Smaller Baseline Brain Volume and Higher Atrophy Rate over Two Years is Associated with Poorer Clinical Outcomes: Post Hoc Analysis of the MS-STAT Trial in Secondary Progressive MS (P7.259)

OBJECTIVE: A post-hoc exploratory analysis of all subjects from the phase 2 MS-STAT trial in secondary progressive MS (SPMS) to determine the relationship between baseline brain volume and atrophy rate with measured clinical parameters. BACKGROUND: The 2 year MS-STAT trial using high dose simvastatin (80mg) versus placebo, demonstrated a 43[percnt] annualised reduction in whole-brain atrophy rate with indications of effect on both clinician and patient-observed disability outcomes. DESIGN/METHODS:Linear regression was used to examine the associations between brain volume and clinical outcomes (Expanded Disability Status Scale [EDSS]; 9 Hole Peg Test, 25ft walk, Paced Auditory Serial Addition Test [PASAT]: components of the MS Functional Composite [MSFC]). In all models the clinical outcomes, or change in clinical outcome was treated as the dependent variable with baseline brain volume or brain atrophy rate included as the predictor variable of interest. All models were adjusted for potential confounders. RESULTS:At baseline, smaller brain volume was associated with slower 25ft walk speed, 9 Hole Peg test and lower PASAT scores. Greater whole brain atrophy was associated with increasing (worsening) EDSS and 25ft walk test slowing, but not associated with change in 9 Hole Peg test or PASAT. A 1[percnt] per year higher atrophy rate was associated with 0.24 points increase in EDSS, and 0.57 ft/s slowing of walk speed. In addition, 1[percnt] per year higher atrophy rate between baseline and 12 months was predictive of 0.17 points increase in EDSS between 12 and 25 months. CONCLUSIONS: Both baseline brain volume and change in brain volume, demonstrate important associations with clinical parameters, supporting the use of brain atrophy rate as a suitable biologically plausible outcome for clinical disease progression. Study Supported by:Moulton Foundation, Berkeley Foundation, MSTC, NIHR UCL/UCLH BRC.