Peng Jilin, Wang Yixu, Chi Zhenye, Li Shichao, Zhang Yuan, Li Ling, Bian Di, Zhai Ziyu, Yuan Sijie, Zhang Yulin, Li Weijie, Ye Fanglei, Wang Le
Department of Otolaryngology Head and Neck Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
Department of Otolaryngology, Head and Neck Surgery, People's Hospital, Peking University, No. 11 Xizhimen South Street Xicheng District, Beijing 100044, China.
Pharmacol Res. 2024 Dec;210:107475. doi: 10.1016/j.phrs.2024.107475. Epub 2024 Nov 20.
Multiple brands of immune checkpoint inhibitors (ICIs), including domestic and imported agents, have been approved as front-line therapy in China. However, little is known about the difference in efficacy and safety of these agents of different origins. This study aims to systematically compare the difference between National Medical Products Administration (NMPA) approved domestic and imported ICIs regarding their efficacy, safety, and price.
We systematically searched PubMed, Embase, and Cochrane Central, from inception to July 1st, 2023, for phase III trials evaluating ICIs as first- or second-line settings that have available hazard ratio (HR) for Asians or non-Asians. Studies of domestic and imported ICIs were screened and paired by the matching clinical characteristics as mirror groups. The primary endpoint was to assess the difference in efficacy between domestic and imported ICIs regarding overall survival. An effect size was derived from each mirror group and then pooled across all groups using a random-effects model. Heterogeneity was assessed by I statistics. Monthly treatment costs for each drug were calculated based on dosing information on National Medical Products Administration (NMPA) label and prices extracted from INSIGHT database. The difference in monthly treatment costs was compared by unpaired T-test. The protocol is registered on PROSPERO, CRD42024580753.
Overall, domestic ICIs exhibited better efficacy regarding overall survival (HR, 0.87; 95 % CI, 0.79-0.97; P < 0.05; I = 0) compared with imported agents. No difference was observed regarding benefits in progression free survival (HR, 0.95; 95 % CI, 0.82-1.09; P > 0.05; I = 0). Consistent results were obtained through frequentists and Bayesian approaches. The differences in safety; measured by relative risk of treatment-related adverse events (TARE) of any grade, TARE of grade 3 or higher, immune-related adverse events(irAE) of any grade, irAE of grade 3 or higher, discontinuation due to treatment, and death due to treatment; were also similar between domestic and imported ICIs. Moreover, in current Chinese market, the monthly treatment prices of domestic ICIs was statistically lower than that of imported ICIs (P < 0.01).
Our research provides an essential reference of cost-effectiveness of ICIs manufactured in China for clinicians in routine practice of cancer care as well as public health authorities for decision making process.
包括国产和进口药物在内的多种品牌免疫检查点抑制剂（ICI）已在中国获批作为一线治疗药物。然而，对于这些不同来源药物在疗效和安全性方面的差异，人们了解甚少。本研究旨在系统比较国家药品监督管理局（NMPA）批准的国产和进口ICI在疗效、安全性和价格方面的差异。
我们系统检索了PubMed、Embase和Cochrane Central，检索时间从建库至2023年7月1日，以查找评估ICI作为一线或二线治疗且有亚洲人或非亚洲人可用风险比（HR）的III期试验。对国产和进口ICI的研究进行筛选，并根据匹配的临床特征配对为镜像组。主要终点是评估国产和进口ICI在总生存期方面的疗效差异。从每个镜像组得出效应量，然后使用随机效应模型在所有组中进行汇总。通过I统计量评估异质性。根据NMPA标签上的给药信息和从INSIGHT数据库提取的价格，计算每种药物的每月治疗费用。通过非配对t检验比较每月治疗费用的差异。该方案已在PROSPERO注册，注册号为CRD42024580753。
总体而言，与进口药物相比，国产ICI在总生存期方面显示出更好的疗效（HR，0.87；95%CI，0.79 - 0.97；P < 0.05；I = 0）。在无进展生存期方面未观察到差异（HR，0.95；95%CI，0.82 - 1.09；P > 0.05；I = 0）。通过频率学派和贝叶斯方法获得了一致的结果。国产和进口ICI在安全性方面的差异，以任何级别的治疗相关不良事件（TARE）、3级或更高等级的TARE、任何级别的免疫相关不良事件（irAE）、3级或更高等级的irAE、因治疗停药以及因治疗死亡的相对风险衡量，也相似。此外，在当前中国市场，国产ICI的每月治疗价格在统计学上低于进口ICI（P < 0.01）。
我们的研究为癌症护理常规实践中的临床医生以及公共卫生当局在决策过程中提供了中国生产的ICI成本效益的重要参考。
