Mealy Maureen A, Shin Kyong, John Gareth, Levy Michael
Department of Neurology, Johns Hopkins University, Baltimore, MD, USA.
Department of Neurology, Mount Sinai Hospital, New York, NY, USA.
Clin Exp Neuroimmunol. 2015 Nov 1;6(4):413-418. doi: 10.1111/cen3.12239. Epub 2015 Aug 24.
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.
视神经脊髓炎（NMO）是一种复发性自身免疫性疾病，以脊髓和视神经为靶点，可导致瘫痪和失明。目前针对急性NMO发作的治疗方法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，贝伐单抗可能通过减少血脑屏障的破坏，在限制NMO复发期间的炎症程度方面发挥有益作用。
我们对10名NMO免疫球蛋白G血清阳性的NMO患者、NMO谱系疾病患者以及有发展为NMO/NMO谱系疾病高风险且出现急性横贯性脊髓炎、视神经炎或脑干炎症发作的患者进行了一项开放标签的1b期安全性和概念验证试验。除了每天静脉注射1g甲泼尼龙进行治疗外，我们在治疗第1天静脉输注10mg/kg的贝伐单抗。主要结局指标是安全性，次要结局指标是疗效。
在纳入的10名参与者中，5名表现为急性横贯性脊髓炎，4名表现为急性视神经炎，1名表现为脑干病变。贝伐单抗在所有10名参与者中均安全，在90天随访期内仅有1例严重不良事件，且该事件不归因于用药。3名患者恢复到发作前的神经功能或更好，没有患者需要升级到血浆置换治疗。
对于出现急性复发的NMO/NMO谱系疾病患者，贝伐单抗是一种安全的、可添加到高剂量皮质类固醇治疗中的疗法。
