European journal of neurology | 2021
Baseline characteristics and effects of fingolimod on cognitive performance in patients with relapsing-remitting multiple sclerosis.
Abstract
BACKGROUND\nStudies reporting baseline determinants of cognitive performance and treatment effect on cognition in patients with MS are limited. We investigated the baseline correlates of cognition and the long-term treatment effects with fingolimod 0.5 mg once daily on cognitive processing speed (CPS) and attention in patients with relapsing-remitting MS (RRMS).\n\n\nMETHODS\nThis post-hoc analysis pooled data from the phase 3 FREEDOMS and FREEDOMS II trials (N=1556). We assessed the correlation between baseline patient demographic and disease characteristics and baseline Paced Auditory Serial Addition Test 3 (PASAT-3) scores (Spearman s rank test) and the changes from baseline in PASAT-3 (Mixed model repeated measures model) in the fingolimod and placebo (up to 24 months) or placebo-fingolimod switched (from Month 24 up to 120 months) groups. Additionally, predictive value of PASAT-3 for future disease outcomes was assessed (Cox or logistic regression models).\n\n\nRESULTS\nAmong the variables assessed, lower PASAT-3 score at baseline correlated with higher disease burden (total brain volume, T2 lesion volume, and Expanded Disability Status Scale score), longer disease duration and older age (p<0.0001 for all). Fingolimod significantly improved PASAT-3 scores from baseline versus placebo at 6 (1.3; p=0.0007), 12 (1.1; p=0044) and 24 months (1.1; p=0.0028), with sustained effect (overall treatment effect p=0.0012) up to 120 months. Improvements were seen regardless of the baseline cognitive status (PASAT quartiles). Baseline PASAT-3 score was predictive of both clinical and MRI measures of disease activity at Month 24 (p<0.001 for all).\n\n\nCONCLUSION\nEarly fingolimod treatment may offer long-term cognitive benefit in patients with RRMS.