Plasma Neurofilament Light Chain and Glial Fibrillary Acidic Protein Levels Are Prognostic of Disability Worsening: A Biosignature That Helps Differentiating Active From Non-active SPMS (2580)

Objective: To explore the value of a biosignature of combined plasma neurofilament light chain (pNfL) and plasma glial fibrillary acidic protein (pGFAP) as a prognostic marker of disability worsening in secondary progressive multiple sclerosis (SPMS). Background: NfL correlated with disease activity and was shown to be a treatment response marker mainly in active SPMS (aSPMS), whereas GFAP was responsive to treatment effects in both aSPMS and non-active SPMS (naSPMS) patients. Therefore, the combined information of both markers may enable to refine the identification of patients at risk for progression. Design/Methods: In this post-hoc analysis of the EXPAND study (core+extension), we quantified baseline pNfL and pGFAP levels using Single Molecule Array technology. Time-to-3-month confirmed disability worsening (3mCDW), time-to-Expanded Disability Status Scale (EDSS)7.0, and time-to-1-point-sustained EDSS worsening by baseline pNfL and pGFAP categories (pNfL: low [ Results: Samples from 1369/1651 patients were analyzed. In naSPMS patients (n=704), the high-high signature showed the higher hazard ratios (HRs) versus the low-low signature across all disability outcomes: time-to-EDSS 7.0 (2.65, p=0.0014), time-to-1-point-sustained EDSS worsening (1.57, p=0.0176), and time-to-3mCDW (1.45, p=0.0151). Higher HRs were also found with the high-low signature (range: 2.09–1.17 across all three outcomes; p 0.05). Conclusions: High-pNfL in combination with high-pGFAP signature consistently indicated a higher risk of disability worsening in naSPMS, while the added value of combining GFAP and NfL was less apparent in aSPMS. Disclosure: Jens Kuhle, MD has nothing to disclose. Aleksandra Maleska Maceski has nothing to disclose. Rolf Meinert has received personal compensation for serving as an employee of Datamap GmbH. Inga Ludwig has received personal compensation for serving as an employee of Novartis. An immediate family member of Inga Ludwig has received personal compensation for serving as an employee of Novartis. Inga Ludwig has received stock or an ownership interest from Novartis. An immediate family member of Inga Ludwig has received stock or an ownership interest from Novartis. Inga Ludwig has received stock or an ownership interest from Alcon. An immediate family member of Inga Ludwig has received stock or an ownership interest from Alcon. Thomas Hach has received personal compensation for serving as an employee of Novartis Pharma AG. Thomas Hach has received stock or an ownership interest from Novartis. The institution of Dr. Kappos has received research support from Bayer. The institution of Dr. Kappos has received research support from Biogen. The institution of Dr. Kappos has received research support from Celgene. The institution of Dr. Kappos has received research support from Genentech. The institution of Dr. Kappos has received research support from Gemzyme. The institution of Dr. Kappos has received research support from Janssen. The institution of Dr. Kappos has received research support from Merck Serono. The institution of Dr. Kappos has received research support from Minoryx. The institution of Dr. Kappos has received research support from Novartis. The institution of Dr. Kappos has received research support from Roche. The institution of Dr. Kappos has received research support from Sanofi. The institution of Dr. Kappos has received research support from Santhera. The institution of Dr. Kappos has received research support from TG Therapeutics. The institution of Dr. Kappos has received research support from Abbvie. The institution of Dr. Kappos has received research support from Eisai. The institution of Dr. Kappos has received research support from Swiss MS Society, Swiss National Research Foundation, European Union, Roche Research Foundation, Innosuisse. Dr. Leppert has received personal compensation for serving as an employee of GeNeuro. Dr. Leppert has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Leppert has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche. Dr. Leppert has received personal compensation in the range of $0-$499 for serving as a Consultant for Orion. Dr. Leppert has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. Dr. Leppert has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Quanterix. Dr. Leppert has received stock or an ownership interest from Novartis. Harald Kropshofer has nothing to disclose.