Blood Neurofilament Light Chain Levels and Association with Brain Volume Change in Patients with Primary Progressive Multiple Sclerosis and Relapsing Multiple Sclerosis Before and During Ocrelizumab Treatment (3926)

Objective: To assess whether neurofilament light chain (NfL) levels measured before and during ocrelizumab treatment were associated with brain volume (BV) changes in patients with primary progressive multiple sclerosis (PPMS) or relapsing MS (RMS). Background: Blood NfL is a biomarker of neuroaxonal injury that correlates with disease activity in MS. In previous studies, NfL predicted relapses, Expanded Disability Status Scale (EDSS) score worsening and BV loss. Ocrelizumab significantly reduced brain atrophy and NfL levels in RMS and PPMS. Design/Methods: Longitudinal blood NfL and brain MRI data from patients with PPMS (ORATORIO; n=399) or RMS (OPERA I; n=477) were analyzed. Brain atrophy was calculated as percentage BV change (PBVC) from Week 24 to the end of the controlled treatment period (ORATORIO, Week 120; OPERA I, Week 96). Log-transformed NfL, normalized BV (NBV), log-transformed T2 lesion volume (T2LV), T1 gadolinium-enhancing lesion count, age and EDSS score at baseline were examined for associations with brain atrophy. In the ocrelizumab arms, log(NfL) at Weeks 12, 24, 48, 72, 96 and 120 (ORATORIO only) was assessed for associations. Results: Baseline NfL (−0.18 and −0.19 PBVC per SD, both p 45 (+0.23 [p=0.008] and +0.18 [p=0.017] PBVC) and subsequent ocrelizumab treatment (+0.25% BV vs placebo [p=0.004] and +0.19% BV vs interferon β-1a [p=0.002]), were independently associated with PBVC in patients with PPMS and RMS, respectively. Following ocrelizumab initiation, NfL levels at Weeks 12, 24, 48, 96 and 120 (p Conclusions: Lower baseline NfL levels and treatment with ocrelizumab were both associated with lesser BV loss in PPMS and RMS independent of measures of disease severity. Disclosure: Dr. Jia has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Genentech Inc.Dr. Herman has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Genentech. Dr. Harp has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Genentech. Biogen, Celgene, EMD Serono, Genentech/Roche, Novartis and TG Therapeutics not outside of multi-center clinical trialsDr. Fiore has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities as an employee of Genentech, Inc., and a shareholder of F. Hoffmann-La Roche Ltd.. Dr. Hauser has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Alector, Annexon, Bionure, Molecular Stethoscope, Symbiotix. Dr. Hauser has received compensation for serving on the Board of Directors of Neurona. Dr. Hauser has received research support from F. Hoffmann-La Roche Ltd, and Novartis.Dr. Kappos has received research support from Bayer, Biogen, Innosuisse, Novartis, the Swiss MS Society, the Swiss National Research Foundation, and the European Union.Dr. Koendgen has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with - H Koendgen is an employee and shareholder of F. Hoffmann-La Roche Ltd. Dr. Koendgen has received research support from Employee and shareholder of F. Hoffmann-La Roche. Dr. Kuhle has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, Genzyme, Novartis, Roche, Teva, Merck. Dr. Kuhle has received research support from ECTRIMS Research Fellowship Programme, University of Basel, Swiss MS Society, Swiss National Research Foundation (320030_160221), Bayer, Biogen, Genzyme, Celgene, Novartis, Roche, Teva, Merck.Dr. Leppert has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with David Leppert has been Therapeutic Area Head at Novartis, Neuroscience Development Unit, until January 2019. He has received personal compensation for consulting and speaking, and travel reimbursement from Quanterix, Orion and Sanofi.. Dr. Manfrini has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee and shareholder of F. Hoffmann-La Roche Ltd.. Dr. Model has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with F. Hoffmann-La Roche Ltd.. Dr. Oksenberg has received research support from Research support from Genentech.. Dr. Sauter has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of F. Hoffmann-La Roche Ltd. Dr. Thanei has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with F. Hoffmann-La Roche Ltd. Amit Bar-Or has participated as a speaker in meetings sponsored by, and received consulting fees from, Atara Biotherapeutics, Biogen Idec, Celgene/Receptos, Genentech/Roche, Janssen/Actelion, MAPI, MedImmune, Merck/EMD Serono, Novartis and Sanofi-Genzyme. Grant support from Janssen/Actelion, Atara Biotherapeutics, Biogen Idec, Celgene/Receptos, Roche/Genentech, MAPI, MedImmune, Merck/EMD Serono, Novartis and Sanofi-Genzyme.