Advanced

Monitoring of long-term thiopurine therapy among adults with inflammatory bowel disease

Hindorf, Ulf LU ; Lyrenas, E; Nilsson, Åke LU and Schmiegelow, K (2004) In Scandinavian Journal of Gastroenterology 39(11). p.1105-1112
Abstract
Background: The immunosuppressive effects of thiopurine drugs are mainly mediated through their intracellular metabolism into active 6-thioguanine nucleotide (6-TGN) metabolites, which are incorporated into DNA. Erythrocyte 6-TGN (E-6TGN) levels have been proposed as an instrument for monitoring treatment. The aim of the study was to use erythrocyte E-6TGN, methylated mercaptopurine (MeMP) metabolites, and thiopurine methyltransferase (TPMT) measurements in a clinical setting to determine the clinical outcome in relation to thiopurine metabolism. Methods: Fifty-five adult patients with inflammatory bowel disease were included in a prospective study and followed for 6 months. Metabolite levels were measured and correlated to outcome and... (More)
Background: The immunosuppressive effects of thiopurine drugs are mainly mediated through their intracellular metabolism into active 6-thioguanine nucleotide (6-TGN) metabolites, which are incorporated into DNA. Erythrocyte 6-TGN (E-6TGN) levels have been proposed as an instrument for monitoring treatment. The aim of the study was to use erythrocyte E-6TGN, methylated mercaptopurine (MeMP) metabolites, and thiopurine methyltransferase (TPMT) measurements in a clinical setting to determine the clinical outcome in relation to thiopurine metabolism. Methods: Fifty-five adult patients with inflammatory bowel disease were included in a prospective study and followed for 6 months. Metabolite levels were measured and correlated to outcome and AZA/6-MP dose. Results: The E-6TGN level was significantly related to the TPMT genotype ( P = 0.008). Patients in disease remission had higher E-6TGN levels than patients with disease activity both at baseline ( P < 0.05) and after 6 months ( P = 0.02). Active disease was more frequent among subjects with E-6TGN &LE; 125 nmol/mmol Hb at baseline ( P = 0.04), but not at 6 months. AZA/6-MP drug dose was positively correlated to E-MeMP levels (r(s) = 0.48; P < 0.001) and E-MeMP/E-6TGN ratio (r(s) = 0.41; P = 0.002). Dose changes were positively correlated with the changes in E-MeMP levels ( P = 0.01) and E-MeMP/E-6TGN ratio (P = 0.03). Conclusions: E-6TGN level was the only factor in this study related to disease activity, while there was no relationship between AZA/6-MP dose and E-6TGN levels. This finding illustrates the clinical usefulness of E-6TGN monitoring in the evaluation of treatment intensity. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
immunosuppressive agents, inflammatory bowel diseases, pharmacology, drug monitoring
in
Scandinavian Journal of Gastroenterology
volume
39
issue
11
pages
1105 - 1112
publisher
Taylor & Francis
external identifiers
  • wos:000224866200012
  • pmid:15545169
  • scopus:8844267645
ISSN
1502-7708
DOI
10.1080/00365520410007980
language
English
LU publication?
yes
id
763ab9cf-ba15-4ea7-833e-7ba4da24ffc0 (old id 262263)
date added to LUP
2007-10-30 14:17:04
date last changed
2017-09-17 07:48:32
@article{763ab9cf-ba15-4ea7-833e-7ba4da24ffc0,
  abstract     = {Background: The immunosuppressive effects of thiopurine drugs are mainly mediated through their intracellular metabolism into active 6-thioguanine nucleotide (6-TGN) metabolites, which are incorporated into DNA. Erythrocyte 6-TGN (E-6TGN) levels have been proposed as an instrument for monitoring treatment. The aim of the study was to use erythrocyte E-6TGN, methylated mercaptopurine (MeMP) metabolites, and thiopurine methyltransferase (TPMT) measurements in a clinical setting to determine the clinical outcome in relation to thiopurine metabolism. Methods: Fifty-five adult patients with inflammatory bowel disease were included in a prospective study and followed for 6 months. Metabolite levels were measured and correlated to outcome and AZA/6-MP dose. Results: The E-6TGN level was significantly related to the TPMT genotype ( P = 0.008). Patients in disease remission had higher E-6TGN levels than patients with disease activity both at baseline ( P &lt; 0.05) and after 6 months ( P = 0.02). Active disease was more frequent among subjects with E-6TGN &amp;LE; 125 nmol/mmol Hb at baseline ( P = 0.04), but not at 6 months. AZA/6-MP drug dose was positively correlated to E-MeMP levels (r(s) = 0.48; P &lt; 0.001) and E-MeMP/E-6TGN ratio (r(s) = 0.41; P = 0.002). Dose changes were positively correlated with the changes in E-MeMP levels ( P = 0.01) and E-MeMP/E-6TGN ratio (P = 0.03). Conclusions: E-6TGN level was the only factor in this study related to disease activity, while there was no relationship between AZA/6-MP dose and E-6TGN levels. This finding illustrates the clinical usefulness of E-6TGN monitoring in the evaluation of treatment intensity.},
  author       = {Hindorf, Ulf and Lyrenas, E and Nilsson, Åke and Schmiegelow, K},
  issn         = {1502-7708},
  keyword      = {immunosuppressive agents,inflammatory bowel diseases,pharmacology,drug monitoring},
  language     = {eng},
  number       = {11},
  pages        = {1105--1112},
  publisher    = {Taylor & Francis},
  series       = {Scandinavian Journal of Gastroenterology},
  title        = {Monitoring of long-term thiopurine therapy among adults with inflammatory bowel disease},
  url          = {http://dx.doi.org/10.1080/00365520410007980},
  volume       = {39},
  year         = {2004},
}