Smolen Josef S, Cohen Stanley B, Tony Hans-Peter, Scheinberg Morton, Kivitz Alan, Balanescu Andra, Gomez-Reino Juan, Cen Liyi, Zhu Peijuan, Shisha Tamas
Department of Rheumatology, Medical University of Vienna, Vienna, Austria.
Metroplex Clinical Research, Dallas, Texas, USA.
Ann Rheum Dis. 2017 Sep;76(9):1598-1602. doi: 10.1136/annrheumdis-2017-211281. Epub 2017 Jun 21.
The aim of this report is to demonstrate pharmacokinetic (PK) and pharmacodynamic (PD) equivalence as well as similar efficacy, safety and immunogenicity between GP2013, a biosimilar rituximab, and innovator rituximab (RTX) in patients with rheumatoid arthritis (RA) with inadequate response or intolerance to tumour necrosis factor inhibitor (TNFi) treatment.
In this multinational, randomised, double-blind, parallel-group study, 312 patients with active disease despite prior TNFi therapy were randomised to receive GP2013 or either the EU (RTX-EU) or the US (RTX-US) reference product, along with methotrexate (MTX) and folic acid. The primary endpoint was the area under the serum concentration-time curve from study drug infusion to infinity (AUC). Additional PK and PD parameters, along with efficacy, immunogenicity and safety outcomes were also assessed up to week 24.
The 90% CI of the geometric mean ratio of the AUCs were within the bioequivalence limits of 80% to 125% for all three comparisons; GP2013 versus RTX-EU: 1.106 (90% CI 1.010 to 1.210); GP2013 versus RTX-US: 1.012 (90% CI 0.925 to 1.108); and RTX-EU versus RTX-US: 1.093 (90% CI 0.989 to 1.208). Three-way PD equivalence of B cell depletion was also demonstrated. Efficacy, safety and immunogenicity profiles were similar between GP2013 and RTX.
Three-way PK/PD equivalence of GP2013, RTX-EU and RTX-US was demonstrated. Efficacy, safety and immunogenicity profiles were similar between GP2013 and RTX.
NCT01274182; Results.
本报告旨在证明生物类似药利妥昔单抗GP2013与原研利妥昔单抗（RTX）在对肿瘤坏死因子抑制剂（TNFi）治疗反应不足或不耐受的类风湿关节炎（RA）患者中的药代动力学（PK）和药效学（PD）等效性，以及相似的疗效、安全性和免疫原性。
在这项多国、随机、双盲、平行组研究中，312例尽管先前接受过TNFi治疗但仍患有活动性疾病的患者被随机分配接受GP2013或欧盟（RTX-EU）或美国（RTX-US）的参比产品，同时服用甲氨蝶呤（MTX）和叶酸。主要终点是从研究药物输注至无穷大时血清浓度-时间曲线下面积（AUC）。还评估了直至第24周的其他PK和PD参数，以及疗效、免疫原性和安全性结果。
所有三项比较中，AUC几何平均比值的90%置信区间均在生物等效性限度80%至125%内；GP2013与RTX-EU比较：1.106（90%置信区间1.010至1.210）；GP2013与RTX-US比较：1.012（90%置信区间0.925至1.108）；RTX-EU与RTX-US比较：1.093（90%置信区间0.989至1.208）。还证明了B细胞耗竭的三方PD等效性。GP2013和RTX之间的疗效、安全性和免疫原性特征相似。
证明了GP2013、RTX-EU和RTX-US的三方PK/PD等效性。GP2013和RTX之间的疗效、安全性和免疫原性特征相似。
NCT01274182；结果
