Schaefer Franz, Al-Dakkak Imad, Anokhina Katerina, Cohen David, Greenbaum Larry A, Ariceta Gema
Division of Pediatric Nephrology, Heidelberg University Hospital, Heidelberg, Germany.
Epidemiology, Alexion, AstraZeneca Rare Disease, Boston, Massachusetts, USA.
Kidney Int Rep. 2024 Jun 20;9(9):2648-2656. doi: 10.1016/j.ekir.2024.06.020. eCollection 2024 Sep.
Atypical hemolytic uremic syndrome (aHUS) is a progressive rare disease that, if untreated, can result in severe organ damage and death. Ravulizumab, a next-generation terminal complement inhibitor, provides immediate, complete, and sustained complement C5 inhibition. Real-world data in patients with aHUS who switched to ravulizumab from eculizumab are lacking.
The Global aHUS Registry is a multicenter study (NCT01522183) collecting data on adult or pediatric patients with an aHUS diagnosis, regardless of treatment. Patient characteristics, genetic data, hematological and renal parameters, clinical events (e.g., dialysis and kidney transplantation), and adverse events (AEs) were extracted from patients who switched to ravulizumab from eculizumab up to July 3, 2023.
Overall, 60 patients switched to ravulizumab (adult: = 43; pediatric: = 17); 11 patients were excluded from effectiveness and genetic analyses ( = 49; adult: = 40; pediatric: = 9) because they received <3 months ravulizumab treatment and/or had >1 month between eculizumab discontinuation and ravulizumab initiation. Pathogenic complement variants were identified in 11 of 49 patients (22%); the most common was a complement factor H variant ( = 5/49 [10%]). During ravulizumab treatment, 20 AEs occurred in 13 patients, with no unexpected AEs and only 3 treatment-related AEs (infusion reaction, headaches, and fatigue). No meningococcal infections or deaths were reported. No new events of dialysis, kidney transplantation, or thrombotic microangiopathy were reported. Renal and hematological parameters remained stable after switching to ravulizumab.
This is the first real-world cohort analysis of data from patients treated with ravulizumab and reinforces the real-world safety and effectiveness data of ravulizumab in patients with aHUS who switched from eculizumab.
非典型溶血性尿毒症综合征（aHUS）是一种进行性罕见疾病，若不治疗，可导致严重器官损害甚至死亡。ravulizumab是一种新一代末端补体抑制剂，可立即、完全且持续地抑制补体C5。目前缺乏从依库珠单抗转换为ravulizumab治疗的aHUS患者的真实世界数据。
全球aHUS注册研究是一项多中心研究（NCT01522183），收集确诊为aHUS的成人或儿童患者的数据，无论其接受何种治疗。从截至2023年7月3日从依库珠单抗转换为ravulizumab治疗的患者中提取患者特征、基因数据、血液学和肾脏参数、临床事件（如透析和肾移植）以及不良事件（AE）。
总体而言，60例患者转换为ravulizumab治疗（成人：n = 43；儿童：n = 17）；11例患者被排除在疗效和基因分析之外（n = 49；成人：n = 40；儿童：n = 9），因为他们接受ravulizumab治疗<3个月和/或在依库珠单抗停药和ravulizumab开始治疗之间间隔>1个月。49例患者中有11例（22%）鉴定出致病性补体变异；最常见的是补体因子H变异（n = 5/49 [10%]）。在ravulizumab治疗期间，13例患者发生20次AE，无意外AE，仅3次与治疗相关的AE（输液反应、头痛和疲劳）。未报告脑膜炎球菌感染或死亡。未报告透析、肾移植或血栓性微血管病的新事件。转换为ravulizumab治疗后，肾脏和血液学参数保持稳定。
这是首次对接受ravulizumab治疗患者的数据进行的真实世界队列分析，并强化了ravulizumab在从依库珠单抗转换而来的aHUS患者中的真实世界安全性和有效性数据。
