Trial reportAlimentary pharmacology & therapeutics2017
Risk factors for thiopurine-induced myelosuppression and infections in inflammatory bowel disease patients with a normal TPMT genotype.
Trial report in Alimentary pharmacology & therapeutics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 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
27 citing papers in PubMed, 3 syntheses or guidelines pooled it, 40 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
- Association ofHaematologica · 2024Pooled it
- Pooled it
- Risk factors for thiopurine-induced myelosuppression and infections in inflammatory bowel disease patients with a normal TPMT genotype.Alimentary pharmacology & therapeutics · 2017Trial
- Frequency of thiopurine methyltransferase variants and exploratory predictors of azathioprine-induced leukopenia in Saudi patients with inflammatory bowel disease.Saudi journal of gastroenterology : official journal of the Saudi Gastroenterology Association · 2026Article
- Systemic Consequences of Inflammatory Bowel Disease Beyond Immune-Mediated Manifestations.Journal of clinical medicine · 2025Review
- Monitoring for 5-aminosalicylate nephrotoxicity in adults with inflammatory bowel disease: prognostic model development and validation using data from the Clinical Practice Research Datalink.BMJ open gastroenterology · 2025Article
- Development and Validation of a Predictive Nomogram for Myelosuppression Risk in Chronic Hepatitis B Patients Treated with Peginterferon.Infection and drug resistance · 2025Article
- Proactive pharmacogenomics in azathioprine-treated pediatric inflammatory bowel disease at a Chinese tertiary hospital.Frontiers in pharmacology · 2025Article
- Development and validation of a prediction model for myelosuppression in lung cancer patients after platinum-based doublet chemotherapy: a multifactorial analysis approach.American journal of cancer research · 2025Article
- Article
- Risk-stratified monitoring for thiopurine toxicity in immune-mediated inflammatory diseases: prognostic model development, validation, and, health economic evaluation.EClinicalMedicine · 2023Article
- Feasibility of Reduced Clinical Monitoring in Patients with Inflammatory Bowel Disease Treated with Thiopurine Therapy.Digestive diseases and sciences · 2023Article
- Genetic variants of genes involved in thiopurine metabolism pathway are associated with 6-mercaptopurine toxicity in pediatric acute lymphoblastic leukemia patients from Ethiopia.Frontiers in pharmacology · 2023Article
- Race, Genotype, and Azathioprine Discontinuation : A Cohort Study.Annals of internal medicine · 2022Article
- Effect of NUDT15 polymorphisms on early hematological safety of low-dose azathioprine in Chinese patients with pemphigus vulgaris: A prospective cohort study.The Journal of dermatology · 2022Article
- Precision medicine for rheumatologists: lessons from the pharmacogenomics of azathioprine.Clinical rheumatology · 2021Review
- Article
- Combining clinical and candidate gene data into a risk score for azathioprine-associated leukopenia in routine clinical practice.The pharmacogenomics journal · 2020Article
- Thiopurines' Metabolites and Drug Toxicity: A Meta-Analysis.Journal of clinical medicine · 2020Review
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundLeucopenia is a common side effect in patients treated with thiopurines. Variants in the thiopurine S-methyltransferase (TPMT) gene are the best-known risk factor, but only explain up to 25% of leucopenia cases.
aimTo identify the clinical risk factors for thiopurine-induced leucopenia in patients without a common TPMT variant, and explore if these patients are at increased risk for infections.
methodsPost hoc analysis of the Thiopurine response Optimisation by Pharmacogenetic testing in Inflammatory bowel disease Clinics (TOPIC) trial. For this analysis, patients without a variant in TPMT (*2, *3A or*3C) were included. Uni- and multivariate Cox-proportional hazard models were used to identify risk factors for leucopenia and infections. Leucopenia was defined as a white blood cell (WBC) count <3.0 × 10
resultsSixty hundred and ninety-five patients (90.6%) included in the TOPIC-trial had no variant in TPMT, of which 45 (6.5%) developed leucopenia. Median time to leucopenia was 56 (29-112) days. Multivariate analysis showed that use of mercaptopurine compared to azathioprine was associated with leucopenia (hazard ratio [HR] 2.61 [95% CIs, 1.39-4.88; P < .01]) and a higher baseline WBC count was protective (HR 0.80 [95% CIs, 0.71-0.89; P < .01]). Risk factors for infections were older age (per 10 year; HR 2.07 [95% CIs, 1.18-3.63; P = .01]) and concomitant use of biologic drugs (HR 2.15 [95% CIs, 1.14-4.07; P = .02]).
conclusionsLow baseline WBC count and mercaptopurine, due to a relatively higher dose, were risk factors for thiopurine-induced leucopenia in patients without a TPMT variant.
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