Mayo Clinic, 200 1st St SW, Rochester, MN, United States of America.
Thermo Fisher Scientific, Uppsala, Sweden.
AAPS J. 2024 Jul 24;26(5):86. doi: 10.1208/s12248-024-00953-3.
Monitoring anti-drug antibodies (ADAs) to infliximab and adalimumab is critical to treatment management in various autoimmune disorders. The growing need for proactive therapeutic monitoring further requires the detection of ADAs in the presence of measurable concentrations of infliximab or adalimumab. To provide robust analytical assays for clinical application, we evaluated two automated immunoassays developed using ImmunoCAP™ technology and based on the bridging format to measure serum ADAs to infliximab and adalimumab respectively. Without an acid-dissociation step, these research prototype assays can detect a positive control monoclonal ADA towards infliximab and adalimumab, ranging from < 25 ng/ml to 10,000 ng/mL. Both assays exhibit imprecision less than 20% at different ADA titer levels and can distinguish ADAs towards different drug targets. In method comparison using authentic patient samples, the quantitative results of the ADA assays are not directly comparable to two existing clinical immunoassays for ADAs (correlation coefficient r = 0.673 for infliximab ADAs; r = 0.510 for adalimumab ADAs), presumably due to the lack of commutable ADA standards and the polyclonal nature of ADAs. Nevertheless, there is qualitative agreement between the methods when evaluating putative positive and negative patient samples (overall agreement 0.83 for infliximab ADAs; 0.76 for adalimumab ADAs). Biotin and high levels of rheumatoid factors may interfere with the performance of the automated assays due to competitive binding with the biotinylated drug and non-specific formation of bridging complexes. The two ImmunoCAP assays can provide new analytical methods for proactive therapeutic monitoring of adalimumab and infliximab.
监测英夫利昔单抗和阿达木单抗的抗药物抗体（ADA）对于各种自身免疫性疾病的治疗管理至关重要。主动治疗监测的需求不断增长，这进一步要求在存在可测量浓度的英夫利昔单抗或阿达木单抗的情况下检测 ADA。为了为临床应用提供强大的分析检测方法，我们评估了两种使用 ImmunoCAP™技术开发的自动化免疫测定法，这些方法基于桥接格式分别用于测量血清中的 ADA 对英夫利昔单抗和阿达木单抗。由于没有酸解离步骤，这些研究原型测定法可以检测针对英夫利昔单抗和阿达木单抗的阳性对照单克隆 ADA，范围从<25ng/ml 到 10,000ng/ml。两种测定法在不同 ADA 滴度水平下的不精密度均小于 20%，并且可以区分针对不同药物靶标的 ADA。在使用真实患者样本的方法比较中，ADA 测定法的定量结果与两种现有的 ADA 临床免疫测定法（英夫利昔单抗 ADA 的相关系数 r=0.673；阿达木单抗 ADA 的 r=0.510）不可直接比较，可能是由于缺乏可互换的 ADA 标准和 ADA 的多克隆性质。然而，在评估假定的阳性和阴性患者样本时，方法之间存在定性一致（英夫利昔单抗 ADA 的总一致性为 0.83；阿达木单抗 ADA 的总一致性为 0.76）。生物素和高水平的类风湿因子可能会由于与生物素化药物的竞争结合和桥接复合物的非特异性形成而干扰自动测定法的性能。这两种 ImmunoCAP 测定法可以为英夫利昔单抗和阿达木单抗的主动治疗监测提供新的分析方法。
