J Neurogastroenterol Motil 2018; 24(4): 577-583  https://doi.org/10.5056/jnm18036
Pathophysiology of Potassium-competitive Acid Blocker–refractory Gastroesophageal Reflux and the Potential of Potassium-competitive Acid Blocker Test
Tatsuhiro Masaoka,1* Hisako Kameyama,1 Tsuyoshi Yamane,1 Yuta Yamamoto,1 Hiroya Takeuchi,2,3 Hidekazu Suzuki,4 Yuko Kitagawa,2 and Takanori Kanai1
1Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan; 2Department of Surgery, Keio University School of Medicine, Tokyo, Japan; 3Department of Surgery, Hamamatsu University School of Medicine, Shizuoka, Japan; and 4Medical Education Center, Keio University School of Medicine, Tokyo, Japan
Correspondence to: Tatsuhiro Masaoka, MD, PhD
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
Tel: +81-3-5363-3790, Fax: +81-3-3353-6247, E-mail: masaoka@keio.jp
Received: March 3, 2018; Revised: June 8, 2018; Accepted: June 17, 2018; Published online: October 1, 2018.
© The Korean Society of Neurogastroenterology and Motility. All rights reserved.

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Abstract
Background/Aims
Potassium-competitive acid blockers are expected to be the next generation of drugs for the treatment of diseases caused by gastric acid. In 2015, vonoprazan fumarate, a novel potassium-competitive acid blocker, was approved by the Japanese health insurance system. Since its approval, patients refractory to vonoprazan can be encountered in clinical settings. We designed this study to clarify the pathophysiology of gastroesophageal reflux disease refractory to vonoprazan.
Methods
In this retrospective study, we involved patients who had refractory symptoms after administration of standard-dose proton pump inhibitors or vonoprazan and underwent diagnostic testing with esophageal high-resolution manometry and 24-hour multichannel intraluminal impedance and pH monitoring while using proton pump inhibitors or vonoprazan. Patients were diagnosed based on the Rome IV criteria for functional gastrointestinal disorders and diagnostic test results.
Results
Twenty-seven patients were analyzed during this study. Gastric pH ≥ 4 was sustained for a longer period of time, and the esophageal acid exposure time and number of acid reflux events were shorter in the vonoprazan group than in the proton pump inhibitor group. The percentage of patients diagnosed with acidic gastroesophageal reflux disease in the vonoprazan group was lower than that in the proton pump inhibitor group.
Conclusions
Intra-gastric pH and acid reflux were strongly suppressed by 20-mg vonoprazan. When patients with gastroesophageal reflux disease present symptoms after administration of 20-mg vonoprazan, the possibility of pathophysiologies other than acid reflux should be considered.
Keywords: Esophageal motility disorders; Esophageal pH monitoring; Gastroesophageal reflux; Proton pump inhibitors


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