The FLUENT study design: investigating immune cell subset and neurofilament changes in patients with relapsing multiple sclerosis treated with fingolimod

Abstract

BackgroundFingolimod 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.ObjectiveThe 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.MethodsFLUENT 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.ResultsThe study is ongoing.ConclusionFLUENT may provide evidence for the use of immunologic profiling in predicting efficacy and risk of infection in patients with RMS treated with fingolimod.

Immune cell subset profiling in multiple sclerosis after fingolimod initiation and continued treatment: The FLUENT study

“…The design of FLUENT has been reported previously. 11 Briefly, FLUENT was a prospective, multicenter, non-randomized, open-label, phase IV study in adult participants with RMS in the United States. Participants were stratified by fingolimod experience: Cohort 1 included fingolimod-naive individuals initiating therapy, and Cohort 2 comprised participants continuously treated with fingolimod 0.5 mg/day for ≥2 years.…”

“…9,10 The FLUENT study investigated short-and long-term effects of fingolimod treatment on immune cell subsets, JCV index, NfL, and safety outcomes in participants with relapsing MS (RMS) who were either fingolimod-naive or had received fingolimod continuously for 2-12 years in routine clinical practice. 11…”

Signaling through the S1P−S1PR Axis in the Gut, the Immune and the Central Nervous System in Multiple Sclerosis: Implication for Pathogenesis and Treatment

“…Recent findings have suggested that S1PR1-myeloid cell signaling is considered to impact the initiation and progress of CNS autoimmunity [39]. Studies have focused on unravelling their role in CD14 and CD16 myeloid cells [40]. (Table 1)…”