Evidence map›Paper›PMID 40755082›Full record

Observational studyAnnals of clinical and translational neurology2025

Serum Neurofilament Light Chain in Multiple Sclerosis: Superiority of Age- and BMI-Corrected Z Scores/Percentiles Over Absolute Cutoff Values for Prediction of Treatment Response.

Maximilian Einsiedler, Aleksandra Maleska Maceski, Sofia Sandgren, Johanna Oechtering, Sabine Schaedelin, Lisa Hofer, Amar Zadic, Juan Francisco Vilchez Gomez, Lester Melie-Garcia, Alessandro Cagol and 34 more

Abstract readObservational Study
PubMed Full text at PMC Publisher
In one paragraph

Observational study in Annals of clinical and translational neurology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
–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

8 citing papers in PubMed.

  1. Article
  2. Impact of age, BMI, and renal function adjustment on interpretation of serum NfL and GFAP in multiple sclerosis progression: a scoping review.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026
    Article
  3. Review
  4. Article
  5. Article
  6. Big data in multiple sclerosis.Current opinion in neurology · 2026
    Review
  7. Review
  8. Review
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

44 authors.

Maximilian EinsiedlerMultiple Sclerosis Centre and Research Center for Clinical Neuroimmunology and Neuroscience (RC2NB), Neurology, Departments of Biomedicine and Clinical Research, University Hospital and University of Basel, Basel, Switzerland.ORCID https://orcid.org/0000-0002-0786-2872
Aleksandra Maleska MaceskiMultiple Sclerosis Centre and Research Center for Clinical Neuroimmunology and Neuroscience (RC2NB), Neurology, Departments of Biomedicine and Clinical Research, University Hospital and University of Basel, Basel, Switzerland.
Sofia SandgrenDepartment of Clinical Neuroscience, Institute of Neuroscience and Physiology at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.ORCID https://orcid.org/0000-0001-6206-3339
Johanna OechteringMultiple Sclerosis Centre and Research Center for Clinical Neuroimmunology and Neuroscience (RC2NB), Neurology, Departments of Biomedicine and Clinical Research, University Hospital and University of Basel, Basel, Switzerland.ORCID https://orcid.org/0000-0001-5359-7961
Sabine SchaedelinMultiple Sclerosis Centre and Research Center for Clinical Neuroimmunology and Neuroscience (RC2NB), Neurology, Departments of Biomedicine and Clinical Research, University Hospital and University of Basel, Basel, Switzerland.
Lisa HoferMultiple Sclerosis Centre and Research Center for Clinical Neuroimmunology and Neuroscience (RC2NB), Neurology, Departments of Biomedicine and Clinical Research, University Hospital and University of Basel, Basel, Switzerland.ORCID https://orcid.org/0000-0001-9312-2522
Amar ZadicMultiple Sclerosis Centre and Research Center for Clinical Neuroimmunology and Neuroscience (RC2NB), Neurology, Departments of Biomedicine and Clinical Research, University Hospital and University of Basel, Basel, Switzerland.
Juan Francisco Vilchez GomezMultiple Sclerosis Centre and Research Center for Clinical Neuroimmunology and Neuroscience (RC2NB), Neurology, Departments of Biomedicine and Clinical Research, University Hospital and University of Basel, Basel, Switzerland.
Lester Melie-GarciaMultiple Sclerosis Centre and Research Center for Clinical Neuroimmunology and Neuroscience (RC2NB), Neurology, Departments of Biomedicine and Clinical Research, University Hospital and University of Basel, Basel, Switzerland.
Alessandro CagolMultiple Sclerosis Centre and Research Center for Clinical Neuroimmunology and Neuroscience (RC2NB), Neurology, Departments of Biomedicine and Clinical Research, University Hospital and University of Basel, Basel, Switzerland.ORCID https://orcid.org/0000-0002-7703-0553
Riccardo GalbuseraMultiple Sclerosis Centre and Research Center for Clinical Neuroimmunology and Neuroscience (RC2NB), Neurology, Departments of Biomedicine and Clinical Research, University Hospital and University of Basel, Basel, Switzerland.ORCID https://orcid.org/0000-0002-3092-8737
Sebastian FinkenerDepartment of Neurology, Cantonal Hospital Aarau, Aarau, Switzerland.
Patrice LaliveDepartment of Clinical Neurosciences, Division of Neurology, and Department of Medicine, Translational Biomarker Group, Geneva, Switzerland.
Marjolaine UginetDepartment of Clinical Neurosciences, Division of Neurology, and Department of Medicine, Translational Biomarker Group, Geneva, Switzerland.
Stefanie MüllerDepartment of Neurology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland.
