Background/Aim: The effects of vonoprazan and proton pump inhibitors (PPIs) in patients with reflux esophagitis (RE) have not yet been compared using multichannel intraluminal impedance-pH (MII-pH). Methods: A total of 8 patients with persistent gastric mucosal injury, despite completing an 8-week standard PPI therapy, were enrolled in the study. While they were on standard PPI therapy, the baseline values of reflux parameters, holding time ratio (HTR) of gastric pH >4, and esophageal pH <4 were obtained by using 24 h MII-pH monitoring. They were re-evaluated after discontinuation of the therapy and 4 weeks of subsequent treatment with vonoprazan 20 mg/day. Results: The patients were found to be CYP2C19 extensive metabolizers and negative for Helicobacter pylori infection. In 7 patients (87.5%), the mucosal lesions had healed completely after vonoprazan therapy. A significant increase in gastric pH >4 HTR was observed, from 26.5 to 78.0% (p = 0.029). A reduction in esophageal pH <4 HTR was also observed but it was not statistically significant. Furthermore, acid clearance time and the total number of reflux events, including acid and proximal reflux events, were significantly reduced. Conclusion: Vonoprazan may be a better therapy for the treatment of patients with PPI-refractory RE.

Fujiwara Y, Arakawa T: Epidemiology and clinical characteristics of GERD in the Japanese population. J Gastroenterol 2009;44:518-534.
Gastroesophageal Reflux Disease (GERD) Treatment Guideline, Compiled by the Japanese Society of Gastroenterology. Tokyo Nankodo, 2010, pp 44-61.
Chiba N, De Gara CJ, Wilkinson JM, Hunt RH: Speed of healing and symptom relief in grade II to IV gastroesophageal reflux disease: a meta-analysis. Gastroenterology 1997;112:1798-1810.
Dimenas E: Methodological aspects of evaluation of quality of life in upper gastrointestinal diseases. Scand J Gastroenterol Suppl 1993;199:18-21.
Vakil N, van Zanten SV, Kahrilas P, Dent J, Jones R: The Montreal definition and classification of gastroesophageal reflux disease: a global evidence-based consensus. Am J Gastroenterol 2006;101:1900-1920.
Kawamura M, Ohara S, Koike T, Iijima K, Suzuki J, Kayaba S, Noguchi K, Hamada S, Noguchi M, Shimosegawa T: The effects of lansoprazole on erosive reflux oesophagitis are influenced by CYP2C19 polymorphism. Aliment Pharmacol Ther 2003;17:965-973.
Kinoshita Y, Hongo M; The Japan TWICE Study Group: Efficacy of twice-daily rabeprazole for reflux esophagitis patients refractory to standard once-daily administration of PPI: the Japan-Based TWICE Study. Am J Gastroenterol 2012;107:522-530.
Andersson K, Carlsson E: Potassium-competitive acid blockade: a new therapeutic strategy in acid-related diseases. Pharmacol Ther 2005;108:294-307.
Hori Y, Imanishi A, Matsukawa J, Tsukimi Y, Nishida H, Arikawa Y, Hirase K, Kajino M, Inatomi N: 1-[5-(2-Fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl]-N-methylmethanamine monofumarate (TAK-438), a novel and potent potassium-competitive acid blocker for the treatment of acid-related diseases. J Pharmacol Exp Ther 2010;335:231-238.
Matsukawa J, Hori Y, Nishida H, et al: A comparative study on the modes of action of TAK-438, a novel potassium-competitive acid blocker, and lansoprazole in primary cultured rabbit gastric glands. Biochem Pharmacol 2011;81:1145-1151.
Hori Y, Matsukawa J, Takeuchi T, Nishida H, Kajino M, Inatomi N: A study comparing the antisecretory effect of TAK-438, a novel potassium-competitive acid blocker, with lansoprazole in animals. J Pharmacol Exp Ther 2011;337:797-804.
Ashida K, Sakurai Y, Hori T, Kudou K, Nishimura A, Hiramatsu N, Umegaki E, Iwakiri K: Randomised clinical trial: vonoprazan, a novel potassium-competitive acid blocker, vs. lansoprazole for the healing of erosive oesophagitis. Aliment Pharmacol Ther 2016;43:240-251.
Murakami K, Sakurai Y, Shiino M, Funao N, Nishimura A, Asaka M: Vonoprazan, a novel potassium-competitive acid blocker, as a component of first-line and second-line triple therapy for Helicobacter pylori eradication: a phase III, randomised, double-blind study. Gut 2016;65:1439-1446.
Tsujimae M, Yamashita H, Hashimura H, Kano C, Shimoyama K, Kanamori A, Matsumoto K, Koizumi A, Momose K, Eguchi T, Fukuchi T, Fujita M, Okada A: A comparative study of a new class of gastric acid suppressant agent named vonoparazan versus esomeprazole for the eradication of helicobacter pylori. Digestion 2016;94:240-246.
