Thiopurine methyltransferase activity combined with 6-thioguanine metabolite levels predicts clinical response to thiopurines in patients with inflammatory bowel disease

Digestive and Liver Disease

Volumn 40, Issue 6, 2008, Pages 425-432

  Kwan, L Y ^a   Devlin, S M ^a   Mirocha, J M ^a   Papadakis, K A ^a  

^a CEDARS SINAI MEDICAL CENTER   (United States)

Author keywords

Crohn's disease; Inflammatory bowel diseases; Metabolite monitoring; Thiopurines; Ulcerative colitis

Indexed keywords

6 MERCAPTOPURINE DERIVATIVE; AMINOSALICYLIC ACID; AZATHIOPRINE; PREDNISONE; STEROID; THIOPURINE METHYLTRANSFERASE; TIOGUANINE;

ADULT; ARTICLE; CLINICAL ARTICLE; CONTROLLED STUDY; CORRELATION ANALYSIS; CROHN DISEASE; DRUG DOSE REDUCTION; DRUG HYPERSENSITIVITY; DRUG RESPONSE; DRUG WITHDRAWAL; ENZYME ACTIVITY; ENZYME ASSAY; ERYTHROCYTE; FEMALE; HUMAN; LEUKOPENIA; LIVER TOXICITY; MALE; PHENOTYPE; PREDICTION; THROMBOCYTOPENIA; TREATMENT DURATION; ULCERATIVE COLITIS;

6-MERCAPTOPURINE; ADULT; ANTIMETABOLITES, ANTINEOPLASTIC; AZATHIOPRINE; FEMALE; FORECASTING; GUANINE NUCLEOTIDES; HUMANS; INFLAMMATORY BOWEL DISEASES; MALE; METHYLTRANSFERASES; THIONUCLEOTIDES; TREATMENT OUTCOME;

EID: 42649093472     PISSN: 15908658     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.dld.2008.01.003     Document Type: Article

References (34)

