Gray Matter Volume Correlates with Information Processing as Measured by the Symbol Digit Modalities Test (SDMT) but Not with Physical Disability as Measured by the Expanded Disability Status Scale (EDSS) in Patients with Secondary Progressive Multiple Sclerosis (SPMS): Analysis of Baseline Correlations from the ASCEND Natalizumab Study (P6.143)

OBJECTIVE: To evaluate clinical correlates of brain tissue loss in progressive multiple sclerosis using baseline data from the ASCEND study of patients with SPMS. BACKGROUND: Previous studies showed that most brain tissue loss in SPMS affects gray matter (GM) rather than cerebral white matter. Clinical correlates of GM loss in SPMS are not well understood. DESIGN/METHODS: ASCEND is a phase 3b, randomized, double-blind, placebo-controlled study of natalizumab in SPMS patients. The primary endpoint is a composite of the EDSS, Timed 25-Foot Walk (T25FW), and Nine-Hole Peg Test (9HPT). Additional endpoints measure whole-brain (WB) and GM volumes with MRI and assess cognitive function using the SDMT in all patients and a composite measure (MS-COG) in a substudy. Pairwise correlations between brain volumes and measures of physical disability and cognitive function were evaluated from pooled blinded ASCEND baseline data using Spearman’s rank correlation coefficient (rho). RESULTS: Baseline mean EDSS score was 5.6 (N=889 enrolled patients). Median baseline WB, total GM, and cortical GM volumes were 1426.58 mL, 654.50 mL, and 518.84 mL, respectively. Mean (SD) baseline SDMT score was 38.76 (13.661). GM volumes were moderately correlated with SDMT (rho: total GM, 0.47; cortical GM, 0.45) but not with EDSS (rho: total GM, −0.06; cortical GM, −0.05) or T25FW (rho: total GM, −0.11; cortical GM, −0.11). Correlations between brain volumes and 9HPT ranged from −0.20 to −0.21 (dominant hand) and from −0.21 to −0.22 (nondominant hand). Similar correlation patterns were observed in patient subgroups with higher (蠅6.0) or lower (≤5.5) baseline EDSS scores. Correlations involving additional measures including WB volume and MS-COG results will also be presented. CONCLUSIONS: In ASCEND patients at baseline, GM volumes correlated with measures of information processing but not with EDSS or T25FW, demonstrating the importance of measuring cognitive function in SPMS clinical trials. Study supported by: Biogen Idec. Disclosure: Dr. Kapoor received personal compensation for activities with Biogen Idec, Novartis, Genzyme, and Teva. Dr. Arnold has received personal compensation for activities with Acorda, Bayer Healthcare, Biogen Idec, Merck Serono, Genentech, Genzyme, GlaxoSmithKline, Medimmune, Novartis, Receptos, Inc., Roche, Sanofi-Aventis, and Teva. Dr. Miller received research support for participation in clinical trials from Acorda, Biogen Idec, Genentech, Genzyme/sanofi-aventis, Novartis, Questcor, and Roche. Dr. Freedman has received personal compensation for activities with Bayer Healthcare, Biogen Idec, Chugai, EMD Canada, Genzyme, Novartis, Sanofi-Aventis, and Teva Canada Innovation. Dr. Goldman has received personal compensation for activities with Concert Pharmaceuticals. Dr. Hartung has holds stock and/or stock options from Opexa Therapeutics. Dr. Havrdova has received research support from the Czech Ministries of Education and Health. Dr. Jeffery has received personal compensation for activities with Bayer Pharmaceuticals, Biogen Idec, Teva, Serono, Acorda Therapeutics, Novartis, Genzyme, Genentech, GlaxoSmithKline, and Questcor Diagnostics as a speaker and/or consultant. Dr. Sellebjerg has received personal compensation for activities with Biogen Idec, Novartis, Merck & Co., Inc., Teva Neuroscience, Genzyme Corporation as a consultant. Dr. Catrillo-Viguera has received personal compensation for activities with Biogen Idec as an employee. Dr. Chen has received personal compensation for activities with Biogen Idec as an employee. Dr. Cadavid has received personal compensation for activities with Biogen Idec as an employee. Dr. Mikol has received personal compensation for activities with Biogen Idec as an employee.