Fingolimod First-Dose Effects in the PREFERMS Real-World Study of Patients with Relapsing–Remitting Multiple Sclerosis

Background: Fingolimod treatment initiation is associated with transient, typically asymptomatic bradycardia. Phase 3 study data have demonstrated that symptomatic bradycardia and atrioventricular block (AVB) are uncommon and do not require intervention. Real-world evidence supports these findings.

Objectives: To compare the first-dose effects of fingolimod in a real-world cohort of US patients with findings from pivotal phase 3 clinical studies.

Methods: In the PREFERMS (Prospective, Randomized, active-controlled, open-label study to Evaluate patient retention of Fingolimod versus approved first-line disease modifying thErapies in adults with Relapsing–remitting Multiple Sclerosis) 12-month study, patients were either treatment-naïve or previously treated with interferon, glatiramer acetate, or dimethyl fumarate (<2-month exposure). Patients randomized to fingolimod 0.5mg underwent electrocardiogram monitoring at baseline and 6 hours after first dose, with vital signs recorded hourly. This study provides Descriptive comparisons with pooled data from FREEDOMS, FREEDOMS II, and TRANSFORMS patient populations.

Results: Baseline demographics in PREFERMS (n=637) were generally consistent with those in pooled phase 3 studies (n=1212), although a higher proportion of patients in PREFERMS had existing hypertension (15.7% and 7.8%, respectively). Consistent with phase 3 study findings, the lowest mean heart rate in PREFERMS was reached at 5 hours post-dose (mean change from baseline, –7.3bpm) and began to recover by 6 hours. A similar proportion of patients experienced first-degree AVB in PREFERMS and phase 3 studies (5.6% and 4.7%, respectively), and the incidence of Mobitz I AVB was low in both analyses (0.5% and 0.2%, respectively). A higher proportion of patients in PREFERMS were discharged at 6 hours than in phase 3 studies (90.3% and 83.0%, respectively), fewer patients required extended monitoring after 6 hours (8.3% and 12.9%, respectively), and no patients discontinued on day 1. Patient subgroup analyses will be provided.

Conclusions: The results of this real-world study were consistent with those of previous controlled fingolimod trials and confirmed the benign nature of fingolimod first-dose effects.