to be associated with significantly fewer clinical upper gastrointestinal (UGI) events (although relatively small numbers of clinical gastrointestinal (GI) and myocardial infarction (MI) events were reported across trials). Subgroup analyses of clinical and complicated UGI events and MI events in relation to aspirin use, steroid use, prior GI history and Helicobacter pylori status were based on relatively small numbers and were inconclusive. In the RCTs that included direct COX-2 comparisons, the drugs were equally tolerated and of equal efficacy. Trials were of insufficient size and duration to allow comparison of risk of clinical UGI events, complicated UGI events and MIs. One RCT compared COX-2 (celecoxib) with a non-selective NSAID combined with a gastroprotective agent (diclofenac combined with omeprazole); this included arthritis patients who had recently suffered a GI haemorrhage. Although no significant difference in clinical GI events was reported, the number of events was small and more such studies, where patients genuinely need NSAIDs, are required to confirm these data. A second trial showed that rofecoxib was associated with fewer diarrhoea events than a combination of diclofenac and misoprostol (Arthrotec). Previously published cost-effectiveness analyses indicated a wide of range of possible incremental cost per quality-adjusted life-year (QALY) gained estimates. Using the simpler AGM, with ibuprofen or diclofenac alone as the comparator, all of the COX-2 products are associated with higher costs (i.e. positive incremental costs) and small increases in effectiveness (i.e. positive incremental effectiveness), measured in terms of QALYs. The magnitude of the incremental costs and the incremental effects, and therefore the incremental cost-effectiveness ratios, vary considerably across all COX-2 selective NSAIDs. The base-case incremental cost per QALY results for COX-2 selective NSAIDs compared with diclofenac for the simpler model are: celecoxib (low dose) 68,400 pounds; celecoxib (high dose) 151,000 pounds; etodolac (branded) 42,400 pounds; etodolac (generic) 17,700 pounds; etoricoxib 31,300 pounds; lumiracoxib 70,400 pounds; meloxicam (low dose) 10,300 pounds; meloxicam (high dose) 17,800 pounds; rofecoxib 97,400 pounds; and valdecoxib 35,500 pounds. When the simpler AGM was run using ibuprofen or diclofenac combined with proton pump inhibitor (PPI) as the comparator, the results change substantially, with the COX-2 selective NSAIDs looking generally unattractive from a cost-effectiveness point of view (COX-2 selective NSAIDs were dominated by ibuprofen or diclofenac combined with PPI in most cases). This applies both to 'standard' and 'high-risk' arthritis patients defined in terms of previous GI ulcers. The full AGM produced results broadly in line with the simpler model.
CONCLUSIONS
The COX-2 selective NSAIDs examined were found to be similar to non-selective NSAIDs for the symptomatic relief of RA and OA and to provide superior GI tolerability (the majority of evidence is in patients with OA). Although COX-2 selective NSAIDs offer protection against serious GI events, the amount of evidence for this protective effect varied considerably across individual drugs. The volume of trial evidence with regard to cardiovascular safety also varied substantially between COX-2 selective NSAIDs. Increased risk of MI compared to non-selective NSAIDs was observed among those drugs with greater volume of evidence in terms of exposure in patient-years. Economic modelling shows a wide range of possible costs per QALY gained in patients with OA and RA. Costs per QALY also varied if individual drugs were used in 'standard' or 'high'-risk patients, the choice of non-selective NSAID comparator and whether that NSAID was combined with a PPI. With reduced costs of PPIs, future primary research needs to compare the effectiveness and cost-effectiveness of COX-2 selective NSAIDs relative to non-selective NSAIDs with a PPI. Direct comparisons of different COX-2 selective NSAIDs, using equivalent doses, that compare GI and MI risk are needed. Pragmatic studies that include a wider range of people, including the older age groups with a greater burden of arthritis, are also necessary to inform clinical practice.
Topics: Anti-Ulcer Agents; Arthritis, Rheumatoid; Cost-Benefit Analysis; Cyclooxygenase 2 Inhibitors; Gastrointestinal Diseases; Humans; Markov Chains; Models, Econometric; Omeprazole; Osteoarthritis; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; Risk Factors; Technology Assessment, Biomedical; Thrombosis
PubMed: 18405470
DOI: 10.3310/hta12110 -
Alimentary Pharmacology & Therapeutics Sep 2006No randomized controlled trial has compared all the licensed standard dose proton pump inhibitors in the healing of reflux oesophagitis. (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND
No randomized controlled trial has compared all the licensed standard dose proton pump inhibitors in the healing of reflux oesophagitis.
AIM
To compare the effectiveness of esomeprazole with licensed standard dose proton pump inhibitors for healing of reflux oesophagitis (i.e. lansoprazole 30 mg, omeprazole 20 mg, pantoprazole 40 mg and rabeprazole 20 mg).
