Acta Pharmaceutica (Sep 2024)

Personalization of thiopurine therapy: Current recommendations and future perspectives

  • Urbančič Dunja,
  • Pasha Flaka,
  • Šmid Alenka,
  • Mlinarič-Raščan Irena

DOI
https://doi.org/10.2478/acph-2024-0030
Journal volume & issue
Vol. 74, no. 3
pp. 355 – 381

Abstract

Read online

Despite great therapeutic advances in the field of biologics, small synthetic molecules such as thiopurines, including azathioprine, mercaptopurine, and thioguanine, remain an important therapeutic pillar in the treatment of inflammatory bowel disease, other autoimmune disorders, and cancer. This review presents the latest guidelines for thiopurine administration, highlighting the importance of individualized therapy guided by pharmacogenomics. It emphasizes dose adjustment based on nudix hydrolase 15 (NUDT15) and thiopurine S-methyltransferase (TPMT) genotype, along side thiopurine S-methyltransferase activity and thiopurine metabolic profile. In addition, the article takes a critical look at emerging research in the field of thiopurine pharmaco genomics featuring novel genetic markers and technological developments in genetic testing. Finally, the potential of integrated approaches that combine genetic, meta bolic, and clinical factors to further individualize thiopurine therapy is highlighted.

Keywords