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Investigation of pretreatment prediction of proton pump inhibitor (PPI)-resistant patients with gastroesophageal reflux disease and the dose escalation challenge of PPIs—TORNADO study: a multicenter prospective study by the Acid-Related Symptom Research Group in Japan

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Abstract

Backgrounds

Some non-erosive reflux disease (NERD) and reflux esophagitis (RE) patients are unresponsive to a proton pump inhibitor (PPI) at standard dose. We investigated the predictive marker of the efficacy of PPI for GERD patients including NERD and RE treated with standard and increased doses of a PPI.

Methods

Patients with symptomatic gastroesophageal reflux disease (GERD) (NERD and RE) were treated with rabeprazole (RPZ) 10 mg once daily for 4 weeks. The RPZ dosage was increased to 10 mg twice daily for an additional 2 weeks and again to 20 mg twice daily for another 2 weeks if heartburn was not relieved. Baseline characteristics and efficacy of RPZ were assessed on the basis of a heartburn diary and frequency scale for symptoms of GERD (FSSG).

Results

Complete heartburn relief rates after 4 weeks were 42.5% (31/73) and 67.9% (19/28) in NERD and RE groups, respectively, which rose to 68.9 and 91.7% after dose escalation. Multivariate analysis revealed that parameters associated with resistance to RPZ 10 mg once daily were female, non-smoking, frequent heartburn, low score for question 4 (Q4) of the FSSG (subconsciously rubbing the chest), and high scores for Q3 (heavy stomach after meal) and Q7 (unusual sensation in the throat). Frequent heartburn and a high score for Q7 were associated with resistance to RPZ 20 mg twice daily. FSSG scores of patients resistant to RPZ were significantly higher in comparison with responders before and during treatment.

Conclusions

FSSG could predict response to a PPI for symptomatic GERD. Increase of RPZ dose is useful for treatment of GERD refractory to the standard dose of RPZ.

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Acknowledgments

Eisai Co., Ltd. made a contribution with no restrictions on use.

Conflict of interest

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Authors and Affiliations

  1. Center for Clinical Research, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, 431-3192, Japan

    Takahisa Furuta

  2. Department of General Medicine, Hiroshima University Hospital, Hiroshima, Japan

    Tomohiko Shimatani

  3. First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan

    Mitsushige Sugimoto

  4. Department of Internal Medicine II, Shimane University Faculty of Medicine, Izumo, Japan

    Shunji Ishihara & Yoshikazu Kinoshita

  5. Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan

    Yasuhiro Fujiwara

  6. Department of Endoscopy and Endoscopic Surgery, Gunma University Hospital, Maebashi, Japan

    Motoyasu Kusano

  7. Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan

    Tomoyuki Koike

  8. Departments of Comprehensive Medicine and Psychosomatic Medicine, Tohoku University Hospital, Sendai, Japan

    Michio Hongo

  9. Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan

    Tsutomu Chiba

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  1. Takahisa Furuta
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  2. Tomohiko Shimatani
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  7. Tomoyuki Koike
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Consortia

The Acid-Related Symptom Research Group

Corresponding author

Correspondence to Takahisa Furuta.

Additional information

The authors of the Acid-Related Symptom (ARS) Research Group are given in the Appendix.

Appendix: Members of the ARS (Acid-Related Symptom) Research Group

Appendix: Members of the ARS (Acid-Related Symptom) Research Group

Shuichi Ohara, Department of Gastroenterology, Tohoku Rosai Hospital, Sendai, Japan; Yasuyuki Shimoyama, Department of Endoscopy and Endoscopic Surgery, Gunma University Hospital, Maebashi, Japan; Osamu Kawamura, Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, Japan; Yoshio Hoshihara, Clinic of the Ministry of Economy, Trade and Industry, Tokyo, Japan; Kouji Yakabi and Susumu Kurosawa, Department of Gastroenterology and Hepatology, Saitama Medical Center, Saitama Medical University, Kawagoe, Japan; Yusuke Watanabe, Department of Otorhinolaryngology, International University of Health and Welfare Mita Hospital, Tokyo, Japan; Masafumi Nishino, First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan; Takashi Joh, Makoto Sasaki and Tsuneya Wada, Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan; Kazuhide Higuchi, Second Department of Internal Medicine, Osaka Medical College, Takatsuki, Japan; Yasuki Habu, Department of Gastroenterology, Saiseikai Noe Hospital, Osaka, Japan; Hiroto Miwa, Tadayuki Oshima and Junji Tanaka, Division of Upper Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan; Ken Haruma, Division of Gastroenterology, Department of Internal Medicine, Kawasaki Medical School, Kurashiki, Japan; Noriaki Manabe, Division of Endoscopy and Ultrasonography, Kawasaki Medical School, Kurashiki, Japan; Kyoichi Adachi, Department of Clinical Nursing, Shimane University Faculty of Medicine, Izumo, Japan; Kenji Furuta, Department of Internal Medicine II, Shimane University Faculty of Medicine, Izumo, Japan; Masanori Ito, Department of Medicine and Molecular Science, Hiroshima University, Hiroshima, Japan; Kazuma Fujimoto, Department of Internal Medicine, Saga Medical School, Saga, Japan.

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Furuta, T., Shimatani, T., Sugimoto, M. et al. Investigation of pretreatment prediction of proton pump inhibitor (PPI)-resistant patients with gastroesophageal reflux disease and the dose escalation challenge of PPIs—TORNADO study: a multicenter prospective study by the Acid-Related Symptom Research Group in Japan. J Gastroenterol 46, 1273–1283 (2011). https://doi.org/10.1007/s00535-011-0446-2

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  • DOI: https://doi.org/10.1007/s00535-011-0446-2

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