Abstract Details

Title The Predictive Value of Neurofilament Light Chain Levels in Blood for Cognitive Impairment in Patients with Secondary Progressive Multiple Sclerosis

Topic Multiple Sclerosis

Presentation(s) S12 - Progressive Multiple Sclerosis (2:28 PM-2:39 PM)

Poster/Presentation
Number 009

Background

NfL, a cytoskeletal protein of neurons, reflects neuroaxonal damage. Blood NfL is elevated in MS patients and is predictive of disability progression. Cognitive impairment increases with MS disease duration; in the EXPAND study, high NfL levels correlated with low Symbol Digit Modalities Test (SDMT) scores at baseline.

Objective To explore the predictive value of blood neurofilament light chain (NfL) levels for cognitive impairment in patients with secondary progressive multiple sclerosis.

Design/Methods This analysis included patients treated with siponimod or placebo in a Phase 3 clinical trial (EXPAND, N=1397/1651 randomized). NfL in EDTA plasma samples was quantified using the Single Molecule Array technology. Time to 6-month confirmed worsening on SDMT (by 4-points from baseline, 6mCW_SDMT) by NfL categories (low [<30 pg/mL] versus high [≥30 pg/mL]) was assessed using Cox regression model corrected for age, treatment, and baseline SDMT. Data from patients treated for >21 months were used.

Results Patients with high baseline NfL levels had a 41.4% higher risk of reaching 6mCW_SDMT compared to patients with low NfL levels (hazard ratio [HR] (95% CI): 1.41 (1.09; 1.84); p=0.0103). In the subgroup of patients without gadolinium-enhancing (Gd+) T1 lesions at baseline (N=1060/1397), the risk difference between patients with high versus low baseline NfL levels was 34.2% (HR (95% CI): 1.34 (0.99; 1.83); p=0.061). Larger risk difference for 6mCW_SDMT was observed in the subgroup of patients with Gd+ T1 lesions at baseline (N=296/1397), with a 135.2% higher risk in patients with high baseline NfL (HR (95% CI): 2.35 (1.09; 5.06); p=0.0289). Paced Auditory Serial Addition Test data are currently being analyzed.

Conclusions

High blood NfL levels at baseline were associated with an elevated risk for prolonged cognitive worsening speed regardless of the presence or absence of Gd+ T1 lesions, with more pronounced risk of worsening observed in patients with Gd+ T1 lesions at baseline.

Authors/Disclosures
Jens Kuhle, MD PRESENTER	Dr. Kuhle has nothing to disclose.
Harald Kropshofer	Harald Kropshofer has nothing to disclose.
Christian Barro, MD, PhD (Brigham and Women's Hospital)	Dr. Barro has nothing to disclose.
	No disclosure on file
Dieter Haering	Dieter Haering has received personal compensation for serving as an employee of Novartis.
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.
Frank Dahlke, MD, PhD	Dr. Dahlke has received personal compensation for serving as an employee of Novartis.
Davorka Tomic	Davorka Tomic has stock in Meck KGaA.
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.

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