多生物标志物疾病活动评分在类风湿关节炎患者治疗生物相似性研究中的应用。
Use of multibiomarker disease activity scores in biosimilarity studies for the treatment of patients with rheumatoid arthritis.
作者信息
Kay Jonathan, Bock Amy E, Rehman Muhammad, Zhang Wuyan, Zhang Min, Iikuni Noriko, Alvarez Daniel F
机构信息
Division of Rheumatology, Department of Medicine, UMass Chan Medical School, Worcester, Massachusetts, USA
Division of Epidemiology, Department of Population and Quantitative Health Sciences, UMass Chan Medical School, Worcester, Massachusetts, USA.
出版信息
RMD Open. 2022 Sep;8(2). doi: 10.1136/rmdopen-2022-002423.
OBJECTIVES
This exploratory analysis investigated the potential use of the multibiomarker disease activity (MBDA) score to support biosimilarity assessments using data from two randomised controlled trials (RCTs) of biosimilar infliximab (IFX-qbtx) and biosimilar adalimumab (ADL-afzb) versus EU-sourced infliximab (Remicade; IFX-EU) and adalimumab (Humira; ADL-EU) reference products, respectively, both conducted in adult patients with active rheumatoid arthritis.
METHODS
In one study, patients (N=650) were randomised 1:1 to IFX-qbtx or IFX-EU (3 mg/kg intravenous at weeks 0, 2 and 6, then every 8 weeks). In the other, patients (N=597) were randomised 1:1 to ADL-afzb or ADL-EU (40 mg subcutaneous every other week). All treatments were given with MTX. Mean values of MBDA scores were calculated at baseline (BL), based on the concentrations of 12 serum proteins using the Vectra disease activity algorithm, and at timepoints throughout treatment period 1 (TP1) of the IFX (weeks 6, 14, 30) and ADL (weeks 6, 12, 26) studies. Data were summarised using descriptive statistics for the intent-to-treat population, without imputation for missing data.
RESULTS
At BL, mean (±SD) MBDA scores were 61.3 (±12.5) and 58.8 (±13.2) for IFX-qbtx (n=236) and IFX-EU (n=248), respectively, and 57.2 (±14.44) and 58.3 (±15.34) for ADL-afzb (n=292) and ADL-EU (n=293), respectively. Mean MBDA scores were highly comparable between IFX-qbtx and IFX-EU and between ADL-afzb and ADL-EU at all measured timepoints during TP1 in each study.
CONCLUSIONS
These RCTs are the first to incorporate MBDA score as an exploratory assessment of biosimilarity. MBDA scores may provide objective, quantitative evidence of biosimilarity using an assessment of disease activity that is independent of the potential subjectivity inherent in joint counts, or in patient or physician global assessments.
TRIAL REGISTRATION NUMBERS
NCT02222493 and NCT02480153.
目的
本探索性分析利用两项随机对照试验（RCT）的数据，研究多生物标志物疾病活动度（MBDA）评分在支持生物类似药相似性评估方面的潜在用途。这两项试验分别为生物类似药英夫利昔单抗（IFX-qbtx）和生物类似药阿达木单抗（ADL-afzb）与欧盟来源的英夫利昔单抗（Remicade；IFX-EU）和阿达木单抗（Humira；ADL-EU）对照产品的试验，均在成年活动性类风湿关节炎患者中进行。
方法
在一项研究中，患者（N = 650）按1:1随机分为IFX-qbtx组或IFX-EU组（在第0、2和6周静脉注射3 mg/kg，然后每8周一次）。在另一项研究中，患者（N = 597）按1:1随机分为ADL-afzb组或ADL-EU组（每隔一周皮下注射40 mg）。所有治疗均联合甲氨蝶呤（MTX）使用。基于12种血清蛋白的浓度，采用Vectra疾病活动度算法，在基线（BL）以及英夫利昔单抗研究（第6、14、30周）和阿达木单抗研究（第6、12、26周）的整个治疗期1（TP1）的各时间点计算MBDA评分的平均值。对意向性治疗人群的数据使用描述性统计进行总结，不对缺失数据进行插补。
结果
在BL时，IFX-qbtx组（n = 236）和IFX-EU组（n = 248）的平均（±标准差）MBDA评分分别为61.3（±12.5）和58.8（±13.2），ADL-afzb组（n = 292）和ADL-EU组（n = 293）的平均MBDA评分分别为57.2（±14.44）和58.3（±15.34）。在每项研究的TP1期间的所有测量时间点，IFX-qbtx与IFX-EU之间以及ADL-afzb与ADL-EU之间的平均MBDA评分具有高度可比性。
结论
这些RCT首次将MBDA评分纳入生物类似药相似性的探索性评估。MBDA评分可通过对疾病活动度的评估提供生物类似性的客观、定量证据，该评估独立于关节计数或患者或医生整体评估中固有的潜在主观性。
试验注册号
NCT02222493和NCT02480153。
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