title: Safety and efficacy of reduced fingolimod dosage treatment.
abstract: BACKGROUND
  Oral fingolimod is a sphingosine-1-phosphate-receptor modulator that prevents the egress of lymphocytes from lymph nodes. Fingolimod reduces relapse rate and delays disability progression in patients with relapsing forms of multiple sclerosis (MS). Elevation of liver function tests (LFTs) and reduction in peripheral-blood lymphocyte counts were among the most common adverse events reported in phase II, phase III, and extension studies.
  
  
  OBJECTIVE
  To describe eight patients in whom fingolimod dose was reduced to every other day (n=6) or every third day (n=2) due to increased LFTs more than 3 times the upper limit of normal (ULN) (n=2) or decreased lymphocyte count by ≤0.2×10(9)/L (n=6).
  
  
  RESULTS
  Fingolimod dose reduction resulted in reversal of laboratory abnormalities. Clinically, none of the 8 patients developed clinical relapses, but five patients had new lesions on magnetic resonance imaging (MRI), one of whom with disability progression, and one patient converted to secondary progressive MS (SPMS).
  
  
  CONCLUSIONS
  Reducing the frequency of fingolimod administration can reverse laboratory abnormalities but may have a negative impact on drug efficacy.
authors.affiliation: Multiple Sclerosis Center, Department of Neurology, American University of Beirut Medical Center, Beirut, Lebanon.
authors.forename: Bassem I
authors.initials: BI
authors.lastname: Yamout
authors.affiliation: Multiple Sclerosis Center, Department of Neurology, American University of Beirut Medical Center, Beirut, Lebanon.
authors.forename: Maya M
authors.initials: MM
authors.lastname: Zeineddine
authors.affiliation: Multiple Sclerosis Center, Department of Neurology, American University of Beirut Medical Center, Beirut, Lebanon.
authors.forename: Raja A
authors.initials: RA
authors.lastname: Sawaya
authors.affiliation: Multiple Sclerosis Center, Department of Neurology, American University of Beirut Medical Center, Beirut, Lebanon. Electronic address: sk88@aub.edu.lb.
authors.forename: Samia J
authors.initials: SJ
authors.lastname: Khoury
mesh_terms: D000284:Administration, Oral; D000328:Adult; D004305:Dose-Response Relationship, Drug; D005260:Female; D000068876:Fingolimod Hydrochloride; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D008111:Liver Function Tests / Q000639:trends; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000175:diagnosis* / Q000188:drug therapy*; D011409:Propylene Glycols / Q000008:administration & dosage* / Q000009:adverse effects; D013110:Sphingosine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D011409:Propylene Glycols; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine
keywords: Dose; Fingolimod; Liver enzymes; Lymphopenia; Multiple sclerosis; Reduced