Abstract
BACKGROUND: Isoniazid is metabolized by the N-acetyltransferase 2 (NAT2) enzyme. Individuals classified as slow acetylators are increased risk of developing hepatotoxicity. This study aims to evaluate the clinical and economic impact of incorporating NAT2 genotype-guided dosing of isoniazid to prevent anti-tuberculosis drug-induced hepatitis in the Thai healthcare system. METHODS: A decision tree and Markov model were developed to assess the costs, clinical outcomes, and quality-adjusted life years (QALYs) of NAT2 genotype-guided isoniazid dosing compared to the standard regimen in newly diagnosed pulmonary tuberculosis patients in Thailand. The primary outcomes were costs, QALYs, and incremental cost-effectiveness ratios (ICERs). RESULTS: The analysis revealed that the discounted costs for the NAT2 genotype-stratified isoniazid dosing group were 28,538 THB (USD 870), compared to 18,727 THB (USD 570) for the standard regimen. The corresponding discounted QALYs were 9.92 years and 7.66 years, respectively. The ICER was 4,333 THB (USD 132) per QALY gained. One-way sensitivity analysis showed that the intervention was cost-effective across all input parameters. Probabilistic sensitivity analysis indicated that 99.98% of simulations were below the threshold for cost-effectiveness. CONCLUSION: Stratified isoniazid dosing by NAT2 genotype would be cost-effective in treatment of pulmonary tuberculosis in Thailand.