Cardiac Effects of Fingolimod in Patients with Multiple Sclerosis

Background: Treatment initiation with fingolimod can induce a transient, generally asymptomatic reduction in heart rate that is maximal by 4 to 6 hours after the first dose and attenuates over the following weeks with continued dosing.

Objectives: To present first-dose observation data (FDO) from the Evaluate Patient OutComes (EPOC) study after switch from standard-of-care disease-modifying therapy (DMT) to fingolimod 0.5 mg.

Methods: Eligible patients for the 6-month, multicenter, phase 4 EPOC study (NCT01216072) had relapsing multiple sclerosis (MS), were fingolimod-naive, and had received ≥6 months' continuous treatment with a standard DMT (interferon β or glatiramer acetate) before study initiation. Patients with significant cardiac history or poorly controlled hypertension were excluded. Patients were assigned 3:1 to open-label fingolimod 0.5 mg or standard DMT with no washout of prior DMT. First-dose observation assessments included a predose electrocardiogram (ECG) and predose (plus hourly postdose) measurements of sitting heart rate (HR) and blood pressure (BP), and a subgroup of patients had a 6-hour postdose ECG.

Results: Patients receiving fingolimod (n=783) were mostly women (75.9%) with a mean age of 46.0 years. Mean predose HR was 74.1 bpm. Nadir HR was reached by 5 hours postdose (mean change from baseline, −8.3 bpm) and began to recover by 6 hours. Eight patients (1%) had symptomatic bradycardia, most frequently dizziness, and all spontaneously recovered with no treatment. No second-degree AV block was observed in the postdose ECG substudy (n=139).

Conclusions: Consistent with previous studies, cardiac effects after fingolimod treatment initiation were transient and benign in nature.