title: Update on the cardiovascular profile of fingolimod in the therapy of relapsing-remitting multiple sclerosis (MS).
abstract: BACKGROUND
  Fingolimod (FTY720) has been approved as the first oral representative of the class of sphingosine-1-phosphate (S1P) receptor modulators for the treatment of relapsing-remitting multiple sclerosis (MS). Besides inducing vaso-relaxation, fingolimod can also influence electrical conduction in the myocardium and vascular endothelium by having a transient negative chronotropic effect on the sinus node.
  
  
  METHODS
  Cardiac safety and tolerability of fingolimod in the cardiac sense were reviewed by analysing the data collected from the FREEDOMS and TRANSFORMS studies -both relevant studies for marketing authorisation, from their extension studies, as well as the clinical data collected from a practice-related MS patient cohort with cardiovascular risk factors and corresponding co-medication (FIRST study).
  
  
  RESULTS
  The safety analyses on file gave no indication of any increased cardiovascular risk. The 2-3mmHg increase in blood pressure observed after the first dose of fingolimod has no therapeutic consequences. The first dose of 0.5mg fingolimod resulted in an average decrease in heart rate of 7-8beats/min. The onset of effect occurred approximately 1-2h after the first dose and the nadir was reached after approximately 4-5h. This negative chronotropic effect returned to normal after internalisation of the S1P1 receptors on maintenance therapy. There were no indications that patients with cardiac risk factors required closer observation beyond the monitoring recommended by the EMA following the first dose of fingolimod. Case study observations from the routine clinical setting show that patients accept this method of monitoring, which they assess as being a positive aspect of attentive medical care and concern.
authors.affiliation: Department of Cardiology, Rhythmology and Internal Intensive Care Cologne-Merheim Hospital, Academic Hospital of the University of Cologne, Ostmerheimerstr. 200, 51109 Köln, Germany. Electronic address: meissnera@kliniken-koeln.de.
authors.forename: Axel
authors.initials: A
authors.lastname: Meissner
authors.affiliation: Department of Neurology und Palliative Medicine, Cologne-Merheim Hospital Cologne-Merheim Hospital, Academic Hospital of the University of Cologne, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Limmroth
mesh_terms: D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000503:physiopathology; D002986:Clinical Trials as Topic; D000068876:Fingolimod Hydrochloride / Q000009:adverse effects / Q000627:therapeutic use*; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000453:epidemiology / Q000503:physiopathology*
chemical_list: D007166:Immunosuppressive Agents; D000068876:Fingolimod Hydrochloride
keywords: Cardiovascular profile; Fingolimod; Multiple sclerosis (MS); Relapsing-remitting