Safe and effective use of immunomodulators for inflammatory bowel disease

Practical Gastroenterology

Volumn 30, Issue 7, 2006, Pages 31-44

  Siegel, Corey A ^a,b  

^a DARTMOUTH MEDICAL SCHOOL   (United States)

^b Dartmouth Hitchcock Inflammatory Bowel Disease Center   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ADENOSINE RECEPTOR BLOCKING AGENT; ALLOPURINOL; ANTIEMETIC AGENT; AZATHIOPRINE; CAFFEINE; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; DRUG METABOLITE; FOLIC ACID; FUROSEMIDE; IMMUNOMODULATING AGENT; IMMUNOSUPPRESSIVE AGENT; INFLIXIMAB; MERCAPTOPURINE; MESALAZINE; METHOTREXATE; STEROID; SULFONAMIDE; THEOPHYLLINE; THIOPURINE METHYLTRANSFERASE; WARFARIN;

ABORTION; ALLERGIC PNEUMONITIS; ALLERGIC REACTION; BACTERIAL INFECTION; BLOOD DYSCRASIA; BONE MARROW SUPPRESSION; BONE MARROW TOXICITY; CLINICAL TRIAL; COST EFFECTIVENESS ANALYSIS; CROHN DISEASE; DRUG DOSE REGIMEN; DRUG EFFICACY; DRUG METABOLISM; DRUG SAFETY; DRUG WITHDRAWAL; ENTERITIS; FEVER; FLU LIKE SYNDROME; FOLIC ACID DEFICIENCY; HUMAN; INFLAMMATION; LABORATORY TEST; LEUKOPENIA; LIVER CIRRHOSIS; LIVER FIBROSIS; LIVER TOXICITY; LONG TERM CARE; LYMPHOMA; META ANALYSIS; MOUTH ULCER; NAUSEA; PANCREATITIS; PANCYTOPENIA; PATIENT MONITORING; PHARMACOGENETICS; RASH; REMISSION; REVIEW; RISK BENEFIT ANALYSIS; SEPSIS; SKIN CANCER; STEROID THERAPY; SYSTEMATIC REVIEW; TERATOGENICITY; TOXIC HEPATITIS; ULCERATIVE COLITIS; UTERINE CERVIX CANCER; VIRUS INFECTION;

EID: 33746887755     PISSN: 02774208     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (76)

