Newman, William G, Payne, Katherine, Tricker, Karen, Roberts, Stephen A, Fargher, Emily, Pushpakom, Sudeep, Alder, Jane, Sidgwick, Gary P, Payne, Debbie, Elliott, Rachel A, Heise, Marco, Elles, Robert, Ramsden, Simon C, Andrews, Julie, Houston, J Brian, Qasim, Faeiza, Shaffer, Jon, Griffiths, Christopher EM, Ray, David W, Bruce, Ian and Ollier, William ER (2011) A pragmatic randomized controlled trial of thiopurine methyltransferase genotyping prior to azathioprine treatment: the TARGET study. Pharmacogenomics, 12 (6). pp. 815-826. ISSN 1462-2416
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Official URL: http://dx.doi.org/10.2217/pgs.11.32
Aim: To conduct a pragmatic, randomized controlled trial to assess whether thiopurine methyltransferase (TPMT) genotyping prior to azathioprine reduces adverse drug reactions (ADRs). Methods: A total of 333 participants were randomized 1:1 to undergo TPMT genotyping prior to azathioprine or to commence treatment without genotyping. Results: 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 TPMT heterozygotes compared with wild-type individuals. The single individual with TPMT variant homozygosity experienced severe neutropenia. Conclusion: Our work supports the strong evidence that individuals with TPMT variant homozygosity are at high risk of severe neutropenia, whereas TPMT heterozygotes are not at increased risk of ADRs at standard doses of azathioprine.
|Subjects:||R Medicine > RS Pharmacy and materia medica|
|Schools:||College of Clinical & Biomedical Sciences > School of Pharmacy and Biomedical Sciences|
|Deposited By:||Michael Bowerman|
|Deposited On:||29 Mar 2012 19:28|
|Last Modified:||20 Mar 2014 15:16|
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