A prospective, open-label trial of 6-thioguanine in patients with ulcerative or indeterminate colitis

Scandinavian Journal of Gastroenterology

Volumn 40, Issue 10, 2005, Pages 1205-1213

  Teml, Alexander ^a   Schwab, Matthias ^b   Harrer, Marieluise ^a   Miehsler, Wolfgang ^a   Schaeffeler, Elke ^b   Dejaco, Clemens ^a   Mantl, Martina ^a   Schneider, Barbara ^a   Vogelsang, Harald ^a   Reinisch, Walter ^a  

^a MEDICAL UNIVERSITY OF VIENNA   (Austria)

^b DR MARGARETE FISCHER BOSCH INSTITUTE OF CLINICAL PHARMACOLOGY   (Germany)

Author keywords

6 thioguanine; 6 thioguanine nucleotides; Azathioprine or 6 mercaptopurine intolerance; Azathioprine or 6 mercaptopurine resistance; Endoscopy; Immunosuppression; Indeterminate colitis; Inflammatory bowel disease; Ulcerative colitis

Indexed keywords

AZATHIOPRINE; C REACTIVE PROTEIN; CYCLOSPORIN A; INFLIXIMAB; MERCAPTOPURINE; PREDNISOLONE; STEROID; THIOGUANIN; TIOGUANINE;

ABDOMINAL DISTENSION; ABNORMALLY HIGH SUBSTRATE CONCENTRATION IN BLOOD; ADOLESCENT; ADULT; ADVERSE DRUG REACTION; ALKALINE PHOSPHATASE BLOOD LEVEL; ALOPECIA; ARTHRALGIA; ARTICLE; BILIRUBIN BLOOD LEVEL; CHOLESTASIS; CLINICAL ARTICLE; CLINICAL TRIAL; COLITIS; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DIARRHEA; DRUG BLOOD LEVEL; DRUG DEPENDENCE; DRUG EFFICACY; DRUG RESPONSE; DRUG SAFETY; DRUG SCREENING; DRUG TOLERANCE; DRUG USE; DRUG WITHDRAWAL; EPIGASTRIC PAIN; FEMALE; GAMMA GLUTAMYL TRANSFERASE BLOOD LEVEL; GASTROINTESTINAL ENDOSCOPY; GASTROINTESTINAL SYMPTOM; HEADACHE; HUMAN; INDETERMINATE COLITIS; LEUKOPENIA; LIVER TOXICITY; MALE; MYALGIA; NAUSEA; OCCULT BLOOD; OUTPATIENT DEPARTMENT; PANCREATITIS; PATIENT COMPLIANCE; PRIORITY JOURNAL; RASH; RISK ASSESSMENT; SIDE EFFECT; STEROID THERAPY; THROMBOCYTOPENIA; TREATMENT FAILURE; ULCERATIVE COLITIS;

6-MERCAPTOPURINE; ADULT; AGED; ANTI-INFLAMMATORY AGENTS; AZATHIOPRINE; BIOLOGICAL MARKERS; C-REACTIVE PROTEIN; COLITIS, ULCERATIVE; DOSE-RESPONSE RELATIONSHIP, DRUG; ENDOSCOPY, GASTROINTESTINAL; FEMALE; GENOTYPE; GUANINE NUCLEOTIDES; HUMANS; MALE; METHYLTHIOINOSINE; METHYLTRANSFERASES; MIDDLE AGED; OROSOMUCOID; PATIENT COMPLIANCE; PROSPECTIVE STUDIES; QUALITY OF LIFE; THIOGUANINE; THIONUCLEOTIDES; TREATMENT OUTCOME;

EID: 27144448052     PISSN: 00365521     EISSN: 15027708     Source Type: Journal    
DOI: 10.1080/00365520510023369     Document Type: Article

References (52)

