Case Report: Variable Pharmacokinetic Profile of Eculizumab in an aHUS Patient.
Case Report: Variable Pharmacokinetic Profile of Eculizumab in an aHUS Patient.
复制标题
DOI：
10.3389/fimmu.2020.612706
复制
发表时间：
2020
影响因子：
7.3
通讯作者：
van de Kar NCAJ
中科院分区：
文献类型：
--
作者：
Bouwmeester RN;Ter Avest M;Wijnsma KL;Duineveld C;Ter Heine R;Volokhina EB;Van Den Heuvel LPWJ;Wetzels JFM;van de Kar NCAJ
随着C5抑制剂艾库组单抗的引入，非典型溶血性尿毒综合征（阿胡斯）患者的发病率和死亡率显著改善。鉴于高成本、药物的实际需求以及文献中越来越多的证据，阿胡斯患者可以根据限制性依库珠单抗方案进行治疗。我们回顾性分析了依库珠单抗在1例患者中的药代动力学和动力学参数，强调了在逐渐减量治疗过程中可以考虑的各种因素。一名18岁的男性，由于杂合CFH/CFHR 1基因与纯合因子H单倍型的组合，患有严重的、经常复发的非典型HUS形式，需要长期血浆治疗（PT），包括血浆输注期，从5个月大的发病年龄开始，直到11岁时开始使用依库珠单抗。轻度但稳定的慢性肾脏疾病（CKD）和9年的疾病缓解使依库珠单抗间隔延长。在15岁时，观察到慢性肾脏疾病（CKD）的突然但多因素进展，没有任何疾病复发的迹象。然而，获得性肾小球疾病，左肾功能下降，腹部静脉系统异常的病因不明。此外，在阿胡斯复发后，患者体内依库珠单抗浓度的变异性意外增加。回顾性药代动力学分析显示依库珠单抗清除率的变化，与蛋白尿的同时增加相关。随着时间的推移，观察到艾库珠单抗药代动力学的患者内变异性很高，这强调了对阿胡斯患者进行充分且连续的治疗药物监测的必要性。应经常评估依库珠单抗血清谷浓度和补体激活标志物（CH 50），尤其是在药物治疗逐渐减量和/或患者临床状况变化期间。此外，蛋白尿增加可能导致尿依库珠单抗损失，表明依库珠单抗的尿液监测在血清浓度不明原因下降的阿胡斯患者中可能很重要。
With the introduction of eculizumab, a C5-inhibitor, morbidity and mortality improved significantly for patients with atypical hemolytic uremic syndrome (aHUS). In view of the high costs, actual needs of the drug, and increasing evidence in literature, aHUS patients can be treated according to a restrictive eculizumab regimen. We retrospectively analyzed the pharmacokinetic and dynamic parameters of eculizumab in one patient in time, emphasizing various factors which could be taken into account during tapering of treatment. A nowadays 18-year-old male with a severe, frequently relapsing form of atypical HUS due to a hybrid CFH/CFHR1 gene in combination with the homozygous factor H haplotype, required chronic plasma therapy (PT), including periods with plasma infusion, from the age of onset at 5 months until initiation of eculizumab at the age of 11 years. A mild but stable chronic kidney disease (CKD) and 9 years of disease remission enabled prolongation of eculizumab interval. At the age of 15 years, a sudden yet multifactorial progression of chronic kidney disease (CKD) was observed, without any signs of disease recurrence. However, an acquired glomerulocystic disease, a reduced left kidney function, and abnormal abdominal venous system of unknown etiology were found. In addition, after an aHUS relapse, an unexpected increase in intra-patient variability of eculizumab concentrations was seen. Retrospective pharmacokinetic analysis revealed a change in eculizumab clearance, associated with a simultaneous increase in proteinuria. High intra-patient variability of eculizumab pharmacokinetics were observed over time, emphasizing the necessity for adequate and continuous therapeutic drug monitoring in aHUS patients. Eculizumab serum trough levels together with complement activation markers (CH50) should be frequently assessed, especially during tapering of drug therapy and/or changing clinical conditions in the patient. In addition, an increase in proteinuria could result in urinary eculizumab loss, indicating that urinary monitoring of eculizumab may be important in aHUS patients with an unexplained decline in serum concentrations.