Cohen Jeffrey A, Bar-Or Amit, Cree Bruce A C, Mao-Draayer Yang, Han May H, Singer Barry, Jannu Ann, Kolodny Scott, Meng Xiangyi, Winger Ryan C
Mellen Center, Cleveland Clinic, Cleveland, OH, USA.
Center for Neuroinflammation and Experimental Therapeutics and Department of Neurology, University of Pennsylvania, Philadelphia, PA, USA.
Mult Scler J Exp Transl Clin. 2019 Jan 2;5(1):2055217318819245. doi: 10.1177/2055217318819245. eCollection 2019 Jan-Mar.
Fingolimod is a sphingosine 1-phosphate receptor modulator for the treatment of patients with relapsing forms of multiple sclerosis (RMS). Fingolimod sequesters lymphocytes within lymphoid tissue thereby reducing the counts of circulating lymphocytes. However, fingolimod's effects on the innate and adaptive components of the immune system are incompletely understood.
The FLUENT study will investigate temporal changes in circulating immune cell subsets in patients with RMS treated with fingolimod. Secondary objectives include examining the association between anti-John Cunningham virus (JCV) antibody status/index and phenotypic changes in innate and T and B cell subsets in patients on fingolimod therapy, and the association between serum neurofilament levels and clinical outcomes.
FLUENT is a prospective, multicenter, two-cohort, nonrandomized, open-label Phase IV study. Cohort 1 will include fingolimod-naïve patients and Cohort 2 will include patients who have received fingolimod 0.5 mg/day continuously for ≥2 years. Changes in the cellular components of the innate and adaptive immune system will be characterized over 12 months.
The study is ongoing.
FLUENT may provide evidence for the use of immunologic profiling in predicting efficacy and risk of infection in patients with RMS treated with fingolimod.
芬戈莫德是一种鞘氨醇-1-磷酸受体调节剂，用于治疗复发型多发性硬化症（RMS）患者。芬戈莫德将淋巴细胞隔离在淋巴组织内，从而减少循环淋巴细胞计数。然而，芬戈莫德对免疫系统先天性和适应性成分的影响尚未完全了解。
FLUENT研究将调查接受芬戈莫德治疗的RMS患者循环免疫细胞亚群的时间变化。次要目标包括检查抗约翰·坎宁安病毒（JCV）抗体状态/指数与接受芬戈莫德治疗患者的先天性、T细胞和B细胞亚群表型变化之间的关联，以及血清神经丝水平与临床结局之间的关联。
FLUENT是一项前瞻性、多中心、双队列、非随机、开放标签的IV期研究。队列1将包括未使用过芬戈莫德的患者，队列2将包括连续接受0.5mg/天芬戈莫德治疗≥2年的患者。将在12个月内对先天性和适应性免疫系统的细胞成分变化进行特征描述。
研究正在进行中。
FLUENT可能为利用免疫分析预测接受芬戈莫德治疗的RMS患者的疗效和感染风险提供证据。
