Natalizumab Reduces Serum Concentrations of Neurofilament Light Chain in Secondary Progressive Multiple Sclerosis Patients From the Phase 3 ASCEND Study (S12.008)

Objective: To evaluate the associations of serum neurofilament light chain (sNfL) concentrations and disease activity, disability progression and response to natalizumab treatment in participants with secondary progressive multiple sclerosis (SPMS). Background: sNfL is a promising biomarker of disease activity and treatment response in relapsing-remitting multiple sclerosis (RRMS). The role of sNfL as a biomarker in SPMS is not well understood. ASCEND was a Phase 3 study of natalizumab in individuals with SPMS for ≥2 years. Design/Methods: sNfL concentrations were measured using SIMOA NF-light® Advantage Kit (Quanterix) at baseline, week 48, and week 96 in 748 participants (natalizumab/n=379, placebo/n=365) from ASCEND. Statistical analyses included Spearman correlation, mixed model for repeated measure, and ANCOVA. Results: Baseline sNfL concentrations were associated (p Conclusions: Similar to observations in RRMS, baseline sNfL in SPMS participants was associated with baseline disease activity measures and future brain atrophy rates. Natalizumab reduced sNfL versus placebo in SPMS participants with/without acute inflammation. These findings suggest that sNfL may reflect both acute inflammation-driven neuro-axonal damage and chronic neurodegeneration in MS. Disclosure: Dr. Kapoor has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Actelion, Biogen, Sanofi Genzyme, Novartis Pharmaceuticals, Roche, and Teva. Dr. Kapoor has received research support from UK National Institute of Health Research UCL/H Biomedical Research Centre. Dr. Sellebjerg has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, EMD Serono, Genzyme, Lundbeck, Merck Serono, Novartis and Teva. Dr. Hartung has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Bayer Healthcare, Biogen, Geneuro, Genzyme, Medimmune, Merck, Receptos Celgene, Novartis, Roche, CSL Behring. Dr. Arnold has nothing to disclose. Dr. Freedman has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Bayer HealthCare, Biogen, Chugai, EMD Canada, Hoffmann–La Roche, Merck Serono, Novartis, Sanofi Genzyme, Teva Canada Innovation. Participation in a company-sponsored speakers’ bureau for Genzyme. Dr. Freedman has received personal compensation in an editorial capacity for Actelion, Bayer HealthCare, Biogen, Hoffmann–La Roche, Merck Serono, Novartis, Opexa, Sanofi Genzyme. Dr. Freedman has received compensation for serving on the Board of Directors of Actelion, Bayer HealthCare, Biogen, Hoffmann–La Roche, Merck Serono, Novartis, Opexa, Sanofi Genzyme. Dr. Jeffery has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Personal compensation for speaking or consulting services from Acorda, Bayer, Biogen, Genentech, GlaxoSmithKline, Novartis, Questcor, Serono and Teva. Dr. Jeffery has received research support from Research funding from Biogen and Genentech. Dr. Miller has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Accordant Health Services (Caremark), Adamas, BiogenIdec, Celgene, Corrona, EMD Serono, Genzyme/Sanofi, Mallinckrodt, Mapi-Pharma, Novartis, and Roche/Genentech. Dr. Miller has received personal compensation in an editorial capacity for Continuum Audio. Dr. Miller has received research support from BiogenIdec, Genzyme/Sanofi, Mallickrodt, Novartis, Roche/Genentech, and MedDay. Dr. Edwards has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, Genzyme, EMD Serono. Dr. Edwards has received research support from Biogen, Eli Lilly, Genentech, Genzyme/Sanofi, Hoffmann-La Roche, and Novartis. Dr. Singh has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen. Dr. Singh holds stock and/or stock options in Biogen. Dr. Chang has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen. Dr. Chang holds stock and/or stock options in Biogen. Dr. Ren has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen. Dr. Ren holds stock and/or stock options in Biogen. Dr. Sangurdekar has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities as an employee of Biogen. Dr. Sangurdekar holds stock and/or stock options in Biogen. Dr. Zhu has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen. Dr. Zhu holds stock and/or stock options in Biogen. 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Dr. Fisher has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen. Dr. Fisher holds stock and/or stock options in Biogen which sponsored research in which Dr. Fisher was involved as an investigator. Dr. Fisher holds stock and/or stock options in Biogen. Dr. Kieseier has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen. Dr. Kieseier holds stock and/or stock options in Biogen. Dr. Rudick has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen. Dr. Rudick holds stock and/or stock options in Biogen. Dr. Plavina has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen. Dr. Plavina holds stock and/or stock options in Biogen.