Monitoring and safety of azathioprine therapy in inflammatory bowel disease

Pediatric Gastroenterology, Hepatology and Nutrition

Volumn 16, Issue 2, 2013, Pages 65-70

  Kim, Mi Jin ^a   Choe, Yon Ho ^b  

^a Inje University College of Medicine   (South Korea)

^b Sungkyunkwan University School of Medicine   (South Korea)

Author keywords

Azathioprine; Inflammatory bowel diseases

Indexed keywords

EID: 84900427844     PISSN: 22348646     EISSN: 22348840     Source Type: Journal    
DOI: 10.5223/pghn.2013.16.2.65     Document Type: Article

References (58)

1. Sandborn W, Sutherland L, Pearson D, May G, Modigliani R, Prantera C. Azathioprine or 6-mercaptopurine for inducing remission of Crohn's disease. Cochrane Database Syst Rev 2000;(2):CD000545.
2. Hibi T, Ogata H. Novel pathophysiological concepts of inflammatory bowel disease. J Gastroenterol 2006;41:10-6.
3. Hindorf U, Lindqvist M, Peterson C, Söderkvist P, Ström M, Hjortswang H, et al. Pharmacogenetics during standardised initiation of thiopurine treatment in inflammatory bowel disease. Gut 2006;55:1423-31.
4. Gearry RB, Barclay ML, Burt MJ, Collett JA, Chapman BA. Thiopurine drug adverse effects in a population of New Zealand patients with inflammatory bowel disease. Pharmacoepidemiol Drug Saf 2004;13:563-7.
5. Goldenberg BA, Rawsthorne P, Bernstein CN. The utility of 6-thioguanine metabolite levels in managing patients with inflammatory bowel disease. Am J Gastroenterol 2004;99:1744-8.
6. Cuffari C, Hunt S, Bayless T. Utilisation of erythrocyte 6-thioguanine metabolite levels to optimise azathioprine therapy in patients with inflammatory bowel disease. Gut 2001;48:642-6.
7. Derijks LJ, Gilissen LP, Hooymans PM, Hommes DW. Review article: thiopurines in inflammatory bowel disease. Aliment Pharmacol Ther 2006;24:715-29.
8. Zelinkova Z, Derijks LJ, Stokkers PC, Vogels EW, van Kampen AH, Curvers WL, et al. Inosine triphosphate pyrophosphatase and thiopurine s-methyltransferase genotypes relationship to azathioprine-induced myelosuppression. Clin Gastroenterol Hepatol 2006;4:44-9.
9. Gearry RB, Barclay ML. Azathioprine and 6-mercaptopurine pharmacogenetics and metabolite monitoring in inflammatory bowel disease. J Gastroenterol Hepatol 2005;20:1149-57.
10. Sahasranaman S, Howard D, Roy S. Clinical pharmacology and pharmacogenetics of thiopurines. Eur J Clin Pharmacol 2008;64:753-67.
11. Sandborn WJ. Rational dosing of azathioprine and 6-mercaptopurine. Gut 2001;48:591-2.
12. Palmieri O, Latiano A, Bossa F, Vecchi M, D'Incà R, Guagnozzi D, et al. Sequential evaluation of thiopurine methyltransferase, inosine triphosphate pyrophosphatase, and HPRT1 genes polymorphisms to explain thiopurines' toxicity and efficacy. Aliment Pharmacol Ther 2007;26:737-45.
13. Dubinsky MC, Lamothe S, Yang HY, Targan SR, Sinnett D, Théorêt Y, et al. Pharmacogenomics and metabolite measurement for 6-mercaptopurine therapy in inflammatory bowel disease. Gastroenterology 2000;118:705-13.
14. Ooi CY, Bohane TD, Lee D, Naidoo D, Day AS. Thiopurine metabolite monitoring in paediatric inflammatory bowel disease. Aliment Pharmacol Ther 2007;25:941-7.
15. Wright S, Sanders DS, Lobo AJ, Lennard L. Clinical significance of azathioprine active metabolite concentrations in inflammatory bowel disease. Gut 2004;53: 1123-8.
16. Dubinsky MC. Optimizing immunomodulator therapy for inflammatory bowel disease. Curr Gastroenterol Rep 2003;5:506-11.
17. Dubinsky MC, Yang H, Hassard PV, Seidman EG, Kam LY, Abreu MT, et al. 6-MP metabolite profiles provide a biochemical explanation for 6-MP resistance in patients with inflammatory bowel disease. Gastroenterology 2002;122:904-15.
18. Derijks LJ, Gilissen LP, Engels LG, Bos LP, Bus PJ, Lohman JJ, et al. Pharmacokinetics of 6-mercaptopurine in patients with inflammatory bowel disease: implications for therapy. Ther Drug Monit 2004;26:311-8.
19. Haines ML, Ajlouni Y, Irving PM, Sparrow MP, Rose R, Gearry RB, et al. Clinical usefulness of therapeutic drug monitoring of thiopurines in patients with inadequately controlled inflammatory bowel disease. Inflamm Bowel Dis 2011;17:1301-7.
