Long-term safety of naproxen and esomeprazole magnesium fixed-dose combination: phase III study in patients at risk for NSAID-associated gastric ulcers

Sostek, Mark; Fort, John G.; Estborn, Lennart; Vikman, Kerstin

doi:10.1185/03007995.2011.555756

Cited by 22 publications

(13 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…To reduce the expected upper GI toxicity of the combination of an NSAID and low-dose aspirin, PPIs are typically prescribed as well. Indeed, there are now fixed-dose, enteric-coated, combination tablets available that contain an NSAID and a PPI [34] . While there is strong evidence for PPIs reducing the severity of damage and bleeding in the stomach and duodenum, where the role of acid in the production of damage has been clearly demonstrated [1,35] , there is no evidence to suggest that a PPI (or other anti-secretory drug) would reduce the severity of NSAID-induced enteropathy.…”

Section: Polypharmacy Conundrum: Shifting Gi Injury More Distallymentioning

confidence: 99%

Mechanisms, prevention and clinical implications of nonsteroidal anti-inflammatory drug-enteropathy

Wallace¹

2013

WJG

146

148

View full text Add to dashboard Cite

This article reviews the latest developments in understanding the pathogenesis, detection and treatment of small intestinal damage and bleeding caused by nonsteroidal anti-inflammatory drugs (NSAIDs). With improvements in the detection of NSAID-induced damage in the small intestine, it is now clear that this injury and the associated bleeding occurs more frequently than that occurring in the stomach and duodenum, and can also be regarded as more dangerous. However, there are no proven-effective therapies for NSAIDenteropathy, and detection remains a challenge, particularly because of the poor correlation between tissue injury and symptoms. Moreover, recent studies suggest that commonly used drugs for protecting the upper gastrointestinal tract (i.e. , proton pump inhibitors) can significantly worsen NSAID-induced damage in the small intestine. The pathogenesis of NSAIDenteropathy is complex, but studies in animal models are shedding light on the key factors that contribute to ulceration and bleeding, and are providing clues to the development of effective therapies and prevention strategies. Novel NSAIDs that do not cause small in- FRONTIER

show abstract

Section: Polypharmacy Conundrum: Shifting Gi Injury More Distallymentioning

confidence: 99%

Mechanisms, prevention and clinical implications of nonsteroidal anti-inflammatory drug-enteropathy

Wallace¹

2013

WJG

146

148

View full text Add to dashboard Cite

show abstract

“…NAP/ESO significantly reduced the incidence of endoscopic ulcers compared with PBO and improved upper gastrointestinal tolerability compared with enteric-coated naproxen alone in previous trials [24,33,34]. No new or emerging safety issues, including the predefined cardiovascular endpoints, were observed in long-term NAP/ESO trials [35]. The objective of the present analysis was to further characterize time-to-first pain relief, effect size, correlations between various outcome measures, and durability of pain relief for oral NAP/EPO (500 mg/20 mg BID) versus matching PBO (BID), with oral CEL (200 mg once daily) as an active control.…”

Section: Introductionmentioning

confidence: 89%

Onset and durability of pain relief in knee osteoarthritis: Pooled results from two placebo trials of naproxen/esomeprazole combination and celecoxib

