Masanneck Lars, Rolfes Leoni, Regner-Nelke Liesa, Willison Alice, Räuber Saskia, Steffen Falk, Bittner Stefan, Zipp Frauke, Albrecht Philipp, Ruck Tobias, Hartung Hans-Peter, Meuth Sven G, Pawlitzki Marc
Department of Neurology, Medical Faculty University Hospital Düsseldorf, Düsseldorf, Germany; Hasso Plattner Institute, University of Potsdam, 14482 Potsdam, Germany.
Department of Neurology, Medical Faculty University Hospital Düsseldorf, Düsseldorf, Germany.
Mult Scler Relat Disord. 2022 Jul;63:103927. doi: 10.1016/j.msard.2022.103927. Epub 2022 May 28.
The current range of disease-modifying treatments (DMTs) for relapsing-remitting multiple sclerosis (RRMS) has placed more importance on the accurate monitoring of disease progression for timely and appropriate treatment decisions. With a rising number of measurements for disease progression, it is currently unclear how well these measurements or combinations of them can monitor more mildly affected RRMS patients.
To investigate several composite measures for monitoring disease activity and their potential relation to the biomarker neurofilament light chain (NfL) in a clearly defined early RRMS patient cohort with a milder disease course.
From a total of 301 RRMS patients, a subset of 46 patients being treated with a continuous first-line therapy was analyzed for loss of no evidence of disease activity (lo-NEDA-3) status, relapse-associated worsening (RAW) and progression independent of relapse activity (PIRA), up to seven years after treatment initialization. Kaplan-Meier estimates were used for time-to-event analysis. Additionally, a Cox regression model was used to analyze the effect of NfL levels on outcome measures in this cohort.
In this mildly affected cohort, both lo-NEDA-3 and PIRA frequently occurred over a median observational period of 67.2 months and were observed in 39 (84.8%) and 23 (50.0%) patients, respectively. Additionally, 12 out of 26 PIRA manifestations (46.2%) were observed without a corresponding lo-NEDA-3 status. Jointly, either PIRA or lo-NEDA-3 showed disease activity in all patients followed-up for at least the median duration (67.2 months). NfL values demonstrated an association with the occurrence of relapses and RAW.
The complementary use of different disease progression measures helps mirror ongoing disease activity in mildly affected early RRMS patients being treated with continuous first-line therapy.
目前用于复发缓解型多发性硬化症(RRMS)的疾病修饰治疗(DMTs)范围使得准确监测疾病进展对于及时做出恰当的治疗决策变得更加重要。随着用于疾病进展的测量数量不断增加,目前尚不清楚这些测量或它们的组合对病情较轻的RRMS患者的监测效果如何。
在病程较轻的明确早期RRMS患者队列中,研究几种监测疾病活动的综合指标及其与生物标志物神经丝轻链(NfL)的潜在关系。
在总共301例RRMS患者中,分析了46例接受连续一线治疗的患者子集,直至治疗开始后七年的无疾病活动证据丢失(lo-NEDA-3)状态、复发相关恶化(RAW)和与复发活动无关的进展(PIRA)情况。采用Kaplan-Meier估计进行事件发生时间分析。此外,使用Cox回归模型分析该队列中NfL水平对结局指标的影响。
在这个病情较轻的队列中,在中位观察期67.2个月内,lo-NEDA-3和PIRA均频繁出现,分别在39例(84.8%)和23例(50.0%)患者中观察到。此外,在26例PIRA表现中有12例(46.2%)在没有相应lo-NEDA-3状态的情况下被观察到。联合起来,PIRA或lo-NEDA-3在所有随访至少中位持续时间(67.2个月)的患者中均显示出疾病活动。NfL值与复发和RAW的发生相关。
不同疾病进展指标的互补使用有助于反映接受连续一线治疗的病情较轻的早期RRMS患者正在进行的疾病活动。