Aims: We aimed to evaluate the efficacy of vonoprazan (VPZ) as maintenance therapy for healed reflux esophagitis (RE). Methods: We enrolled 74 patients diagnosed with RE with frequency scale for the symptoms of gastroesophageal reflux disease (FSSG) total score ≥8 after at least 8 weeks of treatment with standard proton pump inhibitors (PPIs). These patients were switched to VPZ 20 mg for 4 weeks. We also enrolled 71 patients with no endoscopic evidence of erosive esophagitis who received maintenance therapy with VPZ 10 mg for 48 weeks. The primary end point was the proportion of patients who maintained healed RE refractory to PPIs after 48 weeks of maintenance therapy with on demand 10 mg VPZ. Secondary assessment included the proportion of patients with symptomatic nonrelapse at 48 weeks. Results: Fifty patients successfully completed 48-week maintenance therapy. Maintenance therapy with VPZ 10 mg prevented the relapse of esophageal mucosal breaks in 43 (86.0%) of 50 patients at 48 weeks. During the 48-week maintenance therapy, symptomatic nonrelapse rate for acid reflux-related symptom score of FSSG and acid reflux score of Gastrointestinal Symptom Rating Scale at 48 weeks were 70.0 and 72.0%, respectively. No serious adverse events were reported during the study. Conclusion: VPZ 10 mg is clinically effective for maintenance of healed RE for 48 weeks.

1.
Fujiwara Y, Arakawa T. Epidemiology and clinical characteristics of GERD in the Japanese population. J Gastroenterol. 2009;44(6):518–34.
2.
Kahrilas PJ, Shaheen NJ, Vaezi MF; American Gastroenterological Association Institute; Clinical Practice and Quality Management Committee. American Gastroenterological Association Institute technical review on the management of gastroesophageal reflux disease. Gastroenterology. 2008 Oct;135(4):1392–413.
3.
Pace F, Negrini C, Wiklund I, Rossi C, Savarino V; ITALIAN ONE INVESTIGATORS STUDY GROUP. Quality of life in acute and maintenance treatment of non-erosive and mild erosive gastro-oesophageal reflux disease. Aliment Pharmacol Ther. 2005 Aug 15;22(4):349–56.
4.
Wada T, Sasaki M, Kataoka H, Tanida S, Itoh K, Ogasawara N, et al. Efficacy of famotidine and omeprazole in healing symptoms of non-erosive gastro-oesophageal reflux disease: randomized-controlled study of gastro-oesophageal reflux disease. Aliment Pharmacol Ther. 2005 Jun;21(Suppl 2):2–9.
5.
Iwakiri K, Kinoshita Y, Habu Y, Oshima T, Manabe N, Fujiwara Y, et al. Evidence-based clinical practice guidelines for gastroesophageal reflux disease 2015. J Gastroenterol. 2016 Aug;51(8):751–67.
6.
Ariizumi K, Ohara S, Koike T, Inomata Y, Iijima K, Sekine H, et al. Therapeutic effects of 10 mg/day rabeprazole administration on reflux esophagitis was not influenced by the CYP2C19 polymorphism. J Gastroenterol Hepatol. 2006 Sep;21(9):1428–34.
7.
Kinoshita Y, Miwa H, Kasugai K. [Efficacy and safety of esomeprazole, compared with omeprazole, in maintenance therapy for reflux esophagitis -a phase III, multicenter, randomized, double-blind trial-] [in Japanese]. Nihon Shokakibyo Gakkai Zasshi. 2013 Aug;110(8):1428–38.
8.
Mizuno H, Matsuhashi N, Sakaguchi M, Inoue S, Nakada K, Higuchi K, et al. Recent effectiveness of proton pump inhibitors for severe reflux esophagitis: the first multicenter prospective study in Japan. J Clin Biochem Nutr. 2015 Nov;57(3):233–8.
9.
Armstrong D. Systematic review: persistence and severity in gastro-oesophageal reflux disease. Aliment Pharmacol Ther. 2008 Oct;28(7):841–53.
10.
Fujimoto K, Hongo M; Maintenance Study Group. Safety and efficacy of long-term maintenance therapy with oral dose of rabeprazole 10 mg once daily in Japanese patients with reflux esophagitis. Intern Med. 2011;50(3):179–88.
11.
Nagahara A, Hojo M, Asaoka D, Watanabe S. Maintenance therapy of gastroesophageal reflux disease. Clin J Gastroenterol. 2010 Apr;3(2):61–8.
12.
Caro JJ, Salas M, Ward A. Healing and relapse rates in gastroesophageal reflux disease treated with the newer proton-pump inhibitors lansoprazole, rabeprazole, and pantoprazole compared with omeprazole, ranitidine, and placebo: evidence from randomized clinical trials. Clin Ther. 2001 Jul;23(7):998–1017.
13.
Donnellan C, Sharma N, Preston C, Moayyedi P. Medical treatments for the maintenance therapy of reflux oesophagitis and endoscopic negative reflux disease. Cochrane Database Syst Rev. 2005 Apr;2(2):CD003245.
14.