METHODS
Systematic review of CENTRAL, BIOSIS, EMBASE and MEDLINE for randomized controlled trials in patients with reflux oesophagitis. Searching was completed in February 2005. Data on endoscopic healing rates at 4 and 8 weeks were extracted and re-analysed if not analysed by intention-to-treat. Meta-analysis was conducted using a fixed effects model.
RESULTS
Of 133 papers identified in the literature search, six were of sufficient quality to be included in the analysis. No studies were identified comparing rabeprazole with esomeprazole. A meta-analysis of healing rates of esomeprazole 40 mg compared with standard dose proton pump inhibitors gave the following results: at 4 weeks [relative risk (RR) 0.92; 95% CI: 0.90, 0.94; P < 0.00001], and 8 weeks (RR 0.95; 95% CI: 0.94, 0.97; P < 0.00001). Publication bias did not have a significant impact on the results. The results were robust to changes in the inclusion/exclusion criteria and using a random effects model.
CONCLUSION
Esomeprazole consistently demonstrates higher healing rates when compared with standard dose proton pump inhibitors.
Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Clinical Trials as Topic; Enzyme Inhibitors; Esomeprazole; Esophagitis, Peptic; Humans; Lansoprazole; Omeprazole; Pantoprazole; Proton Pump Inhibitors; Rabeprazole; Treatment Outcome
PubMed: 16918878
DOI: 10.1111/j.1365-2036.2006.03074.x -
Canadian Family Physician Medecin de... Jul 2006A 36-year-old pregnant patient has symptoms of peptic disease. Treatment with diet and lifestyle modifications and also antacids has given her little relief. If she were... (Review)
Review
QUESTION
A 36-year-old pregnant patient has symptoms of peptic disease. Treatment with diet and lifestyle modifications and also antacids has given her little relief. If she were not pregnant, I would prescribe a proton pump inhibitor (PPI) for her. She is now 4 weeks pregnant, and I need to determine whether PPIs are safe during pregnancy.
ANSWER
Data currently available suggest that omeprazole is not teratogenic in humans. While information on other PPIs is limited, a systematic review of the evidence suggests that they are also not teratogenic.
Topics: Anti-Ulcer Agents; Breast Feeding; Drug-Related Side Effects and Adverse Reactions; Female; Gastroesophageal Reflux; Humans; Pregnancy; Pregnancy Complications; Proton Pump Inhibitors
PubMed: 16893146
DOI: No ID Found -
Alimentary Pharmacology & Therapeutics Jun 2005To perform a systematic review on the efficacy of intermittent and on-demand therapy with either histamine H2-receptor antagonists or proton pump inhibitors for patients... (Review)
Review
Systematic review: the efficacy of intermittent and on-demand therapy with histamine H2-receptor antagonists or proton pump inhibitors for gastro-oesophageal reflux disease patients.
AIM
To perform a systematic review on the efficacy of intermittent and on-demand therapy with either histamine H2-receptor antagonists or proton pump inhibitors for patients with erosive oesophagitis or symptomatic heartburn.
METHOD
We conducted randomized-controlled trials of non-continuous therapy in gastro-oesophageal reflux disease patients.
RESULTS
Fourteen studies met inclusion criteria. Because of variation in outcome measures statistical pooling of results was not possible. Results were analysed qualitatively. Four studies evaluated intermittent therapy of treatment 3 days a week with omeprazole 20 mg or daily with ranitidine which were not efficacious compared to a daily proton pump inhibitor. Famotidine 10 and 20 mg, ranitidine 75 mg and cimetidine 200 mg were efficacious in five on-demand studies for relief of symptomatic heartburn episodes. In three of four studies, evaluating only non-erosive (endoscopy-negative) gastro-oesophageal reflux disease patients, esomeprazole 20 and 40 mg and omeprazole 10 and 20 mg a day were efficacious using willingness to continue as an endpoint. Lansoprazole 30 mg and omeprazole 20 mg maintained symptom control in 60-70% of healed oesophagitis patients.
CONCLUSIONS
Intermittent proton pump inhibitor or H2-receptor antagonist therapy is not effective in maintaining control in oesophagitis patients. H2-receptor antagonists are effective for relief of heartburn episodes. On-demand proton pump inhibitor therapy may work in a proportion of non-erosive gastro-oesophageal reflux disease patients.
Topics: Drug Administration Schedule; Gastroesophageal Reflux; Histamine H2 Antagonists; Humans; Proton Pump Inhibitors; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 15932360
DOI: 10.1111/j.1365-2036.2005.02490.x -
Alimentary Pharmacology & Therapeutics Mar 2003To perform a systematic review of the efficacy of rabeprazole-based therapies in Helicobacter pylori eradication, and to conduct a meta-analysis comparing the efficacy... (Meta-Analysis)
Meta-Analysis Review
AIM
To perform a systematic review of the efficacy of rabeprazole-based therapies in Helicobacter pylori eradication, and to conduct a meta-analysis comparing the efficacy of rabeprazole and other proton pump inhibitors when co-prescribed with antibiotics.
