Optimized, end-to-end thiopurine testing
For children who require thiopurine medications (such as azathioprine and 6-mercaptopurine) to treat inflammatory bowel disease (IBD), understanding how thiopurines are metabolized is vital to choosing the most effective treatment. Because some pediatric patients display disparities in thiopurine metabolization, laboratory testing is important to prevent thiopurine toxicity.
Mayo Clinic Laboratories’ full-spectrum thiopurine testing uses emerging technologies that provide accurate results to guide treatment decisions.
Pre-therapy testing can identify patients at risk for bone marrow suppression or organ toxicity from thiopurines due to low thiopurine methyltransferase (TPMT) activity and a diminished ability to rid the body of the medication’s active form. Enzyme activity testing can detect both deficient and hyperactive TPMT activity and identify individuals at risk for therapeutic resistance.
Our TPMT enzyme activity evaluation uses three enzyme substrates in separate reactions to determine TPMT’s ability to metabolize thiopurines. This approach improves the assay’s specificity and reduces potential inconclusive results encountered when using only one substrate.
A likelihood of having carrier status or deficient or hyperactive TPMT is determined through a bioinformatics approach that integrates results from the three enzyme reactions using Collaborative Laboratory Integrated Reports (CLIR). This Mayo Clinic-developed, multivariate, pattern recognition software combines covariate adjusted results of different tests into a set of precision reference ranges that physicians can use to better distinguish between false positives and true positive results.
Genotype testing for thiopurine metabolization
Enzyme and genotype testing can be used together to assess patient risk prior to therapy initiation. TPMT3 enzyme testing can detect individuals with increased metabolism and rare variants not included in the genotyping test. However, genotyping is required to test for genetic variations in NUDT15, an enzyme that helps break down thiopurines in the body and has been shown to affect thiopurine toxicity.1,2
TPMT3 and TPNUQ are complementary tests that:
Test in Focus
Ann Moyer, M.D., Ph.D., discusses TPNUQ, Mayo Clinic Laboratories' genotyping test for identifying patients at risk for thiopurine toxicity. Used prior to therapy initiation, our assay evaluates for nuances in both TPMT and NUDT15, which have associations to thiopurine metabolization.
Testing after therapy initiation
Metabolite monitoring after initiation of therapy enables clinicians to optimize therapy and identify elevated metabolite concentrations that may result in toxicity. Additionally, clinicians should order testing as needed for dose changes, flare-ups, signs of toxicity, and suspicion of noncompliance, as well as in patients who do not respond to therapy as expected.
Recommended time points for testing: