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)	Dr. Kappos has nothing to disclose.
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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