日本国立神经科学研究所Takashi Yamamura研究小组取得一项新突破。他们研究了Satralizumab治疗视神经脊髓炎的临床疗效。相关论文于2019年11月28日发表在《新英格兰医学杂志》上。

视神经脊髓炎（NMOSD）是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（AQP4-IgG）自身抗体有关。白细胞介素-6参与了这种疾病的发病机制。Satralizumab是一种人源化单克隆抗体，靶向白细胞介素-6受体。但Satralizumab联合免疫抑制剂治疗NMOSD的疗效尚不清楚。

在这项临床3期、随机、双盲、安慰剂对照试验中，研究组招募了83名血清AQP4-IgG阳性或阴性的NMOSD患者，将其按1：1随机分组，其中41名接受Satralizumab治疗，42名接受安慰剂治疗，两组均联合稳定的免疫抑制剂治疗。采用视觉模拟量表（VAS）疼痛评分（0-100，分数越高越疼痛）和慢性病治疗功能评估-疲劳量表（FACIT-F）评分（0-52，分数越低越疲劳）对治疗效果进行评价。

中位治疗107.4周后，Satralizumab组中有8名（20%）患者复发，安慰剂组有18名（43%），差异显著。在55例AQP4-IgG阳性的患者中，Satralizumab组的复发率为11%，安慰剂组为43%，风险比为0.21；在28例AQP4-IgG阴性的患者中，两组的复发率分别为36%和43%，风险比为0.66。Satralizumab组的VAS疼痛评分比安慰剂组高4.08分，FACIT-F评分低3.10分。两组间严重不良事件和感染的发生率无差异。

总之，Satralizumab+免疫抑制剂治疗NMOSD患者可显著降低复发率，但对疼痛和疲劳的影响与安慰剂无异。

附：英文原文

Title: Trial of Satralizumab in Neuromyelitis Optica Spectrum Disorder

Author: Takashi Yamamura, M.D., Ph.D.,, Ingo Kleiter, M.D.,, Kazuo Fujihara, M.D., Ph.D.,, Jacqueline Palace, D.M.,, Benjamin Greenberg, M.D.,, Beata Zakrzewska-Pniewska, M.D., Ph.D.,, Francesco Patti, M.D.,, Ching-Piao Tsai, M.D.,, Albert Saiz, M.D., Ph.D.,, Hayato Yamazaki, M.D., Ph.D.,, Yuichi Kawata, Ph.D.,, Padraig Wright, M.D., Ph.D.,, and Jerome De Seze, M.D., Ph.D.

Issue&Volume: 2019-11-27

Abstract: 

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. opens in new tab.)

DOI: 10.1056/NEJMoa1901747

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa1901747