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Serum neurofilament light chain levels predict long-term disability progression in patients with progressive multiple sclerosis
  1. Manuel Comabella1,
  2. Jaume Sastre-Garriga1,
  3. Pere Carbonell-Mirabent1,
  4. Nicolás Fissolo1,
  5. Carmen Tur1,
  6. Sunny Malhotra1,
  7. Deborah Pareto2,
  8. Francesc X Aymerich2,3,
  9. Jordi Río1,
  10. Alex Rovira2,
  11. Mar Tintoré1,
  12. Xavier Montalban1
  1. 1Servei de Neurologia-Neuroimmunologia, Centre d’Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d’Hebron (VHIR), Hospital Universitari Vall d’Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain
  2. 2Section of Neuroradiology, Department of Radiology, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain
  3. 3Department of Automatic Control (ESAII), Universitat Politècnica de Catalunya, Barcelona, Spain
  1. Correspondence to Manuel Comabella, Multiple Sclerosis Centre of Catalonia, Neurology-Neuroimmunology Department, Vall d'Hebron University Hospital, Barcelona, Catalunya, Spain; manuel.comabella{at}vhir.org

Objective

There is a lack of sensitive and specific biomarkers for use in progressive multiple sclerosis (MS). The study aimed to assess the potential of serum neurofilament light chain (sNfL) levels as biomarker of disability progression in patients with progressive MS.

Methods We performed a prospective observational cohort study in 51 patients with progressive MS who participated in a 2-year phase II single-centre, randomised, double-blind, placebo-controlled trial of interferon-beta. Mean (SD) follow-up duration was 13.9 (6.2) years. Levels of sNfL were measured using a single molecule array immunoassay at baseline, 1, 2 and 6 years. Univariable and multivariable analyses were carried out to evaluate associations between sNfL levels and disability progression at short term (2 years), medium term (6 years) and long term (at the time of the last follow-up).

Results A sNfL cut-off value of 10.2 pg/mL at baseline discriminated between long-term progressors and non-progressors with a 75% sensitivity and 67% specificity (adjusted OR 7.8; 95% CI 1.8 to 46.4; p=0.01). Similar performance to discriminate between long-term progressors and non-progressors was observed using age/body mass index-adjusted sNfL Z-scores derived from a normative database of healthy controls. A cut-off increase of 5.1 pg/mL in sNfL levels between baseline and 6 years also discriminated between long-term progressors and non-progressors with a 71% sensitivity and 86% specificity (adjusted OR 49.4; 95% CI 4.4 to 2×103; p=0.008).

Conclusions sNfL can be considered a prognostic biomarker of future long-term disability progression in patients with progressive MS. These data expand the little knowledge existing on the role of sNfL as long-term prognostic biomarker in patients with progressive MS.

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Data availability statement

Data are available on reasonable request. Anonymised data will be shared upon request from a qualified investigator.

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Data availability statement

Data are available on reasonable request. Anonymised data will be shared upon request from a qualified investigator.

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Footnotes

  • Contributors MC, JS-G and XM contributed to conception and design of the study. PC-M contributed to analysis of data. NF, CT, SM, DP, FXA, JR, AR and MT contributed to acquisition of data. All coauthors contributed to editing and approval of the final draft. MC accepts full responsibility for the work and/or the conduct of the study, had access to the data, and controlled the decision to publish.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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