中国新药杂志

治疗类风湿关节炎领域生物类似药与其参照药临床相似性评估的Meta分析

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陈瑶 ¹^,² , 周庆欣 ¹^,² , 曾保起 ¹^,² , 杨继春 ³ , 高乐 ⁴ , 颜钰淞 ¹ , 孙凤 ¹^,²

中国新药杂志 | 临床研究 2021,30(8): 723-731

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中国新药杂志 |临床研究 2021 , 30 (8) : 723 -731

治疗类风湿关节炎领域生物类似药与其参照药临床相似性评估的Meta分析

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陈瑶¹^,², 周庆欣¹^,², 曾保起¹^,², 杨继春³, 高乐⁴, 颜钰淞¹, 孙凤¹^,²

作者信息

¹北京大学公共卫生学院，北京　100191

²北京大学循证医学中心，北京　100191

³昆明医科大学第二附属医院中心实验室，昆明　650011

⁴香港大学李嘉诚医学院药理及药剂学系，香港　999077

通讯作者:

孙凤，女，副教授，硕士生导师，研究方向：循证医学与药物流行病学。联系电话：（010）82801191，E-mail：sunfeng@bjmu.edu.cn。

作者简介:

陈瑶，女，硕士研究生，研究方向：循证医学。E-mail：chen_yao@pku.edu.cn。

Evaluation of the clinical equivalence of biosimilars to their reference drugs in the treatment of rheumatoid arthritis: a Meta-analysis

Yao CHEN¹^,², Qing-xin ZHOU¹^,², Bao-qi ZENG¹^,², Ji-chun YANG³, Le GAO⁴, Yu-song YAN¹, Feng SUN¹^,²

Affiliations

¹Institute of Public Health, Peking University, Beijing 100191, China

²Peking University Center for Evidence Based Medical and Clinical Research, Beijing 100191, China

³Key Laboratory, the Second Affiliated Hospital of Kunming Medical University, Kunming 650011, China

⁴Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong 999077, China

出版时间: 2021-04-30

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摘要

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目的：

评价治疗类风湿关节炎（rheumatoid arthritis，RA）领域阿达木单抗（ADA）、依那西普（ETA）、英夫利昔单抗（INF）和利妥昔单抗（RIT）的生物类似药及其参照药在临床有效性、安全性和免疫性的相似性。

方法：

本文系统检索PubMed，Embase，Cochrane Library，Web of Science，SinoMed，ClinicalTrial.gov及中国知网和万方数据库，收集关于治疗RA的生物类似药及其参照药比较的随机对照试验（RCTs），检索时限均为建库至2019年12月17日，由2名研究者独立进行文献筛选、数据提取和偏倚风险评价后，使用STATA 15.0软件进行数据分析，分别对每一类生物类似药与其参照药进行Meta分析，并按照随访观察周期进行亚组分析。

结果：

最终纳入了27个RCTs，共10 405例对一线治疗方案效果不理想的RA患者；ADA，ETA，INF和RIT分别涉及10，6，7和4个RCTs，Meta分析及其亚组分析结果显示，4类生物类似药与其参照药在临床有效性和安全性方面均是可比的，在免疫原性方面，除ETA外其他3组比较差异均未发现有统计学意义，但鉴于免疫原性结局的相关证据的GRADE质量评级结果为非常低，因此免疫原性的比较结果还有待后续相关研究的进一步证明。

结论：

本研究证明了RA治疗领域的4类生物类似药与其参照药具有良好的临床相似性，为生物类似药的临床使用提供了证据支持。

关键词

生物类似药 / 类风湿关节炎 / 随机对照试验 / 系统综述 / Meta分析

Abstract

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Objective:

To demonstrate equivalent clinical efficacy of all biosimilars of adalimumab (ADA), etanercept (ETA), infliximab (INF), and rituximab (RIT) with their reference drugs as well as to evaluate the relative safety and immunogenicity of biosimilars in the treatment of rheumatoid arthritis (RA).

Methods:

Pubmed, Embase, Cochrane Library, Web of Science, Sinomed, ClinicalTrial.gov, CNKI and Wanfang database were searched to collect the randomized controlled trials (RCTs) about the comparisons between biosimilars and their reference drugs for the treatments of RA published from inception to December 17, 2019. Two researchers screened literature, extracted data and assessed risk of bias independently. STATA 15.0 software was used to perform data analysis. To reduce heterogeneity, subgroup analysis in accordance with the drug treatment duration was conducted.

Results:

A total of 27 RCTs were included (ADA: 10, ETA: 6, INF: 7, RIT: 4), involving 10 405 RA patients with inadequate response to the first-line treatment regimen. The clinical efficacy and safety of the four biosimilar drugs were comparable with their reference drugs. In terms of immunogenicity, no statistically significant differences were found between the other three groups except for ETA. It should be noted that the quality rating of the evidence related to the immunogenicity outcome was low, so the results of the immunogenicity need to be further verified by subsequent relevant studies.

Conclusion:

This study supports the similarity of the four biosimilars to their respective reference drugs, which may serve as evidence for related clinical practice, guideline development, and policy making.

Key words

biosimilars / rheumatoid arthritis / randomized controlled trials / systematic review / Meta-analysis

引用本文

陈瑶, 周庆欣, 曾保起, 杨继春, 高乐, 颜钰淞, 孙凤. 治疗类风湿关节炎领域生物类似药与其参照药临床相似性评估的Meta分析. 中国新药杂志, 2021 , 30 (8) : 723 -731 .

Yao CHEN, Qing-xin ZHOU, Bao-qi ZENG, Ji-chun YANG, Le GAO, Yu-song YAN, Feng SUN. Evaluation of the clinical equivalence of biosimilars to their reference drugs in the treatment of rheumatoid arthritis: a Meta-analysis[J]. Chinese Journal of New Drugs, 2021 , 30 (8) : 723 -731 .

基金

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国家自然科学基金资助项目(71673003)

参考文献

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文献

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参考文献引证文献

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2021年第30卷第8期

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首发时间：2026-10-28
出版时间：2021-04-30

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录用日期：2020-03-24

基金

国家自然科学基金资助项目(71673003)

作者信息

¹北京大学公共卫生学院，北京　100191

²北京大学循证医学中心，北京　100191

³昆明医科大学第二附属医院中心实验室，昆明　650011

⁴香港大学李嘉诚医学院药理及药剂学系，香港　999077

通讯作者:

孙凤，女，副教授，硕士生导师，研究方向：循证医学与药物流行病学。联系电话：（010）82801191，E-mail：sunfeng@bjmu.edu.cn。

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2种不同金属材料的力学参数

科 Family	属数 Number of genus	种数 Number of species	占总种数比例 Percentage of total species (%)	属 Genus	种数 Number of species	占总种数比例 Percentage of total species (%)
鹅膏菌科Amanitaceae	2	11	5.26	鹅膏菌属 Amanita	10	4.78
小菇科 Mycenaceae	2	12	5.74	丝盖伞属 Inocybe	5	2.39
多孔菌科 Polyporaceae	8	14	6.70	蜡蘑属 Laccaria	5	2.39
红菇科 Russulaceae	3	23	11.00	小皮伞属 Marasmius	6	2.87
				小菇属 Mycena	11	5.26
				光柄菇属 Pluteus	5	2.39
				红菇属 Russula	17	8.13
				栓菌属 Trametes	5	2.39

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