Eculizumab in Aquaporin-4-Positive Neuromyelitis Optica Spectrum Disorder
Eculizumab in Aquaporin-4-Positive Neuromyelitis Optica Spectrum Disorder
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DOI：
10.1056/nejmoa1900866
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发表时间：
2019-08-15
影响因子：
158.5
通讯作者：
Wingerchuk, D. M.
中科院分区：
文献类型：
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作者：
Pittock, S. J.;Berthele, A.;Wingerchuk, D. M.
视神经脊髓炎是一种复发性中枢神经系统炎症性疾病。三分之二的患者有抗水通道蛋白-4的抗体，中枢神经系统损伤是补体依赖性的。终端补体C5切割抑制剂eculizumab可减少NMOSD的复发。视神经脊髓炎谱系障碍（NMOSD）是一种复发性自身免疫性炎症性疾病，通常影响视神经和脊髓。至少三分之二的病例与水通道蛋白-4抗体（AQP4-IgG）和补体介导的中枢神经系统损伤有关。在先前一项涉及aqp4 - igg阳性疾病患者的小型开放标签研究中，eculizumab（一种终末补体抑制剂）被证明可以降低复发频率。在这项随机、双盲、时间-事件试验中，143名成年人以2:1的比例随机分配，接受静脉注射eculizumab（从第1天开始，前4次剂量为每周900毫克，从第4周开始，每2周1200毫克）或匹配的安慰剂。允许继续使用稳定剂量的免疫抑制治疗。主要终点是首次确诊复发。次要结果包括确定的年复发率、生活质量测量和扩展残疾状态量表（EDSS）得分，其范围从0（无残疾）到10（死亡）。结果在24例预先确定的复发中，有23例因无法估计最终事件何时发生而停止试验。入组前24个月的平均（+/- SD）年复发率为1.99 +/- 0.94；76%的患者在试验期间继续接受先前的免疫抑制治疗。eculizumab组96例患者中有3例（3%）确诊复发，安慰剂组47例患者中有20例（43%）确诊复发(风险比0.06；95%可信区间[CI]， 0.02 ~ 0.20
Neuromyelitis optica spectrum disorder is a relapsing inflammatory disorder of the central nervous system. Two thirds of patients have antibodies against aquaporin-4, and CNS damage is complement dependent. The inhibitor of terminal complement C5 cleavage, eculizumab, reduced relapses of NMOSD.Background Neuromyelitis optica spectrum disorder (NMOSD) is a relapsing, autoimmune, inflammatory disorder that typically affects the optic nerves and spinal cord. At least two thirds of cases are associated with aquaporin-4 antibodies (AQP4-IgG) and complement-mediated damage to the central nervous system. In a previous small, open-label study involving patients with AQP4-IgG-positive disease, eculizumab, a terminal complement inhibitor, was shown to reduce the frequency of relapse. Methods In this randomized, double-blind, time-to-event trial, 143 adults were randomly assigned in a 2:1 ratio to receive either intravenous eculizumab (at a dose of 900 mg weekly for the first four doses starting on day 1, followed by 1200 mg every 2 weeks starting at week 4) or matched placebo. The continued use of stable-dose immunosuppressive therapy was permitted. The primary end point was the first adjudicated relapse. Secondary outcomes included the adjudicated annualized relapse rate, quality-of-life measures, and the score on the Expanded Disability Status Scale (EDSS), which ranges from 0 (no disability) to 10 (death). Results The trial was stopped after 23 of the 24 prespecified adjudicated relapses, given the uncertainty in estimating when the final event would occur. The mean (+/- SD) annualized relapse rate in the 24 months before enrollment was 1.99 +/- 0.94; 76% of the patients continued to receive their previous immunosuppressive therapy during the trial. Adjudicated relapses occurred in 3 of 96 patients (3%) in the eculizumab group and 20 of 47 (43%) in the placebo group (hazard ratio, 0.06; 95% confidence interval [CI], 0.02 to 0.20; P