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Published in: Digestive Diseases and Sciences 1/2012

01-01-2012 | Original Article

Outcome Predictors for Thiopurine Maintenance Therapy in Patients with Crohn’s Disease

Authors: Jae Jun Park, Jae Hee Cheon, Sung Pil Hong, Tae Il Kim, Won Ho Kim

Published in: Digestive Diseases and Sciences | Issue 1/2012

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Abstract

Background

Little is known about the factors that predict clinical relapse in Crohn’s disease patients receiving thiopurine therapy to maintain remission. The objective of this study was, therefore, to investigate these factors.

Methods

A total of 82 Crohn’s disease patients who received their first course of azathioprine or 6-mercaptopurine treatment at Severance Hospital between June 1996 and July 2007 were recruited to the study. During the follow-up period (25.5 ± 16.6 months) 19 patients (23.2%) discontinued the medication because of significant adverse effects. Forty-five patients who continued to receive thiopurines to maintain medically or surgically induced remission were enrolled in the study. After adjusting the maintenance dose, patients in remission were followed at 2–3 month intervals. Relapse was defined as a Crohn’s disease activity index ≥150.

Results

The male-to-female ratio was 1.5:1 and the mean age was 26.3 ± 7.1 years. Cumulative relapse was 18.0% after one year and 49.2% after three years. According to multivariate Cox regression analysis, younger age (<30 years) at thiopurine therapy and increased C-reactive protein level (≥0.5 mg/dL) at remission were independent predictors of relapse (hazard ratio 19.751, 95%-confidence interval (CI) 1.996–195.402, P = 0.011 and hazard ratio 9.001, 95% CI 1.583–51.181, P = 0.013, respectively).

