Comparison of the Efficacy and Safety of Adalimumab (Humira) and the Adalimumab Biosimilar Candidate (HS016) in Chinese Patients with Active Ankylosing Spondylitis: A Multicenter, Randomized, Double-Blind, Parallel, Phase III Clinical Trial
单位：[1]Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, No. 1 Shuaifuyuan, Dongcheng District, Beijing 100730, China[2]National Clinical Research Center for Immunologic Diseases, Ministry of Science and Technology, No. 1 Shuaifuyuan, Dongcheng District, Beijing 100730, China[3]Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, No. 1 Shuaifuyuan, Dongcheng District, Beijing 100730, China[4]Department of Rheumatology and Immunology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, China[5]Department of Rheumatology, Changhai Hospital, Shanghai 200433, China[6]Department of Rheumatology, Huashan Hospital, Fudan University, Shanghai 201907, China[7]Department of Rheumatology, West China Hospital, Sichuan University, Chengdu 610000, China四川大学华西医院[8]Department of Rheumatology, The First Affiliated Hospital of Anhui Medical University, Hefei 230001, China[9]Department of Rheumatology, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, China昆明医科大学附属第一医院[10]Department of Rheumatology, Qilu Hospital of Shandong University, Jinan 250001, China[11]Department of Rheumatology, Zhongshan Hospital, Fudan University, Shanghai 200032, China[12]Department of Rheumatology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310009, China[13]Department of Rheumatology, Xiangya Hospital, Central South University, Changsha 410008, China[14]Department of Rheumatology, Beijing Hospital, Beijing 100010, China[15]Department of Rheumatology, The First Affiliated Hospital of Shanxi Medical University, Taiyuan 30001, China[16]Department of Rheumatology, The Second Xiangya Hospital of Central South University, Changsha 410007, China[17]Department of Rheumatology, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China[18]Department of Rheumatology, Peking University Third Hospital, Beijing 100089, China[19]Department of Rheumatology, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430030, China华中科技大学同济医学院附属同济医院[20]Department of Rheumatology, Guangdong Second Provincial General Hospital, Guangzhou 510310, China[21]Department of Rheumatology, The Third Hospital of Hebei Medical University, Shijiazhuang 050000, China[22]Department of Rheumatology, Zhuzhou Central Hospital, Zhuzhou 412000, China[23]Department of Rheumatology, Shanghai Guanghua Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai 200052, China[24]Department of Rheumatology, China-Japan Friendship Hospital, Beijing 100020, China[25]Department of Rheumatology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430022, China华中科技大学同济医学院附属协和医院[26]Department of Rheumatology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, China[27]Department of Rheumatology, Jiangsu Province Hospital, Nanjing 210000, China江苏省人民医院[28]Department of Rheumatology, Peking University First Hospital, Beijing 100034, China[29]Department of Rheumatology, Tianjian Medical University General Hospital, Tianjin 300052, China[30]Department of Rheumatology, The Second Affiliated Hospital of Shanxi Medical University, Taiyuan 030001, China
Objective The aim of this study was to evaluate the efficacy and safety of the biosimilar candidate of adalimumab (HS016) compared with adalimumab (Humira) for the treatment of active ankylosing spondylitis. Methods A multicenter, randomized, double-blind, parallel, positive control, phase III clinical trial was conducted at 28 locations in China. Patients with active ankylosing spondylitis were randomized in a 2:1 ratio to subcutaneously receive 40 mg of either HS016 or adalimumab every other week for 24 weeks. The primary endpoint was to achieve at least a 20% improvement (ASAS20) in patients at 24 weeks according to the Assessment of Spondyloarthritis International Society criteria. The secondary endpoint included other efficacy assessment parameters, health evaluations, safety, pharmacokinetic, and immunogenicity parameters. Results Following the random assignment of 648 patients into HS016 (n = 416) and adalimumab (n = 232) groups, no significant difference was found in the ASAS20 response rates at 24 weeks between the HS016 (364/416, 87.5%) and adalimumab (209/232, 90.1%) treatments and the difference between the response rates (- 2.59%; 90% confidence interval [CI] - 6.77 to 1.60) was within the predefined equivalence margin (+/- 15%). There were also no significant differences when the secondary endpoints were compared (all p > 0.05). Similarly, the rates of treatment-emergent adverse events (TEAEs) were not significantly different between the two groups, with most TEAEs being mild to moderate. Only nine severe cases were found, including seven within the HS016 group, three (0.7%) of which were tuberculosis cases. Plasma concentrations of HS016 and adalimumab from weeks 12 to 14 were similar during the steady-state period and steady-state maximal concentration (C-max,C-ss) was equivalent for HS016 (7356.6 ng/mL) and adalimumab (7600.3 ng/mL). The accumulated proportion of patients with positive human anti-human antibodies (HAHAs) at week 24 was 326/412 (79.1%) in the HS016 group and 183/229 (79.9%) in the adalimumab group (p > 0.05), while the accumulated proportion of patients with positive neutralizing antibody (NAb) tests were 72/412 (17.5%) in the HS016 group and 43/229 (18.8%) in the adalimumab group (p > 0.05). Conclusion HS016 resembled adalimumab in efficacy and safety over the 24-week treatment period.
基金：
Chinese National Key Technology R&D Program, Ministry of Science and Technology [2017YFC0907601]; Medicine and Health Technology Innovation Project, Chinese Academy of Medical Sciences [2019-I2M-2-008]; ZHEJIANG HISUN PHARMACEUTICAL CO., LTD.; Haisun BioRay Bio-pharmaceutical., Ltd.
第一作者单位：[1]Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, No. 1 Shuaifuyuan, Dongcheng District, Beijing 100730, China[2]National Clinical Research Center for Immunologic Diseases, Ministry of Science and Technology, No. 1 Shuaifuyuan, Dongcheng District, Beijing 100730, China[3]Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, No. 1 Shuaifuyuan, Dongcheng District, Beijing 100730, China
共同第一作者：
通讯作者：
通讯机构：[1]Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, No. 1 Shuaifuyuan, Dongcheng District, Beijing 100730, China[2]National Clinical Research Center for Immunologic Diseases, Ministry of Science and Technology, No. 1 Shuaifuyuan, Dongcheng District, Beijing 100730, China[3]Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, No. 1 Shuaifuyuan, Dongcheng District, Beijing 100730, China
推荐引用方式(GB/T 7714)：
Su Jinmei,Li Mengtao,He Lan,et al.Comparison of the Efficacy and Safety of Adalimumab (Humira) and the Adalimumab Biosimilar Candidate (HS016) in Chinese Patients with Active Ankylosing Spondylitis: A Multicenter, Randomized, Double-Blind, Parallel, Phase III Clinical Trial[J].BIODRUGS.2020,34(3):381-393.doi:10.1007/s40259-020-00408-z.
APA：
Su, Jinmei,Li, Mengtao,He, Lan,Zhao, Dongbao,Wan, Weiguo...&Zeng, Xiaofeng.(2020).Comparison of the Efficacy and Safety of Adalimumab (Humira) and the Adalimumab Biosimilar Candidate (HS016) in Chinese Patients with Active Ankylosing Spondylitis: A Multicenter, Randomized, Double-Blind, Parallel, Phase III Clinical Trial.BIODRUGS,34,(3)
MLA：
Su, Jinmei,et al."Comparison of the Efficacy and Safety of Adalimumab (Humira) and the Adalimumab Biosimilar Candidate (HS016) in Chinese Patients with Active Ankylosing Spondylitis: A Multicenter, Randomized, Double-Blind, Parallel, Phase III Clinical Trial".BIODRUGS 34..3(2020):381-393
