Safety and efficacy of satralizumab monotherapy in neuromyelitis optica spectrum disorder: a randomised, double-blind, multicentre, placebo-controlled phase 3 trial.
Safety and efficacy of satralizumab monotherapy in neuromyelitis optica spectrum disorder: a randomised, double-blind, multicentre, placebo-controlled phase 3 trial.
复制标题
satralizumab单药治疗视神经肌病谱系障碍的安全性和有效性：一项随机、双盲、多中心、安慰剂对照的3期试验
DOI：
10.1016/s1474-4422(20)30078-8
复制
发表时间：
2020-05
期刊：
影响因子：
--
通讯作者：
Weinshenker BG
中科院分区：
文献类型：
--
作者：
Traboulsee A;Greenberg BM;Bennett JL;Szczechowski L;Fox E;Shkrobot S;Yamamura T;Terada Y;Kawata Y;Wright P;Gianella-Borradori A;Garren H;Weinshenker BG
Satralizumab是一种靶向白细胞介素-6受体的人源化单克隆抗体，当加入免疫抑制剂治疗时，可降低视神经肌病谱系障碍（NMOSD）患者的复发风险。本研究评估了satralizumab单药治疗在该疾病患者中的安全性和有效性。在这项III期、双盲、安慰剂对照、平行组试验中，我们在13个国家的44个研究中心招募了18-74岁的水通道蛋白-4抗体血清阳性或血清阴性NMOSD成人。合格的参与者在过去12个月内至少经历过一次有记录的NMOSD发作或复发，并且扩展残疾状态量表评分为6·5或更低。排除标准包括基线前30天或更短时间内的临床复发。受试者被随机分配（2：1），在第0、2、4周和此后每4周皮下接受satralizumab 120 mg或视觉匹配的安慰剂。禁止同时使用免疫抑制剂。主要终点是至首次方案定义的复发的时间，基于意向治疗人群，并对两个随机化因素（既往预防发作的治疗和最近发作的性质）进行分层分析。在所有接受至少一剂satralizumab或安慰剂的参与者中评估安全性。双盲期持续至发生44例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;参与者可在发生方案定义的复发后或双盲期结束时进入开放标签期。本研究注册于ClinicalTrials.gov，NCT 02073279。在2014年8月5日至2017年4月2日期间，168名筛选的参与者中有95名（57%）被随机分配到治疗组（63名接受satralizumab; 32名接受安慰剂）。19例（30%）接受satralizumab治疗的患者和16例（50%）接受安慰剂治疗的患者发生了方案定义的复发（风险比0.45，95%CI 0.23 - 0.89; p=0-018）。satralizumab组每100患者年发生473.9起不良事件，安慰剂组每100患者年发生495.2起不良事件;两组之间严重不良事件和导致退出的不良事件的发生率相似。在整个试验人群中，与安慰剂相比，Satralizumab单药治疗降低了NMOSD复发率，具有有利的安全性特征。患者人群包括反映临床实践的水通道蛋白-4抗体血清阳性和血清阴性患者的比例。Satralizumab有可能成为NMOSD患者的一种有价值的治疗选择。
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% Cl 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.