Laboratoire d'Immunologie et d'Immunomonitoring, CHU Saint-Etienne, Saint-Etienne.
Unité de Mathématiques, Université de Lyon, Lyon, France.
Ther Drug Monit. 2019 Aug;41(4):459-466. doi: 10.1097/FTD.0000000000000629.
Golimumab is a monoclonal anti-tumor necrosis factor alpha antibody, which is used in ulcerative colitis with an exposure-response relationship. The goal of this study was to compare results obtained with different immunoassays (golimumab and antigolimumab antibodies trough levels).
This study was based on samples from 78 ulcerative colitis patients on golimumab treatment. Golimumab was quantified by either an anti-IgG detection antibody (Theradiag, Marne la Vallée, France) or an antibody directed against golimumab (Sanquin, Amsterdam, The Netherlands, KU Leuven, Leuven, Belgium, and Janssen R&D, San Diego, CA). Bridging drug-sensitive enzyme-linked immunosorbent assays (Theradiag, Janssen R&D, and KU Leuven), a bridging drug-tolerant enzyme-linked immunosorbent assay (Janssen R&D), and a radioimmunoassay (Sanquin) were used to quantify antidrug antibody.
Median serum golimumab levels were 4.5, 3.5, 4.9, and 2.4 mcg/mL with Theradiag, Sanquin, KU Leuven, and Janssen R&D assay, respectively (P < 0.05). Correlation coefficients between assays ranged from 0.9 to 0.97. When using the KU Leuven and Janssen R&D assays, 86% of samples were in the same quartile of distribution of values, and for Sanquin and Janssen R&D assays, this overlap was 80%. The concordance observed for the other pairs was 83% (Sanquin/KU Leuven R&D), 71% (Theradiag/KU Leuven), and 68% (Theradiag/Janssen R&D and Theradiag/Sanquin). The specificity of assays for golimumab was demonstrated. Antidrug antibodies were detected in 28.2% of the samples with the Janssen R&D drug-tolerant assay and in the same 2 patients by the 3 other assays.
Performances of these immunoassays were similar in terms of quality, but differences in the quantitative results point to the importance of using the same assay consistently to monitor a patient's treatment.
戈利木单抗是一种抗肿瘤坏死因子-α的单克隆抗体，已被应用于溃疡性结肠炎的治疗，并呈现出剂量反应关系。本研究的目的是比较不同免疫分析法（戈利木单抗及抗戈利木单抗抗体的药物浓度）的结果。
本研究基于 78 例接受戈利木单抗治疗的溃疡性结肠炎患者的样本。采用抗 IgG 检测抗体（Theradiag，法国马恩河谷；Sanquin，荷兰阿姆斯特丹；KU Leuven，比利时鲁汶；Janssen R&D，美国圣地亚哥）或针对戈利木单抗的抗体（Sanquin，KU Leuven，Janssen R&D）对戈利木单抗进行定量。采用桥接药物敏感酶联免疫吸附试验（Theradiag、Janssen R&D 和 KU Leuven）、桥接药物耐受酶联免疫吸附试验（Janssen R&D）和放射免疫分析（Sanquin）来定量检测抗药物抗体。
Theradiag、Sanquin、KU Leuven 和 Janssen R&D 检测法的血清戈利木单抗中位水平分别为 4.5、3.5、4.9 和 2.4 mcg/mL（P<0.05）。检测方法间的相关系数范围为 0.9 至 0.97。当使用 KU Leuven 和 Janssen R&D 检测法时，86%的样本在值分布的相同四分位数中，而 Sanquin 和 Janssen R&D 检测法的重叠率为 80%。其余对的一致性观察结果为 83%（Sanquin/KU Leuven R&D）、71%（Theradiag/KU Leuven）和 68%（Theradiag/Janssen R&D 和 Theradiag/Sanquin）。检测法对戈利木单抗的特异性得到了证明。在 28.2%的样本中，Janssen R&D 药物耐受检测法检测到了抗药物抗体，而在其余 3 种检测法中仅在 2 例患者中检测到了抗药物抗体。
这些免疫分析法在质量方面表现相似，但定量结果的差异表明，为了监测患者的治疗情况，应始终使用相同的检测法。