20. Lichtenstein GR, Abreu MT, Cohen R, Tremaine W; American Gastroenterological Association. American Gastroenterological Association Institute medical position statement on corticosteroids, immunomodulators, and infliximab in inflammatory bowel disease. Gastroenterology 2006;130:935-9.
21. Dignass A, Van Assche G, Lindsay JO, Lémann M, Söderholm J, Colombel JF, et al; European Crohn's and Colitis Organisation (ECCO). The second European evidence-based Consensus on the diagnosis and management of Crohn's disease: current management. J Crohns Colitis 2010;4:28-62.
22. Andoh A, Tsujikawa T, Ban H, Hashimoto T, Bamba S, Ogawa A, et al. Monitoring 6-thioguanine nucleotide concentrations in Japanese patients with inflammatory bowel disease. J Gastroenterol Hepatol 2008;23:1373-7.
23. Komiyama T, Yajima T, Kubota R, Iwao Y, Sakuraba A, Funakoshi S, et al. Lower doses of 6-mercaptopurine/azathioprine bring enough clinical efficacy and therapeutic concentration of erythrocyte 6-mercaptopurine metabolite in Japanese IBD patients. J Crohns Colitis 2008;2:315-21.
24. Ohtsuka Y, Arai K, Aoyagi Y, Fujii T, Yamakawa Y, Ohtani K, et al. Monitoring 6-thioguanine nucleotide concentrations in Japanese children and adolescents with inflammatory bowel disease. J Gastroenterol Hepatol 2010;25:1626-30.
25. Schwab M, Schäffeler E, Marx C, Fischer C, Lang T, Behrens C, et al. Azathioprine therapy and adverse drug reactions in patients with inflammatory bowel disease: impact of thiopurine S-methyltransferase polymorphism. Pharmacogenetics 2002;12:429-36.
26. Lewis LD, Benin A, Szumlanski CL, Otterness DM, Lennard L, Weinshilboum RM, et al. Olsalazine and 6-mercaptopurine-related bone marrow suppression: a possible drug-drug interaction. Clin Pharmacol Ther 1997;62:464-75.
27. Green JR. Balsalazide and azathioprine or 6-mercaptopurine. Gastroenterology 1999;117:1513-4.
28. Kennedy DT, Hayney MS, Lake KD. Azathioprine and allopurinol: the price of an avoidable drug interaction. Ann Pharmacother 1996;30:951-4.
29. Roblin X, Serre-Debeauvais F, Phelip JM, Bessard G, Bonaz B. Drug interaction between infliximab and azathioprine in patients with Crohn's disease. Aliment Pharmacol Ther 2003;18:917-25.
30. Schaeffeler E, Fischer C, Brockmeier D, Wernet D, Moerike K, Eichelbaum M, et al. Comprehensive analysis of thiopurine S-methyltransferase phenotype-genotype correlation in a large population of German-Caucasians and identification of novel TPMT variants. Pharmacogenetics 2004;14:407-17.
31. Weinshilboum RM, Sladek SL. Mercaptopurine pharmacogenetics: monogenic inheritance of erythrocyte thiopurine methyltransferase activity. Am J Hum Genet 1980;32:651-62.
32. Derijks LJ, Wong DR. Pharmacogenetics of thiopurines in inflammatory bowel disease. Curr Pharm Des 2010;16:145-54.
33. Hon YY, Fessing MY, Pui CH, Relling MV, Krynetski EY, Evans WE. Polymorphism of the thiopurine S-methyltransferase gene in African-Americans. Hum Mol Genet 1999;8:371-6.
34. Otterness D, Szumlanski C, Lennard L, Klemetsdal B, Aarbakke J, Park-Hah JO, et al. Human thiopurine methyltransferase pharmacogenetics: gene sequence polymorphisms. Clin Pharmacol Ther 1997;62:60-73.
35. Yates CR, Krynetski EY, Loennechen T, Fessing MY, Tai HL, Pui CH, et al. Molecular diagnosis of thiopurine S-methyltransferase deficiency: genetic basis for azathioprine and mercaptopurine intolerance. Ann Intern Med 1997;126:608-14.
36. Cao Q, Zhu Q, Shang Y, Gao M, Si J. Thiopurine methyltransferase gene polymorphisms in Chinese patients with inflammatory bowel disease. Digestion 2009;79: 58-63.
37. Zhu Q, Cao Q. Thiopurine methyltransferase gene polymorphisms and activity in Chinese patients with inflammatory bowel disease treated with azathioprine. Chin Med J (Engl) 2012;125:3665-70.
38. Hibi T, Naganuma M, Kitahora T, Kinjyo F, Shimoyama T. Low-dose azathioprine is effective and safe for maintenance of remission in patients with ulcerative colitis. J Gastroenterol 2003;38:740-6.
39. Kim S, Lee HW, Lee W, Chun S, Min WK. Validation of new allele-specific real-time PCR system for thiopurine methyltransferase genotyping in Korean population. Biomed Res Int 2013;2013:305704.
