ArticleClinical pharmacology and therapeutics2022
TPMT and NUDT15 Variants Predict Discontinuation of Azathioprine for Myelotoxicity in Patients with Inflammatory Disease: Real-World Clinical Results.
Article in Clinical pharmacology and therapeutics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 3 of them syntheses that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed, 3 syntheses or guidelines pooled it, 24 citations in OpenAlex.
- Blood-test monitoring strategies for patients established on immune-suppressing drugs: a mixed-methods study.Health technology assessment (Winchester, England) · 2026Pooled it
- Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for Thiopurine Dosing Based on TPMT and NUDT15 Genotypes: 2025 Update.Clinical pharmacology and therapeutics · 2026Guideline
- Pooled it
- Diagnostic, prognostic, and therapeutic challenges in patients with hypersensitivity pneumonitis.ERJ open research · 2026Review
- Association between genetically predicted expression of TPMT and azathioprine adverse events.BMC pharmacology & toxicology · 2026Article
- Comparison of Azathioprine-Induced Pancreatitis and Gastrointestinal Intolerance in IBD: Role of Demographics, Clinical Variables, and HLA DQA1/DRB1 Alleles.Journal of clinical medicine · 2025Article
- RAB19, SERPINB9P1, and Pancreatitis in Patients Taking Azathioprine in Routine Clinical Practice: Genome and Transcriptome-Wide Association Studies.Clinical pharmacology and therapeutics · 2025Article
- PTPN2 and Leukopenia in Individuals With Normal TPMT and NUDT15 Metabolizer Status Taking Azathioprine.Clinical and translational science · 2025Article
- Proactive pharmacogenomics in azathioprine-treated pediatric inflammatory bowel disease at a Chinese tertiary hospital.Frontiers in pharmacology · 2025Article
- Landscape of TPMT and NUDT15 Pharmacogenetic Variation in a Cohort of Canadian Pediatric Inflammatory Bowel Disease Patients.Inflammatory bowel diseases · 2024Article
- The Contribution of Genetic and Epigenetic Factors: An Emerging Concept in the Assessment and Prognosis of Inflammatory Bowel Diseases.International journal of molecular sciences · 2024Review
- Estimation of the benefit from pre-emptive genotyping based on the nationwide cohort data in South Korea.Clinical and translational science · 2024Review
- The Genetics of Inflammatory Bowel Disease.Molecular diagnosis & therapy · 2024Review
- Pharmacogenetic testing and monitoring of complete blood counts among Veterans newly prescribed thiopurine treatments: a retrospective cohort study.Journal of pharmaceutical policy and practice · 2023Article
- Article
- Risk-stratified monitoring for thiopurine toxicity in immune-mediated inflammatory diseases: prognostic model development, validation, and, health economic evaluation.EClinicalMedicine · 2023Article
- Comparison of variants in TPMT and NUDT15 between sequencing and genotyping methods in a multistate pediatric institution.Clinical and translational science · 2023Article
- Race, Genotype, and Azathioprine Discontinuation : A Cohort Study.Annals of internal medicine · 2022Article
- Predicted expression of genes involved in the thiopurine metabolic pathway and azathioprine discontinuation due to myelotoxicity.Clinical and translational science · 2022Article
Corrections and comments
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Authors and funding
16 authors at 2 institutions in 1 country.
Funding
Abstract
Azathioprine is used frequently to treat several inflammatory conditions. However, treatment is limited by adverse events-in particular, myelotoxicity. Thiopurine-S-methyltransferase (TPMT) and nudix hydrolase-15 (NUDT15) are enzymes involved in azathioprine metabolism; variants in the genes encoding these enzymes increase the risk for azathioprine myelotoxicity. The Clinical Pharmacogenetics Implementation Consortium (CPIC) has recommended dose adjustments based on the results of TPMT and NUDT15 genotyping. However, little is known about the importance of this genetic information in routine clinical care. We hypothesized that in patients with inflammatory diseases, TPMT and NUDT15 genotype data predict the risk of discontinuing azathioprine due to myelotoxicity. This was a retrospective cohort study in 1,403 new adult azathioprine users for the management of inflammatory conditions for whom we had genetic information and clinical data. Among patients who discontinued azathioprine, we adjudicated the reason(s). Genotyping was performed using the Illumina Infinium Expanded Multi-Ethnic Genotyping Array plus custom content. We used CPIC guidelines to determine TPMT and NUDT15 metabolizer status; patients were grouped as either: (i) poor/intermediate, or (ii) normal/indeterminate metabolizers. We classified 110 patients as poor/intermediate, and 1,293 patients as normal/indeterminate metabolizers. Poor/intermediate status was associated with a higher risk for azathioprine discontinuation due to myelotoxicity compared to normal/indeterminate metabolizers (hazard ratio (HR) = 2.90, 95% confidence interval (CI): 1.58-5.31, P = 0.001). This association remained significant after adjustment for race, age at initiation, sex, primary indication, and initial daily dose of azathioprine (adjusted HR (aHR) = 2.67, 95% CI: 1.44-4.94, P = 0.002). In conclusion, TPMT and NUDT15 metabolizer status predicts discontinuation due to myelotoxicity for patients taking azathioprine for inflammatory conditions.
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Registered trials
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.