Background/Aim: We evaluated the efficacy of vonoprazan (VPZ), a novel potassium-competitive acid blocker, in patients with proton pump inhibitor (PPI)-refractory gastroesophageal reflux disease (GERD), exhibiting continued pathological esophageal acid exposure (EAE). Methods: Despite ≥8 weeks of appropriate PPI therapy, patients with -persistent reflux symptoms and pathological EAE times (EAETs ≥4%) were invited to switch to VPZ treatment. After an 8-week-course of once-daily VPZ (20 mg), multichannel intraluminal impedance-pH (MII-pH) monitoring was repeated to compare gastric acid exposure times (GAETs), EAETs, and other reflux parameters relative to the baseline values. Before each MII-pH study, reflux symptom severities were scored using the Gastrointestinal Symptom Rating Scale; erosive esophagitis and fasting plasma gastrin levels were also assessed. Results: From among the 124 patients undergoing MII-pH monitoring, 13 patients (median age, 69 years; females, 64%) were monitored at baseline (while on PPI therapy) and after VPZ therapy. The median GAET associated with VPZ treatment (23.8%) was less than that for PPI treatment (41.1%; p = 0.01), including both daytime and nighttime measurements. VPZ therapy resulted in better median EAET values (4.5%) than did PPI therapy (10.6%) during the 24-h monitoring period (p = 0.055). EAE normalization was achieved in 46% of VPZ-treated patients and was associated with complete gastric acid suppression (p = 0.005). After switching to VPZ, reflux symptoms (p < 0.01) and erosive esophagitis (p = 0.01) improved. Conclusion: In patients with PPI-refractory GERD, VPZ provides more potent gastric acid suppression, more effective EAE control, enhanced symptom improvement, and better esophagitis healing than PPIs.

1.
Fass R, Sifrim D. Management of heartburn not responding to proton pump inhibitors.
Gut
. 2009 Feb; 58(2): 295–309.
2.
Gerson LB, Kahrilas PJ, Fass R. Insights into gastroesophageal reflux disease-associated dyspeptic symptoms.
Clin Gastroenterol Hepatol
. 2011 Oct; 9(10): 824–33.
3.
Katz PO, Gerson LB, Vela MF. Guidelines for the diagnosis and management of gastroesophageal reflux disease.
Am J Gastroenterol
. 2013 Mar; 108(3): 308–28.
4.
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.
5.
Scarpellini E, Ang D, Pauwels A, De Santis A, Vanuytsel T, Tack J. Management of refractory typical GERD symptoms.
Nat Rev Gastroenterol Hepatol
. 2016 May; 13(5): 281–94.
6.
Sakurai Y, Nishimura A, Kennedy G, Hibberd M, Jenkins R, Okamoto H, et al. Safety, tolerability, pharmacokinetics, and pharmacodynamics of single rising TAK-438 (vonoprazan) doses in healthy male Japanese/non-Japanese subjects.
Clin Transl Gastroenterol
. 2015 Jun; 6(6):e94.
7.
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.
8.
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.
9.
Matsukawa J, Hori Y, Nishida H, Kajino M, Inatomi N. 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 May; 81(9): 1145–51.
10.
Ashida K, Sakurai Y, Hori T, Kudou K, Nishimura A, Hiramatsu N, et al. Randomised clinical trial: vonoprazan, a novel potassium-competitive acid blocker, vs. lansoprazole for the healing of erosive oesophagitis.
Aliment Pharmacol Ther
. 2016 Jan; 43(2): 240–51.
11.
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.
12.
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.
13.
Yamashita H, Kanamori A, Kano C, Hashimura H, Matsumoto K, Tsujimae M, et al. The effects of switching to vonoprazan, a novel potassium-competitive acid blocker, on gastric acidity and reflux patterns in patients with erosive esophagitis refractory to proton pump inhibitors.
Digestion
. 2017; 96(1): 52–9.
14.
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.
15.
Graham DY, Tansel A. Interchangeable use of proton pump inhibitors based on relative potency.
Clin Gastroenterol Hepatol
. 2018 Jun; 16(6): 800–808.e7.
16.
Kirchheiner J, Glatt S, Fuhr U, Klotz U, Meineke I, Seufferlein T, et al. Relative potency of proton-pump inhibitors-comparison of effects on intragastric pH.
Eur J Clin Pharmacol
. 2009 Jan; 65(1): 19–31.
17.
Howden CW, Burget DW, Hunt RH. Appropriate acid suppression for optimal healing of duodenal ulcer and gastro-oesophageal reflux disease.
Scand J Gastroenterol Suppl
. 1994; 201 sup201: 79–82.
18.
Dimenäs E, Glise H, Hallerbäck B, Hernqvist H, Svedlund J, Wiklund I. Well-being and gastrointestinal symptoms among patients referred to endoscopy owing to suspected duodenal ulcer.
Scand J Gastroenterol
. 1995 Nov; 30(11): 1046–52.
19.
Dimenäs E, Carlsson G, Glise H, Israelsson B, Wiklund I. Relevance of norm values as part of the documentation of quality of life instruments for use in upper gastrointestinal disease.
Scand J Gastroenterol Suppl
. 1996; 221: 8–13.
20.
Makuuchi H. [Clinical study of sliding esophageal hernia–with special reference to the diagnostic criteria and classification of the severity of the disease] [in Japanese, with English abstract].
Nihon Shokakibyo Gakkai Zasshi
. 1982 Aug; 79(8): 1557–67.
21.
Sharma P, Dent J, Armstrong D, Bergman JJ, Gossner L, Hoshihara Y, et al. The development and validation of an endoscopic grading system for Barrett’s esophagus: the Prague C & M criteria.
Gastroenterology
. 2006 Nov; 131(5): 1392–9.
22.
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.
23.
Patel A, Sayuk GS, Gyawali CP. Acid-based parameters on pH-impedance testing predict symptom improvement with medical management better than impedance parameters.
Am J Gastroenterol
. 2014 Jun; 109(6): 836–44.
24.
Patel A, Sayuk GS, Gyawali CP. Parameters on esophageal pH-impedance monitoring that predict outcomes of patients with gastroesophageal reflux disease.
Clin Gastroenterol Hepatol
. 2015 May; 13(5): 884–91.
25.
Gerson LB, Mitra S, Bleker WF, Yeung P. Control of intra-oesophageal pH in -‑patients with Barrett’s oesophagus on omeprazole-sodium bicarbonate therapy.
Aliment Pharmacol Ther
. 2012 Apr; 35(7): 803–9.
26.
Okuyama M, Nakahara K, Iwakura N, Ha segawa 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.
27.
Stern EK, Carlson DA, Falmagne S, Hoffmann AD, Carns M, Pandolfino JE, et al. Abnormal esophageal acid exposure on high-dose proton pump inhibitor therapy is common in systemic sclerosis patients.
Neurogastroenterol Motil
. 2018 Feb; 30(2):e13247.
28.
Echizen H. The first-in-class potassium-competitive acid blocker, vonoprazan fumarate: pharmacokinetic and pharmacodynamic considerations.
Clin Pharmacokinet
. 2016 Apr; 55(4): 409–18.
29.
Uemura N, Kinoshita Y, Haruma K, Yao T, Kushima R, Kanoo T. Rationale and design of the VISION study: a randomized, open-label study to evaluate the long-term safety of vonoprazan as maintenance treatment in patients with erosive esophagitis.
Clin Exp Gastroenterol
. 2018 Jan; 11: 51–6.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.