Clinical trial: the incidence of NSAID‐associated endoscopic gastric ulcers in patients treated with PN 400 (naproxen plus esomeprazole magnesium) vs. enteric‐coated naproxen alone

Goldstein, Jay L.; Hochberg, Marc C.; Fort, John G.; Zhang, Y.; Hwang, Clara; Sostek, Mark

doi:10.1111/j.1365-2036.2010.04378.x

Cited by 70 publications

(65 citation statements)

References 41 publications

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“…Up to 1 year of dosing with the combination product was completed by patients in the phase 3, US multicenter, double-blind studies and the extension study. These studies, and others with a naproxen/esomeprazole combination, indicate that the relative decrease in endoscopic damage is similar to that found with celecoxib (relative risk reduction of 40% to 50%) 30,31,34,35 . Over the 1-year analysis, the incidence of AEs, AEs leading to discontinuation, and SAEs were similar between the ibuprofen/famotidine and the ibuprofen group with TEAEs reported more frequently among the ibuprofen group.…”

Section: Discussionsupporting

confidence: 50%

“…Goldstein and colleagues 34 enrolled subjects in two randomized, double-blind, parallel-group, controlled, multicenter studies comparing a fixed combination of 20 mg omeprazole and 500 mg naproxen to 500 mg naproxen alone for 6 months. In these two naproxen studies, the reported premature discontinuation rate was 6.9% and 10.5% for the combination therapy group and 15.7% and 18.1% for the naproxen only group, respectively.…”

Section: Discussionmentioning

confidence: 99%

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One-year safety of ibuprofen/famotidine fixed combination versus ibuprofen alone: pooled analyses of two 24-week randomized, double-blind trials and a follow-on extension

Bello

Grahn

Ball

et al. 2015

Current Medical Research and Opinion

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Objective:To evaluate the safety of the fixed combination of ibuprofen and famotidine compared with ibuprofen alone from two 24-week, multicenter, double-blind trials designed to evaluate the comparative incidence of endoscopically documented upper gastrointestinal ulcers and a 28-week double-blind extension study. Research design and methods:Safety was analyzed by pooling data from the two double-blind trials and the follow-on study. Safety was assessed by monitoring the incidence, causality, and severity of adverse events (AEs). Results:In the pivotal efficacy and safety trials, discontinuation rates due to any cause and dyspepsia were significantly lower for the ibuprofen/famotidine combination versus ibuprofen alone. Other than dyspepsia, gastrointestinal and cardiovascular AEs of special interest were similar. Events judged to be treatment related were significantly lower with the ibuprofen/famotidine combination (20.6% vs. 25%). In the safety extension population, there were no differences in the discontinuation rates and the reporting of AEs or serious AEs (SAEs) between the two groups. Gastrointestinal-related events were similar between the groups. Incidence of cardiovascular-related AEs of special interest were 11% (ibuprofen/famotidine) and 2% (ibuprofen) (p ¼ 0.06), possibly due to a higher number of rheumatoid arthritis patients in the combination group. Of these, 80% were reports of hypertension (8% ibuprofen/famotidine vs. 2% ibuprofen). Three cases of hypertension in the ibuprofen/famotidine group were considered treatment related. The probability of a cardiovascular event decreased during days 112-167 of treatment and remained low with continued treatment. Conclusions:One-year safety data from two pivotal trials and a long-term extension study indicate that the ibuprofen/ famotidine combination demonstrates a favorable gastrointestinal safety profile and more patients continued on therapy compared to ibuprofen alone. No new safety signals have been identified. These data offer additional evidence supporting a new therapeutic option to improve gastrointestinal safety and adherence for patients who require long-term ibuprofen.

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Section: Discussionsupporting

confidence: 50%

Section: Discussionmentioning

confidence: 99%

One-year safety of ibuprofen/famotidine fixed combination versus ibuprofen alone: pooled analyses of two 24-week randomized, double-blind trials and a follow-on extension

Bello

Grahn

Ball

et al. 2015

Current Medical Research and Opinion

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“…COX-2 selective inhibitors were associated with a lower risk of peptic ulcers and UGIB than non-selective NSAIDs in taking with LDA [141,142], whereas in patients at high risk for recurrence of gastric ulcer taking with NSAIDs plus LDA, use of cotherapy with misoprostol or lansoprazole significantly lowered the risk for gastric ulcer recurrence [110]. Then, in LDA users, naproxen plus esomeprazole was associated with a lower combined incidence of gastric ulcers compared to naproxen [143]. Moreover, in patients with taking LDA, the use of celecoxib or naproxen plus lansoprazole resulted in similar rates of gastroduodenal ulceration [144].…”

