Abstract Details

Title Elevated Serum Glial Fibrillary Acidic Protein is a Biomarker of Disease Progression in Progressive Multiple Sclerosis Patients

Topic Multiple Sclerosis

Presentation(s) P2 - Poster Session 2 (11:45 AM-12:45 PM)

Poster/Presentation
Number 12-001

Objective

To investigate serum glial fibrillary acidic protein (sGFAP) and neurofilament light chain (sNfL) as tools for monitoring progression in progressive multiple sclerosis (PMS) patients stratified by disease activity status.

Background

Neurodegeneration and astrocytic activation are pathological hallmarks of PMS. These processes can be quantified by sNfL and sGFAP. Previous studies exploring sGFAP had limited follow-up and number of PMS patients. PMS has been stratified in active/non-active status which may inform differential biomarkers.

Design/Methods

sNfL and sGFAP were analyzed in 259 MS patients within 6-months from confirmed EDSS≥3, corresponding with our definition of PMS onset (baseline, BL). Median follow-up after BL was 7.6 years. Patients were further classified as active/non-active based on new brain/spinal lesions or relapses i) in the two years prior or ii) any time after BL. Statistical analysis on log transformed sGFAP/sNfL assessed the baseline association with clinical features and used Cox regression to estimate the association between biomarkers and time to 6-months confirmed disability progression (6mCDP). Analyses were adjusted for age and sex.

Results sGFAP levels were positively associated with higher risk of 6mCDP (adjusted HR:1.64, p=0.006). The association was stronger in patients with low sNfL (adjusted HR:2.30, p=0.006). sNfL was not prognostic for 6mCDP. sNfL and sGFAP did not differ between patients with or without disease activity prior to BL. However, sNfL but not sGFAP was increased in patients with disease activity after BL (active: sNfL 12.5pg/mL, non-active: sNfL 11.7pg/mL; adjusted difference in log-transformed mean 0.16; p=0.036). When comparing PMS patients classified based on active status and progression, there was no difference in sNfL or sGFAP.

Conclusions

Higher levels of sGFAP were an indicator of progression, whereas sNfL reflected acute disease activity in our progressive MS cohort. Thus, sGFAP and sNfL levels may be used to stratify PMS patients at enrollment in clinical research studies and clinical trials.

Authors/Disclosures
Christian Barro, MD, PhD (Brigham and Women's Hospital) PRESENTER	Dr. Barro has nothing to disclose.
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.
Mariann Polgar-Turcsanyi (Brigham and Women's Hospital)	No disclosure on file
Harald Kropshofer	Harald Kropshofer has nothing to disclose.
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 $500-$4,999 for serving as a Consultant for Octave Biosciences. Dr. Chitnis has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sanofi. The institution of Dr. Chitnis has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. 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. The institution of Dr. Chitnis has received research support from Tiziana Life Sciences. The institution of Dr. Chitnis has received research support from Bristol-Myers Squibb. The institution of Dr. Chitnis has received research support from Wesley Clover.

��ɫ��

��ɫ��