Anonymous User
Login / Registration

Gastroenterologie
a hepatologie

Gastroenterology and Hepatology

Gastroent Hepatol 2016; 70(4): 335–339. doi:10.14735/amgh2016335.

Thiopurine undertreatment among inflammatory bowel disease patients referred for anti-TNF therapy

Veronika Suchá1, Barbora Kadlečková2, Beáta Repáková3, Ľubica Krajčíová4, Ľubomír Jurgoš1, Soňa Kiňová5, Zuzana Zelinková2

+ Affiliation

Summary


Thiopurines are effective in maintaining remission in inflammatory bowel disease (IBD) patients. Their effect is dose-dependent, and the optimal daily dose of azathioprine (AZA) is 2–2.5 mg/kg. Inadequate dosing may result in lack of efficacy and ensuing premature referral for biological therapy. Aim: The aims were to assess the rate of deviation from the normal thiopurine dose among IBD patients referred for biological therapy and to analyze the reasons for this deviation. Patients and Methods: All the IBD patients referred for anti-TNF therapy in one referral center by November 2014 were included. The dose of AZA at the time of indication for step-up to anti-TNF was noted, as well as the reasons for the use of a reduced dose of AZA, which was defined as a dose lower than 2 mg/kg. Results: In total, 176 IBD patients were included. The mean age was 37 years (range 18–76 years), 92 (52%) were men, 120 (68%) had Crohn‘s disease, 54 (31%) had ulcerative colitis, and two (1%) were IBD unclassified. Twenty-eight patients (16%) were receiving an unreduced dose of AZA; 93 (53%) patients had not used AZA previously (8 patients; 5%) or were using a low dose of AZA (85 patients; 48%) without documented reasons; 55 patients (32%) had discontinued AZA (38 patients; 22%) or undergone a dose reduction (17 patients; 10%) of AZA because of adverse events. Conclusion: In a real life clinical practice a substantial proportion of IBD patients referred for anti-TNF therapy are using low dose AZA with only a minority for well documented reasons of biologically-determined  intolerance.

Keywords

treatment, inflammatory bowel disease, thiopurines

To read this article in full, please register for free on this website.

