Abstract Details

Title Baseline MRI Predictors of Cognitive Processing Speed in Participants with Secondary Progressive Multiple Sclerosis from the Phase 3 EXPAND study

Topic Multiple Sclerosis

Presentation(s) MS and CNS Inflammatory Disease Posters (7:00 AM-5:00 PM)

Poster/Presentation
Number 009

Objective To explore the predictive value of a variety of magnetic resonance imaging (MRI) measures of brain tissue damage on time-to-6-month confirmed ≥4-points cognitive worsening/improvement on Symbol Digit Modalities Test (SDMT; 6mCW_SDMT/6mCI_SDMT) in siponimod-treated secondary progressive multiple sclerosis (SPMS) EXPAND study participants over short- (Core) and long-term (Core+Extension) periods (total up-to-5 years).

Background Siponimod showed beneficial effects on MRI lesion activity, total brain and gray matter (GM) atrophy, MTR measures and cognitive processing speed in SPMS participants from the EXPAND study.

Design/Methods

Siponimod-treated participants (MRI cohort [N=1099]; MTR cohort [n=402]) were stratified into quartiles of baseline total normalized brain volume (NBV), cortical GM (cGM) and thalamic volume, T1-hypointense lesion volume (T1HLV), T2-lesion volume (T2LV), median normalized MTR of normal-appearing brain tissue (nMTR-NABT), normal-appearing white matter (NAWM) and cGM (cGM), and by absence/presence of gadolinium-enhancing (Gd+) T1 lesions. 6mCW_SDMT/6mCI_SDMT and absolute SDMT change from baseline were analyzed by Cox-regression analysis with respective outcome as baseline covariate comparing worst (WQ) vs best quartile (BQ).

Results

Over both short- and longer-terms, thalamic and cGM volume were the strongest MRI predictors of 6mCW for participants in the worst vs best quartile (HR_WQ/BQrange: 1.46–2.30, p<0.05 both); participants in WQ of nMTR (cGM, NAWM and NABT), T1HLV, T2LV and thalamic volume were significantly less likely to experience 6mCI (HR_WQ/BQrange: 0.24–0.52, p<0.0120 all). All parameters except Gd+ T1 lesions at baseline were significantly associated with absolute SDMT change, which showed strongest association for thalamic volume followed by T1HLV, T2LV and nMTR-NABT (delta range_WQ/BQ: 4.19–6.15; all p≤0.0005 except nMTR-NABT p=0.0107).

Conclusions

Baseline GM volume (especially thalamic volume), and MTR-reflected myelination were associated with clinically meaningful worsening and improvement in cognitive processing speed in siponimod-treated SPMS participants, suggesting relevance as prognostic MRI measures of decline in cognitive processing speed both in short and longer-terms.

