Effect of dimethyl fumarate on lymphocytes in RRMS Implications for clinical practice
Effect of dimethyl fumarate on lymphocytes in RRMS Implications for clinical practice
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DOI：
10.1212/wnl.0000000000007262
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发表时间：
2019-04-09
期刊：
影响因子：
9.9
通讯作者：
Fox, Robert J.
中科院分区：
文献类型：
--
作者：
Mehta, Devangi;Miller, Catherine;Fox, Robert J.
目的评估延迟释放富马酸二甲酯（DMF）治疗多发性sclerosis.MethodsUsing外周血从几个临床试验的DMF，免疫细胞亚群的功能变化和随后的临床意义进行了定量流式细胞术。对于一些患者，在DMF停药后评估淋巴细胞计数。不良事件的发生率，包括严重和机会性感染，assessed. ResultsInDMF治疗的患者，绝对淋巴细胞计数（ALCs）表现出一种模式的下降，然后稳定，这也反映在全球减少循环功能淋巴细胞亚群的数量。循环记忆T细胞和B细胞群的相对频率下降，幼稚细胞增加。即使按ALC或T细胞亚群频率分层，也未观察到DMF治疗患者的严重感染或恶性肿瘤发生率增加。对于因淋巴细胞减少而停用DMF的患者，停用DMF后ALC增加;恢复时间因停药时ALC水平而异。T细胞亚群密切相关的ALCs在纵向和横截面analysis.ConclusionsDMF转移循环淋巴细胞亚群的免疫表型。ALC与CD 4（+）和CD 8（+）T细胞计数密切相关，表明安全性警戒不需要监测淋巴细胞亚群。在T细胞亚群计数低的患者中未观察到严重感染的风险增加。监测ALC仍然是识别患者是否存在随后发生长期中度至重度淋巴细胞减少症风险的最有效方法，淋巴细胞减少症是DMF治疗患者中进行性多灶性白质脑病的风险因素。
ObjectiveTo assess functional changes in lymphocyte repertoire and subsequent clinical implications during delayed-release dimethyl fumarate (DMF) treatment in patients with multiple sclerosis.MethodsUsing peripheral blood from several clinical trials of DMF, immune cell subsets were quantified using flow cytometry. For some patients, lymphocyte counts were assessed after DMF discontinuation. Incidence of adverse events, including serious and opportunistic infections, was assessed.ResultsInDMF-treated patients, absolute lymphocyte counts (ALCs) demonstrated a pattern of decline followed by stabilization, which also was reflected in the global reduction in numbers of circulating functional lymphocyte subsets. The relative frequencies of circulatingmemory T-and B-cell populations declined and naive cells increased. No increased incidence of serious infection or malignancy was observed for patients treated with DMF, even when stratified by ALC or T-cell subset frequencies. For patients who discontinued DMF due to lymphopenia, ALCs increased after DMF discontinuation; recovery time varied by ALC level at discontinuation. T-cell subsets closely correlated with ALCs in both longitudinal and cross-sectional analyses.ConclusionsDMF shifted the immunophenotype of circulating lymphocyte subsets. ALCs were closely correlated with CD4(+) and CD8(+) T-cell counts, indicating that lymphocyte subset monitoring is not required for safety vigilance. No increased risk of serious infection was observed in patients with low T-cell subset counts. Monitoring ALC remains the most effective way of identifying patients at risk of subsequently developing prolongedmoderate to severe lymphopenia, a risk factor for progressive multifocal leukoencephalopathy in DMF-treated patients.