The Blizard Institute, Barts and The London School of Medicine & Dentistry, Queen Mary University of London, London, United Kingdom; Clinical Board: Medicine (Neuroscience), The Royal London Hospital, Barts Health NHS Trust, London, United Kingdom.
The Blizard Institute, Barts and The London School of Medicine & Dentistry, Queen Mary University of London, London, United Kingdom; Department of Neurology, Shenzhen University General Hospital, Shenzhen University, Shenzhen, China; Shenzhen University Clinical Medical Academy, Shenzhen University, Shenzhen, China.
Mult Scler Relat Disord. 2018 Aug;24:20-27. doi: 10.1016/j.msard.2018.05.010. Epub 2018 Jun 1.
Evidence suggests people with non-relapsing deteriorating ("progressive") multiple sclerosis (pwPMS) may benefit from disease-modifying immune therapy (DMT). However, only one such treatment (ocrelizumab) has been licensed and is highly restricted to pwPMS suffering from the primary progressive phenotype. The difficulties assessing treatment outcome in pwPMS is one important reason for the lack of respective DMT. The concentration of neurofilaments in the cerebrospinal fluid (CSF) provides a biomarker of neuro-axonal damage, and both neurofilament light (NfL) and heavy chain (NfH) levels have been used as outcome indices and to guide treatment choices.
We report on two pwPMS, who were treated with subcutaneous cladribine undergoing CSF NfL testing, alongside MRI and clinical follow-up, before and after treatment.
Cladribine treatment was well tolerated without any side effects. CSF NfL after treatment revealed significant reduction (by 73% and 80%, respectively) corroborating the MRI detectable drop in disease activity. Disability mildly progressed in one, and remained stable in the other pwPMS.
pwPMS with detectable disease activity (MRI, elevated NfL) should be considered for DMT. NfL appears to be a sensitive index of treatment effect in pwPMS, and may be a useful outcome in clinical trials targeting this patient group. Over and above its licensed indication (relapsing MS), cladribine may be an effective treatment option for pwPMS.
有证据表明，非复发恶化（“进行性”）多发性硬化症（pwPMS）患者可能受益于疾病修正免疫疗法（DMT）。然而，只有一种这样的治疗方法（奥瑞珠单抗）获得了许可，并且仅限于患有原发性进行性表型的 pwPMS。评估 pwPMS 治疗效果的困难是缺乏相应 DMT 的一个重要原因。脑脊液（CSF）中的神经丝浓度提供了神经轴突损伤的生物标志物，神经丝轻链（NfL）和重链（NfH）水平都被用作疗效指标和指导治疗选择。
我们报告了两名接受皮下 cladribine 治疗的 pwPMS 患者，他们在治疗前后进行了 CSF NfL 测试、MRI 和临床随访。
cladribine 治疗耐受性良好，无任何副作用。治疗后的 CSF NfL 显著降低（分别降低了 73%和 80%），与 MRI 检测到的疾病活动减少相符。一名 pwPMS 患者的残疾轻度进展，另一名则保持稳定。
有可检测到疾病活动（MRI、NfL 升高）的 pwPMS 应考虑进行 DMT。NfL 似乎是 pwPMS 治疗效果的敏感指标，可能是针对该患者群体的临床试验中的有用疗效指标。除了其许可的适应症（复发型 MS）外， cladribine 可能是 pwPMS 的有效治疗选择。
