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[Thiopurine methyltransferase activity in inflammatory bowel disease. A study on 7046 Spanish patients].

Abstract：

BACKGROUND AND OBJECTIVE:Our objective was to assess the activity of thiopurine methyltransferase (TPMT) in a very large number of Spanish patients with inflammatory bowel disease (IBD), to evaluate the influence of several variables (including azathioprine or 6-mercaptopurine) on that activity, and to know the proportion of patients with low TPMT activity and therefore high risk of myelotoxicity when treated with these drugs. PATIENTS AND METHOD:TPMT activity in red blood cells (RBCs) was measured by a radiochemical method. The association between several variables and TPMT values was assessed by multiple lineal regression. RESULTS:7046 patients were included (mean age: 37 years; 53% males): 70% with Crohn's disease, 22% with ulcerative colitis, and 8% with indeterminate colitis. Mean TPMT value was 20 (6) U/ml RBCs (minimum 0 and maximum 46). TPMT activity distribution was as follows: low levels (< 5 U/ml), 0.5%; intermediate (5-13.7), 11.1%; and high (> or = 13.8), 88.4%. TPMT values did not follow a normal distribution (p < 0.001). In the univariate study, statistically significant differences (p < 0.001), yet of doubtly clinical significance because its minimal magnitude, were demonstrated in TPMT values depending on age, sex, type of disease, and treatment with azathioprine/6-mercaptopurine. In the multivariate study, the variables associated with TPMT activity were: sex, treatment with 5-aminosalicylates, steroids and azathioprine/6-mercaptopurine. CONCLUSIONS:This study shows that 0.5% of the Spanish patients with IBD have low TPMT activity (< 5 U/ml RBCs), a figure similar to that reported in other countries, these patients being at higher risk of myelotoxicity when treated with azathioprine or 6-mercaptopurine. The drugs usually prescribed for the treatment of IBD, including 5-aminosalicylates and azathioprine/6-mercaptopurine, do not seem to modify in a clinically relevant manner TPMT activity.

journal_name

Med Clin (Barc)

journal_title

Medicina clinica

authors

Gisbert JP,Gomollón F,Cara C,Luna M,González-Lama Y,Pajares JM,Maté J,Guijarro LG

doi

10.1157/13078420

keywords:

subject

Has Abstract

pub_date

2005-09-10 00:00:00

pages

281-5

issue

eissn

0025-7753

issn

1578-8989

pii

S0025-7753(05)72019-4

journal_volume

125

pub_type

杂志文章

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[Thiopurine methyltransferase activity in inflammatory bowel disease. A study on 7046 Spanish patients].