Abstract Details

Title Serum neurofilament light chain (NfL)and CSF glial fibrillary acidic protein (GFAP) together improve the prediction of long-term clinical outcomes in multiple sclerosis

Topic Multiple Sclerosis

Presentation(s) S9 - MS Biomarkers, Immunology, and Basic Science (3:30 PM-3:42 PM)

Poster/Presentation
Number 001

Background NfL and GFAP in serum and CSF have shown promise as prognostic markers in MS.

Objective To evaluate the prognostic utility of neurofilament light chain(NfL) and glial fibrillary acidic protein(GFAP) in serum and CSF from disease onset in predicting long-term clinical outcomes in multiple sclerosis (MS).

Design/Methods We identified paired serum and CSF samples from MS patients obtained within 5 years of first MS symptom for whom there was >15 years of routine clinical follow-up. NfL and GFAP were quantified by SiMOA. sNfL was converted to age-adjusted percentiles using normative data (Swiss MS cohort). Clinical outcomes included reaching EDSS≥4 and being diagnosed with clinically progressive MS.

Results 60 patients met inclusion criteria. Over a mean of 15.8 years(s.d.2.5), 24 patients developed progressive disease and 26 reached EDSS≥4. Serum NfL was strongly correlated to CSF levels (r=0.86, 95% CI 0.78-0.92), while serum GFAP had weaker correlation with CSF (r=0.05, 95% CI 0.29-0.67). Age-adjusted serum NfL (AAsNfL) and CSF GFAP (cGFAP) were the two strongest predictors of reaching EDSS≥4 (AAsNfL AUC 0.72, p=0.0028; cGFAP AUC 0.068 , p=0.017) and clinical progression (AAsNfL AUC 0.66, p=0.036; cGFAP AUC 0.068, p=0.021). The combination of AAsNfL and cGFAP improved prediction of progressive MS compared to either of the markers in isolation. Comparing the patients in the highest versus lowest quintiles for both AAsNfL and cGFAP (i.e. high-high, n=17 vs. low-low, n=13), high-high patients had a 5.5x and 3.6x higher risk of developing EDSS≥4 and progressive MS respectively (p=0.0048 and p=0.012). The combination of AAsNfL and cGFAP quintile groupings improved the prediction of EDSS≥4 (log-rank p=0.0083) or progressive MS (p=0.042) compared to either individual marker.

Conclusions

The combination sNfL with other markers such as cGFAP could meaningfully contribute to long-term prognostication in MS.

Authors/Disclosures
Simon Thebault, MD (University of Pennsylvania, Department of Medicine) PRESENTER	Dr. Thebault has nothing to disclose.
Seyed-Mohammad Fereshtehnejad, MD, PhD	Dr. Fereshtehnejad has nothing to disclose.
	No disclosure on file
Gauruv Bose, MD (The University of Ottawa and Ottawa Hospital Research Institute)	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.
Mark S. Freedman, MD, FAAN (University of Ottawa)	Dr. Freedman has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Actelion(Janssen/J&J). Dr. Freedman has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Alexion. Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BiogenIdec. Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BMS/Celgene. Dr. Freedman has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for EMD Inc. Dr. Freedman has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi-Genzyme. Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Freedman has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Actelion (Janssen/J&J). Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Atara Biotherapeutics. Dr. Freedman has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Bayer Healthcare. Dr. Freedman has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for BiogenIdec. Dr. Freedman has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Clene Nanomedicine. Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for GRI Bio. Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Magenta Therapeutics. Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck Serono. Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Freedman has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi Genzyme. Dr. Freedman has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Sanofi Genzyme. Dr. Freedman has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for EMD Serono. The institution of Dr. Freedman has received research support from Sanofi Genzyme.