Conclusions

Younger age (<30 years) and increased C-reactive protein level at remission were independent predictors of relapse in Crohn’s disease patients receiving thiopurines to maintain remission. These high-risk groups warrant closer observation and possibly early introduction of biological agents.
Literature
1.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
2.
go back to reference Loftus EV Jr, Sandborn WJ. Epidemiology of inflammatory bowel disease. Gastroenterol Clin North Am. 2002;31:1–20.PubMedCrossRef Loftus EV Jr, Sandborn WJ. Epidemiology of inflammatory bowel disease. Gastroenterol Clin North Am. 2002;31:1–20.PubMedCrossRef
3.
go back to reference Munkholm P, Langholz E, Nielsen OH, et al. Incidence and prevalence of Crohn’s disease in the county of Copenhagen, 1962–1987: a sixfold increase in incidence. Scand J Gastroenterol. 1992;27:609–614.PubMedCrossRef Munkholm P, Langholz E, Nielsen OH, et al. Incidence and prevalence of Crohn’s disease in the county of Copenhagen, 1962–1987: a sixfold increase in incidence. Scand J Gastroenterol. 1992;27:609–614.PubMedCrossRef
4.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
5.
go back to reference Kim ES, Kim WH. Inflammatory bowel disease in Korea: epidemiological, genomic, clinical, and therapeutic characteristics. Gut Liver. 2010;4:1–14.PubMedCrossRef Kim ES, Kim WH. Inflammatory bowel disease in Korea: epidemiological, genomic, clinical, and therapeutic characteristics. Gut Liver. 2010;4:1–14.PubMedCrossRef
6.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
7.
go back to reference Pearson DC, May GR, Fick G, et al. Azathioprine for maintaining remission of Crohn’s disease. Cochrane Database Syst Rev. 2000;2:CD000067. Pearson DC, May GR, Fick G, et al. Azathioprine for maintaining remission of Crohn’s disease. Cochrane Database Syst Rev. 2000;2:CD000067.
8.
go back to reference 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;104:2089–2096.PubMedCrossRef 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;104:2089–2096.PubMedCrossRef
9.
go back to reference Candy S, Wright J, Gerber M, et al. A controlled double blind study of azathioprine in the management of Crohn’s disease. Gut. 1995;37:674–678.PubMedCrossRef Candy S, Wright J, Gerber M, et al. A controlled double blind study of azathioprine in the management of Crohn’s disease. Gut. 1995;37:674–678.PubMedCrossRef
10.
go back to reference Lennard-Jones JE. Classification of inflammatory bowel disease. Scand J Gastroenterol Suppl. 1989;170:2–6; discussion 16–19. Lennard-Jones JE. Classification of inflammatory bowel disease. Scand J Gastroenterol Suppl. 1989;170:2–6; discussion 16–19.
11.
go back to reference Sandborn WJ, Feagan BG, Hanauer SB, et al. A review of activity indices and efficacy endpoints for clinical trials of medical therapy in adults with Crohn’s disease. Gastroenterology. 2002;122:512–530.PubMedCrossRef Sandborn WJ, Feagan BG, Hanauer SB, et al. A review of activity indices and efficacy endpoints for clinical trials of medical therapy in adults with Crohn’s disease. Gastroenterology. 2002;122:512–530.PubMedCrossRef
12.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
13.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
14.
go back to reference Murakami Y, Matsui T, Hirai F, et al. Efficacy of azathioprine in mild or moderate relapse in Crohn’s disease: clinical and endoscopic evaluation. Dig Endosc. 2010;22:25–32.PubMedCrossRef Murakami Y, Matsui T, Hirai F, et al. Efficacy of azathioprine in mild or moderate relapse in Crohn’s disease: clinical and endoscopic evaluation. Dig Endosc. 2010;22:25–32.PubMedCrossRef
15.
go back to reference Thia KT, Loftus EV Jr, Sandborn WJ, et al. An update on the epidemiology of inflammatory bowel disease in Asia. Am J Gastroenterol. 2008;103:3167–3182.PubMedCrossRef Thia KT, Loftus EV Jr, Sandborn WJ, et al. An update on the epidemiology of inflammatory bowel disease in Asia. Am J Gastroenterol. 2008;103:3167–3182.PubMedCrossRef
