title: Fingolimod and CSF neurofilament light chain levels in relapsing-remitting multiple sclerosis.
abstract: OBJECTIVE
  We assessed CSF levels of the light chain subunit of neurofilaments (NfL) at baseline and after fingolimod therapy or placebo in patients with relapsing-remitting multiple sclerosis (RRMS). Changes in NfL levels were also correlated with relapse and MRI outcomes.
  
  
  METHODS
  CSF samples were available, at baseline and 12 months after treatment initiation, from a subset of 36 patients with RRMS (fingolimod 0.5 mg: n = 9; fingolimod 1.25 mg: n = 15; placebo: n = 12) participating in the 2-year, phase 3 Fingolimod (FTY720) Research Evaluating Effects of Daily Oral Therapy in Multiple Sclerosis (FREEDOMS) study. NfL levels were determined in a blinded fashion using a commercial ELISA kit.
  
  
  RESULTS
  Median NfL levels did not differ between treatment groups at baseline (0.5 mg: 644 pg/mL; 1.25 mg: 659 pg/mL; pooled 0.5/1.25 mg: 652 pg/mL, placebo: 886 pg/mL; p value [fingolimod vs placebo] = 0.619, 0.495, and 0.481, respectively). Following 12 months of treatment, median changes from baseline in NfL levels were lower than zero in the fingolimod groups (0.5 mg: -346 pg/mL, p = 0.039; 1.25 mg: -313 pg/mL, p = 0.035) and pooled 0.5/1.25 mg fingolimod group (-326 pg/mL, 83.3% with reduction, p = 0.002) but not in the placebo group (-214 pg/mL, 66.7% with reduction, p = 0.388). Reductions in NfL levels at month 12 correlated with an improvement in relapse and MRI outcomes.
  
