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Novel assay to improve therapeutic drug monitoring of thiopurines in inflammatory bowel disease.
MedLine Citation:
PMID:  25239576     Owner:  NLM     Status:  Publisher    
BACKGROUND AND AIMS: The thiopurines are widely used in the treatment of inflammatory bowel disease, but are limited by poor dose-effect relationship. The objective was to assess the ability of a novel assay, determining the mono-, di-, and triphosphates, of thioguanine as well as methylthioinosine as individual metabolites in erythrocytes, to predict clinical outcome compared to a routine assay, determining metabolites as sums.
METHODS: Samples from 79 patients with Crohn's disease or ulcerative colitis treated with azathioprine or mercaptopurine were analysed by both assays. Clinical status was determined by the Harvey-Bradshaw and Walmsley indices. The genotypes of thiopurine methyltransferase (TPMT) and inosine triphosphatase were determined.
RESULTS: TPMT wild-type patients with thioguanine nucleotide (TGN) levels below the cut-off level were more likely to have active disease when TGN was measured by the novel assay (p=0.02), and when thioguanosine triphosphate (TGTP) was measured separately (p=0.01). When TGN was measured by the routine assay the correlation was not evident (p=0.12). Neither TGN levels nor TGTP correlated to disease activity in TPMT deficient patients. Patients with methyl thioinosine nucleotide (meTIN) levels above 1500pmol/8×10^8 RBCs were more likely to have active disease (p=0.07). We observed good correlations between the mono-, di-, and triphosphates and their respective sums (R(2)>0.88).
CONCLUSIONS: The novel TGN assay was better in predicting clinical outcome compared to the routine assay, while determination of TGTP had no clinical advantage and TGTP ratio was not correlated to disease activity.
Svante Vikingsson; David Andersson; Sven Almer; Curt Peterson; Ulf Hindorf
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-9-16
Journal Detail:
Title:  Journal of Crohn's & colitis     Volume:  -     ISSN:  1876-4479     ISO Abbreviation:  J Crohns Colitis     Publication Date:  2014 Sep 
Date Detail:
Created Date:  2014-9-20     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101318676     Medline TA:  J Crohns Colitis     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2014 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.
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