Proportion Of Patients With Brain Volume Loss Comparable To Healthy Adults In Fingolimod Phase 3 Multiple Sclerosis Studies (S13.006)

OBJECTIVE: Pooled data from the 2-year, placebo-controlled, phase 3 studies of fingolimod were used to assess the proportions of patients with multiple sclerosis (MS) with yearly rates of brain volume (BV) loss comparable to those reported in healthy adults (HAs). BACKGROUND: Data from previous studies show a yearly rate of BV loss in HAs of approximately -0.2% to -0.3% up to 55 years of age, while the equivalent rate in patients with MS ranges from approximately -0.6% to -1.0%. DESIGN/METHODS: Percentage change in BV from baseline was assessed in patients aged 17-57 years in FREEDOMS or FREEDOMS II at 6, 12 and 24 months by structural image evaluation using normalization of atrophy (SIENA). An arbitrary, conservative cut-off of -0.2% for BV loss was selected, which represents the lowest estimate reported in the literature for age-adjusted BV loss in HAs using the SIENA method. Then, the proportions of patients with BV loss that did not exceed an annual rate of -0.2% were calculated by age category (17-30, 31-40, 41-50, 51-57 years) for each treatment group during months 0-24. Age stratification was performed owing to the strong influence of age on BV loss. RESULTS: By increasing age group, the proportions of patients (fingolimod versus placebo) with BV loss of less than -0.2% per annum were 33% versus 22%, respectively, (age 17-30 years), 27% versus 18% (age 31-40 years), 27% versus 21% (age 41-50 years), and 39% versus 19% (age 51-57 years). CONCLUSIONS: The proportions of patients who had the least degree of global brain tissue loss as measured by the yearly rate of BV loss, which was comparable to that reported in cohorts of HA, was greater with fingolimod than placebo over 2 years. This result was consistent across the age categories assessed. Study Supported by: Novartis Pharma AG. Disclosure: Dr. De Stefano has received personal compensation for activities with Teva Neuroscience, Bayer, Sanofi-Aventis, Biogen Idec, Novartis, and Merck Serono. Dr. Tomic has received personal compensation for activities with Novartis as an employee. Dr. Tomic holds stock and/or stock options in Novartis. Dr. Haering has received personal compensation for activities with Novartis as an employee. Dr. Dibernardo has received personal compensation for activities with Novartis as an employee. Dr. Dibernardo holds stock and/or stock options in Novartis. Dr. Francis has received personal compensation for activities with Novartis as an employee. Dr. Francis holds stock and/or stock options in Novartis which sponsored research in which Dr. Francis was involved as an investigator. Dr. Radu has received personal compensation for activities with Biogen Idec, Novartis, Merck Serono and Bayer Schering as a speaker and consultant. Dr. Radu has received research support from Actelion, Basilea Pharmaceutica, Bayer Schering, Biogen Idec, Merck Serono and Novartis. Dr. Kappos has received personal compensation for activities with the University Hospital Basel. Dr. Kappos has received research support from the Swiss MS Society, Swiss National Research Foundation, the European Union, Gianni Rubatto Foundation, Novartis, and Roche Diagnostics Corp.