ABSTRACT Background: The role of azathioprine (AZA) and 6-mercaptopurine (6-MP) in the induction of remission in patients with ulcerative colitis (UC) remains unclear. Aims: To compare the efficacy and safety of low-dose thiopurine (AZA/6-MP) and cytapheresis (CAP) for the induction of remission in patients with steroid- dependent UC. Patients and Methods: We reviewed the clinical course of 65 patients with steroid-dependent UC with moderate activity, who were treated with either low-dose AZA/6-MP (T-group, n = 38) or with CAP (C-group, n = 27). The efficacy and safety for the first 10 weeks after the start of the therapies were compared between the two groups. The cumulative probability curves of treatment failure were estimated by the Kaplan-Meier method. Clinical remission was defined as an ulcerative colitis activity index value of less than 150 without any other treatments. Results: Neither clinical characteristics, concomitant therapies, nor laboratory data (except for serum albumin levels) were different between the two groups. The remission rate at 10 weeks was not different between the two groups (55.3% in the T-group and 70.4% in the C-group, p = 0.22 in the intention-to-treat analysis). The frequencies of adverse events did not differ be- tween the two groups (p = 0.12). The cumulative pro- bability of treatment failure at 10 weeks was 44.7% for the T-group and 29.6% for the C-group (p = 0.23). Conclusions: Low-dose thiopurine therapy is an alter- native candidate for the induction of remission in pa- tients with steroid-dependent, moderate UC.
Cite this paper
Kochi, S. , Nakamura, S. and Matsumoto, T. (2012) Efficacy of low-dose thiopurine therapy for the induction of remission in steroid-dependent ulcerative colitis: Comparison with cytapheresis. Open Journal of Gastroenterology, 2, 9-14. doi: 10.4236/ojgas.2012.21002.
 Timmer, A., McDonald, J.W. and Macdonald, J.K. (2007) Aza-thioprine and 6-mercaptopurine for maintenance of remission in ulcerative colitis. Cochrane Database of Sys- tematic Reviews, 1, CD000478.
 Gisbert, J.P., Linares, P.M., McNicholl, A.G., et al. (2009) Meta-analysis: The efficacy of azathioprine and mercap- topurine in ulcerative colitis. Aliment Pharmacol & The- rapeutics, 30, 126-137.
 Ardizzone, S., Maconi, G., Russo, A., et al. (2006) Ran- domised controlled trial of azathioprine and 5-aminosali- cylic acid for treatment of steroid dependent ulcerative colitis. Gut, 55, 47-53. doi:10.1136/gut.2005.068809
 Kirk, A.P. and Len-nard-Jones, J.E. (1982) Controlled trial of azathioprine in chronic ulcerative colitis. British Medi- cine Journal, 284, 1291-1292.
 Caprilli, R., Carratù, R. and Babbini, M. (1975) Double- blind comparison of the effec-tiveness of azathioprine and sulfasalazine in idiopathic procto-colitis. Preliminary re- port. The American Journal of Digestive Diseases, 20, 115-120. doi:10.1007/BF01072336
 Orth, T., Peters, M., Schlaak, J.F., et al. (2000) Myco- phenolate mofetil versus azathioprine in patients with chronic active ulcerative colitis: A 12-month pilot study. The American Journal of Gas-troenterology, 95, 1201- 1207. doi:10.1111/j.1572-0241.2000.02010.x
 Adler, D.J. and Korelitz, B.I. (1990) The therapeutic ef- ficacy of 6-mercaptopurine in refractory ulcerative colitis. The American Journal of Gastroenterology, 85, 717-722.
 Maté-Jiménez, J., Hermida, C., Cantero-Perona, J., et al. (2000) 6-Mercaptopurine or methotrexate added to pred- nisone induces and maintains remission in steroid-de- pendent inflammatory bowel disease. European Journal of Gastroenterology and Hepatology, 12, 1227-1233.
 Lichtenstein, G.R., Abreu, M.T., Cohen, R., et al. (2006) American Gastroen-terological Association Institute tech- nical review on corticos-teroids, immunomodulators, and infliximab in inflammatory bowel disease. Gastroenter- ology, 130, 940-987. doi:10.1053/j.gastro.2006.01.048
 Hibi, T., Naganuma, M., Kitahora, T., et al. (2003) Low- dose azathioprine is effective and safe for maintenance of remission in patients with ulcerative colitis. Journal of Gastrotenterology, 38, 740-746.
