Fingolimod First-Dose Effects in Hispanic Patients with Relapsing–Remitting Multiple Sclerosis

Background: A transient decrease in heart rate (HR) and typically asymptomatic atrioventricular (AV) conduction delays in a small minority of patients are well-characterized pharmacological effects of fingolimod treatment initiation. A previous in-clinic study demonstrated the safety profile of fingolimod on initiation of therapy in Hispanic patients. Data provided here expand on those findings.

Objectives: To evaluate the first-dose effects of fingolimod in Hispanic patients with relapsing–remitting multiple sclerosis, using a large, integrated, clinical trial data set.

Methods: The data set included all patients randomized to receive fingolimod (0.5 mg or 1.25 mg once daily), placebo or intramuscular interferon β-1a (IFNβ-1a IM; 30 µg weekly) in the core, controlled phases of all phase 2 and 3 fingolimod studies, comprising FREEDOMS, FREEDOMS II, TRANSFORMS and a phase 2 study. In the Hispanic subgroup, vital signs, including HR, were recorded hourly for 6 hours; electrocardiogram (ECG) readings were obtained on day 1 pre-dose and 6 hours post-dose. Here, results are reported only for fingolimod 0.5 mg, placebo and IFNβ-1a IM. 

Results: At treatment initiation, 89 Hispanic patients were receiving fingolimod 0.5 mg, compared with 27 receiving placebo and 65 receiving IFNβ-1a IM. A maximum mean decrease in HR of 8.1 beats per minute (bpm) occurred after 5 hours in the fingolimod group. During the first 6 hours, 79.8% of patients in the fingolimod group had a HR of at least 55 bpm, 20.2% had a HR of 45–54 bpm and no patient had a HR lower than 45 bpm. No adverse events of symptomatic bradycardia were reported. Transient, newly occurring post-dose ECG abnormalities were reported in 11.4% (10/88) of patients receiving fingolimod, 3.8% (1/26) receiving placebo and 9.4% (6/64) receiving IFNβ-1a IM. The incidence of first-degree AV block was low, occurring in 4.5% of those receiving fingolimod compared with 3.8% receiving placebo and 3.1% taking IFNβ-1a IM. One patient treated with fingolimod had a Mobitz type I AV block.

Conclusions: The effects of fingolimod initiation on HR and AV conduction in Hispanic patients were as expected, benign and similar to those in the general treated population.