Abstract Details

Title Combined MRI Measure of Active Lesions and Brain Atrophy as a Surrogate for Disability in Multiple Sclerosis: A Meta-Analysis of Randomized Trials

Topic MS and Related Diseases

Presentation(s) P07 - (-)

Poster/Presentation
Number 096

Objective

Background BACKGROUND: Recent trial-level studies have shown that in MS the treatment effect on active MRI lesions strongly predicts the effect on clinical relapses and, to a lesser extent, on disability progression. Whether measures of brain atrophy rates can add to this relationship is unknown.

Design/Methods DESIGN/METHODS: We collected all published randomized clinical trials in relapsing-remitting (RR) MS lasting at least 2 years and including as endpoints: disability progression (defined as 6 or 3 months confirmed increase of 1 Expanded Disability Status Scale point), active MRI lesions (defined as new/enlarging lesions), and brain atrophy (defined as change in brain volume between year 2 and year 1 or month 6). A linear regression, weighted for trial size and duration, was used to assess the relationship between the treatment effects on MRI lesions, brain atrophy and disability progression.

Results RESULTS: 13 trials (8 placebo-controlled, 5 active-controlled with interferon or glatiramer acetate) including more than 13500 RRMS patients were included in the meta-analysis. Treatment effects on disability progression were correlated both with treatment effects on brain atrophy (R2=0.4, p=0.001) and on MRI lesions (R2=0.6, p<0.001). When the effects on brain atrophy and MRI lesions were included in a multivariate model, the correlation was higher still (R2=0.7, p<0.001) and both variables were retained as independently related to the treatment effect on disability progression.

Conclusions CONCLUSIONS: In RRMS, the treatment effect on brain atrophy predicts the effect on disability progression over 2 years. This effect is independent of the effect of lesions on disability, suggesting it relates to a different mechanism of progression. The two MRI measures predict the treatment effect on disability more strongly when used in combination.

Authors/Disclosures
PRESENTER	No disclosure on file
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.
Walter R. Royal III, MD	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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