Bevacizumab is safe in acute relapses of neuromyelitis optica.
Bevacizumab is safe in acute relapses of neuromyelitis optica.
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DOI：
10.1111/cen3.12239
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发表时间：
2015-11-01
影响因子：
--
通讯作者：
Levy M
中科院分区：
文献类型：
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作者：
Mealy MA;Shin K;John G;Levy M
视神经脊髓炎 (NMO) 是一种针对脊髓和视神经的复发性自身免疫性疾病，导致瘫痪和失明。目前对急性 NMO 发作的治疗是使用大剂量皮质类固醇和/或血浆置换进行免疫抑制。临床前动物研究表明，贝伐珠单抗可能通过减少血脑屏障的破坏来限制 NMO 复发期间的炎症程度。我们对 10 名患有 NMO 免疫球蛋白 G 血清阳性 NMO、NMO 谱系疾病以及患有 NMO/NMO 谱系疾病高风险且出现横贯性脊髓炎、视神经炎或脑干炎症急性发作的受试者进行了一项开放标签 1b 期安全性和概念验证试验。除了每日静脉注射 1 g 甲基泼尼松龙外，我们还在治疗第 1 天静脉注射 10 mg/kg 贝伐珠单抗。主要结果指标是安全性，次要结果指标是疗效。在登记的 10 名参与者中，5 名患有急性横贯性脊髓炎，4 名患有急性视神经炎，1 名患有脑干病变。贝伐珠单抗对所有 10 名参与者都是安全的，在 90 天的随访中仅发生了 1 起非药物引起的严重不良事件。三名患者的神经功能恢复到发作前或更好，没有患者需要升级到血浆置换。贝伐珠单抗是高剂量皮质类固醇的安全附加疗法，适用于急性复发的 NMO/NMO 谱系疾病患者。
Neuromyelitis optica (NMO) is a relapsing autoimmune disease targeting the spinal cord and optic nerve leading to paralysis and blindness. Current treatment for acute NMO attacks is immunosuppression with high-dose corticosteroids and/or plasmapheresis. Preclinical animal studies suggest that bevacizumab might be beneficial in limiting the extent of inflammation during a NMO relapse by reducing the disruption of the blood–brain barrier. We carried out an open-label phase 1b safety and proof-of-concept trial in 10 participants with NMO immunoglobulin G seropositive NMO, NMO spectrum disease and those at high risk for developing NMO/NMO spectrum disease who presented with an acute attack of transverse myelitis, optic neuritis or brainstem inflammation. In addition to treating with 1 g of daily intravenous methylprednisolone, we infused 10 mg/kg of bevacizumab intravenously on day 1 of treatment. The primary outcome measure was safety and the secondary outcome measure was efficacy. Of the 10 participants enrolled, five presented with acute transverse myelitis, four with acute optic neuritis and one with a brainstem lesion. Bevacizumab was safe in all 10 participants, with only one serious adverse event within the 90-day follow up that was not attributed to the medication. Three patients recovered to pre-attack neurological function or better, and no patients required escalation to plasmapheresis. Bevacizumab is a safe add-on therapy to high-dose corticosteroids for NMO/NMO spectrum disease patients presenting with an acute relapse.