Institute of Haematology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia; Anzac Research Institute, University of Sydney, Concord, NSW, Australia.
Institute of Haematology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia.
Pathology. 2022 Oct;54(6):755-762. doi: 10.1016/j.pathol.2022.02.006. Epub 2022 May 14.
Emicizumab is a recombinant, humanised bispecific antibody which acts as a FVIII mimetic and is a therapeutic option for haemophilia A. Plasma emicizumab levels may sometimes be required. Multiple one-stage clotting assays (OSA) and one human component chromogenic assay (CSA) were used to measure emicizumab both centrally and by a field study. The study samples drug concentrations range included within therapy range of 35-70 μg/mL. All assays were modified from traditional FVIII assays to enable replacement of plasma calibrators with emicizumab calibrators. Central laboratory OSA mean recovery levels (target) for six spike levels of emicizumab were close to target at 120.5 (120), 81.6 (80), 40.9 (40), 21.4 (20), 10.7 (10) and 5.5 (5) μg/mL. Field study OSA mean recoveries were similarly close to target. Between method coefficients of variation were <9% in both the central laboratory and field study assays, except for the 5 μg/mL sample which was 12.3%. CSA mean recoveries were within 10% of target at 80, 50 and 20 μg/mL levels. This study affirms that emicizumab can be measured by OSA using many types of activated partial thromboplastin time (APTT) reagents and is also measurable by the human CSA. The assays showed good precision, accuracy and linearity both locally and in a field study setting.
依库珠单抗是一种重组的、人源化的双特异性抗体，作为一种 FVIII 模拟物，是治疗 A 型血友病的一种选择。有时可能需要检测血浆依库珠单抗水平。使用多种一步法凝血检测法（OSA）和一种人源成分显色检测法（CSA），在中心实验室和现场研究中测量依库珠单抗。研究样本药物浓度范围包括治疗范围内的 35-70μg/mL。所有检测法均从传统的 FVIII 检测法进行修改，以允许用依库珠单抗校准品替代血浆校准品。中心实验室 OSA 对于六个依库珠单抗加标水平的平均回收率（目标）接近 120.5（120）、81.6（80）、40.9（40）、21.4（20）、10.7（10）和 5.5（5）μg/mL。现场研究 OSA 的平均回收率也接近目标。在中心实验室和现场研究检测法中，除了 5μg/mL 样本的变异系数为 12.3%外，其他方法的变异系数均<9%。CSA 对于 80、50 和 20μg/mL 水平的平均回收率接近目标值的 10%。本研究证实，OSA 可以使用多种类型的活化部分凝血活酶时间（APTT）试剂测量依库珠单抗，并且还可以用人 CSA 进行测量。这些检测法在本地和现场研究环境中均显示出良好的精密度、准确性和线性度。
