Difficulties and possibilities with thiopurine therapy in inflammatory bowel disease-Proceedings of the first Thiopurine Task Force meeting

Digestive and Liver Disease

Volumn 43, Issue 4, 2011, Pages 270-276

  Van Asseldonk, Dirk P ^a   Sanderson, Jeremy ^b   de Boer, Nanne K H ^a   Sparrow, Miles P ^c   Lémann, Marc ^d   Ansari, Azhar ^e   Almer, Sven H ^f   Florin, Timothy H J ^g   Gearry, Richard B ^h   Mulder, Chris J ^a   Mantzaris, Gerassimos ⁱ   van Bodegraven, Ad A ^a  

^a VU UNIVERSITY MEDICAL CENTER   (Netherlands)

^b GUY'S AND ST THOMAS' NHS FOUNDATION TRUST   (United Kingdom)

^c ALFRED HOSPITAL   (Australia)

^d SAINT LOUIS HOSPITAL   (France)

^e EAST SURREY HOSPITAL   (United Kingdom)

^f LINKÖPING UNIVERSITY   (Sweden)

^g UNIVERSITY OF QUEENSLAND   (Australia)

^h UNIVERSITY OF OTAGO   (New Zealand)

ⁱ Evangelisms Hospital   (Greece)

Author keywords

Adverse events; Inflammatory bowel disease; Therapeutic drug monitoring; Thiopurines

Indexed keywords

6 METHYL MERCAPTOPURINE RIBONUCLEOTIDE; 6 THIOGUANINE NUCLEOTIDE; ALLOPURINOL; AMINOSALICYLIC ACID; AZATHIOPRINE; DRUG METABOLITE; MERCAPTOPURINE; MESALAZINE; METHYLTRANSFERASE; METRONIDAZOLE; NITROIMIDAZOLE; ORNIDAZOLE; PLACEBO; THIOGUANINE DERIVATIVE; THIOPURINE S METHYL TRANSFERASE; TIOGUANINE; TUMOR NECROSIS FACTOR INHIBITOR; UNCLASSIFIED DRUG;

ANTIBIOTIC PROPHYLAXIS; ARTICLE; BONE MARROW TOXICITY; BURKITT LYMPHOMA; CANCER RISK; CARCINOGENICITY; CELL DAMAGE; COMPUTER MODEL; CROHN DISEASE; CYTOMEGALOVIRUS INFECTION; DISEASE ASSOCIATION; DOSE RESPONSE; DRUG METABOLISM; DRUG MONITORING; DRUG POTENTIATION; DRUG SAFETY; DRUG TOLERABILITY; ENDOTHELIUM CELL; ENZYME ACTIVITY; EPSTEIN BARR VIRUS INFECTION; ERYTHROCYTE; GENOTYPE; HERPES SIMPLEX; HERPES ZOSTER; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; HYPERPLASIA; INFECTION RISK; INFECTION SENSITIVITY; INFORMATION RETRIEVAL; LIVER TOXICITY; LYMPHOMA; MATHEMATICAL PARAMETERS; MEDLINE; METHYLATION; NODULAR REGENERATIVE HYPERPLASIA; OPPORTUNISTIC INFECTION; PANCREATITIS; PERIPHERAL BLOOD MONONUCLEAR CELL; POLYMERASE CHAIN REACTION; PRESCRIPTION; PRIORITY JOURNAL; REMISSION; RISK ASSESSMENT; RISK REDUCTION; SIDE EFFECT; ULCERATIVE COLITIS; VEIN OCCLUSION;

AMINOSALICYLIC ACIDS; DRUG THERAPY, COMBINATION; HUMANS; IMMUNOSUPPRESSIVE AGENTS; INFLAMMATORY BOWEL DISEASES; PURINES;

EID: 79952191733     PISSN: 15908658     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.dld.2010.09.001     Document Type: Article

References (62)

