ArticlePloS one2018
Thiopurine methyltransferase genotype and activity cannot predict outcomes of azathioprine maintenance therapy for antineutrophil cytoplasmic antibody associated vasculitis: A retrospective cohort study.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 13 citations in OpenAlex.
- Azathioprine Hypersensitivity Syndrome Mimicking Herpes Zoster and Linear IgA Dermatosis Presentation: A Case Report.Acta dermato-venereologica · 2025Article
- TPMT and NUDT15 Variants Predict Discontinuation of Azathioprine for Myelotoxicity in Patients with Inflammatory Disease: Real-World Clinical Results.Clinical pharmacology and therapeutics · 2022Article
- Review
- Predicting relapse in anti-neutrophil cytoplasmic antibody-associated vasculitis: a Systematic review and meta-analysis.Rheumatology advances in practice · 2021Article
- Gene variants and treatment outcomes in antineutrophil cytoplasmic antibody-associated vasculitis.The pharmacogenomics journal · 2020Review
- Combining clinical and candidate gene data into a risk score for azathioprine-associated leukopenia in routine clinical practice.The pharmacogenomics journal · 2020Article
- Mycophenolate mofetil, azathioprine and tacrolimus: mechanisms in rheumatology.Nature reviews. Rheumatology · 2020Review
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveAzathioprine is a widely used immunosuppressive drug. Genetic polymorphisms and activity of the enzyme thiopurine methyltransferase (TPMT) have been associated with azathioprine efficacy and toxicity in several populations. We investigated whether these associations also exist for ANCA associated vasculitis (AAV) patients, who receive azathioprine maintenance therapy after remission induction with cyclophosphamide.
methods207 AAV patients treated with cyclophosphamide induction and azathioprine maintenance therapy were included and followed for 60 months. TPMT genotype and tertiles of TPMT activity were compared to relapse free survival and occurrence of adverse events, particularly leukopenia. Multivariable regression was performed to account for confounders.
resultsIn univariable analysis, relapse free survival was not significantly associated with TPMT genotype (P = 0.41) or TPMT activity (P = 0.07), although it tended to be longer in lower tertiles of TPMT activity. There was no significant association of TPMT genotype and activity with occurrence of any adverse event. In multiple regression, leukocyte counts at the end of cyclophosphamide induction were related to risk of leukopenia during azathioprine therapy [P<0.001; OR 0.54 (95% CI 0.43-0.68)] and risk of relapse during follow-up [P = 0.001; HR 1.17 (95% CI 1.07-1.29)] irrespective of TMPT genotype or activity.
conclusionTPMT genotype and activity were not independent predictors of relapse, and could not predict leukopenia or other adverse effects from azathioprine. Leukocyte counts after cyclophosphamide induction were related to both outcomes, implying a greater influence of cyclophosphamide response compared to azathioprine and TPMT in AAV patients.
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