Effects of teriflunomide treatment on cognitive performance and brain volume in patients with relapsing multiple sclerosis: Post hoc analysis of the TEMSO core and extension studies

Background: In post hoc analyses of Teriflunomide Multiple Sclerosis Oral study (TEMSO; NCT00134563), teriflunomide 14 mg significantly reduced brain volume loss (BVL) versus placebo in patients with relapsing multiple sclerosis (MS). Objective: In this post hoc analysis of TEMSO and its long-term extension (NCT00803049), we examined the relationship between teriflunomide's effects on BVL and cognition. Methods: We analyzed data from 709 patients who received teriflunomide 14 mg in TEMSO or its extension. The change in cognitive performance, assessed using the Paced Auditory Serial Addition Test 3 (PASAT-3), was measured in subgroups stratified by BVL over 2 years (least BVL: ⩽ 0.52%; intermediate BVL: >0.52%-2.18%; most BVL: >2.18%). BVL, MRI lesions, and relapses over 2 years were evaluated as potential mediators of the effect of teriflunomide on cognition. Results: Teriflunomide 14 mg significantly improved PASAT-3 Z-scores versus placebo through year 2. In the least- and intermediate-BVL groups, significant improvements in PASAT-3 Z-score were demonstrated versus the most-BVL group over 3 years in the extension. According to the mediation analysis, 44% of the teriflunomide effect on cognition was due to effects on BVL at year 2. Conclusion: Teriflunomide improves cognition largely through its effects on BVL. Accelerated BVL earlier in the disease course may predict cognitive outcomes. Clinicaltrials.gov identifier: NCT00134563, NCT00803049