1. Podolsky DK. Inflammatory bowel disease. NEJM, 2002;347(6): 417-429.
2. Rhodes J, Bainton D, Beck P, Campbell H. Controlled trial of azathioprine in Crohn's disease. Lancet, 1971;2(7737):1273-1276.
3. Willoughby JM, Beckett J, Kumar PJ, Dawson AM. Controlled trial of azathioprine in Crohn's disease. Lancet, 1971;2(7731): 944-947.
4. 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. NEJM, 1980; 302(18):981-987.
5. 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.
6. Kirk AP, Lennard-Jones JE. Controlled trial of azathioprine in chronic ulcerative colitis. Br Med J (Clin Res Ed), 1982; 284(6325):1291-1292.
7. Hawthorne AB, Logan RF, Hawkey CJ, Foster PN, Axon AT, Swarbrick ET, et al. Randomised controlled trial of azathioprine withdrawal in ulcerative colitis. BMJ, 1992;305(6844):20-22.
8. 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.
9. George J, Present DH, Pou R, Bodian C, Rubin PH. The long-term outcome of ulcerative colitis treated with 6-mercaptopurine. Am J Gastroenterol, 1996;91(9):1711-1714.
10. Kim PS, Zlatanic J, Korelitz BI, Gleim GW. Optimum duration of treatment with 6-mercaptopurine for Crohn's disease. Am J Gastroenterol, 1999;94(11):3254-3257.
11. Lemann M, Bouthnik Y, Colombel J, et al. Randomized, doubleblind, placebo-controlled, multicenter, azathioprine (AZA) withdrawal trial in Crohn's disease (CD). Gastroenterology, 2002; 122:A23.
12. Lobel EZ, Korelitz BI, Xuereb MA, Panagopoulos G. A search for the optimal duration of treatment with 6-mercaptopurine for ulcerative colitis. Am J Gastroenterol, 2004;99(3):462-465.
13. Treton X, Bouhnik Y, Mary J, Colembel J, Duclos B, Soule J, et al. Azathioprine withdrawal in patients with Crohn's Disease (CD) maintained on prolonged remission under treatment is associated with a high risk of relapse. Gastroenterology, 2004;126(4): A113.
14. Present DH, Meltzer SJ, Krumholz MP, Wolke A, Korelitz BI. 6-Mercaptopurine in the management of inflammatory bowel disease: short- and long-term toxicity. Ann Intern Med, 1989; 111(8):641-649.
15. de Jong DJ, Goullet M, Naber TH. Side effects of azathioprine in patients with Crohn's disease. Eur J Gastroenterol Hepatol, 2004;16(2):207-212.
16. Hookey LC, Depew W, Boag A, Vanner S. 6-mercaptopurine and inflammatory bowel disease: hidden ground for the cytomegalovirus. Can J Gastroenterol, 2003;17(5):319-322.
17. Lemyze M, Tavernier JY, Chevalon B, Lamblin C. Severe varicella zoster pneumonia during the course of treatment with azathioprine for Crohn's disease. Rev Mal Respir, 2003;20(5 Pt 1): 773-776.
18. Posthuma EF, Westendorp RG, van der Sluys Veer A, Kluin-Nelemans JC, Kluin PM, Lamers CB. Fatal infectious mononucleosis: a severe complication in the treatment of Crohn's disease with azathioprine. Gut, 1995;36(2):311-313.
19. Vergara M, Brullet E, Campo R, Calvet X, Blanch L. Fulminant infection caused by varicella herpes zoster in patient with Crohn's disease undergoing treatment with azathioprine. Gastroenterol Hepatol, 2001;24(1):47.
20. Siegel C, Olenec C, Wartman D, Bensen S, Ely P. Hemophagocytic syndrome: A complication of ulcerative colitis or side-effect of 6-MP therapy? Am J Gastroenterol, 2004;99(10):S134.
21. Bouhnik Y, Lemann M, Mary JY, Scemama G, Tai R, Matuchansky C, et al. Long-term follow-up of patients with Crohn's disease treated with azathioprine or 6-mercaptopurine. Lancet, 1996;347(8996):215-219.
22. Khan ZH, Mayberry JF, Spiers N, Wicks AC. Retrospective case series analysis of patients with inflammatory bowel disease on azathioprine. A district general hospital experience. Digestion. 2000;62(4):249-254.
23. O'Brien JJ, Bayless TM, Bayless JA. Use of azathioprine or 6-mercaptopurine in the treatment of Crohn's disease. Gastroenterology, 1991;101(1):39-46.
24. Warman JI, Korelitz BI, Fleisher MR, Janardhanam R. Cumulative experience with short- and long-term toxicity to 6-mercaptopurine in the treatment of Crohn's disease and ulcerative colitis. J Clin Gastroenterol, 2003;37(3):220-225.
25. Fraser AG, Orchard TR, Robinson EM, Jewell DP. Long-term risk of malignancy after treatment of inflammatory bowel disease with azathioprine. Aliment Pharmacol Ther, 2002;16(7):1225-1232.
26. Loftus EV, Jr., Tremaine WJ, Habermann TM, Harmsen WS, Zinsmeister AR, Sandborn WJ. Risk of lymphoma in inflammatory bowel disease. Am J Gastroenterol, 2000;95(9):2308-2312.
27. Lewis JD, Schwartz JS, Lichtenstein GR. Azathioprine for maintenance of remission in Crohn's disease: benefits outweigh the risk of lymphoma. Gastroenterology, 2000;118(6):1018-1024.
