Application of risk priority number of failure mode and effects analysis to drug-variant pairs for severe cutaneous adverse reactions in Korean and American populations.

OBJECTIVES Given the varying frequency and significance of genetic factors associated with severe cutaneous adverse reactions (SCARs) across different ethnicities, this study aimed to identify high-risk priority drug-variant pairs by considering genetic differences between Korea and the USA to inform preventive strategies.

METHODS A list of drug-variant pairs associated with SCARs was identified using the Pharmacogenomics Knowledge Base. Prioritization of drug-variant pairs for preventive strategies was conducted using the risk priority number (RPN) method incorporating expert opinions in the field of drug allergy. The RPN for each drug-variant was calculated based on severity, probability, and detectability, with each parameter derived as an odds ratio of the genetic variant associated with SCARs, the occurrence frequency of drug-associated SCARs, and the variant prevalence in Korean and American populations, respectively. Higher values were evaluated as higher priority.

RESULTS A total of 80 drug-variant pairs from 16 drugs associated with SCARs were identified in Koreans, and 12 drug-variant pairs from four drugs in Americans. Six drug-variant pairs were included in Korean drug labels, while only two drug-variant pairs were included in US drug labels. In Koreans, the highest priority drug-variant pair was rs3131003 for allopurinol, which is in moderate linkage disequilibrium with HLA-B*58:01, whereas in Americans, HLA-B*58:01 itself for allopurinol was the highest priority variant.

CONCLUSION Drug-variant pairs with high RPN scores can be prioritized in clinical strategies to prevent SCARs in Korean and American populations. Incorporating these findings into clinical practices could ultimately contribute to the safe use of drugs.