Abstract
Background
Gastroesophageal reflux disease (GERD) can be treated using a vonoprazan-first strategy (first-line treatment with vonoprazan), or esomeprazole-first/rabeprazole-first strategies (first-line treatment with proton-pump inhibitors [PPIs], esomeprazole/rabeprazole, followed by a switch to vonoprazan). This cost-utility analysis used long-term simulation modeling to evaluate the cost-effectiveness of a vonoprazan-first strategy compared with the esomeprazole-first and rabeprazole-first strategies.
Methods
A Markov simulation model was developed to evaluate the cost-effectiveness of vonoprazan-first, esomeprazole-first, and rabeprazole-first strategies, comprising healing and maintenance therapies, over 5 years (4-week cycles). Healing therapy began with the administration of a normal dose of drug per real-world practice. If patients were not healed endoscopically, either a longer duration of healing therapy was provided (vonoprazan), the dose was increased (rabeprazole), or patients were switched to vonoprazan (immediately for esomeprazole, and after dose-escalation for rabeprazole, respectively). Healed patients received maintenance (lower/same dose as healing therapy). Recurrence resulted in re-challenge with healing therapy. Transition probabilities were derived from the results of indirect comparisons (network meta-analysis) and costs calculated from the Japanese payer perspective. Outcomes were defined as quality-adjusted life years (QALYs), with utilities based on published values.
Results
Expected costs of the vonoprazan-, esomeprazole-, and rabeprazole-first strategies were ¥36,194, ¥76,719, and ¥41,105, respectively, over 5 years. QALY gains for vonoprazan-first strategy versus the esomeprazole- and rabeprazole-first strategies were 0.014 and 0.003, respectively. Both estimated incremental cost-effectiveness ratios were dominant and robust to two sensitivity analyses.
Conclusions
Vonoprazan-first strategy increased QALYs and appeared to be cost-effective for GERD patients compared with the esomeprazole- or rabeprazole-first strategies.
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References
El-Serag HB, Sweet S, Winchester CC, et al. Update on the epidemiology of gastro-oesophageal reflux disease: a systematic review. Gut. 2014;63:871–80.
Vakil N, van Zanten SV, Kahrilas P, et al. The Montreal definition and classification of gastroesophageal reflux disease: a global evidence-based consensus. Am J Gastroenterol. 2006;101:1900–20.
Tack J, Becher A, Mulligan C, et al. Systematic review: the burden of disruptive gastro-oesophageal reflux disease on health-related quality of life. Aliment Pharmacol Ther. 2012;35:1257–66.
Wahlqvist P, Reilly MC, Barkun A. Systematic review: the impact of gastro-oesophageal reflux disease on work productivity. Aliment Pharmacol Ther. 2006;24:259–72.
Iwakiri K, Kinoshita Y, Habu Y, et al. Evidence-based clinical practice guidelines for gastroesophageal reflux disease 2015. J Gastroenterol. 2016;51:751–67.
Katz PO, Gerson LB, Vela MF. Guidelines for the diagnosis and management of gastroesophageal reflux disease. Am J Gastroenterol. 2013;108:308–28.
Strand DS, Kim D, Peura DA. 25 years of proton pump inhibitors: a comprehensive review. Gut Liver. 2017;11:27–37.
Zhang C, Kwong JS, Yuan RX, et al. Effectiveness and tolerability of different recommended doses of PPIs and H(2)RAs in GERD: network meta-analysis and GRADE system. Sci Rep. 2017;7:41021.
Kawara F, Fujita T, Morita Y, et al. Factors associated with residual gastroesophageal reflux disease symptoms in patients receiving proton pump inhibitor maintenance therapy. World J Gastroenterol. 2017;23:2060–7.
Kimiya T. The association between persistent reflux symptoms and health-related quality of life in Japanese patients with gastroesophageal reflux disease. Jpn J Psychosom Med. 2017;57:357–61.
Kimura Y, Kamiya T, Senoo K, et al. Persistent reflux symptoms cause anxiety, depression, and mental health and sleep disorders in gastroesophageal reflux disease patients. J Clin Biochem Nutr. 2016;59:71–7.
