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

Bruce Hughes, Mark Cascione, Mark S. Freedman, Mark Agius, Daniel Kantor, Mark Gudesblatt, Lawrence P. Goldstick, Neetu Agashivala, Lesley Schofield, Kevin McCague, Ron Hashmonay, Luigi Barbato

Research output: Contribution to journalArticle

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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 languageEnglish (US)
Pages (from-to)620-628
Number of pages9
JournalMultiple Sclerosis and Related Disorders
Volume3
Issue number5
DOIs
StatePublished - 2014

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Multiple Sclerosis
Outcome Assessment (Health Care)
Injections
Heart Rate
Preexisting Condition Coverage
Therapeutics
Patient Advocacy
Vital Signs
Dizziness
Bradycardia
Fingolimod Hydrochloride
Gait
Dyspnea
Population
Multicenter Studies
Fatigue
Electrocardiography
Clinical Trials
Blood Pressure
Incidence

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 journalArticle

Hughes, B, Cascione, M, Freedman, MS, Agius, M, Kantor, D, Gudesblatt, M, Goldstick, LP, Agashivala, N, Schofield, L, McCague, K, Hashmonay, R & Barbato, L 2014, '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', Multiple Sclerosis and Related Disorders, vol. 3, no. 5, pp. 620-628. https://doi.org/10.1016/j.msard.2014.06.006
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. / 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. In: Multiple Sclerosis and Related Disorders. 2014 ; Vol. 3, No. 5. pp. 620-628.
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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.",
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AU - Freedman, Mark S.

AU - Agius, Mark

AU - Kantor, Daniel

AU - Gudesblatt, Mark

AU - Goldstick, Lawrence P.

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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.

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