London School of Hygiene and Tropical Medicine
Department of Medical Statistics, Faculty of Epidemiology and Population Health

Author Of 1 Presentation

Biomarkers and Bioinformatics Poster Presentation

P0158 - Serum neurofilaments in Secondary Progressive Multiple Sclerosis: analysis from the MS-STAT trial (ID 1605)

Presentation Number
Presentation Topic
Biomarkers and Bioinformatics



There is a clear need for biomarker development in progressive multiple sclerosis (PMS). Serum neurofilament light (sNFL), and to a lesser extent neurofilament heavy (sNFH), are leading candidates. Whilst sNFL in particular has been examined in relapsing remitting MS, data from PMS are limited and in contrast to immunosuppressive treatments, candidate neuroprotective treatments show a variable effect on these biomarkers [1]. We examine data from the original MS-STAT trial [2].


To analyses serum neurofilament data from the MS-STAT trial, assessing cross-sectional and longitudinal sNFL and sNFH and their relationship with MRI and clinical variables.


Serum samples were acquired at months 0, 6, 12 and 24. sNFL and sNFH were quantified using Single Molecule Array (Simoa). Linear mixed models were used to assess for treatment effects between simvastatin and placebo, and regression, linear mixed and bivariate models to assess association with MRI and clinical variables.


Median baseline sNFL was 14.6pg/ml (IQR 10.8-20.2) and sNFH 64.2pg/ml (23.9-119), rising to 16.0pg/ml (11.9-22.2) and 70.9pg/ml (26.5-123) by 24 months. Higher baseline sNFL was associated with greater subsequent brain atrophy. Similarly, higher sNFL was associated with higher T2 lesion volume (T2LV), and increases in sNFL were associated with increases in T2LV.

High baseline sNFL was associated with worse baseline EDSS (95% CI of coefficient: 0.120 to 0.633), 9-hole peg test (-0.009 to -0.002) and 25 foot walk (-0.515 to -0.019), and a greater deterioration in 25 foot walk from baseline to 2 years (-0.448 to -0.152). There was no evidence of an association between sNFH and these variables.

There was no evidence of a simvastatin treatment effect on either sNFL (95% CI -0.07 to 0.10, p=0.716) or sNFH (95% CI -0.17 to 0.22, p=0.827).


The mode of action of simvastatin in reducing brain atrophy remains to be elucidated, with actions upon vascular comorbidity and intermediate metabolites from cholesterol synthesis pathways as possible candidates [3]. Simvastatin is not immunosuppressive, and in common with other purportedly neuroprotective treatments, there is no evidence from this study that sNFL or sNFH can act as biomarkers of simvastatin treatment. The relationship between sNFL and T2LV supports the hypothesis that in MS, sNFL may act predominantly as a marker of neuroinflammation, even in this typical SPMS cohort.

1. Williams T et al (2020) Neurofilaments in progressive multiple sclerosis: a systematic review. J Neurol.

2. Chataway J et al (2014) Effect of high-dose simvastatin on brain atrophy and disability in secondary progressive multiple sclerosis (MS-STAT): a randomised, placebo-controlled, phase 2 trial. Lancet

3. Palladino R et al (2020) Evaluating the Risk of Macrovascular Events and Mortality among People with Multiple Sclerosis in England. JAMA Neurol