Inebilizumab for the treatment of neuromyelitis optica spectrum disorder (N-MOmentum): a double-blind, randomised placebo-controlled phase 2/3 trial
Inebilizumab for the treatment of neuromyelitis optica spectrum disorder (N-MOmentum): a double-blind, randomised placebo-controlled phase 2/3 trial
复制标题
DOI：
10.1016/s0140-6736(19)31817-3
复制
发表时间：
2019-10-12
期刊：
影响因子：
168.9
通讯作者：
Felton, Warren, III
中科院分区：
文献类型：
--
作者：
Cree, Bruce A. C.;Bennett, Jeffrey L.;Felton, Warren, III
视神经肌萎缩症谱系障碍（NMOSD）是一种罕见的、复发性、自身免疫性、中枢神经系统炎症性疾病，可导致失明和瘫痪，目前尚无批准的治疗方法。我们的目的是评估inebilizumab的疗效和安全性，抗CD 19，B细胞耗竭抗体，在减少NMOSD.Methods的攻击和残疾的风险，我们做了一个多中心，双盲，随机安慰剂对照的2/3期研究，在99个门诊专科诊所或医院在25个国家。符合条件的参与者是诊断为NMOSD的成年人（≥ 18岁），扩展残疾状态量表评分为8.0或更低，并且在筛选前一年内至少有一次需要补救治疗的发作史或在筛选前2年内至少有两次需要补救治疗的发作史。通过中央交互式语音应答系统或交互式网络应答系统和排列区组随机化，将参与者随机分配（3：1）至300 mg静脉注射inebilizumab或安慰剂组。在第1天和第15天给予Inebilizumab或安慰剂。参与者、研究者和所有临床工作人员均对治疗设盲，inebilizumab和安慰剂在外观上无法区分。主要终点是至NMOSD发作的时间，由裁定委员会确定。在接受至少一剂研究干预药物的所有随机分配患者中评估疗效终点，在实际治疗人群中评估安全性终点。该研究注册于www.example.com，编号NCT 02200770。结果在2015年1月6日至2018年9月24日期间，230名参与者被随机分配到治疗和给药组，其中174名参与者接受inebilizumab治疗，56名接受安慰剂治疗。根据独立数据监测委员会的建议，由于疗效已得到明确证明，因此在完成入组前停止随机对照期。174名接受inebilizumab的参与者中有21名（12%）发生了发作，而56名接受安慰剂的参与者中有22名（39%）发生了发作（风险比0.272 [95%CI 0.150 - 0.496]; p
Background No approved therapies exist for neuromyelitis optica spectrum disorder (NMOSD), a rare, relapsing, autoimmune, inflammatory disease of the CNS that causes blindness and paralysis. We aimed to assess the efficacy and safety of inebilizumab, an anti-CD19, B cell-depleting antibody, in reducing the risk of attacks and disability in NMOSD.Methods We did a multicentre, double-blind, randomised placebo-controlled phase 2/3 study at 99 outpatient specialty clinics or hospitals in 25 countries. Eligible participants were adults (>= 18 years old) with a diagnosis of NMOSD, an Expanded Disability Status Scale score of 8.0 or less, and a history of at least one attack requiring rescue therapy in the year before screening or at least two attacks requiring rescue therapy in the 2 years before screening. Participants were randomly allocated (3:1) to 300 mg intravenous inebilizumab or placebo with a central interactive voice response system or interactive web response system and permuted block randomisation. Inebilizumab or placebo was administered on days 1 and 15. Participants, investigators, and all clinical staff were masked to the treatments, and inebilizumab and placebo were indistinguishable in appearance. The primary endpoint was time to onset of an NMOSD attack, as determined by the adjudication committee. Efficacy endpoints were assessed in all randomly allocated patients who received at least one dose of study intervention, and safety endpoints were assessed in the as-treated population. The study is registered with ClinicalTrials.gov, number NCT02200770.Findings Between Jan 6, 2015, and Sept 24, 2018, 230 participants were randomly assigned to treatment and dosed, with 174 participants receiving inebilizumab and 56 receiving placebo. The randomised controlled period was stopped before complete enrolment, as recommended by the independent data-monitoring committee, because of a clear demonstration of efficacy. 21 (12%) of 174 participants receiving inebilizumab had an attack versus 22 (39%) of 56 participants receiving placebo (hazard ratio 0.272 [95% CI 0.150-0.496]; p