A prospective, open-label trial of 6-thioguanine in patients with ulcerative or indeterminate colitis

Scand J Gastroenterol. 2005 Oct;40(10):1205-13. doi: 10.1080/00365520510023369.

Abstract

Objective: 6-thioguanine (6-TG) has emerged as a promising therapeutic alternative in patients with Crohn's disease intolerant or resistant to azathioprine (AZA) and/or 6-mercaptopurine (6-MP). The aim of the present study was to evaluate the safety and efficacy of 6-TG in patients with ulcerative colitis (UC) or indeterminate colitis (IC) intolerant or resistant to AZA/6-MP.

Material and methods: Twenty patients with an acute flare, steroid-dependent or steroid-refractory disease attending our outpatient department were included in the study. Measurement of 6-TG nucleotide levels was done to check compliance. Complete, partial and non-response were defined by means of the clinical activity index and the daily steroid demand. Secondary outcome parameters included changes in cumulative steroid doses, C-reactive protein (CRP) levels, and an endoscopic score.

Results: Out of 20 patients 4 were excluded owing to noncompliance; 2/16 compliant patients (13%) had to be prematurely withdrawn because of adverse events, which ceased upon drug discontinuation. By per-protocol analysis, 5/14 patients (36%) were complete, 6/14 (43%) partial and 3/14 (21%) non-responders. In addition to the reduction of the cumulative steroid dose over 3 months, CRP decreased in the study population and the endoscopic score decreased in treatment responders.

Conclusions: Treatment with 6-TG was effective in patients with UC or IC previously intolerant or resistant to AZA/6-MP. Future work is needed to define a subpopulation of patients at low risk for its potential hepatotoxicity, which we assume will benefit from 6-TG.

Publication types

  • Clinical Trial
  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / adverse effects
  • Anti-Inflammatory Agents / therapeutic use*
  • Azathioprine / adverse effects
  • Azathioprine / metabolism
  • Biomarkers / blood
  • C-Reactive Protein / metabolism
  • Colitis, Ulcerative / blood
  • Colitis, Ulcerative / drug therapy*
  • Colitis, Ulcerative / metabolism
  • Dose-Response Relationship, Drug
  • Endoscopy, Gastrointestinal
  • Female
  • Genotype
  • Guanine Nucleotides / blood
  • Humans
  • Male
  • Mercaptopurine / adverse effects
  • Mercaptopurine / metabolism
  • Methylthioinosine / blood
  • Methyltransferases / genetics
  • Methyltransferases / metabolism
  • Middle Aged
  • Orosomucoid / metabolism
  • Patient Compliance
  • Prospective Studies
  • Quality of Life
  • Thioguanine / administration & dosage
  • Thioguanine / adverse effects
  • Thioguanine / therapeutic use*
  • Thionucleotides / blood
  • Treatment Outcome

Substances

  • Anti-Inflammatory Agents
  • Biomarkers
  • Guanine Nucleotides
  • Orosomucoid
  • Thionucleotides
  • 6-thioguanylic acid
  • Methylthioinosine
  • C-Reactive Protein
  • Mercaptopurine
  • Methyltransferases
  • thiopurine methyltransferase
  • Thioguanine
  • Azathioprine