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A skewed thiopurine metabolism is a common clinical phenomenon that can be successfully managed with a combination of low-dose azathioprine and allopurinol

Appell, Malin Lindqvist ; Wagner, Agnieszka and Hindorf, Ulf LU (2013) In Journal of Crohn's & Colitis 7(6). p.510-513
Abstract
Background and aims: A skewed thiopurine metabolism is a phenomenon associated with both poor treatment response and toxicity. Our aim was to evaluate the frequency of this phenomenon and the relationship to thiopurine methyltransferase (TPMT) function. Methods: All thiopurine metabolite measurements in adult patients (n=4033) between January 2006 and April 2012 were assessed to evaluate the occurrence of a skewed metabolism and the relationship to TPMT genotype and activity. Results: A skewed metabolism was observed in 14% of all patients. It only developed in patients with a normal TPMT genotype, but was observed at all TPMT activity levels within the normal range (9.1-24.2 U/ml RBC). Two cases that illustrate typical clinical scenarios... (More)
Background and aims: A skewed thiopurine metabolism is a phenomenon associated with both poor treatment response and toxicity. Our aim was to evaluate the frequency of this phenomenon and the relationship to thiopurine methyltransferase (TPMT) function. Methods: All thiopurine metabolite measurements in adult patients (n=4033) between January 2006 and April 2012 were assessed to evaluate the occurrence of a skewed metabolism and the relationship to TPMT genotype and activity. Results: A skewed metabolism was observed in 14% of all patients. It only developed in patients with a normal TPMT genotype, but was observed at all TPMT activity levels within the normal range (9.1-24.2 U/ml RBC). Two cases that illustrate typical clinical scenarios of a skewed metabolism and the effect of combination treatment with low-dose azathioprine and allopurinol are presented. Conclusions: A skewed metabolism is a common clinical phenomenon in patients with a normal TPMT function, which can develop at all TPMT activity levels within the normal range. We suggest that metabolite measurements should be considered in patients not responding to treatment and in those with hepatotoxicity or myelotoxicity in order to detect a skewed metabolism, since this phenomenon can be successfully managed by a combination of low-dose azathioprine and allopurinol. (C) 2012 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved. (Less)
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author
; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Thiopurine methyltransferase, Thiopurines, Inflammatory bowel diseases
in
Journal of Crohn's & Colitis
volume
7
issue
6
pages
510 - 513
publisher
Oxford University Press
external identifiers
  • wos:000319370300010
  • scopus:84877058183
  • pmid:23168376
ISSN
1873-9946
DOI
10.1016/j.crohns.2012.10.016
language
English
LU publication?
yes
id
c321b972-dc21-4e99-9ad5-8253ae5c2c7d (old id 3930519)
date added to LUP
2016-04-01 09:57:53
date last changed
2024-02-21 01:10:12
@article{c321b972-dc21-4e99-9ad5-8253ae5c2c7d,
  abstract     = {{Background and aims: A skewed thiopurine metabolism is a phenomenon associated with both poor treatment response and toxicity. Our aim was to evaluate the frequency of this phenomenon and the relationship to thiopurine methyltransferase (TPMT) function. Methods: All thiopurine metabolite measurements in adult patients (n=4033) between January 2006 and April 2012 were assessed to evaluate the occurrence of a skewed metabolism and the relationship to TPMT genotype and activity. Results: A skewed metabolism was observed in 14% of all patients. It only developed in patients with a normal TPMT genotype, but was observed at all TPMT activity levels within the normal range (9.1-24.2 U/ml RBC). Two cases that illustrate typical clinical scenarios of a skewed metabolism and the effect of combination treatment with low-dose azathioprine and allopurinol are presented. Conclusions: A skewed metabolism is a common clinical phenomenon in patients with a normal TPMT function, which can develop at all TPMT activity levels within the normal range. We suggest that metabolite measurements should be considered in patients not responding to treatment and in those with hepatotoxicity or myelotoxicity in order to detect a skewed metabolism, since this phenomenon can be successfully managed by a combination of low-dose azathioprine and allopurinol. (C) 2012 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.}},
  author       = {{Appell, Malin Lindqvist and Wagner, Agnieszka and Hindorf, Ulf}},
  issn         = {{1873-9946}},
  keywords     = {{Thiopurine methyltransferase; Thiopurines; Inflammatory bowel diseases}},
  language     = {{eng}},
  number       = {{6}},
  pages        = {{510--513}},
  publisher    = {{Oxford University Press}},
  series       = {{Journal of Crohn's & Colitis}},
  title        = {{A skewed thiopurine metabolism is a common clinical phenomenon that can be successfully managed with a combination of low-dose azathioprine and allopurinol}},
  url          = {{http://dx.doi.org/10.1016/j.crohns.2012.10.016}},
  doi          = {{10.1016/j.crohns.2012.10.016}},
  volume       = {{7}},
  year         = {{2013}},
}