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  1. C Constantinescu1,
  2. N De Stefano2,
  3. L Kappos3,
  4. EW Radue4,
  5. T Sprenger3,4,
  6. D Piani Meier6,
  7. D Häring5,
  8. D Tomic5
  1. 1Nottingham University, UK
  2. 2University of Siena, Siena, Italy
  3. 3University Hospital, Department of Neurology, Basel, Switzerland
  4. 4Medical Image Analysis Center (MIAC), University Hospital, Basel, Switzerland
  5. 5Novartis Pharma AG, Basel, Switzerland
  6. 6University of Genoa, Genoa, Italy


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 relapses

Results 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.

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