Abstract Details

Title Plasma Glial Fibrillary Acidic Protein Correlates with Characteristics of Advanced Disease and Treatment Response in Secondary Progressive Multiple Sclerosis

Topic Multiple Sclerosis

Presentation(s) S10 - Multiple Sclerosis: Biomarkers and Outcome Measures (4:30 PM-4:42 PM)

Poster/Presentation
Number 006

Objective

Assess whether plasma glial fibrillary acidic protein (GFAP) qualifies as a marker of disease activity and progression and treatment response in secondary progressive multiple sclerosis (SPMS) patients with/without relapses.

Background

Upregulation of GFAP, an astrocyte-specific skeletal protein, is thought to be associated with disease activity and progression in MS.

Design/Methods

GFAP levels were measured in a batch of 475 randomly selected SPMS patients from the Phase 3 EXPAND study (siponimod vs. placebo) by Single Molecule Array technology at baseline (BL) and end of study (EOS, median time on study: 21 months). Crossectional associations of GFAP at BL with disease characteristics (Mantel-Haenszel trend/Jonckheere-Terpstra test), treatment effect on GFAP levels at EOS (Wilcoxon rank), and patient/disease parameters predictive of GFAP levels at EOS (multiple-linear regression model) were analyzed.

Results At BL, older age, longer disease duration (p<0.0001, both), high Expanded Disability Status Scale (EDSS) score (p=0.0003), low Symbol Digit Modalities Test (SDMT) score (p=0.016), number of contrast enhancing lesions (p=0.0137) and volume of T2 lesions (p<0.0001) were associated with higher GFAP levels, while the presence of relapses in the 2 years before BL was not. GFAP levels increased by 7.0% (92.1 vs 98.6 pg/mL) at EOS with placebo but decreased by 1.0% (91.5 vs 90.6 pg/mL) with siponimod treatment (p<0.0001). In the subgroup with relapses before study (n=181), GFAP decreased by 0.5% (92.9 vs 92.4 pg/mL) with siponimod, and increased by 6.3% (98.2 vs 104.4 pg/mL) with placebo (p=0.0296). In the subgroup without relapses before study (n=293), GFAP decreased by 1.5% (90.4 vs 89.1 pg/mL) with siponimod, and increased by 7.3% (89.3 vs 95.8 pg/mL) with placebo (p=0.0004).

Conclusions

These results in SPMS support the value of plasma GFAP as a treatment responsive marker of MS pathology related to both inflammatory activity and accumulating disease burden.

Authors/Disclosures
Jens Kuhle, MD PRESENTER	Dr. Kuhle has nothing to disclose.
Harald Kropshofer	Harald Kropshofer has nothing to disclose.
	No disclosure on file
Frank Dahlke, MD, PhD	Dr. Dahlke has received personal compensation for serving as an employee of Novartis.
Thomas Hach	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.
Davorka Tomic	Davorka Tomic has stock in Meck KGaA.
Ludwig Kappos, MD, FAAN (RC2NB, University Hospital Basel)	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 Genentech. The institution of Dr. Kappos has received research support from Genzyme. 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 Swiss MS Society, Swiss National Research Foundation, European Union, Roche Research Foundation, Innosuisse. The institution of Dr. Kappos has received research support from Shionogi. The institution of Dr. Kappos has received research support from Japan Tobacco. The institution of Dr. Kappos has received research support from Auriga Vision AG. The institution of Dr. Kappos has received research support from EMD Serono. The institution of Dr. Kappos has received research support from Glaxo Smith Kline. The institution of Dr. Kappos has received research support from Wellmera AG. The institution of Dr. Kappos has received research support from Eli Lilly (Suisse) SA. The institution of Dr. Kappos has received research support from Bristol Myers Squibb. The institution of Dr. Kappos has received research support from Celltrion Inc. Dr. Kappos has received intellectual property interests from a discovery or technology relating to health care.
David Leppert, MD (University Hospital Basel)	Dr. Leppert has received personal compensation for serving as an employee of GeNeuro. Dr. Leppert has received personal compensation for serving as an employee of GeNeuro. 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 stock in Novartis.

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