Ravulizumab is a new C5 inhibitor therapeutic monoclonal antibody with a longer half-life than eculizumab. Monitoring complete complement blockade by eculizumab has allowed personalized therapy in specific settings. Similar action is expected with ravulizumab. Ravulizumab has 4 different amino acids from eculizumab, which allow greater affinity for the FcRn immunoglobulin receptor and change the affinity of the molecule for C5. Here we investigate if clinical lab tests traditionally used to monitor complement blockade for eculizumab are appropriate for monitoring complement blockade caused by ravulizumab.

De-identified serum samples with known normal complement activity were spiked with increasing amounts of ravulizumab, from zero to 1000 μg/mL. Measurement of classical pathway function (CH50) and C5 function using a liposome method (Wako Diagnostics) showed >50% complement inhibition starting with 50 μg/mL of ravulizumab, but inhibition >95% of complement activity was not achieved, with residual measurements of 11% at 700 μg/mL. In contrast, measurement of alternative pathway function using an ELISA (AH50, Wieslab) showed alternative pathway function inhibition of 80% at 50 μg/mL of ravulizumab and > 95% at 200 μg/mL, which is consistent with expected therapeutic concentrations of ravulizumab >175 μg/mL. If replicated in patient sera, AH50 could be a suitable therapeutic monitoring tool.

Ravulizumab 是一种新型 C5 抑制剂治疗性单克隆抗体，其半衰期比依库珠单抗更长。通过依库珠单抗监测补体完全阻断允许在特定情况下进行个性化治疗。预计 ravulizumab 也会有类似的作用。Ravulizumab 有 4 个与依库丽单抗不同的氨基酸，这使得对 FcRn 免疫球蛋白受体的亲和力更大，并改变了分子对 C5 的亲和力。在这里，我们调查了传统上用于监测依库珠单抗补体阻断的临床实验室测试是否适用于监测由雷武珠单抗引起的补体阻断。

具有已知正常补体活性的去标识化血清样品中加入逐渐增加的 ravulizumab，从 0 到 1000 μg/mL。使用脂质体方法 (Wako Diagnostics) 测量经典途径功能 (CH50) 和 C5 功能显示，从 50 μg/mL ravulizumab 开始，补体抑制 > 50%，但未实现补体活性的 > 95% 抑制，残留测量结果为700 μg/mL 时为 11%。相比之下，使用 ELISA（AH50，Wieslab）测量旁路功能，显示 50 μg/mL 的 ravulizumab 抑制 80% 和 200 μg/mL 的旁路功能抑制 > 95%，这与预期的 ravulizumab 治疗浓度一致>175 微克/毫升。如果在患者血清中复制，AH50 可能是一种合适的治疗监测工具。