Objective Pharmacological treatments, primarily oral NSAIDs, constituted 73.9% usage for knee osteoarthritis. Despite the known adverse effects of NSAIDs, they are recommended for KOA management. Hyaluronic acid injections, an emerging alternative, lack consensus and evidence of cost-effectiveness in Vietnam. This study aimed to analyze the cost-effectiveness of hyaluronic acid injections relative to oral medication treatment in patients with KOA from health insurance payer’s perspective. Methods: A retrospective study was conducted using electronic medical records of KOA patients from March 1, 2022, to May 31, 2023, at Nguyen Trai Hospital to analyze costs. A cross-sectional descriptive study of two groups receiving hyaluronic acid injections (HA) or oral medication treatment (PO) was conducted using the WOMAC scale converted to EQ-5D-5L to measure treatment effectiveness in QALYs. Seemingly unrelated regression equation was utilized to estimate the Incremental Cost-effectiveness Ratio (ICER) of HA relative to PO while simutaneously adjusting for other confounding factors. Results: The PO group exhibited a higher total WOMAC score than the HA group (PO group: 45.12
HA group: 44.29), indicating greater severity in the WOMAC Pain, Function, and Stiffness categories. The QALYs of HA group was higher than those of the PO group, with QALYs values of 0,719 and 0,661, respectively. The total medical direct costs increased by 6.232.445 VND, and QALYs increased by 0,041 when using HA compared to PO. The ICER reached a 151.184.110 VND/QALY gained. With WTP of 1GDP and 3GDP, the probability of achieving cost-effectiveness of HA compared to using PO was respectively 20.06% and 100%. Conclusions: The study demonstrated that ICER based on QALYs of hyaluronic acid injections is cost-effective compared to the standard oral medication approach.