Thiopurine immunomodulators in ulcerative colitis: Moving forward with current evidence

Current Drug Targets

Volumn 12, Issue 10, 2011, Pages 1406-1412

  la Nauze, Richard J ^a   Sparrow, Miles P ^a  

^a ALFRED HOSPITAL   (Australia)

Author keywords

6 mercaptopurine; Azathioprine; Immunomodulators; Inflammatory bowel disease; Thiopurines; Ulcerative colitis

Indexed keywords

AZATHIOPRINE; CORTICOSTEROID; IMMUNOMODULATING AGENT; MERCAPTOPURINE; PLACEBO; PREDNISOLONE;

CANCER RISK; COLORECTAL CANCER; CYTOMEGALOVIRUS INFECTION; DRUG SAFETY; EPSTEIN BARR VIRUS INFECTION; EVIDENCE BASED PRACTICE; HERPES SIMPLEX; HERPES ZOSTER; HOSPITALIZATION; HUMAN; LYMPHOMA; LYMPHOPROLIFERATIVE DISEASE; PREGNANCY; REMISSION; REVIEW; ULCERATIVE COLITIS;

6-MERCAPTOPURINE; ANIMALS; CLINICAL TRIALS AS TOPIC; COLITIS, ULCERATIVE; HUMANS; IMMUNOLOGIC FACTORS; IMMUNOSUPPRESSIVE AGENTS;

EID: 80051689352     PISSN: 13894501     EISSN: 18735592     Source Type: Journal    
DOI: 10.2174/138945011796818180     Document Type: Review

References (50)

