6-Tioguanine monitoring in steroid-dependent patients with inflammatory bowel diseases receiving azathioprine
Article first published online: 24 MAR 2005
Alimentary Pharmacology & Therapeutics
Volume 21, Issue 7, pages 829–839, April 2005
How to Cite
Roblin, X., Serre-Debeauvais, F., Phelip, J.-M., Faucheron, J.-L., Hardy, G., Chartier, A., Helluwaert, F., Bessard, G. and Bonaz, B. (2005), 6-Tioguanine monitoring in steroid-dependent patients with inflammatory bowel diseases receiving azathioprine. Alimentary Pharmacology & Therapeutics, 21: 829–839. doi: 10.1111/j.1365-2036.2005.02419.x
- Issue published online: 24 MAR 2005
- Article first published online: 24 MAR 2005
- Accepted for publication 28 January 2005
Background : 6-Thioguanine (6-tioguanine) nucleotides are the active metabolites of azathioprine.
Aim : The aim of the study was to evaluate the rate of clinical remission without steroids in steroid-dependent Crohn's disease and ulcerative colitis patients receiving azathioprine, the medium- and long-term efficacy and the predictive factors of clinical response when monitoring 6-tioguanine.
Methods : Steroid-dependent Crohn's disease and ulcerative colitis patients receiving either azathioprine or not (treated later with a daily dose of 2.5 mg/kg) were prospectively included. 6-Tioguanine was monitored at 1 and 2 months and every 3 months thereafter for 1 year. The azathioprine dose was adapted to reach a 6-tioguanine level of >250 pmol/8 × 108 red blood cells. Thiopurine methyltransferase genotype/phenotype was evaluated in some patients.
Results : A total of 106 patients were prospectively included (70 Crohn's disease, 36 ulcerative colitis). The clinical remission rate without steroids in patients receiving azathioprine, in intention-to-treat analysis, was 72% and 59% at 6 and 12 months, respectively. The remission rate was significantly higher in patients with 6-tioguanine >250 pmol/8 × 108 RBC (86% and 69% at 6 and 12 months, respectively; P < 0.01). No significant difference was observed between Crohn's disease and ulcerative colitis patients whether treated by azathioprine or not on inclusion. In the univariate analysis, the absence of Crohn's disease stenosis, a 6-tioguanine level >250 pmol/8 × 108 RBC, and an increase of erythrocyte mean corpuscular volume were the factors predictive of a favourable clinical response. In the multivariate analysis, only a 6-tioguanine level of >250 pmol/8 × 108 red blood cells was a predictive factor of favourable clinical remission.
Conclusions : Clinical remission without steroids is significantly more likely when monitoring 6-tioguanine so as to reach a level of >250 pmol/8 × 108 red blood cells in steroid-dependent Crohn's disease and ulcerative colitis patients receiving azathioprine (86% and 69% at 6 and 12 months, respectively).