Abstract:
Atypical hemolytic uremic syndrome (aHUS) is a type of thrombotic microangiopathy and is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney failure. The complement cascade plays an integral role in aHUS. Mutations in the complement cascade, especially in the alternative pathway (AP) lead to an unregulated and continuous activation of the cascade. Eculizumab and ravulizumab are humanized monoclonal antibodies that inhibit the complement cascade. This systematic analysis reviews the evidence for both antibodies to compare them in terms of safety and efficacy. This review will also assess the evidence for biomarker associations with interventions, the role of genetic mutations in the prognosis of disease, and the financial burden of both treatment options. An in-depth search was conducted across PubMed, Science Direct, and Cochrane Library following the PRISMA 2020 guidelines. Both eculizumab and ravulizumab were comparable in safety and efficacy but ravulizumab was preferred by patients and their caregivers as it posed a lower financial burden and had less frequent dosing. Soluble complement 5b-9 (sC5b), especially in urine, has the potential to be used as a biomarker to assess response to treatment. Genetic mutations, especially mutations in complement factor I (CFI), membrane cofactor protein (MCP), and complement factor H (CFH), were associated with a higher risk of recurrence, and therefore care should be taken when attempting to discontinue treatment in this subset of patients. Treatment with a monoclonal antibody should be initiated as soon as a genetic mutation is identified. Blinded, double-arm, clinical trials preferably with larger sample sizes are needed to effectively compare both the monoclonal antibodies.
摘要:
非典型溶血性尿毒综合征(aHUS)是一种血栓性微血管病,以微血管病性溶血性贫血为特征,血小板减少症,和急性肾衰竭.补体级联在aHUS中起着不可或缺的作用。补体级联突变,特别是在替代途径(AP)导致级联的不调节和连续激活。Eculizumab和ravulizumab是抑制补体级联的人源化单克隆抗体。这项系统分析回顾了两种抗体的证据,以比较它们的安全性和有效性。这篇综述还将评估生物标志物与干预措施相关的证据,基因突变在疾病预后中的作用,以及两种治疗方案的经济负担。在PubMed进行了深入搜索,科学直接,和科克伦图书馆遵循PRISMA2020指南。eculizumab和ravulizumab在安全性和有效性方面具有可比性,但ravulizumab是患者及其护理人员的首选,因为它造成较低的经济负担并且给药频率较低。可溶性补体5b-9(sC5b),尤其是在尿液中,有可能用作生物标志物来评估对治疗的反应。基因突变,尤其是补体因子I(CFI)的突变,膜辅因子蛋白(MCP),和补体因子H(CFH),与较高的复发风险相关,因此,在尝试停止这一部分患者的治疗时,应谨慎行事.一旦发现基因突变,就应开始使用单克隆抗体进行治疗。失明,双臂,为了有效地比较两种单克隆抗体,需要进行临床试验,优选使用更大的样本量.