Cost‐effectiveness analysis of pharmacogenetic‐guided antiseizure medication therapy based on the risk of HLA‐A*31:01 allele variants in Japan

Aim Carbamazepine (CBZ) remains a common antiseizure medication for focal epilepsy but carries the risk of cutaneous adverse drug reactions (cADRs), including Stevens–Johnson syndrome and toxic epidermal necrolysis. The HLA‐A*31:01 allele is associated with increased risk of CBZ‐induced cADRs, with notably high prevalence (8.4%) in the Japanese population. While genetic screening before CBZ treatment has proven cost‐effective in other populations, its economic value in Japan remains unexplored. Methods We conducted a cost‐effectiveness analysis comparing two strategies for newly diagnosed focal epilepsy treatment: (1) screening HLA‐A*31:01 before CBZ treatment, with CBZ for negative results and levetiracetam for positive results, and (2) CBZ treatment without screening. Effectiveness was measured in quality‐adjusted life years (QALYs) based on utility values scored from 0 ( death ) to 1 ( perfect health ). We developed a decision tree model based on a Markov model with monthly cycles and a 20‐year follow‐up, analyzed from the Japanese healthcare perspective. We utilized clinical trial data and regional cost estimates to conduct base‐case and sensitivity analyses. The willingness‐to‐pay (WTP) threshold was set at 33,784 USD. Results The incremental cost‐effectiveness ratio was 6956 USD/QALY, below the WTP threshold of 33,784 USD, indicating high cost‐effectiveness. Probabilistic sensitivity analyses revealed that the probability of the HLA screening strategy being cost‐effective was 97.0%, confirming stable cost‐effectiveness. Conclusion HLA‐A*31:01 screening before CBZ treatment is cost‐effective in the Japanese population. These findings support incorporating genetic screening into Japan's healthcare coverage system to enable more personalized medicine approaches in epilepsy treatment.