Safety and efficacy of long-term esomeprazole 20 mg in Japanese patients with a history of peptic ulcer receiving daily non-steroidal anti-inflammatory drugs

BMC Gastroenterology

Tsutomu Takeuchi²  Hiroto Miwa³  Yoshikazu Kinoshita⁴  Kentaro Sugano¹ 

[1] Department of Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan;Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan;Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan;Department of Gastroenterology and Hepatology, Shimane University School of Medicine, Shimane, Japan

关键词: Safety;    Peptic ulcer;    Non-steroidal anti-inflammatory drugs;    Esomeprazole;   

Others  :  858109
DOI  :  10.1186/1471-230X-13-54

 received in 2012-07-10, accepted in 2013-03-18,  发布年份 2013

【 摘 要 】

Background

Non-steroidal anti-inflammatory drugs (NSAIDs) are an effective and common treatment for chronic pain disorders, but long-term use is associated with risk of potentially life-threatening gastrointestinal adverse events (AEs). The proton pump inhibitor esomeprazole has been found to be effective for gastroprotection in NSAID users, but few long-term studies have been conducted in Japan.

Methods

This was an open-label, multicentre, single-arm, prospective 1-year study of treatment with esomeprazole (20 mg once daily) in Japanese patients (aged ≥20 years) with endoscopic evidence of previous peptic ulcer and receiving daily oral NSAID therapy (at a stable dose) for a chronic condition. Eligibility was not dictated by type of oral NSAID. The primary objective was to determine long-term safety and tolerability of esomeprazole. Efficacy for prevention of peptic ulcers was also determined (Kaplan-Meier method). All statistical analyses were descriptive.

Results

A total of 130 patients (73.1% women, mean age 62.1 years, 43.8% Helicobacter pylori-positive) received treatment with esomeprazole in addition to long-term NSAID therapy (most commonly for rheumatoid arthritis [n=42] and osteoarthritis [n=34]). Loxoprofen, meloxicam and diclofenac were the most commonly used NSAIDs; cyclo-oxygenase (COX)-2 selective agents were used by 16.2% of patients (n=21). Long-term compliance with esomeprazole (capsule counts) was >75% for the majority of patients. Although 16.9% of patients (n=22) experienced AEs judged to be possibly related to treatment with esomeprazole, they were mostly mild and transient. The most commonly reported possibly treatment-related AEs were abnormal hepatic function, headache, increased γ-glutamyltransferase levels and muscle spasms (2 patients each). Overall, 95.9% (95% confidence interval: 92.3, 99.4) of patients remained ulcer free at 1 year.

Conclusion

Long-term treatment with esomeprazole (20 mg once daily) is well tolerated and efficacious for preventing ulcer recurrence in Japanese NSAID users with a history of peptic ulcer.

Trial registration

ClinicalTrials.gov identifier NCT00595517.

