Lax Naama, Davidovits Miriam, Chodick Gabriel, Bernfeld Yael, Peled Orit
Department of Pharmacy, Schneider Children's Medical Center of Israel, Petah Tikva, Israel.
Institute of Nephrology, Schneider Children's Medical Center of Israel, Petah Tikva, Israel.
Front Pharmacol. 2025 Apr 4;16:1535407. doi: 10.3389/fphar.2025.1535407. eCollection 2025.
Eculizumab, a terminal complement inhibitor, prevents thrombotic microangiopathy (TMA) and multiorgan damage in hemolytic uremic syndrome (HUS). We evaluated its efficacy and safety in pediatric patients with TMA sub-types: atypical HUS (aHUS), Shiga toxin-producing (STEC)-HUS, and transplant-associated TMA (TA-TMA).
This retrospective study included all pediatric patients treated with eculizumab for HUS at Schneider Children's Medical Center (2011-2020), including those with pre-existing end-stage kidney disease. Clinical and laboratory parameters were analyzed over 28 weeks. The primary endpoint was achievement of complete TMA response, defined by sustained normalization of hematologic parameters and renal function. Secondary endpoints included TMA event-free status and additional clinical improvements.
Twenty-four pediatric patients (median age 5.8 years) were included: 13 with aHUS, 5 with STEC-HUS, and 6 with TA-TMA. A complete TMA response was achieved in 12 (50%) of the patients overall: 7 (54%) with aHUS, 3 (60%) with STEC-HUS, and 2 (33%) with TA-TMA. TMA event-free status was reached in 15 (63%) patients. Significant improvements were observed in platelet count (63%), lactate dehydrogenase levels (76% within the first week), hemoglobin (60%), and estimated glomerular filtration rate (79%); while CH-50 levels decreased. No severe adverse events were attributed to eculizumab. Chronic kidney disease stage improved for 17 (90%).
The efficacy and safety of eculizumab for three TMA subtypes in pediatric patients potentially expands its therapeutic applications. The complete TMA response rate in aHUS supports eculizumab as a first-line use, while the response rate in STEC-HUS suggests potential efficacy beyond eculizumab's primary indication. The early hematologic responses and reduced CH-50 levels confirm the role of eculizumab complement-mediated HUS and underscore the need for further research in TA-TMA.
依库珠单抗是一种终末补体抑制剂，可预防溶血性尿毒症综合征（HUS）中的血栓性微血管病（TMA）和多器官损伤。我们评估了其在患有TMA亚型的儿科患者中的疗效和安全性，这些亚型包括非典型HUS（aHUS）、产志贺毒素（STEC）-HUS和移植相关TMA（TA-TMA）。
这项回顾性研究纳入了施耐德儿童医学中心（2011 - 2020年）所有接受依库珠单抗治疗HUS的儿科患者，包括那些已患有终末期肾病的患者。对临床和实验室参数进行了28周的分析。主要终点是实现完全TMA缓解，定义为血液学参数和肾功能持续正常化。次要终点包括无TMA事件状态和其他临床改善情况。
纳入了24名儿科患者（中位年龄5.8岁）：13例aHUS、5例STEC-HUS和6例TA-TMA。总体上12名（50%）患者实现了完全TMA缓解：aHUS患者中有7名（54%），STEC-HUS患者中有3名（60%），TA-TMA患者中有2名（33%）。15名（63%）患者达到无TMA事件状态。血小板计数（63%）、乳酸脱氢酶水平（第一周内76%）、血红蛋白（60%）和估计肾小球滤过率（79%）有显著改善；而CH-50水平下降。没有严重不良事件归因于依库珠单抗。17名（90%）患者的慢性肾脏病分期得到改善。
依库珠单抗在儿科患者中对三种TMA亚型的疗效和安全性可能会扩大其治疗应用范围。aHUS中的完全TMA缓解率支持依库珠单抗作为一线用药，而STEC-HUS中的缓解率表明其疗效可能超出依库珠单抗的主要适应症。早期血液学反应和CH-50水平降低证实了依库珠单抗在补体介导的HUS中的作用，并强调了对TA-TMA进行进一步研究的必要性。
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