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Review
. 2022 Apr;57(4):267-285.
doi: 10.1007/s00535-022-01861-z. Epub 2022 Feb 28.

Evidence-based clinical practice guidelines for gastroesophageal reflux disease 2021

Katsuhiko Iwakiri  1   2 , Yasuhiro Fujiwara  3 , Noriaki Manabe  3 , Eikichi Ihara  3 , Shiko Kuribayashi  3 , Junichi Akiyama  3 , Takashi Kondo  3 , Hiroshi Yamashita  3 , Norihisa Ishimura  3 , Yuichi Kitasako  3 , Katsunori Iijima  3 , Tomoyuki Koike  3 , Nobuo Omura  3 , Tsutomu Nomura  3 , Osamu Kawamura  3 , Shuichi Ohara  3 , Soji Ozawa  3 , Yoshikazu Kinoshita  3 , Satoshi Mochida  3 , Nobuyuki Enomoto  3 , Tooru Shimosegawa  3 , Kazuhiko Koike  3
Affiliations
Review

Evidence-based clinical practice guidelines for gastroesophageal reflux disease 2021

Katsuhiko Iwakiri et al. J Gastroenterol. 2022 Apr.

Abstract

In Japan, with the increasing prevalence of gastroesophageal reflux disease (GERD) and growing public interest, the Japanese Society of Gastroenterology issued Evidence-based Clinical Practice Guidelines for GERD (1st edition) in 2009 and a revised 2nd edition in 2015. A number of studies on GERD were subsequently conducted in Japan and abroad, and vonoprazan, a potassium-competitive acid blocker (P-CAB), became available for the first time in Japan in February 2015. The revised 3rd edition (Japanese edition), which incorporates new findings and information, was published in April 2021. These guidelines are summarized herein, particularly sections related to the treatment of GERD. The important clinical issues addressed in the present revision are (i) the introduction of treatment algorithms that classify GERD into reflux esophagitis and non-erosive reflux disease, (ii) the clarification of treatment algorithms based on to the severity of reflux esophagitis, and (iii) the positioning of vonoprazan in the treatment for GERD. The present guidelines propose vonoprazan as the initial/maintenance treatment for severe reflux esophagitis. They also recommend vonoprazan or PPI as an initial treatment for mild reflux esophagitis and recommended PPI and proposed vonoprazan as maintenance treatment. These updated guidelines offer the best clinical strategies for GERD patients in Japan and hope that they will be of global use for the diagnosis and treatment for GERD.

Keywords: Algorithm; Gastroesophageal reflux disease (GERD); Guidelines; Heartburn; Japanese traditional medicine; Non-erosive reflux disease; Potassium-competitive acid blocker (P-CAB); Prokinetic drug; Proton pump inhibitor; Reflux esophagitis; Vonoprazan.

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Conflict of interest statement

Any financial relationship with enterprises, businesses or academic institutions in the subject matter or materials discussed in the manuscript are as follows: (1) those from which the authors, the spouse, partner or immediate relatives of the authors have received individually any income, honoraria or any other type of renumeration; Astellas Pharma, AstraZeneca, Otsuka Pharmaceutical, Daiichi Sankyo, Takeda Pharmaceutical, Mochida Pharmaceutical, Tsumura & CO., EA Pharma, Mylan EPD, and (2) those from which the authors have received research grant: Fujifilm, Taiho Pharmaceutical, Tsumura & CO, Bristol-Myers Squibb, and (3) those from which the authors have received scholarship; Astellas Pharma, AbbVie, EA Pharma, Eisai, MSD, Ono Pharmaceutical, Covidien Japan, Taiho Pharmaceutical, Takeda Pharmaceutical, Chugai Pharmaceutical, Novartis Pharma, Bayer Yakuhin, Asahi Kasei Pharma, Nippon Kayaku, Mochida Pharmaceutical, Zeria Pharmaceutical, Daiichi Sankyo, Otsuka Pharmaceutical, and (4) those from which the authors have received individually endowed chair; Ohga Pharmacy, Otsuka Pharmaceutical, Ono Pharmaceutical, Sanwa Kagaku Kenkyusho, Terumo, FANCL, Fujifilm Medical, Miyarisan Pharmaceutical, and (5) those from which the authors have received individually contribution; EA Pharma, Otsuka Pharmaceutical, Daiichi Sankyo, Takeda Pharmaceutical.

