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

## TL;DR

This study shows that testing for a genetic variant before prescribing a common epilepsy drug in Japan is cost-effective and can prevent severe skin reactions.

## Contribution

First evaluation of HLA-A*31:01 genetic screening cost-effectiveness for carbamazepine use in Japanese patients.

## Key findings

- HLA-A*31:01 screening before carbamazepine treatment is cost-effective in Japan.
- The incremental cost-effectiveness ratio was 6956 USD/QALY, below the willingness-to-pay threshold.
- Probabilistic sensitivity analysis showed a 97.0% probability of cost-effectiveness for the screening strategy.

## Abstract

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.

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.

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.

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.

This study was the first to evaluate the cost‐effectiveness of genetic testing (HLA‐A*31:01) before prescribing carbamazepine, an epilepsy medication, to prevent severe skin reactions in Japanese patients. The HLA screening strategy, which uses alternative medications for high‐risk patients, was found to be cost‐effective compared to the conventional approach of treating all patients with the same medication without testing.