Effects of Ibudilast on MRI Measures in the Phase 2 SPRINT-MS Study
Robert T. Naismith, Robert Bermel, Christopher S. Coffey, Andrew Goodman, Janel Fedler, Marianne Kearney, Eric C. Klawiter, Kunio Nakamura, Sridar Narayanan, Christopher Goebel, Jon Yankey, Elizabeth Klingner, Robert J. Fox, on behalf of the SPRINT-MS investigators Shlomo Shinnar MD Daniel Ontaneda MD Claire S. Riley MD Jai Perumal MD Neil Lava MD Eric Klawiter MD Bruce Cohen MD Michael Racke MD Vijayshree Yadav MD Burk Jubelt MD Bianca WeinstockGutman MD Patricia Coyle MD Pavle Repovic MD, PhD Khurram Bashir MD Michelle Apperson MD Barbara Giesser MD Aram Zabeti MD Augusto Miravalle MD Sharon Lynch MD Silvia Delgado MD Valerie Suski MD Andrew Goodman MD Angela Flores MD Dana DeWitt MD Myla Goldman MD Harold Moses M
Abstract
<h3>Objective</h3> To determine whether ibudilast has an effect on brain volume and new lesions in progressive forms of multiple sclerosis (MS). <h3>Methods</h3> A randomized, placebo-controlled, blinded study evaluated ibudilast at a dose of up to 100 mg over 96 weeks in primary and secondary progressive MS. In this secondary analysis of a previously reported trial, secondary and tertiary endpoints included gray matter atrophy, new or enlarging T2 lesions as measured every 24 weeks, and new T1 hypointensities at 96 weeks. Whole brain atrophy measured by structural image evaluation, using normalization, of atrophy (SIENA) was a sensitivity analysis. <h3>Results</h3> A total of 129 participants were assigned to ibudilast and 126 to placebo. New or enlarging T2 lesions were observed in 37.2% on ibudilast and 29.0% on placebo (<i>p</i> = 0.82). New T1 hypointense lesions at 96 weeks were observed in 33.3% on ibudilast and 23.5% on placebo (<i>p</i> = 0.11). Gray matter atrophy was reduced by 35% for those on ibudilast vs placebo (<i>p</i> = 0.038). Progression of whole brain atrophy by SIENA was slowed by 20% in the ibudilast group compared with placebo (<i>p</i> = 0.08). <h3>Conclusion</h3> Ibudilast treatment was associated with a reduction in gray matter atrophy. Ibudilast treatment was not associated with a reduction in new or enlarging T2 lesions or new T1 lesions. An effect on brain volume contributes to prior data that ibudilast appears to affect markers associated with neurodegenerative processes, but not inflammatory processes. <h3>Classification of Evidence</h3> This study provides Class II evidence that for people with MS, ibudilast does not significantly reduce new or enlarging T2 lesions or new T1 lesions.