28. Dayharsh GA, Loftus EV, Jr., Sandborn WJ, Tremaine WJ, Zinsmeister AR, Witzig TE, et al. Epstein-Barr virus-positive lymphoma in patients with inflammatory bowel disease treated with azathioprine or 6-mercaptopurine. Gastroenterology, 2002; 122(1):72-77.
29. Connell WR, Kamm MA, Dickson M, Balkwill AM, Ritchie JK, Lennard-Jones JE. Long-term neoplasia risk after azathioprine treatment in inflammatory bowel disease. Lancet, 1994; 343(8908):1249-1252.
30. Austin AS, Spiller RC. Inflammatory bowel disease, azathioprine and skin cancer: case report and literature review. Eur J Gastroenterol Hepatol, 2001;13(2):193-194.
31. Ansari A, Soon S, Lindsay J, Arenas M, Morris D, Greenfield S, et al. Thiopurine methyl transferase activity predicts both toxicity and clinical response to azathioprine in inflammatory bowel disease: The London IBD forum prospective study. Gastroenterology, 2004;126(4):A463.
32. Dubinsky MC, Lamothe S, Yang HY, Targan SR, Sinnett D, Theoret Y, et al. Pharmacogenomics and metabolite measurement for 6-mercaptopurine therapy in inflammatory bowel disease. Gastroenterology, 2000;118(4):705-713.
33. Lennard L. TPMT in the treatment of Crohn's disease with azathioprine. Gut. 2002;51(2):143-146.
34. 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(5):410-417.
35. Winter J, Walker A, Shapiro D, Gaffney D, Spooner RJ, Mills PR. Cost-effectiveness of thiopurine methyltransferase genotype screening in patients about to commence azathioprine therapy for treatment of inflammatory bowel disease. Aliment Pharmacol Ther, 2004;20(6):593-599.
36. Dubinsky MC, Reyes E, Ofman J, Chiou CF, Wade S, Sandborn WJ. 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(10):2239-2247.
37. Colombel JF, Ferrari N, Debuysere H, Marteau P, Gendre JP, Bonaz B, et al. Genotypic analysis of thiopurine S-methyltransferase in patients with Crohn's disease and severe myelosuppression during azathioprine therapy. Gastroenterology, 2000; 118(6):1025-1030.
38. Marinaki AM, Ansari A, Duley JA, Arenas M, Sumi S, Lewis CM, et al. Adverse drug reactions to azathioprine therapy are associated with polymorphism in the gene encoding inosine triphosphate pyrophosphatase (ITPase). Pharmacogenetics, 2004;14(3):181-187.
39. Ansari A, Soon S, Raoof S, Arenas M, Lewis C, Duley J, et al. Pharmacogenetic profiling in azathioprine therapy: the role of TPMT, ITPA and MTHFR polymorphisms in drug therapy. Gastroenterology, 2004;126(4):A215.
40. 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(1):44-49.
41. Sandborn WJ. A review of immune modifier therapy for inflammatory bowel disease: azathioprine, 6-mercaptopurine, cyclosporine, and methotrexate. Am J Gastroenterol, 1996;91(3):423-433.
42. Cuffari C, Hunt S, Bayless TM. Enhanced bioavailability of azathioprine compared to 6-mercaptopurine therapy in inflammatory bowel disease: correlation with treatment efficacy. Aliment Pharmacol Ther, 2000;14(8):1009-1014.
43. Sandborn WJ, Van OE, Zins BJ, Tremaine WJ, Mays DC, Lipsky JJ. An intravenous loading dose of azathioprine decreases the time to response in patients with Crohn's disease. Gastroenterology, 1995;109(6):1808-1817.
44. Castiglione F, Del Vecchio Blanco G, Rispo A, Mazzacca G. Prevention of pancreatitis by weekly amylase assay in patients with Crohn's disease treated with azathioprine. Am J Gastroenterol, 2000;95(9):2394-2395.
45. Bokemeyer B. Asymptomatic elevation of serum lipase and amylase in conjunction with Crohn's disease and ulcerative colitis. J. Gastroenterol, 2002;40(1):5-10.
46. Katz S, Bank S, Greenberg RE, Lendvai S, Lesser M, Napolitano B. Hyperamylasemia in inflammatory bowel disease. J Clin Gastroenterol, 1988;10(6):627-630.
47. 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(5):642-646.
48. Seidman EG, Theoret Y, Fisher R, Seidman J, Amre D. Thiopurine drug metabolite levels guide treatment in ulcerative colitis. Gastroenterology, 2004;126(4):A209.
49. Achkar JP, Stevens T, Easley K, Brzezinski A, Seidner D, Lashner B. Indicators of clinical response to treatment with six-mercaptopurine or azathioprine in patients with inflammatory bowel disease. Inflamm Bowel Dis, 2004;10(4):339-345.
50. 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(9):1744-1748.
51. Lowry PW, Franklin CL, Weaver AL, Pike MG, Mays DC, Tremaine WJ, et al. Measurement of thiopurine methyltransferase activity and azathioprine metabolites in patients with inflammatory bowel disease. Gut, 2001;49(5):665-670.
52. Reuther LO, Sonne J, Larsen NE, Larsen B, Christensen S, Rasmussen SN, et al. Pharmacological monitoring of azathioprine therapy. Scand J Gastroenterol, 2003;38(9):972-977.
