Department of Neurology, Memorial University of Newfoundland, Newfoundland and Labrador, Canada.
Department of Clinical Neurological Sciences, Western University, University Hospital - London Health Sciences Center, 339 Windermere Road, London, ON N6A 5Q5, Canada.
Mult Scler Relat Disord. 2022 Jan;57:103384. doi: 10.1016/j.msard.2021.103384. Epub 2021 Nov 8.
Dimethyl fumarate (DMF) is a disease-modifying therapy (DMT) used to treat relapsing multiple sclerosis (MS). Its precise mechanism in treating MS involves nuclear factor erythroid-derived 2-related factor-dependent and -independent pathways. Lymphopenia, defined according to NIH Common Terminology for Adverse Events v5.0, is one potential adverse effect. It is unclear whether lymphopenia correlates with disease activity; existing studies have yielded conflicting results.
To determine whether lymphopenia in DMF-treated persons with MS (PwMS) correlates with disease activity.
A retrospective chart review of 66 PwMS treated with DMF between January 1, 2013 and September 30, 2020.
Participants who experienced lymphopenia were older (p < 0.001), and had a longer disease duration (p = 0.012) and lower baseline absolute lymphocyte count (ALC) (p < 0.001). Breakthrough disease activity was the most common reason for DMF discontinuation (53.0%). Lymphopenia occurred in 36.4%, with ALCs decreasing over the first 12 months of therapy before plateauing. Lymphopenia was associated with a trend towards reduced relapses (p = 0.059) and significantly improved MRI activity (p = 0.001) and no evidence of disease activity (NEDA-3) (p = 0.022), but not disability progression (p = 0.549). Persons with lymphopenia were significantly less likely to be treated with another DMT after DMF (p = 0.036).
Risk factors for and rates of lymphopenia resembled existing data. Lymphopenia was associated with significantly improved MRI activity and achievement of NEDA-3, and whether PwMS were treated with another DMT after DMF. Further studies are required to clarify the mechanism of DMF, lymphocyte subsets and their relationship with disease activity, and which characteristics predict response to DMF.
富马酸二甲酯（DMF）是一种用于治疗复发型多发性硬化症（MS）的疾病修正治疗（DMT）。其在治疗 MS 中的精确机制涉及核因子红细胞衍生 2 相关因子依赖性和非依赖性途径。根据 NIH 常见不良事件术语标准 5.0 定义的淋巴细胞减少症是一种潜在的不良影响。目前尚不清楚淋巴细胞减少症是否与疾病活动度相关；现有的研究结果相互矛盾。
确定 DMF 治疗的多发性硬化症患者（PwMS）的淋巴细胞减少症是否与疾病活动度相关。
对 2013 年 1 月 1 日至 2020 年 9 月 30 日期间接受 DMF 治疗的 66 名 PwMS 进行回顾性图表审查。
发生淋巴细胞减少症的患者年龄更大（p<0.001），疾病持续时间更长（p=0.012），基线绝对淋巴细胞计数（ALC）更低（p<0.001）。突破性疾病活动是 DMF 停药的最常见原因（53.0%）。淋巴细胞减少症的发生率为 36.4%，治疗的前 12 个月内 ALC 逐渐下降，然后趋于平稳。淋巴细胞减少症与复发减少的趋势相关（p=0.059），与 MRI 活动显著改善（p=0.001）和无疾病活动证据（NEDA-3）（p=0.022）相关，但与残疾进展无关（p=0.549）。与 DMF 治疗后接受另一种 DMT 治疗的患者相比，发生淋巴细胞减少症的患者的可能性显著降低（p=0.036）。
淋巴细胞减少症的风险因素和发生率与现有数据相似。淋巴细胞减少症与 MRI 活动显著改善和达到 NEDA-3 相关，以及 DMF 治疗后 PwMS 是否接受另一种 DMT 治疗相关。需要进一步的研究来阐明 DMF、淋巴细胞亚群及其与疾病活动的关系，以及哪些特征预测对 DMF 的反应。
