瑞巴派特治疗NSAIDs相关性肠病疗效的Meta分析

doi:10.3969/j.issn.1004-583X.2022.08.002

摘要/Abstract

摘要：

目的评价瑞巴派特治疗非甾体抗炎药(nonsteroidal anti-inflammatory drugs,NSAIDs)相关性肠病的临床疗效。方法计算机检索PubMed、MedLine、Embase、The Cochrane Library、中国生物医学文献数据库、中国知网和万方数据库发表的有关瑞巴派特治疗NSAIDs相关性肠病的随机对照试验。设定时间期限为各数据库建库至2021年6月。依据Cochrane系统评价指导手册推荐的评价标准对纳入研究进行质量评价,对文献主要的结局指标数据录入后采用 Review Manager 5.3软件进行Meta分析。结果最终研究纳入符合条件的随机对照试验6个,研究对象共纳入255例;3篇主要对瑞巴派特治疗后肠道损伤例数进行观察,均可提取有效数据;4篇观察了治疗后肠黏膜糜烂数,均可提取有效数据;3篇观察了治疗后肠黏膜溃疡数,均可提取有效数据;将全部结局指标数据录入后,经Meta分析结果显示,与常规方案组治疗NSAIDs相关性肠病比较,瑞巴派特组肠道损伤的例数减少(OR=0.34,95%CI为0.15~0.75,P<0.05);肠黏膜糜烂数明显减少(MD=-4.71,95%CI为-6.40~-3.02,P<0.05);肠黏膜溃疡数明显减少(MD=-0.45,95%CI为-0.89~-0.01, P<0.05)。结论瑞巴派特在预防和治疗NSAIDs相关性肠病方面具有优势,可以减轻服用NSAIDs药物患者的肠道损伤。

关键词: NSAIDS相关性肠病, 瑞巴派特, 疗效, Meta分析

Abstract:

Objective To evaluate the clinical efficacy of Rebamipide in the treatment of nonsteroidal anti-inflammatory drugs (NSAIDs)-associated intestinal disease. Methods PubMed, MedLine, Embase, The Cochrane Library, China Biomedical Literature Database (CBM), CNKI and Wanfang Data were searched for randomized controlled trials(RCTs)in the treatment of NSAIDs-associated bowel diseases. Set a time limit for each database to be built until January 2021. According to the evaluation criteria recommended by the Cochrane system evaluation guide manual, the quality of the included study was evaluated, and Review Manager 5.3 software was used for Meta analysis after entering the main outcome indicators of the literatures. Results Finally, eligible 6 RCTs were included, with a total of 255 subjects; 3 articles mainly observed the number of cases of intestinal injury after treatment with Rebamipide, and all of them could extract effective data; the effective data could be extracted from 4 articles focused the number of intestinal mucosal erosion after treatment, 3 articles observed the number of intestinal mucosal ulcers after treatment with extracted effective data. The results of Meta analysis showed that the number of intestinal injuries (OR=0.34, 95%CI: 0.15-0.75, P<0.05), intestinal mucosal erosion(MD=-4.71, 95%CI:-6.40 to -3.02, P<0.05) and intestinal mucosal ulcers (MD =-0.45, 95% CI: -0.89 to -0.01, P<0.05) decreased significantly in the Rebamipide group as compared to the routine regimen group. Conclusion Rebamipide has advantages in the prevention and treatment of NSAIDs-associated intestinal disease and can reduce intestinal injury in patients who take NSAIDs drugs for a long time.

Key words: NSAIDS-related intestinal disease, Rebamipide, efficacy, Meta-analysis

中图分类号:

R516.1

王腾燕, 何雅军, 舒建昌. 瑞巴派特治疗NSAIDs相关性肠病疗效的Meta分析[J]. 临床荟萃, 2022, 37(8): 685-690.

Wang Tengyan, He Yajun, Shu Jianchang. Rebamipide in the treatment of nonsteroidal anti-inflammatory drug-associated intestinal disease: A meta-analysis[J]. Clinical Focus, 2022, 37(8): 685-690.

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链接本文: https://huicui.hebmu.edu.cn/CN/10.3969/j.issn.1004-583X.2022.08.002

