BACKGROUND Neuromyelitis 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. METHODS In 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. RESULTS A 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. CONCLUSIONS Among 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. (Funded by Chugai Pharmaceutical; ClinicalTrials.gov number, NCT02028884.).

中文翻译：

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沙特拉珠单抗治疗神经性脊髓炎性光谱障碍的临床试验。

背景技术视神经脊髓炎光谱疾病（NMOSD）是中枢神经系统的自身免疫疾病，并且在约三分之二的患者中与抗水通道蛋白4（AQP4-IgG）的自身抗体相关。白介素6参与该疾病的发病机理。Satralizumab是靶向白介素6受体的人源化单克隆抗体。目前尚不清楚在NMOSD患者的免疫抑制剂治疗中加入沙雷珠单抗的疗效。方法在一项3期，随机，双盲，安慰剂对照试验中，我们以1：1的比例随机分配了对AQP4-IgG呈血清反应阳性或血清反应阴性的NMOSD患者，以120剂量的剂量接受沙曲单抗治疗在第0、2和4周以及此后每4周皮下注射1 mg或安慰剂，以稳定的免疫抑制剂治疗。主要终点是事件发生时间分析中第一个协议定义的复发。关键的次要终点是视觉模拟量表（VAS）疼痛评分（范围从0到100，评分越高，表明疼痛越多）从基线到第24周的变化以及慢性病治疗疲劳的功能评估（FACIT- F）得分（范围从0到52，得分越低表示疲劳越多）。还评估了安全性。结果总共招募了83例患者，其中41例归于satralizumab组，而42例归于安慰剂组。在双盲期间使用沙妥珠单抗的中位治疗持续时间为107.4周。接受satralizumab治疗的8例患者（20％）和接受安慰剂的18例患者（43％）发生复发（危险比，0.38； 95％可信区间[CI]，0.16至0.88）。对审查数据进行多次插补可得出危险比范围为0.34至0.44（相应的P值为0.01至0.04）。在55名AQP4-IgG血清反应阳性患者中，satralizumab组和安慰剂组的复发率分别为11％和43％（危险比为0.21； 95％CI为0.06至0.75）。在28例AQP4-IgG血清阴性患者中，复发率分别为36％和43％（危险比，0.66； 95％CI，0.20至2.24）。组间平均VAS疼痛评分变化的差异为4.08（95％CI，-8.44至16.61）；组间FACIT-F平均得分变化的差异为-3.10（95％CI，-8.38至2.18）。两组之间的严重不良事件和感染发生率没有差异。结论在NMOSD患者中，免疫抑制剂治疗中加入沙雷珠单抗导致的复发风险低于安慰剂，但在疼痛或疲劳方面与安慰剂没有区别。（由Chugai Pharmaceutical资助； ClinicalTrials.gov编号，NCT02028884。）。