OBJECTIVE: Compared with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), biologics are more effective and are recommended to be included in the sequential treatment for psoriatic arthritis (PsA) patients. However, biologics are expensive and the cost-effectiveness of sequential biologic therapy in China remains unknown. The purpose of this study is to evaluate the cost-effectiveness of different sequential treatment option for PsA patients who have not responded to csDMARDs from the perspective of Chinese healthcare system. METHODS: We constructed a discrete event simulation model to evaluate the cost-effectiveness of 7 monotherapy treatments and 32 sequential treatments. In sequential therapy, two different types of biologics were used as first-line and second-line treatments, respectively, with the best supportive care (BSC) as the third-line treatment. The primary outcomes included total treatment costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). One-way and probability sensitivity analyses were performed to explore the uncertainty of our model. RESULTS: Compared to all other strategies, initiating with secukinumab followed by etanercept (SEC-ETN) provided the highest health benefits. At a willingness-to-pay (WTP) threshold of US 8,161 per QALY, SEC-ETN was the most cost-effective strategy, with an ICER of 0,837 per QALY. One-way sensitivity analysis and probabilistic sensitivity analysis results confirmed the robust of this conclusion. CONCLUSIONS: In China, SEC-ETN may be the most cost-effective strategy for patients who have failed treatment with csDMARDs and have not previously used biologics. The results provide evidence for identifying the optimal biologic treatment strategy for PsA patients in China. Key Points • Compared with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), biologics are more effective and are recommended to be included in the sequential treatment for psoriatic arthritis (PsA) patients. However, the cost-effectiveness of sequential biologic therapy in China remains unclear. • At a willingness-to-pay threshold of 8,161, initiating with secukinumab followed by etanercept (SEC-ETN) was cost-effective strategy, outperforming other strategies. • From the perspective of the Chinese healthcare system, the optimal biologic treatment strategy was SEC-ETN in China.