Individual Variability of CD19+ B-Cell Repopulation in People With Multiple Sclerosis Treated With Extended Interval Dosing of Ocrelizumab

IF 4.3 2区医学 Q1 CLINICAL NEUROLOGY

European Journal of Neurology Pub Date : 2026-07-07 DOI:10.1111/ene.70695

Laura Hogenboom, Lisa G. Schoof, Liza M. Y. Gelissen, Jop Mostert, Luuk van Rooij, Elske Hoitsma, Caspar E. P. van Munster, Jeroen van Eijk, Nienke F. Kalkers, Kirsten S. Adriani, Anke Vennegoor, Ilse M. P. Arts, Liselore Mensing, Marijke Eurelings, Koen de Gans, Oliver Gerlach, Erwin L. J. Hoogervorst, Mark E. Kloosterziel, Jolijn J. Kragt, Ruben P. Portier, Ide Smets, Björn M. van Geel, Jessica Nielsen, Christiaan M. Roosendaal, Jurgen R. Piet, Esther Zeinstra, Onno N. Groeneveld, Bob W. van Oosten, Brigit A. de Jong, Bernard M. J. Uitdehaag, Eva M. M. Strijbis, Birgit I. Lissenberg-Witte, Joep Killestein, Zoé L. E. van Kempen

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Abstract

Background and Objectives

B-cell repopulation patterns in ocrelizumab treated patients with multiple sclerosis are highly variable between individuals, but the course of B-cell reoccurrence after subsequent doses within an individual is not yet determined. Our aim was to determine the intraindividual variability of CD19+ B-cell repopulation after each ocrelizumab dose when using CD19+ B-cell guided interval dosing.

Methods

This was a prospective cohort study, as part of the ongoing BLOOMS trial, investigating participants randomised for B-cell guided interval dosing of ocrelizumab with ≥ 2 dosing intervals. Coefficients of variation were calculated for time from last ocrelizumab dose to first CD19+ B-cell measurement ≥ 0.01 × 10⁹ cells/L.

Results

Seventy-five participants with a total of 209 B-cell guided intervals were included. Time from last dose to first appearance of CD19+ B-cell count ≥ 0.01 × 10⁹ cells/L showed wide variability between individuals (20.6–72.1 weeks), but the median variation was 5.6% (IQR: 3.1–8.4) within an individual. This translated to a variation of 2 weeks per dosing interval on average.

Discussion

Time to CD19+ B-cell repopulation after each ocrelizumab dose is individually stable. This finding could pave the way for easier and more accessible future personalised interval dosing of B-cell depleting therapies if this stability is confirmed in long-term treatment.

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延长间隔给药Ocrelizumab治疗多发性硬化患者CD19+ b细胞再生的个体变异性

背景和目的：在ocrelizumab治疗的多发性硬化症患者中，b细胞再生模式在个体之间是高度可变的，但在个体内后续剂量后b细胞复发的过程尚未确定。我们的目的是在使用CD19+ b细胞引导间隔给药时，确定每次ocrelizumab给药后CD19+ b细胞再生的个体变异性。方法：这是一项前瞻性队列研究，作为正在进行的bloom试验的一部分，调查随机分配b细胞引导间隔给药ocrelizumab≥2个给药间隔的参与者。计算从最后一次ocrelizumab剂量到第一次CD19+ b细胞测量时间的变异系数≥0.01 × 109个细胞/L。结果：共纳入75名参与者，共209次b细胞引导间隔。从最后一次给药到CD19+ b细胞计数≥0.01 × 109个/L的时间在个体之间（20.6-72.1周）差异很大，但个体内的中位差异为5.6% （IQR: 3.1-8.4）。这转化为每个给药间隔平均2周的变化。讨论：每次ocrelizumab剂量后CD19+ b细胞再生的时间是单独稳定的。如果这种稳定性在长期治疗中得到证实，这一发现将为未来更容易和更容易获得的个性化间隔给药b细胞消耗疗法铺平道路。

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

European Journal of Neurology 医学-临床神经学

CiteScore

9.70

自引率

2.00%

发文量

418

审稿时长

1 months

期刊介绍： The European Journal of Neurology is the official journal of the European Academy of Neurology and covers all areas of clinical and basic research in neurology, including pre-clinical research of immediate translational value for new potential treatments. Emphasis is placed on major diseases of large clinical and socio-economic importance (dementia, stroke, epilepsy, headache, multiple sclerosis, movement disorders, and infectious diseases).