Thioguanine-nucleotides do not predict efficacy of tioguanine in Crohn's disease
Article first published online: 4 JUN 2004
Alimentary Pharmacology & Therapeutics
Volume 19, Issue 12, pages 1269–1276, June 2004
How to Cite
Herrlinger, K. R., Fellermann, K., Fischer, C., Kreisel, W., Deibert, P., Schoelmerich, J., Fleig, W. E., Ruhl, A., Reinshagen, M., Greinwald, R., Stange, E. F. and Schwab, M. (2004), Thioguanine-nucleotides do not predict efficacy of tioguanine in Crohn's disease. Alimentary Pharmacology & Therapeutics, 19: 1269–1276. doi: 10.1111/j.1365-2036.2004.01947.x
- Issue published online: 4 JUN 2004
- Article first published online: 4 JUN 2004
- Accepted for publication 17 March 2004
Background : 6-Thioguanine-nucleotides seem to be the active metabolites of thiopurine therapy, and their monitoring has been considered a useful tool for optimizing response in inflammatory bowel diseases. Tioguanine (thioguanine) therapy results in much higher levels of 6-thioguanine-nucleotide levels when compared with azathioprine or mercaptopurine.
Aim : To elucidate the influence of 6-thioguanine-nucleotide and methylated 6-thioguanine-nucleotide levels under tioguanine on efficacy and toxicity in Crohn's disease.
Methods : 6-Thioguanine-nucleotide and methylated 6-tioguanine-nucleotide levels were measured regularly in 26 Crohn's disease patients treated with tioguanine. Nucleotide levels were related to efficacy and toxicity.
Results : 6-Thioguanine-nucleotide levels rose very high [median 1241 pmol/8 × 108 red blood cells (range 313–1853)]. Methylated 6-thioguanine-nucleotide levels were detected in all patients [491 pmol/8 × 108 red blood cells (154–1775)]. 6-Thioguanine-nucleotide and methylated 6-thioguanine-nucleotide concentrations correlated significantly (r = 0.7, P < 0.0001). Nucleotide levels from patients achieving remission (n = 14) did not differ significantly from non-remitters (n = 12) [6-thioguanine-nucleotide: 1077 (599–2160) vs. 1210 (534–4665); methylated 6-thioguanine-nucleotide: 510 (214–1222) vs. 421 (145–1284)]. One patient with intermediate thiopurine S-methyltransferase activity experienced bone marrow toxicity upon dose escalation parallel with excessively high thioguanine-nucleotide levels.
Conclusions : 6-Thioguanine-nucleotide as well as methylated 6-thioguanine-nucleotide levels under tioguanine therapy were not related to efficacy. This suggests that monitoring of 6-thioguanine-nucleotide levels is not a useful tool to predict response to thiopurines.