Centre for Human Drug Research, Zernikedreef 8, 2333CL, Leiden, The Netherlands.
Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
Cardiovasc Drugs Ther. 2017 Aug;31(4):381-389. doi: 10.1007/s10557-017-6746-x.
Aim of this study was to demonstrate that MDCO-216 (human recombinant Apolipoprotein A-I Milano) does not induce adverse immunostimulation, in contrast to its predecessor, ETC-216, which was thought to contain host cell proteins (HCPs) that elicited an inflammatory reaction.
Data were taken from a clinical trial in which 24 healthy volunteers (HV) and 24 patients with proven stable coronary artery disease (sCAD) received a single intravenous dose of MDCO-216, ranging 5-40 mg/kg. Additionally, whole blood from 35 HV, 35 sCAD patients and 35 patients requiring acute coronary intervention (aCAD group) was stimulated ex vivo with MDCO-216 and ETC-216.
No inflammatory reaction was observed in HV and sCAD patients following MDCO-216 treatment, judging by body temperature, white cell counts, neutrophil counts, C-reactive protein, circulating cytokines (IL-6, TNF-α), and adverse events. In the ex vivo experiment, the geometric means (SD) of the ratio of MDCO-216 stimulated IL-6 over background levels were 0.8 (1.9), 0.7 (1.5), 1.0 (2.0) for respectively HV, sCAD, aCAD. The corresponding ETC-216 stimulated values were 15.8 (2.9), 9.5 (3.6), 3.8 (4.0). TNF-α results were comparable. Because many ETC-216 stimulated samples had cytokine concentrations >ULOQ, ratios were categorised and marginal homogeneity of the contingency table (MDCO-216 versus ETC-216) was assessed with the Stuart-Maxwell test. P-values were ≤0.0005 for all populations.
MDCO-216 did not induce adverse immunostimulation in HV and sCAD patients, in contrast to ETC-216. Results from the ex vivo stimulation suggests the same holds true for aCAD patients.
本研究旨在证明 MDCO-216（人重组载脂蛋白 A-I 米兰）不会引起不良的免疫刺激，与它的前体 ETC-216 相反，后者被认为含有引起炎症反应的宿主细胞蛋白（HCPs）。
数据来自一项临床试验，其中 24 名健康志愿者（HV）和 24 名确诊稳定型冠状动脉疾病（sCAD）患者接受了 5-40mg/kg 单剂量静脉注射 MDCO-216。此外，还从 35 名 HV、35 名 sCAD 患者和 35 名需要急性冠状动脉介入治疗（aCAD 组）的患者中提取全血，并用 MDCO-216 和 ETC-216 进行体外刺激。
HV 和 sCAD 患者在接受 MDCO-216 治疗后，通过体温、白细胞计数、中性粒细胞计数、C 反应蛋白、循环细胞因子（IL-6、TNF-α）和不良事件，没有观察到炎症反应。在体外实验中，MDCO-216 刺激的 IL-6 与背景水平的比值的几何平均值（SD）分别为 HV（0.8（1.9））、sCAD（0.7（1.5））、aCAD（1.0（2.0））。相应的 ETC-216 刺激值分别为 15.8（2.9）、9.5（3.6）、3.8（4.0）。TNF-α 的结果相当。由于许多 ETC-216 刺激的样本中细胞因子浓度>ULOQ，因此对比例进行了分类，并使用 Stuart-Maxwell 检验评估了列联表（MDCO-216 与 ETC-216）的边缘同质性。所有人群的 P 值均≤0.0005。
与 ETC-216 相比，MDCO-216 未在 HV 和 sCAD 患者中引起不良的免疫刺激。体外刺激的结果表明，对于 aCAD 患者也是如此。
