Evidence map›Paper›PMID 25809304›Full record

Trial reportNeurology2015

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

Jens Kuhle, Giulio Disanto, Johannes Lorscheider, Tracy Stites, Yu Chen, Frank Dahlke, Gordon Francis, Anupama Shrinivasan, Ernst-Wilhelm Radue, Gavin Giovannoni and 1 more

Abstract readClinical Trial, Phase IIIControlled Clinical Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Neurology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
88citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

88 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Trial
  3. Neurofilament light levels are associated with long-term outcomes in multiple sclerosis.Multiple sclerosis (Houndmills, Basingstoke, England) · 2020
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  8. Article
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  13. Multiple Sclerosis: Pathogenesis Mechanism and Biomarkers.Central nervous system agents in medicinal chemistry · 2025
    Review
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  17. Review
  18. Review
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28 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors.

Jens KuhleFrom 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.
Giulio DisantoFrom 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.
Johannes LorscheiderFrom 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.
Tracy StitesFrom 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.
Yu ChenFrom 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.
Frank DahlkeFrom 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.
Gordon FrancisFrom 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.
Anupama ShrinivasanFrom 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.
Ernst-Wilhelm RadueFrom 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.
Gavin GiovannoniFrom 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.
Ludwig KapposFrom 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.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveWe 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.

methodsCSF 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.

resultsMedian 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.

conclusionsOur 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.

Indexed as

Intermediate FilamentsNeurofibrilsAdultAxonsBiomarkersFemaleFingolimod HydrochlorideHumansImmunosuppressive AgentsMaleMultiple Sclerosis, Relapsing-RemittingPlacebosPropylene GlycolsSphingosineTreatment OutcomeBiomarkersFingolimod HydrochlorideImmunosuppressive AgentsPlacebosPropylene GlycolsSphingosine

Identifiers

PMID25809304
PMCPMC4409586

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.