Clinical and Economic Impact of Expanded <scp>TPMT</scp> Testing to Prevent Thiopurine‐Induced Myelosuppression in Australia: A Budget Impact Analysis

Testing thiopurine methyltransferase (TPMT) enzyme activity or genotype prior to thiopurine prescribing is recommended to reduce the risk of moderate to severe-and potentially fatal-myelosuppression in poor or intermediate TPMT metabolizers. Despite this, only about one-third of individuals prescribed thiopurines in Australia currently receive TPMT testing. The budgetary implications of expanding testing to align with guidelines remain unclear. We conducted a budget impact analysis from the Australian healthcare system perspective, comparing costs under current versus increased TPMT testing uptake. Phenotype frequencies among thiopurine users were estimated using ancestry-stratified prescribing data from the Person Level Integrated Data Asset of the Australian Bureau of Statistics combined with published phenotype distribution by ancestry. A simulation model was developed, incorporating phenotype frequencies, phenotype-specific hospitalization risks, and costs of testing and hospitalizations. In a hypothetical cohort of 10,000 thiopurine users, current testing rates of 32.5%-39.8% identify approximately 296 poor or intermediate metabolizers, leaving 586 individuals at elevated risk undetected. Increasing testing uptake by 10 percentage points from baseline could prevent 16 hospitalizations and save AUD$88,113 in hospital costs, leading to a mean net saving of AUD$42,728 (95% CI: AUD$41,685-AUD$43,770). The number needed to test to prevent one hospitalization was approximately 63. As myelosuppression represents a serious and potentially life-threatening adverse drug reaction, expanding TPMT testing offers a cost-effective, high-yield strategy to enhance patient safety and reduce preventable healthcare burden. These findings support more systematic integration of pharmacogenomic testing into routine thiopurine prescribing in Australia.