TY - JOUR
T1 - Thiopurine metabolite ratios for monitoring therapy in pediatric crohn disease
AU - Kopylov, U.
AU - Amre, D.
AU - Theoret, Y.
AU - Deslandres, C.
AU - Seidman, E. G.
N1 - Publisher Copyright:
© 2014 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.
PY - 2014/10/8
Y1 - 2014/10/8
N2 - 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.
AB - 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.
KW - 6-Methylmecaptopurine
KW - 6-Thioguanine
KW - Azathioprine
KW - Crohn disease
KW - Drug monitoring
KW - Thiopurines
UR - http://www.scopus.com/inward/record.url?scp=84917742200&partnerID=8YFLogxK
U2 - 10.1097/MPG.0000000000000455
DO - 10.1097/MPG.0000000000000455
M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???
C2 - 24918978
AN - SCOPUS:84917742200
SN - 0277-2116
VL - 59
SP - 511
EP - 515
JO - Journal of Pediatric Gastroenterology and Nutrition
JF - Journal of Pediatric Gastroenterology and Nutrition
IS - 4
ER -