促动力药联合质子泵抑制剂与单独质子泵抑制剂治疗胃食管反流疾病疗效的荟萃分析

doi:10.5246/jcps.2021.04.028

摘要/Abstract

摘要：

本研究旨在系统评价促动力药联合质子泵抑制剂与单独质子泵抑制剂治疗胃食管反流疾病的疗效, 为临床用药提供循证参考。通过检索PubMed和Embase英文数据库, 收集促动力药联合质子泵抑制剂与单独使用质子泵抑制剂治疗胃食管反流疾病的随机对照研究, 采用RevMan 5.3偏倚风险评分工具对纳入研究进行质量评估并按预先设定的数据收集表提取相关资料。使用RevMan 5.3和Stata 12.0统计软件进行分析, 连续变量采用均差(Mean difference, MD)表示, 分类变量采用相对比(Relative ratio, RR)表示。共纳入13个随机对照研究1388例患者, Meta分析结果显示: 与质子泵抑制剂单药治疗相比, 联合促动力药显著提高总有效率(RR = 1.15, 95% CI: (1.07, –1.24), P < 0.001), 胃食管反流问卷GERD-Q评分(MD = –1.38, 95% CI: (–2.12, –0.64), P < 0.001), 胃食管反流症状频率量表FSSG评分(MD = 2.11, 95% CI: (1.68, 2.54), P < 0.001)和直观模拟评分(MD = –0.69, 95% CI: (–0.93, –0.45), P < 0.001), 具有显著统计学差异。而两组内镜响应(RR = 1.08, 95% CI: (0.99, 1.18), P = 0.10)和症状响应(RR = 1.22, 95% CI: (0.94, 1.59), P = 0.13)比较无显著统计学差异。因此, 对于胃食管反流患者, 联合促动力药能明显提高总有效率(内镜响应和/或症状响应)及生活质量评分, 但不能改善单独的内镜响应或症状响应。但考虑到本文纳入研究样本量较小, 且合并一些混杂因素, 因此期待大样本高质量的随机对照研究验证本文观点。

关键词: 胃食管反流病, 质子泵抑制剂, 促动力药, 疗效, 荟萃分析

Abstract:

In the present study, we aimed to systematically evaluate the efficacy of the combination therapy of prokinetics and proton pump inhibitors (PPIs) in patients with gastroesophageal reflux disease (GERD), and to provide an evidence-based reference for clinical use. The pertinent randomized controlled trials (RCTs) were retrieved from PubMed and Embase. The quality of included studies was evaluated using the "risk of bias" tool for RCTs using the RevMan 5.3. Related data were extracted according to the preset data collection forms. Meta-analysis was performed using RevMan 5.3 and Stata 12.0 statistical software. Mean difference (MD) was used to describe the continuous variables, and relative ratio (RR) was used for classification variables. A total of 13 RCTs involving 1388 patients were included. Results of the meta-analysis showed that compared with PPI monotherapy, the combination therapy significantly improved the total response rate (RR = 1.15, 95% confidence interval (CI): (1.07, –1.24), P < 0.001), gastroesophageal reflux disease questionnaire (GERD-Q) score (MD = –1.38, 95% CI: (–2.12, –0.64), P < 0.001), the frequency scale for the symptoms of gastroesophageal reflux (FSSG) score (MD = 2.11, 95% CI: (1.68, 2.54), P < 0.001) and visual analogue scale (MD = –0.69, 95% CI: (–0.93, –0.45), P < 0.001). However, the endoscopic response (RR = 1.08, 95% CI: (0.99, 1.18), P = 0.10) and symptomatic response (RR = 1.22, 95% CI: (0.94, 1.59), P = 0.13) were not significantly different between the two groups. For patients with GERD, the combination therapy could markedly improve the total response rate (symptomatic response and/or endoscopic response) and quality of life, while no benefits were found in symptomatic and endoscopic response. In view of the small number of participants included and some confounding factors in this study, the conclusion made in this study needs to be further confirmed by including a large number of participants and performing high-quality RCTs.

Key words: Gastroesophageal reflux disease, Proton pump inhibitors, Prokinetic drugs, Efficacy, Meta-analysis

Supporting:

李春杏, 朱元明, 刘桦, 徐钊. 促动力药联合质子泵抑制剂与单独质子泵抑制剂治疗胃食管反流疾病疗效的荟萃分析[J]. 中国药学(英文版), 2021, 30(4): 347-356.

