Thiopurine metabolite ratios for monitoring therapy in pediatric crohn disease

U. Kopylov, D. Amre, Y. Theoret, C. Deslandres, E. G. Seidman

Research output: Contribution to journalArticle

Abstract

Results: The study included 238 pediatric patients with CD with a total of 1648 evaluation points. The patients were in steroid-free remission at 59.1% of the evaluation points. 6-MMP/6-TGN ratios of 4 to 24 were protective against relapse (odds ratio [OR] 0.52, 95% confidence interval [CI] -0.39 to 0.69, P=0.001). Hepatotoxicity was associated with high 6-MMP levels (> 3919 pmol/8× 108 red blood cell count: OR 7.65, 95% CI 3.7-15.9, P=0.001) and high 6-MMP/6-TGN ratios (> 24: OR 5.35, 95% CI -3.43 to 8.43, P=0.001).

Objectives: Thiopurines (azathioprine, 6-mercaptopurine) are a mainstay of treatment in Crohn disease (CD). Monitoring intracellular metabolite (6-thioguanine nucleotides [6-TGN] and 6-methylmercaptopurine [6-MMP]) levels can help optimize therapeutic efficacy and minimize potential toxicity. Determination of 6-MMP/6-TGN ratios may provide additional useful information, such as the identification of individuals with excessive thiopurine methyltransferase activity and disadvantageous 6-MMP overproduction. These patients are at increased risk of therapeutic failure and hepatotoxicity. The aim of the study was to evaluate the correlation of 6-MMP/6-TGN ratios with therapeutic efficacy and risk of hepatotoxicity in CD.

Methods: The present study was a single-center cross-sectional study including pediatric patients with CD studied prospectively with clinical and laboratory assessments along with serial measurements of 6-MMP and 6-TGN. Clinical response was determined using established clinical indices.

Conclusions: We observed significant associations between 6-MMP/6-TGN ratios and clinical response, and risk of hepatotoxicity. Our results suggest that determination of thiopurine metabolite ratios is a valuable tool for identification of patients at increased risk of therapeutic failure and hepatotoxicity.

Original languageEnglish (US)
Pages (from-to)511-515
Number of pages5
JournalJournal of pediatric gastroenterology and nutrition
Volume59
Issue number4
DOIs
StatePublished - Oct 8 2014

Keywords

  • 6-Methylmecaptopurine
  • 6-Thioguanine
  • Azathioprine
  • Crohn disease
  • Drug monitoring
  • Thiopurines

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Gastroenterology

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