【 授权许可】

   
2013 Sugano et al.; licensee BioMed Central Ltd.

【 图 表 】

【 参考文献 】

• [1]Yoshida S, Aoyagi K, Felson DT, Aliabadi P, Shindo H, Takemoto T-I: Comparison of the prevalence of radiographic osteoarthritis of the knee and hand between Japan and the United States. J Rheumatol 2002, 29(7):1545-1558.
• [2]National patients survey. 2002. http://www.mhlw.go.jp/toukei/saikin/hw/kanja/02/5.html webcite. Accessed April 2, 2013
• [3]Wolfe F, Zhao S, Lane N: Preference for nonsteroidal antiinflammatory drugs over acetaminophen by rheumatic disease patients: a survey of 1,799 patients with osteoarthritis, rheumatoid arthritis, and fibromyalgia. Arthritis Rheum 2000, 43(2):378-385.
• [4]Arakawa T, Fujiwara Y, Sollano JD, Zhu Q, Kachintorn U, Rani AA, Hahm KB, Takahashi S, Joh T, Kinoshita Y, Matsumoto T, Naito Y, Takeuchi K, Yamagami H, Agustanti N, Xiong H, Chen X, Jang EJ, Furuta K, Terano A: A questionnaire-based survey on the prescription of non-steroidal anti-inflammatory drugs by physicians in East Asian countries in 2007. Digestion 2009, 79(3):177-185.
• [5]Chan FK, Goto S, Wu MS, Abola MT, Yeoh KG, Sutrisna B, Chua SS, Mahachai V, Turajane T, Wu B, Zeng QY, Sugano K: Burden of nonsteroidal anti-inflammatory and antiplatelet drug use in Asia: a multidisciplinary working party report. Clin Gastroenterol Hepatol 2012, 10(7):753-760.
• [6]Niculescu L, Li C, Huang J, Mallen S: Pooled analysis of GI tolerability of 21 randomized controlled trials of celecoxib and nonselective NSAIDs. Curr Med Res Opin 2009, 25(3):729-740.
• [7]Lanza FL, Chan FK, Quigley EM: Guidelines for prevention of NSAID-related ulcer complications. Am J Gastroenterol 2009, 104(3):728-738.
• [8]Sikes DH, Agrawal NM, Zhao WW, Kent JD, Recker DP, Verburg KM: Incidence of gastroduodenal ulcers associated with valdecoxib compared with that of ibuprofen and diclofenac in patients with osteoarthritis. Eur J Gastroenterol Hepatol 2002, 14(10):1101-1111.
• [9]Yuan YH, Wang C, Yuan Y, Hunt RH: Meta-analysis: incidence of endoscopic gastric and duodenal ulcers in placebo arms of randomized placebo-controlled NSAID trials. Aliment Pharmacol Ther 2009, 30(3):197-209.
• [10]Laine L, Curtis SP, Cryer B, Kaur A, Cannon CP: Risk factors for NSAID-associated upper GI clinical events in a long-term prospective study of 34 701 arthritis patients. Aliment Pharmacol Ther 2010, 32(10):1240-1248.
• [11]Lanas A, Tornero J, Zamorano JL: Assessment of gastrointestinal and cardiovascular risk in patients with osteoarthritis who require NSAIDs: the LOGICA study. Ann Rheum Dis 2010, 69(8):1453-1458.
• [12]Hawkey CJ, Svedberg LE, Naesdal J, Byrne C: Esomeprazole for the management of upper gastrointestinal symptoms in patients who require NSAIDs: a review of the NASA and SPACE double-blind, placebo-controlled studies. Clin Drug Investig 2009, 29(10):677-687.
• [13]Scheiman JM, Yeomans ND, Talley NJ, Vakil N, Chan FK, Tulassay Z, Rainoldi JL, Szczepanski L, Ung KA, Kleczkowski D, Ahlbom H, Naesdal J, Hawkey C: Prevention of ulcers by esomeprazole in at-risk patients using non-selective NSAIDs and COX-2 inhibitors. Am J Gastroenterol 2006, 101(4):701-710.
• [14]Sugano K, Kinoshita Y, Miwa H, Takeuchi T, on behalf of the Esomeprazole NSAID Preventive Study Group: Randomised clinical trial: esomeprazole for the prevention of nonsteroidal anti-inflammatory drug-related peptic ulcers in Japanese patients. Aliment Pharmacol Ther 2012, 36(2):115-125.
• [15]Ministry of Health Labour and Welfare: Good clinical practice for trials on drugs, ordnance No. 28. 1997. http://www.pmda.go.jp/english/service/pdf/ministerial/20130329No_28.pdf webcite. Accessed April 2, 2013
• [16]Miyake T, Suzaki T, Oishi M: Correlation of gastric ulcer healing features by endoscopy, stereoscopic microscopy, and histology, and a reclassification of the epithelial regenerative process. Dig Dis Sci 1980, 25(1):8-14.
• [17]Lanza FL, Aspinall RL, Swabb EA, Davis RE, Rack MF, Rubin A: Double-blind, placebo-controlled endoscopic comparison of the mucosal protective effects of misoprostol versus cimetidine on tolmetin-induced mucosal injury to the stomach and duodenum. Gastroenterology 1988, 95(2):289-294.
• [18]Sugano K, Kontani T, Katsuo S, Takei Y, Sakaki N, Ashida K, Mizokami Y, Asaka M, Matsui S, Kanto T, Soen S, Takeuchi T, Hiraishi H, Hiramatsu N: Lansoprazole for secondary prevention of gastric or duodenal ulcers associated with long-term non-steroidal anti-inflammatory drug (NSAID) therapy: results of a prospective, multicenter, double-blind, randomized, double-dummy, active-controlled trial. J Gastroenterol 2012, 47(5):540-552.
• [19]Ji KY, Hu FL: Interaction or relationship between Helicobacter pylori and non-steroidal anti-inflammatory drugs in upper gastrointestinal diseases. World J Gastroenterol 2006, 12(24):3789-3792.
• [20]Äbelö A, Andersson TB, Antonsson M, Naudot AK, Skanberg I, Weidolf L: Stereoselective metabolism of omeprazole by human cytochrome P450 enzymes. Drug Metab Dispos 2000, 28(8):966-972.
• [21]Schwab M, Klotz U, Hofmann U, Schaeffeler E, Leodolter A, Malfertheiner P, Treiber G: Esomeprazole-induced healing of gastroesophageal reflux disease is unrelated to the genotype of CYP2C19: evidence from clinical and pharmacokinetic data. Clin Pharmacol Ther 2005, 78(6):627-634.
• [22]Brun J, Jones R: Nonsteroidal anti-inflammatory drug-associated dyspepsia: the scale of the problem. Am J Med 2001, 110(1A):12S-13S.
• [23]Uemura S, Ochi T, Sugano K, Makuch RW: Systematic review for evaluation of tolerability of nonsteroidal antiinflammatory drugs in osteoarthritis patients in Japan. J Orthop Sci 2003, 8(3):279-287.
• [24]Yu EW, Bauer SR, Bain PA, Bauer DC: Proton pump inhibitors and risk of fractures: a meta-analysis of 11 international studies. Am J Med 2011, 124(6):519-526.
• [25]Eom CS, Jeon CY, Lim JW, Cho EG, Park SM, Lee KS: Use of acid-suppressive drugs and risk of pneumonia: a systematic review and meta-analysis. Can Med Assoc J 2011, 183(3):310-319.
• [26]Estborn L, Joelson S: Occurrence of community-acquired respiratory tract infection in patients receiving esomeprazole: retrospective analysis of adverse events in 31 clinical trials. Drug Saf 2008, 31(7):627-636.