53. 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.
54. 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(4):904-915.
55. 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(4):464-475.
56. Achkar JP, Brzezinski A, Lashner B, Vogel D, Seidner D, Shen B. A double-blind, placebo-controlled randomized clinical trial evaluating the effects of sulfasalazine on 6-mercaptopurine metabolism in patients with Crohn's disease. Am J Gastroenterol, 2004;99(10):S264.
57. Izumiya M, Yoshizawa S, Yajima T, Tadakazu H, Susumu O, Takaishi H, et al. 6-MP metabolite interacts with purine analogs in patients with inflammatory bowel disease. Gastroenterology, 2004;126(4):A631.
58. Sparrow MP, Hande SA, Friedman S, Lim WC, Reddy SI, Cao D, et al. Allopurinol safely and effectively optimizes tioguanine metabolites in inflammatory bowel disease patients not responding to azathioprine and mercaptopurine. Aliment Pharmacol Ther, 2005;22(5):441-446.
59. 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(9):917-925.
60. Feagan BG, Rochon J, Fedorak RN, Irvine EJ, Wild G, Sutherland L, et al. Methotrexate for the treatment of Crohn's disease. The North American Crohn's Study Group Investigators. NEJM, 1995;332(5):292-297.
61. Feagan BG, Fedorak RN, Irvine EJ, Wild G, Sutherland L, Steinhart AH, et al. A comparison of methotrexate with placebo for the maintenance of remission in Crohn's disease. North American Crohn's Study Group Investigators. NEJM, 2000;342(22):1627-1632.
62. Cummings JRF, Herrlinger KR, Travis SPL, Gorard DA, McIntyre AS, Jewell DP. Oral methotrexate in ulcerative colitis. Aliment Pharmacol Ther, 2005;21:385-389.
63. Kozarek RA, Patterson DJ, Gelfand MD, Botoman VA, Ball TJ, Wilske KR. Methotrexate induces clinical and histologic remission in patients with refractory inflammatory bowel disease. Ann Intern Med, 1989;110(5):353-356.
64. Mate-Jimenez J, Hermida C, Cantero-Perona J, Moreno-Otero R. 6-mercaptopurine or methotrexate added to prednisone induces and maintains remission in steroid-dependent inflammatory bowel disease. Eur J Gastroenterol Hepatol, 2000;12(11):1227-1233.
65. Oren R, Arber N, Odes S, Moshkowitz M, Keter D, Pomeranz I, et al. Methotrexate in chronic active ulcerative colitis: a doubleblind, randomized, Israeli multicenter trial. Gastroenterology, 1996;110(5):1416-1421.
66. Paoluzi OA, Pica R, Marcheggiano A, Crispino P, Iacopini F, Iannoni C, et al. Azathioprine or methotrexate in the treatment of patients with steroid-dependent or steroid-resistant ulcerative colitis: results of an open-label study on efficacy and tolerability in inducing and maintaining remission. Aliment Pharmacol Ther, 2002;16(10):1751-1759.
67. Malatjalian DA, Ross JB, Williams CN, Colwell SJ, Eastwood BJ. Methotrexate hepatotoxicity in psoriatics: report of 104 patients from Nova Scotia, with analysis of risks from obesity, diabetes and alcohol consumption during long term follow-up. Can J Gastroenterol, 1996;10(6):369-375.
68. Kremer JM, Alarcon GS, Lightfoot RW, Jr., Willkens RF, Furst DE, Williams HJ, et al. Methotrexate for rheumatoid arthritis. Suggested guidelines for monitoring liver toxicity. American College of Rheumatology. Arthritis Rheum, 1994;37(3):316-328.
69. Te HS, Schiano TD, Kuan SF, Hanauer SB, Conjeevaram HS, Baker AL. Hepatic effects of long-term methotrexate use in the treatment of inflammatory bowel disease. Am J Gastroenterol, 2000;95(11):3150-3156.
70. Bohon P, Dugernier T, Debongnie JC, Pirenne B. Hypersensitivity interstitial pneumopathy and ulcero-hemorrhagic rectocolitis: role of methotrexate. Acta Gastroenterol Belg, 1993;56(5-6):352-357.
71. Morris LF, Harrod MJ, Menter MA, Silverman AK. Methotrexate and reproduction in men: case report and recommendations. J Am Acad Dermatol, 1993;29(5 Pt 2):913-916.
72. Sussman A, Leonard JM. Psoriasis, methotrexate, and oligospermia. Arch Dermatol, 1980;116(2):215-217.
73. Brooks PJ, Spruill WJ, Parish RC, Birchmore DA. Pharmacokinetics of methotrexate administered by intramuscular and subcutaneous injections in patients with rheumatoid arthritis. Arthritis Rheum, 1990;33(1):91-94.
74. Kurnik D, Loebstein R, Fishbein E, Almog S, Halkin H, Bar-Meir S, et al. Bioavailability of oral vs. subcutaneous low-dose methotrexate in patients with Crohn's disease. Aliment Pharmacol Ther, 2003;18(1):57-63.
75. Feagan BG, Alfadhli A. Methotrexate in inflammatory bowel disease. Gastroenterol Clin North Am, 2004;33(2):407-420.
76. Chan ES, Cronstein BN. Molecular action of methotrexate in inflammatory diseases. Arthritis Res, 2002;4(4):266-273.