Abstract Details

Title Effects of Fingolimod and Natalizumab on Slowly Expanding Lesion Occurrence over Two Years of Treatment in Relapsing-remitting Multiple Sclerosis

Topic Multiple Sclerosis

Presentation(s) S5 - Multiple Sclerosis: Clinical Trials and Disease-modifying Therapy (1:48 PM-2:00 PM)

Poster/Presentation
Number 005

Objective To compare the effects of fingolimod and natalizumab on the occurrence of white matter lesions showing a progressive linear enlargement over two years of treatment, a putative biomarker of smouldering inflammation.

Background Fingolimod and natalizumab are highly effective treatments to reduce disease activity in relapsing-remitting multiple sclerosis (RRMS). However, their ability to limit slowly expanding lesion (SEL) accrual has not been evaluated yet.

Design/Methods RRMS patients starting fingolimod (n=25) or natalizumab (n=30) underwent 3T brain MRI scans at baseline, month 6, 12 and 24. We identified SELs among baseline lesions, by linearly fitting the Jacobian of the non-linear deformation field between timepoints, obtained using T1- and T2-weighted scans. A threshold ≥10% of annual increase was applied and neighbour voxels were grouped in clusters. Total number, percentage, volume of lesions defined as SELs, and their average magnetization transfer ratio (MTR) were calculated considering clusters ≥10 voxels.

Results

Treatment-groups were matched for baseline variables. The proportion of fingolimod-patients showing ≥1 SEL was higher compared to natalizumab (96% vs 50%, p<0.001). Compared to natalizumab-patients, fingolimod-patients showed a higher mean number (6.44 vs 3.40, p=0.004), and volume (0.20 vs 0.13 ml, p=0.002) of SELs, and mean percentages of lesions (7.30% vs 4.32%, p=0.007) and of lesional volume (2.12% vs 0.92%, p<0.001) defined as SELs. In both groups, compared to not-SELs, SELs showed significantly lower baseline mean MTR values (26.87 vs 34.36 in fingolimod-group; 26.79 vs 34.41 in natalizumab-group, p<0.001), without significant between-group differences and longitudinal changes.

Conclusions SELs assessment using T1-, T2-weighted and MTR sequences is feasible and allow to identify chronic active lesions typically described in MS pathology and characterized by smouldering inflammation, ongoing demyelination and axonal loss. Natalizumab seems to have a stronger effect in limiting the burden of SELs, while both drugs similarly prevent the accumulation of microstructural tissue damage in both SELs and not-SELs.

Authors/Disclosures
Paolo Preziosa (Ospedale San Raffaele) PRESENTER	Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bristol Myers Squibb . Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi Genzyme. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck.
Elisabetta Pagani	Elisabetta Pagani has nothing to disclose.
Lucia Moiola, MD, PhD (Fondazione Centro San Raffaele)	Dr. Moiola has nothing to disclose.
	No disclosure on file
Massimo Filippi, MD, FAAN (Ospedale San Raffaele, Neuroimaging Research Unit)	Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Alexion, Almirall, Biogen, Merck, Novartis, Roche, Sanofi. Dr. Filippi has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion, Biogen, Bristol-Myers Squibb, Merck, Novartis, Roche, Sanofi, Sanofi-Aventis, Sanofi-Genzyme, Takeda. Dr. Filippi has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bayer, Biogen, Celgene, Chiesi Italia SpA, Eli Lilly, Genzyme, Janssen, Merck-Serono, Neopharmed Gentili, Novartis, Novo Nordisk, Roche, Sanofi, Takeda, and TEVA. Dr. Filippi 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 Springer Nature. The institution of Dr. Filippi has received research support from Biogen Idec, Merck-Serono, Novartis, Roche, the Italian Ministry of Health, the Italian Ministry of University and Research, and Fondazione Italiana Sclerosi Multipla.
Maria A. Rocca (Neuroimaging Research Unit)	Maria Assunta Rocca has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen, Bristol Myers Squibb, Eli Lilly, Janssen, Roche. Maria Assunta Rocca has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for AstraZaneca, Biogen, Bristol Myers Squibb, Bromatech, Celgene, Genzyme, Horizon Therapeutics Italy, Merck Serono SpA, Novartis, Roche, Sanofi and Teva. The institution of Maria Assunta Rocca has received research support from MS Society of Canada, the Italian Ministry of Health, the Italian Ministry of University and Research, and Fondazione Italiana Sclerosi Multipla.

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