1. Remuzzi G., Lesti M., Gotti E., et al. Mycophenolate mofetil versus azathioprine for prevention of acute rejection in renal transplantation (MYSS): a randomised trial. Lancet 2004, 364:503-512.
2. Yu P., Johnson S., Wang S.T., et al. Cost utility of adalimumab versus infliximab maintenance therapies in the United States for moderately to severely active Crohn's disease. Pharmacoeconomics 2009, 27:609-621.
3. Jharap B., Seinen M.L., De Boer N.K., et al. Thiopurine therapy in inflammatory bowel disease patients: analyses of two 8-year intercept cohorts. Inflamm Bowel Dis 2010, 16:1541-1549.
4. Prefontaine E., Sutherland L.R., MacDonald J.K., et al. Azathioprine or 6-mercaptopurine for maintenance of remission in Crohn's disease. Cochrane Database Syst Rev 2009, CD000067.
5. Timmer A., McDonald J.W., MacDonald J.K. Azathioprine and 6-mercaptopurine for maintenance of remission in ulcerative colitis. Cochrane Database Syst Rev 2007, CD000478.
6. Hindorf U., Johansson M., Eriksson A., et al. Mercaptopurine treatment should be considered in azathioprine intolerant patients with inflammatory bowel disease. Aliment Pharmacol Ther 2009, 29:654-661.
7. Hindorf U., Lindqvist M., Peterson C., et al. Pharmacogenetics during standardised initiation of thiopurine treatment in inflammatory bowel disease. Gut 2006, 55:1423-1431.
8. Colombel J.F., Ferrari N., Debuysere H., et al. Genotypic analysis of thiopurine S-methyltransferase in patients with Crohn's disease and severe myelosuppression during azathioprine therapy. Gastroenterology 2000, 118:1025-1030.
9. Schwab M., Schaeffeler E., Marx C., et al. Shortcoming in the diagnosis of TPMT deficiency in a patient with Crohn's disease using phenotyping only. Gastroenterology 2001, 121:498-499.
10. Duley J.A., Florin T.H. Azathioprine: when less is more. J Gastroenterol Hepatol 2008, 23:1317-1319.
11. Priest V.L., Begg E.J., Gardiner S.J., et al. Pharmacoeconomic analyses of azathioprine, methotrexate and prospective pharmacogenetic testing for the management of inflammatory bowel disease. Pharmacoeconomics 2006, 24:767-781.
12. Dubinsky M.C., Reyes E., Ofman J., et al. A cost-effectiveness analysis of alternative disease management strategies in patients with Crohn's disease treated with azathioprine or 6-mercaptopurine. Am J Gastroenterol 2005, 100:2239-2247.
13. Tiede I., Fritz G., Strand S., et al. CD28-dependent Rac1 activation is the molecular target of azathioprine in primary human CD4+ T lymphocytes. J Clin Invest 2003, 111:1133-1145.
14. Thomas C.W., Myhre G.M., Tschumper R., et al. Selective inhibition of inflammatory gene expression in activated T lymphocytes: a mechanism of immune suppression by thiopurines. J Pharmacol Exp Ther 2005, 312:537-545.
15. Osterman M.T., Kundu R., Lichtenstein G.R., et al. Association of 6-thioguanine nucleotide levels and inflammatory bowel disease activity: a meta-analysis. Gastroenterology 2006, 130:1047-1053.
16. Dubinsky M.C., Lamothe S., Yang H.Y., et al. Pharmacogenomics and metabolite measurement for 6-mercaptopurine therapy in inflammatory bowel disease. Gastroenterology 2000, 118:705-713.
17. Gearry R.B., Barclay M.L. Azathioprine and 6-mercaptopurine pharmacogenetics and metabolite monitoring in inflammatory bowel disease. J Gastroenterol Hepatol 2005, 20:1149-1157.
18. Duley J.A., Florin T.H.J. Thiopurine therapies: problems, complexities, and progress with monitoring thioguanine nucleotides. Ther Drug Monit 2005, 27:647-654.
19. Vikingsson S., Carlsson B., Almer S.H., et al. Monitoring of thiopurine metabolites in patients with inflammatory bowel disease-what is actually measured?. Ther Drug Monit 2009, 31:345-350.
20. De Boer N.K., Wong D.R., Jharap B., et al. Dose-dependent influence of 5-aminosalicylates on thiopurine metabolism. Am J Gastroenterol 2007, 102:2747-2753.
21. Andrews J.M., Travis S.P., Gibson P.R., et al. Systematic review: does concurrent therapy with 5-ASA and immunomodulators in inflammatory bowel disease improve outcomes?. Aliment Pharmacol Ther 2009, 29:459-469.
