Evidence map›Paper›PMID 34292643›Full record

Trial reportEuropean journal of neurology2021

Plasma neurofilament light chain concentrations as a biomarker of clinical and radiologic outcomes in relapsing multiple sclerosis: Post hoc analysis of Phase 3 ozanimod trials.

Sarah Harris, Giancarlo Comi, Bruce A C Cree, Douglas L Arnold, Lawrence Steinman, James K Sheffield, Harry Southworth, Ludwig Kappos, Jeffrey A Cohen, Ozanimod Study Investigators

Abstract readClinical Trial, Phase IIIRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in European journal of neurology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed, 4 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

18 citing papers in PubMed, 4 syntheses or guidelines pooled it.

  1. Pooled it
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  7. Article
  8. Observational
  9. Article
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  13. Experimental laboratory biomarkers in multiple sclerosis.Wiener medizinische Wochenschrift (1946) · 2022
    Review
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  15. Decreased neurofilament light chain levels in estriol-treated multiple sclerosis.Annals of clinical and translational neurology · 2022
    Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Sarah HarrisBristol Myers Squibb, Princeton, New Jersey, USA.
Giancarlo ComiVita-Salute San Raffaele University, Milan, Italy.ORCID 0000-0002-6989-1054
Bruce A C CreeWeill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, California, USA.
Douglas L ArnoldNeuroRx Research and Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.
Lawrence SteinmanDepartment of Neurology and Neurological Sciences, Beckman Center for Molecular Medicine, Stanford University Medical Center, Stanford, California, USA.
James K SheffieldBristol Myers Squibb, Princeton, New Jersey, USA.
Harry SouthworthData Clarity Consulting, Stockport, UK.
Ludwig KapposResearch Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), Departments of Head, Spine and Neuromedicine, Clinical Research, Biomedicine, and Biomedical Engineering, University Hospital and University of Basel, Basel, Switzerland.
Jeffrey A CohenMellen Center for MS Treatment and Research, Department of Neurology, Cleveland Clinic, Cleveland, Ohio, USA.
Ozanimod Study Investigators

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

background and purposeWe investigated plasma neurofilament light chain concentration (pNfL) as a biomarker for neuroaxonal damage and disease activity using data from Phase 3 trials of ozanimod in relapsing multiple sclerosis (RMS).

methodspNfL was measured before and after ozanimod 0.46 mg or 0.92 mg daily or interferon β-1a 30 µg weekly in the randomized, double-blind SUNBEAM and RADIANCE trials. In these post hoc analyses, we investigated relationships between pNfL (at baseline and median percentage change from baseline to Month 12 [SUNBEAM] or 24 [RADIANCE]) and clinical and magnetic resonance imaging outcomes.

resultsMedian (Q1, Q3) baseline pNfL, available in 1244 of 1346 SUNBEAM participants, was 14.70 (10.16, 23.26) pg/ml and in 1109 of 1313 RADIANCE participants was 13.35 (9.42, 20.41) pg/ml. Baseline gadolinium-enhancing (GdE) and T2 lesion counts increased and brain volume decreased with increasing baseline pNfL. Baseline pNfL was higher in those with versus without on-treatment relapse. Median percentage reduction in pNfL at 12 months in SUNBEAM (n = 1238) and 24 months in RADIANCE (n = 1088) was greater for ozanimod (20%-27%) than interferon β-1a (13%-16%; p < 0.01). Greater pNfL reduction was associated with fewer GdE lesions, fewer new/enlarging T2 lesions per scan, less loss of brain volume, lower annualized relapse rate (ARR), and no evidence of disease activity. The following models predicted ARR: 0.5111 + 0.0116 × ΔNfL at 12 months (SUNBEAM) and 0.4079 + 0.0088 × ΔNfL at 24 months (RADIANCE).

conclusionspNfL was associated with clinical and radiologic measures of disease and treatment effects in RMS, supporting its use as a biomarker.

Indexed as

Multiple SclerosisMultiple Sclerosis, Relapsing-RemittingBiomarkersDouble-Blind MethodHumansIndansInterferon beta-1aIntermediate FilamentsMagnetic Resonance ImagingOxadiazolesRecurrenceBiomarkersIndansInterferon beta-1aOxadiazolesozanimodblood biomarkersmultiple sclerosisneurofilament lightrelapsetreatment outcome

Identifiers

PMID34292643
PMCPMC9291872

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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 OpenQuestion graph.