For children who require thiopurine medications (e.g., azathioprine and 6-mercaptopurine), understanding how these drugs are metabolized is vital to choosing the best treatment. Because some patients display disparities in thiopurine metabolization, laboratory testing is important to prevent thiopurine toxicity.
Pre-therapy testing can identify patients at risk for bone marrow suppression or organ toxicity from thiopurines due to low 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.
Measures enzyme activity in patient's blood to determine thiopurine metabolization.
Measures TPMT activity using three enzyme substrates in separate reactions, which do not interfere with each other and compete for TPMT.
Reduces inconclusive results obtained when using only one substrate to measure TPMT activity.
Integrates results from the three enzyme reactions into a likelihood score of having reduced, deficient, or hyperactive TPMT activity determined through bioinformatic analysis using Collaborative Laboratory Integrated Reports (CLIR).
Learn moreCollaborative Laboratory Integrated Reports (CLIR) is a Mayo Clinic-developed, multivariate pattern-recognition software that combines covariate adjusted results of different testing into a set of precision reference ranges that can help physicians better distinguish between false positives and true positive results.
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
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. This testing is recommended at four weeks post-therapy initiation, 12–16 weeks after therapy initiation, and annually. It can also be ordered as needed for dose changes, flare-ups, signs of toxicity, and suspicion of noncompliance, and for patients who do not respond to therapy as expected.