Efficacy and Safety of Rituximab Therapy in Neuromyelitis Optica Spectrum Disorders A Systematic Review and Meta-analysis
Efficacy and Safety of Rituximab Therapy in Neuromyelitis Optica Spectrum Disorders A Systematic Review and Meta-analysis
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DOI：
10.1001/jamaneurol.2016.1637
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发表时间：
2016-11-01
期刊：
影响因子：
29
通讯作者：
Iorio, Raffaele
中科院分区：
文献类型：
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作者：
Damato, Valentina;Evoli, Amelia;Iorio, Raffaele
重要性 视神经脊髓炎谱系疾病 (NMOSD) 是一种自身免疫性星形细胞病，其特征是主要累及视神经和脊髓。在大多数患者中，检测到与星形细胞水通道蛋白 4（中枢神经系统的主要水通道）结合的 IgG 自身抗体。利妥昔单抗是一种针对 CD20 B 淋巴细胞表面抗原特异性的嵌合单克隆抗体，已越来越多地被用作 NMOSD 患者的一线超说明书治疗。 目的 对利妥昔单抗在 NMOSD 中使用的疗效和安全性进行系统评价和阿元分析，考虑与患者对该疾病的利妥昔单抗反应相关的潜在预测因素。 证据审查 1 月 1 日至 1 月 1 日发表的英文研究2000 年和 2015 年 7 月 31 日的数据在 MEDLINE、对照试验中央注册库 (CENTRAL) 和临床试验中进行了检索。政府数据库。提取了患者特征、结果测量、治疗方案和记录的不良反应。结果 系统评价纳入了 46 项研究。荟萃分析中纳入了 25 项研究，其中包括 2 名或更多接受利妥昔单抗治疗的 NMOSD 患者。利妥昔单抗治疗前后年化复发率比和扩展残疾状态量表评分的差异是主要疗效指标。安全性结果包括死亡比例、因毒性作用和不良反应而退出的比例。 结果 在涉及 438 名患者（381 名女性和 56 名男性[1 名患者未指定性别]；治疗开始时的平均年龄，32 岁[年龄范围，2-77 岁]）的 46 项研究中，利妥昔单抗治疗的平均 (SE) 为 0.79 (0.15) (95% CI,-1.08)平均年化复发率比率降低至-0.49），扩展残疾状态量表评分平均（SE）降低0.64（0.27）（95% CI，-1.18至-0.10）。在疾病持续时间和扩展残疾状态量表评分之间观察到显着相关性。 438 名接受利妥昔单抗治疗的患者中，有 114 名 (26%) 出现不良反应。具体而言，45 名患者 (10.3%) 经历了输注相关不良反应，40 名患者 (9.1%) 出现感染，20 名患者 (4.6%) 出现持续性白细胞减少症，2 名患者 (0.5%) 被诊断为后可逆性脑病，7 名患者 (1.6%) 死亡。 结论和相关性 这项系统评价和荟萃分析提供了利妥昔单抗治疗降低频率的证据NMOSD 患者的 NMOSD 复发和神经功能障碍。然而，安全性表明将利妥昔单抗作为一线治疗时要谨慎。
IMPORTANCE Neuromyelitis optica spectrum disorders (NMOSDs) are autoimmune astrocytopathies characterized by predominant involvement of the optic nerves and spinal cord. In most patients, an IgG autoantibody binding to astrocytic aquaporin 4, the principal water channel of the central nervous system, is detected. Rituximab, a chimeric monoclonal antibody specific for the CD20 B-lymphocyte surface antigen, has been increasingly adopted as a first-line off-label treatment for patients with NMOSDs.OBJECTIVE To perform a systematic review and ameta-analysis of the efficacy and safety of rituximab use in NMOSDs, considering the potential predictive factors related to patient response to rituximab in this disease.EVIDENCE REVIEW English-language studies published between January 1, 2000, and July 31, 2015, were searched in the MEDLINE, Central Register of Controlled Trials (CENTRAL), and clinicaltrials. gov databases. Patient characteristics, outcome measures, treatment regimens, and recorded adverse effects were extracted.FINDINGS Forty-six studies were included in the systematic review. Twenty-five studies that included 2 or more patients with NMOSDs treated with rituximab were included in the meta-analysis. Differences in the annualized relapse rate ratio and Expanded Disability Status Scale score before and after rituximab therapy were the main efficacy measures. Safety outcomes included the proportion of deaths, withdrawals because of toxic effects, and adverse effects.RESULTS Among 46 studies involving 438 patients (381 female and 56 male [sex was not specified in 1 patient]; mean age at the outset of treatment, 32 years [age range, 2-77 years]), rituximab therapy resulted in a mean (SE) 0.79 (0.15) (95% CI,-1.08 to-0.49) reduction in the mean annualized relapse rate ratio and a mean (SE) 0.64 (0.27) (95% CI,-1.18 to-0.10) reduction in the mean Expanded Disability Status Scale score. A significant correlation was observed between disease duration and the Expanded Disability Status Scale score. Adverse effects were recorded in 114 of 438 (26%) patients treated with rituximab. Specifically, 45 patients (10.3%) experienced infusion-related adverse effects, 40 patients (9.1%) had an infection, 20 patients (4.6%) developed persistent leukopenia, 2 patients (0.5%) were diagnosed as having posterior reversible encephalopathy, and 7 patients (1.6%) died.CONCLUSIONS AND RELEVANCE This systematic review and meta-analysis provides evidence that rituximab therapy reduces the frequency of NMOSD relapses and neurological disability in patients with NMOSDs. However, the safety profile suggests caution in prescribing rituximab as a first-line therapy.