Combe Bernard, Allanore Yannick, Alten Rieke, Caporali Roberto, Durez Patrick, Iannone Florenzo, Nurmohamed Michael T, Toumi Mondher, Lee Sang Joon, Kwon Taek Sang, Noh Jiwon, Park Gahee, Yoo Dae Hyun
Department of Rheumatology, CHU Montpellier, Montpellier University, Montpellier, France.
Rheumatology Department, Hôpital Cochin, Paris Descartes University, Paris, France.
Arthritis Res Ther. 2021 Apr 16;23(1):119. doi: 10.1186/s13075-021-02487-x.
A subcutaneous (SC) formulation of infliximab biosimilar CT-P13 is approved in Europe for the treatment of adult patients with rheumatoid arthritis (RA). It may offer improved efficacy versus intravenous (IV) infliximab formulations.
A network meta-regression was conducted using individual patient data from two randomised trials in patients with RA, which compared CT-P13 SC with CT-P13 IV, and CT-P13 IV with reference infliximab IV. In this analysis, CT-P13 SC was compared with CT-P13 IV, reference infliximab IV and pooled data for both reference infliximab IV and CT-P13 IV. Outcomes included changes from baseline in 28-joint Disease Activity Score based on C-reactive protein (DAS28-CRP), Simplified Disease Activity Index (SDAI) and Clinical Disease Activity Index (CDAI), and rates of remission, low disease activity or clinically meaningful improvement in functional disability per Health Assessment Questionnaire-Disability Index (HAQ-DI).
The two studies enrolled 949 patients with RA; pooled data for 840 and 751 patients were evaluable at weeks 30 and 54, respectively. For the CT-P13 SC versus pooled IV treatment arm comparison, differences in changes from baseline in DAS28-CRP (- 0.578; 95% confidence interval [CI] - 0.831, - 0.325; p < 0.0001), CDAI (- 3.502; 95% CI - 5.715, - 1.289; p = 0.002) and SDAI (- 4.031; 95% CI - 6.385, - 1.677; p = 0.0008) scores at 30 weeks were statistically significant in favour of CT-P13 SC. From weeks 30 to 54, the magnitude of the differences increased and remained statistically significant in favour of CT-P13 SC. Similar results were observed for the comparison of CT-P13 SC with CT-P13 IV and with reference infliximab IV. Statistically significant differences at week 30 favoured CT-P13 SC over the pooled IV treatment arms for the proportions of patients achieving EULAR-CRP good response, American College of Rheumatology (ACR) 50 and ACR70 responses, DAS28-CRP-defined remission, low disease activity (DAS28-CRP, CDAI and SDAI criteria) and clinically meaningful HAQ-DI improvement.
CT-P13 SC was associated with greater improvements in DAS28-CRP, CDAI and SDAI scores and higher rates of clinical response, low disease activity and clinically meaningful improvement in functional disability, compared with CT-P13 IV and reference infliximab IV.
EudraCT, 2016-002125-11 , registered 1 July 2016; EudraCT 2010-018646-31 , registered 23 June 2010.
英夫利昔单抗生物类似药CT-P13的皮下注射（SC）制剂在欧洲被批准用于治疗成年类风湿关节炎（RA）患者。与静脉注射（IV）英夫利昔单抗制剂相比，它可能具有更高的疗效。
使用来自两项RA患者随机试验的个体患者数据进行网络meta回归分析，试验比较了CT-P13皮下注射与CT-P13静脉注射，以及CT-P13静脉注射与参比英夫利昔单抗静脉注射。在此分析中，将CT-P13皮下注射与CT-P13静脉注射、参比英夫利昔单抗静脉注射以及参比英夫利昔单抗静脉注射和CT-P13静脉注射的汇总数据进行了比较。结局指标包括基于C反应蛋白的28关节疾病活动评分（DAS28-CRP）、简化疾病活动指数（SDAI）和临床疾病活动指数（CDAI）相对于基线的变化，以及缓解率、低疾病活动率或根据健康评估问卷残疾指数（HAQ-DI）得出的功能残疾临床有意义改善率。
两项研究共纳入949例RA患者；分别有840例和751例患者的数据在第30周和第54周可进行评估。对于CT-P13皮下注射与静脉注射汇总治疗组的比较，第30周时DAS28-CRP（-0.578；95%置信区间[CI]-0.831，-0.325；p<0.0001）、CDAI（-3.502；95%CI-5.715，-1.289；p=0.002）和SDAI（-4.031；95%CI-6.385，-1.677；p=0.0008）评分相对于基线的变化差异具有统计学意义，有利于CT-P13皮下注射。从第30周到第54周，差异幅度增大且仍具有统计学意义，有利于CT-P13皮下注射。CT-P13皮下注射与CT-P13静脉注射以及参比英夫利昔单抗静脉注射的比较也观察到类似结果。第30周时，在达到欧洲抗风湿病联盟（EULAR）-CRP良好反应、美国风湿病学会（ACR）50和ACR70反应、DAS28-CRP定义的缓解、低疾病活动（DAS28-CRP、CDAI和SDAI标准）以及HAQ-DI临床有意义改善的患者比例方面，相对于静脉注射汇总治疗组，CT-P13皮下注射具有统计学显著差异。
与CT-P13静脉注射和参比英夫利昔单抗静脉注射相比，CT-P13皮下注射与DAS28-CRP、CDAI和SDAI评分的更大改善相关，临床反应率、低疾病活动率以及功能残疾临床有意义改善率更高。
欧洲临床试验数据库（EudraCT），2016-002125-11，于2016年7月1日注册；EudraCT 2010-018646-31，于2010年6月23日注册。
