Blood neurofilament light chain as a biomarker of MS disease activity and treatment response
Blood neurofilament light chain as a biomarker of MS disease activity and treatment response
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DOI：
10.1212/wnl.0000000000007032
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发表时间：
2019-03-05
期刊：
影响因子：
9.9
通讯作者：
Kappos, Ludwig
中科院分区：
文献类型：
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作者：
Kuhle, Jens;Kropshofer, Harald;Kappos, Ludwig
目的评价血神经细丝轻链(NFL)作为近期、持续和未来疾病活动和组织损伤的生物标志物的价值及其在监测复发-缓解型多发性硬化症治疗反应中的作用。方法检测589例复发缓解期多发性硬化症患者(Fingolimod与安慰剂、自由和干扰素-β-1a转化的3期研究)和35例健康对照的血NFL水平，并将其与临床和MRI相关结果进行比较。结果在基线状态下，患者的NFL水平(pg/m L)高于健康对照组(30.5和27.0vs16.9，p=0.0001)，并与T2病灶负荷和Gd增强T1病灶数目(p<；0.0001)相关。基线NFL水平、治疗和研究期间新的或扩大的T2病变的数量预测了研究结束时的NFL水平(均P<；0.01)。高基线水平与低基线水平相关(估计[95%可信区间])与增加的新的或扩大的T2病变的数目(比率：2.64[1.51-4.60]；p=0.0006)，复发(比率：2.53[1.67-3.83]；p<；0.0001)，脑体积损失(平均值差异：-0.78%[-1.02to-0.54]；p<；0.0001)和确认残疾恶化的风险(危险比：1.94[0.97-3.87]；p=0.0605)。Fingolimod在6个月时就显著降低了NFL水平(vs.安慰剂组0.73[0.656-0.813]和干扰素0.789[0.704-0.884])，一直持续到研究结束(vs.安慰剂0.628[0.552-0.714]和干扰素0.794[0.705-0.894]；p<；0.001，这两项研究在所有评估中都是如此)。结论血NFL水平与疾病活动性和神经轴突损害的临床和MRI相关指标相关，并具有预后价值。我们的结果支持血液NFL作为一种容易获得的疾病演变和治疗反应的生物标志物的用途。
Objective To assess the value of blood neurofilament light chain (NfL) as a biomarker of recent, ongoing, and future disease activity and tissue damage and its utility to monitor treatment response in relapsing-remitting multiple sclerosis. Methods We measured NfL in blood samples from 589 patients with relapsing-remitting multiple sclerosis (from phase 3 studies of fingolimod vs placebo, FREEDOMS and interferon [IFN]-beta-1a, TRANSFORMS) and 35 healthy controls and compared NfL levels with clinical and MRI-related outcomes. Results At baseline, NfL levels (pg/mL) were higher in patients than in healthy controls (30.5 and 27.0 vs 16.9, p = 0.0001) and correlated with T2 lesion load and number of gadolinium-enhancing T1 lesions (p < 0.0001, both). Baseline NfL levels, treatment, and number of new or enlarging T2 lesions during the studies predicted NfL levels at the end of study (all p < 0.01). High vs low baseline NfL levels were associated (estimate [95% confidence interval]) with an increased number of new or enlarging T2 lesions (ratio of mean: 2.64 [1.51-4.60]; p = 0.0006), relapses (rate ratio: 2.53 [1.67-3.83]; p < 0.0001), brain volume loss (difference in means: -0.78% [-1.02 to -0.54]; p < 0.0001), and risk of confirmed disability worsening (hazard ratio: 1.94 [0.97-3.87]; p = 0.0605). Fingolimod significantly reduced NfL levels already at 6 months (vs placebo 0.73 [0.656-0.813] and IFN 0.789 [0.704-0.884]), which was sustained until the end of the studies (vs placebo 0.628 [0.552-0.714] and IFN 0.794 [0.705-0.894]; p < 0.001, both studies at all assessments). Conclusions Blood NfL levels are associated with clinical and MRI-related measures of disease activity and neuroaxonal damage and have prognostic value. Our results support the utility of blood NfL as an easily accessible biomarker of disease evolution and treatment response.