Effect of Ibudilast on Thalamus and Spinal Cord in Progressive MS: Analysis from a Phase II Trial

Objective: To report the effect of ibudilast on thalamus and spinal cord in progressive MS. Background: The thalamus and spinal cord are CNS regions commonly affected in MS. The SPRINT-MS phase 2 trial, where ibudilast slowed brain atrophy progression by 48%, provides an ideal setting to evaluate the impact of ibudilast on measures of tissue integrity in these regions. Design/Methods: 255 subjects with progressive MS received either ibudilast or placebo for two years and imaged every 24 weeks using Siemens or GE 3T systems. Acquisitions included 3D spoiled gradient-recalled echo; proton density weighted and T2 weighted 2D turbo/fast spin-echo; 3D spoiled gradient-recalled echo with and without magnetization transfer pulse. Upper cervical spinal cord area was determined by atlas-based segmentation; thalamic volume was measured using multi-modal atlas-based segmentation and Jacobian integration; mean MTR was calculated within the thalamic mask. All imaging endpoints were assessed for differing rates of change between the treatment groups over time using linear mixed modeling. Results: Change in thalamic MTR was −0.01 units/month with placebo and +0.005 with ibudilast (difference 0.0154; p Conclusions: In a phase II trial in progressive MS, ibudilast treatment had differential effects on the thalamus: thalamic MTR improved with ibudilast, but progression of thalamic atrophy was unaffected, which suggests that MTR and atrophy are measuring different aspects of MS. Similarly with whole brain atrophy, progression of spinal cord atrophy was cut in half, although this difference was not statistically significant. These analyses provide further insight into the effect of ibudilast in progressive MS and the utility of these imaging modalities. Disclosure: Dr. Nakamura has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Speaking fees (Biogen, Novartis, and Sanofi).. Dr. Nakamura has received royalty, license fees, or contractual rights payments from Royalty fees for licenses (Biogen).. Dr. Nakamura has received research support from Research support (Biogen, Novartis, and Sanofi).. Dr. Raska has nothing to disclose. Dr. Goebel has nothing to disclose. Dr. Fox has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Robert Fox has received compensation for serving as a consultant or speaker from Actelion, Biogen, Celgene, EMD Serono, Genentech, Immunic, Novartis, and Teva. He, or the institution he works for, has received research support from Novartis.. Dr. Fox has received research support from He, or the institution he works for, has received research support from Novartis..