TY - JOUR
T1 - Effects of Ibudilast on MRI Measures in the Phase 2 SPRINT-MS Study
AU - on behalf of the SPRINT-MS investigators
AU - Naismith, Robert T.
AU - Bermel, Robert A.
AU - Coffey, Christopher S.
AU - Goodman, Andrew D.
AU - Fedler, Janel
AU - Kearney, Marianne
AU - Klawiter, Eric C.
AU - Nakamura, Kunio
AU - Narayanan, Sridar
AU - Goebel, Christopher
AU - Yankey, Jon
AU - Klingner, Elizabeth
AU - Fox, Robert J.
AU - Shinnar, Shlomo
AU - Ontaneda, Daniel
AU - Riley, Claire S.
AU - Perumal, Jai
AU - Lava, Neil
AU - Klawiter, Eric
AU - Cohen, Bruce
AU - Racke, Michael
AU - Yadav, Vijayshree
AU - Jubelt, Burk
AU - Weinstockgutman, Bianca
AU - Coyle, Patricia
AU - Repovic, Pavle
AU - Bashir, Khurram
AU - Apperson, Michelle
AU - Giesser, Barbara
AU - Zabeti, Aram
AU - Miravalle, Augusto
AU - Lynch, Sharon
AU - Delgado, Silvia
AU - Suski, Valerie
AU - Goodman, Andrew
AU - Flores, Angela
AU - Dewitt, Dana
AU - Goldman, Myla
AU - Moses, Harold
AU - Naismith, Robert
AU - Peng, Qi
AU - Sakaie, Ken
AU - Jambawalikar, Sachin
AU - Dyke, Jonathan P.
AU - Kitajima, Hiroumi
AU - Panych, Lawrence
AU - Witzel, Thomas
AU - Parrish, Todd
AU - Layman, Rick
AU - Kim, Edward
N1 - Publisher Copyright:
© American Academy of Neurology.
PY - 2021/1/26
Y1 - 2021/1/26
N2 - ObjectiveTo determine whether ibudilast has an effect on brain volume and new lesions in progressive forms of multiple sclerosis (MS).MethodsA 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.ResultsA 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 (p = 0.82). New T1 hypointense lesions at 96 weeks were observed in 33.3% on ibudilast and 23.5% on placebo (p = 0.11). Gray matter atrophy was reduced by 35% for those on ibudilast vs placebo (p = 0.038). Progression of whole brain atrophy by SIENA was slowed by 20% in the ibudilast group compared with placebo (p = 0.08).ConclusionIbudilast 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.Classification of EvidenceThis study provides Class II evidence that for people with MS, ibudilast does not significantly reduce new or enlarging T2 lesions or new T1 lesions.
AB - ObjectiveTo determine whether ibudilast has an effect on brain volume and new lesions in progressive forms of multiple sclerosis (MS).MethodsA 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.ResultsA 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 (p = 0.82). New T1 hypointense lesions at 96 weeks were observed in 33.3% on ibudilast and 23.5% on placebo (p = 0.11). Gray matter atrophy was reduced by 35% for those on ibudilast vs placebo (p = 0.038). Progression of whole brain atrophy by SIENA was slowed by 20% in the ibudilast group compared with placebo (p = 0.08).ConclusionIbudilast 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.Classification of EvidenceThis study provides Class II evidence that for people with MS, ibudilast does not significantly reduce new or enlarging T2 lesions or new T1 lesions.
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U2 - 10.1212/WNL.0000000000011314
DO - 10.1212/WNL.0000000000011314
M3 - Article
C2 - 33268562
AN - SCOPUS:85100445479
SN - 0028-3878
VL - 96
SP - E491-E500
JO - Neurology
JF - Neurology
IS - 4
ER -