T2 Lesion Burden Modifies The Association Between Serum Neurofilament And Clinical Outcomes In MS PATHS (Partners Advancing Technology And Health Solutions) (1063)

Objective: To determine whether the association between serum neurofilament light chain (sNfL) and clinical outcomes is modified by T2 lesion volume (T2LV) in multiple sclerosis (MS). Background: sNfL and MRI-based metrics correlate with disease activity and severity, but it remains unclear whether sNfL and MRI provide complementary information. Design/Methods: In MS PATHS standardized clinical information and biosamples are acquired during routine clinic visits. Clinical outcome is determined using the Multiple Sclerosis Performance Test, sNfL using SIMOA (Quanterix), and T2LV using the MSPie prototype. Age-specific sNfL cut-points were derived from local healthy controls (HC). Levels were classified as elevated (sNfL-E) if they were ≥age-specific 97.5th percentile; or normal (sNfL-N) if Results: 984 MS patients (74% female; mean age 47y [SD:11.4y]; 18% non-white) had clinical assessments, sNfL levels, and MRI data. 239/984 (24%) were classified as sNfL-E. Of those with sNfL-E, 136/239 (65%) also had T2LV ≥median (T2LV-H). The association between sNfL and walking speed was modified by T2LV burden (pinteraction=0.003). Patients with sNfL-E and T2LV-H had significantly slower walking speeds compared with sNfL-E and T2LV Conclusions: In this large, cross-sectional MS population, the association between sNfL and clinical outcomes was modified by T2LV burden. Longitudinal studies are needed to assess if sNfL and MRI, alone or in combination improves prediction of disability worsening. Disclosure: Dr. Fitzgerald has nothing to disclose. Dr. Sotirchos has nothing to disclose. Dr. Smith has nothing to disclose. Dr. Fisher has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Full-time employee of and holds stock/stock options in Biogen. Dr. Fisher holds stock and/or stock options as a full-time employee of and holds stock/stock options in Biogen which sponsored research in which Dr. Fisher was involved as an investigator. Dr. Singh has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of and hold 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 Employee of Biogen at the time of this analysis. Dr. Plavina holds stock and/or stock options in Hold stock/stock options in Biogen which sponsored research in which Dr. Plavina was involved as an investigator. Dr. Williams has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Biogen. Dr. Williams holds stock and/or stock options in Holds stock/stock options in Biogen which sponsored research in which Dr. Williams was involved as an investigator. Dr. Williams holds stock and/or stock options in Holds stock/stock options in Biogen. Dr. DeMoor has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Biogen. Dr. DeMoor holds stock and/or stock options in Hold stock/stock options in Biogen which sponsored research in which Dr. DeMoor was involved as an investigator. Dr. Rudick has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Biogen. Dr. Rudick holds stock and/or stock options in Holds stock/stock options in Biogen which sponsored research in which Dr. Rudick was involved as an investigator. Dr. Mowry has received personal compensation in an editorial capacity for UpToDate. Dr. Mowry has received research support from Biogen, Genzyme, Teva, and Sun Pharma.Dr. Calabresi has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen and Disarm Therapeutics. Dr. Calabresi has received personal compensation in an editorial capacity for JCI Editorial Board. Dr. Calabresi has received research support from Biogen.