22. Lowry P.W., Franklin C.L., Weaver A.L., et al. Leucopenia resulting from a drug interaction between azathioprine or 6-mercaptopurine and mesalamine, sulphasalazine, or balsalazide. Gut 2001, 49:656-664.
23. Chocair P., Duley J., Simmonds H.A., et al. Low-dose allopurinol plus azathioprine/cyclosporin/prednisolone, a novel immunosuppressive regimen. Lancet 1993, 342:83-84.
24. Sparrow M.P., Hande S.A., Friedman S., et al. Effect of allopurinol on clinical outcomes in inflammatory bowel disease nonresponders to azathioprine or 6-mercaptopurine. Clin Gastroenterol Hepatol 2007, 5:209-214.
25. Ansari A., Patel N., Sanderson J., et al. Low-dose azathioprine or mercaptopurine in combination with allopurinol can bypass many adverse drug reactions in patients with inflammatory bowel disease. Aliment Pharmacol Ther 2010, 31:640-647.
26. Seksik P., Cosnes J., Sokol H., et al. Incidence of benign upper respiratory tract infections, HSV and HPV cutaneous infections in inflammatory bowel disease patients treated with azathioprine. Aliment Pharmacol Ther 2009, 29:1106-1113.
27. Toruner M., Loftus E.V., Harmsen W.S., et al. Risk factors for opportunistic infections in patients with inflammatory bowel disease. Gastroenterology 2008, 134:929-936.
28. Rahier J., Ben-Horin S., Chowers Y., et al. European evidence-based consensus on the prevention, diagnosis and management of opportunistic infections in inflammatory bowel disease. J Crohns Colitis 2009, 3:47-91.
29. Vernier-Massouille G., Cosnes J., Lemann M., et al. Nodular regenerative hyperplasia in patients with inflammatory bowel disease treated with azathioprine. Gut 2007, 56:1404-1409.
30. De Boer N.K., Tuynman H., Bloemena E., et al. Histopathology of liver biopsies from a thiopurine-naive inflammatory bowel disease cohort: prevalence of nodular regenerative hyperplasia. Scand J Gastroenterol 2008, 43:604-608.
31. Wanless I.R. Micronodular transformation (nodular regenerative hyperplasia) of the liver: a report of 64 cases among 2,500 autopsies and a new classification of benign hepatocellular nodules. Hepatology 1990, 11:787-797.
32. Kandiel A., Fraser A.G., Korelitz B.I., et al. Increased risk of lymphoma among inflammatory bowel disease patients treated with azathioprine and 6-mercaptopurine. Gut 2005, 54:1121-1125.
33. Beaugerie L., Brousse N., Bouvier A.M., et al. Lymphoproliferative disorders in patients receiving thiopurines for inflammatory bowel disease: a prospective observational cohort study. Lancet 2009, 374:1617-1625.
34. Colombel J.F., Sandborn W.J., Reinisch W., et al. Infliximab, azathioprine, or combination therapy for Crohn's disease. N Engl J Med 2010, 362:1383-1395.
35. Mackey A.C., Green L., Leptak C., et al. Hepatosplenic T cell lymphoma associated with infliximab use in young patients treated for inflammatory bowel disease: update. J Pediatr Gastroenterol Nutr 2009, 48:386-388.
36. Burger D.C., Florin T.H. Hepatosplenic T-cell lymphoma following infliximab therapy for Crohn's disease. Med J Aust 2009, 190:341-342.
37. Siegel C.A., Marden S.M., Persing S.M., et al. Risk of lymphoma associated with combination anti-tumor necrosis factor and immunomodulator therapy for the treatment of Crohn's disease: a meta-analysis. Clin Gastroenterol Hepatol 2009, 7:874-881.
38. Long M.D., Herfarth H.H., Pipkin C., et al. Increased risk for non-melanoma skin cancer in patients with inflammatory bowel disease. Clin Gastroenterol Hepatol 2010, 8:268-274.
39. Bermejo F., Lopez-Sanroman A., Taxonera C., et al. Acute pancreatitis in inflammatory bowel disease, with special reference to azathioprine-induced pancreatitis. Aliment Pharmacol Ther 2008, 28:623-628.
40. Van Geenen E.J., De Boer N.K., Stassen P., et al. Azathioprine or mercaptopurine induced acute pancreatitis is not a disease specific phenomenon. Aliment Pharmacol Ther 2010, 31:1322-1329.
41. Van Dieren J.M., Hansen B.E., Kuipers E.J., et al. Meta-analysis: inosine triphosphate pyrophosphatase polymorphisms and thiopurine toxicity in the treatment of inflammatory bowel disease. Aliment Pharmacol Ther 2007, 26:643-652.
42. Vilien M., Dahlerup J.F., Munck L.K., et al. Randomized controlled azathioprine withdrawal after more than two years treatment in Crohn's disease: increased relapse rate the following year. Aliment Pharmacol Ther 2004, 19:1147-1152.
