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托珠单抗治疗对利妥昔单抗难治的自身免疫性脑炎:一项机构队列研究。

Tocilizumab in Autoimmune Encephalitis Refractory to Rituximab: An Institutional Cohort Study.

作者信息

Lee Woo-Jin, Lee Soon-Tae, Moon Jangsup, Sunwoo Jun-Sang, Byun Jung-Ick, Lim Jung-Ah, Kim Tae-Joon, Shin Yong-Won, Lee Keon-Joo, Jun Jin-Sun, Lee Han Sang, Kim Soyun, Park Kyung-Il, Jung Keun-Hwa, Jung Ki-Young, Kim Manho, Lee Sang Kun, Chu Kon

机构信息

Department of Neurology, Comprehensive Epilepsy Center, Laboratory for Neurotherapeutics, Biomedical Research Institute, Seoul National University Hospital, Seoul, South Korea.

Program in Neuroscience, Neuroscience Research Institute of SNUMRC, College of Medicine, Seoul National University, Seoul, South Korea.

出版信息

Neurotherapeutics. 2016 Oct;13(4):824-832. doi: 10.1007/s13311-016-0442-6.

Abstract

A considerable portion of autoimmune encephalitis (AE) does not respond to conventional immunotherapies and subsequently has poor outcomes. We aimed to determine the efficacy of tocilizumab, an anti-interleukin-6 antibody, in rituximab-refractory AE compared with other treatment options. From an institutional cohort of AE, 91 patients with inadequate clinical response to first-line immunotherapy and following rituximab were retrospectively reviewed. Patients were grouped according to their further immunotherapy strategies. Thirty (33.0 %) patients were included in the tocilizumab group, 31 (34.0 %) in the additional rituximab group, and 30 (33.0 %) in the observation group. Outcomes were defined as the favorable modified Rankin Scale scores (≤2) at 1 and 2 months from the initiation of each treatment strategy and at the last follow-up. Favorable clinical response (improvement of the modified Rankin Scale scores by ≥ 2 points or achievement of the mRS scores ≤ 2) at the last follow-up was also analyzed. The tocilizumab group showed more frequent favorable mRS scores at 2 months from treatment initiation and at the last follow-up compared with those at the relevant time points of the remaining groups. The majority (89.5 %) of the patients with clinical improvement at 1 month from tocilizumab treatment maintained a long-term favorable clinical response. No serious adverse effects of rituximab or tocilizumab were reported. Therefore, we suggest that tocilizumab might be a good treatment strategy for treating AE refractory to conventional immunotherapies and rituximab. The tocilizumab-mediated clinical improvement manifests as early at 1 month after treatment initiation.

摘要

相当一部分自身免疫性脑炎(AE)对传统免疫疗法无反应,因此预后较差。我们旨在确定抗白细胞介素-6抗体托珠单抗在难治性AE中的疗效,并与其他治疗方案进行比较。从一个AE机构队列中,回顾性分析了91例对一线免疫疗法及利妥昔单抗治疗临床反应不佳的患者。根据进一步的免疫治疗策略对患者进行分组。托珠单抗组纳入30例(33.0%)患者,额外使用利妥昔单抗组纳入31例(34.0%)患者,观察组纳入30例(33.0%)患者。结局定义为从每种治疗策略开始后1个月和2个月以及最后一次随访时改良Rankin量表评分良好(≤2)。还分析了最后一次随访时的良好临床反应(改良Rankin量表评分提高≥2分或mRS评分≤2)。与其余组的相关时间点相比,托珠单抗组在治疗开始后2个月和最后一次随访时显示出更频繁的良好mRS评分。托珠单抗治疗1个月时临床改善的患者中,大多数(89.5%)维持了长期良好的临床反应。未报告利妥昔单抗或托珠单抗的严重不良反应。因此,我们认为托珠单抗可能是治疗对传统免疫疗法和利妥昔单抗难治的AE的良好治疗策略。托珠单抗介导的临床改善在治疗开始后1个月就已显现。

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