Abstract Details

Title The Correlation of Blood Neurofilament Light Chain with Brain Atrophy is Partly Independent from Inflammation

Topic Multiple Sclerosis

Presentation(s) S37 - MS Biomarkers (1:55 PM-2:06 PM)

Poster/Presentation
Number 006

Background

Blood NfL has recently been identified as a biomarker of neuroaxonal loss in MS. The aim of this analysis was to understand whether the association of NfL with BVL is mediated by its association with inflammation, or whether NfL levels have an additional independent correlation with BVL.

Objective

To assess if the correlation of blood neurofilament light chain (NfL) with brain volume loss (BVL) is independent of inflammatory activity (new/enlarging T2 lesions and relapses).

Design/Methods

We included 215 patients (placebo:93, fingolimod 0.5 mg:122) enrolled in the FREEDOMS study with relapses, new/enlarging T2 lesions, BVL, and NfL level assessed at Month (M) 24. NfL levels were measured using SIMOA^TM technology at M6, M12 and M24. The correlation of M24 NfL levels with BVL after adjusting for inflammatory activity was estimated. The proportion of treatment effect (PTE) on BVL explained by M24 NfL, active T2 lesions and relapses was estimated by a multivariate linear model.

Results M24 BVL significantly correlated with active T2 lesions (r=−0.36, p<0.001), relapses (r=−0.26, p<0.001) and M24 NfL (r=−0.46, p<0.001). M24 NfL levels correlated with new/enlarging T2 lesions (r=0.57, p<0.001) and relapses (r=0.35, p<0.001). The correlation of NfL with BVL after adjusting for treatment, new/enlarging T2 lesions and relapses was r=−0.30 (p<0.001) indicating an impact of NfL on BVL not mediated by detectable inflammation. The PTE on BVL explained by new/enlarging T2 lesions was 89%, 33% by relapses and 97% by NfL levels.

Conclusions

Blood NfL has an impact on BVL that is independent from inflammation; the PTE on BVL mediated by NfL was 97%, indicating that NfL outperforms inflammatory markers as a surrogate for BVL. This analysis further supports the role of NfL as a highly informative marker of the neurodegenerative aspects in MS.

Authors/Disclosures
Maria Pia Sormani (University of Genoa) PRESENTER	Maria Pia Sormani has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Maria Pia Sormani has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Maria Pia Sormani has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. Maria Pia Sormani has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Maria Pia Sormani has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Celgene. Maria Pia Sormani has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Maria Pia Sormani has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Geneuro. Maria Pia Sormani has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Immunic. Maria Pia Sormani has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Medday. Maria Pia Sormani has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Maria Pia Sormani has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche.
Ludwig Kappos, MD, FAAN (RC2NB, University Hospital Basel)	The institution of Dr. Kappos has received research support from Bayer. The institution of Dr. Kappos has received research support from Biogen. The institution of Dr. Kappos has received research support from Genentech. The institution of Dr. Kappos has received research support from Genzyme. The institution of Dr. Kappos has received research support from Janssen. The institution of Dr. Kappos has received research support from Merck Serono. The institution of Dr. Kappos has received research support from Minoryx. The institution of Dr. Kappos has received research support from Novartis. The institution of Dr. Kappos has received research support from Roche. The institution of Dr. Kappos has received research support from Sanofi. The institution of Dr. Kappos has received research support from Santhera. The institution of Dr. Kappos has received research support from Swiss MS Society, Swiss National Research Foundation, European Union, Roche Research Foundation, Innosuisse. The institution of Dr. Kappos has received research support from Shionogi. The institution of Dr. Kappos has received research support from Japan Tobacco. The institution of Dr. Kappos has received research support from Auriga Vision AG. The institution of Dr. Kappos has received research support from EMD Serono. The institution of Dr. Kappos has received research support from Glaxo Smith Kline. The institution of Dr. Kappos has received research support from Wellmera AG. The institution of Dr. Kappos has received research support from Eli Lilly (Suisse) SA. The institution of Dr. Kappos has received research support from Bristol Myers Squibb. The institution of Dr. Kappos has received research support from Celltrion Inc. Dr. Kappos has received intellectual property interests from a discovery or technology relating to health care.
Dieter Haering	Dieter Haering has received personal compensation for serving as an employee of Novartis.
Harald Kropshofer	Harald Kropshofer has nothing to disclose.
Christian Barro, MD, PhD (Brigham and Women's Hospital)	Dr. Barro has nothing to disclose.
David Leppert, MD (University Hospital Basel)	Dr. Leppert has received personal compensation for serving as an employee of GeNeuro. Dr. Leppert has received personal compensation for serving as an employee of GeNeuro. Dr. Leppert has received personal compensation for serving as an employee of Geneuro. Dr. Leppert has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Leppert has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche. Dr. Leppert has received personal compensation in the range of $0-$499 for serving as a Consultant for Orion. Dr. Leppert has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. Dr. Leppert has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Quanterix. Dr. Leppert has stock in Novartis.
Davorka Tomic	Davorka Tomic has stock in Meck KGaA.
Jens Kuhle, MD	Dr. Kuhle has nothing to disclose.

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