Caroline PotService of Neurology and Laboratories of Neuroimmunology, Department of Clinical Neurosciences, Lausanne University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland.
Amandine MathiasService of Neurology and Laboratories of Neuroimmunology, Department of Clinical Neurosciences, Lausanne University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland.
Renaud Du PasquierService of Neurology and Laboratories of Neuroimmunology, Department of Clinical Neurosciences, Lausanne University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland.
Robert HoepnerDepartment of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Andrew ChanDepartment of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Giulio DisantoMultiple Sclerosis Center, Neurocenter of Southern Switzerland, EOC, Lugano, Switzerland.ORCID https://orcid.org/0000-0002-8512-6096
Chiara ZeccaMultiple Sclerosis Center, Neurocenter of Southern Switzerland, EOC, Lugano, Switzerland.
Marcus D'SouzaMultiple Sclerosis Centre and Research Center for Clinical Neuroimmunology and Neuroscience (RC2NB), Neurology, Departments of Biomedicine and Clinical Research, University Hospital and University of Basel, Basel, Switzerland.
Lars G HemkensMultiple Sclerosis Centre and Research Center for Clinical Neuroimmunology and Neuroscience (RC2NB), Neurology, Departments of Biomedicine and Clinical Research, University Hospital and University of Basel, Basel, Switzerland.
Tobias DerfussMultiple Sclerosis Centre and Research Center for Clinical Neuroimmunology and Neuroscience (RC2NB), Neurology, Departments of Biomedicine and Clinical Research, University Hospital and University of Basel, Basel, Switzerland.
Özgür YaldizliMultiple Sclerosis Centre and Research Center for Clinical Neuroimmunology and Neuroscience (RC2NB), Neurology, Departments of Biomedicine and Clinical Research, University Hospital and University of Basel, Basel, Switzerland.
Patrick RothDepartment of Neurology and Clinical Neuroscience Center, University Hospital Zurich and University of Zurich, Zurich, Switzerland.
Claudio GobbiMultiple Sclerosis Center, Neurocenter of Southern Switzerland, EOC, Lugano, Switzerland.
David BrassatNovartis Pharma AG, Basel, Switzerland.
Björn TackenbergDepartment of Neurology, Philipps-University, Marburg, Germany.
Henrik ZetterbergDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Tjalf ZiemssenCenter of Clinical Neuroscience, Department of Neurology, University Hospital Carl Gustav Carus, Dresden, Technical University of Dresden, Dresden, Germany.
Heinz WiendlDepartment of Neurology and Neurophysiology, University Hospital Freiburg, Freiburg, Germany.
Klaus BergerInstitute of Epidemiology and Social Medicine, University of Münster, Münster, Germany.
Marco HermesdorfInstitute of Epidemiology and Social Medicine, University of Münster, Münster, Germany.ORCID https://orcid.org/0000-0003-3541-7212
Fredrik PiehlDepartment of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Ludwig KapposMultiple Sclerosis Centre and Research Center for Clinical Neuroimmunology and Neuroscience (RC2NB), Neurology, Departments of Biomedicine and Clinical Research, University Hospital and University of Basel, Basel, Switzerland.
Cristina GranzieraMultiple Sclerosis Centre and Research Center for Clinical Neuroimmunology and Neuroscience (RC2NB), Neurology, Departments of Biomedicine and Clinical Research, University Hospital and University of Basel, Basel, Switzerland.
Ahmed AbdelhakDepartment of Neurology and Weill Institute for Neurosciences, University of California, San Francisco, CA, USA.ORCID https://orcid.org/0000-0001-9731-4169
David LeppertMultiple Sclerosis Centre and Research Center for Clinical Neuroimmunology and Neuroscience (RC2NB), Neurology, Departments of Biomedicine and Clinical Research, University Hospital and University of Basel, Basel, Switzerland.ORCID https://orcid.org/0000-0001-6172-801X
Eline A J WillemseMultiple Sclerosis Centre and Research Center for Clinical Neuroimmunology and Neuroscience (RC2NB), Neurology, Departments of Biomedicine and Clinical Research, University Hospital and University of Basel, Basel, Switzerland.
Pascal BenkertMultiple Sclerosis Centre and Research Center for Clinical Neuroimmunology and Neuroscience (RC2NB), Neurology, Departments of Biomedicine and Clinical Research, University Hospital and University of Basel, Basel, Switzerland.
Jens KuhleMultiple Sclerosis Centre and Research Center for Clinical Neuroimmunology and Neuroscience (RC2NB), Neurology, Departments of Biomedicine and Clinical Research, University Hospital and University of Basel, Basel, Switzerland.ORCID https://orcid.org/0000-0002-6963-8892
Swiss Multiple Sclerosis Cohort Study (SMSC)

