进行性多灶性白质脑病继发于芬戈莫德治疗后。
Progressive multifocal leukoencephalopathy after fingolimod treatment.
机构信息
From the Department of Neurology (J.R.B.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; Multiple Sclerosis Centre (B.A.C.), University of California, San Francisco; University of Texas Southwestern Medical Center (B.G.), Multiple Sclerosis Program, Dallas, TX; Department of Neurology (B.H.), Klinikum Rechts der Isar, Technical University of Munich; Munich Cluster for Systems Neurology (SyNergy) (B.H.), Munich, Germany; Infectious Diseases Division (B.J.W.), Research Institute of the McGill University Health Centre, Montreal, Canada; Novartis Pharmaceuticals Corporation (V.M.D.), East Hanover, NJ; and Novartis Pharma AG (M.M.), Basel, Switzerland.
出版信息
Neurology. 2018 May 15;90(20):e1815-e1821. doi: 10.1212/WNL.0000000000005529. Epub 2018 Apr 18.
OBJECTIVE
We describe the characteristics of the 15 patients with fingolimod-associated progressive multifocal leukoencephalopathy (PML) identified from the Novartis data safety base and provide risk estimates for the disorder.
METHODS
The Novartis safety database was searched for PML cases with a data lock point of August 31, 2017. PML classification was based on previously published criteria. The risk and incidence were estimated using the 15 patients with confirmed PML and the overall population of patients treated with fingolimod.
RESULTS
As of August 31, 2017, 15 fingolimod-treated patients had developed PML in the absence of natalizumab treatment in the preceding 6 months. Eleven (73%) were women and the mean age was 53 years (median: 53 years). Fourteen of the 15 patients were treated with fingolimod for >2 years. Two patients had confounding medical conditions. Two patients had natalizumab treatment. This included one patient whose last dose of natalizumab was 3 years and 9 months before the diagnosis of PML. The second patient was receiving fingolimod for 4 years and 6 months, which was discontinued to start natalizumab and was diagnosed with PML 3 months after starting natalizumab. Absolute lymphocyte counts were available for 14 of the 15 patients and none exhibited a sustained grade 4 lymphopenia (≤200 cells/μL).
CONCLUSIONS
The risk of PML with fingolimod in the absence of prior natalizumab treatment is low. The estimated risk was 0.069 per 1,000 patients (95% confidence interval: 0.039-0.114), and the estimated incidence rate was 3.12 per 100,000 patient-years (95% confidence interval: 1.75-5.15). Neither clinical manifestations nor radiographic features suggested any unique features of fingolimod-associated PML.
目的
我们描述了从诺华数据安全基础中确定的 15 例与芬戈莫德相关的进行性多灶性白质脑病（PML）患者的特征，并提供了该疾病的风险估计。
方法
搜索了诺华安全数据库，以确定截至 2017 年 8 月 31 日的 PML 病例。根据先前发表的标准对 PML 进行分类。使用 15 例确诊的 PML 患者和接受芬戈莫德治疗的总体患者人群，估计了风险和发病率。
结果
截至 2017 年 8 月 31 日，在过去 6 个月内未接受那他珠单抗治疗的情况下，15 例接受芬戈莫德治疗的患者出现 PML。11 例（73%）为女性，平均年龄为 53 岁（中位数：53 岁）。15 例患者中有 14 例接受芬戈莫德治疗时间超过 2 年。有 2 例患者存在混杂的医疗状况。有 2 例患者接受那他珠单抗治疗。其中 1 例患者最后一次使用那他珠单抗的时间是在诊断 PML 前 3 年零 9 个月，另 1 例患者接受芬戈莫德治疗 4 年零 6 个月，因停用芬戈莫德开始使用那他珠单抗，并在开始使用那他珠单抗后 3 个月诊断为 PML。对 15 例患者中的 14 例进行了绝对淋巴细胞计数检查，没有 1 例患者持续出现 4 级淋巴细胞减少症（≤200 个细胞/μL）。
结论
在没有先前接受那他珠单抗治疗的情况下，芬戈莫德引起 PML 的风险较低。估计风险为每 1000 例患者 0.069 例（95%置信区间：0.039-0.114），估计发病率为每 100000 患者年 3.12 例（95%置信区间：1.75-5.15）。临床表现和影像学特征均未提示芬戈莫德相关 PML 具有任何独特特征。
Zotero 插件