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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 620-628 |
| Number of pages | 9 |
| Journal | Multiple Sclerosis and Related Disorders |
| Volume | 3 |
| Issue number | 5 |
| DOIs | |
| State | Published - 2014 |
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Keywords
- Fingolimod
- First-dose effects
- Multiple sclerosis
- Patient outcomes
- Transient bradycardia
ASJC Scopus subject areas
- Clinical Neurology
- Neurology
Cite this
First-dose effects of fingolimod after switching from injectable therapies in the randomized, open-label, multicenter, Evaluate Patient OutComes (EPOC) study in relapsing multiple sclerosis. / Hughes, Bruce; Cascione, Mark; Freedman, Mark S.; Agius, Mark; Kantor, Daniel; Gudesblatt, Mark; Goldstick, Lawrence P.; Agashivala, Neetu; Schofield, Lesley; McCague, Kevin; Hashmonay, Ron; Barbato, Luigi.
In: Multiple Sclerosis and Related Disorders, Vol. 3, No. 5, 2014, p. 620-628.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - First-dose effects of fingolimod after switching from injectable therapies in the randomized, open-label, multicenter, Evaluate Patient OutComes (EPOC) study in relapsing multiple sclerosis
AU - Hughes, Bruce
AU - Cascione, Mark
AU - Freedman, Mark S.
AU - Agius, Mark
AU - Kantor, Daniel
AU - Gudesblatt, Mark
AU - Goldstick, Lawrence P.
AU - Agashivala, Neetu
AU - Schofield, Lesley
AU - McCague, Kevin
AU - Hashmonay, Ron
AU - Barbato, Luigi
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
KW - Fingolimod
KW - First-dose effects
KW - Multiple sclerosis
KW - Patient outcomes
KW - Transient bradycardia
UR - http://www.scopus.com/inward/record.url?scp=84906312694&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84906312694&partnerID=8YFLogxK
U2 - 10.1016/j.msard.2014.06.006
DO - 10.1016/j.msard.2014.06.006
M3 - Article
C2 - 26265274
AN - SCOPUS:84906312694
VL - 3
SP - 620
EP - 628
JO - Multiple Sclerosis and Related Disorders
JF - Multiple Sclerosis and Related Disorders
SN - 2211-0348
IS - 5
ER -