瑞武利单抗治疗非典型溶血性尿毒症综合征：两项3期试验的2年疗效和安全性结果分析
Ravulizumab in Atypical Hemolytic Uremic Syndrome: An Analysis of 2-Year Efficacy and Safety Outcomes in 2 Phase 3 Trials.
作者信息
Dixon Bradley P, Kavanagh David, Aris Alvaro Domingo Madrid, Adams Brigitte, Kang Hee Gyung, Wang Edward, Garlo Katherine, Ogawa Masayo, Amancha Praveen, Chakravarty Sourish, Heyne Nils, Kim Seong Heon, Cataland Spero, Yoon Sung-Soo, Miyakawa Yoshitaka, Luque Yosu, Muff-Luett Melissa, Tanaka Kazuki, Greenbaum Larry A
机构信息
Renal Section, Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO.
National Renal Complement Therapeutics Centre, Newcastle upon Tyne Hospitals NHS Foundation Trust and Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom.
出版信息
Kidney Med. 2024 Jun 14;6(8):100855. doi: 10.1016/j.xkme.2024.100855. eCollection 2024 Aug.
RATIONALE & OBJECTIVE: Atypical hemolytic uremic syndrome (aHUS) is a rare form of thrombotic microangiopathy (TMA) caused by complement dysregulation. Ravulizumab is a C5i approved for the treatment of aHUS. This analysis assessed long-term outcomes of ravulizumab in adults and pediatric patients with aHUS.
STUDY DESIGN
This analysis reports 2-year data from 2 phase 3, single-arm studies.
SETTING & PARTICIPANTS: One study included C5i-naïve adults (NCT02949128), and the other included 2 cohorts of pediatric patients (C5i-naïve and those who switched to ravulizumab from eculizumab [pediatric switch patients]; NCT03131219).
EXPOSURE
Patients received intravenous ravulizumab every 4-8 weeks, with the dose depending on body weight.
OUTCOMES
The primary endpoint in the studies of C5i-naïve patients was complete TMA response, which consisted of platelet count normalization, lactate dehydrogenase normalization, and ≥25% improvement in serum creatinine concentrations from baseline, at 2 consecutive assessments ≥4 weeks apart.
ANALYTICAL APPROACH
All analyses used descriptive statistics. No formal statistical comparisons were performed.
RESULTS
In total, 86 and 92 patients were included in efficacy and safety analyses, respectively. Complete TMA response rates over 2 years were 61% and 90% in C5i-naïve adults and pediatric patients, respectively. The median increase in estimated glomerular filtration rate from baseline was maintained over 2 years in C5i-naïve adults (35 mL/min/1.73 m) and pediatric patients (82.5 mL/min/1.73 m). Most adverse events and serious adverse events occurred during the first 26 weeks. No meningococcal infections were reported. Improvement in the Functional Assessment of Chronic Illness Therapy - Fatigue score achieved by 26 weeks was maintained over 2 years.
LIMITATIONS
Limitations were the small sample of pediatric switch patients and limited availability of genetic data.
CONCLUSIONS
Long-term treatment with ravulizumab is well tolerated and associated with improved hematologic and renal parameters and quality of life in adults and pediatric patients with aHUS.
原理与目的
非典型溶血尿毒综合征（aHUS）是一种由补体调节异常引起的罕见血栓性微血管病（TMA）。ravulizumab是一种被批准用于治疗aHUS的C5i抑制剂。本分析评估了ravulizumab在成年和儿科aHUS患者中的长期疗效。
研究设计
本分析报告了来自两项3期单臂研究的2年数据。
研究背景与参与者
一项研究纳入了未使用过C5i抑制剂的成年患者（NCT02949128），另一项研究纳入了两组儿科患者（未使用过C5i抑制剂的患者以及从依库珠单抗转换为ravulizumab的患者[儿科转换患者]；NCT03131219）。
暴露
患者每4 - 8周静脉注射一次ravulizumab，剂量根据体重而定。
研究结果
研究中未使用过C5i抑制剂患者的主要终点是TMA完全缓解，定义为血小板计数恢复正常、乳酸脱氢酶恢复正常，且在连续两次间隔≥4周的评估中，血清肌酐浓度较基线改善≥25%。
分析方法
所有分析均采用描述性统计。未进行正式的统计比较。
结果
分别有86例和92例患者纳入疗效和安全性分析。在未使用过C5i抑制剂的成年和儿科患者中，2年期间TMA完全缓解率分别为61%和90%。在未使用过C5i抑制剂的成年患者（35 mL/min/1.7³m²）和儿科患者（82.5 mL/min/1.7³m²）中，估计肾小球滤过率较基线的中位数增加在2年期间得以维持。大多数不良事件和严重不良事件发生在最初26周内。未报告脑膜炎球菌感染。慢性疾病治疗功能评估 - 疲劳评分在26周时取得的改善在2年期间得以维持。
局限性
局限性在于儿科转换患者样本量小以及基因数据可用性有限。
结论
ravulizumab长期治疗耐受性良好，且与成年和儿科aHUS患者血液学和肾脏参数改善以及生活质量提高相关。
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