Funding

BiogenCelgeneMerckNovartisProgressive MS Alliance PA-2007-36872RocheSwiss Multiple Sclerosis SocietySwiss National Science Foundation 320030189140/1
6 · The paper itself

Abstract

objectivePrognostication of disease course and prediction of treatment response in multiple sclerosis is an unmet need. We compared the performance of serum neurofilament light chain Z scores (age- and BMI-adjusted) with absolute concentrations for the prediction of response to disease-modifying therapy.

methodsObservational cohort study including the first serum sample of participants after the start of fingolimod therapy. We estimated hazard ratios for future relapses comparing participants with high (upper quartile) versus lower neurofilament light chain levels, based on either absolute concentration or Z score cutoffs. We compared the prognostic/predictive performance of these two measures for the occurrence of new/enlarging T2w lesions in longitudinal MRI.

resultsWe included 447 participants (median [IQR] age, 41.3 [32.1-49.2] years; 65.1% female); median follow-up 8.3 years [6.0-10.3]. Participants with a high neurofilament light chain Z score (Z ≥ 1.2/88.5 percentile) were more likely to experience future relapses (HR: 1.80, 95% CI 1.27-2.54, p < 0.001) compared to those below this threshold while this dichotomy could not be demonstrated with absolute concentration cutoffs (≥ vs. < 10.8 pg/mL; HR: 0.94, 95% CI 0.64-1.38, p = 0.75). Furthermore, patients with upper quartile Z scores were associated with a higher incidence of new/enlarging T2w lesions compared with those below this threshold (OR: 1.88, 95% CI 1.31-2.70, p < 0.001); again, absolute concentration cutoffs failed to identify this risk (OR: 1.20, 95% CI 0.82-1.77, p = 0.34). These findings were confirmed when patients having started alternative oral treatments were also included (n = 713).

interpretationSerum neurofilament light chain Z scores consistently outperformed absolute concentration cutoffs for prognostication of clinical/radiological disease activity and may facilitate individual prediction of treatment response.

Indexed as

Multiple SclerosisNeurofilament ProteinsAdultAge FactorsBiomarkersBody Mass IndexCohort StudiesFemaleHumansImmunosuppressive AgentsMagnetic Resonance ImagingMaleMiddle AgedPrognosisBiomarkersImmunosuppressive Agentsneurofilament protein LNeurofilament Proteinsmultiple sclerosisneurofilamentpredictionZ scores

Identifiers

PMID40755082
PMCPMC12623839

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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.