奥瑞珠单抗治疗多发性硬化症患者中先前疾病修饰药物暴露对 T 淋巴细胞动态的影响。
Influence of Previous Disease-Modifying Drug Exposure on T-Lymphocyte Dynamic in Patients With Multiple Sclerosis Treated With Ocrelizumab.
机构信息
From the Multiple Sclerosis Research and Clinical Unit (D.L., A.G., G.C., C.G.N., G.M., G.A.M.); Department of Systems Medicine (D.L., G.C., C.G.N., G.M., D.C., G.A.M.), Tor Vergata University, Rome; Department of Health Sciences (DISSAL) (F. Bovis, M.P.), University of Genoa; Unit of Neurology and Neurorehabilitation (R.F., F. Buttari, D.C., G.A.M.), IRCCS Neuromed, Pozzilli; Multiple Sclerosis Center (E.S., G.L.), Second Division of Neurology, Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Naples; Multiple Sclerosis Center (M.L., M.M.), Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Rome; Università Cattolica Del Sacro Cuore (M.L., M.M.), CERSM, Rome; Department of Neuroscience (M.C., M.I.), Rehabilitation, Maternal and Child Health (DINOGMI), University of Genoa; and IRCCS Ospedale Policlinico San Martino (M.I.), Genoa, Italy.
出版信息
Neurol Neuroimmunol Neuroinflamm. 2022 Mar 10;9(3). doi: 10.1212/NXI.0000000000001157. Print 2022 May.
BACKGROUND AND OBJECTIVES
To investigate the longitudinal dynamic of lymphocyte subsets during treatment with ocrelizumab (OCR) in patients with multiple sclerosis (PwMS).
METHODS
A multicenter retrospective study was conducted in 161 PwMS starting treatment with OCR grouped in naive (naive, n = 40), switching from fingolimod (FTY, n = 52), and switching from other immunomodulating drugs (other, n = 69). Mean lymphocyte subset (total, CD3, CD4, CD8, CD20, and natural killer) counts were analyzed at baseline, 6 months, and 12 months. Rate of lymphocytopenia for each subset was calculated at all time points in all groups.
RESULTS
Mean total, CD3, and CD4 counts were significantly different among groups ( < 0.001) at all time points, whereas CD8 and CD20 counts only at baseline ( = 0.0157; < 0.001), consistently lower in FTY. After adjustment for baseline values, interaction time*group was not statistically significant ( > 0.05 for each subset). The odds of lymphopenia were significantly higher among FTY patients compared with naive for total, CD3, CD4, and CD20 cells at baseline, for total and CD4 cells at the sixth month, and for total cells at the 12th month.
DISCUSSION
OCR per se exerts a modest depleting effect on T cells that seems rather due to a carryover phenomenon of previous therapies, particularly FTY. These data may help in the overall evaluation of the risk/benefit profile of treatment sequencing.
背景与目的
研究奥瑞珠单抗（OCR）治疗多发性硬化症（PwMS）患者过程中淋巴细胞亚群的纵向动态变化。
方法
在一项多中心回顾性研究中，纳入了 161 名开始接受 OCR 治疗的 PwMS，根据初始治疗方案分为初治组（naive，n=40）、从芬戈莫德（FTY）转换组（n=52）和从其他免疫调节药物转换组（other，n=69）。分析基线、6 个月和 12 个月时所有患者的淋巴细胞亚群（总计数、CD3、CD4、CD8、CD20 和自然杀伤细胞）计数。在所有组的所有时间点，计算每个亚群的淋巴细胞减少发生率。
结果
在所有时间点，各组间总计数、CD3 和 CD4 计数均存在显著差异（<0.001），而仅在基线时 CD8 和 CD20 计数存在差异（=0.0157；<0.001），FTY 组的计数较低。在调整基线值后，时间*组间交互作用无统计学意义（各亚群均>0.05）。与初治组相比，FTY 组患者在基线时的总计数、CD3、CD4 和 CD20 细胞、第 6 个月时的总计数和 CD4 细胞、第 12 个月时的总计数发生淋巴细胞减少的可能性显著更高。
讨论
OCR 本身对 T 细胞具有适度的耗竭作用，这似乎主要是由于先前治疗的延续现象，特别是 FTY。这些数据可能有助于全面评估治疗序贯的风险/获益特征。
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