Leukopenia Predicts Remission in Patients with Inflammatory Bowel Disease and Behcet’s Disease on Thiopurine Maintenance

Digestive Diseases and Sciences

Volumn 60, Issue 1, 2015, Pages 195-204

  Park, Mi Sung ^a   Kim, Dong Hyun ^a   Kim, Duk Hwan ^a   Park, Soo Jung ^a   Hong, Sung Pil ^a   Kim, Tae Il ^a   Kim, Won Ho ^a,b   Cheon, Jae Hee ^a,b  

^a Yonsei University College of Medicine   (South Korea)

^b Brain Korea 21 Project for Medical Science   (South Korea)

Author keywords

Inflammatory bowel disease; Leukopenia; Relapse; Remission; Thiopurine

Indexed keywords

AZATHIOPRINE; MERCAPTOPURINE; IMMUNOSUPPRESSIVE AGENT;

ADOLESCENT; ADULT; AGED; ARTHRALGIA; ARTICLE; BEHCET DISEASE; CROHN DISEASE; DRUG WITHDRAWAL; FEBRILE NEUTROPENIA; FEMALE; HEADACHE; HEPATITIS; HERPES ZOSTER; HUMAN; HUMAN CELL; INFLAMMATORY BOWEL DISEASE; LEUKOCYTE COUNT; LEUKOPENIA; LUNG TUBERCULOSIS; MAINTENANCE DRUG DOSE; MAINTENANCE THERAPY; MAJOR CLINICAL STUDY; MALE; MEGALOCYTOSIS; NAUSEA; PANCREATITIS; PNEUMONIA; PRIORITY JOURNAL; PROGNOSIS; RASH; RECURRENCE FREE SURVIVAL; RELAPSE; REMISSION; RETROSPECTIVE STUDY; SURVIVAL; SURVIVAL RATE; ULCERATIVE COLITIS; URINARY TRACT INFECTION; VOMITING; BEHCET SYNDROME; CHEMICALLY INDUCED; COLITIS, ULCERATIVE; COMORBIDITY; KAPLAN MEIER METHOD; MIDDLE AGED; MULTIVARIATE ANALYSIS; YOUNG ADULT;

6-MERCAPTOPURINE; ADOLESCENT; ADULT; AGED; AZATHIOPRINE; BEHCET SYNDROME; COLITIS, ULCERATIVE; COMORBIDITY; CROHN DISEASE; FEMALE; HUMANS; IMMUNOSUPPRESSIVE AGENTS; KAPLAN-MEIER ESTIMATE; LEUKOPENIA; MALE; MIDDLE AGED; MULTIVARIATE ANALYSIS; PROGNOSIS; REMISSION INDUCTION; RETROSPECTIVE STUDIES; YOUNG ADULT;

EID: 84922004297     PISSN: 01632116     EISSN: 15732568     Source Type: Journal    
DOI: 10.1007/s10620-014-3355-4     Document Type: Article

References (49)

