Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden.
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Acta Neurol Scand. 2019 May;139(5):462-468. doi: 10.1111/ane.13078. Epub 2019 Mar 5.
The main objective of this study was to evaluate the axonal component neurofilament light protein (NFL) in plasma and cerebrospinal fluid (CSF) as an outcome measure in a clinical trial on disease-modifying treatments in multiple sclerosis.
Seventy-five patients with clinically stable relapsing-remitting multiple sclerosis (RRMS) participating in the clinical trial "Switch-To RItuXimab in MS" (STRIX-MS) were switched to rituximab from first-line injectable therapy and then followed up for 2 years. Thirty patients from the extension trial (STRIX-MS extension), accepting repeated lumbar punctures, were followed up for an additional 3 years. Plasma and CSF samples were collected yearly during the follow-up. NFL concentration in plasma was measured by an in-house NF-light assay on the Simoa platform with a Homebrew kit. NFL concentration in CSF was measured by sandwich ELISA.
The mean levels of NFL, in both CSF and plasma, were low. The reduction of CSF-NFL was 25% during the first year of follow-up (from a mean of 471 [SD 393] to 354 [SD 174] pg/mL; P = 0.006) and was statistically significant. The corresponding reduction in plasma NFL was 18% (from 9.73 [SD 7.04] to 7.94 [SD 3.10] pg/mL; P = 0.055) and did not reach statistical significance.
This study indicates that NFL in plasma is less sensitive as an endpoint in group comparisons than NFL in CSF. Given that plasma NFL is far easier to access, it is a promising and awaited method but further studies are needed to optimize the use in clinical trials.
本研究的主要目的是评估血浆和脑脊液（CSF）中的轴索神经丝轻链蛋白（NFL）作为多发性硬化症（MS）疾病修饰治疗临床试验中的一种结局指标。
本研究纳入了 75 例接受临床试验“多发性硬化症 Switch-To RItuXimab”（STRIX-MS）的临床稳定的复发缓解型多发性硬化症（RRMS）患者，这些患者从一线注射治疗转换为利妥昔单抗，随后随访 2 年。在扩展试验（STRIX-MS 扩展）中，30 例接受重复腰椎穿刺的患者，随访时间延长至 3 年。在随访期间，每年采集血浆和 CSF 样本。血浆 NFL 浓度采用 Simoa 平台上的 Homebrew 试剂盒进行的内部 NF-light 测定进行测量。CSF-NFL 浓度采用夹心 ELISA 法进行测量。
血浆和 CSF 中 NFL 的平均水平均较低。在随访的第一年，CSF-NFL 下降了 25%（从平均 471[SD 393]pg/mL 降至 354[SD 174]pg/mL；P=0.006），具有统计学意义。相应的血浆 NFL 下降了 18%（从 9.73[SD 7.04]pg/mL 降至 7.94[SD 3.10]pg/mL；P=0.055），但未达到统计学意义。
本研究表明，与 CSF-NFL 相比，血浆 NFL 作为组间比较的终点指标敏感性较低。鉴于血浆 NFL 更容易获取，它是一种有前途且备受期待的方法，但仍需要进一步研究以优化其在临床试验中的应用。