40. Kim JH, Cheon JH, Hong SS, Eun CS, Byeon JS, Hong SY, et al. Influences of thiopurine methyltransferase genotype and activity on thiopurine-induced leukopenia in Korean patients with inflammatory bowel disease: a retrospective cohort study. J Clin Gastroenterol 2010;44:e242-8.
41. Jung YS, Cheon JH, Park JJ, Moon CM, Kim ES, Lee JH, et al. Correlation of genotypes for thiopurine methyltransferase and inosine triphosphate pyrophosphatase with long-term clinical outcomes in Korean pa tients with inflammatory bowel diseases during treatment with thiopurine drugs. J Hum Genet 2010;55:121-3.
42. Lennard L, Van Loon JA, Lilleyman JS, Weinshilboum RM. Thiopurine pharmacogenetics in leukemia: correlation of erythrocyte thiopurine methyltransferase activity and 6-thioguanine nucleotide concentrations. Clin Pharmacol Ther 1987;41:18-25.
43. Lennard L, Van Loon JA, Weinshilboum RM. Pharmacogenetics of acute azathioprine toxicity: relationship to thiopurine methyltransferase genetic polymorphism. Clin Pharmacol Ther 1989;46:149-54.
44. Cuffari C, Dassopoulos T, Turnbough L, Thompson RE, Bayless TM. Thiopurine methyltransferase activity influences clinical response to azathioprine in inflammatory bowel disease. Clin Gastroenterol Hepatol 2004;2:410-7.
45. Lennard L, Lilleyman JS, Van Loon J, Weinshilboum RM. Genetic variation in response to 6-mercaptopurine for childhood acute lymphoblastic leukaemia. Lancet 1990;336:225-9.
46. Hindorf U, Lindqvist M, Hildebrand H, Fagerberg U, Almer S. Adverse events leading to modification of therapy in a large cohort of patients with inflammatory bowel disease. Aliment Pharmacol Ther 2006;24:331-42.
47. Prefontaine E, Macdonald JK, Sutherland LR. Azathioprine or 6-mercaptopurine for induction of remission in Crohn's disease. Cochrane Database Syst Rev 2009;(4):CD000545.
48. Fraser AG, Orchard TR, Jewell DP. The efficacy of azathioprine for the treatment of inflammatory bowel disease: a 30 year review. Gut 2002;50:485-9.
49. Derijks LJ, Gilissen LP, Engels LG, Bos LP, Bus PJ, Lohman JJ, et al. Pharmacokinetics of 6-thioguanine in patients with inflammatory bowel disease. Ther Drug Monit 2006;28:45-50.
50. Haglund S, Taipalensuu J, Peterson C, Almer S. IMPDH activity in thiopurine-treated patients with inflammatory bowel disease-relation to TPMT activity and metabolite concentrations. Br J Clin Pharmacol 2008;65:69-77.
51. Gilissen LP, Derijks LJ, Bos LP, Bus PJ, Hooymans PM, Engels LG. Therapeutic drug monitoring in patients with inflammatory bowel disease and established azathioprine therapy. Clin Drug Investig 2004;24:479-86.
52. Kandiel A, Fraser AG, Korelitz BI, Brensinger C, Lewis JD. Increased risk of lymphoma among inflammatory bowel disease patients treated with azathioprine and 6-mercaptopurine. Gut 2005;54:1121-5.
53. Kotlyar DS, Osterman MT, Diamond RH, Porter D, Blonski WC, Wasik M, et al. A systematic review of factors that contribute to hepatosplenic T-cell lymphoma in patients with inflammatory bowel disease. Clin Gastroenterol Hepatol 2011;9:36-41.
54. Shale M, Kanfer E, Panaccione R, Ghosh S. Hepatosplenic T cell lymphoma in inflammatory bowel disease. Gut 2008;57:1639-41.
55. Belhadj K, Reyes F, Farcet JP, Tilly H, Bastard C, Angonin R, et al. Hepatosplenic gammadelta T-cell lymphoma is a rare clinicopathologic entity with poor outcome: report on a series of 21 patients. Blood 2003;102:4261-9.
56. Tey SK, Marlton PV, Hawley CM, Norris D, Gill DS. Post-transplant hepatosplenic T-cell lymphoma successfully treated with HyperCVAD regimen. Am J Hematol 2008;83:330-3.
57. François A, Lesesve JF, Stamatoullas A, Comoz F, Lenormand B, Etienne I, et al. Hepatosplenic gamma/delta T-cell lymphoma: a report of two cases in immunocompromised patients, associated with isochromosome 7q. Am J Surg Pathol 1997;21:781-90.
58. Armstrong RG, West J, Card TR. Risk of cancer in inflammatory bowel disease treated with azathioprine: a UK population-based case-control study. Am J Gastroenterol 2010;105:1604-9.