1. 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.
2. Prefontaine E, Sutherland LR, Macdonald JK, Cepoiu M. Azathioprine or 6-mercaptopurine for maintenance of remission in Crohn's disease. Cochrane Database Syst Rev 2009(1): CD000067.
3. 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(8): 2089-2096.
4. Punati J, Markowitz J, Lerer T, et al. Effect of early immunomodulator use in moderate to severe pediatric Crohn disease. Inflamm Bowel Dis 2008; 14(7): 949-954.
5. Gisbert JP, Linares PM, McNicholl AG, Mate J, Gomollon F. Meta-analysis: the efficacy of azathioprine and mercaptopurine in ulcerative colitis. Aliment Pharmacol Ther 2009; 30(2): 126-137.
6. Timmer A, McDonald JW, Macdonald JK. Azathioprine and 6-mercaptopurine for maintenance of remission in ulcerative colitis. Cochrane Database Syst Rev 2007(1): CD000478.
7. Lichtenstein GR, Rutgeerts P. Importance of mucosal healing in ulcerative colitis. Inflamm Bowel Dis 2010; 16(2): 338-346.
8. Faubion WA, Jr., Loftus EV, Jr., Harmsen WS, Zinsmeister AR, Sandborn WJ. The natural history of corticosteroid therapy for inflammatory bowel disease: a population-based study. Gastroenterology 2001; 121(2): 255-260.
9. Jewell DP, Truelove SC. Azathioprine in ulcerative colitis: final report on controlled therapeutic trial. Br Med J 1974; 4(5945): 627-630.
10. 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(1): 96-99.
11. Kirk AP, Lennard-Jones JE. Controlled trial of azathioprine in chronic ulcerative colitis. Br Med J (Clin Res Ed) 1982; 284(6325): 1291-1292.
12. Hawthorne AB, Logan RF, Hawkey CJ, et al. Randomised controlled trial of azathioprine withdrawal in ulcerative colitis. BMJ 1992; 305(6844): 20-22.
13. Ardizzone S, Maconi G, Russo A, Imbesi V, Colombo E, Bianchi Porro G. Randomised controlled trial of azathioprine and 5-aminosalicylic acid for treatment of steroid dependent ulcerative colitis. Gut 2006; 55(1): 47-53.
14. Fraser AG, Orchard TR, Jewell DP. The efficacy of azathioprine for the treatment of inflammatory bowel disease: a 30 year review. Gut 2002; 50(4): 485-489.
15. Chebli LA, Chaves LD, Pimentel FF, et al. Azathioprine maintains long-term steroid-free remission through 3 years in patients with steroid-dependent ulcerative colitis. Inflamm Bowel Dis 2010; 16(4): 613-619.
16. Actis GC, Rossetti S, Rizzetto M, Fadda M, Palmo A. [Need for hospital admission in patients with ulcerative colitis during maintenance with azathioprine]. Minerva Gastroenterol Dietol 2004; 50(1): 97-101.
17. Gisbert JP, Nino P, Cara C, Rodrigo L. Comparative effectiveness of azathioprine in Crohn's disease and ulcerative colitis: prospective, long-term, follow-up study of 394 patients. Aliment Pharmacol Ther 2008; 28(2): 228-238.
18. Frøslie KF, Jahnsen J, Moum BA, Vatn MH. Mucosal healing in inflammatory bowel disease: results from a Norwegian populationbased cohort. Gastroenterology 2007; 133(2): 412-422.
19. Karran P, Attard N. Thiopurines in current medical practice: molecular mechanisms and contributions to therapy-related cancer. Nat Rev Cancer 2008; 8(1): 24-36.
20. Actis GC, Pellicano R, David E, Sapino A. Azathioprine, mucosal healing in ulcerative colitis, and the chemoprevention of colitic cancer: a clinical-practice-based forecast. Inflamm Allergy Drug Targets 2010; 9(1): 6-9.
21. Matula S, Croog V, Itzkowitz S, et al. Chemoprevention of colorectal neoplasia in ulcerative colitis: the effect of 6-mercaptopurine. Clin Gastroenterol Hepatol 2005; 3(10): 1015-1021.
22. Beaugerie L, Seksik P, Bouvier A, et al. Thiopurine Therapy Is Associated with a Three-Fold Decrease in the Incidence of Advanced Colorectal Neoplasia in IBD Patients with Longstanding Extensive Colitis: Results from the CESAME cohort. Gastroenterology 2009; 5(1): A-54.
23. Rayner CK, Hart AL, Hayward CM, Emmanuel AV, Kamm MA. Azathioprine dose escalation in inflammatory bowel disease. Aliment Pharmacol Ther 2004; 20(1): 65-71.
24. Osterman MT, Kundu R, Lichtenstein GR, Lewis JD. Association of 6-thioguanine nucleotide levels and inflammatory bowel disease activity: a meta-analysis. Gastroenterology 2006; 130(4): 1047-1053.
25. Dubinsky MC, Lamothe S, Yang HY, et al. Pharmacogenomics and metabolite measurement for 6-mercaptopurine therapy in inflammatory bowel disease. Gastroenterology 2000; 118(4): 705-713.
26. Dubinsky MC, Yang H, Hassard PV, et al. 6-MP metabolite profiles provide a biochemical explanation for 6-MP resistance in patients with inflammatory bowel disease. Gastroenterology 2002; 122(4): 904-915.
