A pragmatic randomized controlled trial of thiopurine methyltransferase genotyping prior to azathioprine treatment: The TARGET study

William G. Newman; Katherine Payne; Karen Tricker; Stephen A. Roberts; Emily Fargher; Sudeep Pushpakom; Jane E. Alder; Gary P. Sidgwick; Debbie Payne; Rachel A Elliott; Marco Heise; Robert Elles; Simon C. Ramsden; Julie Andrews; J. Brian Houston; Faeiza Qasim; Jon Shaffer; Christopher E M Griffiths; David W. Ray; Ian Bruce; William E R Ollier

doi:10.2217/pgs.11.32

A pragmatic randomized controlled trial of thiopurine methyltransferase genotyping prior to azathioprine treatment: The TARGET study

William G. Newman, Katherine Payne, Karen Tricker, Stephen A. Roberts, Emily Fargher, Sudeep Pushpakom, Jane E. Alder, Gary P. Sidgwick, Debbie Payne, Rachel A Elliott, Marco Heise, Robert Elles, Simon C. Ramsden, Julie Andrews, J. Brian Houston, Faeiza Qasim, Jon Shaffer, Christopher E M Griffiths, David W. Ray, Ian BruceWilliam E R Ollier

Division of Population Health, Health Services Research & Primary Care (L5)

Research output: Contribution to journal › Article › peer-review

Abstract

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. © 2011 Future Medicine Ltd.

Original language	English
Pages (from-to)	815-826
Number of pages	11
Journal	Pharmacogenomics
Volume	12
Issue number	6
DOIs	https://doi.org/10.2217/pgs.11.32
Publication status	Published - Jun 2011

Keywords

azathioprine
pharmacogenetics
randomized controlled trial
thiopurine methyltransferase
TPMT

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http://zetoc.mimas.ac.uk/wzgw?db=etoc&terms=RN293458903&field=zid

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Newman, W. G., Payne, K., Tricker, K., Roberts, S. A., Fargher, E., Pushpakom, S., Alder, J. E., Sidgwick, G. P., Payne, D., Elliott, R. A., Heise, M., Elles, R., Ramsden, S. C., Andrews, J., Houston, J. B., Qasim, F., Shaffer, J., Griffiths, C. E. M., Ray, D. W., ... Ollier, W. E. R. (2011). A pragmatic randomized controlled trial of thiopurine methyltransferase genotyping prior to azathioprine treatment: The TARGET study. Pharmacogenomics, 12(6), 815-826. https://doi.org/10.2217/pgs.11.32

@article{123db8fa3bbf4420bfe757001a3883d3,

title = "A pragmatic randomized controlled trial of thiopurine methyltransferase genotyping prior to azathioprine treatment: The TARGET study",

abstract = "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. {\textcopyright} 2011 Future Medicine Ltd.",

keywords = "azathioprine, pharmacogenetics, randomized controlled trial, thiopurine methyltransferase, TPMT",

author = "Newman, {William G.} and Katherine Payne and Karen Tricker and Roberts, {Stephen A.} and Emily Fargher and Sudeep Pushpakom and Alder, {Jane E.} and Sidgwick, {Gary P.} and Debbie Payne and Elliott, {Rachel A} and Marco Heise and Robert Elles and Ramsden, {Simon C.} and Julie Andrews and Houston, {J. Brian} and Faeiza Qasim and Jon Shaffer and Griffiths, {Christopher E M} and Ray, {David W.} and Ian Bruce and Ollier, {William E R}",

year = "2011",

month = jun,

doi = "10.2217/pgs.11.32",

language = "English",

volume = "12",

pages = "815--826",

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Newman, WG , Payne, K, Tricker, K, Roberts, SA, Fargher, E, Pushpakom, S, Alder, JE, Sidgwick, GP, Payne, D, Elliott, RA, Heise, M, Elles, R, Ramsden, SC, Andrews, J, Houston, JB, Qasim, F, Shaffer, J, Griffiths, CEM , Ray, DW , Bruce, I & Ollier, WER 2011, 'A pragmatic randomized controlled trial of thiopurine methyltransferase genotyping prior to azathioprine treatment: The TARGET study', Pharmacogenomics, vol. 12, no. 6, pp. 815-826. https://doi.org/10.2217/pgs.11.32

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T1 - A pragmatic randomized controlled trial of thiopurine methyltransferase genotyping prior to azathioprine treatment: The TARGET study

AU - Newman, William G.

AU - Payne, Katherine

AU - Tricker, Karen

AU - Roberts, Stephen A.

AU - Fargher, Emily

AU - Pushpakom, Sudeep

AU - Alder, Jane E.

AU - Sidgwick, Gary P.

AU - Payne, Debbie

AU - Elliott, Rachel A

AU - Heise, Marco

AU - Elles, Robert

AU - Ramsden, Simon C.

AU - Andrews, Julie

AU - Houston, J. Brian

AU - Qasim, Faeiza

AU - Shaffer, Jon

AU - Griffiths, Christopher E M

AU - Ray, David W.

AU - Bruce, Ian

AU - Ollier, William E R

PY - 2011/6

Y1 - 2011/6

N2 - 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. © 2011 Future Medicine Ltd.

AB - 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. © 2011 Future Medicine Ltd.

KW - azathioprine

KW - pharmacogenetics

KW - randomized controlled trial

KW - thiopurine methyltransferase

KW - TPMT

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DO - 10.2217/pgs.11.32

M3 - Article

C2 - 21692613

SN - 1462-2416

VL - 12

SP - 815

EP - 826

JO - Pharmacogenomics

JF - Pharmacogenomics

IS - 6

ER -

A pragmatic randomized controlled trial of thiopurine methyltransferase genotyping prior to azathioprine treatment: The TARGET study

Abstract

Keywords

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