title: 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.
abstract: BACKGROUND
  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.
authors.affiliation: Center for Clinical Research, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192, Japan. furuta@hama-med.ac.jp
authors.forename: Takahisa
authors.initials: T
authors.lastname: Furuta
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Shimatani
authors.forename: Mitsushige
authors.initials: M
authors.lastname: Sugimoto
authors.forename: Shunji
authors.initials: S
authors.lastname: Ishihara
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Fujiwara
authors.forename: Motoyasu
authors.initials: M
authors.lastname: Kusano
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Koike
authors.forename: Michio
authors.initials: M
authors.lastname: Hongo
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Chiba
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Kinoshita
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000008:administration & dosage*; D000328:Adult; D000897:Anti-Ulcer Agents / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D004942:Esophagitis, Peptic / Q000150:complications / Q000188:drug therapy*; D005260:Female; D005764:Gastroesophageal Reflux / Q000150:complications / Q000188:drug therapy*; D006356:Heartburn / Q000209:etiology / Q000517:prevention & control*; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D054328:Proton Pump Inhibitors / Q000008:administration & dosage*; D064750:Rabeprazole; D012720:Severity of Illness Index; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents; D054328:Proton Pump Inhibitors; D064750:Rabeprazole