Effect of ibudilast on thalamic magnetization transfer ratio and volume in progressive multiple sclerosis

Abstract

Background: Thalamic volume (TV) is a sensitive biomarker of disease burden of injury in multiple sclerosis (MS) and appears to reflect overall lesion loads. Ibudilast showed significant treatment effect on brain atrophy and magnetization transfer ratio (MTR) of normal-appearing brain tissue but not in new/enlarging T2 lesion in the SPRINT-MS randomized clinical trial. Objective: To evaluate the effect of ibudilast on thalamic tissue integrity and volume in the SPRINT-MS. Methods: A total of 255 participants with progressive MS were randomized to oral ibudilast or placebo, and thalamic MTR and normalized TV over 96 weeks were quantified. Mixed-effect modeling assessed treatment effects on the thalamic MTR and TV, separately. Similarly, the measures were compared between the participants with confirmed disability progression (CDP). Results: Ibudilast’s treatment effect was observed compared to placebo for thalamic MTR ( p = 0.03) but not for TV ( p = 0.68) while TV correlated with T2 lesion volume ( p < 0.001). CDP associated with thalamic MTR ( p = 0.04) but not with TV ( p = 0.7). Conclusion: Ibudilast showed an effect on thalamic MTR, which was associated with CDP, suggesting a clinically relevant effect on thalamic tissue integrity. However, the treatment effect was not observed in TV, suggesting that thalamic atrophy is more closely associated with global inflammatory activity than local tissue integrity. ClinicalTrials.gov: NCT01982942