1. Cuffari C., Theoret Y., Latour S., and Seidman G. 6-Mercaptopurine metabolism in Crohn's disease: correlation with efficacy and toxicity. Gut 39 (1996) 401-406
2. Dubinsky M.C. Azathioprine, 6-mercaptopurine in inflammatory bowel disease: pharmacology, efficacy, and safety. Clin Gastroenterol Hepatol 2 (2004) 731-743
3. Sandborn W.J. A review of immune modifier therapy for inflammatory bowel disease: azathioprine, 6-mercaptopurine, cyclosporine, and methotrexate. Am J Gastroenterol 91 (1996) 423-433
4. Ardizzone S., Maconi G., Russo A., Imbesi V., Colombo E., and Bianchi Porro G. Randomised controlled trial of azathioprine and 5-aminosalicylic acid for treatment of steroid dependent ulcerative colitis. Gut 55 (2006) 47-53
5. Lennard L. TPMT in the treatment of Crohn's disease with azathioprine. Gut 51 (2002) 143-146
6. Aarbakke J., Janka-Schaub G., and Elion G.B. Thiopurine biology and pharmacology. Trends Pharmacol Sci 18 (1997) 3-7
7. Tiede I., Fritz G., Strand S., Poppe D., Dvorsky R., Strand D., et al. CD28-dependent Rac1 activation is the molecular target of azathioprine in primary human CD4+ T lymphocytes. J Clin Invest 111 (2003) 1133-1145
8. Thomas C.W., Myhre G.M., Tschumper R., Sreekumar R., Jelinek D., McKean D.J., et al. Selective inhibition of inflammatory gene expression in activated T lymphocytes: a mechanism of immune suppression by thiopurines. J Pharmacol Exp Ther 312 (2005) 537-545
9. Dubinsky M.C., Lamothe S., Yang H.Y., Targan S.R., Sinnett D., Theoret Y., et al. Pharmacogenomics and metabolite measurement for 6-mercaptopurine therapy in inflammatory bowel disease. Gastroenterology 118 (2000) 705-713
10. Weinshilboum R.M., and Sladek S.L. Mercaptopurine pharmacogenetics: monogenic inheritance of erythrocyte thiopurine methyltransferase activity. Am J Hum Genet 32 (1980) 651-662
11. Otterness D., Szumlanski C., Lennard L., Klemetsdal B., Aarbakke J., Park-Hah J.O., et al. Human thiopurine methyltransferase pharmacogenetics: gene sequence polymorphisms. Clin Pharmacol Ther 62 (1997) 60-73
12. Hindorf U., Lindqvist M., Peterson C., Soderkvist P., Strom M., Hjortswang H., et al. Pharmacogenetics during standardised initiation of thiopurine treatment in inflammatory bowel disease. Gut 55 (2006) 1423-1431
13. Lennard L., and Lilleyman J.S. Variable mercaptopurine metabolism and treatment outcome in childhood lymphoblastic leukemia. J Clin Oncol 7 (1989) 1816-1823
14. Colombel J.F., Ferrari N., Debuysere H., Marteau P., Gendre J.P., Bonaz B., et al. Genotypic analysis of thiopurine S-methyltransferase in patients with Crohn's disease and severe myelosuppression during azathioprine therapy. Gastroenterology 118 (2000) 1025-1030
15. Dubinsky M.C., Yang H., Hassard P.V., Seidman E.G., Kam L.Y., Abreu M.T., et al. 6-MP metabolite profiles provide a biochemical explanation for 6-MP resistance in patients with inflammatory bowel disease. Gastroenterology 122 (2002) 904-915
16. Sandborn W.J., Tremaine W.J., Wolf D.C., Targan S.R., Sninsky C.A., Sutherland L.R., et al. Lack of effect of intravenous administration on time to respond to azathioprine for steroid-treated Crohn's disease. North American Azathioprine Study Group. Gastroenterology 117 (1999) 527-535
17. Ansari A., Hassan C., Duley J., Marinaki A., Shobowale-Bakre E.M., Seed P., et al. Thiopurine methyltransferase activity and the use of azathioprine in inflammatory bowel disease. Aliment Pharmacol Ther 16 (2002) 1743-1750
18. Belaiche J., Desager J.P., Horsmans Y., and Louis E. Therapeutic drug monitoring of azathioprine and 6-mercaptopurine metabolites in Crohn disease. Scand J Gastroenterol 36 (2001) 71-76
19. Lowry P.W., Franklin C.L., Weaver A.L., Pike M.G., Mays D.C., Tremaine W.J., et al. Measurement of thiopurine methyltransferase activity and azathioprine metabolites in patients with inflammatory bowel disease. Gut 49 (2001) 665-670
20. Campbell S., Kingstone K., and Ghosh S. Relevance of thiopurine methyltransferase activity in inflammatory bowel disease patients maintained on low-dose azathioprine. Aliment Pharmacol Ther 16 (2002) 389-398
21. Cuffari C., Dassopoulos T., Turnbough L., Thompson R.E., and Bayless T.M. Thiopurine methyltransferase activity influences clinical response to azathioprine in inflammatory bowel disease. Clin Gastroenterol Hepatol 2 (2004) 410-417
22. Gisbert J.P., Nino P., Rodrigo L., Cara C., and Guijarro L.G. Thiopurine methyltransferase (TPMT) activity and adverse effects of azathioprine in inflammatory bowel disease: long-term follow-up Study of 394 Patients. Am J Gastroenterol 101 (2006) 2769-2776
23. Sayani F.A., Prosser C., Bailey R.J., Jacobs P., and Fedorak R.N. Thiopurine methyltransferase enzyme activity determination before treatment of inflammatory bowel disease with azathioprine: effect on cost and adverse events. Can J Gastroenterol 19 (2005) 147-151
24. Harvey R.F., and Bradshaw J.M. A simple index of Crohn's-disease activity. Lancet 1 (1980) 514
25. Walmsley R.S., Ayres R.C., Pounder R.E., and Allan R.N. A simple clinical colitis activity index. Gut 43 (1998) 29-32
26. Kroplin T., Weyer N., Gutsche S., and Iven H. Thiopurine S-methyltransferase activity in human erythrocytes: a new HPLC method using 6-thioguanine as substrate. Eur J Clin Pharmacol 54 (1998) 265-271
27. Lennard L., and Singleton H.J. High-performance liquid chromatographic assay of human red blood cell thiopurine methyltransferase activity. J Chromatogr B Biomed Appl 661 (1994) 25-33
28. Neurath M.F., Kiesslich R., Teichgraber U., Fischer C., Hofmann U., Eichelbaum M., et al. 6-Thioguanosine diphosphate and triphosphate levels in red blood cells and response to azathioprine therapy in Crohn's disease. Clin Gastroenterol Hepatol 3 (2005) 1007-1014
29. Osterman M.T., Kundu R., Lichtenstein G.R., and Lewis J.D. Association of 6-thioguanine nucleotide levels and inflammatory bowel disease activity: a meta-analysis. Gastroenterology 130 (2006) 1047-1053
30. Coulthard S.A., Hogarth L.A., Little M., Matheson E.C., Redfern C.P., Minto L., et al. The effect of thiopurine methyltransferase expression on sensitivity to thiopurine drugs. Mol Pharmacol 62 (2002) 102-109
31. Dervieux T., Blanco J.G., Krynetski E.Y., Vanin E.F., Roussel M.F., and Relling M.V. Differing contribution of thiopurine methyltransferase to mercaptopurine versus thioguanine effects in human leukemic cells. Cancer Res 61 (2001) 5810-5816
32. Hande S., Wilson-Rich N., Bousvaros A., Zholudev A., Maurer R., Banks P., et al. 5-aminosalicylate therapy is associated with higher 6-thioguanine levels in adults and children with inflammatory bowel disease in remission on 6-mercaptopurine or azathioprine. Inflamm Bowel Dis 12 (2006) 251-257
33. Lowry P.W., Franklin C.L., Weaver A.L., Szumlanski C.L., Mays D.C., Loftus E.V., et al. Leucopenia resulting from a drug interaction between azathioprine or 6-mercaptopurine and mesalamine, sulphasalazine, or balsalazide. Gut 49 (2001) 656-664
34. Dubinsky M.C., Reyes E., Ofman J., Chiou C.F., Wade S., and Sandborn W.J. A cost-effectiveness analysis of alternative disease management strategies in patients with Crohn's disease treated with azathioprine or 6-mercaptopurine. Am J Gastroenterol 100 (2005) 2239-2247