Trial of Satralizumab in Neuromyelitis Optica Spectrum Disorder
Trial of Satralizumab in Neuromyelitis Optica Spectrum Disorder
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DOI：
10.1056/nejmoa1901747
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发表时间：
2019-11-28
影响因子：
158.5
通讯作者：
De Seze, Jerome
中科院分区：
文献类型：
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作者：
Yamamura, Takashi;Kleiter, Ingo;De Seze, Jerome
研究背景视神经肌萎缩症谱系障碍（NMOSD）是一种中枢神经系统自身免疫性疾病，约三分之二的患者与抗水通道蛋白4（AQP 4-IgG）的自身抗体有关。白细胞介素-6参与了该疾病的发病机制。Satralizumab是一种靶向白细胞介素-6受体的人源化单克隆抗体。satralizumab添加到免疫抑制剂治疗NMOSD.METHODSIn 3期，随机，双盲，安慰剂对照试验的患者的疗效是不清楚的，我们随机分配，在1：1的比例，NMOSD患者谁是血清阳性或血清阴性的AQP 4-IgG接受satralizumab，在剂量为120毫克，或安慰剂，皮下注射给药，在0，2，4周和此后每4周，添加到稳定的免疫抑制剂治疗。主要终点是在至事件发生时间分析中第一次方案定义的复发。关键次要终点是视觉模拟量表（VAS）疼痛评分（范围0 - 100，评分越高表明疼痛越严重）和慢性疾病治疗疲劳功能评估（FACIT-F）评分（范围0 - 52，评分越低表明疲劳越严重）从基线至第24周的变化。安全性也进行了评估。共有83名患者参加了SATTSA，其中41名被分配到satralizumab组，42名被分配到安慰剂组。在双盲期，satralizumab的中位治疗持续时间为107.4周。Satralizumab组8例（20%）患者和安慰剂组18例（43%）患者复发（风险比，0.38; 95%置信区间[CI]，0.16 - 0.88）。删失数据的多重插补导致风险比范围为0.34 - 0.44（相应的P值为0.01 - 0.04）。在55名AQP 4-IgG血清阳性患者中，satralizumab组11%的患者和安慰剂组43%的患者复发（风险比，0.21; 95%CI，0.06 - 0.75）;在28例AQP 4-IgG血清阴性患者中，复发率分别为36%和43%，（风险比，0.66; 95% CI，0.20 - 2.24）。平均VAS疼痛评分变化的组间差异为4.08（95% CI，-8.44至16.61）;平均FACIT-F评分变化的组间差异为-3.10（95% CI，-8.38至2.18）。严重不良事件和感染的发生率在两组之间没有差异。CONCLUSIONSAmong NMOSD患者中，satralizumab加入免疫抑制剂治疗导致复发风险低于安慰剂，但在疼痛或疲劳方面与安慰剂没有差异。
BACKGROUNDNeuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disease of the central nervous system and is associated with autoantibodies to anti-aquaporin-4 (AQP4-IgG) in approximately two thirds of patients. Interleukin-6 is involved in the pathogenesis of the disorder. Satralizumab is a humanized monoclonal antibody targeting the interleukin-6 receptor. The efficacy of satralizumab added to immunosuppressant treatment in patients with NMOSD is unclear.METHODSIn a phase 3, randomized, double-blind, placebo-controlled trial, we randomly assigned, in a 1:1 ratio, patients with NMOSD who were seropositive or seronegative for AQP4-IgG to receive either satralizumab, at a dose of 120 mg, or placebo, administered subcutaneously at weeks 0, 2, and 4 and every 4 weeks thereafter, added to stable immunosuppressant treatment. The primary end point was the first protocol-defined relapse in a time-to-event analysis. Key secondary end points were the change from baseline to week 24 in the visual-analogue scale (VAS) pain score (range, 0 to 100, with higher scores indicating more pain) and the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) score (range, 0 to 52, with lower scores indicating more fatigue). Safety was also assessed.RESULTSA total of 83 patients were enrolled, with 41 assigned to the satralizumab group and 42 to the placebo group. The median treatment duration with satralizumab in the double-blind period was 107.4 weeks. Relapse occurred in 8 patients (20%) receiving satralizumab and in 18 (43%) receiving placebo (hazard ratio, 0.38; 95% confidence interval [CI], 0.16 to 0.88). Multiple imputation for censored data resulted in hazard ratios ranging from 0.34 to 0.44 (with corresponding P values of 0.01 to 0.04). Among 55 AQP4-IgG-seropositive patients, relapse occurred in 11% of those in the satralizumab group and in 43% of those in the placebo group (hazard ratio, 0.21; 95% CI, 0.06 to 0.75); among 28 AQP4-IgG-seronegative patients, relapse occurred in 36% and 43%, respectively (hazard ratio, 0.66; 95% CI, 0.20 to 2.24). The between-group difference in the change in the mean VAS pain score was 4.08 (95% CI, -8.44 to 16.61); the between-group difference in the change in the mean FACIT-F score was -3.10 (95% CI, -8.38 to 2.18). The rates of serious adverse events and infections did not differ between groups.CONCLUSIONSAmong patients with NMOSD, satralizumab added to immunosuppressant treatment led to a lower risk of relapse than placebo but did not differ from placebo in its effect on pain or fatigue.