Highlights
- •In this phase 4 study over 900 patients received fingolimod for the treatment of MS.
- •First-dose effects were examined in a population representative of real-world patients.
- •A mild decrease in heart rate was the most common manifestation of the first-dose effect.
- •Few patients (1.5%) required additional monitoring after the 6-hour observation period.
Abstract
Background
In pivotal phase 3 studies, fingolimod treatment initiation was associated with a
transient reduction in heart rate (HR). Atrioventricular (AV) conduction delays, which
were typically asymptomatic, were detected in a small minority of patients.
Objective
We report the first-dose effects of fingolimod in patients who switched from injectable
therapies during the Evaluate Patient OutComes (EPOC) study (ClinicalTrials.gov Identifier:
NCT01216072).
Methods
This was a phase 4, 6-month, randomized, active-comparator, open-label, multicenter
study. It included over 900 fingolimod-treated patients with relapsing multiple sclerosis,
with subgroups of individuals who were receiving common concomitant HR-lowering medications
or had pre-existing cardiac conditions (PCCs). Vital signs were recorded hourly for
6 h post-dose. A 12-lead electrocardiogram was obtained at baseline and at 6 h post-dose.
Results
A transient decrease in mean HR and blood pressure occurred within 6 h of the first fingolimod dose. The incidence of symptomatic bradycardia was low (1%);
eight patients reported dizziness and there was one case each of fatigue, palpitations,
dyspnea, cardiac discomfort, and gait disturbance. These symptomatic events were typically
mild or moderate in severity and all resolved spontaneously, without intervention
or fingolimod discontinuation.
Conclusion
First-dose effects in patients with PCCs and in those receiving concomitant HR-lowering
medications were consistent with effects observed in the overall study population
and with results from previous clinical trials. The EPOC study provides additional
data demonstrating the transient and generally benign nature of fingolimod first-dose
effects on HR and AV conduction in a large population that is more representative
of patients encountered in routine clinical practice than in the pivotal trials.
Keywords
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Article info
Publication history
Published online: July 03, 2014
Accepted:
June 25,
2014
Received in revised form:
June 20,
2014
Received:
March 31,
2014
Identification
Copyright
© 2014 Elsevier B.V. Published by Elsevier Inc. All rights reserved.
