Hellgren Johan, Ahlström Isabella, Strandberg Maria Compagno, Jonsson Magnus Förnvik, Hansson Oskar, Janelidze Shorena, Svenningsson Anders, Källén Kristina
Clinical Sciences Helsingborg Unit, Department of Clinical Sciences Lund, Lund University, Lund, Sweden; Neurology Section, Department of Specialised Medicine, Helsingborg General Hospital, Helsingborg, Sweden.
Clinical Sciences Helsingborg Unit, Department of Clinical Sciences Lund, Lund University, Lund, Sweden.
Mult Scler Relat Disord. 2025 Jul;99:106479. doi: 10.1016/j.msard.2025.106479. Epub 2025 Apr 30.
Patients with relapsing remitting multiple sclerosis (RRMS) treated with the high-efficacy drugs natalizumab (NTZ) or rituximab (RTX) generally show no evidence of disease activity. Currently, there is no head-to-head comparison between NTZ and RTX of neurodegenerative and neuroinflammatory biomarkers in cerebrospinal fluid (CSF).
To compare CSF biomarkers in a stable RRMS cohort treated with NTZ or RTX. A secondary objective was to explore potential associations between CSF biomarkers, fatigue, and cognition.
This Swedish multicentre cross-sectional study assessed kappa-free light chain (k-FLC) index, oligoclonal bands (OCBs), glial fibrillary acidic protein (GFAP) and neurofilament light (NfL) in CSF of 30 RRMS patients on NTZ or RTX for at least 24 months. A longitudinal comparison of biomarkers was performed for IgG Indices. Fatigue and cognition outcomes were explored in relation to CSF biomarkers.
GFAP level was significantly higher in the NTZ group compared to RTX (mean difference (CI): 2 716 (155; 5278) ng/L, p=0.047). NfL concentration did not differ between the groups. OCBs and k-FLC index were present and elevated in 97 % and 87 % of participants, respectively. IgG-index was significantly reduced only for NTZ. No significant associations were found between fatigue, cognition and the biomarkers.
Our results support that intrathecal inflammatory activity is still ongoing in patients with NTZ and RTX. Cross-sectional GFAP might indicate a lower risk for long-term disability in the RTX group. Our data should be interpreted with caution because of small sample size, making it difficult to control for multiple confounders.
接受高效药物那他珠单抗（NTZ）或利妥昔单抗（RTX）治疗的复发缓解型多发性硬化症（RRMS）患者通常无疾病活动迹象。目前，脑脊液（CSF）中神经退行性和神经炎症生物标志物在NTZ和RTX之间尚无直接比较。
比较接受NTZ或RTX治疗的稳定RRMS队列中的脑脊液生物标志物。次要目的是探讨脑脊液生物标志物、疲劳和认知之间的潜在关联。
这项瑞典多中心横断面研究评估了30例接受NTZ或RTX治疗至少24个月的RRMS患者脑脊液中的游离κ轻链（k-FLC）指数、寡克隆带（OCB）、胶质纤维酸性蛋白（GFAP）和神经丝轻链（NfL）。对IgG指数进行生物标志物的纵向比较。探讨了与脑脊液生物标志物相关的疲劳和认知结果。
与RTX组相比，NTZ组的GFAP水平显著更高（平均差异（CI）：2716（155；5278）ng/L，p = 0.047）。两组之间的NfL浓度无差异。分别有97%和87%的参与者存在并升高了OCB和k-FLC指数。仅NTZ的IgG指数显著降低。未发现疲劳、认知与生物标志物之间存在显著关联。
我们的结果支持，接受NTZ和RTX治疗的患者鞘内炎症活动仍在持续。横断面GFAP可能表明RTX组长期残疾风险较低。由于样本量小，难以控制多个混杂因素，我们的数据应谨慎解释。