Habu Y, Yoshino T, Shio S, Hayakumo T, Kawai K. [Evaluation of the efficacy and the cost-effectiveness of maintenance treatment of gastroesophageal reflux disease: proton pump inhibitor versus histamine-2-receptor antagonist] [in Japanese]. Nihon Rinsho. 2004 Aug;62(8):1504–9.
15.
Caos A, Breiter J, Perdomo C, Barth J. Long-term prevention of erosive or ulcerative gastro-oesophageal reflux disease relapse with rabeprazole 10 or 20 mg vs. placebo: results of a 5-year study in the United States. Aliment Pharmacol Ther. 2005 Aug;22(3):193–202.
16.
Oshima T, Miwa H. Potent Potassium-competitive Acid Blockers: A New Era for the Treatment of Acid-related Diseases. J Neurogastroenterol Motil. 2018 Jul;24(3):334–44.
17.
Kinoshita Y, Ishimura N, Ishihara S. Management of GERD: Are Potassium-Competitive Acid Blockers Superior to Proton Pump Inhibitors? Am J Gastroenterol. 2018 Oct;113(10):1417–9.
18.
Hoshino S, Kawami N, Takenouchi N, Umezawa M, Hanada Y, Hoshikawa Y, et al. Efficacy of Vonoprazan for Proton Pump Inhibitor-Resistant Reflux Esophagitis. Digestion. 2017;95(2):156–61.
19.
Okuyama M, Nakahara K, Iwakura N, Hasegawa T, Oyama M, Inoue A, et al. Factors Associated with Potassium-Competitive Acid Blocker Non-Response in Patients with Proton Pump Inhibitor-Refractory Gastroesophageal Reflux Disease. Digestion. 2017;95(4):281–7.
20.
Iwakiri K, Sakurai Y, Shiino M, Okamoto H, Kudou K, Nishimura A, et al. A randomized, double-blind study to evaluate the acid-inhibitory effect of vonoprazan (20 mg and 40 mg) in patients with proton-pump inhibitor-resistant erosive esophagitis. Therap Adv Gastroenterol. 2017 Jun;10(6):439–51.
21.
Oshima T, Arai E, Taki M, Kondo T, Tomita T, Fukui H, et al. Randomised clinical trial: vonoprazan versus lansoprazole for the initial relief of heartburn in patients with erosive oesophagitis. Aliment Pharmacol Ther. 2019 Jan;49(2):140–6.
22.
Kusano M, Shimoyama Y, Sugimoto S, Kawamura O, Maeda M, Minashi K, et al. Development and evaluation of FSSG: frequency scale for the symptoms of GERD. J Gastroenterol. 2004 Sep;39(9):888–91.
23.
Lundell LR, Dent J, Bennett JR, Blum AL, Armstrong D, Galmiche JP, et al. Endoscopic assessment of oesophagitis: clinical and functional correlates and further validation of the Los Angeles classification. Gut. 1999 Aug;45(2):172–80.
24.
Miwa H, Yokoyama T, Hori K, Sakagami T, Oshima T, Tomita T, et al. Interobserver agreement in endoscopic evaluation of reflux esophagitis using a modified Los Angeles classification incorporating grades N and M: a validation study in a cohort of Japanese endoscopists. Dis Esophagus. 2008;21(4):355–63.
25.
Kinoshita Y, Adachi K. Hiatal hernia and gastroesophageal flap valve as diagnostic indicators in patients with gastroesophageal reflux disease. J Gastroenterol. 2006 Jul;41(7):720–1.
26.
Kimura K, Takemoto T. An endoscopic recognition of the atrophic border and its significance in chronic gastritis. Endoscopy. 1969;1(03):87–97.
27.
Hongo M, Fukuhara S, Green J. Gastrointestinal-related QOL-QOL assessment using the Japanese version of GSRS. Diagnosis and Treatment. 1999;87:731–6.
28.
Kanazawa M, Nakajima S, Oshima T, Whitehead WE, Sperber AD, Palsson OS, et al. Validity and Reliability of the Japanese Version of the Rome III Diagnostic Questionnaire for Irritable Bowel Syndrome and Functional Dyspepsia. J Neurogastroenterol Motil. 2015 Oct;21(4):537–44.
29.
Dent J, Brun J, Fendrick A, Fendrick M, Janssens J, Kahrilas P, et al. An evidence-based appraisal of reflux disease management–the Genval Workshop Report. Gut. 1999 Apr;44(Suppl 2):S1–16.
30.
DeVault KR, Castell DO; American College of Gastroenterology. Updated guidelines for the diagnosis and treatment of gastroesophageal reflux disease. Am J Gastroenterol. 2005 Jan;100(1):190–200.
31.
Röhss K, Lind T, Wilder-Smith C. Esomeprazole 40 mg provides more effective intragastric acid control than lansoprazole 30 mg, omeprazole 20 mg, pantoprazole 40 mg and rabeprazole 20 mg in patients with gastro-oesophageal reflux symptoms. Eur J Clin Pharmacol. 2004 Oct;60(8):531–9.
32.