Figures

Fig. 1
Fig. 1
Algorithm for the diagnosis and treatment of gastroesophageal reflux disease (GERD). a Diagnosis of GERD with endoscopy. b Treatment strategy for severe reflux esophagitis (RE). c Treatment strategy for mild RE. d Treatment strategy for non-erosive reflux disease (NERD). e Diagnosis of GERD without endoscopy. Red arrows: judged to be negative or unsuccessful treatment. Blue arrows: judged to be positive or successful treatment. *Prokinetics or Japanese herbal medicine. **Minimal dose of PPI used in cases with good control during 10 mg of vonoprazan. ***Minimal doses of PPI or on-demand therapy may be used
Fig. 1
Fig. 1
Algorithm for the diagnosis and treatment of gastroesophageal reflux disease (GERD). a Diagnosis of GERD with endoscopy. b Treatment strategy for severe reflux esophagitis (RE). c Treatment strategy for mild RE. d Treatment strategy for non-erosive reflux disease (NERD). e Diagnosis of GERD without endoscopy. Red arrows: judged to be negative or unsuccessful treatment. Blue arrows: judged to be positive or successful treatment. *Prokinetics or Japanese herbal medicine. **Minimal dose of PPI used in cases with good control during 10 mg of vonoprazan. ***Minimal doses of PPI or on-demand therapy may be used
Fig. 2
Fig. 2
Comparison of the non-healing rate for mild reflux esophagitis between vonoprazan (VPZ) at 20 mg once daily for 4 weeks and lansoprazole (LPZ) at 30 mg once daily for 4 weeks by a meta-analysis
Fig. 3
Fig. 3
Comparison of the non-healing rate for mild reflux esophagitis between vonoprazan (VPZ) at 20 mg once daily for 8 weeks and lansoprazole (LPZ) at 30 mg once daily for 8 weeks by a meta-analysis
Fig. 4
Fig. 4
Comparison of the non-healing rate of mucosal injury (damage) between vonoprazan (VPZ) at 20 mg once daily for 4 weeks and lansoprazole (LPZ) at 30 and 20 mg once daily for 4 weeks by a meta-analysis limited to two domestic studies
Fig. 5
Fig. 5
Comparison of the non-healing rate of mucosal damage between vonoprazan (VPZ) at 20 mg once daily for 8 weeks and lansoprazole (LPZ) at 30 mg once daily for 8 weeks by a meta-analysis limited to two domestic studies
Fig. 6
Fig. 6
Comparison of the non-healing rate of mucosal injury between vonoprazan (VPZ) at 20 mg once daily for 4 and 8 weeks by a meta-analysis
Fig. 7
Fig. 7
Comparison of the non-healing rate of mucosal injury between vonoprazan (VPZ) at 20 mg once daily for 4 and 8 weeks by a meta-analysis limited to two domestic studies
Fig. 8
Fig. 8
Comparison of the non-healing rate of severe reflux esophagitis between vonoprazan (VPZ) at 20 mg once daily for 4 weeks and lansoprazole (LPZ) at 30 mg once daily for 4 weeks by a meta-analysis
Fig. 9
Fig. 9
Comparison of the non-healing rate of severe reflux esophagitis between vonoprazan (VPZ) at 20 mg once daily for 8 weeks and lansoprazole (LPZ) at 30 mg once daily for 8 weeks by a meta-analysis
Fig. 10
Fig. 10
Comparison of the non-healing rate of severe reflux esophagitis between vonoprazan (VPZ) at 20 mg once daily for 4 weeks and lansoprazole (LPZ) at 30 mg once daily for 4 weeks by a meta-analysis limited to two domestic studies
Fig. 11
Fig. 11
Comparison of the non-healing rate of severe reflux esophagitis between vonoprazan (VPZ) at 20 mg once daily for 8 weeks and lansoprazole (LPZ) at 30 mg once daily for 8 weeks by a meta-analysis limited to two domestic studies
Fig. 12
Fig. 12
Comparison of the non-healing rate of severe reflux esophagitis between vonoprazan (VPZ) at 20 mg once daily for 4 and 8 weeks by a meta-analysis
Fig. 13
Fig. 13
Comparison of the non-healing rate of severe reflux esophagitis between vonoprazan (VPZ) at 20 mg once daily for 4 and 8 weeks by a meta-analysis limited to two domestic studies
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