Abstract Details

Title Increased Serum Neurofilament Light and Thin Ganglion Cell–Inner Plexiform Layer Are Additive Risk Factors for Disease Activity in Early Multiple Sclerosis

Topic Multiple Sclerosis

Presentation(s) S19 - MS Biomarkers and Symptom Management (1:48 PM-2:00 PM)

Poster/Presentation
Number 005

Objective To investigate the association of combined serum neurofilament light chain (sNfL) and retinal optical coherence tomography (OCT) measurements with future disease activity in patients with early multiple sclerosis (MS).

Background Both increased sNfL level and reduced retinal layer thicknesses have individually been shown to be promising biomarkers for reflecting neuroaxonal damage in MS.

Design/Methods We analyzed sNfL by single molecule array technology and performed OCT measurements in a prospective cohort of 78 patients with clinically isolated syndrome and early relapsing remitting MS with a median (interquartile range) follow-up of 23.9 (23.3–24.7) months. Patients were grouped into those with abnormal or normal sNfL levels, defined as sNfL ≥/< 80th percentile of age-corrected reference values. Likewise, patients were grouped by a median split into those with thin or thick ganglion cell and inner plexiform layer (GCIPL), peripapillary retinal nerve fiber layer and inner nuclear layer in non-optic neuritis eyes. Outcome parameters were violation of no evidence of disease activity (NEDA-3) criteria or its components.

Results Patients with abnormal baseline sNfL had a higher risk of violating NEDA-3 (Hazard Ratio (HR) [95% confidence interval] = 2.28 [1.27–4.09], p = 0.006) and developing a new brain lesion (HR=2.47 [1.30–4.69], p = 0.006), but not for a new relapse (HR = 2.21 [0.97–5.03], p = 0.058). Patients with both abnormal sNfL and thin GCIPL had an even higher risk for NEDA-3 violation (HR = 3.61 [1.77–7.36], p = 4.2e^-4), new brain lesion (HR = 3.19 [1.51–6.76], p = 0.002), and new relapse (HR = 5.38 [1.61–17.98], p = 0.006) than patients with abnormal sNfL alone.

Conclusions In patients with early MS, presence of both abnormal sNfL and thin GCIPL is a stronger risk factor for future disease activity than presence of each parameter alone.

Authors/Disclosures
Ting-Yi Lin, MD (Charité–Universitätsmedizin Berlin) PRESENTER	Dr. Lin has nothing to disclose.
	No disclosure on file
	No disclosure on file
	No disclosure on file
Seyedamirhosein Motamedi, PhD (Charité University Medicine Berlin)	Mr. Motamedi has nothing to disclose.
	No disclosure on file
	No disclosure on file
Athina Papadopoulou, MD (University Hospital Basel)	The institution of Dr. Papadopoulou has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lundbeck Schweiz AG. The institution of Dr. Papadopoulou has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for AbbVie AG. The institution of Dr. Papadopoulou has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Eli Lilly. The institution of Dr. Papadopoulou has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for TEVA. The institution of Dr. Papadopoulou has received research support from Freie Akademische Gesellschaft Basel . Dr. Papadopoulou has received personal compensation in the range of $500-$4,999 for serving as a Travel Support (for Congress) with Eli Lilly. Dr. Papadopoulou has received personal compensation in the range of $500-$4,999 for serving as a Travel support (for Congress) with TEVA.
Pascal Benkert	Pascal Benkert has nothing to disclose.
Jens Kuhle, MD	Dr. Kuhle has nothing to disclose.
Judith Bellmann-Strobl, MD (Bharite University of Medicine Berlin)	Judith Bellmann-Strobl, MD has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Judith Bellmann-Strobl, MD has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Judith Bellmann-Strobl, MD has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi Genzyme. Judith Bellmann-Strobl, MD has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. The institution of Judith Bellmann-Strobl, MD has received research support from Bayer. The institution of Judith Bellmann-Strobl, MD has received research support from NEMOS.
Klemens Ruprecht, MD (Klinik fur Neurologie)	Dr. Ruprecht has received research support from European Union (821283-2). Dr. Ruprecht has received research support from Merck Serono. Dr. Ruprecht has received research support from Stiftung Charite. Dr. Ruprecht has received research support from Arthur Arnstein Foundation. Dr. Ruprecht has received publishing royalties from a publication relating to health care.
Friedemann Paul (Charite Universitatsmedizin in Berlin)	Dr. Paul has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Hexal. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Hexal. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Hoffmann-La Roche. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bristol-Myers Squibb GmbH & Co. KGaA (BMS. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Hexal. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Teva. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Horizon Therapeutics GmbH. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Hexal. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Paul has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for UCB. Dr. Paul has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Roche. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Paul has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for UCB. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for sanofi. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche . Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for F&U Confirm. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bristol Myers Squibb GesmbH. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for MICE Service. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Amgen. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for VINDICO medical education. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Amgen. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for UCB. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Beijing Novartis. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sandoz Internation GmbH. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Amgen. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche Thailand. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche . Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion.
Alexander U. Brandt, MD (Charite - Universitatsmedizin Berlin)	No disclosure on file
	No disclosure on file

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