Cabal-Herrera Ana M, Mateen Farrah J
Department of Neurology, Massachusetts General Hospital, Boston, MA.
Neurologist. 2021 Nov 30;27(1):14-20. doi: 10.1097/NRL.0000000000000376.
Neuromyelitis optica spectrum disorder (NMOSD) is a relapsing inflammatory disease that primarily affects the optic nerves and the spinal cord. Randomized controlled trials (RCTs) assessing treatments for NMOSD have only been performed in the past decade, and to date, there are 3 drugs approved by the US Food and Drug Administration (FDA) for antiaquaporin-4 immunoglobulin G seropositive NMOSD. This review assesses the characteristics and challenges of RCTs when evaluating treatments for NMOSD.
We conducted a review using the terms ("neuromyelitis optica" OR "NMO" OR "NMOSD") AND "clinical trial" in any language on March 28, 2021. Seven RCTs were included, and the trials' architecture was analyzed and synthesized. Overall, 794 subjects were randomized [monoclonal antibody intervention group, n= 493 (62.1%), placebo, n=196 (24.7%), and active control, n=105 (13.2%)]; 709 (89.3%) were females; and 658 (82.9%) were aquaporin-4 (AQP4) antibody seropositive. The primary outcome was time to relapse in 6/7 of the trials, and annualized relapse rate in the remaining one. Four RCTs used placebo in their design. Among the seven published RCTs, the trial design differed by the criteria used to define NMOSD relapse, selection of subjects, proportion of AQP4 immunoglobulin G seronegative patients, and baseline characteristics indicating NMO disease severity.
Ethical considerations for the use of placebo should change in light of the approval of 3 therapies for seropositive NMOSD. Remaining challenges for clinical trials in NMOSD include the assessment of long-term safety and efficacy, standardization of trial design and endpoints, and head-to-head study designs.
视神经脊髓炎谱系障碍（NMOSD）是一种复发性炎症性疾病，主要影响视神经和脊髓。评估NMOSD治疗方法的随机对照试验（RCT）仅在过去十年中进行，迄今为止，美国食品药品监督管理局（FDA）已批准3种药物用于抗水通道蛋白4免疫球蛋白G血清阳性的NMOSD。本综述评估了评估NMOSD治疗方法时RCT的特点和挑战。
我们于2021年3月28日使用任何语言的术语（“视神经脊髓炎”或“NMO”或“NMOSD”）和“临床试验”进行了一项综述。纳入了7项RCT，并对试验结构进行了分析和综合。总体而言，794名受试者被随机分组[单克隆抗体干预组，n = 493（62.1%），安慰剂组，n = 196（24.7%），活性对照组，n = 105（13.2%）]；709名（89.3%）为女性；658名（82.9%）水通道蛋白4（AQP4）抗体血清阳性。6/7的试验主要结局为复发时间，其余一项试验为年化复发率。4项RCT在设计中使用了安慰剂。在已发表的7项RCT中，试验设计在定义NMOSD复发的标准、受试者选择、AQP4免疫球蛋白G血清阴性患者比例以及表明NMO疾病严重程度的基线特征方面存在差异。
鉴于3种血清阳性NMOSD治疗方法的获批，使用安慰剂的伦理考量应有所改变。NMOSD临床试验的剩余挑战包括长期安全性和有效性评估、试验设计和终点的标准化以及直接比较的研究设计。