1. Podolsky DK. Inflammatory bowel disease. I. N Engl J Med 1991;325:928 -37.
2. Podolsky DK. Inflammatory bowel disease. II. N Engl J Med 1991;325:1008-16.
3. Price AB. Overlap in the spectrum of non-specific inflammatory bowel disease: "colitis indeterminate". J Clin Pathol 1978;31:567-77.
4. Geboes K, De Hertogh G. Indeterminate colitis. Inflamm Bowel Dis 2003;9:324-31.
5. Jewell DP, Truelove SC. Azathioprine in ulcerative colitis: final report on controlled therapeutic trial. Br Med J 1974;4:627-30.
6. Rosenberg JL, Wall AJ, Levin B, Binder HJ, Kirsner JB. A controlled trial of azathioprine in the management of chronic ulcerative colitis. Gastroenterology 1975;69:96-9.
7. Kirk AP, Lennard-Jones JE. Controlled trial of azathioprine in chronic ulcerative colitis. Br Med J (Clin Res Ed) 1982;284:1291-2.
8. Hawthorne AB, Logan RF, Hawkey CJ, Foster PN, Axon AT, Swarbrick ET, et al. Randomised controlled trial of azathioprine withdrawal in ulcerative colitis. Br Med J 1992;305:20-2.
9. Sood A, Midha V, Sood N, Kaushal V. Role of azathioprine in severe ulcerative colitis: one-year, placebo-controlled, randomized trial. Indian J Gastroenterol 2000;19:14-6.
10. 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.
11. Present DH, Korelitz BI, Wisch N, Glass JL, Sachar DB, Pasternack BS. Treatment of Crohn's disease with 6-mercaptopurine. A long-term, randomized, double-blind study. N Engl J Med 1980;302:981-7.
12. Ludwig D, Stange EF. Treatment of ulcerative colitis. Hepatogastroenterology 2000;47:83-9.
13. Lennard L. The clinical pharmacology of 6-mercaptopurine. Eur J Clin Pharmacol 1992;43:329-39.
14. 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.
15. Lancaster DL, Lennard L, Rowland K, Vora AJ, Lilleyman JS. Thioguanine versus mercaptopurine for therapy of childhood lymphoblastic leukaemia: a comparison of haematological toxicity and drug metabolite concentrations. Br J Haematol 1998;102:439-43.
16. Erb N, Harms DO, Janka-Schaub G. Pharmacokinetics and metabolism of thiopurines in children with acute lymphoblastic leukemia receiving 6-thioguanine versus 6-mercaptopurine. Cancer Chemother Pharmacol 1998;42:266-72.
17. Shepherd PC, Fooks J, Gray R, Allan NC. Thioguanine used in maintenance therapy of chronic myeloid leukaemia causes non-cirrhotic portal hypertension. Results from MRC CML. II. Trial comparing busulphan with busulphan and thioguanine. Br J Haematol 1991;79:185-92.
18. Harms DO, Gobel U, Spaar HJ, Graubner UB, Jorch N, Gutjahr P, et al. COALL Study Group. Thioguanine offers no advantage over mercaptopurine in maintenance treatment of childhood ALL: results of the randomized trial COALL-92. Blood 2003;102:2736-40.
19. Lennard L, Davies HA, Lilleyman JS. Is 6-thioguanine more appropriate than 6-mercaptopurine for children with acute lymphoblastic leukaemia? Br J Cancer 1993;68:186-90.
20. Mason C, Krueger GG. Thioguanine for refractory psoriasis: a 4-year experience. J Am Acad Dermatol 2001;44:67-72.
21. Bean RHD. Treatment of ulcerative colitis with antimetabolites. Br Med J 1966;1:1081-4.
22. Dubinsky MC, Hassard PV, Seidman EG, Kam LY, Abreu MT, Targan SR, et al. An open-label pilot study using thioguanine as a therapeutic alternative in Crohn's disease patients resistant to 6-mercaptopurine therapy. Inflamm Bowel Dis 2001;7:181-9.
23. Herrlinger KR, Kreisel W, Schwab M, Schoelmerich J, Fleig WE, Ruhl A, et al. 6-thioguanine: efficacy and safety in chronic active Crohn's disease. Aliment Pharmacol Ther 2003;17:503-8.
24. Herrlinger KR, Deibert P, Schwab M, Kreisel W, Fischer C, Fellermann K, et al. Remission maintenance by thioguanine in chronic active Crohn's disease. Aliment Pharmacol Ther 2003;17:1459-64.
25. Bonaz B, Boitard J, Marteau P, Lemann M, Coffin B, Flourie B, et al. Tioguanine in patients with Crohn's disease intolerant or resistant to azathioprine/mercaptopurine. Aliment Pharmacol Ther 2003;18:401-8.
26. Derijks LJ, de Jong DJ, Gilissen LP, Engels LG, Hooymans PM, Jansen JB, et al. 6-Thioguanine seems promising in azathioprine- or 6-mercaptopurine- intolerant inflammatory bowel disease patients: a short-term safety assessment. Eur J Gastroenterol Hepatol 2003;15:63-7.
27. Dubinsky MC, Feldman EJ, Abreu MT, Targan SR, Vasiliauskas EA. Thioguanine: a potential alternate thiopurine for IBD patients allergic to 6-mercaptopurine or azathioprine. Am J Gastroenterol 2003;98:1058-63.
28. Cheung TK, Florin TH. 6-thioguanine: a new old drug to procure remission in inflammatory bowel disease. Intern Med J 2003;33:44-6.
29. Dubinsky MC, Vasiliauskas EA, Singh H, Abreu MT, Papadakis KA, Tran T, et al. 6-thioguanine can cause serious liver injury in inflammatory bowel disease patients. Gastroenterology 2003;125:298-303.
