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Thiopurine S-methyltransferase testing for averting drug toxicity: a meta-analysis of diagnostic test accuracy

The Pharmacogenomics Journal volume 16, pages 305–311 (2016)Cite this article

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Abstract

Thiopurine S-methyltransferase (TPMT) deficiency increases the risk of serious adverse events in persons receiving thiopurines. The objective was to synthesize reported sensitivity and specificity of TPMT phenotyping and genotyping using a latent class hierarchical summary receiver operating characteristic meta-analysis. In 27 studies, pooled sensitivity and specificity of phenotyping for deficient individuals was 75.9% (95% credible interval (CrI), 58.3–87.0%) and 98.9% (96.3–100%), respectively. For genotype tests evaluating TPMT*2 and TPMT*3, sensitivity and specificity was 90.4% (79.1–99.4%) and 100.0% (99.9–100%), respectively. For individuals with deficient or intermediate activity, phenotype sensitivity and specificity was 91.3% (86.4–95.5%) and 92.6% (86.5–96.6%), respectively. For genotype tests evaluating TPMT*2 and TPMT*3, sensitivity and specificity was 88.9% (81.6–97.5%) and 99.2% (98.4–99.9%), respectively. Genotyping has higher sensitivity as long as TPMT*2 and TPMT*3 are tested. Both approaches display high specificity. Latent class meta-analysis is a useful method for synthesizing diagnostic test performance data for clinical practice guidelines.

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Acknowledgements

This research was supported by a Canadian Institutes of Health Research Knowledge Synthesis Grant, grant #305352. We thank Mr Ian Schiller, MSc, Division of Clinical Epidemiology, McGill University Health Centre and Dr. Nandini Dendekuri, PhD, Director, Technology Assessment Unit of the McGill University Health Centre for technical assistance. We thank Ms Christine Millan for administrative assistance. The funding agency did not have a role in the design, conduct and analysis of the study or the decision to submit the manuscript for publication.

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Authors and Affiliations

  1. Child Health Evaluative Sciences, The Hospital for Sick Children Research Institute, Peter Gilgan Centre for Research and Learning, Toronto, Canada

    R M Zur, L M Roy & W J Ungar

  2. Division of Clinical Pharmacology and Toxicology, The Hospital for Sick Children, Toronto, Canada

    S Ito

  3. Departments of Pharmacology & Pharmacy, Department of Paediatrics, Faculty of Medicine, University of Toronto, Toronto, Canada

    S Ito

  4. Department of Clinical Epidemiology & Biostatistics, McMaster University, Hamilton, Canada

    J Beyene

  5. Centre for Genetic Medicine, The Hospital for Sick Children, Toronto, Canada

    C Carew

  6. Institute for Health Policy, Management & Evaluation, University of Toronto, Toronto, Canada

    W J Ungar

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Zur, R., Roy, L., Ito, S. et al. Thiopurine S-methyltransferase testing for averting drug toxicity: a meta-analysis of diagnostic test accuracy. Pharmacogenomics J 16, 305–311 (2016). https://doi.org/10.1038/tpj.2016.37

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