Abstract Details

Title Early Levels of Neurofilament Light Chain and Glial Fibrillary Acidic Protein Improve Prediction of MS Outcomes

Topic Multiple Sclerosis

Presentation(s) S19 - MS Biomarkers and Symptom Management (1:12 PM-1:24 PM)

Poster/Presentation
Number 002

Background

Serum biomarkers are promising predictors of MS prognosis. NFL correlates with gadolinium-enhancing lesions, brain parenchymal fraction (BPF), and quality of life, and GFAP correlates with progressive MS. The method of measuring these biomarkers, and prognostic value early in the disease course, is incompletely understood.

Objective

To assess early serum neurofilament light (NFL) and glial fibrillary acidic protein (GFAP) in predicting long-term outcomes in multiple sclerosis (MS).

Design/Methods

Patients with two serum samples within 3 years of MS onset and 10-year follow-up were included. Serum NFL and GFAP were measured by Quanterix™ Simoa® assay. We measured 38 clinical and MRI predictors and 6 biomarker measurements: initial time-point, follow-up time-point, and relative change over two time-points, for NFL and GFAP. Outcomes at 10-year follow-up included development of secondary-progressive MS (SPMS), Expanded Disability Status Score (EDSS), timed 25-foot walk (T25FW), brain T2-lesion volume (T2LV), and BPF. Prediction of SPMS without and with biomarker measurements was compared by area under the receiver operating characteristic curve (AUC) analysis. Predictive models for each outcome were developed by elastic-net to determine if biomarker measurements were selected in the final models.

Results

144 patients were included with median (IQR) age at onset of 37.4 years (29.6–45.4). Samples were separated by median (IQR) 1.02 years (0.87–1.33). SPMS developed in 25 patients (17.4%) by 10-year follow-up, with predictive clinical models attaining an AUC of 0.755, while the addition of biomarkers improved the AUC to 0.873 (p=0.0031). Elastic-net models selected NFL as a predictor of 10-year EDSS, T2LV, and BPF; and GFAP for 10-year EDSS, SPMS and T25FW.

Conclusions

Measurement of serum biomarkers after MS onset improves predictive models of long-term outcomes. GFAP is predictive of clinical outcomes while NFL is predictive of both clinical and MRI outcomes. Prospective studies investigating the dynamics of serum biomarkers for monitoring disease-activity and response to treatment are needed.

Authors/Disclosures
Gauruv Bose, MD (The University of Ottawa and Ottawa Hospital Research Institute) PRESENTER	Dr. Bose has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Bose has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EMD Serono. Dr. Bose has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Teva Pharmaceuticals. The institution of Dr. Bose has received research support from Multiple Sclerosis Society of Canada.
Brian C. Healy	The institution of Mr. Healy has received research support from Analysis Group. The institution of Mr. Healy has received research support from Bristol-Myers Squibb. The institution of Mr. Healy has received research support from Verily Life Sciences. The institution of Mr. Healy has received research support from Novartis. The institution of Mr. Healy has received research support from Merck Serono. The institution of Mr. Healy has received research support from Genzyme.
	No disclosure on file
	No disclosure on file
Anu Paul, PhD (Brigham and Women's Hospital)	Anu Paul has nothing to disclose.
Marinos G. Sotiropoulos, MD (Massachusetts General Hospital)	The institution of Dr. Sotiropoulos has received research support from Mallinckrodt. The institution of Dr. Sotiropoulos has received research support from United States Department of Defense. Dr. Sotiropoulos has received research support from World Health Organization.
Hrishikesh A. Lokhande (Brigham and Womens Hospital)	Mr. Lokhande has nothing to disclose.
Mariann Polgar-Turcsanyi (Brigham and Women's Hospital)	No disclosure on file
Bonnie Glanz (Brigham and Women'S Hospital)	The institution of Ms. Glanz has received research support from CMSC. The institution of Ms. Glanz has received research support from NIH.
Charles R. Guttmann	Charles R.G. Guttmann has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sintetica SA. Charles R.G. Guttmann has received stock or an ownership interest from Alnylam. Charles R.G. Guttmann has received stock or an ownership interest from Roche. Charles R.G. Guttmann has received stock or an ownership interest from Novartis. Charles R.G. Guttmann has received stock or an ownership interest from Arrowhead Pharmaceuticals. Charles R.G. Guttmann has received stock or an ownership interest from Protalix. Charles R.G. Guttmann has received stock or an ownership interest from Promethee. Charles R.G. Guttmann has received stock or an ownership interest from GSK. Charles R.G. Guttmann has received stock or an ownership interest from Sangamo. Charles R.G. Guttmann has received stock or an ownership interest from Alcon. Charles R.G. Guttmann has received stock or an ownership interest from Cocrystal Pharma. The institution of Charles R.G. Guttmann has received research support from NIH. The institution of Charles R.G. Guttmann has received research support from McGill University. The institution of Charles R.G. Guttmann has received research support from National Multiple Sclerosis Society. The institution of Charles R.G. Guttmann has received research support from BrightFocus Foundation. The institution of Charles R.G. Guttmann has received research support from National Multiple Sclerosis Society. The institution of Charles R.G. Guttmann has received research support from University of Connecticut Health Center. The institution of Charles R.G. Guttmann has received research support from U.S. Office of Naval Research.
Rohit Bakshi, MD, FAAN	Dr. Bakshi has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for EMD Serono. The institution of Dr. Bakshi has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Journal of Neuroimaging. An immediate family member of Dr. Bakshi has received stock or an ownership interest from Biogen. The institution of Dr. Bakshi has received research support from BMS/Celgene. The institution of Dr. Bakshi has received research support from EMD Serono.
Howard L. Weiner, MD (Brigham and Women'S Hospital)	Dr. Weiner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech. Dr. Weiner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Medday Pharmaceuticals. Dr. Weiner has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for vTv Therapeutics. Dr. Weiner has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Tiziana Life Sciences. Dr. Weiner has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for vTv Therapeutics. Dr. Weiner has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Medday Pharmaceuticals. Dr. Weiner has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for vTv Therapeutics. Dr. Weiner has stock in vTv Therapeutics. The institution of Dr. Weiner has received research support from National Institute of Health. The institution of Dr. Weiner has received research support from National MS Society. The institution of Dr. Weiner has received research support from Genzyme Corp. The institution of Dr. Weiner has received research support from Genentech, Inc. . The institution of Dr. Weiner has received research support from Verily Life Sciences LLC. The institution of Dr. Weiner has received research support from EMD Serono, Inc..
Tanuja Chitnis, MD, FAAN (Brigham and Women's Hospital)	Dr. Chitnis has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. Dr. Chitnis has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Roche-Genentech. Dr. Chitnis has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Siemens. Dr. Chitnis has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Octave Biosciences. Dr. Chitnis has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Academic CME. The institution of Dr. Chitnis has received research support from Novartis. The institution of Dr. Chitnis has received research support from Sanofi. The institution of Dr. Chitnis has received research support from Octave. The institution of Dr. Chitnis has received research support from Genentech-Roche.