BackgroundPatients with moderate-to-severe rheumatoid arthritis (RA) in China experience multi-system dysfunction, resulting in a substantial economic burden. This study aimed to compare the cost-effectiveness of Upadacitinib and Tofacitinib as treatment options for moderate-to-severe RA patients in China.Materials and MethodsA Decision Tree-Markov model with a 24-week cycle was constructed, simulating health status transitions based on the tsDMARDs-TNFi-PC clinical pathway. The analysis included the calculation of treatment costs (yuan) and QALYs (quality-adjusted life-years) for the Upadacitinib and Tofacitinib groups. Cost-effectiveness was evaluated using the incremental cost-effectiveness ratio (ICER) and compared against a willingness-to-pay (WTP) threshold. One-way sensitivity analysis and probabilistic sensitivity analysis (PSA) were conducted to verify the robustness of the results.ResultsCompared with Tofacitinib, the Upadacitinib group incurred an additional cost of 1,375 yuan per patient, with an incremental gain of 0.17 QALYs. The ICER was 7,880.38 yuan/QALY, which is well below the WTP threshold of 1.5 times China's GDP per capita, indicating favorable cost-effectiveness.ConclusionsIn the context of China's healthcare system, Upadacitinib represents a cost-effective long-term first-line treatment option for moderate-to-severe RA patients.