27. Ansari A, Hassan C, Duley J, et al. Thiopurine methyltransferase activity and the use of azathioprine in inflammatory bowel disease. Aliment Pharmacol Ther 2002; 16(10): 1743-1750.
28. Roberts RL, Gearry RB, Bland MV, et al. Trinucleotide repeat variants in the promoter of the thiopurine S-methyltransferase gene of patients exhibiting ultra-high enzyme activity. Pharmacogenet Genomics 2008; 18(5): 434-438.
29. de Boer NK, Wong DR, Jharap B, et al. Dose-dependent influence of 5-aminosalicylates on thiopurine metabolism. Am J Gastroenterol 2007; 102(12): 2747-2753.
30. Sparrow MP, Hande SA, Friedman S, Cao D, Hanauer SB. Effect of allopurinol on clinical outcomes in inflammatory bowel disease nonresponders to azathioprine or 6-mercaptopurine. Clin Gastroenterol Hepatol 2007; 5(2): 209-214.
31. Witte TN, Ginsberg AL. Use of allopurinol with low-dose 6- mercaptopurine in inflammatory bowel disease to achieve optimal active metabolite levels: a review of four cases and the literature. Can J Gastroenterol 2008; 22(2): 181-185.
32. Rahhal RM, Bishop WP. Initial clinical experience with allopurinol-thiopurine combination therapy in pediatric inflammatory bowel disease. Inflamm Bowel Dis 2008; 14(12): 1678-1682.
33. Ansari A, Elliott T, Baburajan B, et al. Long-term outcome of using allopurinol co-therapy as a strategy for overcoming thiopurine hepatotoxicity in treating inflammatory bowel disease. Aliment Pharmacol Ther 2008; 28(6): 734-741.
34. Leung Y, Sparrow MP, Schwartz M, Hanauer SB. Long term efficacy and safety of allopurinol and azathioprine or 6-mercaptopurine in patients with inflammatory bowel disease. 2009; 3(3): 162-167.
35. 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(8): 563-567.
36. Gisbert JP, Gomollon F. Thiopurine-induced myelotoxicity in patients with inflammatory bowel disease: a review. Am J Gastroenterol 2008; 103(7): 1783-1800.
37. Gisbert JP, Gonzalez-Lama Y, Mate J. Thiopurine-induced liver injury in patients with inflammatory bowel disease: a systematic review. Am J Gastroenterol 2007; 102(7): 1518-1527.
38. Pearson DC, May GR, Fick GH, Sutherland LR. Azathioprine and 6-mercaptopurine in Crohn disease. A meta-analysis. Ann Intern Med 1995; 123(2): 132-142.
39. Toruner M, Loftus EV, Jr., Harmsen WS, et al. Risk factors for opportunistic infections in patients with inflammatory bowel disease. Gastroenterology 2008; 134(4): 929-936.
40. Beaugerie L, Brousse N, Bouvier AM, et al. Lymphoproliferative disorders in patients receiving thiopurines for inflammatory bowel disease: a prospective observational cohort study. Lancet 2009; 374(9701): 1617-1625.
41. 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(8): 1121-1215.
42. Vernier-Massouille G, Cosnes J, Lemann M, et al. Nodular regenerative hyperplasia in patients with inflammatory bowel disease treated with azathioprine. Gut 2007; 56(10): 1404-1409.
43. Stephansson O, Larsson H, Pedersen L, et al. Congenital abnormalities and other birth outcomes in children born to women with ulcerative colitis in Denmark and Sweden. Inflamm Bowel Dis 2010(Epub ahead of print).
44. Burdett DN, Waterfield JD, Shah RM. Vertical development of the secondary palate in hamster embryos following exposure to 6-mercaptopurine. Teratology 1988; 37(6): 591-597.
45. Polifka JE, Friedman JM. Teratogen update: azathioprine and 6-mercaptopurine. Teratology 2002; 65(5): 240-261.
46. Gisbert JP. Safety of immunomodulators and biologics for the treatment of inflammatory bowel disease during pregnancy and breast-feeding. Inflamm Bowel Dis 2010; 16(5): 881-895.
47. Treton X, Bouhnik Y, Mary JY, et al. Azathioprine withdrawal in patients with Crohn's disease maintained on prolonged remission: a high risk of relapse. Clin Gastroenterol Hepatol 2009; 7(1): 80-85.
48. Cassinotti A, Actis GC, Duca P, et al. Maintenance treatment with azathioprine in ulcerative colitis: outcome and predictive factors after drug withdrawal. Am J Gastroenterol 2009; 104(11): 2760-2767.
49. Andrews JM, Travis SP, Gibson PR, Gasche C. Systematic review: does concurrent therapy with 5-ASA and immunomodulators in inflammatory bowel disease improve outcomes? Aliment Pharmacol Ther 2009; 29(5): 459-469.
50. Sokol H, Seksik P, Carrat F, et al. Usefulness of co-treatment withimmunomodulators in patients with inflammatory bowel disease treated with scheduled infliximab maintenance therapy. Gut 2010; 59(10): 1363-1368.