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.
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 6h post-dose. A 12-lead electrocardiogram was obtained at baseline and at 6h post-dose.


RESULTS
A transient decrease in mean HR and blood pressure occurred within 6h 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.


CONCLUSIONS
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.
Mercy Ruan Neuroscience Center, Des Moines, IA, USA. Electronic address: brucehughes@mac.com.
Bruce
B
Hughes
Tampa Neurology Associates, Tampa, FL, USA. Electronic address: me@markcascione.com.
Mark
M
Cascione
University of Ottawa and the Ottawa Hospital Research Institute, Ottawa, ON, Canada. Electronic address: MFREEDMAN@Ottawahospital.on.ca.
Mark S
MS
Freedman
University of California Davis, Veterans Affairs Northern California Health Care System (VANCHCS), CA, USA. Electronic address: markaagius@hotmail.com.
Mark
M
Agius
Neurologique Foundation, Inc., Jacksonville, FL, USA. Electronic address: dkantor@neurologique.org.
Daniel
D
Kantor
Multiple Sclerosis Comprehensive Care Center, St Islip, NY, USA. Electronic address: mgudesbl@southshoreneurologic.com.
Mark
M
Gudesblatt
Neurology Specialists Inc, Dayton, OH, USA. Electronic address: lgoldstick@hotmail.com.
Lawrence P
LP
Goldstick
Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA. Electronic address: neetu.agashivala@novartis.com.
Neetu
N
Agashivala
Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA. Electronic address: lesley.schofield@novartis.com.
Lesley
L
Schofield
Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA. Electronic address: kevin.mccague@novartis.com.
Kevin
K
McCague
Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA. Electronic address: ronny.hashmonay@novartis.com.
Ron
R
Hashmonay
Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA. Electronic address: lou.barbato@novartis.com.
Luigi
L
Barbato
D000284:Administration, Oral; D002170:Canada; D004305:Dose-Response Relationship, Drug; D057915:Drug Substitution / Q000379:methods*; D005260:Female; D000068876:Fingolimod Hydrochloride / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000175:diagnosis* / Q000188:drug therapy*; D016896:Treatment Outcome; D014481:United States
D007166:Immunosuppressive Agents; D000068876:Fingolimod Hydrochloride
Fingolimod; First-dose effects; Multiple sclerosis; Patient outcomes; Transient bradycardia