Department of Molecular Medicine and Medical Biotechnology, Federico II University of Naples, Naples, Italy.
Multiple Sclerosis Unit, Policlinico Federico II University Hospital, Via Sergio Pansini 5, 80131, Naples, Italy.
J Neurol. 2024 Aug;271(8):5012-5024. doi: 10.1007/s00415-024-12434-w. Epub 2024 May 23.
The wearing-off phenomenon is common in people with multiple sclerosis (MS) treated with ocrelizumab. We aim to evaluate the presence and severity of wearing-off to ocrelizumab in relation to demographic and MS clinical variables, immune profiling, and a marker of neuroaxonal damage (plasma neurofilament light chain (pNfl)).
This cross-sectional study included MS patients treated with ocrelizumab from at least 1 year. Wearing-off questionnaire and blood samples were collected between 21 and 23 weeks after the previous ocrelizumab infusion. Lymphocyte subpopulations were evaluated on peripheral blood using flow cytometry. PNfl was evaluated using fully automated chemiluminescent enzyme immunoassay.
We included 106 people with MS (age 49.5 ± 11.6 years; females 42.3%; wearing-off 57.6%). On regression models, wearing-off was associated with higher pNfl, CD8, CD3, and CD3CD27 lymphocytes. Most frequent wearing-off symptoms were cognitive, sensory, and balance problems; wearing-off started < 1 week (9.4%), 1-4 weeks (10.7%) or > 4 weeks (10.7%) before infusion; 44.8% of the complaints were moderate to severe. Severity of wearing-off was associated with higher pNfl and CD8 lymphocytes.
Wearing-off is common in people with MS treated with ocrelizumab, and is associated with reduced immunomodulation (higher T lymphocytes) and increased neuroaxonal damage, suggesting reduced treatment response.
奥瑞珠单抗治疗多发性硬化症（MS）患者中常出现“失效现象”。本研究旨在评估奥瑞珠单抗失效的发生及严重程度与人口统计学和 MS 临床变量、免疫特征以及神经轴突损伤标志物（血浆神经丝轻链（pNfl））之间的关系。
这是一项横断面研究，纳入了至少接受过 1 年奥瑞珠单抗治疗的 MS 患者。在末次奥瑞珠单抗输注后 21-23 周收集失效问卷和血液样本。采用流式细胞术评估外周血淋巴细胞亚群。使用全自动化学发光酶免疫分析法评估 pNfl。
共纳入 106 例 MS 患者（年龄 49.5±11.6 岁；女性占 42.3%；失效者占 57.6%）。回归模型显示，失效与较高的 pNfl、CD8、CD3 和 CD3CD27 淋巴细胞有关。最常见的失效症状为认知、感觉和平衡问题；失效开始于输注前<1 周（9.4%）、1-4 周（10.7%）或>4 周（10.7%）；44.8%的患者报告的症状为中重度。失效的严重程度与较高的 pNfl 和 CD8 淋巴细胞有关。
奥瑞珠单抗治疗的 MS 患者中常出现失效现象，与免疫调节减弱（T 淋巴细胞增加）和神经轴突损伤增加有关，提示治疗反应降低。
