title: Efficacy of twice-daily rabeprazole for reflux esophagitis patients refractory to standard once-daily administration of PPI: the Japan-based TWICE study.
abstract: OBJECTIVE
  Approximately 10% of patients with reflux esophagitis (RE) are not cured with the standard 8-week q.d. regimen with a proton pump inhibitor (PPI). Thus, b.i.d. dosing is often used in refractory RE (rRE) patients, although there has been no report of endoscopically confirmed healing with b.i.d. dosing of PPIs. This study aimed to assess the efficacy and safety of 8-week therapy with rabeprazole (RPZ) sodium at 20 mg b.i.d. or 10 mg b.i.d. as compared with RPZ at 20 mg q.d. in patients with RE refractory to the standard PPI regimen in Japan.
  
  
  METHODS
  Endoscopically confirmed rRE patients (Los Angeles grade A-D) who had received a standard PPI regimen for at least 8 weeks were randomized in a double-blind manner into groups receiving RPZ at 20 and 10 mg b.i.d. or 20 mg q.d. (control) daily for up to 8 weeks. The primary efficacy endpoint was the rate of endoscopically confirmed healing after week 8.
  
  
  RESULTS
  A total of 337 rRE patients treated at 71 sites were randomized. The rate of endoscopically confirmed healing after 8 weeks was significantly higher in those who received RPZ at 20 mg b.i.d. (77.0%, P = 0.003) and 10 mg b.i.d. (78.4%, P = 0.001) as compared with 20 mg q.d. (58.8%), and the rates of resolution of heartburn after week 8 were 80.0%, 74.0%, and 56.4%, respectively. All treatment regimens were well tolerated.
  
  
  CONCLUSIONS
  Regimens of RPZ at 20 and 10 mg b.i.d. for 8 weeks were more effective than 20 mg q.d. with regard to endoscopically confirmed healing and symptom resolution of RE refractory to a standard PPI regimen.
authors.affiliation: Department of Gastroenterology and Hepatology, Shimane University School of Medicine, Izumo, Shimane, Japan.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Kinoshita
authors.forename: Michio
authors.initials: M
authors.lastname: Hongo
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004311:Double-Blind Method; D004942:Esophagitis, Peptic / Q000188:drug therapy*; D004945:Esophagoscopy; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D054328:Proton Pump Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D064750:Rabeprazole; D016896:Treatment Outcome
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents; D054328:Proton Pump Inhibitors; D064750:Rabeprazole