Eculizumab is a safe and effective treatment in pediatric patients with atypical hemolytic uremic syndrome
Eculizumab is a safe and effective treatment in pediatric patients with atypical hemolytic uremic syndrome
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DOI：
10.1016/j.kint.2015.11.026
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发表时间：
2016-03-01
影响因子：
19.6
通讯作者：
Licht, Christoph
中科院分区：
文献类型：
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作者：
Greenbaum, Larry A.;Fila, Marc;Licht, Christoph
非典型溶血性尿毒症综合征 (aHUS) 是由替代补体途径失调引起的，导致系统性血栓性微血管病 (TMA) 和严重的终末器官损伤。基于两项主要针对成人的前瞻性研究和针对儿童的回顾性数据，依库丽单抗（一种末端补体抑制剂）被批准用于 aHUS 治疗。在此，我们在一项开放标签 II 期研究中前瞻性评估了基于体重的依库丽单抗给药对符合条件的 aHUS 儿科患者的疗效和安全性。主要终点是 26 周时完成 TMA 缓解。 22 名患者（年龄 5 个月至 17 岁）接受了治疗； 16 人是新诊断的，12 人在当前 TMA 症状期间没有进行过血浆置换/输注，11 人接受了基线透析，2 人之前接受过肾移植。到第 26 周，14 名患者实现了完全 TMA 缓解，18 名患者实现了血液学正常化，16 名患者的血清肌酐改善了 25% 或更好。血浆置换/输注全部停止，基线时需要透析的 11 名患者中有 9 名停止，而没有人开始新的透析。依库珠单抗耐受性良好；没有发生死亡或脑膜炎球菌感染。骨髓衰竭、腕部骨折和急性呼吸衰竭被报告为不相关的严重不良事件。因此，我们的研究结果证实了依库丽单抗对 aHUS 儿科患者的有效性和安全性，并且与儿童诊断后立即开始依库丽单抗的建议一致。
Atypical hemolytic uremic syndrome (aHUS) is caused by alternative complement pathway dysregulation, leading to systemic thrombotic microangiopathy (TMA) and severe end-organ damage. Based on 2 prospective studies in mostly adults and retrospective data in children, eculizumab, a terminal complement inhibitor, is approved for aHUS treatment. Here we prospectively evaluated efficacy and safety of weight-based dosing of eculizumab in eligible pediatric patients with aHUS in an open-label phase II study. The primary end point was complete TMA response by 26 weeks. Twenty-two patients (aged 5 months-17 years) were treated; 16 were newly diagnosed, 12 had no prior plasma exchange/infusion during current TMA symptomatology, 11 received baseline dialysis, and 2 had prior renal transplants. By week 26, 14 achieved a complete TMA response, 18 achieved hematologic normalization, and 16 had 25% or better improvement in serum creatinine. Plasma exchange/infusion was discontinued in all, and 9 of the 11 patients who required dialysis at baseline discontinued, whereas none initiated new dialysis. Eculizumab was well tolerated; no deaths or meningococcal infections occurred. Bone marrow failure, wrist fracture, and acute respiratory failure were reported as unrelated severe adverse events. Thus, our findings establish the efficacy and safety of eculizumab for pediatric patients with aHUS and are consistent with proposed immediate eculizumab initiation following diagnosis in children.