30. Joossens S, Reinisch W, Vermeire S, Sendid B, Poulain D, Peeters M, et al. The value of serologic markers in indeterminate colitis: a prospective follow-up study. Gastroenterology 2002;122:1242-7.
31. Rachmilewitz D. Coated mesalazine (5-aminosalicylic acid) versus sulphasalazine in the treatment of active ulcerative colitis: a randomised trial. Br Med J 1989;298:82-6.
32. Lichtiger S, Present DH, Kornbluth A, Gelernt I, Bauer J, Galler G, et al. Cyclosporine in severe ulcerative colitis refractory to steroid therapy. N Engl J Med 1994;330:1841-5.
33. Rose M, Fliege H, Hildebrandt M, Korber J, Arck P, Dignass A, et al. Validierung der deutschsprachigen Version des "Short Inflammatory Bowel Disease Questionnaire" (SIBDQ) (Validation of the new German translation version of the "Short Inflammatory Bowel Disease Questionnaire" (SIBDQ)). Z Gastroenterol 2000;38:277-86.
34. Moser G, Tillinger W, Sachs G, Genser D, Maier-Dobersberger T, Spiess K, et al. Disease-related worries and concerns: a study on out-patients with inflammatory bowel disease. Eur J Gastroenterol Hepatol 1995;7:853-8.
35. Schaeffeler E, Lang T, Zanger UM, Eichelbaum M, Schwab M. High-throughput genotyping of thiopurine S-methyltransferase by denaturing HPLC. Clin Chem 2001;47:548-55.
36. 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.
37. Herrlinger KR, Fellermann K, Fischer C, Kreisel W, Deibert P, Schoelmerich J, et al. Thioguanine-nucleotides do not predict efficacy of 6-tioguanine in Crohn's disease. Aliment Pharmacol Ther 2004;19:1269-76.
38. Miller AB, Hoogstraten B, Staquet M, Winkler A. Reporting results of cancer treatment. Cancer 1981;47:207-14.
39. Connell WR, Kamm MA, Ritchie JK, Lennard-Jones JE. Bone marrow toxicity caused by azathioprine in inflammatory bowel disease: 27 years of experience. Gut 1993;34:1081-5.
40. Guyatt G, Michell A, Irvine EJ, Singer J, Williams N, Goodacre R, Tompkins C. A new measure of health status for clinical trials in inflammatory bowel disease. Gastroenterology 1989;96:804-10.
41. Irvine EJ, Zhou Q, Thompson AK. The Short Inflammatory Bowel Disease Questionnaire: a quality of life instrument for community physicians managing inflammatory bowel disease. CCRPT investigators. Canadian Crohn's Relapse Prevention Trial. Am J Gastroenterol 1996;91:1571-8.
42. Drossman DA, Patrick DL, Mitchell CM, Zagami EA, Appelbaum MI. Health-related quality of life in inflammatory bowel disease. Functional status and patient worries and concerns. Dig Dis Sci 1989;34:1379-86.
43. Drossman DA, Leserman J, Li ZM, Mitchell CM, Zagami EA, Patrick DL. The rating form of IBD patient concerns: a new measure of health status. Psychosom Med 1991;53:701-12.
44. Wright S, Sanders DS, Lobo AJ, Lennard L. Clinical significance of azathioprine active metabolite concentrations in inflammatory bowel disease. Gut 2004;53:1123-8.
45. D'Haens G, Lemmens L, Geboes K, Vandeputte L, Van Acker F, Mortelmans L, et al. Intravenous cyclosporine versus intravenous corticosteroids as single therapy for severe attacks of ulcerative colitis. Gastroenterology 2001;120:1323-9.
46. D'Haens G, Van Deventer S, Van Hogezand R, Chalmers D, Kothe C, Baert F, et al. Endoscopic and histological healing with infliximab anti-tumor necrosis factor antibodies in Crohn's disease: a European multicenter trial. Gastroenterology 1999;116:1029-34.
47. Kaser A, Mairinger T, Vogel W, Tilg H. Infliximab in severe steroid-refractory ulcerative colitis: a pilot study. Wien Klin Wochenschr 2001;113:930-3.
48. Shastri S, Dubinsky MC, Poordad FF, Vasiliauskas EA, Geller SA. Early nodular hyperplasia of the liver occurring with inflammatory bowel diseases in association with thioguanine therapy. Arch Pathol Lab Med 2004;128:49-53.
49. Geller SA, Dubinsky MC, Poordad FF, Vasiliauskas EA, Cohen AH, Abreu MT, et al. Early hepatic nodular hyperplasia and submicroscopic fibrosis associated with 6-thioguanine therapy in inflammatory bowel disease. Am J Surg Pathol 2004;28:1204-11.
50. Mion F, Napoleon B, Berger F, Chevallier M, Bonvoisin S, Descos L. Azathioprine-induced liver disease: nodular regenerative hyperplasia of the liver and perivenous fibrosis in a patient treated for multiple sclerosis. Gut 1991;32:715-7.
51. Arnott ID, Ghosh S. Portal hypertension in the presence of minimal liver damage in Crohn's disease on long-term azathioprine: possible endothelial cell injury. Eur J Gastroenterol Hepatol 2000;12:569-73.
52. Fady D, Cadranel JF, Seksik P, Cazier A, Duong JP, Ziol M, et al. Azathioprine-induced nodular regenerative hyperplasia (NRH) of the liver in IBD patients [abstract]. Gastroenterol 2004;126:S1376.