1. Munkholm P, Langholz E, Davidsen M, et al. Disease activity courses in a regional cohort of Crohn’s disease patients. Scand J Gastroenterol. 1995;30:699–706.
2. Kobayashi K, Ueno F, Bito S, et al. Development of consensus statements for the diagnosis and management of intestinal Behcet’s disease using a modified Delphi approach. J Gastroenterol. 2007;42:737–745.
3. Edwards FC, Truelove SC. The course and prognosis of ulcerative colitis. Gut. 1963;4:299–315.
4. Loftus EV Jr, Sandborn WJ. Epidemiology of inflammatory bowel disease. Gastroenterol Clin North Am. 2002;31:1–20.
5. Yang SK, Yun S, Kim JH, et al. Epidemiology of inflammatory bowel disease in the Songpa-Kangdong district, Seoul, Korea, 1986–2005: a KASID study. Inflamm Bowel Dis. 2008;14:542–549.
6. Kim ES, Kim WH. Inflammatory bowel disease in Korea: epidemiological, genomic, clinical, and therapeutic characteristics. Gut Liver. 2010;4:1–14.
7. Chang HK, Cheon KS. The clinical significance of a pathergy reaction in patients with Behcet’s disease. J Korean Med Sci. 2002;17:371–374.
8. Cosnes J, Cattan S, Blain A, et al. Long-term evolution of disease behavior of Crohn’s disease. Inflamm Bowel Dis. 2002;8:244–250.
9. Ebert EC. Gastrointestinal manifestations of Behcet’s disease. Dig Dis Sci. 2009;54:201–207.
10. Pearson DC, May GR, Fick GH, et al. Azathioprine and 6-mercaptopurine in Crohn disease. A meta-analysis. Ann Internal Med. 1995;123:132–142.
11. Timmer A, McDonald JW, Tsoulis DJ, et al. Azathioprine and 6-mercaptopurine for maintenance of remission in ulcerative colitis. Cochrane Database Syst Rev. 2012;9:CD000478.
12. Jung YS, Cheon JH, Hong SP, et al. Clinical outcomes and prognostic factors for thiopurine maintenance therapy in patients with intestinal Behcet’s disease. Inflamm Bowel Dis. 2012;18:750–757.
13. Fraser AG, Orchard TR, Jewell DP. The efficacy of azathioprine for the treatment of inflammatory bowel disease: a 30 year review. Gut. 2002;50:485–489.
14. Present DH, Meltzer SJ, Krumholz MP, et al. 6-Mercaptopurine in the management of inflammatory bowel disease: short- and long-term toxicity. Ann Intern Med. 1989;111:641–649.
15. Tanis AA. Azathioprine in inflammatory bowel disease, a safe alternative? Mediat Inflamm. 1998;7:141–144.
16. Gisbert JP, Gomollon F. Thiopurine-induced myelotoxicity in patients with inflammatory bowel disease: a review. Am J Gastroenterol. 2008;103:1783–1800.
17. Lichtenstein GR, Abreu MT, Cohen R, et al. American Gastroenterological Association Institute technical review on corticosteroids, immunomodulators, and infliximab in inflammatory bowel disease. Gastroenterology. 2006;130:940–987.
18. Kirschner BS. Safety of azathioprine and 6-mercaptopurine in pediatric patients with inflammatory bowel disease. Gastroenterology. 1998;115:813–821.
19. Markowitz J, Grancher K, Kohn N, Lesser M, Daum F. A multicenter trial of 6-mercaptopurine and prednisone in children with newly diagnosed Crohn’s disease. Gastroenterology. 2000;119:895–902.
20. Connell WR, Kamm MA, Ritchie JK, et al. Bone marrow toxicity caused by azathioprine in inflammatory bowel disease: 27 years of experience. Gut. 1993;34:1081–1085.
21. Sandborn WJ. Rational dosing of azathioprine and 6-mercaptopurine. Gut. 2001;48:591–592.
22. Kim JH, Cheon JH, Kim WH. The frequency and the course of the adverse effects of azathioprine/6-mercaptopurine treatment in patients with inflammatory bowel disease. Korean J Gastroenterol (Taehan Sohwagi Hakhoe chi). 2008;51:291–297.
23. Gisbert JP, Nino P, Rodrigo L, et al. Thiopurine methyltransferase (TPMT) activity and adverse effects of azathioprine in inflammatory bowel disease: long-term follow-up study of 394 patients. Am J Gastroenterol. 2006;101:2769–2776.
24. Jung YS, Cheon JH, Park JJ, et al. Correlation of genotypes for thiopurine methyltransferase and inosine triphosphate pyrophosphatase with long-term clinical outcomes in Korean patients with inflammatory bowel diseases during treatment with thiopurine drugs. J Hum Genet. 2010;55:121–123.
25. Kim JH, Cheon JH, Hong SS, 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–e248.