  
  CONCLUSIONS
  Our results suggest a beneficial effect of fingolimod on this marker of axonal injury and support the utility of NfL as a quantitative biomarker in multiple sclerosis.
authors: From the Neuroimmunology Unit (J.K., G.D., G.G.), Blizard Institute, Barts and the London School of Medicine and Dentistry, London, UK; Neurology, Departments of Medicine, Clinical Research and Biomedicine (J.K., J.L., L.K.), and the Medical Image Analysis Center (MIAC) (E.-W.R.), University Hospital, Basel, Switzerland; Novartis Pharmaceuticals Corporation (T.S., Y.C., G.F.), East Hanover, NJ; Novartis Pharma AG (F.D.), Basel, Switzerland; and Novartis Healthcare Pvt Ltd (A.S.), Hyderabad, India. jens.kuhle@usb.ch.
authors: Jens
authors: J
authors: Kuhle
authors: From the Neuroimmunology Unit (J.K., G.D., G.G.), Blizard Institute, Barts and the London School of Medicine and Dentistry, London, UK; Neurology, Departments of Medicine, Clinical Research and Biomedicine (J.K., J.L., L.K.), and the Medical Image Analysis Center (MIAC) (E.-W.R.), University Hospital, Basel, Switzerland; Novartis Pharmaceuticals Corporation (T.S., Y.C., G.F.), East Hanover, NJ; Novartis Pharma AG (F.D.), Basel, Switzerland; and Novartis Healthcare Pvt Ltd (A.S.), Hyderabad, India.
authors: Giulio
authors: G
authors: Disanto
authors: From the Neuroimmunology Unit (J.K., G.D., G.G.), Blizard Institute, Barts and the London School of Medicine and Dentistry, London, UK; Neurology, Departments of Medicine, Clinical Research and Biomedicine (J.K., J.L., L.K.), and the Medical Image Analysis Center (MIAC) (E.-W.R.), University Hospital, Basel, Switzerland; Novartis Pharmaceuticals Corporation (T.S., Y.C., G.F.), East Hanover, NJ; Novartis Pharma AG (F.D.), Basel, Switzerland; and Novartis Healthcare Pvt Ltd (A.S.), Hyderabad, India.
authors: Johannes
authors: J
authors: Lorscheider
authors: From the Neuroimmunology Unit (J.K., G.D., G.G.), Blizard Institute, Barts and the London School of Medicine and Dentistry, London, UK; Neurology, Departments of Medicine, Clinical Research and Biomedicine (J.K., J.L., L.K.), and the Medical Image Analysis Center (MIAC) (E.-W.R.), University Hospital, Basel, Switzerland; Novartis Pharmaceuticals Corporation (T.S., Y.C., G.F.), East Hanover, NJ; Novartis Pharma AG (F.D.), Basel, Switzerland; and Novartis Healthcare Pvt Ltd (A.S.), Hyderabad, India.
authors: Tracy
authors: T
authors: Stites
authors: From the Neuroimmunology Unit (J.K., G.D., G.G.), Blizard Institute, Barts and the London School of Medicine and Dentistry, London, UK; Neurology, Departments of Medicine, Clinical Research and Biomedicine (J.K., J.L., L.K.), and the Medical Image Analysis Center (MIAC) (E.-W.R.), University Hospital, Basel, Switzerland; Novartis Pharmaceuticals Corporation (T.S., Y.C., G.F.), East Hanover, NJ; Novartis Pharma AG (F.D.), Basel, Switzerland; and Novartis Healthcare Pvt Ltd (A.S.), Hyderabad, India.
authors: Yu
authors: Y
authors: Chen
authors: From the Neuroimmunology Unit (J.K., G.D., G.G.), Blizard Institute, Barts and the London School of Medicine and Dentistry, London, UK; Neurology, Departments of Medicine, Clinical Research and Biomedicine (J.K., J.L., L.K.), and the Medical Image Analysis Center (MIAC) (E.-W.R.), University Hospital, Basel, Switzerland; Novartis Pharmaceuticals Corporation (T.S., Y.C., G.F.), East Hanover, NJ; Novartis Pharma AG (F.D.), Basel, Switzerland; and Novartis Healthcare Pvt Ltd (A.S.), Hyderabad, India.
authors: Frank
authors: F
authors: Dahlke
authors: From the Neuroimmunology Unit (J.K., G.D., G.G.), Blizard Institute, Barts and the London School of Medicine and Dentistry, London, UK; Neurology, Departments of Medicine, Clinical Research and Biomedicine (J.K., J.L., L.K.), and the Medical Image Analysis Center (MIAC) (E.-W.R.), University Hospital, Basel, Switzerland; Novartis Pharmaceuticals Corporation (T.S., Y.C., G.F.), East Hanover, NJ; Novartis Pharma AG (F.D.), Basel, Switzerland; and Novartis Healthcare Pvt Ltd (A.S.), Hyderabad, India.
authors: Gordon
authors: G
authors: Francis
authors: From the Neuroimmunology Unit (J.K., G.D., G.G.), Blizard Institute, Barts and the London School of Medicine and Dentistry, London, UK; Neurology, Departments of Medicine, Clinical Research and Biomedicine (J.K., J.L., L.K.), and the Medical Image Analysis Center (MIAC) (E.-W.R.), University Hospital, Basel, Switzerland; Novartis Pharmaceuticals Corporation (T.S., Y.C., G.F.), East Hanover, NJ; Novartis Pharma AG (F.D.), Basel, Switzerland; and Novartis Healthcare Pvt Ltd (A.S.), Hyderabad, India.
authors: Anupama
authors: A
authors: Shrinivasan
authors: From the Neuroimmunology Unit (J.K., G.D., G.G.), Blizard Institute, Barts and the London School of Medicine and Dentistry, London, UK; Neurology, Departments of Medicine, Clinical Research and Biomedicine (J.K., J.L., L.K.), and the Medical Image Analysis Center (MIAC) (E.-W.R.), University Hospital, Basel, Switzerland; Novartis Pharmaceuticals Corporation (T.S., Y.C., G.F.), East Hanover, NJ; Novartis Pharma AG (F.D.), Basel, Switzerland; and Novartis Healthcare Pvt Ltd (A.S.), Hyderabad, India.
authors: Ernst-Wilhelm
authors: EW
authors: Radue
authors: From the Neuroimmunology Unit (J.K., G.D., G.G.), Blizard Institute, Barts and the London School of Medicine and Dentistry, London, UK; Neurology, Departments of Medicine, Clinical Research and Biomedicine (J.K., J.L., L.K.), and the Medical Image Analysis Center (MIAC) (E.-W.R.), University Hospital, Basel, Switzerland; Novartis Pharmaceuticals Corporation (T.S., Y.C., G.F.), East Hanover, NJ; Novartis Pharma AG (F.D.), Basel, Switzerland; and Novartis Healthcare Pvt Ltd (A.S.), Hyderabad, India.
authors: Gavin
authors: G
authors: Giovannoni
authors: From the Neuroimmunology Unit (J.K., G.D., G.G.), Blizard Institute, Barts and the London School of Medicine and Dentistry, London, UK; Neurology, Departments of Medicine, Clinical Research and Biomedicine (J.K., J.L., L.K.), and the Medical Image Analysis Center (MIAC) (E.-W.R.), University Hospital, Basel, Switzerland; Novartis Pharmaceuticals Corporation (T.S., Y.C., G.F.), East Hanover, NJ; Novartis Pharma AG (F.D.), Basel, Switzerland; and Novartis Healthcare Pvt Ltd (A.S.), Hyderabad, India.
authors: Ludwig
authors: L
authors: Kappos
mesh_terms: D000328:Adult; D001369:Axons / Q000473:pathology; D015415:Biomarkers; D005260:Female; D000068876:Fingolimod Hydrochloride; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D007382:Intermediate Filaments; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000134:cerebrospinal fluid* / Q000188:drug therapy*; D009454:Neurofibrils; D010919:Placebos; D011409:Propylene Glycols / Q000008:administration & dosage / Q000494:pharmacology*; D013110:Sphingosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D007166:Immunosuppressive Agents; D010919:Placebos; D011409:Propylene Glycols; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine