Effect of Rebamipide on the Premalignant Progression of Chronic Gastritis: A Randomized Controlled Study

Clin Drug Investig. 2015 Oct;35(10):665-73. doi: 10.1007/s40261-015-0329-z.

Abstract

Background and objective: Chronic gastritis frequently progresses into precancerous intestinal metaplasia and intraepithelial neoplasia lesions. Rebamipide is a free radical scavenger and we assessed its efficacy on clinical symptoms, gastric mucosal lesions, pathologic grade, and immunohistochemistry in chronic gastritis patients.

Methods: 178 eligible patients were randomized into treatment and control groups. Both groups followed an optimized lifestyle for 26 weeks, but the treatment group was additionally medicated with rebamipide 0.1 g three times per day. Upper gastrointestinal endoscopy was performed in all patients to evaluate the severity of gastritis by the Modified Lanza Scoring (MLS) and histological changes were evaluated by the Updated Sydney System Score (USSS). Gastric mucosa immunohistochemistry in the treatment group was performed using the intestinal metaplasia markers caudal type homeobox transcription factor 2 (CDX2) and trefoil factor 3 (TFF3) detection.

Results: There were significant outcome differences between the treatment and control groups regarding the clinical symptom scores (2.62 ± 1.86 vs. 1.55 ± 1.61, P = 0.0001), gastric mucosal lesion scores (0.57 ± 1.05 vs. 0.16 ± 0.90, P = 0.002), and inflammation (P < 0.05). Only in the treated patients were the rates of intestinal metaplasia (P = 0.017 vs. P = 0.123) and low-grade intraepithelial neoplasia (P = 0.005 vs. P = 0.226) significantly reduced after 26 weeks. The percentages of CDX2 (31.5 vs. 15.7%, P = 0.021) and TFF3 (44.9 vs. 25.8%, P = 0.012) expressing gastric mucosa cells were significantly lower after rebamipide medication than pre-treatment values.

Conclusions: Rebamipide improved the clinical symptoms, gastric mucosal lesions, and pathological grades of chronic gastritis patients and decreased the expression rates of CDX2 and TFF3 in gastric cells.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Alanine / analogs & derivatives*
  • Alanine / therapeutic use
  • CDX2 Transcription Factor
  • Disease Progression*
  • Female
  • Gastric Mucosa / drug effects*
  • Gastric Mucosa / metabolism
  • Gastric Mucosa / pathology
  • Gastritis / drug therapy*
  • Gastritis / pathology*
  • Helicobacter Infections / drug therapy*
  • Helicobacter Infections / pathology*
  • Homeodomain Proteins / metabolism
  • Humans
  • Male
  • Metaplasia / drug therapy
  • Metaplasia / pathology
  • Middle Aged
  • Peptides / metabolism
  • Precancerous Conditions / drug therapy*
  • Precancerous Conditions / pathology
  • Quinolones / therapeutic use*
  • Stomach Neoplasms / drug therapy
  • Stomach Neoplasms / pathology
  • Trefoil Factor-3

Substances

  • CDX2 Transcription Factor
  • CDX2 protein, human
  • Homeodomain Proteins
  • Peptides
  • Quinolones
  • TFF3 protein, human
  • Trefoil Factor-3
  • rebamipide
  • Alanine