26. Cheon JH, Kim ES, Shin SJ, et al. Development and validation of novel diagnostic criteria for intestinal Behcet’s disease in Korean patients with ileocolonic ulcers. Am J Gastroenterol. 2009;104:2492–2499.
27. Lennard-Jones JE. Classification of inflammatory bowel disease. Scand J Gastroenterol Suppl. 1989;170:2–6 (discussion 16–19).
28. Lee HW, Kim WH, Cheon JH. The medical treatments of intestinal Behçet’s disease: an update. Intest Res. 2013;11:155–160.
29. Stange EF, Travis SP, Vermeire S, et al. European evidence-based Consensus on the diagnosis and management of ulcerative colitis: definitions and diagnosis. J Crohn’s Colitis. 2008;2:1–23.
30. Park JJ, Cheon JH, Hong SP, et al. Outcome predictors for thiopurine maintenance therapy in patients with Crohn’s disease. Dig Dis Sci. 2012;57:133–141.
31. Burke DA, Dixon MF, Axon AT. Ulcerative colitis: prolonged remission following azathioprine-induced pancytopenia. J Clin Gastroenterol. 1989;11:327–330.
32. Choi YS, Suh JP, Song KH, et al. A case of Crohn’s disease with improvement after azathioprine-induced pancytopenia. Case Rep Gastroenterol. 2011;5:344–349.
33. Colonna T, Korelitz BI. The role of leukopenia in the 6-mercaptopurine-induced remission of refractory Crohn’s disease. Am J Gastroenterol. 1994;89:362–366.
34. Korelitz BI, Zlatanic J, Smith MJ, et al. Significance of WBC differential when leukopenia is induced by 6-MP for IBD. Gastroenterology. 1997;113:1810–1811.
35. Teahon K, Bjarnason I. Comparison of leukocyte excretion and blood loss in inflammatory disease of the bowel. Gut. 1993;34:1535–1538.
36. Campbell S, Ghosh S. Is neutropenia required for effective maintenance of remission during azathioprine therapy in inflammatory bowel disease? Eur J Gastroenterol Hepatol. 2001;13:1073–1076.
37. Persley KM, Present DH. Neutropenia is not required for clinical remission during azathioprine therapy in inflammatory bowel disease. Eur J Gastroenterol Hepatol. 2001;13:1053–1055.
38. Hande S, Wilson-Rich N, Bousvaros A, et al. 5-aminosalicylate therapy is associated with higher 6-thioguanine levels in adults and children with inflammatory bowel disease in remission on 6-mercaptopurine or azathioprine. Inflamm Bowel Dis. 2006;12:251–257.
39. Lowry PW, Franklin CL, Weaver AL, et al. Leucopenia resulting from a drug interaction between azathioprine or 6-mercaptopurine and mesalamine, sulphasalazine, or balsalazide. Gut. 2001;49:656–664.
40. Kim PS, Zlatanic J, Korelitz BI, et al. Optimum duration of treatment with 6-mercaptopurine for Crohn’s disease. Am J Gastroenterol. 1999;94:3254–3257.
41. Sahmoud T, Hoctin-Boes G, Modigliani R, et al. Identifying patients with a high risk of relapse in quiescent Crohn’s disease. The GETAID Group. The Groupe d’Etudes Therapeutiques des Affections Inflammatoires Digestives. Gut 1995;37:811–818.
42. Bouma G, Strober W. The immunological and genetic basis of inflammatory bowel disease. Nat Rev Immunol. 2003;3:521–533.
43. Macdonald TT, Monteleone G. Immunity, inflammation, and allergy in the gut. Science (New York, NY). 2005;307:1920–1925.
44. Ginaldi L, De Martinis M, D’Ostilio A, et al. The immune system in the elderly: II. Specific cellular immunity. Immunol Res. 1999;20:109–115.
45. D’Inca R, Bertomoro P, Mazzocco K, et al. Risk factors for non-adherence to medication in inflammatory bowel disease patients. Aliment Pharmacol Ther. 2008;27:166–172.
46. Horne R, Parham R, Driscoll R, et al. Patients’ attitudes to medicines and adherence to maintenance treatment in inflammatory bowel disease. Inflamm Bowel Dis. 2009;15:837–844.
47. Pearson DC, May GR, Fick G, et al. Azathioprine for maintaining remission of Crohn’s disease. Cochrane Database Syst Rev. 2000:CD000067.
48. Hibi T, Naganuma M, Kitahora T, et al. Low-dose azathioprine is effective and safe for maintenance of remission in patients with ulcerative colitis. J Gastroenterol. 2003;38:740–746.
49. Ha C, Dassopoulos T. Thiopurine therapy in inflammatory bowel disease. Expert Rev Gastroenterol Hepatol. 2010;4:575–588.