Effect of Cumulative Exposure to Ocrelizumab on Memory B-Cell Repopulation Dynamics in Multiple Sclerosis.

IF 8.1 1区医学 Q1 CLINICAL NEUROLOGY

Annals of Neurology Pub Date : 2025-06-11 DOI:10.1002/ana.27281

Giulio Disanto, Rosaria Sacco, Giulia Mallucci, Chiara Zecca, Claudio Gobbi

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引用次数: 0

Abstract

Objective: Extended interval dosing protocols of B-cell-depleting therapies in multiple sclerosis (MS) are being developed, but intervals between infusions are often arbitrary. We describe total and memory B-cell repopulation dynamics in MS patients on a memory B-cell-guided extended interval dosing ocrelizumab (OCR) protocol.

Methods: OCR was administered on peripheral CD19+ CD27+ memory B-cell repopulation (≥1 cell/μL), monitored using fluorescence-activated cell sorting. Associations with CD19+ B cells and CD19+ CD27+ memory B cells were tested using mixed-effect hurdle models, with rate ratios (RR) predicting cell counts and odds ratios (OR) predicting cell depletion.

Results: We collected 1,369 samples from 101 patients, 61.4% women, aged 42.2 years (IQR 32.3-51.1 years) and follow up 4.1 years (IQR 2.9-5.2 years). The median time between samples and previous OCR infusion was 6.6 months (IQR 4.7-8.8 months). Time since previous OCR infusion was positively associated with CD19+ B cells (RR = 1.11, 95% CI 1.10-1.11, p < 0.001) and CD19+ CD27+ memory B-cell counts (RR = 1.11, 95% CI 1.09-1.13, p < 0.001). A greater cumulative OCR dose was associated with persistent CD19+ CD27+ memory B-cell depletion (OR 1.90, 1.57-2.31, p < 0.001). CD19+ B-cell repopulation was inversely associated with age (RR = 0.82, 95% CI 0.71-0.95, p = 0.010). Female patients showed a lower ratio of CD19+ CD27+ memory B cells/total CD19+ B cells (RR = 0.42, 95% CI 0.26-0.69, p = 0.001). Disease activity was low, with most radiological activity observed within the first year of OCR treatment.

Interpretation: Memory B-cell repopulation becomes slower with increasing cumulative OCR dose. Age- and sex-related mechanisms probably influence repopulation dynamics. Given the evidence for a pathogenic role of memory B cells, these observations could be considered when planning extended interval dosing strategies of OCR treatment. ANN NEUROL 2025.

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Ocrelizumab对多发性硬化症患者记忆性b细胞再生动力学的影响。

目的：b细胞消耗治疗多发性硬化症（MS）的延长间隔给药方案正在开发中，但输注之间的间隔通常是任意的。我们描述了MS患者在记忆b细胞引导下延长间隔给药ocrelizumab （OCR）方案中的总b细胞和记忆b细胞再生动力学。方法：外周CD19+ CD27+记忆b细胞再生（≥1个/μL）给予OCR，荧光活化细胞分选监测。使用混合效应障碍模型测试与CD19+ B细胞和CD19+ CD27+记忆B细胞的关联，比率比（RR）预测细胞计数，比值比（OR）预测细胞消耗。结果：共收集101例患者1,369份样本，其中61.4%为女性，年龄42.2岁（IQR 32.3-51.1岁），随访4.1年（IQR 2.9-5.2年）。样本与先前OCR输注之间的中位时间为6.6个月（IQR 4.7-8.8个月）。自上次OCR输注后的时间与CD19+ B细胞呈正相关（RR = 1.11, 95% CI 1.10-1.11, p）解释：随着OCR累积剂量的增加，记忆B细胞的再生速度变慢。年龄和性别相关的机制可能会影响种群的动态。鉴于记忆B细胞致病作用的证据，在计划延长OCR治疗间隔剂量策略时，可以考虑这些观察结果。Ann neurol 2025。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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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.