16.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
17.
go back to reference Consigny Y, Modigliani R, Colombel JF, et al. A simple biological score for predicting low risk of short-term relapse in Crohn’s disease. Inflamm Bowel Dis. 2006;12:551–557.PubMedCrossRef Consigny Y, Modigliani R, Colombel JF, et al. A simple biological score for predicting low risk of short-term relapse in Crohn’s disease. Inflamm Bowel Dis. 2006;12:551–557.PubMedCrossRef
18.
go back to reference Cosnes J, Carbonnel F, Beaugerie L, et al. Effects of cigarette smoking on the long-term course of Crohn’s disease. Gastroenterology. 1996;110:424–431.PubMedCrossRef Cosnes J, Carbonnel F, Beaugerie L, et al. Effects of cigarette smoking on the long-term course of Crohn’s disease. Gastroenterology. 1996;110:424–431.PubMedCrossRef
19.
go back to reference Bouma G, Strober W. The immunological and genetic basis of inflammatory bowel disease. Nat Rev Immunol. 2003;3:521–533.PubMedCrossRef Bouma G, Strober W. The immunological and genetic basis of inflammatory bowel disease. Nat Rev Immunol. 2003;3:521–533.PubMedCrossRef
20.
go back to reference Macdonald TT, Monteleone G. Immunity, inflammation, and allergy in the gut. Science. 2005;307:1920–1925.PubMedCrossRef Macdonald TT, Monteleone G. Immunity, inflammation, and allergy in the gut. Science. 2005;307:1920–1925.PubMedCrossRef
21.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
22.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
23.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
24.
go back to reference Vermeire S, Van Assche G, Rutgeerts P. C-reactive protein as a marker for inflammatory bowel disease. Inflamm Bowel Dis. 2004;10:661–665.PubMedCrossRef Vermeire S, Van Assche G, Rutgeerts P. C-reactive protein as a marker for inflammatory bowel disease. Inflamm Bowel Dis. 2004;10:661–665.PubMedCrossRef
25.
go back to reference Desai D, Faubion WA, Sandborn WJ. Review article: biological activity markers in inflammatory bowel disease. Aliment Pharmacol Ther. 2007;25:247–255.PubMedCrossRef Desai D, Faubion WA, Sandborn WJ. Review article: biological activity markers in inflammatory bowel disease. Aliment Pharmacol Ther. 2007;25:247–255.PubMedCrossRef
26.
go back to reference Boirivant M, Leoni M, Tariciotti D, et al. The clinical significance of serum C reactive protein levels in Crohn’s disease. Results of a prospective longitudinal study. J Clin Gastroenterol. 1988;10:401–405.PubMedCrossRef Boirivant M, Leoni M, Tariciotti D, et al. The clinical significance of serum C reactive protein levels in Crohn’s disease. Results of a prospective longitudinal study. J Clin Gastroenterol. 1988;10:401–405.PubMedCrossRef
27.
go back to reference Papi C, Festa V, Leandro G, et al. Long-term outcome of Crohn’s disease following corticosteroid-induced remission. Am J Gastroenterol. 2007;102:814–819.PubMedCrossRef Papi C, Festa V, Leandro G, et al. Long-term outcome of Crohn’s disease following corticosteroid-induced remission. Am J Gastroenterol. 2007;102:814–819.PubMedCrossRef
28.
go back to reference Solem CA, Loftus EV Jr, Tremaine WJ, et al. Correlation of C-reactive protein with clinical, endoscopic, histologic, and radiographic activity in inflammatory bowel disease. Inflamm Bowel Dis. 2005;11:707–712.PubMedCrossRef Solem CA, Loftus EV Jr, Tremaine WJ, et al. Correlation of C-reactive protein with clinical, endoscopic, histologic, and radiographic activity in inflammatory bowel disease. Inflamm Bowel Dis. 2005;11:707–712.PubMedCrossRef
29.
go back to reference Schnitzler F, Fidder H, Ferrante M, et al. Mucosal healing predicts long-term outcome of maintenance therapy with infliximab in Crohn’s disease. Inflamm Bowel Dis. 2009;15:1295–1301.PubMedCrossRef Schnitzler F, Fidder H, Ferrante M, et al. Mucosal healing predicts long-term outcome of maintenance therapy with infliximab in Crohn’s disease. Inflamm Bowel Dis. 2009;15:1295–1301.PubMedCrossRef
30.