Chunxing Li, Yuanmin Zhu, Hua Liu, Zhao Xu. Efficacy of prokinetic drugs in combination with proton pump inhibitors versus proton pump inhibitors alone in the treatment of gastroesophageal reflux disease: a meta-analysis[J]. Journal of Chinese Pharmaceutical Sciences, 2021, 30(4): 347-356.

图/表 8

Figure 1. The flow chart of study selection.

Table 1. Summary of studies included.

Figure 2. Risk of bias summary and risk of bias graph.

Figure 3. Forest plot of meta-analysis of total response.

Figure 4. Forest plot of meta-analysis of endoscopic response.

Figure 5. Forest plot of meta-analysis of symptomatic response.

Table 2. The results of meta-analysis of second outcome measures.

Figure 6. Inverted funnel plot of total response.

参考文献 26

[1]	Katz, P.O.; Gerson, L.B.; Vela, M.F. Guidelines for the diagnosis and management of gastroesophageal reflux disease. Am. J. Gastroenterol. 2013, 108, 308–328.
[2]	Iwakiri, K.; Kinoshita, Y.; Habu, Y.; Oshima, T.; Manabe, N.; Fujiwara, Y.; Nagahara, A.; Kawamura, O.; Iwakiri, R.; Ozawa, S.; Ashida, K.; Ohara, S.; Kashiwagi, H.; Adachi, K.; Higuchi, K.; Miwa, H.; Fujimoto, K.; Kusano, M.; Hoshihara, Y.; Kawano, T.; Haruma, K.; Hongo, M.; Sugano, K.; Watanabe, M.; Shimosegawa, T. Evidence-based clinical practice guidelines for gastroesophageal reflux disease 2015. J. Gastroenterol. 2016, 51, 751–767.
[3]	El-Serag, H.B.; Sweet, S.; Winchester, C.C.; Dent, J. Update on the epidemiology of gastro-oesophageal reflux disease: a systematic review. Gut. 2014, 63, 871–880.
[4]	Mermelstein, J.; Chait Mermelstein, A.; Chait, M.M. Proton pump inhibitor-refractory gastroesophageal reflux disease: challenges and solutions. Clin. Exp. Gastroenterol. 2018, 11, 119–134.
[5]	Wang, Y.P.; Ji, L.S.; Ni, M.; Fan, H.W.; Sha, J.P. Clinical effects of esomeprazole combined with mosapride for treatment of gastroesophageal reflux disease. World Chin. J. Dig. 2014, 22, 5671.
[6]	Wu, Q.Y. Rabeprazole combined with trimebutine for treatment of patients with gastroesophageal reflux cough: Clinical efficacy and impact on serum levels of motilin and gastrin. World Chin. J. Dig. 2018, 26, 418.
[7]	Cho, Y.K.; Choi, M.G.; Park, E.Y.; Lim, C.H.; Kim, J.S.; Park, J.M.; Lee, I.S.; Kim, S.W.; Choi, K.Y. Effect of mosapride combined with esomeprazole improves esophageal peristaltic function in patients with gastroesophageal reflux disease: a study using high resolution manometry. Dig. Dis. Sci. 2013, 58, 1035–1041.
[8]	van Rensburg, C.J.; Bardhan, K.D. No clinical benefit of adding cisapride to pantoprazole for treatment of gastro-oesophageal reflux disease. Eur. J. Gastroenterol. Hepatol. 2001, 13, 909–914.
[9]	Hsu, Y.C.; Yang, T.H.; Hsu, W.L.; Wu, H.T.; Cheng, Y.C.; Chiang, M.F.; Wang, C.S.; Lin, H.J. Mosapride as an adjunct to lansoprazole for symptom relief of reflux oesophagitis. Br. J. Clin. Pharmacol. 2010, 70, 171–179.
[10]	Higgins, J.P.; Green, S. Cochrane handbook for systematic reviews of interventions. Chichester, UK: John Wiley & Sons, Ltd, 2008.
[11]	Ndraha, S. Combination of PPI with a prokinetic drug in gastroesophageal reflux disease. Acta Med. Indonesiana. 2011, 43, 233–236.
