ArticlePloS one2017
Measurements of 6-thioguanine nucleotide levels with TPMT and NUDT15 genotyping in patients with Crohn's disease.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 3 of them syntheses that pooled it.
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Who cites it
15 citing papers in PubMed, 3 syntheses or guidelines pooled it, 32 citations in OpenAlex.
- Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for Thiopurine Dosing Based on TPMT and NUDT15 Genotypes: 2025 Update.Clinical pharmacology and therapeutics · 2026Guideline
- Clinical Pharmacogenetics Implementation Consortium Guideline for Thiopurine Dosing Based on TPMT and NUDT15 Genotypes: 2018 Update.Clinical pharmacology and therapeutics · 2019Guideline
- Association between the c.415C > T, c.52G > A, and 36_37insGGAGTC polymorphisms ofDrug design, development and therapy · 2019Pooled it
- Genetic Determinants of Hematopoietic Toxicity Risk in Thai Pediatric Patients Undergoing 6-Mercaptopurine Treatment.Clinical and translational science · 2026Article
- The Role of Pharmacogenetics in the Therapeutic Response to Thiopurines in the Treatment of Inflammatory Bowel Disease: A Systematic Review.Journal of clinical medicine · 2023Review
- Is Monitoring of the Intracellular Active Metabolite Levels of Nucleobase and Nucleoside Analogs Ready for Precision Medicine Applications?European journal of drug metabolism and pharmacokinetics · 2022Review
- Immunomodulators: still having a role?Gastroenterology report · 2022Review
- Thiopurines in Inflammatory Bowel Disease. How to Optimize Thiopurines in the Biologic Era?Frontiers in medicine · 2021Review
- Article
- Effects of various genetic polymorphisms on thiopurine treatment-associated outcomes for Korean patients with Crohn's disease.British journal of clinical pharmacology · 2020Article
- Thiopurines' Metabolites and Drug Toxicity: A Meta-Analysis.Journal of clinical medicine · 2020Review
- Thiopurine Methyltransferase Activity and Thiopurine Metabolites in Inflammatory Bowel Disease.Crohn's & colitis 360 · 2020Article
- NUDT15 gene variants and thiopurine-induced leukopenia in patients with inflammatory bowel disease.Intestinal research · 2020Review
- Associations between theOncoTargets and therapy · 2018Article
- Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The association between the 6-thioguanine nucleotide (6-TGN) level and clinical remission in Crohn's disease (CD) remains controversial. Thiopurine-induced leukopenia is a life-threatening complication of CD in Asians that was recently shown to strongly correlate with NUDT15 genetic variants. This study aimed to determine the relationship between thiopurine metabolite levels and therapeutic response, and to investigate the association of NUDT15, TPMT, and thiopurine metabolites with leukopenia in patients with CD. We enrolled 165 adult patients with CD undergoing thiopurine treatment. Clinical evaluation and laboratory examinations were carried out every 2-3 months. We measured thiopurine metabolites levels and genotyped NUDT15 and TPMT. During the median 12-month observational period, 95 (67.9%) patients exhibited clinical response and 45 (32.1%) did not respond to the treatment. The median 6-TGN level was significantly higher in responders than in non-responders (P < 0.001). The odds ratio of patients with a 6-TGN level ≥230 pmol/8 × 108 red blood cells for showing a clinical response was 4.63 (95% CI 1.62-11.9). NUDT15 variant types were strongly associated with developing leukopenia. Patients with NUDT15 homozygous variant genotype developed severe early leukopenia with an average reduction of 88.2% (range, 84-94%) from the baseline white blood cell count at 4 weeks. Our findings support the role of therapeutic drug monitoring in thiopurine maintenance treatment to optimize thiopurine therapy, especially, for non-responding CD patients. Thiopurine treatment should not be recommended to patients with NUDT15 homozygous variant genotype due to severe early leukopenia.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.