Abstract Details

Title Reduced Grey Matter Atrophy in Patients with Relapsing Multiple Sclerosis Treated with Cladribine Tablets

Topic Multiple Sclerosis

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

Poster/Presentation
Number 089

Objective

Post hoc evaluation of grey matter (GM) and white matter (WM) volume changes in patients with relapsing multiple sclerosis (MS) randomized to cladribine tablets 3.5 mg/kg bodyweight (CT3.5; cumulative dose over 2 years) or placebo in the CLARITY study.

Background It is increasingly understood that GM atrophy is associated with disability progression and cognitive decline in patients with MS. Previously, we demonstrated that treatment with CT3.5 in the CLARITY study decreased brain atrophy compared with placebo, which was closely associated with a lower risk of disability progression [De Stefano et al. MSJ 2018].

Design/Methods Images from pre-gadolinium T1-weighted magnetic resonance imaging scans of patients randomized to CT3.5 or placebo for 2 years in CLARITY were evaluated using SIENA-XL software. Images from 0–6 months (CT3.5, n=267; placebo, n=265) were analyzed independently of images from 6–24 months (CT3.5, n=184; placebo, n=186) to account for the potential effects of pseudoatrophy. Annualized mean changes in percentage of GM volume (PGMV) or WM volume (PWMV) between CT3.5 and placebo for 0–6 and 6–24 months were compared using a variance model.

Results

CT3.5 reduced GM and WM volume versus placebo in the first 6 months, consistent with pseudoatrophy (PGMV change: CT3.5 -0.53 vs. placebo -0.25 [p=0.045]; PWMV change: CT3.5 -0.49 vs. placebo -0.34 [p=0.137]). Brain volume loss from 6–24 months was reduced in patients randomized to CT3.5 with the difference between CT3.5 and placebo significant for GM (PGMV change: CT3.5 -0.90 vs. placebo -1.27 [p=0.026]; PWMV change: CT3.5 -0.32 vs. placebo -0.40 [p=0.52]).

Conclusions Volume loss reduction in WM and, particularly, in GM was noted from 6-24 months in CT3.5-treated patients versus placebo, after a period of pseudoatrophy (0-6 months). Such findings suggest that CT3.5 significantly reduces brain atrophy predominantly in the GM, an effect that may contribute to lower risk of disability progression.

Authors/Disclosures
Nektaria Alexandri PRESENTER	Nektaria Alexandri has received personal compensation for serving as an employee of Merck Healthcare KGaA.
	No disclosure on file
Maria Pia Sormani (University of Genoa)	Maria Pia Sormani has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Maria Pia Sormani has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Maria Pia Sormani has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. Maria Pia Sormani has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Maria Pia Sormani has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bristol meyer. Maria Pia Sormani has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Maria Pia Sormani has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Immunic. Maria Pia Sormani 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, Roche. Maria Pia Sormani has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Maria Pia Sormani has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche.
	No disclosure on file
	No disclosure on file
Rosa Cortese (University of Siena)	No disclosure on file
Nicola De Stefano, MD (University of Siena)	Dr. De Stefano has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck Healthcare KGaA. Dr. De Stefano has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Immunic AG. Dr. De Stefano has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis Pharma AG. Dr. De Stefano has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck Serono S.p.A. Dr. De Stefano 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. Dr. De Stefano has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche S.p.A.. The institution of Dr. De Stefano has received research support from Italian MS Society. The institution of Dr. De Stefano has received research support from Merck Healthcare KGaA.

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