Hori Y, Imanishi A, Matsukawa J, et al. 1-[5-(2-Fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl]-N-methylmethanamin e monofumarate (TAK-438), a novel and potent potassium-competitive acid blocker for the treatment of acid-related diseases. J Pharmacol Exp Ther. 2010;335:231–8.
Hori Y, Matsukawa J, Takeuchi T, et al. 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.
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;81:1145–51.
Shin JM, Inatomi N, Munson K, et al. Characterization of a novel potassium-competitive acid blocker of the gastric H, K-ATPase, 1-[5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl]-N-methylmethanamin e monofumarate (TAK-438). J Pharmacol Exp Ther. 2011;339:412–20.
Akiyama J, Hosaka H, Kuribayashi S, et al. Efficacy of vonoprazan, a novel potassium-competitive acid blocker, in patients with proton pump inhibitor-refractory acid reflux. Digestion. 2019. https://doi.org/10.1159/000497775:1-10.
Hoshino S, Kawami N, Takenouchi N, et al. Efficacy of vonoprazan for proton pump inhibitor-resistant reflux esophagitis. Digestion. 2017;95:156–61.
Mizuno H, Nishino M, Yamada K, et al. Efficacy of vonoprazan for 48-week maintenance therapy of patients with healed reflux esophagitis. Digestion. 2019. https://doi.org/10.1159/000500399:1-11.
Umezawa M, Kawami N, Hoshino S, et al. Efficacy of on-demand therapy using 20-mg vonoprazan for mild reflux esophagitis. Digestion. 2018;97:309–15.
Yamashita H, Kanamori A, Kano C, 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;96:52–9.
Yamasaki A, Yoshio T, Muramatsu Y, et al. Vonoprazan is superior to rabeprazole for healing endoscopic submucosal dissection: induced ulcers. Digestion. 2018;97:170–6.
Sugawara K, Koizumi S, Horikawa Y, et al. Is the new potent acid-inhibitory drug vonoprazan effective for healing idiopathic peptic ulcers? A multicenter observational study in Akita Prefecture, Japan. J Gastroenterol. 2019. https://doi.org/10.1007/s00535-019-01587-5.
Sugano K. Vonoprazan fumarate, a novel potassium-competitive acid blocker, in the management of gastroesophageal reflux disease: safety and clinical evidence to date. Therap Adv Gastroenterol. 2018;11:175.
Deguchi H, Uda A, Murakami K. Current status of Helicobacter pylori diagnosis and eradication therapy in Japan using a nationwide database. Digestion. 2019. https://doi.org/10.1159/000500819:1-9.
Tsujimae M, Yamashita H, Hashimura H, et al. A comparative study of a new class of gastric acid suppressant agent named vonoparazan versus esomeprazole for the eradication of Helicobacter pylori. Digestion. 2016;94:240–6.
Takeda Pharmaceutical Company Ltd. Comparison of vonoprazan to esomeprazole in participants with symptomatic GERD who responded partially to a high dose of proton pump inhibitor (PPI). ClinicalTrials.gov: US NIH; 2018. https://clinicaltrials.gov/ct2/show/NCT02743949. Accessed 24 Apr 2019.
Takeda Pharmaceutical Company Ltd. Efficacy and safety of oral once-daily vonoprazan (TAK-438) in participants with erosive esophagitis. ClinicalTrials.gov: US NIH; 2017. https://clinicaltrials.gov/ct2/show/NCT02388724. Accessed 24 Apr 2019.
Sakata Y, Tsuruoka N, Takedomi H, et al. A study on the status of proton pump inhibitor prescriptions using diagnosis procedure combination data in Japan. Digestion. 2019. https://doi.org/10.1159/000498967:1-8.
Sakurai Y, Mori Y, Okamoto H, 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;42:719–30.
Ashida K, Iwakiri K, Hiramatsu N, et al. Maintenance for healed erosive esophagitis: phase III comparison of vonoprazan with lansoprazole. World J Gastroenterol. 2018;24:1550–611.