https://huicui.hebmu.edu.cn/CN/Y2022/V37/I8/685

图/表 9

参考文献 26

[1]	Zhou Y, Boudreau DM, Freedman AN. Trends in the use of aspirin and nonsteroidal anti-inflammatory drugs in the general U.S. population[J]. Pharmacoepidemiol Drug Saf, 2014, 23(1):43-50. doi: 10.1002/pds.3463 pmid: 23723142
[2]	戴新羽, 刘佰纯, 田月丽, 等. 非甾体类抗炎药对肠道黏膜损伤的影响[J]. 中南药学, 2020, 18(6):1042-1045.
[3]	Graham DY, Opekun AR, Willingham FF, et al. Visible small-intestinal mucosal injury in chronic NSAID users[J]. Clin Gastroenterol Hepatol, 2005, 3(1):55-59. doi: 10.1016/S1542-3565(04)00603-2 URL
[4]	Goldstein JL, Eisen GM, Lewis B, et al. Video capsule endoscopy to prospectively assess small bowel injury with celecoxib, naproxen plus omeprazole, and placebo[J]. Clin Gastroenterol Hepatol, 2005, 3(2):133-141. doi: 10.1016/S1542-3565(04)00619-6 URL
[5]	Fujimori S, Seo T, Gudis K, et al. Prevention of nonsteroidal anti-inflammatory drug-induced small-intestinal injury by prostaglandin: A pilot randomized controlled trial evaluated by capsule endoscopy[J]. Gastrointest Endosc, 2009, 69(7):1339-1346. doi: 10.1016/j.gie.2008.08.017 pmid: 19243767
[6]	John LW, Stephanie S, Emmanuel D, et al. Proton pump inhibitors exacerbate NSAID-induced small intestinal injury by inducing dysbiosis[J]. Gastroenterology, 2011, 141(4):1314-1322. doi: 10.1053/j.gastro.2011.06.075 pmid: 21745447
[7]	Tanigawa T, Watanabe T, Higashimori A, et al. Rebamipide ameliorates indomethacin-induced small intestinal damage and proton pump inhibitor-induced exacerbation of this damage by modulation of small intestinal microbiota[J]. PLoS one, 2021, 16(1):e0245995. doi: 10.1371/journal.pone.0245995 URL
[8]	Jaafar MH, Safi SZ, Tan M, et al. Efficacy of rebamipide in organic and functional dyspepsia: A systematic review and meta-analysis[J]. Dig Dis Sci, 2018, 63(5):1250-1260. doi: 10.1007/s10620-017-4871-9 URL
[9]	Niwa Y, Nakamura M, Ohmiya N, et al. Efficacy of rebamipide for diclofenac-induced small-intestinal mucosal injuries in healthy subjects: A prospective, randomized, double-blinded, placebo-controlled, cross-over study[J]. J Gastroenterol, 2008, 43(4):270-276. doi: 10.1007/s00535-007-2155-4 pmid: 18458842
[10]	Nishida U, Kato M, Nishida M, et al. Evaluation of small bowel blood flow in healthy subjects receiving low-dose aspirin[J]. World J Gastroenterol, 2011, 17(2):226-230. doi: 10.3748/wjg.v17.i2.226 URL
[11]	Fujimori S, Takahashi Y, Gudis K, et al. Rebamipide has the potential to reduce the intensity of NSAID-induced small intestinal injury: A double-blind, randomized, controlled trial evaluated by capsule endoscopy[J]. J Gastroenterol, 2011, 46(1):57-64. doi: 10.1007/s00535-010-0332-3 pmid: 20924615
[12]	Kurokawa S, Katsuki S, Fujita T, et al. A randomized, double-blinded, placebo-controlled, multicenter trial, healing effect of rebamipide in patients with low-dose aspirin and/or non-steroidal anti-inflammatory drug induced small bowel injury[J]. J Gastroenterol, 2014, 49(2):239-244. doi: 10.1007/s00535-013-0805-2 pmid: 23595613
[13]	Watanabe T, Takeuchi T, Handa O, et al. A multicenter, randomized, double-blind, placebo-controlled trial of high-dose rebamipide treatment for low-dose aspirin-induced moderate-to-severe small intestinal damage[J]. PLoS one, 2015, 10(4):e0122330. doi: 10.1371/journal.pone.0122330 URL
[14]	Ota K, Takeuchi T, Nouda S, et al. Determination of the adequate dosage of rebamipide, a gastric mucoprotective drug, to prevent low-dose aspirin-induced gastrointestinal mucosal injury[J]. J Clin Biochem Nutr, 2016, 59(3):231-237. pmid: 27895392
[15]	徐家桥, 王景杰. 非甾体抗炎药相关性肠病的临床诊断及药物治疗进展[J]. 医学综述, 2020, 26(9):1797-1801.
[16]	Tachecí I, Bradna P, Douda T, et al. NSAID-induced enteropathy in rheumatoid arthritis patients with chronic occult gastrointestinal bleeding: A prospective capsule endoscopy study[J]. Gastroenterol Res Pract, 2013, 2013:268382.
[17]	Caunedo-Alvarez A, Gomez-Rodriguez BJ, Romero-Vazquez J, et al. Macroscopic small bowel mucosal injury caused by chronic nonsteroidal anti-inflammatory drugs (NSAID) use as assessed by capsule endoscopy[J]. Rev Esp Enferm Dig, 2010, 102(2):80-85. pmid: 20361843
[18]	樊代明, 吴开春. 消化内科学[J]. 中华医学杂志, 1995, 75(12):716-717.
[19]	Mizoguchi H, Ogawa Y, Kanatsu K, et al. Protective effect of rebamipide on indomethacin-induced intestinal damage in rats[J]. J Gastroenterol Hepatol, 2001, 16(10):1112-1119. doi: 10.1046/j.1440-1746.2001.02592.x URL
[20]	Zhang S, Qing Q, Bai Y, et al. Rebamipide helps defend against nonsteroidal anti-inflammatory drugs induced gastroenteropathy: A systematic review and meta-analysis[J]. Dig Dis Sci, 2013, 58(7):1991-2000. doi: 10.1007/s10620-013-2606-0 URL
[21]	Xu N, Zhang C, Jing L, et al. Protective effect and mechanism of rebamipide on NSAIDs associated small bowel injury[J]. Int Immunopharmacol, 2021, 90:107136. doi: 10.1016/j.intimp.2020.107136 URL
[22]	韩涛涛, 陈楚岩, 王静, 等. 瑞巴派特对非甾体抗炎药相关小肠黏膜损伤的保护机制[J]. 中华消化杂志, 2021, 41(3):183-189.
[23]	Wallace JL, Syer S, Denou E, et al. Proton pump inhibitors exacerbate NSAID-induced small intestinal injury by inducing dysbiosis[J]. Gastroenterology, 2011, 141(4):1314-1322. doi: 10.1053/j.gastro.2011.06.075 pmid: 21745447
[24]	Tanigawa T, Watanabe T, Otani K, et al. Rebamipide inhibits indomethacin-induced small intestinal injury: Possible involvement of intestinal microbiota modulation by upregulation of α-defensin 5[J]. Eur J Pharmacol, 2013, 704(1-3):64-69. doi: 10.1016/j.ejphar.2013.02.010 pmid: 23428631
[25]	Imaeda H, Fujimoto T, Takahashi K, et al. Terminal-restriction fragment length polymorphism (T-RFLP) analysis for changes in the gut microbiota profiles of indomethacin- and rebamipide-treated mice[J]. Digestion, 2012, 86(3):250-257. doi: 10.1159/000341508 pmid: 22964750
[26]	Kurata S, Nakashima T, Osaki T, et al. Rebamipide protects small intestinal mucosal injuries caused by indomethacin by modulating intestinal microbiota and the gene expression in intestinal mucosa in a rat model[J]. J Clin Biochem Nutr, 2015, 56(1):20-27. doi: 10.3164/jcbn.14-67 pmid: 25834302

