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视神经脊髓炎谱系疾病的疾病修饰治疗研究进展
李鸿艳
王侃
俞昊君
瑞瑞
姚小英
管阳太
作者及单位信息
·
DOI： 10.3760/cma.j.cn113694-20230814-00052
Advances in disease-modifying therapy of neuromyelitis optica spectrum disorders
Li Hongyan
Wang Kan
Yu Haojun
Rui Rui
Yao Xiaoying
Guan Yangtai
Authors Info & Affiliations
Li Hongyan
Department of Neurology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China
Wang Kan
Department of Neurology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China
Yu Haojun
Department of Neurology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China
Rui Rui
Department of Neurology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China
Yao Xiaoying
Department of Neurology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China
Guan Yangtai
Department of Neurology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China
·
DOI： 10.3760/cma.j.cn113694-20230814-00052
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摘要

视神经脊髓炎谱系疾病（NMOSD）是一组由自身免疫介导、以视神经和脊髓受累为主要表现的中枢神经系统炎性脱髓鞘疾病，具有高复发率、高致残率的特点。缓解期的疾病修饰治疗是预防该疾病复发的关键，包括免疫抑制剂、单克隆抗体、干细胞治疗等。本团队在Pubmed数据库检索2017—2022年发表的有关NMOSD疾病修饰治疗的文献进行系统综述，旨在给NMOSD缓解期的疾病修饰治疗提供建议和参考。

视神经脊髓炎;药物治疗;免疫抑制剂;单克隆抗体;干细胞移植
ABSTRACT

Neuromyelitis optica spectrum disorders (NMOSD) are a group of autoimmune-mediated inflammatory demyelinating diseases of the central nervous system, characterized by optic nerve and spinal cord lesions, with high chance of recurrence and disability. Disease-modifying therapy, including immunosuppressants, monoclonal antibodies, stem cell transplantation etc., is the key to prevent recurrence. This article made a systematic review about the sequential treatment or prognosis of NMOSD by searching for the related articles published on PubMed from 2017 to 2022 to provide recommendations and references for disease-modifying therapy of NMOSD.

Neuromyelitis optica;Drug therapy;Immunosuppressive agents;Monoclonal antibodies;Stem cell transplantation
Guan Yangtai, Email: mocdef.aabnisnaugiatgnay

None declared

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引用本文

李鸿艳,王侃,俞昊君,等. 视神经脊髓炎谱系疾病的疾病修饰治疗研究进展[J]. 中华神经科杂志,2023,56(12)：1435-1446.

DOI:10.3760/cma.j.cn113694-20230814-00052

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视神经脊髓炎谱系疾病（neuromyelitis optica spectrum disorders，NMOSD）是一组自身免疫介导、以视神经和脊髓受累为主要表现的中枢神经系统炎性脱髓鞘疾病，具有高复发率、高致残率的特点 ［ 1 , 2 , 3 , 4 , 5 , 6 ］ 。在全世界范围内，NMOSD的患病率为（0.5~10.0）/100 000 ［ 7 ］ ，目前，我国NMOSD的发病率约为0.278/（10万人·年） ［ 8 ］ ，发病高峰年龄为45~65岁，女性与男性发病率比例为4.71∶1 ［ 9 ］ 。在高达80%NMOSD患者的血清/脑脊液中可以检测出特异性的水通道蛋白-4抗体（aquaporin-4 antibodies，AQP4-IgG），其在NMOSD的发病机制中发挥了重要作用 ［ 10 ］ 。近期有研究发现在AQP4抗体阴性患者中，有部分患者髓鞘少突胶质细胞糖蛋白（myelin oligodendrocyte glycoprotein，MOG）抗体阳性，因此，将该部分患者区别于NMOSD，统称为MOGAD（MOG antibody disease）。有研究发现AQP4抗体阳性的NMOSD患者相较于MOGAD患者的MRI病灶倾向于分布在血供相对稀疏的室管膜下区域 ［ 11 ］ 。
NMOSD的治疗方案包括急性期治疗和缓解期的疾病修饰治疗（disease-modifying therapy，DMT），前者以缓解症状、缩短病程、改善残疾程度和预防并发症为目的，后者主要是为了预防疾病复发。据统计，约60%的NMOSD患者在症状出现的第1年内复发，超过90%的患者在3年内复发，导致患者丧失行动能力或失明，因此DMT对于NMOSD患者至关重要。
DMT包括免疫抑制剂、单克隆抗体、干细胞治疗等。一些免疫抑制疗法因其在其他自身免疫疾病中的有效性，已被用于预防NMOSD的复发。例如，硫唑嘌呤（azathioprine）、吗替麦考酚酯（mycophenolate mofetil，MMF）、利妥昔单抗（rituximab，RTX）等。然而，许多用于多发性硬化的DMT药物，如干扰素β、芬戈莫德、那他珠单抗和阿仑单抗，对NMOSD患者无效，甚至可能会增加NMOSD的年复发率（annualized relapse rates） ［ 12 ］ 。如 图1 所示，随着对病理机制的深入理解，一些单克隆抗体被应用于NMOSD的治疗，如依库珠单抗（eculizumab）、萨特利珠单抗（satralizumab）、托珠单抗（tocilizumab）等。此外，运用干细胞治疗NMOSD等新的研究也正在进行中，可能会成为NMOSD患者新的治疗选择。因此，我们通过文献复习总结DMT不同治疗方案的有效性和安全性，从传统治疗药物、新型治疗药物、评估中的治疗药物和评估中的细胞治疗4个部分叙述，旨在给NMOSD缓解期的DMT提供建议和参考。
视神经脊髓炎谱系疾病的病理机制药物的治疗靶点（本图为原创图片，由笔者运用Figdraw软件绘制）

AQP4：水通道蛋白-4；IL：白细胞介素

Pathophysiologic mechanisms of neuromyelitis optica spectrum disorders and therapeutic targets described herein (The picture is original, drawing with Figraw software)
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备注信息
A
管阳太，Email： mocdef.aabnisnaugiatgnay
B

李鸿艳：文章撰写；王侃、俞昊君：文章修改；瑞瑞：文献检索；姚小英、管阳太：写作指导及修改

C
李鸿艳, 王侃, 俞昊君, 等. 视神经脊髓炎谱系疾病的疾病修饰治疗研究进展[J]. 中华神经科杂志, 2023, 56(12): 1435-1446. DOI: 10.3760/cma.j.cn113694-20230814-00052.
D
所有作者声明无利益冲突
E
None declared
F
国家重点研发计划“干细胞及转化研究”重点专项 (2020YFA0113100)
上海市高水平地方高校创新研究团队
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