Neurofilament Light Shows Utility as Independent Biomarker for Disease Worsening in MS


Patients with high levels of neurofilament light at baseline had an increased risk of developing new T2 lesions and of experiencing a new clinical relapse in the follow-up period, but not of EDSS progression.

Synne Brune, MD, PhD student, Oslo University Hospital

Synne Brune, MD

Data from a multicenter, real-world study showed that elevated serum neurofilament light (sNfL) concentrations at baseline were indicative of worsened disease status among patients with multiple sclerosis (MS) at 2-year follow-up.1

Lead investigator Synne Brune, MD, PhD student, Oslo University Hospital, and colleagues observed a 2.8-fold increased risk of disease worsening, a 4.0-fold increased risk of new T2 lesions, and a 3.3-fold increased risk of relapse activity after 2 years in those with higher baseline sNfL levels. Similar to previous studies, the investigators concluded that sNfL is a promising biomarker in MS that might be relevant in a clinical setting.

The aim of the study was to investigate the individual and the potential combined additive value of clinical, sNfL, optical coherence tomography (OCT), and MRI measures as markers for subsequent disease activity in a heterogenous, real-world MS patient cohort. Using the single molecule Simoa array immunoassay, patients had sNfL concentrations categorized as either high (≥8 pg/mL; ≥75th percentile) or normal (<8 pg/mL; <75th percentile). Complete data sets with sNfL, clinical and imaging measures were obtained from 309 and 226 patients with MS at baseline and 2-year follow-up, respectively.

In those with progressive MS (PMS; n = 52), higher sNfL concentrations at baseline were significantly associated with slower performance on 9-Hole Peg Test (9-HPT; rp= 0.38; P = .01), lower scores on Symbol Digit Modalities Test (SDMT; rp= –0.32; P = .03), higher T2 lesion count (rp= 0.41; P = .004), and increased T2 lesion volume (rp= 0.39; P = .01) at baseline. At follow-up (n = 38), higher sNfL concentrations were significantly associated with higher T2 lesion count (rp= 0.36; P = .04) and reduced thickness of ganglion cell and inner plexiform layer (GCIPL; rp= ­–0.52; P = .02).

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Similar to the PMS group, those with relapsing-remitting MS (RRMS; n = 257) with higher baseline sNfl concentrations had significant associations with higher T2 lesion count at baseline (rp= 0.15; P = .02). Among these patients, higher sNfL levels led to slower performance on both 9-HPT (rp = 0.24; P = .0003) and 25-Foot Walk Test (rp= 0.31; P = .01) at follow-up. Furthermore, the presence of new lesions (rp= 0.28; P <.001) and increasing lesion volumes (rp= 0.21; P = .01) at follow-up significantly correlated with higher concentrations of sNfL at baseline in the RRMS group.

A secondary analysis aimed to assess whether high sNfL concentrations, thinner pRNFL, thinner GCIPL, higher T2 lesion volume, lower normalized total brain volume, slower performance on 9-HPT, or disease-modifying therapy category, separately, were associated with disease worsening at median 2-year follow-up. Not only did high sNfL concentrations at baseline lead to higher risk of disease worsening (odds ratio [OR], 2.8; 95% CI, 1.5-5.3; P = .001), but the risk of disease worsening was also significantly increased in the univariable model using the 80th percentile (OR, 1.98; 95% CI, 1.02-3.8; P = .043).

High levels of sNfL at baseline were associated with increased risk of developing new T2 lesions (OR, 3.97; 95% CI, 1.7-9.3; P = .002) and of experiencing a new clinical relapse (OR, 3.3; 95% CI, 1.38-7.8; P = .007) in the follow-up period, but not of Expanded Disability Status Scale progression. The risk of disease worsening (OR, 1.07; 95% CI, 1.01-1.14; P = .027) and experiencing a new clinical relapse (OR, 3.3; 95% CI, 1.38-7.8; P = .002) were significantly increased when sNfL was used as a continuous variable. Neither thinner GCIPL nor pRNFL, increased T2 lesion volume nor lower normalized total brain volume showed associations with disease worsening at follow-up; although, investigators did find associations between slower performance on 9-HPT and disease worsening at follow-up (OR, 1.09; 95% CI, 1.02-1.17; P = .009).

1. Brune S, Hogestol EA, Benavent SA, et al. Serum neurofilament light chain concentration predicts disease worsening in multiple sclerosis. Published online June 4, 2022. Mult Scler J. doi:10.1177/13524585221097296
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