OBJECTIVE: We investigated the determinants and clinical correlations of MRI-detected brain volume loss (BVL) among RRMSers from the phase 3 trials of fingolimod: FREEDOMS, FREEDOMS II, and TRANSFORMS.
METHODS: Post hoc analyses were conducted in the intent-to-treat populations from each trial and in a combined dataset of 3,635 MSers from the trials and their extensions. The relationship between brain volume changes and demographic, clinical, and MRI parameters was studied in pairwise correlations (Pearson) and in multiple regression models. The relative frequency of confirmed disability progression was evaluated in the combined dataset by strata of concurrent BVL at up to 4 years.
RESULTS: Increasing age, disease duration, T2 lesion volume, T1-hypointense lesion volume, and disability were associated with reduced brain volume (p < 0.001, all). The strongest individual baseline predictors of on-study BVL were T2 lesion volume, gadolinium-enhancing lesion count, and T1-hypointense lesion volume (p < 0.01, all). During each study, BVL correlated most strongly with cumulative gadolinium-enhancing lesion count, new/enlarged T2 lesion count (p < 0.001, both), and number of confirmed on-study relapses (p < 0.01). Over 4 years in the combined dataset (mean exposure to study drug, 2.4 years), confirmed disability progression was most frequent in MSers with greatest BVL.
CONCLUSIONS: Rate of BVL in RRMSers during the fingolimod trials correlated with disease severity at baseline and new disease activity on study, and was associated with worsening disability.