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


Authors: V. Suchá 1;  B. Kadlečková 2;  B. Repákova 2;  Ľ. Krajčíová 3;  Ľ. Jurgoš 1;  S. Kiňová 4;  Z. Zelinková 2,5
Authors‘ workplace: Gastroenterologická ambulancia, Jurgos s. r. o., Bratislava, Slovenská republika 1;  IBD centrum, As­siduo, Bratislava, Slovenská republika 2;  Ústav lekárskej bio­lógie, genetiky a klinickej genetiky, LF UK a UN Bratislava, Slovenská republika 3;  I. interná klinika LF UK a UN Bratislava, Slovenská republika 4;  Gastroenterologické oddelenie a oddelenie digestívnej endoskopie, Nemocnica sv. Michala, a. s., Bratislava, Slovenská republika 5
Published in: Gastroent Hepatol 2016; 70(4): 335-339
Category: IDB: Original Article
doi: https://doi.org/10.14735/amgh2016335

Overview

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.

Key words:
inflammatory bowel disease – treatment – thiopurines

The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manuscript met the ICMJE „uniform requirements“ for biomedical papers.

Submitted:
9. 7. 2016

Accepted:
11. 7. 2016


Sources

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 Aet al. Thiopurine treatment in inflam­matory bowel disease: response predictors, safety, and with-drawal 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 As­sociation 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 WJet al. Clinical pharmacogenetics implementation consortium guidelines for thiopurine me-thyltransferase 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.21494.

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 Set 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.

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.

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