Monitoring of Subclinical Disease Activity by Serum Neurofilament Light Chain Levels in Multiple Sclerosis (S37.005)

Objective: To investigate the ability of serum NfL levels to identify brain MRI activity. Background: Neurofilament light chain (NfL) serum level is associated with disease activity in multiple sclerosis (MS). Its practical value for detecting radiological disease activity as currently assessed by brain MRI has not yet been established. Design/Methods: This longitudinal study included 163 relapsing-remitting MS patients (405 samples) from the SET cohort and 179 relapsing-remitting MS patients (664 samples) from the GeneMSA cohort. Serum NfL levels were evaluated annually using a Single Molecule Array assay. Age-adjusted NfL percentiles were based on normative data from healthy controls. In each cohort, MRI scans were performed annually using single 1.5T scanner and uniform scanning protocol. The accuracy of different NfL cut-offs for the detection of active lesions (new/enlarging lesions compared with MRI in the preceding year or enhancing brain lesions) on annual scans was assessed. Results: NfL levels exceeded 90th percentile in 25.4% of the SET and 26.5% of the GeneMSA samples. 81.6% of the SET (OR=3.4, 95%CI=1.8–6.4) and 48.9% of the GeneMSA cohort (OR=2.6, 95%CI=1.7–3.9) with NfL>90th percentile showed radiological disease activity on their brain MRI. NfL levels Conclusions: Low serum NfL levels help identify MS patients with very low recent radiological disease activity. This result suggests that NfL assessment may help to spare the need for annual brain MRI monitoring in clinically stable patients with very low NfL levels. Disclosure: Dr. Uher has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with T. Uher received financial support for conference travel and honoraria from Biogen Idec, Novartis, Sanofi Genzyme, Roche, and Merck. Dr. Uher has received research support from Biogen Idec. Dr. Hoskova has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Novartis, Sanofi Genzyme and Biogen. Dr. Barro has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Teva and Novartis. Dr. Bergsland has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with EMD Serono. Dr. Dwyer has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Buffalo Neuroimaging Analysis Center. Dr. Dwyer has received research support from Novartis. Dr. Tyblova has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen Idec, Sanofi, Teva and Merck Serono. Dr. Kucerova has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, Novartis and Merck. Dr. Benkert has nothing to disclose. Dr. Michalak has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Novartis Pharma AG, Basel, Switzerland. Dr. Leppert has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Novartis. Dr. Krasensky has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen. Dr. Seidl has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen. Dr. Vaneckova has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen Idec, Novartis, Merck, Teva. Dr. Vaneckova has received research support from Czech Ministry of Health, Biogen Idec. Dr. Havrdova has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Actelion, Biogen, Celgene, Merck, Novartis, Sanofi Genzyme and Teva. Dr. Zivadinov has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with EMD Serono, Genzyme-Sanofi, and Novartis. He received financial support for research activities from Teva Pharmaceuticals, Biogen-Idec, Genzyme-Sanofi, Novartis, Claret Medical, Intekrin-Coherus and IMS Health. Dr. Kuhle’s institution has received compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, Novartis Pharmaceuticals, Protagen AG, Roche, Teva, Sanofi Genzyme, Swiss MS Society, and Merck Serono,. Dr. Kuhle has received research support from ECTRIMS Research Fellowship Programme, Bayer AG, Biogen, Sanofi Genzyme, Merck, Novartis Pharmaceuticals, Roche, Swiss MS Society, Swiss National Research Foundation, and University of Basel. Dr. Kalincik has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Roche, Sanofi Genzyme, Novartis Pharmaceuticals, Merck, Biogen, Brain Atrophy Initiative, WebMD Global, Teva, and BioCSL. Dr. Kalincik has received personal compensation in an editorial capacity from Multiple Sclerosis Journal, BMC Neurology and Frontiers in Neurology. Dr. Kalincik has received research support from Biogen. Dr. Horakova has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen Idec, Novartis, Merck, Bayer, Sanofi Genzyme, Roche and Teva.