Benkert Pascal, Maleska Maceski Aleksandra, Schaedelin Sabine, Oechtering Johanna, Zadic Amar, Vilchez Gomez Juan Francisco, Melie-Garcia Lester, Cagol Alessandro, Galbusera Riccardo, Subramaniam Suvitha, Lorscheider Johannes, Galli Edoardo, Mueller Jannis, Fischer-Barnicol Bettina, Achtnichts Lutz, Findling Oliver, Lalive Patrice H, Bridel Claire, Uginet Marjolaine, Müller Stefanie, Pot Caroline, Mathias Amandine, Du Pasquier Renaud, Salmen Anke, Hoepner Robert, Chan Andrew, Disanto Giulio, Zecca Chiara, D'Souza Marcus, Hemkens Lars G, Yaldizli Özgür, Derfuss Tobias, Roth Patrick, Gobbi Claudio, Brassat David, Tackenberg Björn, Pedotti Rosetta, Raposo Catarina, Oksenberg Jorge, Wiendl Heinz, Berger Klaus, Hermesdorf Marco, Piehl Fredrik, Conen David, Buser Andreas, Kappos Ludwig, Khalil Michael, Granziera Cristina, Abdelhak Ahmed, Leppert David, Willemse Eline A J, Kuhle Jens
Multiple Sclerosis Centre and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), Department of Biomedicine and Clinical Research, University Hospital and University of Basel, Basel, Switzerland.
Department of Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland.
Ann Neurol. 2024 Oct 16;97(1):104-15. doi: 10.1002/ana.27096.
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.
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.
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.
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.
研究接受B细胞清除疗法（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）事件预测未来疾病进展的能力。
纳入瑞士多发性硬化症（MS）队列中开始接受BCDT的362例pwMS患者（1480份样本）。2861名对照者（4943份样本）的sGFAP水平提供了用于计算校正Z分数的标准数据。
在一个综合模型中，1年时sGFAP水平升高（Z分数>1）与PIRA的较高风险相关（风险比[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）。独立于PIRA事件，sGFAP水平在每10年的随访中纵向增加0.49个Z分数单位（估计值，0.49[0.29，0.69]，p<0.0001）。在经历PIRA的患者中，sGFAP Z分数比病情稳定的患者高0.52个Z分数单位（0.52[0.22，0.83]，p=0.0009）。在有和没有PIRA的pwMS患者中发现了不同的sNfL Z分数轨迹（交互作用p=0.0028），在没有PIRA的情况下，每10年平均下降0.92个Z分数单位（-0.92[-1.23，-0.60]，p<0.0001），而有PIRA的患者水平保持较高。
BCDT开始后sGFAP升高和sNfL没有下降与未来PIRA风险增加相关。这些发现为在开始BCDT的pwMS患者中联合监测sNfL和sGFAP以预测PIRA风险提供了理论依据，并为在旨在影响MS进展性疾病生物学的临床试验中使用sGFAP作为结果指标提供了依据。《神经病学年鉴》2024年。
