Teriflunomide Significantly Slows Brain Volume Loss In Ms Patients Irrespective Of Disability Progression

Objective: To explore relationships between brain volume loss (BVL) and disability progression in a subgroup analysis of TEMSO (NCT00134563). Background: Two phase 3 studies, TEMSO and TOWER (NCT00751881), showed significant effects of teriflunomide 14mg in reducing risk of 12-week confirmed disability progression in patients with relapsing forms of MS. Utilizing an established method (Structural Image Evaluation using Normalization of Atrophy; SIENA), we demonstrated teriflunomide was also associated with significant reductions in BVL vs placebo over 2 years. Methods: SIENA analysis was conducted on patient scans (n=969) to determine BVL in the first (n=808) and second (n=709) year of TEMSO. A post hoc subgroup analysis was performed according to confirmed disability progression (defined as an increase from baseline of ≥1.0 point on the Expanded Disability Status Scale [EDSS; or ≥0.5 points for patients with a baseline EDSS score u003e5.5] that persisted for at least 12 weeks). Treatment group comparisons were calculated using rank ANCOVA. Results: Median percentage BVL from baseline for patients without disability progression was lower with teriflunomide 14mg (-0.40; n=211) vs placebo (-0.52; n=211); relative change, 22[percnt] (P=0.0128) at Year 1, and Year 2, teriflunomide 14mg (-0.87; n=185) vs placebo (-1.12; n=174); relative change, 23[percnt] (P=0.0129). For patients with disability progression, median percentage BVL from baseline was lower with teriflunomide 14mg (-0.25; n=52) vs placebo (-0.81; n=65); relative change, 69[percnt] (P=0.0037) at Year 1 and Year 2, teriflunomide 14mg (-0.90; n=50) vs placebo (-1.61; n=60); relative change, 44[percnt] (P=0.0043). BVL was higher in patients with disability progression vs those without progression in the placebo- (P=0.0114 at Year 2) but not in the teriflunomide-treated group. Conclusions: These subgroup analyses confirm teriflunomide slows BVL independently of disability progression, demonstrating a clinically meaningful and consistent benefit of teriflunomide.Study supported by: Genzyme, a Sanofi company. Disclosure: Dr. Sprenger has received personal compensation for activities with Actelion, Biogen Idec, Electrocore, and Genzyme. Dr. Kappos9s institution (University Hospital Basel) has received royalty payments from Neurostatus Systems GmbH. Dr. Radue has received research support from Actelion, Bayer Schering, Biogen Idec, Genzyme, Merck Serono, Novartis, and Sanofi. Dr. Gaetano has nothing to disclose. Dr. Mueller-Lenke has nothing to disclose. Dr. Wuerfel has received research support from Biogen Idec and Novartis. Dr. Thangavelu has received personal compensation for activities with Genzyme as an employee. Dr. Panzara has received personal compensation for activities with Genzyme. Dr. Steven J. Cavalier has received personal compensation for activities with Genzyme as an employee. Dr. Wolinsky has received royalty payments from Chemicon International through the University of Texas Health Science Center at Houston.