纳入研究	发表年份	瑞巴派特组/ 常规治疗组(例)	干预措施		疗程 (周)	结局指标
纳入研究	发表年份	瑞巴派特组/ 常规治疗组(例)	瑞巴派特组	常规治疗组	疗程 (周)	结局指标
Niwa^[9]	2008	10/10	瑞巴派特+双氯芬酸+奥美拉唑	安慰剂+双氯芬酸+奥美拉唑	1	①②③④
Nishida^[10]	2011	10/10	瑞巴派特+阿司匹林	安慰剂+阿司匹林	2	①②③
Fujimori^[11]	2011	34/38	瑞巴派特+双氯芬酸+奥美拉唑	安慰剂+双氯芬酸+奥美拉唑	2	①②③
Kurokawa^[12]	2014	31/30	瑞巴派特+阿司匹林/NSAID/ 阿司匹林+NSAID	安慰剂+阿司匹林/NSAID/ 阿司匹林+NSAID	4	②③④⑤⑥
Watanabe^[13]	2015	25/13	瑞巴派特+阿司匹林	安慰剂+阿司匹林	8	②⑤⑥
Ota^[14]	2016	30/15	瑞巴派特+阿司匹林	奥美拉唑+阿司匹林	2	②③④

纳入研究	发表年份	瑞巴派特组/ 常规治疗组(例)	干预措施		疗程 (周)	结局指标
纳入研究	发表年份	瑞巴派特组/ 常规治疗组(例)	瑞巴派特组	常规治疗组	疗程 (周)	结局指标
Niwa^[9]	2008	10/10	瑞巴派特+双氯芬酸+奥美拉唑	安慰剂+双氯芬酸+奥美拉唑	1	①②③④
Nishida^[10]	2011	10/10	瑞巴派特+阿司匹林	安慰剂+阿司匹林	2	①②③
Fujimori^[11]	2011	34/38	瑞巴派特+双氯芬酸+奥美拉唑	安慰剂+双氯芬酸+奥美拉唑	2	①②③
Kurokawa^[12]	2014	31/30	瑞巴派特+阿司匹林/NSAID/ 阿司匹林+NSAID	安慰剂+阿司匹林/NSAID/ 阿司匹林+NSAID	4	②③④⑤⑥
Watanabe^[13]	2015	25/13	瑞巴派特+阿司匹林	安慰剂+阿司匹林	8	②⑤⑥
Ota^[14]	2016	30/15	瑞巴派特+阿司匹林	奥美拉唑+阿司匹林	2	②③④