To report the results of FLUENT, a Phase IV, 12-month, prospective, multicenter, nonrandomized study in adult patients with relapsing MS (RMS) receiving fingolimod (NCT03257358).

FLUENT explored the relationship between immune cell subset changes in the innate and adaptive immune system in response to fingolimod therapy, and their association with efficacy and safety outcomes.

Patients were stratified into Cohort 1 (fingolimod-naïve) and Cohort 2 (previously treated with fingolimod 0.5mg/day for ≥2 years). Primary outcome was change from Baseline in immune cell subsets. Secondary outcomes included Patient-Determined Disease Steps (PDDS), anti-JC virus (JCV) antibody status, and incidence of adverse events (AEs). Analysis was conducted on patients who completed Month 12 follow-up.

There were 163 and 217 patients treated in Cohort 1 and 2, respectively. At Baseline, patients in Cohort 1 had a higher proportion of CD4+T cells, CD8+T cells, and B cells vs patients in Cohort 2. Adjusted change from Baseline to Month 12 (least squares mean) demonstrated a substantial reduction in these immune cell subset counts in Cohort 1, with a greater effect on naïve and central memory T cells than effector memory T cells and regulatory B cells. Shifts in these immune cell subsets were less pronounced in Cohort 2. There was no demonstrable change from Baseline in anti-JCV antibody index in either cohort. Patients in both cohorts had low Baseline PDDS scores (Cohort 1/2: 1.7/1.8), and showed similarly minor changes at Month 12. Treatment-emergent AEs/serious AEs were reported by 54.6%/5.5% of patients in Cohort 1 and 44.2%/5.5% of patients in Cohort 2. Patients in Cohort 1 reported a higher proportion of AEs that led to discontinuation of study treatment (13.5% vs 5.5%).

These results contribute to our understanding of the temporal changes in the immune cell subtype profile in patients with RMS receiving short- or long-term fingolimod therapy.