From the Department of Medicine Solna, Clinical Epidemiology Division (B.D.), The Karolinska Neuroimmunology & Multiple Sclerosis Centre, Department of Clinical Neuroscience (A.M., I.K., T.O., F.P.), and Institute of Environmental Medicine (L.A.), Karolinska Institutet; Centre for Molecular Medicine (A.M., I.K., T.O., F.P.), Karolinska University Hospital, Stockholm, Sweden; Neurologic Clinic and Policlinic, Departments of Medicine, Biomedicine, and Clinical Research (C.B., Z.M., L.K., D.L., J.K.), and Clinical Trial Unit, Department of Clinical Research (P.B.), University Hospital Basel, University of Basel, Switzerland; Sanofi Genzyme (J.A.T.), Stockholm, Sweden; Biogen (T.P., B.C.K.), Cambridge, MA; Department of Neurology, Medical Faculty (B.C.K.), Heinrich-Heine University, Duesseldorf, Germany; and Institution of Neuroscience and Physiology (J.L.), Sahlgrenska Academy, University of Gothenburg, Sweden.
Neurology. 2020 Mar 17;94(11):e1201-e1212. doi: 10.1212/WNL.0000000000009097. Epub 2020 Feb 11.
To determine factors (including the role of specific disease modulatory treatments [DMTs]) associated with (1) baseline, (2) on-treatment, and (3) change (from treatment start to on-treatment assessment) in plasma neurofilament light chain (pNfL) concentrations in relapsing-remitting multiple sclerosis (RRMS).
Data including blood samples analyses and long-term clinical follow-up information for 1,261 Swedish patients with RRMS starting novel DMTs were analyzed using linear regressions to model pNfL and changes in pNfL concentrations as a function of clinical variables and DMTs (alemtuzumab, dimethyl fumarate, fingolimod, natalizumab, rituximab, and teriflunomide).
The baseline pNfL concentration was positively associated with relapse rate, Expanded Disability Status Scale score, Age-Related MS Severity Score, and MS Impact Score (MSIS-29), and negatively associated with Symbol Digit Modalities Test performance and the number of previously used DMTs. All analyses, which used inverse propensity score weighting to correct for differences in baseline factors at DMT start, highlighted that both the reduction in pNfL concentration from baseline to on-treatment measurement and the on-treatment pNfL level differed across DMTs. Patients starting alemtuzumab displayed the highest reduction in pNfL concentration and lowest on-treatment pNfL concentrations, while those starting teriflunomide had the smallest decrease and highest on-treatment levels, but also starting from lower values. Both on-treatment pNfL and decrease in pNfL concentrations were highly dependent on baseline concentrations.
Choice of DMT in RRMS is significantly associated with degree of reduction in pNfL, which supports a role for pNfL as a drug response marker.
确定与（1）基线、（2）治疗期间和（3）变化（从治疗开始到治疗期间评估）相关的因素（包括特定疾病调节治疗[DMT]的作用），这些因素与复发缓解型多发性硬化症（RRMS）患者的血浆神经丝轻链（pNfL）浓度有关。
使用线性回归分析对 1261 名开始使用新型 DMT 的瑞典 RRMS 患者的血液样本分析和长期临床随访信息进行分析，以将 pNfL 及其浓度变化作为临床变量和 DMT（阿仑单抗、二甲基富马酸、芬戈利莫德、那他珠单抗、利妥昔单抗和特立氟胺）的函数进行建模。
基线 pNfL 浓度与复发率、扩展残疾状态量表评分、年龄相关多发性硬化症严重程度评分和多发性硬化症影响评分（MSIS-29）呈正相关，与符号数字模态测试表现和之前使用的 DMT 数量呈负相关。所有分析均使用逆倾向评分加权来校正 DMT 开始时基线因素的差异，突出显示从基线到治疗期间测量的 pNfL 浓度降低以及治疗期间的 pNfL 水平在 DMT 之间均有所不同。开始使用阿仑单抗的患者的 pNfL 浓度降低最大，治疗期间的 pNfL 浓度最低，而开始使用特立氟胺的患者的下降最小，治疗期间的 pNfL 浓度最高，但起始值也较低。治疗期间的 pNfL 和 pNfL 浓度降低均高度依赖于基线浓度。
RRMS 中 DMT 的选择与 pNfL 的降低程度显著相关，这支持 pNfL 作为药物反应标志物的作用。
Zotero 插件
