Evidence map›Paper›PMID 29775134›Full record

Trial reportMultiple sclerosis (Houndmills, Basingstoke, England)2019

CSF inflammatory biomarkers responsive to treatment in progressive multiple sclerosis capture residual inflammation associated with axonal damage.

Jeppe Romme Christensen, Mika Komori, Marina Rode von Essen, Rikke Ratzer, Lars Börnsen, Bibi Bielekova, Finn Sellebjerg

Open access · greenAbstract readClinical Trial, Phase IIValidation Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Multiple sclerosis (Houndmills, Basingstoke, England), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed, 4 pooled it
2.2field-weighted citation impact, top 13% of its field
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

29 citing papers in PubMed, 4 syntheses or guidelines pooled it, 40 citations in OpenAlex.

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  12. Profiling the Cerebrospinal Fluid Proteome in Progressive Multiple Sclerosis: Treatment Effects and Associations with IgM Oligoclonal Bands.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025
    Article
  13. Review
  14. Current use of fluid biomarkers as outcome measures in Multiple Sclerosis (MS): a review of ongoing pharmacological clinical trials.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2024
    Review
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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

7 authors at 4 institutions in 2 countries.

Jeppe Romme ChristensenDepartment of Neurology, Danish Multiple Sclerosis Center, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Mika KomoriNeuroimmunological Diseases Unit, National Institute of Neurological Diseases and Stroke, National Institute of Health, Bethesda, MD, USA.
Marina Rode von EssenDepartment of Neurology, Danish Multiple Sclerosis Center, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Rikke RatzerDepartment of Neurology, Danish Multiple Sclerosis Center, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Lars BörnsenDepartment of Neurology, Danish Multiple Sclerosis Center, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Bibi BielekovaNeuroimmunological Diseases Unit, National Institute of Neurological Diseases and Stroke, National Institute of Health, Bethesda, MD, USA.
Finn SellebjergDepartment of Neurology, Danish Multiple Sclerosis Center, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Rigshospitalet · DKNational Institute of Neurological Disorders and Stroke · USDanish Multiple Sclerosis Center · DKUniversity of Copenhagen · DK

Funding

From therapeutic mechanisms to unraveling the pathophysiology of MSZIANS003056 · NINDS · NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE · PI BIELEKOVA, BIBIANA · 2009 to 2018
$14.5M
Comprehensive multimodal analysis of patients with neuroimmunological diseasesZIANS003055 · NINDS · NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE · PI BIELEKOVA, BIBIANA · 2009 to 2018
$9.0M
Intramural NIH HHS Z99 AI999999Intramural NIH HHS ZIA NS003055
6 · The paper itself

Abstract

backgroundDevelopment of treatments for progressive multiple sclerosis (MS) is challenged by the lack of sensitive and treatment-responsive biomarkers of intrathecal inflammation.

objectiveTo validate the responsiveness of cerebrospinal fluid (CSF) inflammatory biomarkers to treatment with natalizumab and methylprednisolone in progressive MS and to examine the relationship between CSF inflammatory and tissue damage biomarkers.

methodsCSF samples from two open-label phase II trials of natalizumab and methylprednisolone in primary and secondary progressive MS. CSF concentrations of 20 inflammatory biomarkers and CSF biomarkers of axonal damage (neurofilament light chain (NFL)) and demyelination were analysed using electrochemiluminescent assay and enzyme-linked immunosorbent assay (ELISA).

resultsIn all, 17 natalizumab- and 23 methylprednisolone-treated patients had paired CSF samples. CSF sCD27 displayed superior standardised response means and highly significant decreases during both natalizumab and methylprednisolone treatment; however, post-treatment levels remained above healthy donor reference levels. Correlation analyses of CSF inflammatory biomarkers and NFL before, during and after treatment demonstrated that CSF sCD27 consistently correlates with NFL.

conclusionThese findings validate CSF sCD27 as a responsive and sensitive biomarker of intrathecal inflammation in progressive MS, capturing residual inflammation after treatment. Importantly, CSF sCD27 correlates with NFL, consistent with residual inflammation after anti-inflammatory treatment being associated with axonal damage.

Indexed as

Outcome Assessment, Health CareAdultAnti-Inflammatory AgentsAxonsBiomarkersFemaleFollow-Up StudiesHumansImmunologic FactorsInflammationMaleMethylprednisoloneMiddle AgedMultiple Sclerosis, Chronic ProgressiveNatalizumabNeurofilament ProteinsAnti-Inflammatory AgentsBiomarkersImmunologic FactorsMethylprednisoloneNatalizumabneurofilament protein LNeurofilament Proteinsaxonal damagecerebrospinal fluidinflammationmethylprednisolonenatalizumabPrimary progressive multiple sclerosissecondary progressive multiple sclerosis

Identifiers

PMID29775134
PMCPMC6212343
OpenAlexW2804229363

What OpenQuestion holds

Textmetadata
LicenceTDM
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.