Home Bratislava Medical Journal 2013 Bratislava Medical Journal Vol.114, No.4, p.199–205, 2013

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Published Monthly, in English
Founded: 1919
ISSN 0006-9248
(E)ISSN 1336-0345
 

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Bratislava Medical Journal Vol.114, No.4, p.199–205, 2013

Title: The impact of thiopurine-S-methyltransferase genotype on the adverse drug reactions to azathioprine in patients with inflammatory bowel diseases
Author: T. Hlavaty, M. Batovsky, D. Balakova, I. Pav, P. Celec, M. Gregus, M. Zakuciova, M. Hlista, M. Horakova, B. Desatova, T. Koller, J. Toth, L. Kadasi, M. Huorka

Abstract:

Background and aims: The thiopurine drugs, azathioprine (AZA) and 6-mercaptopurine, are established in the treatment of inflammatory bowel diseases (IBD). Polymorphisms in thiopurine S-methyltransferase (TPMT) gene have been associated with adverse drug reactions (ADRs) to AZA.
Methods: The aim of this study was to evaluate TPMT polymorphisms and AZA-related toxicity in a Slovak cohort of 220 IBD patients treated with AZA. In every patient, the dose and duration of AZA therapy, concomitant 5-aminosalicylate (5-ASA) medication, frequency, type, time to onset, dose of ADR and concomitant 5-ASA at the onset of ADR were recorded. Each patient was also genotyped for the presence of variant TPMT alleles (*2,*3A,*3B,*3C). Frequency, type and circumstances of ADRs were compared according to TPMT status.
Results: Of the 220 patients, 205 (93.2 %) were wild-type (TPMT*1/*1), one (0.5%) carried a TPMT*1/*3C allele, 13 (5.9 %) carried TPMT *1/*3A allele and one was homozygous for TMPT *3A allele. No TPMT *2 mutation was found. The incidence of adverse drug reactions was 62/205 (30.2 %) in the wild-type group as compared to 13/15 (86.7 %) in the TPMT mutation group, p=2.10-5. Leukopenia (WBC< 3.0*10^9/L) occurred in 21/205 (10.2 %) patients with wild type TPMT versus 11/15 (73.3 %) patients with TPMT mutations, p=0.000001. There was no significant difference between TMPT groups in gastrointestinal or other ADRs. No impact of 5-ASA on the incidence and severity of AZA adverse drug reactions was observed.


Conclusion: The incidence of leukopenia in TPMT mutant patients was significantly higher and more severe as compared to TPMT wild type patients. We observed no impact of concomitant 5-ASA therapy on AZA induced toxicity (Tab. 4, Fig. 2, Ref. 37).



Keywords: inflammatory bowel diseases, Crohn’s disease, ulcerative colitis, therapy, azathioprine, 6-mercaptopurine, thiopurine-S-methyltransferase, polymorphisms, adverse drug reaction
Year: 2013, Volume: 114, Issue: 4 Page From: 199, Page To: 205
doi:10.4149/BLL_2013_042


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