Real-World Fingolimod First-Dose Effects in Patients with Hypertension, Cardiac Conditions and/or Receiving Selective Serotonin-Reuptake Inhibitors

Background: Fingolimod is approved for the treatment of patients with relapsing multiple sclerosis (MS). A transient decrease in heart rate (HR) and asymptomatic atrioventricular (AV) conduction delays in a small number of patients are well-characterized pharmacological effects of fingolimod treatment initiation.

Objectives: To examine the first-dose effects of fingolimod in a real-world group of patients with relapsing–remitting MS (RRMS), including individuals with pre-existing hypertension (hypertension subgroup), hypertension with or without pre-existing cardiac conditions (cardiac subgroup) and those receiving a concomitant selective serotonin-reuptake inhibitor on day 1 (SSRI subgroup).

Methods: These analyses included patients randomized to receive fingolimod 0.5 mg in the 12-month, phase 4, open-label, PREFERMS study. Patients underwent electrocardiogram monitoring at baseline and 6 hours post-dose, with vital signs recorded hourly.

Results: There were 687 patients in the overall population of PREFERMS. Patients were assigned post hocto the hypertension (n=119), cardiac (n=127) or SSRI (n=138) subgroups. In the overall population, hypertension, cardiac and SSRI subgroups, 88.1%, 85.7%, 85.8% and 89.9% of patients were discharged at 6 hours post-dose, respectively. At 6 hours, mean HR change from baseline was –6.5, –6.1, –5.9 and –4.5 bpm, respectively. In the overall population, four patients (0.6%) had second-degree Mobitz I AV block at 6 hours post-dose; none were reported in any subgroup. In the overall population only, two patients (0.3%) reported a serious adverse event and were admitted to hospital as per study protocol, one patient (0.1%) had symptomatic bradycardia; none of these events was reported in any subgroup. The maximum increase in QTc interval was less than 30 ms versus the pre-dose value in 66.1%, 68.1%, 68.5% and 67.6% of the overall population, hypertension, cardiac and SSRI subgroups, respectively.

Conclusions: Fingolimod first-dose effects on HR, AV conduction and QTc interval in subgroups were similar to those observed in the overall population, highlighting no additional safety implications.