Higher Thioguanine Nucleotide Metabolite Levels are Associated With Better Long-term Outcomes in Patients With Inflammatory Bowel Diseases

J Clin Gastroenterol. 2018 Jul;52(6):537-544. doi: 10.1097/MCG.0000000000000889.


Goals: The aim of this study was to assess whether sustained 6-thioguaninenucleotide (6-TGN) levels were associated with improved long-term outcomes in patients with inflammatory bowel diseases (IBD).

Background: Cross-sectional data have shown that thiopurine metabolites are correlated with clinical efficacy in patient receiving thiopurines for IBD but the role for serial measurements through treatment course is unclear.

Study: We conducted a retrospective cohort study including patients with IBD on thiopurine monotherapy and had serial 6-TGN levels measured. Predictive variables included demographics, disease phenotype, 6-TGN levels (nadir, median, and peak levels). The primary outcome was the development of a disease relapse. The secondary outcome was the need for IBD surgery.

Results: Two hundred eighteen 6-TGN samples from 87 patients were analyzed. Nadir and median 6-TGN levels were significantly higher in patients who did not relapse [185 and 233 pmol per 8×10 red blood cells (RBCs)] as compared with levels in patients who did relapse (150 and 167 pmol per 8×10 RBCs, P=0.025) but there was no significant difference in peak 6-TGN level. When adjusted for confounding factors, a nadir 6-TGN level ≥161 and a median 6-TGN level ≥264 were associated with a significant decrease in the rate of disease exacerbation (hazard ratio: 0.5; 95% confidence interval, 0.26-0.87; P=0.016 and hazard ratio: 0.4; 95% confidence interval, 0.2-0.82; P=0.14).

Conclusions: Serial thiopurine metabolite level assessments and dose adjustment aiming to maintain higher 6-TGN levels may be helpful to improve long-term outcomes in patients with IBD.

MeSH terms

  • Adult
  • Anti-Inflammatory Agents / therapeutic use*
  • Azathioprine / therapeutic use*
  • Biomarkers / blood
  • Colitis, Ulcerative / blood
  • Colitis, Ulcerative / diagnosis
  • Colitis, Ulcerative / drug therapy*
  • Crohn Disease / blood
  • Crohn Disease / diagnosis
  • Crohn Disease / drug therapy*
  • Digestive System Surgical Procedures
  • Drug Monitoring / methods*
  • Female
  • Gastrointestinal Agents / therapeutic use*
  • Guanine Nucleotides / blood*
  • Humans
  • Longitudinal Studies
  • Male
  • Mercaptopurine / therapeutic use*
  • Middle Aged
  • Predictive Value of Tests
  • Recurrence
  • Remission Induction
  • Retrospective Studies
  • Thionucleotides / blood*
  • Time Factors
  • Treatment Outcome
  • Up-Regulation
  • Young Adult


  • Anti-Inflammatory Agents
  • Biomarkers
  • Gastrointestinal Agents
  • Guanine Nucleotides
  • Thionucleotides
  • 6-thioguanylic acid
  • Mercaptopurine
  • Azathioprine