Effect of the Activity of Thiopurine Methyltransfrase
on the Results of Long-term Immunosuppressive Therapy with Azathioprin (6-mercaptopurine)
in Patients with Inflammatory Bowel Diseases
Chalupná P., Lukáš M., Kumšta M.a,b, Šebesta I.b
Gastroenterologické centrum VFN, IV. interní klinika VFN a 1. LF UK, Praha a Ústav biochemie a mikrobiologie VŠCHT, Praha b Ústav klinické biochemie VFN a 1. LF UK, Praha |
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Summary:
The enzyme thiopurine methyltransferase (TPMT) plays a crucial role in the purine metabolism. The objective
of the study was to assess the influence of TPMT activity on the results of long-term therapy with azathioprin
or 6-mercaptopurine in patients with inflammatory bowel diseases. The prospective trial comprised 50 patients
(28 Crohn’s disease, 22 ulcerative colitis) with a chronically active course of the disease. The mean period
of azathioprin (6-mercaptopurine) treatment was 74 weeks, the mean daily dose was 1.8 mg/kg for azathioprin
and 1.1 mg/kg for 6-mercaptopurine. The median TPMT activity in formed blood elements was in patients
with inflammatory bowel diseases 36.9 pmol/hour mg Hb. The authors detected no relationship between the
patient’ s sex and age and the TPMT activity. The influence of long-term azathioprin therapy on the activity of
ulcerativ colitis expressed by the Truelove-Witts index, in patients with Crohn’s disease by the Activity-Severity
index was not modified by the baseline TPMT activity (p = 0.42 and p = 0.62 resp.). Similar results were
obtained by comparison of the activity of the disease by means of laboratory markers (CRP p = 0.85, leukocytes
p = 0.94, thrombocytes p = 0.59).The authors did not prove any effect of the baseline TPMT activity on the
corticoid sparing effect of azathioprin (6-mercaptopurine ) (p = 0.50, r = 0.097). Undesirable effects of therapy
developed in 10% patients and were not affected by TPMT activity. No correlation was found between the
TPMT activity and long-term therapeutic response during azathioprin (6-mercaptopurine) treatment assessed
by means of clinical activity indexes, laboratory parameters of the inflammation and the corticoid sparing
effect.
Key words:
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