[12]	Miwa, H.; Inoue, K.; Ashida, K.; Kogawa, T.; Nagahara, A.; Yoshida, S.; Tano, N.; Yamazaki, Y.; Wada, T.; Asaoka, D.; Fujita, T.; Tanaka, J.; Shimatani, T.; Manabe, N.; Oshima, T.; Haruma, K.; Azuma, T.; Yokoyama, T. Randomised clinical trial: efficacy of the addition of a prokinetic, mosapride citrate, to omeprazole in the treatment of patients with non-erosive reflux disease - a double-blind, placebo-controlled study. Aliment. Pharmacol. Ther. 2011, 33, 323–332.
[13]	Lee, J.Y.; Kim, S.K.; Cho, K.B.; Park, K.S.; Kwon, J.G.; Jung, J.T.; Kim, E.Y.; Jang, B.I.; Lee, S.H. A double-blind, randomized, multicenter clinical trial investigating the efficacy and safety of esomeprazole single therapy versus mosapride and esomeprazole combined therapy in patients with esophageal reflux disease. J. Neurogastroenterol. Motil. 2017, 23, 218–228.
[14]	Madan, K.; Ahuja, V.; Kashyap, P.C.; Sharma, M.P. Comparison of efficacy of pantoprazole alone versus pantoprazole plus mosapride in therapy of gastroesophageal reflux disease: a randomized trial. Dis. Esophagus. 2004, 17, 274–278.
[15]	Marakhouski, K.Y.; Karaseva, G.A.; Ulasivich, D.N.; Kh Marakhouski, Y. Omeprazole-domperidone fixed dose combination vs omeprazole monotherapy: a phase 4, open-label, comparative, parallel randomized controlled study in mild to moderate gastroesophageal reflux disease. Clin. Med. Insights: Gastroenterol. 2017.https://doi.org/10.1177/1179552217709456
[16]	Yamaji, Y.; Isomura, Y.; Yoshida, S.; Yamada, A.; Hirata, Y.; Koike, K. Randomized controlled trial comparing the efficacy of mosapride plus omeprazole combination therapy to omeprazole monotherapy in gastroesophageal reflux disease. J. Dig. Dis. 2014, 15, 469-476.
[17]	Sharma, B.; Sharma, M.; Daga, M.K.; Sachdev, G.K.; Bondi, E. Effect of omeprazole and domperidone on adult asthmatics with gastroesophageal reflux. World J. Gastroenterol. 2007, 13, 1706–1710.
[18]	Vigneri, S.; Termini, R.; Leandro, G.; Badalamenti, S.; Pantalena, M.; Savarino, V.; Di Mario, F.; Battaglia, G.; Mela, G.S.; Pilotto, A. A comparison of five maintenance therapies for reflux esophagitis. N. Engl. J. Med. 1995, 333, 1106–1110.
[19]	Iwakiri, K.; Kawami, N.; Sano, H.; Tanaka, Y.; Umezawa, M.; Kotoyori, M.; Hoshihara, Y.; Sakamoto, C. Mechanisms of excessive esophageal acid exposure in patients with reflux esophagitis. Dig. Dis. Sci. 2009, 54, 1686–1692.
[20]	Acosta, A.; Camilleri, M. Prokinetics in gastroparesis. Gastroenterol. Clin. N. Am. 2015, 44, 97–111.
[21]	Chang, P.; Friedenberg, F. Obesity and gerd. Gastroenterol. Clin. N. Am. 2014, 43, 161–173.
[22]	Ren, L.H.; Chen, W.X.; Qian, L.J.; Li, S.; Gu, M.; Shi, R.H. Addition of prokinetics to PPI therapy in gastroesophageal reflux disease: a meta-analysis. World J. Gastroenterol. 2014, 20, 2412–2419.
[23]	Liu, Q.; Feng, C.C.; Wang, E.M.; Yan, X.J.; Chen, S.L. Efficacy of mosapride plus proton pump inhibitors for treatment of gastroesophageal reflux disease: a systematic review. World J. Gastroenterol. 2013, 19, 9111–9118.
[24]	Li, M.J.; Li, Q.; Sun, M.; Liu, L.Q. Comparative effectiveness and acceptability of the FDA-licensed proton pump inhibitors for erosive esophagitis: a PRISMA-compliant network meta-analysis. Medicine (Baltimore). 2017, 96, e8120.
[25]	Chen, L.X.; Chen, Y.J.; Li, B. The efficacy and safety of proton-pump inhibitors in treating patients with non-erosive reflux disease: a network meta-analysis. Sci. Rep. 2016, 6, 32126.
[26]	Jarosz, M.; Taraszewska, A. Risk factors for gastroesophageal reflux disease - the role of diet. Gastroenterol. Rev. 2014, 5, 297–301.