Uptake of DPYD and UGT1A1 testing in Italy and adherence to pharmacogenetic guidelines: A 5-year perspective from an...

Pharmacogenetic implementation requires awareness of the state-of-the-art practice of laboratories providing pharmacogenetic testing. This study investigated how pharmacogenetic guidelines and recommendations have been implemented over time by Italian laboratories participating in the external quality assessment (EQA) Pharmaco-scheme established since 2019 by the European Molecular genetics Quality Network (EMQN).

Anonymized clinical pharmacogenetic reports submitted by Italian laboratories participating in the EMQN Pharmaco-scheme between 2019 and 2023 were analysed. A total of 88 reports addressing fluoropyrimidine/DPYD and irinotecan/UGT1A1 drug-gene interactions were evaluated for genotyping panel adopted and methodology, referenced guidelines and accuracy of clinical interpretation.

Over the 5-year period, Italian laboratories accounted for 45% of all European submissions. The adoption of DPYD and UGT1A1 testing increased significantly, with the use of the Italian Society of Pharmacology - Italian Association of Medical Oncology (SIF-AIOM) genotyping panel rising from 0% in 2019 to 97% in 2023. The proportion of laboratories providing accurate clinical interpretations in line with at least one major guideline (the Clinical Pharmacogenetics Implementation Consortium, the Dutch Pharmacogenomics Working Group or SIF-AIOM) increased from 34% in 2021 to 63% in 2023. Notably, only the SIF-AIOM guidelines recommend testing for the DPYD*6 variant in a reactive setting. However, clearer guidance is needed to avoid the risk of undertreatment in these patients. Allelic discrimination emerged as the preferred genotyping method, particularly with the widespread adoption of commercial European Union-marked in vitro diagnostic kits.

This study provides a snapshot of pharmacogenetic testing practices in Italian laboratories participating in an EQA programme. It highlights an encouraging trend toward improved accuracy and guideline adherence, reflecting increasing awareness and harmonization in clinical pharmacogenetic practice.