Monitoring of long-term thiopurine therapy among adults with inflammatory bowel disease
(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:
https://lup.lub.lu.se/record/262263
- author
- Hindorf, Ulf LU ; Lyrenas, E ; Nilsson, Åke LU and Schmiegelow, K
- organization
- publishing date
- 2004
- 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
- 2016-04-01 16:50:47
- date last changed
- 2024-01-11 15:54:45
@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 < 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.}}, author = {{Hindorf, Ulf and Lyrenas, E and Nilsson, Åke and Schmiegelow, K}}, issn = {{1502-7708}}, keywords = {{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}}, doi = {{10.1080/00365520410007980}}, volume = {{39}}, year = {{2004}}, }