go back to reference Baert F, Moortgat L, Van Assche G, et al. Mucosal healing predicts sustained clinical remission in patients with early-stage Crohn’s disease. Gastroenterology. 2010;138:463–468; quiz e410–e461. Baert F, Moortgat L, Van Assche G, et al. Mucosal healing predicts sustained clinical remission in patients with early-stage Crohn’s disease. Gastroenterology. 2010;138:463–468; quiz e410–e461.
31.
go back to reference Devlin SM, Panaccione R. Evolving inflammatory bowel disease treatment paradigms: top-down versus step-up. Gastroenterol Clin North Am. 2009;38:577–594.PubMedCrossRef Devlin SM, Panaccione R. Evolving inflammatory bowel disease treatment paradigms: top-down versus step-up. Gastroenterol Clin North Am. 2009;38:577–594.PubMedCrossRef
32.
go back to reference Colombel JF, Sandborn WJ, Reinisch W, et al. Infliximab, azathioprine, or combination therapy for Crohn’s disease. N Engl J Med. 2010;362:1383–1395.PubMedCrossRef Colombel JF, Sandborn WJ, Reinisch W, et al. Infliximab, azathioprine, or combination therapy for Crohn’s disease. N Engl J Med. 2010;362:1383–1395.PubMedCrossRef
33.
go back to reference Lautenbach E, Berlin JA, Lichtenstein GR. Risk factors for early postoperative recurrence of Crohn’s disease. Gastroenterology. 1998;115:259–267.PubMedCrossRef Lautenbach E, Berlin JA, Lichtenstein GR. Risk factors for early postoperative recurrence of Crohn’s disease. Gastroenterology. 1998;115:259–267.PubMedCrossRef
34.
go back to reference Bitton A, Dobkin PL, Edwardes MD, et al. Predicting relapse in Crohn’s disease: a biopsychosocial model. Gut. 2008;57:1386–1392.PubMedCrossRef Bitton A, Dobkin PL, Edwardes MD, et al. Predicting relapse in Crohn’s disease: a biopsychosocial model. Gut. 2008;57:1386–1392.PubMedCrossRef
35.
go back to reference Prefontaine E, Macdonald JK, Sutherland LR. Azathioprine or 6-mercaptopurine for induction of remission in Crohn’s disease. Cochrane Database Syst Rev. 2010;6:CD000545. Prefontaine E, Macdonald JK, Sutherland LR. Azathioprine or 6-mercaptopurine for induction of remission in Crohn’s disease. Cochrane Database Syst Rev. 2010;6:CD000545.
36.
go back to reference 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;44:242–248.CrossRef 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;44:242–248.CrossRef
37.
go back to reference Hindorf U, Lindqvist M, Peterson C, et al. Pharmacogenetics during standardised initiation of thiopurine treatment in inflammatory bowel disease. Gut. 2006;55:1423–1431.PubMedCrossRef Hindorf U, Lindqvist M, Peterson C, et al. Pharmacogenetics during standardised initiation of thiopurine treatment in inflammatory bowel disease. Gut. 2006;55:1423–1431.PubMedCrossRef
38.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
39.
go back to reference Zelinkova Z, Derijks LJ, Stokkers PC, et al. Inosine triphosphate pyrophosphatase and thiopurine s-methyltransferase genotypes relationship to azathioprine-induced myelosuppression. Clin Gastroenterol Hepatol. 2006;4:44–49.PubMedCrossRef Zelinkova Z, Derijks LJ, Stokkers PC, et al. Inosine triphosphate pyrophosphatase and thiopurine s-methyltransferase genotypes relationship to azathioprine-induced myelosuppression. Clin Gastroenterol Hepatol. 2006;4:44–49.PubMedCrossRef
40.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
41.
go back to reference Gilissen LP, Bierau J, Derijks LJ, et al. The pharmacokinetic effect of discontinuation of mesalazine on mercaptopurine metabolite levels in inflammatory bowel disease patients. Aliment Pharmacol Ther. 2005;22:605–611.PubMedCrossRef Gilissen LP, Bierau J, Derijks LJ, et al. The pharmacokinetic effect of discontinuation of mesalazine on mercaptopurine metabolite levels in inflammatory bowel disease patients. Aliment Pharmacol Ther. 2005;22:605–611.PubMedCrossRef
42.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
43.
go back to reference Shah JA, Edwards CM, Probert CS. Should azathioprine and 5-aminosalicylates be coprescribed in inflammatory bowel disease?: an audit of adverse events and outcome. Eur J Gastroenterol Hepatol. 2008;20:169–173.PubMedCrossRef Shah JA, Edwards CM, Probert CS. Should azathioprine and 5-aminosalicylates be coprescribed in inflammatory bowel disease?: an audit of adverse events and outcome. Eur J Gastroenterol Hepatol. 2008;20:169–173.PubMedCrossRef
