Abstract Details

Title Fingolimod-Effect on Brain Atrophy and Clinical/MRI Correlations in Three Phase 3 Studies - TRANSFORMS, FREEDOMS and FREEDOMS II

Topic MS and Related Diseases

Presentation(s) S51 - (-)

Poster/Presentation
Number 006

Objective

Background Brain atrophy reflects tissue damage and represents an important outcome in multiple sclerosis (MS) clinical trials. Fingolimod, an oral therapy approved for relapsing MS has consistently reduced loss of brain volume (BV) in Phase 3 studies.

Design/Methods Rate of total BV loss was measured in each of three Phase 3 studies (TRANSFORMS, FREEDOMS, FREEDOMS II) using SIENA while baseline BV was measured using SIENAX. Predefined analysis of BV was by rank ANCOVA or Wilcoxon rank sum. Correlations of BV and other disease characteristics were analyzed for each study independently at baseline and during study.

Results Fingolimod significantly reduced the rate of brain atrophy compared to placebo over 2 years by 36% in FREEDOMS (-0.84 % vs. -1.31%) and 33% in FREEDOMS II (-0.86% vs. -1.28%) and over 1 year compared to interferon beta-1a IM by 31% (-0.31% vs. -0.45%) in TRANSFORMS. Effect was apparent by 6 months of treatment in placebo-controlled studies. Baseline BV correlated best with lesion volume (T2 and T1 black holes), disability (EDSS and MSFC), disease duration and age (r values ranged from 0.21 to 0.44) at baseline. High baseline T2 lesion burden and active Gd-T1 lesions were predictive of on-study BV loss. On-study BV loss correlated best with increasing numbers and volume of T2 lesions. Additional correlations of change in BV with change in clinical and MRI outcomes will be presented.

Conclusions Fingolimod consistently reduced the rate of BV loss in all Phase 3 studies. Atrophy at baseline correlated with disease severity/duration while baseline T2 volume and Gd+ lesion status was predictive of future BV loss. On-study BV loss correlated best with increasing numbers and volume of T2 lesions.

Authors/Disclosures
Jeffrey A. Cohen, MD (Cleveland Clinic) PRESENTER	Dr. Cohen has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Convelo. Dr. Cohen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Astoria. Dr. Cohen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bristol Myers Squibb. Dr. Cohen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Atara. Dr. Cohen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Cohen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Viatris. Dr. Cohen has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Celltrion. Dr. Cohen has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Sage.
Ernst-Wilhelm Radue, MD (Medical Image Analysis Center)	Dr. Radue has nothing to disclose.
Frederik Barkhof, MD, PhD (Image Analysis Center)	Frederik Barkhof has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Frederik Barkhof has received personal compensation in the range of $0-$499 for serving as a Consultant for Biogen. Frederik Barkhof has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Combinostics. Frederik Barkhof has received personal compensation in the range of $500-$4,999 for serving as a Consultant for IXICO. Frederik Barkhof has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen. Frederik Barkhof has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for EISAI.
Ludwig Kappos, MD, FAAN (RC2NB, University Hospital Basel)	The institution of Dr. Kappos has received research support from Bayer. The institution of Dr. Kappos has received research support from Biogen. The institution of Dr. Kappos has received research support from Genentech. The institution of Dr. Kappos has received research support from Genzyme. The institution of Dr. Kappos has received research support from Janssen. The institution of Dr. Kappos has received research support from Merck Serono. The institution of Dr. Kappos has received research support from Minoryx. The institution of Dr. Kappos has received research support from Novartis. The institution of Dr. Kappos has received research support from Roche. The institution of Dr. Kappos has received research support from Sanofi. The institution of Dr. Kappos has received research support from Santhera. The institution of Dr. Kappos has received research support from Swiss MS Society, Swiss National Research Foundation, European Union, Roche Research Foundation, Innosuisse. The institution of Dr. Kappos has received research support from Shionogi. The institution of Dr. Kappos has received research support from Japan Tobacco. The institution of Dr. Kappos has received research support from Auriga Vision AG. The institution of Dr. Kappos has received research support from EMD Serono. The institution of Dr. Kappos has received research support from Glaxo Smith Kline. The institution of Dr. Kappos has received research support from Wellmera AG. The institution of Dr. Kappos has received research support from Eli Lilly (Suisse) SA. The institution of Dr. Kappos has received research support from Bristol Myers Squibb. The institution of Dr. Kappos has received research support from Celltrion Inc. Dr. Kappos has received intellectual property interests from a discovery or technology relating to health care.
Peter A. Calabresi, MD, FAAN (Johns Hopkins University)	Dr. Calabresi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis. Dr. Calabresi has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lilly. Dr. Calabresi has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Idorsia. An immediate family member of Dr. Calabresi has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for MyMD. Dr. Calabresi has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Myelin Repair Foundation. The institution of Dr. Calabresi has received research support from Genentech. Dr. Calabresi has received publishing royalties from a publication relating to health care. Dr. Calabresi has received personal compensation in the range of $500-$4,999 for serving as a Study Section Member with NIH. Dr. Calabresi has received personal compensation in the range of $500-$4,999 for serving as a Grant reveiwer with Myelin Repair Foundation. Dr. Calabresi has received personal compensation in the range of $500-$4,999 for serving as a Speaker for CME with NYAS. Dr. Calabresi has received personal compensation in the range of $500-$4,999 for serving as a Speaker with Academic CME.
Dieter Haering	Dieter Haering has received personal compensation for serving as an employee of Novartis.
	No disclosure on file
Isabella L. Simone (Insitute of Neurologist, Univerisity of Bari Italy)	No disclosure on file
	No disclosure on file
Gordon S. Francis, MD, FAAN	No disclosure on file

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