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

doi:10.5246/jcps.2021.04.028

Abstract

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:

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.

Figures/Tables 8

Table 1. Summary of studies included.

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

References 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.