Abstract | BACKGROUND: Metabolite monitoring and response predictors to azathioprine (AZA) in pediatric inflammatory bowel disease (IBD) are debatable. In an attempt to optimize thiopurine therapy and understand the mechanism of action of thiopurines, we correlated metabolites and other factors with AZA efficacy in children with IBD. METHODS: RESULTS: The 6-thioguanine nucleotide levels >250 pmol per 8 × 10 red blood cells correlated with a higher response (odds ratio, 4.14; 95% confidence interval, 1.49-11.46, P = 0.007), whereas 6-methyl-mercaptopurine and 6-methyl- mercaptopurine: 6-thioguanine nucleotide ratio showed no correlation. Other novel response predictors in children with IBD were relative leukopenia (odds ratio, 14.01; 95% confidence interval, 3.77-52.10; P < 0.001) and the absence of lymphopenia (odds ratio, 3.71; 95% confidence interval, 1.26-10.89; P = 0.017). Lower thiopurine methyltransferase activity (P = 0.015), lower platelet count (P = 0.020), and higher aspartate aminotransferase level (P = 0.009) also predicted therapeutic response. Age, gender, patient adherence, the duration of AZA therapy, IBD type, erythrocyte count, and erythrocyte sedimentation rate did not predict efficacy. The high interindividual variability accounting for 57.7% of variance in therapeutic response was observed. CONCLUSIONS: The significant 6-thioguanine nucleotide level-response relationship may support metabolite monitoring to improve thiopurine efficacy in pediatric IBD. The reported response predictors may be helpful for treatment optimization in AZA-treated children with IBD, but should be proved in prospective studies.
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Authors | Thi-Van-Anh Nguyen, Dinh Hoa Vu, Thi-Mai-Hoang Nguyen, Alain Lachaux, Roselyne Boulieu |
Journal | Inflammatory bowel diseases
(Inflamm Bowel Dis)
Vol. 19
Issue 11
Pg. 2404-10
(Oct 2013)
ISSN: 1536-4844 [Electronic] England |
PMID | 24013359
(Publication Type: Journal Article)
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Chemical References |
- Biomarkers
- Thioguanine
- Azathioprine
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Topics |
- Adolescent
- Azathioprine
(therapeutic use)
- Biomarkers
(metabolism)
- Child
- Colitis, Ulcerative
(drug therapy, metabolism, pathology)
- Crohn Disease
(drug therapy, metabolism, pathology)
- Female
- Follow-Up Studies
- Humans
- Male
- Prognosis
- Retrospective Studies
- Thioguanine
(metabolism)
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