BACKGROUND ABP 710 is being developed as a biosimilar to infliximab reference product (RP). Analytical similarity and pharmacokinetic equivalence between the two have been previously demonstrated. Here we report results from a comparative clinical study that evaluated the efficacy and safety of ABP 710 relative to the RP in patients with rheumatoid arthritis (RA). METHODS In this multicenter, randomized, double-blind, 50-week equivalence study, patients with moderate to severe active RA despite methotrexate received 3-mg/kg infusions of ABP 710 or RP at predetermined intervals based on initial randomization and then with re-randomization at week 22. The primary endpoint was response difference (RD) of ACR20 at week 22, with clinical equivalence evaluated based on 90% CI of - 15%, 15%. Secondary endpoints included Disease Activity Score 28-joint count C-reactive protein (DAS28-CRP), ACR20, ACR50, and ACR70 across time, as well as safety and immunogenicity assessments. RESULTS A total of 558 patients were randomized for the initial treatment (ABP 710 n = 279; RP n = 279). The estimated RD of ACR20 at week 22 was 9.37% with 90% CI (2.67%, 15.96%). The lower bound was within the pre-specified criteria, thus confirming non-inferiority; the upper bound exceeded the pre-specified criteria by 0.96% such that superiority could not be ruled out statistically. In a post hoc analysis with adjustment for random imbalance in baseline factors, the CI of RD was narrowed (0.75%, 13.62%). Changes from baseline in DAS28-CRP as well as ACR20, ACR50, and ACR70 response rates across time and hybrid ACR evaluations were similar for the initial and initial/re-randomized treatment groups. Adverse events and incidence of anti-drug antibodies were similar between treatment groups. CONCLUSIONS These efficacy and safety results support similarity with no clinically meaningful differences between ABP 710 and infliximab RP. Although we were unable to statistically confirm non-superiority, post hoc analysis was supportive of non-superiority. DAS28-CRP, ACR20, ACR50, ACR70, and hybrid ACR evaluations over the entire study were consistently comparable as were safety and immunogenicity. TRIAL REGISTRATION ClinicalTrials.gov. Identifier: NCT02937701. Registered August 30, 2016.

中文翻译：

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建议的生物仿制药ABP 710与英夫利昔单抗参考产品在类风湿关节炎患者中的比较临床疗效和安全性。

背景技术ABP 710被开发为与英夫利昔单抗参考产品（RP）的生物仿制药。先前已经证明了两者之间的分析相似性和药代动力学等效性。在这里，我们报告了一项比较临床研究的结果，该研究评估了ABP 710相对于RP在类风湿关节炎（RA）患者中的疗效和安全性。方法在这项多中心，随机，双盲，50周的等效研究中，尽管有甲氨蝶呤的中度至重度活动性RA患者在初始随机分配的基础上以预定的间隔接受3 mg / kg的ABP 710或RP输注，然后再次第22周随机分组。主要终点是22周时ACR20的反应差异（RD），根据90％CI分别为-15％，15％评估临床等效性。次要终点包括疾病活动评分28关节计数C反应蛋白（DAS28-CRP），ACR20，ACR50和ACR70随时间变化，以及安全性和免疫原性评估。结果共有558名患者被随机分配用于初始治疗（ABP 710 n = 279； RP n = 279）。在第22周时，ACR20的估计RD为9.37％，CI为90％（2.67％，15.96％）。下限在预先确定的标准之内，从而证实了自卑性；上限超出了预定标准0.96％，因此无法从统计学上排除优势。在事后分析中，对基线因素的随机失衡进行了调整，使RD的CI缩小了（0.75％，13.62％）。DAS28-CRP以及ACR20，ACR50，初始和初始/重新随机化治疗组在整个时间内的ACR70反应率和混合ACR评估相似。治疗组之间抗药物抗体的不良事件和发生率相似。结论这些功效和安全性结果支持相似性，ABP 710与英夫利昔单抗RP之间无临床意义上的差异。尽管我们无法从统计学上确认非优势，但事后分析支持非优势。在整个研究中，DAS28-CRP，ACR20，ACR50，ACR70和混合ACR的评估在安全性和免疫原性方面均具有可比性。试验注册ClinicalTrials.gov。标识符：NCT02937701。2016年8月30日注册。结论这些功效和安全性结果支持相似性，ABP 710与英夫利昔单抗RP之间无临床意义上的差异。尽管我们无法从统计学上确认非优势，但事后分析支持非优势。在整个研究中，DAS28-CRP，ACR20，ACR50，ACR70和混合ACR的评估在安全性和免疫原性方面均具有可比性。试验注册ClinicalTrials.gov。标识符：NCT02937701。2016年8月30日注册。结论这些功效和安全性结果支持相似性，ABP 710与英夫利昔单抗RP之间无临床意义上的差异。尽管我们无法从统计学上确认非优势，但事后分析支持非优势。在整个研究中，DAS28-CRP，ACR20，ACR50，ACR70和混合ACR的评估在安全性和免疫原性方面均具有可比性。试验注册ClinicalTrials.gov。标识符：NCT02937701。2016年8月30日注册。整个研究中的混合ACR评估和安全性和免疫原性始终具有可比性。试验注册ClinicalTrials.gov。标识符：NCT02937701。2016年8月30日注册。整个研究中的混合ACR评估和安全性和免疫原性始终具有可比性。试验注册ClinicalTrials.gov。标识符：NCT02937701。2016年8月30日注册。