Serum Glial Fibrillary Acidic Protein and Neurofilament Light Chain Levels Reflect Different Mechanisms of Disease Progression under B-Cell Depleting Treatment in Multiple Sclerosis.

IF 8.1 1区医学 Q1 CLINICAL NEUROLOGY

Annals of Neurology Pub Date : 2024-10-16 DOI:10.1002/ana.27096

Pascal Benkert, Aleksandra Maleska Maceski, Sabine Schaedelin, Johanna Oechtering, Amar Zadic, Juan Francisco Vilchez Gomez, Lester Melie-Garcia, Alessandro Cagol, Riccardo Galbusera, Suvitha Subramaniam, Johannes Lorscheider, Edoardo Galli, Jannis Mueller, Bettina Fischer-Barnicol, Lutz Achtnichts, Oliver Findling, Patrice H Lalive, Claire Bridel, Marjolaine Uginet, Stefanie Müller, Caroline Pot, Amandine Mathias, Renaud Du Pasquier, Anke Salmen, Robert Hoepner, Andrew Chan, Giulio Disanto, Chiara Zecca, Marcus D'Souza, Lars G Hemkens, Özgür Yaldizli, Tobias Derfuss, Patrick Roth, Claudio Gobbi, David Brassat, Björn Tackenberg, Rosetta Pedotti, Catarina Raposo, Jorge Oksenberg, Heinz Wiendl, Klaus Berger, Marco Hermesdorf, Fredrik Piehl, David Conen, Andreas Buser, Ludwig Kappos, Michael Khalil, Cristina Granziera, Ahmed Abdelhak, David Leppert, Eline A J Willemse, Jens Kuhle

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引用次数: 0

Abstract

Objective: To investigate the longitudinal dynamics of serum glial fibrillary acidic protein (sGFAP) and serum neurofilament light chain (sNfL) levels in people with multiple sclerosis (pwMS) under B-cell depleting therapy (BCDT) and their capacity to prognosticate future progression independent of relapse activity (PIRA) events.

Methods: A total of 362 pwMS (1,480 samples) starting BCDT in the Swiss Multiple Sclerosis (MS) Cohort were included. sGFAP levels in 2,861 control persons (4,943 samples) provided normative data to calculate adjusted Z scores.

Results: Elevated sGFAP levels (Z score >1) at 1 year were associated with a higher hazard for PIRA (hazard ratio [HR]: 1.80 [95% CI: 1.17-2.78]; p = 0.0079) than elevated sNfL levels (HR, 1.45 [0.95-2.24], p = 0.0886) in a combined model. Independent of PIRA events, sGFAP levels longitudinally increased by 0.49 Z score units per 10 years follow-up (estimate, 0.49 [0.29, 0.69], p < 0.0001). In patients experiencing PIRA, sGFAP Z scores were 0.52 Z score units higher versus stable patients (0.52 [0.22, 0.83], p = 0.0009). Different sNfL Z score trajectories were found in pwMS with versus without PIRA (interaction p = 0.0028), with an average decrease of 0.92 Z score units per 10 years observed without PIRA (-0.92 [-1.23, -0.60], p < 0.0001), whereas levels in patients with PIRA remained high.

Interpretation: Elevated sGFAP and lack of drop in sNfL after BCDT start are associated with increased risk of future PIRA. These findings provide a rationale for combined monitoring of sNfL and sGFAP in pwMS starting BCDT to predict the risk of PIRA, and to use sGFAP as an outcome in clinical trials aiming to impact on MS progressive disease biology. ANN NEUROL 2024.

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血清胶质纤维酸性蛋白和神经丝蛋白轻链水平反映多发性硬化症患者在B细胞耗竭治疗下疾病进展的不同机制

目的研究接受 B 细胞耗竭疗法（BCDT）的多发性硬化症患者（pwMS）血清胶质纤维酸性蛋白（sGFAP）和血清神经丝轻链（sNfL）水平的纵向动态变化，以及它们独立于复发活动（PIRA）事件预示未来进展的能力：方法：纳入瑞士多发性硬化（MS）队列中开始接受BCDT治疗的362名pwMS（1,480个样本）。2,861名对照者（4,943个样本）的sGFAP水平为计算调整后Z评分提供了标准数据：在综合模型中，1 年后 sGFAP 水平升高（Z 评分 >1）与 PIRA 的相关性（危险比 [HR]：1.80 [95% CI：1.17-2.78]；p = 0.0079）高于 sNfL 水平升高（HR：1.45 [0.95-2.24]；p = 0.0886）。与 PIRA 事件无关，sGFAP 水平每随访 10 年纵向增加 0.49 个 Z 评分单位（估计值，0.49 [0.29，0.69]，p 解释：BCDT 开始后，sGFAP 升高和 sNfL 未下降与未来 PIRA 风险增加有关。这些发现为在开始使用 BCDT 的患者中联合监测 sNfL 和 sGFAP 以预测 PIRA 风险提供了依据，也为在旨在影响 MS 进展性疾病生物学的临床试验中使用 sGFAP 作为结果提供了依据。ann neurol 2024。

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来源期刊

Annals of Neurology 医学-临床神经学

CiteScore

18.00

自引率

1.80%

发文量

270

审稿时长

3-8 weeks

期刊介绍： Annals of Neurology publishes original articles with potential for high impact in understanding the pathogenesis, clinical and laboratory features, diagnosis, treatment, outcomes and science underlying diseases of the human nervous system. Articles should ideally be of broad interest to the academic neurological community rather than solely to subspecialists in a particular field. Studies involving experimental model system, including those in cell and organ cultures and animals, of direct translational relevance to the understanding of neurological disease are also encouraged.