Teriflunomide Slows Brain Volume Loss in Relapsing MS: A SIENA Analysis of the TEMSO MRI Dataset (P3.089)

Objective: To assess effects of teriflunomide on brain volume loss (BVL) in patients with relapsing MS (RMS) utilizing SIENA (Structural Image Evaluation using Normalization of Atrophy). Background: Two phase 3 studies, TEMSO (NCT00134563) and TOWER (NCT00751881), showed significant effects of teriflunomide on slowing disability progression in patients with RMS. In TEMSO, teriflunomide significantly reduced lesional magnetic resonance imaging (MRI) disease markers, but did not significantly attenuate BVL (measured by brain parenchymal fraction). Given the associations between BVL and long-term disability, a blinded independent analysis of TEMSO MRI data was warranted using a validated alternative method for measuring brain tissue loss. Methods: In this analysis, primary MRI data from TEMSO were analyzed (blinded to treatment allocation and other study data) to assess change in brain volume from baseline to Weeks 48 and 108 in patients treated with placebo, teriflunomide 7mg, or 14mg. Median annualized percent change in brain volume from baseline was compared across randomized groups via rank ANCOVA. Results: Data from 969 patient scans were included: 808 had baseline and Week 48 scans, 709 had baseline and Week 108 scans. Median percentage BVL from baseline at Year 1 and Year 2 for placebo was 0.61 and 1.29, respectively. For teriflunomide 14mg and 7mg, BVL was 0.39 and 0.90, and 0.40 and 0.94, respectively. BVL was lower for both teriflunomide groups vs placebo at Months 12 and 24: 14mg (36.9[percnt], P=0.0001); 7mg (34.4[percnt], P=0.0011); and 30.6[percnt] (P=0.0001) for 14mg; 27.6[percnt] (P=0.0019) for 7mg, respectively. Conclusions: This blinded analysis demonstrates teriflunomide was associated with significant reductions in BVL vs placebo over 2 years. These findings using SIENA, an established measure of brain tissue loss, are consistent with the effects of teriflunomide on delaying disability progression observed across studies in patients with RMS. Study supported by: Genzyme, a Sanofi company. Disclosure: Dr. Radue has received research support from Actelion, Bayer Schering, Biogen Idec, Genzyme, Merck Serono, Novartis, and Sanofi. Dr. Sprenger has received personal compensation for activities with Actelion, Biogen Idec, Electrocore, and Genzyme. 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. Steven J. Cavalier has received personal compensation for activities with Genzyme as an employee. Dr. Kappos9s institution (University Hospital Basel) has received royalty payments from Neurostatus Systems GmbH.