Host: The Japanese Pharmacological Society
Name : The 96th Annual Meeting of the Japanese Pharmacological Society
Number : 96
Location : [in Japanese]
Date : November 30, 2022 - December 03, 2022
Adverse drug reactions (ADRs) such as skin rash, drug-induced liver injury, and agranulocytosis have long been analyzed in relation to human leukocyte antigen (HLA) that is an important molecule involved in human immunity. HLA is composed of many genes, each of which has dozens of different types (alleles), and many HLA alleles associated with ADRs have been reported, starting with the report of HLA-DRB1*08:03:02 associated with agranulocytosis by methimazole. The odds ratios in the association with HLA alleles range from approximately 5 to several thousand, indicating a very large impact on the risk of ADRs. Thus, HLA genetic testing prior to initiation of drug therapy is expected to make a significant contribution to avoiding ADRs, but to demonstrate the clinical utility of genetic testing, it is necessary to prospectively show the effects of medical interventions based on the test results. We conducted the GENCAT study, a prospective, multicenter, single-arm clinical trial to investigate the impact of a therapeutic intervention based on the HLA-A*31:01 test on the incidence of carbamazepine-induced skin rash. HLA-A*31:01-positive patients were treated with an alternative drug such as valproic acid, and the study showed an approximately 60% reduction in the incidence of carbamazepine-induced skin rash. It is expected that the genetic test, which has demonstrated clinical utility, will lead to the establishment of safer and more appropriate stratified medicine by reflecting the information in clinical practice guidelines.
