RT Journal Article SR Electronic T1 PARTIAL INDEPENDENCE OF FINGOLIMOD EFFECT ON DIFFUSE VS. FOCAL DAMAGE JF Journal of Neurology, Neurosurgery & Psychiatry JO J Neurol Neurosurg Psychiatry FD BMJ Publishing Group Ltd SP e4 OP e4 DO 10.1136/jnnp-2015-312379.112 VO 86 IS 11 A1 C Constantinescu A1 N De Stefano A1 L Kappos A1 EW Radue A1 T Sprenger A1 D Piani Meier A1 D Häring A1 D Tomic YR 2015 UL http://jnnp.bmj.com/content/86/11/e4.16.abstract AB Objective To investigate if the effects of fingolimod 0.5mg on brain volume loss are mediated through effects on focal disease activity (FD) or independent-reduction of diffuse damage (DD).Methods FREEDOMS and FREEDOMS-II data was pooled and analyzed post-hoc. Assessment of the percent brain volume change (PBVC) at M12 and 24, in patients with no evidence of FD, (absence of new Gd+ T1-lesions and/or new/enlarging T2-lesions) and clinical relapses. Regression analysis of the intent-to-treat (ITT) population to quantified whether the extent of the treatment effect was maintained for patients with new/active lesions and relapsesResults Of the 1383 patients included, 808 patients (placebo=142; fingolimod=666) showed no FD at M12 and 573 patients (placebo=79; fingolimod=494) at M24 showed no FD. Fingolimod significantly reduced PBVC by 52% and 42% vs. placebo, over 12M and 24M respectively. In the pooled ITT population, fingolimod reduced 49% of PBVC (p<0.001)vs placebo over 24M. This effect was still evident when adjusting for new-active lesions and relapse activity (28% reduction vs placebo, p<0.001). The regression model suggests 57% of fingolimod effect on PBVC is FD-independent. Fingolimod effect on DD is partly independent of its treatment effect on FD, suggesting fingolimod impacts both inflammatory and neurodegenerative components.