Mao-Draayer Yang, Cohen Jeffrey A, Bar-Or Amit, Han May H, Singer Barry, Williams Ian M, Meng Xiangyi, Elam Chelsea, Weiss Jamie L, Cox Gina Mavrikis, Ziehn Marina, Cree Bruce Ac
Autoimmunity Center of Excellence, Multiple Sclerosis Center, University of Michigan, Ann Arbor, MI, USA.
Mellen Center, Cleveland Clinic, Cleveland, OH, USA.
Mult Scler J Exp Transl Clin. 2022 Aug 1;8(3):20552173221115023. doi: 10.1177/20552173221115023. eCollection 2022 Jul-Sep.
Fingolimod is a sphingosine 1-phosphate receptor modulator approved for relapsing MS. Long-term effects on the immunological profile are not fully understood.
Investigate fingolimod's temporal effects on immune cell subsets, and safety outcomes.
In FLUENT, a 12-month, prospective, non-randomized, open-label, phase IV study, adult participants received fingolimod 0.5 mg/day. Changes in immune cell subsets, anti-John Cunningham virus (JCV) antibody index, and serum neurofilament levels were assessed.
165 fingolimod-naive and 217 participants treated for 2-12 years in routine clinical practice were enrolled. Levels of all monitored peripheral lymphocyte subsets were reduced from month 3 in fingolimod-naive participants. Greatest reductions occurred in naive and central memory CD4+ and CD8+ T cells, and in naive and memory B cells. Most lymphocyte subset levels remained stable in the continuous fingolimod group. Components of the innate immune system remained within reference ranges. No increase in JCV seropositivity was observed. No single cellular subset correlated with anti-JCV antibody index at any time point. Neurofilament levels remained within healthy adult reference limits throughout. No opportunistic infections were reported; no new or unexpected safety signals were observed.
FLUENT provides insights into the utility of immunological profiling to evaluate therapy response and potential infection risk.
芬戈莫德是一种已被批准用于复发型多发性硬化症的1-磷酸鞘氨醇受体调节剂。其对免疫谱的长期影响尚未完全明确。
研究芬戈莫德对免疫细胞亚群的时间效应及安全性结果。
在一项名为FLUENT的为期12个月的前瞻性、非随机、开放标签的IV期研究中，成年参与者每日服用0.5毫克芬戈莫德。评估免疫细胞亚群、抗约翰·坎宁安病毒（JCV）抗体指数及血清神经丝水平的变化。
纳入了165名未使用过芬戈莫德的参与者以及217名在常规临床实践中接受过2至12年治疗的参与者。未使用过芬戈莫德的参与者从第3个月起，所有监测的外周淋巴细胞亚群水平均下降。幼稚和中枢记忆CD4+及CD8+T细胞以及幼稚和记忆B细胞的下降最为明显。在持续使用芬戈莫德的组中，大多数淋巴细胞亚群水平保持稳定。先天性免疫系统的组成部分仍在参考范围内。未观察到JCV血清阳性率增加。在任何时间点，均无单个细胞亚群与抗JCV抗体指数相关。神经丝水平在整个过程中均保持在健康成人参考范围内。未报告机会性感染；未观察到新的或意外的安全信号。
FLUENT研究为利用免疫谱评估治疗反应和潜在感染风险提供了见解。
