Department of Medicine, University of California San Diego, School of Medicine, San Diego, California.
Takeda, Cambridge, Massachusetts.
Ther Drug Monit. 2023 Apr 1;45(2):236-244. doi: 10.1097/FTD.0000000000001068. Epub 2023 Feb 15.
Vedolizumab (VDZ) is an anti-α 4 β 7 integrin monoclonal antibody approved for inflammatory bowel disease treatment. VDZ serum and antidrug antibody (ADA) concentrations may be used for treatment optimization. In this article, the results of 5 commercial assays (Grifols, Immundiagnostik, Progenika, Sanquin, and Theradiag) measuring VDZ concentration and ADA were compared with those of the reference assays used in VDZ clinical studies. Our findings will assist clinicians in interpreting commercial assay results in the context of VDZ clinical trial data.
VDZ-treated patient samples were used to evaluate the agreement between commercial assays and the reference VDZ serum concentration assay, based on linear regression, Bland-Altman, and qualitative agreement analyses. VDZ ADAs were detected using qualitative assays. Specificity, selectivity, accuracy, and precision were assessed using serum samples from healthy donors or patients with IBD (VDZ serum concentration <0.5 mcg/mL) spiked with VDZ, with/without other biologics (identical sample sets per assay).
All assays were specific and selective for VDZ. Overall, the commercial assay results for VDZ-spiked samples correlated well with those of the reference serum concentration assay (R 2 ≥ 0.98). Compared with the Immundiagnostik and Theradiag assays, the Grifols, Sanquin, and Progenika assays had the best reference assay agreement (based on regression analysis, Bland-Altman plots, and qualitative agreement [Cohen's kappa ≥0.92]). All immunogenicity assays detected VDZ ADAs; only the reference assay detected VDZ ADAs in the presence of 15 mcg/mL VDZ, advising caution with commercial ADA assays if VDZ is present.
All 5 commercial assays are suitable for VDZ therapeutic monitoring and ADA testing. However, the absolute values from the reference assays and the different commercial assays were not comparable, indicating that the same assay must be used for repeated monitoring of VDZ serum concentrations.
维得利珠单抗（VDZ）是一种抗 α4β7 整合素单克隆抗体，已被批准用于治疗炎症性肠病。VDZ 血清浓度和抗药物抗体（ADA）浓度可用于优化治疗。在本文中，我们比较了 5 种商业检测方法（Grifols、Immundiagnostik、Progenika、Sanquin 和 Theradiag）与 VDZ 临床试验中使用的参考检测方法测量 VDZ 浓度和 ADA 的结果。我们的研究结果将有助于临床医生在 VDZ 临床试验数据的背景下解读商业检测结果。
使用 VDZ 治疗的患者样本，通过线性回归、Bland-Altman 和定性一致性分析，评估商业检测方法与参考 VDZ 血清浓度检测方法之间的一致性。使用定性检测方法检测 VDZ ADA。使用来自健康供体或 VDZ 血清浓度<0.5 mcg/mL 的 IBD 患者的血清样本（每个检测方法的相同样本集）评估特异性、选择性、准确性和精密度，VDZ 中添加/不添加其他生物制剂。
所有检测方法均对 VDZ 具有特异性和选择性。总体而言，商业检测方法对添加 VDZ 的样本的检测结果与参考血清浓度检测方法的相关性良好（R2≥0.98）。与 Immundiagnostik 和 Theradiag 检测方法相比，Grifols、Sanquin 和 Progenika 检测方法与参考检测方法的一致性最好（基于回归分析、Bland-Altman 图和定性一致性[Cohen's kappa≥0.92]）。所有免疫原性检测方法均检测到 VDZ ADA；只有参考检测方法在存在 15 mcg/mL VDZ 的情况下检测到 VDZ ADA，因此如果存在 VDZ，商业 ADA 检测方法需谨慎使用。
所有 5 种商业检测方法均适用于 VDZ 的治疗监测和 ADA 检测。然而，参考检测方法和不同商业检测方法的绝对数值无法进行比较，这表明在重复监测 VDZ 血清浓度时必须使用相同的检测方法。