43. Bouhnik Y., Lemann M., Mary J.Y., et al. Long-term follow-up of patients with Crohn's disease treated with azathioprine or 6-mercaptopurine. Lancet 1996, 347:215-219.
44. Treton X., Bouhnik Y., Mary J.Y., et al. Azathioprine withdrawal in patients with Crohn's disease maintained on prolonged remission: a high risk of relapse. Clin Gastroenterol Hepatol 2009, 7:80-85.
45. Bernell O., Lapidus A., Hellers G. Risk factors for surgery and postoperative recurrence in Crohn's disease. Ann Surg 2000, 231:38-45.
46. Rutgeerts P., Geboes K., Vantrappen G., et al. Predictability of the postoperative course of Crohn's disease. Gastroenterology 1990, 99:956-963.
47. Peyrin-Biroulet L., Deltenre P., Ardizzone S., et al. Azathioprine and 6-mercaptopurine for the prevention of postoperative recurrence in Crohn's disease: a meta-analysis. Am J Gastroenterol 2009, 104:2089-2096.
48. Rutgeerts P., Van Assche G., Vermeire S., et al. Ornidazole for prophylaxis of postoperative Crohn's disease recurrence: a randomized, double-blind, placebo-controlled trial. Gastroenterology 2005, 128:856-861.
49. Van Assche G., Dignass A., Reinisch W., et al. The second European evidence-based consensus on the diagnosis and management of Crohn's disease: special situations. J Crohn Colitis 2010, 4:63-101.
50. Dubinsky M.C., Vasiliauskas E.A., Singh H., et al. 6-Thioguanine can cause serious liver injury in inflammatory bowel disease patients. Gastroenterology 2003, 125:298-303.
51. Seiderer J., Zech C.J., Reinisch W., et al. A multicenter assessment of liver toxicity by MRI and biopsy in IBD patients on 6-thioguanine. J Hepatol 2005, 43:303-309.
52. Gilissen L.P., Derijks L.J., Driessen A., et al. Toxicity of 6-thioguanine: no hepatotoxicity in a series of IBD patients treated with long-term, low dose 6-thioguanine. Some evidence for dose or metabolite level dependent effects?. Dig Liver Dis 2007, 39:156-159.
53. Teml A., Schwab M., Hommes D.W., et al. A systematic survey evaluating 6-thioguanine-related hepatotoxicity in patients with inflammatory bowel disease. Wien Klin Wochenschr 2007, 119:519-526.
54. De Boer N.K., Zondervan P.E., Gilissen L.P., et al. Absence of nodular regenerative hyperplasia after low-dose 6-thioguanine maintenance therapy in inflammatory bowel disease patients. Dig Liver Dis 2008, 40:108-113.
55. Ansari A., Elliott T., Fong F., et al. Further experience with the use of 6-thioguanine in patients with Crohn's disease. Inflamm Bowel Dis 2008, 14:1399-1405.
56. Ferlitsch A., Teml A., Reinisch W., et al. 6-Thioguanine associated nodular regenerative hyperplasia in patients with inflammatory bowel disease may induce portal hypertension. Am J Gastroenterol 2007, 102:2495-2503.
57. Mayo Medical Laboratories Prometheus Thiopurine Metabolites 2009, Available at: http://www.mayomedicallaboratories.com/test-catalog/print.php?unit_code=91564.
58. Winter J.W., Gaffney D., Shapiro D., et al. Assessment of thiopurine methyltransferase enzyme activity is superior to genotype in predicting myelosuppression following azathioprine therapy in patients with inflammatory bowel disease. Aliment Pharmacol Ther 2007, 25:1069-1077.
59. Schaeffeler E., Fischer C., Brockmeier D., 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, 14:407-417.
60. Shipkova M., Armstrong V.W., Wieland E., et al. Differences in nucleotide hydrolysis contribute to the differences between erythrocyte 6-thioguanine nucleotide concentrations determined by two widely used methods. Clin Chem 2003, 49:260-268.
61. Waljee A.K., Joyce J.C., Wang S., et al. Algorithms outperform metabolite tests in predicting response of patients with inflammatory bowel disease to thiopurines. Clin Gastroenterol Hepatol 2010, 8:143-150.
62. Thomas C.W., Lowry P.W., Franklin C.L., et al. Erythrocyte mean corpuscular volume as a surrogate marker for 6-thioguanine nucleotide concentration monitoring in patients with inflammatory bowel disease treated with azathioprine or 6-mercaptopurine. Inflamm Bowel Dis 2003, 9:237-245.