Hoshino S, Kawami N, Takenouchi N, Umezawa M, Hanada Y, Hoshikawa Y, Kawagoe T, Sano H, Hoshihara Y, Nomura T, Iwakiri K: Efficacy of vonoprazan for proton pump inhibitor-resistant reflux esophagitis. Digestion 2017;95:156-161.
Bredenoord AJ, Weusten BL, Timmer R, Akkermans LM, Smout AJ: Relationships between air swallowing, intragastric air, belching and gastro-oesophageal reflux. Neurogastroenterol Motil 2005;17:341-347.
Roman S, Gyawali CP, Xiao Y, Pandolfino JE, Kahrilas PJ: The Chicago classification of motility disorders: an update. Gastrointest Endosc Clin N Am 2014;24:545-561.
Peghini PL, Katz PO, Bracy NA, Castell DO: Nocturnal recovery of gastric acid secretion with twice-daily dosing of proton pump inhibitors. Am J Gastroenterol 1998;93:763-767.
Miki M, Adachi K, Azumi T, Koshino K, Furuta K, Kinoshita Y: A comparative study of intragastric acidity during post-breakfast and pre-dinner administration of low-dose proton pump inhibitors: a randomized three-way crossover study. Aliment Pharmacol Ther 2006;24:1445-1451.
Ichikawa H, Sugimoto M, Sugimoto K, Andoh A, Furuta T: Rapid metabolizer genotype of CYP2C19 is a risk factor of being refractory to proton pump inhibitor therapy for reflux esophagitis. J Gastroenterol Hepatol 2016;31:716-726.
Kagami T, Sahara S, Ichikawa H, Uotani T, Yamade M, Sugimoto M, Hamaya Y, Iwaizumi M, Osawa S, Sugimoto K, Miyajima H, Furuta T: Potent acid inhibition by vonoprazan in comparison with esomeprazole, with reference to CYP2C19 genotype. Aliment Pharmacol Ther 2016;43:1048-1059.
Bell NJ, Burget D, Howden CW, Wilkinson J, Hunt RH: Appropriate acid suppression for the management of gastro-oesophageal reflux disease. Digestion 1992;51(suppl 1):59-67.
Sakurai Y, Mori Y, Okamoto H, Nishimura A, Komura E, Araki T, Shiramoto M: Acid-inhibitory effects of vonoprazan 20 mg compared with esomeprazole 20 mg or rabeprazole 10 mg in healthy adult male subjects - a randomised open-label cross-over study. Aliment Pharmacol Ther 2015;42:719-730.
The interview form for vonoprazan fumarate (Takecab tablets 10 mg and 20 mg) ver. 3 (in Japanese). Takeda Pharmaceutical Company Limited 2015.
Helm JF, Dodds WJ, Pelc LR, Palmer DW, Hogan WJ, Teeter BC: Effect of esophageal emptying and saliva on clearance of acid from the esophagus. N Engl J Med 1984;310:284-288.
Frazzoni M, Bertani H, Manta R, Mirante VG, Frazzoni L, Conigliaro R, Melotti G: Impairment of chemical clearance is relevant to the pathogenesis of refractory reflux oesophagitis. Dig Liver Dis 2014;46:596-602.
Zerbib F, Duriez A, Roman S, Capdepont M, Mion F: Determinants of gastro-oesophageal reflux perception in patients with persistent symptoms despite proton pump inhibitors. Gut 2008;57:156-160.
Emerenziani S, Ribolsi M, Sifrim D, Blondeau K, Cicala M: Regional oesophageal sensitivity to acid and weakly acidic reflux in patients with non-erosive reflux disease. Neurogastroenterol Motil 2009;21:253-258.
Holloway RH, Hongo M, Berger K, McCallum RW: Gastric distention: a mechanism for postprandial gastroesophageal reflux. Gastroenterology 1985;89:779-884.
Rohof WO, Bennink RJ, Boeckxstaens GE: Proton pump inhibitors reduce the size and acidity of the acid pocket in the stomach. Clin Gastroenterol Hepatol 2014;12:1101-1107.
Babaei A, Bhargava V, Aalam S, Scadeng M, Mittal RK: Effect of proton pump inhibition on the gastric volume: assessed by magnetic resonance imaging. Aliment Pharmacol Ther 2009;29:863-870.
Okuyama M, Nakahara K, Iwakura N, Hasegawa T, Oyama M, Inoue A, Ishizu H, Satoh H, Fujiwara Y: Factors associated with potassium-competitive acid blocker non-response in patients with proton pump inhibitor-refractory gastroesophageal reflux disease. Digestion 2017;95:281-287.
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