 Tanaka, T., Okanobu, H., Yoshimi, S., et al. (2008) In patients with ulcerative colitis, adsorptive depletion of granulocytes and monocytes impacts mucosal level of neutrophils and clinically is most effective in steroid na- ?ve patients. Digestive and Liver Disease, 40, 731-736.
 Shimoyama, T., Sawada, K., Hiwatashi, N., et al. (2001) Safety and efficacy of granulocyte and monocyte adsorp- tion apheresis in patients with active ulcerative colitis: A multicenter study. Journal of Clinical Apheresis, 16, 1-9.
 Suzuki, Y., Yoshimura, N., Sania-badi, A.R., et al. (2004) Selective granulocyte and monocyte adsorptive apheresis as a first-line treatment for steroid na?ve patients with ac- tive ulcerative colitis: A prospective uncon-trolled study. Digestive Diseases and Science, 49, 565-571.
 Sawada, K., Ohnishi, K., Fukui, S., et al. (1995) Leuko- cytapheresis therapy, performed with leukocyte removal filter, for inflammatory bowel disease. Journal of Gastro- enterology, 30, 322-329. doi:10.1007/BF02347507
 Naganuma, M., Funakoshi, S., Sakuraba, A., et al. (2004) Granulocytapheresis is useful as an alternative therapy in patients with steroid-refractory or -dependent ulcerative colitis. Inflammmtory Bowel Diseases, 10, 251-257.
 Hanai, H., Wa-tanabe, F., Yamada, M., et al. (2004) Ad- sorptive granulocyte and monocyte apheresis versus pre- dnisolone in patients with corticosteroid-dependent mod- erately severe ulcerative colitis. Digestion, 70, 36-44.
 Takemoto, K., Kato, J., Kuriyama, M., et al. (2007) Pre- dictive factors of efficacy of leuko-cytapheresis for ster- oid-resistant ulcerative colitis patients. Digestive and Liver Disease, 39, 422-429. doi:10.1016/j.dld.2007.01.010
 Domènech, E., Hinojosa, J., Esteve-Comas, M., et al. (2004) Granulocyteaphaeresis in stero-id-dependent inflammatory bowel disease: A prospective, open, pilot study. Alimen- tary Pharmacology & Therapeutics, 20, 1347-1352.
 Seo, M., Okada, M., Yao, T., et al. (1992) An index of disease activity in patients with ulcerative colitis. The American Journal of Gastro-enterology, 87, 971-976.
 Sandborn, W.J. and Hanauer, S.B. (2003) Systematic re- view: The pharmacokinetic profiles of oral mesalazine formulations and mesalazine pro-drugs used in the man- agement of ulcerative colitis. Alimentary Pharma-cology & Therapeutics, 17, 29-42.
 Jewell, D.P. and Truelove, S.C. (1974) Azathioprine in ulcerative colitis: Final report on controlled therapeutic trial. British Medicine Journal, 4, 627-630.
 Sood, A., Midha, V., Sood, N., et al. (2000) Role of aza- thioprine in severe ulcerative colitis: One-year, placebo- controlled, randomized trial. Indian Journal of Gastroen- terology, 19, 14-16.
 Present, D.H., Korelitz, B.I., Wisch, N., et al. (1980) Treat- ment of Crohn’s disease with 6-mercaptopurine. A long- term, randomized, double-blind study. The New England Journal of Medicine, 302, 981-987.
 Yamamoto, T., Umegae, S. and Matsumoto, K. (2006) Safety and clinical effi-cacy of granulocyte and monocyte adsorptive apheresis therapy for ulcerative colitis. World Journal of Gastroenterology, 12, 520-525.
 Panés, J., Guilera, M., Ginard, D., et al. (2007) Treatment cost of ulcerative colitis is apheresis with Adacolumn cost-effective? Digestive and Liver Disease, 39, 617-625.
 Teml, A., Schaeffeler, E., Herrlinger, K.R., et al. (2007) Thiopurine treatment in inflammatory bowel disease: Clin- ical pharmacology and implication of pharmacogeneti- cally guided dosing. Clinical Pharmacokinetics, 46, 187- 208. doi:10.2165/00003088-200746030-00001