依库珠单抗可用于治疗水通道蛋白-4抗体阳性视神经脊髓炎谱系障碍，这一成果由美国梅奥诊所Sean J. Pittock研究小组取得，相关论文发表在2019年8月15日出版的《新英格兰医学杂志》上。

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，主要影响视神经和脊髓。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。在一项涉及AQP4-IgG阳性患者的小型开放标签研究中，研究者发现末端补体抑制剂依库珠单抗可降低NMOSD的复发率。

在这一项随机、双盲、时间-事件的试验中，143名成年NMOSD患者按2：1随机分配至依库珠单抗组（每周的第1天给药剂量为900毫克，4周后，每2周给药1200毫克）或安慰剂组。在治疗的同时可继续进行稳定剂量的免疫抑制治疗。观察两组患者的第一次复发时间、年复发率、生活质量指标，以及扩展残疾状况量表（EDSS）得分。

这些患者在入组前24个月的平均年复发率为1.99，76%的患者在试验期间继续进行之前的免疫抑制治疗。依库珠单抗组96例患者中有3例复发，复发率为3%，而安慰剂组47例患者中有20例复发，复发率为43%。依库珠单抗组的年复发率为0.02，安慰剂组为0.35。依库珠单抗组和安慰剂组EDSS评分的平均变化值分别为-0.18和0.12。依库珠单抗组中的患者更易发生上呼吸道感染和头痛，其中一例死于肺脓肿。

在AQP4-IgG阳性的NMOSD患者中，接受依库珠单抗治疗可有效降低复发风险，且相对安全，不加重残疾进展。

附：英文原文

Title: Eculizumab in Aquaporin-4–Positive Neuromyelitis Optica Spectrum Disorder

Author: Sean J. Pittock, M.D., Achim Berthele, M.D., Kazuo Fujihara, M.D., Ho Jin Kim, M.D., Ph.D., Michael Levy, M.D., Ph.D., Jacqueline Palace, D.M., Ichiro Nakashima, M.D., Murat Terzi, M.D., Natalia Totolyan, M.D., Shanthi Viswanathan, M.R.C.P., Kai-Chen Wang, M.D., Ph.D., Amy Pace, Sc.D., Kenji P. Fujita, M.D., Róisín Armstrong, Ph.D., and Dean M. Wingerchuk, M.D.

Issue&Volume: VOL. 381 NO. 7. 15 August 2019

Abstract: 

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<0.001). The adjudicated annualized relapse rate was 0.02 in the eculizumab group and 0.35 in the placebo group (rate ratio, 0.04; 95% CI, 0.01 to 0.15; P<0.001). The mean change in the EDSS score was –0.18 in the eculizumab group and 0.12 in the placebo group (least-squares mean difference, –0.29; 95% CI, –0.59 to 0.01). Upper respiratory tract infections and headaches were more common in the eculizumab group. There was one death from pulmonary empyema in the eculizumab group.

CONCLUSIONS
Among patients with AQP4-IgG–positive NMOSD, those who received eculizumab had a significantly lower risk of relapse than those who received placebo. There was no significant between-group difference in measures of disability progression.

DOI: 10.1056/NEJMoa1900866

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa1900866