Ashida K, Sakurai Y, Hori T, et al. Randomised clinical trial: vonoprazan, a novel potassium-competitive acid blocker, vs. lansoprazole for the healing of erosive oesophagitis. Aliment Pharmacol Ther. 2016;43:240–51.
Ashida K, Sakurai Y, Nishimura A, et al. Randomised clinical trial: a dose-ranging study of vonoprazan, a novel potassium-competitive acid blocker, vs. lansoprazole for the treatment of erosive oesophagitis. Aliment Pharmacol Ther. 2015;42:685–95.
Oshima T, Arai E, Taki M, et al. Randomised clinical trial: vonoprazan versus lansoprazole for the initial relief of heartburn in patients with erosive oesophagitis. Aliment Pharmacol Ther. 2019;49:140–6.
Higuchi K, Uda A, Deguchi H, et al. Su1016 - Cost-utility analysis of potassium-competitive acid blocker-based therapeutic strategy for gastroesophageal reflux disease compared with proton-pump inhibitor-based therapeutic strategy [abstract]. Gastroenterology. 2018;154:S455–S456456.
Sugano K, Kobayashi SS. Cost-effectiveness analysis of maintenance therapies for reflux esophagitis–comparison between step-up therapies and step-down therapies. Jpn Pharmacol Ther. 2001;29:459–68.
Miyazaki H, Igarashi A, Takeuchi T, et al. Vonoprazan versus proton-pump inhibitors for healing gastroesophageal reflux disease: a systematic review. J Gastroenterol Hepatol. 2019. https://doi.org/10.1111/jgh.14664.
Miwa H, Igarashi A, Teng L, et al. Systematic review with network meta-analysis: indirect comparison of the efficacy of vonoprazan and proton-pump inhibitors for maintenance treatment of gastroesophageal reflux disease. J Gastroenterol. 2019. https://doi.org/10.1007/s00535-019-01572-y.
Pharmaceutical Industry Association. Insurance medicine encyclopedia plus (30th edition) [in Japanese]. 2018.
Medical Correspondent Company. Medical care quick-point reference chart [in Japanese]. 2018.
Central Social Insurance Medical Council. Analysis guidelines for cost-effectiveness assessment [in Japanese]. Tokyo, Japan: Health, Labor and Welfare Science Research Grants; 2015. https://www.mhlw.go.jp/file/05-Shingikai-12404000-Hokenkyoku-Iryouka/0000104722.pdf. Accessed 24 Apr 2019.
Grant A, Wileman S, Ramsay C, et al. The effectiveness and cost-effectiveness of minimal access surgery amongst people with gastro-oesophageal reflux disease—a UK collaborative study The REFLUX trial. Health Technol Assess. 2008;12(1–181):iii–iv.
Ministry of Health Labour and Welfare. Study on cost-effectiveness evaluation [in Japanese]. Tokyo, Japan2018. https://www.mhlw.go.jp/content/12404000/000435621.pdf. Accessed 24 Apr 2019.
Habu Y, Maeda K, Kusuda T, et al. "Proton-pump inhibitor-first" strategy versus "step-up" strategy for the acute treatment of reflux esophagitis: a cost-effectiveness analysis in Japan. J Gastroenterol. 2005;40:1029–35.
Habu Y. Vonoprazan versus lansoprazole for the initial treatment of reflux esophagitis: a cost-effectiveness analysis in Japan. Intern Med. 2019; doi:10.2169/internalmedicine.2535-18.
Kinoshita Y, Kato M, Fujishiro M, et al. Efficacy and safety of twice-daily rabeprazole maintenance therapy for patients with reflux esophagitis refractory to standard once-daily proton pump inhibitor: the Japan-based EXTEND study. J Gastroenterol. 2018;53:834–44.
Takeuchi T, Hongo H, Kimura T, et al. Efficacy and safety of hangeshashinto for treatment of GERD refractory to proton pump inhibitors : usual dose proton pump inhibitors plus hangeshashinto versus double-dose proton pump inhibitors: randomized, multicenter open label exploratory study. J Gastroenterol. 2019. https://doi.org/10.1007/s00535-019-01588-4.
