An MRI-Defined Measure of Cerebral Lesion Severity to Assess the Therapeutic Effect of Glatiramer Acetate in Multiple Sclerosis (P4.172)

Objective: Assess the sensitivity of the Magnetic Resonance Disease Severity Scale (MRDSS), based on cerebral lesions and atrophy, for treatment monitoring of glatiramer acetate (GA) in relapsing-remitting multiple sclerosis (MS). Background: MRDSS is a cerebral MRI composite scale evaluating MS disease severity shown by lesions and atrophy with inclusion of a unique metric of the destructive potential of lesions, the intrasubject T1/T2 lesion ratio. Methods: This retrospective non-randomized study included patients who started daily GA [n=23, age (median, range) 41 (26.2, 53.1) years, disease duration 1.8 (0.3, 20.3) years, Expanded Disability Status Scale (EDSS) score 1.0 (0, 3.5)], or received no disease-modifying therapy (noDMT) [n=21, age 44.8 (28.2, 55.4), disease duration 6.5 (0.4, 33.5), EDSS 0 (0, 2.5)] for two years. MRDSS was the sum of the z-score (normalized to a reference sample) of T2 hyperintense lesion volume (T2LV), the ratio of T1 hypointense LV to T2LV (T1/T2), and brain parenchymal fraction (BPF) multiplied by negative 1. The two groups were compared by Wilcoxon rank sum tests; within group change was assessed by Wilcoxon signed rank tests. Results: GA subjects had less progression than noDMT on T1/T2 [(median z-score change (range), 0 (-1.07, 1.20) vs. 0.41 (-0.30, 2.51), p=0.003)] and MRDSS [0.01 (-1.33, 1.28) vs. 0.46 (-1.57, 2.46), p=0.01]; however not on BPF [0.12 (-0.18, 0.58) vs. 0.10 (-1.47,0.50), p=0.59] and T2LV [-0.03 (-0.90, 0.57) vs. 0.01 (-1.69, 0.34), p=0.40]. While GA subjects worsened only on BPF [0.12 (-0.18, 0.58), p=0.001], NoDMT worsened on BPF [0.10 (-1.47, 0.50), p=0.002], T1/T2 [0.41 (-0.30, 2.51), p=0.0002], and MRDSS [0.46 (-1.57, 2.46), p=0.0006]. Conclusions: We show the potential of two new cerebral MRI metrics to track therapeutic response in MS. Within the MRDSS, the T1/T2, an index of the destructive potential of lesions, may provide sensitivity to treatment effects. Study Supported by: Teva Neuroscience Disclosure: Dr. Kim has nothing to disclose. Dr. Tauhid has nothing to disclose. Dr. Dupuy has nothing to disclose. Dr. Tummala has nothing to disclose. Dr. Khalid has nothing to disclose. Dr. Healy has received research support from Merck Serono, Novartis and Genzyme. Dr. Bakshi has received research support from Biogen, EMD Serono, Novartis, Questcor, Sanofi/Genzyme, and Teva Neuroscience.