Elsbernd Paul M, Hoffman William R, Carter Jonathan L, Wingerchuk Dean M
Departments of Neurology, Mayo Clinic, Scottsdale, AZ, United States; Brooke Army Medical Center, Fort Sam Houston, TX, United States.
Brooke Army Medical Center, Fort Sam Houston, TX, United States.
Mult Scler Relat Disord. 2021 Feb;48:102696. doi: 10.1016/j.msard.2020.102696. Epub 2020 Dec 16.
Myelin oligodendrocyte glycoprotein-immunoglobulin G (MOG-IgG) associated disorder (MOGAD) is a CNS demyelinating disease distinct from neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis. Some patients with MOGAD exhibit a highly-relapsing and steroid-dependent disease course for which optimal treatment is unknown. Interleukin-6 (IL-6) plays an important pathobiologic role in NMOSD with aquaporin-4 antibodies and preliminary data suggest similar mechanisms of CNS damage may occur in MOGAD.
To summarize our experience with and all current literature on the use of tocilizumab, an IL-6 inhibitor, for highly-relapsing MOGAD along with the underlying immunopathologic rationale.
This is a single-center report from a U.S. military tertiary referral hospital of all patients with clinically, radiographically, and serologically confirmed MOGAD who were treated with tocilizumab compiled with data from five other case series/reports from tertiary referral centers. The main outcomes of interest were reduction in annualized relapse rate and required dose of oral prednisone for symptomatic management.
Ten total patients with relapsing MOGAD who were treated with intravenous or subcutaneous tocilizumab were identified. At our institution, a 20 year-old female with a 9-year history of highly-relapsing and steroid dependent MOGAD was treated with tocilizumab. In 28 months of follow up, she had no clinical relapses and was able to discontinue corticosteroids. Another 35 year-old female at our institution with a 10-year history of highly-relapsing and steroid dependent MOGAD was treated with tocilizumab for 6 months. Tocilizumab therapy was associated with relapse freedom, resolution of eye pain, and ability to discontinue corticosteroids. When compiled with data from all other case reports of relapsing MOGAD treated with tocilizumab, there have been zero clinical or radiographic relapses in 10 patients over an average treatment duration of 28.6 months.
Tocilizumab is an IL-6 inhibitor that may be a promising therapeutic option for patients with relapsing MOGAD that has not responded to other immunotherapies. Our results support a key role for IL-6-related mechanisms in MOGAD disease activity. Its safety and tolerability profile, both in our own experience and based on its use for other FDA approved conditions, may even justify its use a first line therapy in select patients. Further research is needed to establish the safety and efficacy of IL-6 inhibition in MOGAD.
髓鞘少突胶质细胞糖蛋白免疫球蛋白G（MOG-IgG）相关疾病（MOGAD）是一种中枢神经系统脱髓鞘疾病，有别于视神经脊髓炎谱系障碍（NMOSD）和多发性硬化症。一些MOGAD患者表现出高复发率且依赖类固醇的病程，目前尚不清楚最佳治疗方法。白细胞介素-6（IL-6）在伴有水通道蛋白-4抗体的NMOSD中发挥重要的病理生物学作用，初步数据表明MOGAD中可能发生类似的中枢神经系统损伤机制。
总结我们使用白细胞介素-6抑制剂托珠单抗治疗高复发型MOGAD的经验及所有现有文献，并阐述其潜在的免疫病理机制。
这是一份来自美国一家军队三级转诊医院的单中心报告，纳入了所有经临床、影像学和血清学确诊为MOGAD且接受托珠单抗治疗的患者，并汇总了其他五家三级转诊中心的病例系列/报告数据。主要关注的结果是年化复发率的降低以及症状管理所需的口服泼尼松剂量。
共确定了10例接受静脉或皮下托珠单抗治疗的复发型MOGAD患者。在我们机构，一名有9年高复发且依赖类固醇病史的20岁女性MOGAD患者接受了托珠单抗治疗。在28个月的随访中，她没有临床复发，并且能够停用皮质类固醇。我们机构的另一名有10年高复发且依赖类固醇病史的35岁女性MOGAD患者接受了6个月的托珠单抗治疗。托珠单抗治疗与无复发、眼痛缓解以及停用皮质类固醇的能力相关。当汇总所有其他接受托珠单抗治疗的复发型MOGAD病例报告的数据时，10例患者在平均28.6个月的治疗期间内没有临床或影像学复发。
托珠单抗是一种IL-6抑制剂，对于对其他免疫疗法无反应的复发型MOGAD患者可能是一种有前景的治疗选择。我们的结果支持IL-6相关机制在MOGAD疾病活动中起关键作用。根据我们自己的经验以及其在其他FDA批准适应症中的使用情况，其安全性和耐受性甚至可能证明在某些患者中可将其用作一线治疗。需要进一步研究以确定IL-6抑制在MOGAD中的安全性和有效性。
