University of Liverpool, Liverpool, UK.
Department of Musculoskeletal Biology, Institute of Ageing and Chronic Disease, Clinical Sciences Centre, Aintree University Hospital, Longmoor Lane, Liverpool, L9 7AL, UK.
BioDrugs. 2018 Jun;32(3):193-199. doi: 10.1007/s40259-018-0283-4.
Regulatory approval of biosimilar versions of originator biotherapeutics requires that new biological products be highly similar to originator products, with no clinically meaningful differences in safety, purity, and potency. In some trials of biosimilars of tumor necrosis factor inhibitors for the treatment of rheumatoid arthritis (RA) and plaque psoriasis (PsO), pre-specified margins for efficacy and safety have been met, but differences in treatment responses between pivotal originator trials and biosimilar trials have been noted. The objective of this systematic review was to examine these differences.
Searches were conducted to identify comparative randomized clinical trials of approved or proposed biosimilars of adalimumab, etanercept, and infliximab.
Of 83 publications identified, 16 publications were included for analysis (RA: originators, n = 5; biosimilars, n = 6; PsO: originators, n = 2; biosimilars, n = 3). American College of Rheumatology 20% response rates were higher among patients with RA receiving originator biologics and biosimilars in biosimilar trials than among patients receiving the originator biologics in pivotal trials. In etanercept studies in PsO, a difference was observed in Psoriasis Area and Severity Index 75% response rates between biosimilar and pivotal trials. Insufficient efficacy data were available from adalimumab and infliximab biosimilar studies in PsO to determine any differences in treatment responses between pivotal and biosimilar studies.
Observed differences in treatment response rates between pivotal originator trials and trials of originator biologics and their respective biosimilars may be attributable to fundamental differences in study design and/or baseline patient characteristics, which require further analysis.
生物类似药监管审批要求新的生物制品与原创生物制品高度相似，在安全性、纯度和效价方面无临床意义上的差异。在一些肿瘤坏死因子抑制剂生物类似药治疗类风湿关节炎（RA）和斑块状银屑病（PsO）的试验中，已达到预先设定的疗效和安全性界限，但关键的原创试验和生物类似药试验之间的治疗反应存在差异。本系统评价的目的是研究这些差异。
检索以确定已批准或提议的阿达木单抗、依那西普和英夫利昔单抗生物类似药的比较随机临床试验。
在确定的 83 篇文献中，有 16 篇文献被纳入分析（RA：原创生物制剂，n=5；生物类似药，n=6；PsO：原创生物制剂，n=2；生物类似药，n=3）。在生物类似药试验中，接受 RA 原创生物制剂和生物类似药治疗的患者的美国风湿病学会 20%反应率高于接受关键试验中原创生物制剂治疗的患者。在 PsO 的依那西普研究中，观察到生物类似药和关键试验之间的银屑病面积和严重程度指数 75%反应率存在差异。由于 PsO 的阿达木单抗和英夫利昔单抗生物类似药研究中疗效数据不足，无法确定关键试验和生物类似药试验之间的治疗反应差异。
在关键的原创试验和原创生物制剂及其各自的生物类似药试验之间观察到的治疗反应率差异可能归因于研究设计和/或基线患者特征的根本差异，需要进一步分析。