Ozaki H, Harada S, Takeuchi T, et al. Vonoprazan, a novel potassium-competitive acid blocker, should be used for the Helicobacter pylori eradication therapy as first choice: a large sample study of vonoprazan in real world compared with our randomized control trial using second-generation proton pump inhibitors for Helicobacter pylori eradication therapy. Digestion. 2018;97:212–8.
Isshi K, Matsuhashi N, Joh T, et al. Proton pump inhibitor monotherapy is effective to attenuate dyspepsia symptoms associated with gastroesophageal reflux disease: a multicenter prospective observational study. J Gastroenterol. 2019;54:492–500.
Nakada K, Matsuhashi N, Iwakiri K, et al. Development and validation of a simple and multifaceted instrument, GERD-TEST, for the clinical evaluation of gastroesophageal reflux and dyspeptic symptoms. World J Gastroenterol. 2017;23:5216–28.
Acknowledgements
The authors would like to thank Kazuo Ueda, PhD, at the time employed by Takeda Pharmaceutical Co., Ltd., for his contribution to the study design and interpretation of the data. Support in the data analyses was provided, under the direction of the authors, by Sachie Inoue, PhD, an employee of Crecon Medical Assessment. Writing support was provided by Mark Richardson, on behalf of FireKite, and Sabah Farooq of FireKite, an Ashfield company, part of UDG Healthcare plc, during the development of this manuscript, which was funded by Takeda Pharmaceutical Co. Ltd. (Tokyo, Japan), and complied with Good Publication Practice 3 ethical guidelines (Battisti et al., Ann Intern Med. 2015;163:461–464).
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For this research was provided by Japan Medical Affairs, Takeda Pharmaceutical Company Limited, Tokyo, Japan.
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YY: Study conception and design, interpretation of the study data and data analysis, critical revision of the paper, approved the final draft submitted. AI: Study conception and design, interpretation of the study data and data analysis, critical revision of the paper, approved the final draft submitted. AU: Study conception and design, data collection and assembly, interpretation of the study data and data analysis, critical revision of the paper, approved the final draft submitted. HD: Study conception and design, critical revision of the paper, approved the final draft submitted. TT: Interpretation of the study data and data analysis, critical revision of the paper, approved the final draft submitted. KH: Study conception and design, interpretation of the study data and data analysis, critical revision of the paper, approved the final draft submitted.
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Ataru Igarashi received consulting fees from Novartis Pharma K. K., AbbVie GK, Milliman, Sony Inc., and Eli Lilly Japan K. K., and lecture fees from Chugai Pharmaceutical Company, Ltd., CRECON Research and Consulting Inc., Terumo Corporation, Bristol-Myers Squibb K. K., and Creativ Ceutical K. K. Ataru Igarashi also received research grants from Pfizer Japan Inc., CSL Behring Japan Inc., Gilead Science K. K., and Fuji Film K. K. Akihito Uda and Hisato Deguchi are employees of Takeda Pharmaceutical Company Ltd. Toshihisa Takeuchi received honoraria from AstraZeneca K.K., Daiichi Sankyo Company, Ltd., and Takeda Pharmaceutical Company, Ltd. Toshihisa Takeuchi also received research funding from AstraZeneca K.K. Kazuhide Higuchi received research honoraria and research funding from Takeda Pharmaceutical Company, Ltd., Otsuka Pharmaceutical Company, Ltd., AstraZeneca K.K., Daiichi Sankyo Company, Ltd., and Eisai Company, Ltd. Yuta Yokoya has no conflicts of interest to declare.
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Yokoya, Y., Igarashi, A., Uda, A. et al. Cost-utility analysis of a ‘vonoprazan-first’ strategy versus ‘esomeprazole- or rabeprazole-first’ strategy in GERD. J Gastroenterol 54, 1083–1095 (2019). https://doi.org/10.1007/s00535-019-01609-2
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DOI: https://doi.org/10.1007/s00535-019-01609-2