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Neurology. 2015 Apr 21;84(16):1639-43. doi: 10.1212/WNL.0000000000001491. Epub 2015 Mar 25.

Fingolimod and CSF neurofilament light chain levels in relapsing-remitting multiple sclerosis.

Author information

1
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.
2
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.

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.

PMID:
25809304
PMCID:
PMC4409586
DOI:
10.1212/WNL.0000000000001491
[Indexed for MEDLINE]
Free PMC Article

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