Department of Neurology, Neuroscience Campus Amsterdam, VUmc MS Center Amsterdam, VU University Medical Center Amsterdam, Amsterdam, The Netherlands.
Department of Radiology & Nuclear Medicine, Neuroscience Campus Amsterdam, VUmc MS Center Amsterdam, VU University Medical Center Amsterdam, Amsterdam, The Netherlands.
Mult Scler. 2017 Jun;23(7):995-999. doi: 10.1177/1352458516684023. Epub 2016 Dec 13.
In recent years, a small but increasing number of neurologists choose to extend dose intervals of natalizumab with the aim of reducing the risk of progressive multifocal leukoencephalopathy (PML). This idea is based on the hypothesis that high drug concentrations increase the risk of PML.
We investigated the relation between longitudinal natalizumab concentrations in patients who developed PML and patients who did not develop PML.
In a prospective observational cohort study of 219 patients with relapsing-remitting multiple sclerosis treated with natalizumab, serum samples were taken every 12 weeks prior to natalizumab infusion. In this cohort, 5 patients developed PML and were matched with 10 patients from the cohort who did not develop PML. Natalizumab concentrations were measured in available samples, and the longitudinal results were compared between the two patient groups.
Mean natalizumab concentrations in the five patients developing PML was 18.9 µg/mL (standard deviation (SD): ±13.4) versus 23.8 µg/mL (SD: ±11.5) of the control patients. Furthermore, we did not observe a clear rise in concentration levels in patients subsequently developing PML.
Our results provide preliminary evidence that contradicts the hypothesis that exposure to elevated concentrations of natalizumab is a relevant risk factor of developing PML.
近年来，越来越多的神经科医生选择延长那他珠单抗的给药间隔，以降低进行性多灶性白质脑病（PML）的风险。这一想法基于这样一种假设，即高药物浓度会增加 PML 的风险。
我们研究了发生 PML 和未发生 PML 的患者纵向纳他珠单抗浓度之间的关系。
在一项对 219 例接受那他珠单抗治疗的复发性缓解型多发性硬化症患者进行的前瞻性观察队列研究中，在纳他珠单抗输注前每 12 周采集一次血清样本。在该队列中，有 5 例患者发生 PML，与未发生 PML 的队列中的 10 例患者相匹配。测量了可用样本中的纳他珠单抗浓度，并比较了两组患者的纵向结果。
发生 PML 的 5 例患者的平均纳他珠单抗浓度为 18.9µg/ml（标准差 ±13.4），而对照组患者的浓度为 23.8µg/ml（标准差 ±11.5）。此外，我们没有观察到随后发生 PML 的患者浓度水平明显升高。
我们的结果初步提供了与假设相反的证据，即接触高浓度的那他珠单抗并不是发生 PML 的一个相关风险因素。