Benefits for subscribers

Benefits for logged users

Literature

1. Prefontaine E, Sutherland LR, Macdonald JK et al. Azathioprine or 6-mercaptopurine for maintenance of remission in Crohn’s disease. Cochrane Database Syst Rev 2009; 1: CD000067. doi: 10.1002/14651858.CD000067.pub2.
2. Prefontaine E, Macdonald JK, Sutherland LR. Azathioprine or 6-mercaptopurine for induction of remission in Crohn’s disease. Cochrane Database Syst Rev 2010; 4: CD000545. doi: 10.1002/14651858.CD000545.pub2.
3. Timmer A, McDonald JW, Macdonald JK. Azathioprine and 6-mercaptopurine for maintenance of remission in ulcerative colitis. Cochrane Database Syst Rev 2007; 1: CD000478.
4. Dignass A, Van Assche G, Lindsay JO et al. The second European evidence-based Consensus on the diagnosis and management of Crohn’s disease: current management. J Crohns Colitis 2010; 4 (1): 28–62. doi: 10.1016/j.crohns.2009.12.002.
5. Lichtenstein GR, Abreu MT, Cohen R et al. American Gastroenterological Association Institute medical position statement on corticosteroids, immunomodulators, and infliximab in inflammatory bowel disease. Gastroenterology 2006; 130 (3): 935–939.
6. Cosnes J, Gower-Rousseau C, Seksik P et al. Epidemiology and natural history of inflammatory bowel diseases. Gastroenterology 2011; 140 (6): 1785–1794. doi: 10.1053/j.gastro.2011.01.055.
7. Chouchana L, Narjoz C, Beaune P et al. Review article: the benefits of pharmacogenetics for improving thiopurine therapy in inflammatory bowel disease. Aliment Pharmacol Ther 2012; 35 (1): 15–36. doi: 10.1111/j.1365-2036.2011.04905.x.
8. 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.
9. Jharap B, Seinen ML, de Boer NK et al. Thiopurine therapy in inflammatory bowel disease patients: analyses of two 8-year intercept cohorts. Inflamm Bowel Dis 2010; 16 (9): 1541–1549. doi: 10.1002/ibd.21221.
10. Hindorf U, Lindqvist M, Hildebrand H et al. Adverse events leading to modification of therapy in a large cohort of patients with inflammatory bowel disease. Aliment Pharmacol Ther 2006; 24 (2): 331–342.
11. Costantino G, Furfaro F, Belvedere A et al. Thiopurine treatment in inflammatory bowel disease: response predictors, safety, and withdrawal in follow-up. J Crohns Colitis 2012; 6 (5): 588–596. doi: 10.1016/j.crohns.2011.11.007.
12. Frei P, Biedermann L, Nielsen OH et al. Use of thiopurines in inflammatory bowel disease. World J Gastroenterol 2013; 19 (7): 1040–1048. doi: 10.3748/wjg.v19.i7. 1040.
13. Goel RM, Blaker P, Mentzer A et al. Optimizing the use of thiopurines in inflammatory bowel disease. Ther Adv Chronic Dis 2015; 6 (3): 138–146. doi: 10.1177/ 2040622315579063.
14. Greguš M. Riziká imunosupresívnej liečby tiopurínmi u IBD pacientov. Gastroenterol Prax 2013; 12 (3): 130–133.
15. Kopylov U, Ben-Horin S, Seidman E. Therapeutic drug monitoring in inflammatory bowel disease. Ann Gastroenterol 2014; 27 (4): 304–312.
16. Lichtenstein GR, Abreu MT, Cohen R et al. American Gastroenterological Asso-ciation Institute medical position statement on corticosteroids, immunomodulators, and infliximab in inflammatory bowel disease. Gastroenterology 2006; 130 (3): 935–939. doi: 10.1038/ clpt.2010.320.
17. Relling MV, Gardner EE, Sandborn WJ et al. Clinical pharmacogenetics imple- mentation consortium guidelines for thiopurine methyltransferase genotype and thiopurine dosing. Clin Pharmacol Ther 2011; 89 (3): 387–391. doi: 10.1038/clpt. 2010.320.
18. Weinshilboum RM, Sladek SL. Mercaptopurine pharmacogenetics: monogenic inheritance of erythrocyte thiopurine methyltransferase activity. Am J Hum Genet 1980; 32 (5): 651–662.
19. Chevaux JB, Peyrin-Biroulet L, Sparrow MP. Optimizing therapy in inflammatory bowel disease. Inflamm Bowel Dis 2011; 17 (6): 1428–1435. doi: 10.1002/ibd.21 494.
20. Ansari A, Patel N, Sanderson J et al. Low-dose azathioprine or mercaptopurine in combination with allopurinol can bypass many adverse drug reactions in patients with inflammatory bowel disease. Aliment Pharmacol Ther 2010; 31 (6): 640–647. doi: 10.1111/j.1365-2036.2009.04221.x.
21. 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.
22. Sparrow MP, Hande SA, Friedman S et al. Allopurinol safely and effectively optimizes tioguanine metabolites in inflammatory bowel disease patients not re- sponding to azathioprine and mercaptopurine. Aliment Pharmacol Ther 2005; 22 (5):  441–446.
23. Hoentjen F, Seinen ML, Hanauer SB et al. Safety and effectiveness of long-term allopurinol-thiopurine maintenance treatment in inflammatory bowel disease. Inflamm Bowel Dis 2013; 19 (2): 363–369. doi: 10.1002/ibd.23021.
24. Smith MA, Blaker P, Marinaki AM et al. Optimising outcome on thiopurines in inflammatory bowel disease by co-prescription of allopurinol. J Crohns Colitis 2012; 6 (9): 905–912. doi: 10.1016/j.crohns.2012.02.007.

Kreditovaný autodidaktický test