Lauritsen K, Devière J, Bigard MA, Bayerdörffer E, Mózsik G, Murray F, et al.; Metropole study results. Esomeprazole 20 mg and lansoprazole 15 mg in maintaining healed reflux oesophagitis: metropole study results. Aliment Pharmacol Ther. 2003 Feb;17(3):333–41.
33.
Labenz J, Armstrong D, Lauritsen K, Katelaris P, Schmidt S, Schütze K, et al. Esomeprazole 20 mg vs. pantoprazole 20 mg for maintenance therapy of healed erosive oesophagitis: results from the EXPO study. Aliment Pharmacol Ther. 2005 Nov;22(9):803–11.
34.
Devault KR, Johanson JF, Johnson DA, Liu S, Sostek MB. Maintenance of healed erosive esophagitis: a randomized six-month comparison of esomeprazole twenty milligrams with lansoprazole fifteen milligrams. Clin Gastroenterol Hepatol. 2006 Jul;4(7):852–9.
35.
Röhss K, Wilder-Smith C, Nauclér E, Jansson L. Esomeprazole 20mg provides more effective intragastric Acid control than maintenance-dose rabeprazole, lansoprazole or pantoprazole in healthy volunteers. Clin Drug Investig. 2004;24(1):1–7.
36.
Vakil NB, Shaker R, Johnson DA, Kovacs T, Baerg RD, Hwang C, et al. The new proton pump inhibitor esomeprazole is effective as a maintenance therapy in GERD patients with healed erosive oesophagitis: a 6-month, randomized, double-blind, placebo-controlled study of efficacy and safety. Aliment Pharmacol Ther. 2001 Jul;15(7):927–35.
37.
Modlin IM, Sachs G. Acid Related Diseases: Biology and Treatment. Philadelphia: Lippincott, Williams and Wilkins; 2004.
38.
Atug O, Giral A, Kalayci C, Dolar E, Isitan F, Oguz D, et al.; Turkish HEMANEX Study Group. Esomeprazole in acute and maintenance treatment of reflux oesophagitis: a multicentre prospective study. Adv Ther. 2008 Jun;25(6):552–66.
39.
Piche T, Galmiche JP. Pharmacological targets in gastro-oesophageal reflux disease. Basic Clin Pharmacol Toxicol. 2005 Dec;97(6):333–41.
40.
Sachs G, Shin JM, Howden CW. Review article: the clinical pharmacology of proton pump inhibitors. Aliment Pharmacol Ther. 2006 Jun;23(Suppl 2):2–8.
41.
Sakurai Y, Mori Y, Okamoto H, Nishimura A, Komura E, Araki T, et al. 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 Sep;42(6):719–30.
42.
Jenkins H, Sakurai Y, Nishimura A, Okamoto H, Hibberd M, Jenkins R, et al. Randomised clinical trial: safety, tolerability, pharmacokinetics and pharmacodynamics of repeated doses of TAK-438 (vonoprazan), a novel potassium-competitive acid blocker, in healthy male subjects. Aliment Pharmacol Ther. 2015 Apr;41(7):636–48.
43.
Shimatani T, Inoue M, Kuroiwa T, Xu J, Mieno H, Nakamura M, et al. Acid-suppressive effects of rabeprazole, omeprazole, and lansoprazole at reduced and standard doses: a crossover comparative study in homozygous extensive metabolizers of cytochrome P450 2C19. Clin Pharmacol Ther. 2006 Jan;79(1):144–52.
44.
Norris V, Baisley K, Dunn K, Warrington S, Morocutti A. Combined analysis of three crossover clinical pharmacology studies of effects of rabeprazole and esomeprazole on 24-h intragastric pH in healthy volunteers. Aliment Pharmacol Ther. 2007 Feb;25(4):501–10.
45.
Ashida K, Iwakiri K, Hiramatsu N, Sakurai Y, Hori T, Kudou K, et al. Maintenance for healed erosive esophagitis: Phase III comparison of vonoprazan with lansoprazole. World J Gastroenterol. 2018 Apr;24(14):1550–61.
46.
Yamasaki H, Kawaguchi N, Nonaka M, Takahashi J, Morohashi A, Hirabayashi H, et al. In vitro metabolism of TAK-438, vonoprazan fumarate, a novel potassium-competitive acid blocker. Xenobiotica. 2017 Dec;47(12):1027–34.
47.
Collen MJ, Johnson DA, Sheridan MJ. Basal acid output and gastric acid hypersecretion in gastroesophageal reflux disease. Correlation with ranitidine therapy. Dig Dis Sci. 1994 Feb;39(2):410–7.
48.
Collen MJ, Strong RM. Comparison of omeprazole and ranitidine in treatment of refractory gastroesophageal reflux disease in patients with gastric acid hypersecretion. Dig Dis Sci. 1992 Jun;37(6):897–903.
49.
Kusunoki H, Kusaka M, Kido S, Yamauchi R, Fujimura Y, Watanabe Y, et al. Comparison of the effects of omeprazole and famotidine in treatment of upper abdominal symptoms in patients with reflux esophagitis. J Gastroenterol. 2009;44(4):261–70.
You do not currently have access to this content.