Garbo Riccardo, Lorenzut Simone, Del Negro Ilaria, Merlino Giovanni, Gigli Gian Luigi, Cargnelutti Daniela, Valente Mariarosaria
Clinical Neurology Unit, Udine University Hospital, Piazzale Santa Maria della Misericordia 15, 33100, Udine, Italy.
Neurology Unit, Udine University Hospital, Piazzale Santa Maria della Misericordia 15, 33100, Udine, Italy.
Mult Scler Relat Disord. 2021 Apr;49:102781. doi: 10.1016/j.msard.2021.102781. Epub 2021 Jan 20.
delayed-release dimethyl fumarate (DMF) is a disease modifying therapy for relapsing-remitting multiple sclerosis (MS) with antioxidant and anti-inflammatory properties. The drug causes lymphocyte count reduction, which can lead to lymphopenia development during treatment. This is an important safety issue, due to infectious risk, mainly progressive multifocal leukoencephalopathy (PML). If the lymphocyte count influences the response to treatment is still a matter of debate, as there are contrasting contrasting data in the literature. Considering this, we aimed to identify DMF induced lymphopenia risk factors and to evaluate lymphopenia impact on MS disease activity in a real world setting.
a retrospective study on 135 MS patients receiving DMF with a mean treatment duration of 32.3±15.9 months was performed. Baseline and follow-up demographic, clinical, magnetic resonance imaging (MRI) and laboratory data were collected.
44 patients (32.6%) developed lymphopenia, with 11 (8.1%) grade 1, 23 (17.0%) grade 2 and 10 (7.4 %) grade 3. Older age and lower basal absolute lymphocyte count were found to be associated with lymphopenia development on a binary regression model (p<0.001 and p=0.009). When compared with non lymphopenic+lymphopenia grade 1 patients, those experiencing lymphopenia grade 2+3 had longer disease activity free survival (p<0.001), fewer clinical relapses (p=0.005) and lower MRI disease activity (p≤0.001). On Cox regression model, older age and lymphopenia grade 2+3 were found to be protective factors against disease activity (HR=0.966; 95% C.I.=0.942-0.992; p=0.009 for age; HR=0.137; 95% C.I.=0.043-0.439; p=0.001 for lymphopenia grade 2+3) and MRI disease activity (HR=0.968; 95% C.I.=0.941-0.997; p=0.030 for age; HR=0.142; 95% C.I.=0.034-0.591; p=0.007 for lymphopenia grade 2+3). Only lymphopenia grade 2+3 was found to be a predictor of clinical relapses (HR=0.970; 95% C.I.=0.936-1.005; p=0.095 for age; HR=0.115; 95% C.I.=0.016-0.854; p=0.034 for lymphopenia grade 2+3), with a protective effect.
older age and lower basal lymphocyte count were found to be associated with lymphopenia development. Lymphopenia grade 2+3 and older age could be protective against clinical and radiologic disease activity during DMF treatment.
缓释富马酸二甲酯（DMF）是一种用于复发缓解型多发性硬化症（MS）的疾病改善疗法，具有抗氧化和抗炎特性。该药物会导致淋巴细胞计数减少，这可能在治疗期间引发淋巴细胞减少症。由于存在感染风险，主要是进行性多灶性白质脑病（PML），这是一个重要的安全问题。淋巴细胞计数是否会影响治疗反应仍存在争议，因为文献中有相互矛盾的数据。考虑到这一点，我们旨在确定DMF诱导的淋巴细胞减少症的危险因素，并在现实环境中评估淋巴细胞减少症对MS疾病活动的影响。
对135例接受DMF治疗的MS患者进行了一项回顾性研究，平均治疗时间为32.3±15.9个月。收集了基线和随访时的人口统计学、临床、磁共振成像（MRI）和实验室数据。
44例患者（32.6%）出现淋巴细胞减少症，其中11例（8.1%）为1级，23例（17.0%）为2级，10例（7.4%）为3级。在二元回归模型中发现，年龄较大和基础绝对淋巴细胞计数较低与淋巴细胞减少症的发生相关（p<0.001和p=0.009）。与非淋巴细胞减少症+1级淋巴细胞减少症患者相比，2+3级淋巴细胞减少症患者的无疾病活动生存期更长（p<0.001），临床复发次数更少（p=0.005），MRI疾病活动度更低（p≤0.001）。在Cox回归模型中，年龄较大和2+3级淋巴细胞减少症被发现是预防疾病活动的保护因素（年龄的HR=0.966；95%置信区间=0.942-0.992；p=0.009；2+3级淋巴细胞减少症的HR=0.137；95%置信区间=0.043-0.439；p=0.001）以及MRI疾病活动（年龄的HR=0.968；95%置信区间=0.941-0.997；p=0.030；2+3级淋巴细胞减少症的HR=0.142；95%置信区间=0.034-0.591；p=0.007）。仅2+3级淋巴细胞减少症被发现是临床复发的预测因素（年龄的HR=0.970；95%置信区间=0.936-1.005；p=0.095；2+3级淋巴细胞减少症的HR=0.115；95%置信区间=0.016-0.854；p=0.034），具有保护作用。
发现年龄较大和基础淋巴细胞计数较低与淋巴细胞减少症的发生相关。2+3级淋巴细胞减少症和年龄较大可能对DMF治疗期间的临床和放射学疾病活动具有保护作用。
