与原研英夫利昔单抗相比，CMAB008在接受甲氨蝶呤联合治疗的中重度类风湿关节炎患者中的疗效和安全性：一项随机、双盲、多中心、III期非劣效性研究。
Efficacy and Safety of CMAB008 Compared with Innovator Infliximab in Patients with Moderate-to-Severe Rheumatoid Arthritis Receiving Concomitant Methotrexate: A Randomized, Double-blind, Multi-center, Phase III Non-inferiority Study.
作者信息
Ye Hua, Liu Shengyun, Xu Jian, Chai Kexia, He Dongyi, Fang Yongfei, Xie Qibing, Liu Huaxiang, Liu Ying, Hua Bingzhu, Hu Jiankang, Zhang Zhiyi, Zhou Mingxuan, Zhao Dongbao, Li Yan, Jiang Zhenyu, Wang Meimei, Li Jingyang, Zhang Zhuoli, Li Xiaomei, Li Yang, Sun Erwei, Bi Liqi, Wei Wei, Tie Ning, He Lan, Huang Xiangyang, Zhang Yan, Huang Qingchun, Wang Xiaofei, Liu Xiangyuan, Li Jing, Su Yin
机构信息
Rheumatology Department, Peking University People's Hospital, No. 11, XiZhimen South Street, Beijing, 100044, China.
Rheumatology and Immunology Department, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
出版信息
Rheumatol Ther. 2023 Jun;10(3):757-773. doi: 10.1007/s40744-023-00544-2. Epub 2023 Mar 25.
OBJECTIVES
The aim of this work is to verify the non-inferior efficacy and safety of CMAB008 compared with innovator infliximab in rheumatoid arthritis patients combined with methotrexate.
METHODS
We conducted a randomized, double-blinded, parallel, positive control design, multicenter study, with a stable dose of methotrexate. Patients were enrolled randomly with a ratio of 1:1 to receive intravenously CMAB008 3 mg/kg or innovator infliximab 3 mg/kg at weeks 0, 2, 6, 14, 22 and 30. The primary efficacy endpoint was American College of Rheumatology 20% improvement criteria (ACR20) response rate at week 30. The non-inferiority was established if the lower limit of the one-sided 97.5% confidence interval (CI) for the difference was more than - 15% and the equivalence was established if the two-sided 95% CI was within ± 15% in an exploratory equivalence analysis. The secondary endpoints included other efficacy assessment parameters, as well as immunogenicity, safety, and pharmacokinetics.
RESULTS
In the full analysis population (FAS), 110 (57.6%) of 191 patients in the CMAB008 group and 120 (62.2%) of 193 patients in the innovator infliximab group reached the primary outcome of ACR20 at week 30. The differences of the rates were - 4.6% and the lower limit of one-sided 97.5% confidence interval was - 14.29%, not less than the lower limit of the non-inferiority margin (- 15%); so CMAB008 was non-inferior to innovator infliximab. Further, CMAB008 was equivalent to innovator infliximab both in FAS (difference - 4.6%, 95% CI - 14.29% to 5.12%) and PPS (difference - 3.3%, 95% CI - 13.18% to 6.62%). The efficacy, safety, immunogenicity, and pharmacokinetics are highly similar between CMAB008 and innovator infliximab.
CONCLUSIONS
Non-inferior efficacy of CMAB008 to innovator infliximab is illustrated with similar early and lasting therapeutic effects, and the equivalence is further demonstrated. CMAB008 is well tolerated and has semblable safety compared with the innovator infliximab.
TRIAL REGISTRATION NUMBER
NCT03478111.
目的
本研究旨在验证CMAB008与原研英夫利昔单抗相比，在联合甲氨蝶呤治疗类风湿关节炎患者中的非劣效性疗效和安全性。
方法
我们进行了一项随机、双盲、平行、阳性对照设计的多中心研究，甲氨蝶呤剂量稳定。患者按1:1比例随机入组，在第0、2、6、14、22和30周静脉注射3mg/kg的CMAB008或3mg/kg的原研英夫利昔单抗。主要疗效终点为第30周时美国风湿病学会20%改善标准（ACR20）缓解率。如果差异的单侧97.5%置信区间（CI）下限大于-15%，则确定为非劣效性；在探索性等效性分析中，如果双侧95%CI在±15%以内，则确定为等效性。次要终点包括其他疗效评估参数，以及免疫原性、安全性和药代动力学。
结果
在全分析集（FAS）中，CMAB008组191例患者中有110例（57.6%）、原研英夫利昔单抗组193例患者中有120例（62.2%）在第30周达到ACR20主要结局。两组缓解率差异为-4.6%，单侧97.5%置信区间下限为-14.29%，不低于非劣效界值下限（-15%）；因此，CMAB008不劣于原研英夫利昔单抗。此外，在FAS（差异-4.6%，95%CI -14.29%至5.12%）和符合方案集（PPS，差异-3.3%，95%CI -13.18%至6.62%）中，CMAB008与原研英夫利昔单抗等效。CMAB008与原研英夫利昔单抗在疗效、安全性、免疫原性和药代动力学方面高度相似。
结论
CMAB008在疗效上不劣于原研英夫利昔单抗，具有相似的早期和持久治疗效果，并进一步证明了等效性。CMAB008耐受性良好，与原研英夫利昔单抗相比安全性相当。
试验注册号
NCT03478111。
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