Effect of Fingolimod on Brain Atrophy: MRI Data From Phase 3 Studies

Background: Brain atrophy indicates tissue damage and is an important outcome measure in multiple sclerosis (MS) clinical trials. In clinical studies, fingolimod, a once-daily, oral therapy approved for relapsing forms of MS, has consistently reduced the loss of brain volume (BV) and inflammatory lesion activity.

Objectives: To assess the magnitude of treatment effect of fingolimod (0.5 mg/d) vs placebo or interferon (IFN) β-1a intramuscular (IM) on BV in phase 3 trials in patients with relapsing-remitting MS.

Methods: Total BV loss was measured in 3 phase 3 trials (TRANSFORMS, FREEDOMS, FREEDOMS II) with structural image evaluation using normalization of atrophy (SIENA), and baseline BV was measured using a cross-sectional method (SIENAX). MRI was performed within 30 days prior to randomization and at months 6, 12, and 24 (FREEDOMS, FREEDOMS II only). Efficacy was assessed by a blinded central MRI reader. Predefined analysis of BV was conducted by using rank ANCOVA model or Wilcoxon rank sum test. Correlations of BV and other disease characteristics were analyzed for each study independently at baseline and during the studies.

Results: Fingolimod significantly reduced BV loss compared with placebo over 2 years by 36% in FREEDOMS (–0.84 % vs –1.31%) and by 33% in FREEDOMS II (–0.86% vs –1.28%). In TRANSFORMS, fingolimod significantly reduced BV loss over 1 year compared with IFNβ-1a IM by 31% (–0.31% vs –0.45%). The effect was evident by 6 months of treatment in placebo-controlled studies (FREEDOMS and FREEDOMS II)

Conclusions: Fingolimod is the only MS therapy to have consistently reduced the rate of BV loss in three phase 3 studies.