Pharmacogenomics of Thiopurine Drugs: A Bench-To-Bedside Success Story in Thailand

Abstract

Thiopurine drugs are the cornerstone treatment for many diseases such as acute lymphoblastic leukemia (ALL), organ rejection, inflammatory bowel disease (IBD), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and other autoimmune diseases. However, their clinical use faces limitations due to the drug-induced adverse effects, including myelosuppression. Several genetic associations have been evaluated for their association with these adverse drug reactions. TPMT and NUDT15 polymorphisms have emerged as important clinical markers for predicting and optimizing the safety and effectiveness of thiopurine drugs. The bench-to-bedside approach of exploring and assessing the genetic associations of TPMT and NUDT15 variants and the new LC-MS/MS methods for evaluating TPMT is a step forward in the advancement of precision medicine of thiopurine drugs. In Thailand, TPMT and NUDT are routinely genotyped in some hospitals to guide the prescription of thiopurine drugs for optimizing the safety or effectiveness of these drugs. However, the composite effects of these genetic variants remain unexplored at the global scale. Proper large-scale studies with multi-ethnic patients can provide a clear understanding of the TPMT/NUDT15 association and would pave the way towards the optimization of thiopurine drugs to achieve precision medicine.