METHODS
Studies evaluating rabeprazole plus antibiotics were considered. Only randomized trials comparing rabeprazole and other proton pump inhibitors with antibiotics, and differing only in the proton pump inhibitor, were included in the meta-analysis. Electronic and manual bibliographic searches were conducted. The percentage (weighted mean) of successful eradication was calculated. Meta-analysis was performed by combining the odds ratios (OR) of the individual studies.
RESULTS
The eradication rates were as follows: 14-day rabeprazole-amoxicillin, 73%; rabeprazole-amoxicillin-clarithromycin for 3, 5, 7 and 10 days, 44%, 72%, 78% and 75%, respectively; low-dose rabeprazole (20 mg/day), amoxicillin and clarithromycin for 7 days, 81%; high-dose rabeprazole (40 mg/day), amoxicillin and clarithromycin for 7 days, 75%; 7-day rabeprazole-clarithromycin-nitroimidazole, 85%. Twelve comparative studies were included in the meta-analysis. The eradication rate with rabeprazole plus antibiotics was 79%; it was 77% with other proton pump inhibitors (OR = 1.15; 95% confidence interval, 0.93-1.42). Sub-analysis comparing rabeprazole at low doses (10 mg b.d.) with other proton pump inhibitors at standard doses (omeprazole 20 mg b.d. or lansoprazole 30 mg b.d.) showed no differences.
CONCLUSIONS
Rabeprazole achieves similar H. pylori eradication rates to omeprazole and lansoprazole when co-prescribed with antibiotics. Low doses of rabeprazole (10 mg b.d.), when administered with two antibiotics, may be sufficient to eradicate H. pylori infection.
Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Anti-Ulcer Agents; Benzimidazoles; Helicobacter Infections; Helicobacter pylori; Humans; Omeprazole; Rabeprazole; Treatment Outcome
PubMed: 12641497
DOI: 10.1046/j.1365-2036.2003.01450.x -
Alimentary Pharmacology & Therapeutics Feb 2002Gastro-oesophageal reflux disease (GERD) is a common disorder in the primary care setting. Traditional management strategies consist of sequentially intensive... (Review)
Review
BACKGROUND
Gastro-oesophageal reflux disease (GERD) is a common disorder in the primary care setting. Traditional management strategies consist of sequentially intensive therapeutic trials followed by invasive diagnostic testing for nonresponders. A high dose proton pump inhibitor trial (the "proton pump inhibitor test") has been shown to be an accurate diagnostic alternative, and may be an efficient initial approach to patients with GERD symptoms.
AIM
To examine the clinical, economic and policy implications of alternative management strategies for GERD.
METHODS
Decision analysis was used to calculate the clinical and economic outcomes of competing management strategies. The traditional strategy incorporates sequential therapeutic trials with more intensive therapy ("step-up" approach) followed by sequential invasive diagnostic testing of nonresponders. The "proton pump inhibitor test" strategy includes an initial "proton pump inhibitor test" (7 days of omeprazole; 40 mg AM + 20 mg PM daily) followed by less intensive therapeutic trials in those testing positive ("step-down" approach) with sequential invasive diagnostic testing as needed. Cost estimates were based on Medicare reimbursement and average wholesale drug prices. Probability estimates were derived from a systematic review of the published medical literature. Model results are reported as the average and incremental cost-per-symptom free patient and cost-per-quality-adjusted life-years (QALYs) gained.
RESULTS
The average cost per patient was 1045 US dollars for the traditional step-up management strategy, compared to 1172 US dollars for the "proton pump inhibitor test" and step-down strategy. The percentage of patients who were symptom-free at 1 year was 50% for the traditional management strategy compared to 75% for the "proton pump inhibitor test" strategy. The "proton pump inhibitor test" strategy results in QALY gains of 0.01-0.05 depending on the utility estimate employed. The incremental cost-effectiveness ratio for the "proton pump inhibitor test" strategy is 510 US dollars per additional symptomatic cure over 1 year, and between 2822-10,160 US dollars per QALY gained. The traditional management strategy resulted in a greater than 5-fold increase in the utilization of upper endoscopy, which was partially offset by a 47% reduction in the use of ambulatory 24-h oesophageal pH monitoring. The reduced effectiveness of the traditional management strategy may be attributed in part to a 118% increase in the use of "high-dose" H2RAs while reducing the use of standard dose proton pump inhibitors by only 42% and "high-dose" proton pump inhibitors by 57%.
CONCLUSIONS
Based on the results of this analysis, strategies utilizing the initial PPI test followed by a "step-down" approach may result in improved symptom relief and quality of life over 1 year, and more appropriate utilization of invasive diagnostic testing at a small marginal increase in total costs. These findings warrant a prospective trial comparing these competing management strategies.
Topics: Anti-Ulcer Agents; Decision Support Techniques; Gastroesophageal Reflux; Humans; Office Visits; Omeprazole; Proton Pump Inhibitors; Quality-Adjusted Life Years
PubMed: 11860409
DOI: 10.1046/j.1365-2036.2002.01167.x