Neurosciences Unit, Department of Medicine and Surgery, University of Parma, Parma, Italy.
Department of Neurosciences, Azienda Ospedaliero-Universitaria di Modena Ospedale Civile di Baggiovara, Modena, Italy.
Eur J Neurol. 2021 Jan;28(1):269-277. doi: 10.1111/ene.14538. Epub 2020 Oct 17.
Dimethyl fumarate (DMF) causes a mean lymphocyte count drop of approximately 30% in relapsing-remitting multiple sclerosis (RRMS) patients. The relationship between this reduction and DMF effectiveness is controversial. The objective was to investigate if the decrease in absolute lymphocyte count (ALC) from baseline during DMF treatment is associated with clinical and magnetic resonance imaging (MRI) disease activity. A secondary aim was to evaluate ALC variations over time in a real-life cohort of DMF-treated patients.
Demographic, laboratory, clinical and MRI data were collected in this observational multicentre study, conducted on RRMS patients treated with DMF for at least 6 months. Multivariate Cox models were performed to evaluate the impact of 6-month ALC drop on time to no evidence of disease activity (NEDA-3) status loss. NEDA-3 is defined as absence of clinical relapses, MRI disease activity and confirmed disability progression.
In all, 476 patients (312 females, age at DMF start 38.4 ± 9.97 years) were analysed up to 5-year follow-up. A greater lymphocyte decrease was associated with a lower risk of NEDA-3 status loss (hazard ratio 0.87, P = 0.01). A worse outcome in patients with lower ALC drop (<11.5%), compared with higher tertiles (11.5%-40.5% and >40.5%), was observed (P = 0.008). The nadir of ALC drop (-33.6%) and 35% of grade III lymphopaenia cases occurred after 12 months of treatment.
A higher lymphocyte count drop at 6 months is related to better outcomes in DMF-treated patients. A careful ALC monitoring should be pursued up to 24 months of treatment.
富马酸二甲酯（DMF）可导致复发缓解型多发性硬化症（RRMS）患者的淋巴细胞计数平均下降约 30%。这种下降与 DMF 疗效之间的关系存在争议。本研究旨在探讨 DMF 治疗期间绝对淋巴细胞计数（ALC）从基线的下降是否与临床和磁共振成像（MRI）疾病活动相关。次要目的是评估 DMF 治疗患者的真实队列中 ALC 随时间的变化。
在这项观察性多中心研究中收集了人口统计学、实验室、临床和 MRI 数据，对至少接受 6 个月 DMF 治疗的 RRMS 患者进行了研究。采用多变量 Cox 模型评估 6 个月时 ALC 下降对无疾病活动状态（NEDA-3）丧失的影响。NEDA-3 定义为无临床复发、MRI 疾病活动和确认的残疾进展。
在所有 476 例患者（312 例女性，DMF 起始时年龄为 38.4±9.97 岁）的 5 年随访中进行了分析。淋巴细胞下降幅度越大，NEDA-3 状态丧失的风险越低（风险比 0.87，P=0.01）。与较高的三分位组（11.5%-40.5%和>40.5%）相比，ALC 下降幅度较低（<11.5%）的患者预后较差（P=0.008）。ALC 下降的最低点（-33.6%）和 35%的 III 级淋巴细胞减少症病例发生在治疗 12 个月后。
6 个月时淋巴细胞计数下降幅度越大，DMF 治疗患者的结局越好。应在治疗 24 个月内进行更仔细的 ALC 监测。
