Safety and effectiveness of eculizumab for pediatric patients with atypical hemolytic-uremic syndrome in Japan: interim analysis of post-marketing surveillance.
Safety and effectiveness of eculizumab for pediatric patients with atypical hemolytic-uremic syndrome in Japan: interim analysis of post-marketing surveillance.
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DOI：
10.1007/s10157-018-1610-2
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发表时间：
2019-01
影响因子：
2.3
通讯作者：
Kagami S
中科院分区：
文献类型：
--
作者：
Ito S;Hidaka Y;Inoue N;Kaname S;Kato H;Matsumoto M;Miyakawa Y;Mizuno M;Okada H;Shimono A;Matsuda T;Maruyama S;Fujimura Y;Nangaku M;Kagami S
2013年，依库珠单抗在日本获批用于治疗非典型溶血性尿毒症综合征（aHUS），aHUS定义为血栓性微血管病（TMA），不包括产滋贺毒素大肠杆菌-HUS和血栓性血小板减少性紫癜。同时，开始上市后监测，以评估其安全性和有效性。2016年，日本临床指南重新定义了术语，将“阿胡斯”的使用仅限于补体介导的HUS。因此，其他原因引起的TMA被定义为继发性TMA。在这里，我们报告了对阿胡斯和继发性TMA的儿科患者进行上市后监测的中期分析。本观察性真实世界研究纳入了从获批至2017年3月15日接受依库珠单抗治疗的儿科患者。有效性的临床终点是TMA无事件状态、完全TMA应答、血小板计数正常化和估计肾小球滤过率（eGFR）的改善。还分析了依库珠单抗的不良反应。在27例阿胡斯儿科患者中，诊断时的中位年龄为4岁。21例患者中14例（66.7%）检测到补体基因变异。从诊断至开始依库珠单抗治疗的中位时间为2.0天。分别有85.2%、36.4%、78.3%和75.0%的患者达到无TMA事件状态、完全TMA应答、血小板正常化和eGFR改善。3例阿胡斯患者死亡。在31例阿胡斯患者和17例继发性TMA患者中分别报告了24例和10例不良反应;然而，未报告依库珠单抗相关死亡或脑膜炎球菌感染。这项中期分析证实，在真实世界环境中，依库珠单抗对日本阿胡斯儿科患者耐受良好且有效。本文的在线版本（10.1007/s10157-018-1610-2）包含补充材料，可供授权用户使用。
In 2013, eculizumab was approved for treatment of the atypical hemolytic–uremic syndrome (aHUS) in Japan, which was defined as a thrombotic microangiopathy (TMA) excluding Shiga toxin-producing Escherichia coli-HUS and thrombotic thrombocytopenic purpura. Simultaneously, post-marketing surveillance was started to assess its safety and effectiveness. In 2016, Japanese clinical guide redefined terms to limit the use of “aHUS” to complement-mediated HUS only. Accordingly, TMA with other causes was defined as secondary TMA. Here we report the interim analysis of post-marketing surveillance of pediatric patients with aHUS and secondary TMA. Pediatric patients treated with eculizumab from approval to 15 March 2017 were included in this observational real-world study. Clinical endpoints of effectiveness were TMA event–free status, complete TMA response, platelet count normalization, and improvement of estimated glomerular filtration rate (eGFR). Adverse reactions to eculizumab were also analyzed. In 27 pediatric patients with aHUS, median age at diagnosis was 4 years. Complement genes’ variants were detected in 14 of 21 patients (66.7%). Median time from diagnosis to eculizumab initiation was 2.0 days. TMA event–free status, complete TMA response, platelet normalization, and improvement in eGFR were achieved in 85.2, 36.4, 78.3, and 75.0% of patients, respectively. Three patients with aHUS died. Twenty-four and 10 adverse reactions were reported in 31 aHUS patients and 17 secondary TMA patients, respectively; however, no eculizumab-related death or meningococcal infection was reported. This interim analysis confirmed that eculizumab is well-tolerated and effective for Japanese pediatric patients with aHUS in a real-world setting. The online version of this article (10.1007/s10157-018-1610-2) contains supplementary material, which is available to authorized users.
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