To report the effect of ibudilast on thalamus and spinal cord in progressive MS.

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.

Change in thalamic MTR was -0.01 units/month with placebo and +0.005 with ibudilast (difference 0.0154; p<0.05). Change in thalamic volume was -0.0073 mL/month with placebo and -0.0072 with ibudilast (difference 0.0001; p=0.95). Upper cervical cord was analyzed from only 133 subjects. Change in spinal cord area was -0.0567 mm2/month with placebo and -0.298 with ibudilast (difference 0.0269; p=0.48).

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.