Du Xin ¹ Qixiang Guo ² Qixiang Guo ¹ Xiaomeng Jiang ¹ Ziling Su ³ Weiting Zhou ⁴ Zhongjian Wang ⁵ Jiarun Li ¹ Yue Yang ^1* Yi Zhang ^1*

• ¹ Tsinghua University, Beijing, China
• ² Department of Pharmacy, Peking University People's Hospital, Beijing, Beijing Municipality, China
• ³ School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, Guangdong Province, China
• ⁴ School of Pharmacy, MCPHS University, Boston, United States
• ⁵ Pharnexcloud Digital Technology(Chengdu) Co., Ltd, Chengdu, China

Background As China is one of the countries with the highest recorded cases of Immune-Mediated Inflammatory Diseases (IMIDs), these diseases have also emerged as a serious public health concern. Biosimilars, potentially lower-cost versions of biologics, may improve access. This study aims to assess the clinical benefits, cost and uptake of adalimumab biosimilars, tocilizumab biosimilars, and infliximab biosimilars compared with their reference biologics in patients with IMIDs in China. Methods IMIDs biosimilars and their reference drugs approved in China between 2015 and 2024 were identified. Head-to-head randomized clinical trials (RCTs) and real-world cohort studies on adalimumab, tocilizumab and infliximab and their biosimilars for the treatment of IMIDs were assessed. We evaluated the monthly treatment costs and quarterly uptakes of these biosimilars and their reference biologics in China. Besides, we simulated the impact of biosimilar substitution in different scenarios. Meta-analyses were performed using a random-effects model to evaluate the efficacy, safety, and immunogenicity of treatments, including pooled risk ratios (RR) for primary endpoints and secondary endpoints, with 95% credible intervals (CrIs). Findings A total of 12 RCTs involving 5717 patients with IMIDs were analyzed, including 12 approved biosimilars of adalimumab, infliximab, and tocilizumab. The primary endpoints of adalimumab (7 RCTs with 3174 patients; RR, 1.02; 95% CrI, 0.99-1.06, P=.33), infliximab (3 RCTs with 1291 patients; RR, 1.02; 95% CrI, 0.94-1.11, P=.98), tocilizumab (2 RCTs with 1252 patients；RR, 1.01, 95% CrI, 0.94-1.08) met equivalence with reference biologics. These findings were consistent with the cohort studies. In 2024, IMIDs biosimilars are available at 63% to 82% of the price per unit of the reference drugs, with uptake rates of 16.5% to 72.1% in China. Patients with IMIDs using these biosimilars could save between $874 and $2,184 per month in treatment costs, equivalent to 1.8 to 7.0 times the per capita monthly disposable income in China in 2024. Interpretation Our study revealed that IMID biosimilars in China provide clinical benefits comparable to their reference biologics evidenced by high-quality RCTs and cohort studies with offer significant cost savings in China. Encouraging China's national volume-based procurement and multi-stakeholder collaboration may help accelerate the substitution of IMIDs biosimilars.