Authors/Disclosures
Ralph H. Benedict, PhD (University At Buffalo) PRESENTER	Dr. Benedict has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche. Dr. Benedict has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi. Dr. Benedict has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Bristol Meyers Squibb. Dr. Benedict has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Immunic Therapeutics. Dr. Benedict has received intellectual property interests from a discovery or technology relating to health care.
Iris Katharina Penner, PhD (COGITO Center & Heinrich Heine University, Neurology Dept, Medical Faculty)	The institution of Dr. Penner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. The institution of Dr. Penner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. The institution of Dr. Penner has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Janssen. The institution of Dr. Penner has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genzyme. The institution of Dr. Penner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. The institution of Dr. Penner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for TEVA. The institution of Dr. Penner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Celgene. The institution of Dr. Penner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bayer. The institution of Dr. Penner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BMS. The institution of Dr. Penner has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. Dr. Penner has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Janssen. Dr. Penner has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Penner has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Celgene . Dr. Penner 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. Penner has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Dr. Penner 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. Penner has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck.
Ludwig Kappos, MD, FAAN (RC2NB, University Hospital Basel)	Dr. Kappos has nothing to disclose.
Patrick Vermersch (CHR de Lille)	Patrick Vermersch has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Patrick Vermersch has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Patrick Vermersch has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. Patrick Vermersch has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Patrick Vermersch has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Patrick Vermersch has received personal compensation in the range of $500-$4,999 for serving as a Consultant for AB Science. Patrick Vermersch has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Imcyse. Patrick Vermersch has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BMS-Celgene. Patrick Vermersch has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ad Scientiam. Patrick Vermersch has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Patrick Vermersch has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Patrick Vermersch has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Patrick Vermersch has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Patrick Vermersch has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Teva. Patrick Vermersch has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for La revue des microbiotes. The institution of Patrick Vermersch has received research support from Roche. The institution of Patrick Vermersch has received research support from Sanofi.
Bruce A. Cree, MD, PhD, MAS, FAAN (UCSF, Multiple Sclerosis Center)	The institution of Dr. Cree has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. The institution of Dr. Cree has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. The institution of Dr. Cree has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sanofi. The institution of Dr. Cree has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for TG Therapeutics. The institution of Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Dr. Cree has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Neuron23. Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Boston Pharma. Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Hexal/Sandoz. Dr. Cree has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Immunic AG. The institution of Dr. Cree has received research support from Genentech. The institution of Dr. Cree has received research support from Kyverna. Dr. Cree has received publishing royalties from a publication relating to health care.
Ralf Gold, MD (Neurologische Universitaetsklinik)	Dr. Gold has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biogen . Dr. Gold has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis. Dr. Gold has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche. Dr. Gold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genzyme. Dr. Gold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bayer Vital. Dr. Gold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eisai Pharamaceuticals. Dr. Gold has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Gold 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. Gold has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for SAGE Publishers. Dr. Gold has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Novartis. Dr. Gold has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Biogen. The institution of Dr. Gold has received research support from Novartis. The institution of Dr. Gold has received research support from Biogen.
Amit Bar-Or, MD, FRCPC (University of Pennsylvania)	Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche Genentech. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merk/EMD Serono. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi-Genzyme. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for cabaletta. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche/Genentech. Dr. Bar-Or 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. Bar-Or has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck/EMD Serono. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi/Genzyme. The institution of Dr. Bar-Or has received research support from Novartis. The institution of Dr. Bar-Or has received research support from Biogen. The institution of Dr. Bar-Or has received research support from Roche/Genentech.
Daniela Piani Meier	Daniela Piani Meier has received personal compensation for serving as an employee of Novartis Pharma AG.
	No disclosure on file
	No disclosure on file
Goeril Karlsson, PhD	Dr. Karlsson has received personal compensation for serving as an employee of Novartis.
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.
Robert J. Fox, MD, FAAN (Cleveland Clinic)	Dr. Fox has received personal compensation in the range of $500-$4,999 for serving as a Consultant for AB Science. Dr. Fox has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Fox has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for BMS. Dr. Fox has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for EMD Serono. Dr. Fox has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genentech. Dr. Fox has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Immunic. Dr. Fox has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis. Dr. Fox has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sanofi. Dr. Fox has received personal compensation in the range of $500-$4,999 for serving as a Consultant for TG Therapeutics. Dr. Fox has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Siemens. Dr. Fox has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Roche. Dr. Fox has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Astoria Biologica. Dr. Fox has received personal compensation in the range of $500-$4,999 for serving as a Consultant for InnoCare Pharma. Dr. Fox has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Fox has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Immunic. Dr. Fox has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Fox has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for AB Science. Dr. Fox 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. Dr. Fox has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for BMS. The institution of Dr. Fox has received research support from National Institutes of Health. The institution of Dr. Fox has received research support from National MS Society. Dr. Fox has received publishing royalties from a publication relating to health care.
Douglas L. Arnold, MD, FAAN (Montreal Neurological Institute, McGill Univ)	Dr. Arnold has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Arnold has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for BMS. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Frequency Therapeutics. Dr. Arnold has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Merck. Dr. Arnold has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. Dr. Arnold has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche. Dr. Arnold has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Shionogi. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Xfacto communications. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eli Lilly. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EMD Serono. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biohaven. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Find therapeutics. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for GSK. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Idorsia. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Kiniksa. Dr. Arnold has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Clario.

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