44.
go back to reference Szumlanski CL, Weinshilboum RM. Sulphasalazine inhibition of thiopurine methyltransferase: possible mechanism for interaction with 6-mercaptopurine and azathioprine. Br J Clin Pharmacol. 1995;39:456–459.PubMed Szumlanski CL, Weinshilboum RM. Sulphasalazine inhibition of thiopurine methyltransferase: possible mechanism for interaction with 6-mercaptopurine and azathioprine. Br J Clin Pharmacol. 1995;39:456–459.PubMed
45.
go back to reference 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. 2008;51:291–297.PubMed 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. 2008;51:291–297.PubMed
46.
go back to reference Lee HJ, Yang SK, Kim KJ, et al. The safety and efficacy of azathioprine and 6-mercaptopurine in the treatment of Korean patients with Crohn’s disease. Intest Res. 2009;7:22–31. Lee HJ, Yang SK, Kim KJ, et al. The safety and efficacy of azathioprine and 6-mercaptopurine in the treatment of Korean patients with Crohn’s disease. Intest Res. 2009;7:22–31.
47.
go back to reference Cheon JH, Kim JH, Kim BY, et al. Allele frequency of thiopurine methyltransferase and inosine triphosphate pyrophosphatase gene polymorphisms in Korean patients with inflammatory bowel diseases. Hepatogastroenterology. 2009;56:421–423.PubMed Cheon JH, Kim JH, Kim BY, et al. Allele frequency of thiopurine methyltransferase and inosine triphosphate pyrophosphatase gene polymorphisms in Korean patients with inflammatory bowel diseases. Hepatogastroenterology. 2009;56:421–423.PubMed
48.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
49.
go back to reference Kim DU, Kim YH, Kim BJ, et al. The efficacy of low dose azathioprine/6-mercaptopurine in patients with inflammatory bowel disease. Hepatogastroenterology. 2009;56:1395–1402.PubMed Kim DU, Kim YH, Kim BJ, et al. The efficacy of low dose azathioprine/6-mercaptopurine in patients with inflammatory bowel disease. Hepatogastroenterology. 2009;56:1395–1402.PubMed
50.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
51.
go back to reference Andoh A, Tsujikawa T, Ban H, et al. Monitoring 6-thioguanine nucleotide concentrations in Japanese patients with inflammatory bowel disease. J Gastroenterol Hepatol. 2008;23:1373–1377.PubMedCrossRef Andoh A, Tsujikawa T, Ban H, et al. Monitoring 6-thioguanine nucleotide concentrations in Japanese patients with inflammatory bowel disease. J Gastroenterol Hepatol. 2008;23:1373–1377.PubMedCrossRef
52.
go back to reference Thia KT, Li M, Ling KL, et al. Azathioprine is effective in corticosteroid-dependent Asian inflammatory bowel disease patients. Inflamm Bowel Dis. 2011;17:809–815.PubMedCrossRef Thia KT, Li M, Ling KL, et al. Azathioprine is effective in corticosteroid-dependent Asian inflammatory bowel disease patients. Inflamm Bowel Dis. 2011;17:809–815.PubMedCrossRef
53.
go back to reference Korelitz BI, Present DH. Favorable effect of 6-mercaptopurine on fistulae of Crohn’s disease. Dig Dis Sci. 1985;30:58–64.PubMedCrossRef Korelitz BI, Present DH. Favorable effect of 6-mercaptopurine on fistulae of Crohn’s disease. Dig Dis Sci. 1985;30:58–64.PubMedCrossRef
54.
go back to reference Ha C, Dassopoulos T. Thiopurine therapy in inflammatory bowel disease. Expert Rev Gastroenterol Hepatol. 2010;4:575–588.PubMedCrossRef Ha C, Dassopoulos T. Thiopurine therapy in inflammatory bowel disease. Expert Rev Gastroenterol Hepatol. 2010;4:575–588.PubMedCrossRef
Metadata
Title
Outcome Predictors for Thiopurine Maintenance Therapy in Patients with Crohn’s Disease
Authors
Jae Jun Park
Jae Hee Cheon
Sung Pil Hong
Tae Il Kim
Won Ho Kim
Publication date
01-01-2012
Publisher
Springer US
Published in
Digestive Diseases and Sciences / Issue 1/2012
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-011-1955-9

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