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.

Association of brain volume loss and long-term disability outcomes in patients with multiple sclerosis treated with teriflunomide.

BACKGROUND: Teriflunomide 14 mg significantly reduced brain volume loss (BVL) and confirmed disability worsening (CDW) compared with placebo in the TEMSO core study. OBJECTIVE: To investigate the relationship between BVL from Baseline to Year 2 in the TEMSO core study and long-term CDW (Year 7) in the TEMSO long-term extension (NCT00803049). METHODS: Structural Image Evaluation using Normalization of Atrophy determined BVL. Long-term CDW was assessed by Expanded Disability Status Scale confirmed for 12 and 24 weeks. An additional analysis evaluated the relative contribution of BVL (Year 2) and other outcomes as potential mediators of the effect of teriflunomide 14 mg on 12-week CDW. RESULTS: Patients with the least BVL were significantly less likely to have 12- and 24-week CDW at Year 7 compared with patients with the most BVL. A mediation analysis revealed that BVL (Year 2) explained 51.3% of the treatment effect on CDW; new or enlarging T2w lesions over 2 years explained 30.8%, and relapses in the first 2 years explained 38.5%. CONCLUSIONS: These results highlight the potential predictive value of BVL earlier in the disease course on long-term disability outcomes. The mediation analysis suggests that teriflunomide may prevent disability worsening largely through its effects on BVL.

Proportion of alemtuzumab-treated patients converting from relapsing-remitting multiple sclerosis to secondary progressive multiple sclerosis over 6 years.

BACKGROUND: Few data exist concerning conversion to secondary progressive MS in patients treated with disease-modifying therapies. OBJECTIVE: Determine the proportion of alemtuzumab-treated patients converting from relapsing-remitting to secondary progressive MS during the CARE-MS core and extension studies. METHODS: Patients (N = 811) were analyzed post hoc for secondary progressive MS conversion. Optimal conversion definition: Expanded Disability Status Scale (EDSS) score ≥4, pyramidal functional system score ≥2, and confirmed progression over ≥3 months including confirmation within the functional system leading to progression, independent of relapse. RESULTS: Over 6.2 years median follow-up, 20 alemtuzumab-treated patients converted (Kaplan-Meier estimate, 2.7%; 95% confidence interval, 1.8%-4.2%). Sensitivity analysis accounting for dropouts showed similar results (3%), as did analyses using alternative definitions with different EDSS thresholds and/or confirmation periods, and analysis of core study subcutaneous interferon beta-1a-treated patients who received alemtuzumab in the extension. Patients converting to secondary progressive MS were older, and had higher EDSS scores and greater brain lesion volumes at baseline, but did not need additional alemtuzumab or other therapies. CONCLUSIONS: The 6-year conversion rate to secondary progressive MS was low for alemtuzumab-treated patients, supporting further study of the role alemtuzumab may play in reducing risk of secondary progression.ClinicalTrials.gov identifiers: NCT00530348, NCT00548405, NCT00930553.

Consensus panel guidelines for the use of intrathecal baclofen therapy in poststroke spastic hypertonia.

Intrathecal baclofen (ITB) therapy has been increasingly employed for the management of poststroke spastic hypertonia, a complication that can lead to deformity, discomfort, and exacerbation of motor impairments. Because its use in stroke is not as established as other indications, ITB therapy has not been subjected to rigorous investigation. There is limited evidence to guide clinicians regarding application of this therapy in this patient population. This article aims to review the available scientific literature and the opinion of several experts on the topic. It will also describe the recommendations of these experts with regard to addressing common clinical situations that may influence treatment decisions in the stroke population.