Holt

Fort²,

Grahn

et al. 2015

The Physician and Sportsmedicine

Self Cite

View full text Add to dashboard Cite

(2015) Onset and durability of pain relief in knee osteoarthritis: Pooled results from two placebo trials of naproxen/esomeprazole combination and celecoxib, The Physician and Sportsmedicine, 43:3, 200-212, DOI: 10.1080/00913847.2015 AbstractObjective. To further characterize time-to-first pain relief, effect size, correlations between various outcome measures and durability of relief for single-tablet naproxen 500 mg/esomeprazole 20 mg (NAP/ESO) given twice daily and celecoxib (CEL) (200 mg) given once daily versus placebo in knee osteoarthritis (OA). Methods. Unpublished data from two double-blind, double-dummy, placebo-controlled trials in which patients aged ‡50 years with knee OA were randomized to NAP/ESO (n = 487), CEL (n = 486) or placebo (n = 246) were pooled (NCT00664560 and NCT00665431). Acute response endpoints: 1) Time to first significant pain response, 2) Western Ontario and McMaster Osteoarthritis Index (WOMAC) pain subscale and 3) American Pain Society Patient Outcome Questionnaire (APS-POQ) scores. Sustainability endpoints: 1) Routine Assessment of Patient Index Data (RAPID3) and 2) WOMAC Stiffness, Pain and Total scores; and Patient Global Assessment (PGA) at 6 and 12 weeks. Effect sizes for all measures were calculated. Rescue pain medication use also was analyzed, as was the correlation of WOMAC to RAPID3. Results. NAP/ESO produced statistically significant decreases in WOMAC Pain on Days 2-7 and at Weeks 6 and 12 (all p < 0.05); most APS-POQ pain assessments with NAP/ESO were significantly improved on Days 2-7 compared with placebo (all p < 0.05). A good or excellent response occurred in a median of 6 days. RAPID3 and WOMAC total/stiffness/function/PGA scores decreased significantly at Weeks 6 and 12 (all p < 0.05). Placebo-adjusted WOMAC pain effect sizes were 0.44, 0.34 and 0.25 at Day 7, week 6 and week 12, respectively. RAPID3 to WOMAC total and WOMAC pain to RAPID3: Pain scores were highly correlated at 6 and 12 weeks (correlation coefficients >0.80). No significant differences in overall responses were found between CEL and NAP/ESO. Conclusion. Naproxen/esomeprazole produced a significant absolute moderate early pain response, which was maintained for 12 weeks. RAPID3 was found to be highly correlated with the typical OA measure (WOMAC) and might be a useful clinical tool for measuring NSAID response. NCT00664560: https://clinicaltrials.gov/ct2/show/NCT00664560, NCT00665431: https:// www.clinicaltrials.gov/ct2/show/NCT00665431.

show abstract

“…SAEs occurred in 2% or fewer subjects in the active treatment groups. One case of anaphylaxis in a subject [14].…”

Section: Introduction To the Compoundmentioning

confidence: 99%

“…n Long-term safety A 12-month open-label, multicenter, Phase III study was performed with the primary objective to evaluate the long-term safety of NAP/ESO (500/20 mg) in patients at risk of developing NSAID-associated gastric ulcers [14]. The inclusion criteria were the same as the other Phase III studies except that anticipation of the need for 12 months of NSAID therapy was required.…”

Section: Introduction To the Compoundmentioning

confidence: 99%

Naproxen/esomeprazole magnesium in the treatment of osteoarthritis, rheumatoid arthritis and ankylosing spondylitis

Dore¹,

Locks²

2012

International Journal of Clinical Rheumatology

View full text Add to dashboard Cite

Long-term safety of naproxen and esomeprazole magnesium fixed-dose combination: phase III study in patients at risk for NSAID-associated gastric ulcers

Abstract: Based on these outcome measures, long-term treatment with FDC naproxen/esomeprazole is not associated with any new safety issues, including predefined UGI and cardiovascular AEs, in patients requiring NSAID therapy who are at risk of UGI complications.

Cited by 22 publications

References 27 publications

Mechanisms, prevention and clinical implications of nonsteroidal anti-inflammatory drug-enteropathy

Mechanisms, prevention and clinical implications of nonsteroidal anti-inflammatory drug-enteropathy

Onset and durability of pain relief in knee osteoarthritis: Pooled results from two placebo trials of naproxen/esomeprazole combination and celecoxib

Naproxen/esomeprazole magnesium in the treatment of osteoarthritis, rheumatoid arthritis and ankylosing spondylitis

Contact Info

Product

Resources

About