Background We aimed to investigate the potential of serum biomarker levels to predict disability progression in a multicentric real-world cohort of patients with primary progressive multiple sclerosis (PPMS).
Methods A total of 141 patients with PPMS from 18 European MS centres were included. Disability progression was investigated using change in Expanded Disability Status Scale (EDSS) score over three time intervals: baseline to 2 years, 6 years and to the last follow-up. Serum levels of neurofilament light chain (sNfL), glial fibrillar acidic protein (sGFAP) and chitinase 3-like 1 (sCHI3L1) were measured using single-molecule array assays at baseline. Correlations between biomarker levels, and between biomarkers and age were quantified using Spearman’s r. Univariable and multivariable linear models were performed to assess associations between biomarker levels and EDSS change over the different time periods.
Results Median (IQR) age of patients was 52.9 (46.4–58.5) years, and 58 (41.1%) were men. Median follow-up time was 9.1 (7.0–12.6) years. Only 8 (5.7%) patients received treatment during follow-up. sNfL and sGFAP levels were moderately correlated (r=0.43) and both weakly correlated with sCHI3L1 levels (r=0.19 and r=0.17, respectively). In multivariable analyses, levels of the three biomarkers were associated with EDSS changes across all time periods. However, when analysis was restricted to non-inflammatory patients according to clinical and radiological parameters (n=64), only sCHI3L1 levels remained associated with future EDSS change.
Conclusions Levels of sNfL, sGFAP and sCHI3L1 are prognostic biomarkers associated with disability progression in patients with PPMS, being CHI3L1 findings less dependent on the inflammatory component associated with disease progression.
- MULTIPLE SCLEROSIS
Data availability statement
Data are available upon reasonable request.
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NF and PB are joint first authors.
Twitter @J_SastreGarriga, @Enric_Monreal
XM and MC contributed equally.
Contributors NF, XM and MC: Design and conceptualised study; acquisition of the data; drafted the manuscript for intellectual content. PB: Design and conceptualised study; analysed the data; drafted the manuscript for intellectual content. JS-G, NM-O, AV-J, SL, YB, HH, KB, FP-M, KR, LMV, EM, RA-L, OKS, AA, FB, HT, SM-Y, AJS-L, AG-M, LG, TC-T, JL, IR, RF, MF, NT, LR-T, JDL, HW, SE and MK: Acquisition of the data and revised the manuscript for intellectual content. JK: Design and conceptualised study, and revised the manuscript for intellectual content. MC: acts as gurantor and 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.
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