Abstract Details

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

Topic Multiple Sclerosis

Presentation(s) P1 - Poster Session 1 (12:00 PM-1:00 PM)

Poster/Presentation
Number 9-002

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 97.5^th percentile; or normal (sNfL-N) if <97.5^th percentile. We assessed if the association between sNfL and clinical outcomes varied by T2LV using linear models adjusting for age, sex, disease subtype/duration and MS therapy.

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 <median (T2LV-L): mean %difference 16% [9%-25%]; p<0.001. For sNfL-E and T2LV-H versus sNfL-N and T2LV-H: 21% slower walking speed [1%-47%]; p=0.04). A trend toward interaction was observed for manual dexterity (pinteraction=0.06), but not processing speed (pinteraction=0.51).

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.

Authors/Disclosures
Kathryn Fitzgerald, PhD (Johns Hopkins University) PRESENTER	Dr. Fitzgerald has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Setpoint Medical. The institution of Dr. Fitzgerald has received research support from NIH. The institution of Dr. Fitzgerald has received research support from National MS Society.
Elias S. Sotirchos, MD (Johns Hopkins University)	Dr. Sotirchos has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Sotirchos has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Sotirchos has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Amgen. Dr. Sotirchos has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for TG Therapeutics. The institution of Dr. Sotirchos has received research support from National Institutes of Health. The institution of Dr. Sotirchos has received research support from National Multiple Sclerosis Society. The institution of Dr. Sotirchos has received research support from Sumaira Foundation. The institution of Dr. Sotirchos has received research support from Genentech. The institution of Dr. Sotirchos has received research support from UCB. The institution of Dr. Sotirchos has received research support from Astoria Biologica. The institution of Dr. Sotirchos has received research support from Ad Scientiam. The institution of Dr. Sotirchos has received research support from Alexion. The institution of Dr. Sotirchos has received research support from Corevitas. Dr. Sotirchos has received personal compensation in the range of $500-$4,999 for serving as a Ad Hoc Reviewer with National Institutes of Health.
Matthew Smith	Matthew Smith has nothing to disclose.
Elizabeth Fisher	Elizabeth Fisher has received personal compensation for serving as an employee of Biogen. Elizabeth Fisher has stock in Biogen. Elizabeth Fisher has received intellectual property interests from a discovery or technology relating to health care.
	No disclosure on file
Tatiana Plavina, PhD	No disclosure on file
James R. Williams III, PhD	Dr. Williams has received personal compensation for serving as an employee of Biogen. Dr. Williams has received stock or an ownership interest from Biogen.
Carl DeMoor	Carl DeMoor has received personal compensation for serving as an employee of Biogen. Carl DeMoor has received stock or an ownership interest from Biogen. An immediate family member of Carl DeMoor has received personal compensation in the range of $100,000-$499,999 for serving as a Program Director with NIH.
Richard A. Rudick, MD, FAAN (Optimal Brain Health Consultants)	Dr. Rudick has received personal compensation for serving as an employee of Biogen. Dr. Rudick has received stock or an ownership interest from Biogen. Dr. Rudick has received publishing royalties from a publication relating to health care.
Ellen M. Mowry, MD, FAAN (Johns Hopkins University)	Dr. Mowry has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Octave. Dr. Mowry has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for SetPoint. The institution of Dr. Mowry has received research support from Genentech/Roche. The institution of Dr. Mowry has received research support from Biogen. Dr. Mowry has received publishing royalties from a publication relating to health care.
Peter A. Calabresi, MD, FAAN (Johns Hopkins University)	Dr. Calabresi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis. Dr. Calabresi has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lilly. Dr. Calabresi has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Idorsia. An immediate family member of Dr. Calabresi has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for MyMD. Dr. Calabresi has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Myelin Repair Foundation. The institution of Dr. Calabresi has received research support from Genentech. Dr. Calabresi has received publishing royalties from a publication relating to health care. Dr. Calabresi has received personal compensation in the range of $500-$4,999 for serving as a Study Section Member with NIH. Dr. Calabresi has received personal compensation in the range of $500-$4,999 for serving as a Grant reveiwer with Myelin Repair Foundation. Dr. Calabresi has received personal compensation in the range of $500-$4,999 for serving as a Speaker for CME with NYAS. Dr. Calabresi has received personal compensation in the range of $500-$4,999 for serving as a Speaker with Academic CME.