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A pragmatic randomized controlled trial of thiopurine methyltransferase genotyping prior to azathioprine treatment: the TARGET study
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A pragmatic randomized controlled trial of thiopurine methyltransferase genotyping prior to azathioprine treatment: the TARGET study
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Journal Article
A pragmatic randomized controlled trial of thiopurine methyltransferase genotyping prior to azathioprine treatment: the TARGET study
2011
Overview
To conduct a pragmatic, randomized controlled trial to assess whether thiopurine methyltransferase (TPMT) genotyping prior to azathioprine reduces adverse drug reactions (ADRs).
A total of 333 participants were randomized 1:1 to undergo
genotyping prior to azathioprine or to commence treatment without genotyping.
There was no difference in the primary outcome of stopping azathioprine due to an adverse reaction (ADR, p = 0.59) between the two study arms. ADRs were more common in older patients (p = 0.01). There was no increase in stopping azathioprine due to ADRs in
heterozygotes compared with wild-type individuals. The single individual with TPMT variant homozygosity experienced severe neutropenia.
Our work supports the strong evidence that individuals with TPMT variant homozygosity are at high risk of severe neutropenia, whereas
heterozygotes are not at increased risk of ADRs at standard doses of azathioprine.
Original submitted 5 January 2011; Revised submitted 18 February 2011
Publisher
Future Medicine Ltd
Subject
/ Anti-Inflammatory Agents, Non-Steroidal - administration & dosage
/ Anti-Inflammatory Agents, Non-Steroidal - adverse effects
/ Azathioprine - administration & dosage
/ Azathioprine - adverse effects
/ Drug-Related Side Effects and Adverse Reactions - genetics
/ Drug-Related Side Effects and Adverse Reactions - prevention & control
/ Genetic Predisposition to Disease
/ Genotype
/ Humans
/ Methyltransferases - genetics
/ thiopurine methyltransferase
/ TPMT
