Cost-Utility Analysis of HLA-B*15:02 Testing for Preventing Phenytoin-Induced Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN) in Thailand

Abstract

Genetic testing has potential to identify individuals at risk of adverse drug reactions. Meta-analysis data indicated significant association between HLA-B*15:02 and phenytoin-induced Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) with odds ratio of 4.12 (95% CI 1.77-9.59, p=0.001). Additionally, the prevalence of the HLA-B*15:02 gene ranks second in the Thai population. Despite this, there is a lack of evidence from economic evaluation to inform policy decisions for optimizing resource allocation. Therefore, this study aims to conduct cost-utility analysis of HLA-B*15:02 testing before initiating phenytoin treatment to prevent SJS/TEN and alternative drugs with sodium valproate, known to have a lower risk of SJS/TEN but higher cost compared to phenytoin treatment without testing. A decision tree and Markov models were constructed to evaluate the lifetime costs and quality-adjusted life year (QALY) with one-year cycle length in patients newly diagnosed with epilepsy. The analysis was conducted from government and societal perspective within the Thai context. Input parameters, including cost, utility, and transitional probabilities, were obtained from relevant literature predominantly conducted in the Thai population. One-way and probabilistic sensitivity analyses were performed to assess the robustness of the findings. Compared to no-testing, the incremental cost-effectiveness ratios (ICERs) were 57,185 THB/QALY gained for HLA-B*15:02 testing before initiation of phenytoin therapy and 54,842 THB/QALY gained for alternative drugs strategy from societal perspective. One-way sensitivity analysis indicated that the phenytoin-induced other ADRs had the most impact on the ICER. At the Thai cost-effectiveness threshold of 160,000 THB/QALY, the probability of the alternative drugs strategy being the most cost-effective was 79%. Furthermore, the number needed to screen to prevent one case of SJS/TEN was 1,470. Implementing HLA-B*15:02 testing and alternative drugs strategy were determined to be cost-effective compared to the no-testing strategy. These findings provide valuable guidance to physicians in optimizing treatment and policymakers considering decisions to prevent serious ADRs.