Section: Commentmentioning

confidence: 99%

Evidence-based clinical practice guidelines for peptic ulcer disease 2015

et al. 2016

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The Japanese Society of Gastroenterology (JSGE) revised the evidence-based clinical practice guidelines for peptic ulcer disease in 2014 and has created an English version. The revised guidelines consist of seven items: bleeding gastric and duodenal ulcers, Helicobacter pylori (H. pylori) eradication therapy, non-eradication therapy, drug-induced ulcer, non-H. pylori, non-nonsteroidal anti-inflammatory drug (NSAID) ulcer, surgical treatment, and conservative therapy for perforation and stenosis. Ninety clinical questions (CQs) were developed, and a literature search was performed for the CQs using the Medline, Cochrane, and Igaku Chuo Zasshi databases between 1983 and June 2012. The guideline was developed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. Therapy is initially provided for ulcer complications. Perforation or stenosis is treated with surgery or conservatively. Ulcer bleeding is first treated by endoscopic hemostasis. If it fails, surgery or interventional radiology is chosen. Second, medical therapy is provided. In cases of NSAID-related ulcers, use of NSAIDs is stopped, and anti-ulcer therapy is provided. If NSAID use must continue, the ulcer is treated with a proton pump inhibitor (PPI) or prostaglandin analog. In cases with no NSAID use, H. pylori-positive patients receive eradication and anti-ulcer therapy. If first-line eradication therapy fails, second-line therapy is given. In cases of non-H. pylori, non-NSAID ulcers or H. pyloripositive patients with no indication for eradication therapy, non-eradication therapy is provided. The first choice is PPI therapy, and the second choice is histamine 2-receptor antagonist therapy. After initial therapy, maintenance therapy is provided to prevent ulcer relapse.

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“…Older age is a major risk factor for these adverse experiences [1,11,12], and in particular age ‡60 years [1,4,9]. Previous studies have shown that a large proportion of elderly patients experienced GI nuisance adverse events associated with NSAIDs [1,[11][12][13].…”

Section: Introductionmentioning

confidence: 99%

“…Non-steroidal anti-inflammatory drugs (NSAIDs) are a commonly prescribed class for the treatment of pain within this age group, yet chronic use of NSAIDs is known to pose potential cardiovascular and gastrointestinal (GI) risk and may result in non-adherence to NSAID therapy [1,4,9,10]. Older age is a major risk factor for these adverse experiences [1,11,12], and in particular age ‡60 years [1,4,9].…”

Section: Introductionmentioning

confidence: 99%

Gastroprotective efficacy and safety of single-tablet ibuprofen/famotidine vs ibuprofen in older persons

Bello

Kent

Holt

2015

The Physician and Sportsmedicine

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(2015) Gastroprotective efficacy and safety of single-tablet ibuprofen/famotidine vs ibuprofen in older persons, The Physician and Sportsmedicine, 43:3, 193-199, DOI: 10.1080/00913847.2015 Objectives: A combination tablet of ibuprofen 800 mg and famotidine 26.6 mg given three times daily is effective for the treatment of rheumatoid arthritis and osteoarthritis and decreases the risk of developing upper gastrointestinal (GI) ulcers. This analysis evaluated the gastroprotective efficacy and safety of the single-tablet combination of ibuprofen/famotidine compared with ibuprofen alone on the basis of age and the presence of one or more risk factors for development of upper GI ulcer. Methods: Pooled data from the 24-week, randomized, double-blind, parallel-group REDUCE-1 and REDUCE-2 trials were used. Endoscopies were performed in patients aged 40-80 years. The proportion of patients who developed ‡1 upper GI ulcer during treatment with ibuprofen/famotidine versus ibuprofen alone stratified on the basis of age (<60 or ‡60 years) was evaluated. Further, analyses were performed on additional risk factors for ulcer development. Results: Gastroprotective efficacy of the combination was not affected by age. Pooled results demonstrated statistically significantly fewer upper GI (10.0 vs 19.5%, p < 0.0001), gastric (8.9 vs 16.8%, p = 0.0004), and duodenal ulcers (1.1 vs 5.4%, p < 0.0001) in patients <60 years treated with ibuprofen/famotidine versus ibuprofen alone compared with 12.9 vs 26.6% (p = 0.0002), 11.9 vs 23.4% (p = 0.0011), and 1.0 vs 4.5% (p = 0.0096), respectively, in patients ‡60 years. The ibuprofen/famotidine combination provided nearly 51 and 59% reduction in the risk of developing a GI ulcer in patients <60 years and ‡60 of age, respectively. Efficacy was maintained in the presence of additional risk factors, as well. Conclusions: These results indicate that the fixed-combination of ibuprofen/famotidine provides gastroprotection in those of older age, with or without additional risk factors for the development of upper GI ulcers, as compared with ibuprofen alone. US National Institutes of Health registry, http://www.clinicaltrials.gov, NCT00450658 and NCT00450216.

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Clinical trial: the incidence of NSAID‐associated endoscopic gastric ulcers in patients treated with PN 400 (naproxen plus esomeprazole magnesium) vs. enteric‐coated naproxen alone

Abstract: SUMMARY BackgroundGastroprotective co-therapy may reduce the risk of nonsteroidal anti-inflammatory drug (NSAID)-associated gastric ulcers, but adherence is suboptimal.

Cited by 70 publications

References 41 publications

One-year safety of ibuprofen/famotidine fixed combination versus ibuprofen alone: pooled analyses of two 24-week randomized, double-blind trials and a follow-on extension

One-year safety of ibuprofen/famotidine fixed combination versus ibuprofen alone: pooled analyses of two 24-week randomized, double-blind trials and a follow-on extension

Evidence-based clinical practice guidelines for peptic ulcer disease 2015

Gastroprotective efficacy and safety of single-tablet ibuprofen/famotidine vs ibuprofen in older persons

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