Department of Neurology, University of British Columbia, Vancouver, BC, Canada.
Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Lancet Neurol. 2020 May;19(5):402-412. doi: 10.1016/S1474-4422(20)30078-8.
Satralizumab, a humanised monoclonal antibody targeting the interleukin-6 receptor, reduced the risk of relapse in patients with neuromyelitis optica spectrum disorder (NMOSD) when added to immunosuppressant therapy. This study assessed the safety and efficacy of satralizumab monotherapy in patients with the disorder.
In this phase 3, double-blind, placebo-controlled, parallel-group trial, we enrolled adults aged 18-74 years with aquaporin-4 antibody seropositive or seronegative NMOSD at 44 investigational sites in 13 countries. Eligible participants had experienced at least one documented NMOSD attack or relapse in the past 12 months and had a score of 6·5 or less on the Expanded Disability Status Scale. Exclusion criteria included clinical relapse 30 days or fewer before baseline. Participants were randomly assigned (2:1) to receive satralizumab 120 mg or visually matched placebo subcutaneously at weeks 0, 2, 4, and every 4 weeks thereafter. Taking immunosuppressants concomitantly was prohibited. The primary endpoint was time to the first protocol-defined relapse, based on the intention-to-treat population and analysed with stratification for two randomisation factors (previous therapy for prevention of attacks and nature of the most recent attack). Safety was assessed in all participants who received at least one dose of satralizumab or placebo. The double-blind phase was due to last until 44 protocol-defined relapses occurred or 1·5 years after random assignment of the last patient enrolled, whichever occurred first; participants could enter an open-label phase after the occurrence of a protocol-defined relapse or at the end of the double-blind phase. The study is registered with ClinicalTrials.gov, NCT02073279.
95 (57%) of 168 screened participants were randomly assigned to treatment (63 to satralizumab; 32 to placebo) between Aug 5, 2014, and April 2, 2017. Protocol-defined relapses occurred in 19 (30%) patients receiving satralizumab and 16 (50%) receiving placebo (hazard ratio 0·45, 95% CI 0·23-0·89; p=0·018). 473·9 adverse events per 100 patient-years occurred in the satralizumab group, as did 495·2 per 100 patient-years in the placebo group; the incidence of serious adverse events and adverse events leading to withdrawal was similar between groups.
Satralizumab monotherapy reduced the rate of NMOSD relapse compared with placebo in the overall trial population, with a favourable safety profile. The patient population included a ratio of aquaporin-4 antibody seropositive and seronegative patients that was reflective of clinical practice. Satralizumab has the potential to become a valuable treatment option for patients with NMOSD.
Chugai Pharmaceutical (Roche).
靶向白细胞介素-6 受体的人源化单克隆抗体沙利鲁单抗与免疫抑制剂联合治疗可降低视神经脊髓炎谱系疾病（NMOSD）患者的复发风险。本研究评估了沙利鲁单抗单药治疗该疾病患者的安全性和疗效。
在这项 3 期、双盲、安慰剂对照、平行分组试验中，我们在 13 个国家的 44 个研究点招募了年龄在 18-74 岁之间、水通道蛋白-4 抗体阳性或阴性 NMOSD 的成人。合格参与者在过去 12 个月中经历了至少一次有记录的 NMOSD 发作或复发，扩展残疾状态量表评分<6.5。排除标准包括基线前 30 天内出现临床复发。参与者被随机分配（2:1）接受沙利鲁单抗 120mg 或视觉匹配的安慰剂皮下注射，在第 0、2、4 周以及此后每 4 周一次。禁止同时使用免疫抑制剂。主要终点是基于意向治疗人群的首次方案定义的复发时间，分析时分层了两个随机因素（预防发作的先前治疗和最近一次发作的性质）。在至少接受一次沙利鲁单抗或安慰剂治疗的所有参与者中评估安全性。双盲阶段持续到发生 44 次方案定义的复发或随机分配最后一名入组患者后 1.5 年，以先发生者为准；发生方案定义的复发后或双盲阶段结束后，参与者可进入开放标签阶段。该研究在 ClinicalTrials.gov 注册，NCT02073279。
95 名（57%）接受筛查的参与者于 2014 年 8 月 5 日至 2017 年 4 月 2 日之间被随机分配至治疗组（63 名接受沙利鲁单抗；32 名接受安慰剂）。在接受沙利鲁单抗治疗的 19 名（30%）患者和接受安慰剂治疗的 16 名（50%）患者中发生了方案定义的复发（风险比 0.45，95%CI 0.23-0.89；p=0.018）。沙利鲁单抗组发生了 473.9 例不良事件/100 患者年，安慰剂组发生了 495.2 例/100 患者年；两组严重不良事件和导致停药的不良事件发生率相似。
与安慰剂相比，沙利鲁单抗单药治疗在整个试验人群中降低了 NMOSD 复发率，具有良好的安全性。患者人群中，水通道蛋白-4 抗体阳性和阴性患者的比例反映了临床实践。沙利鲁单抗有望成为 NMOSD 患者的一种有价值的治疗选择。
中外制药（罗氏）。
