From Washington University (R.T.N.), St. Louis, MO; Cleveland Clinic Foundation (R.A.B., K.N., C.G., R.J.F.), OH; University of Iowa (C.S.C., J.F., J.Y., E.K.), Iowa City; University of Rochester (A.D.G.), NY; Massachusetts General Hospital (M.K., E.C.K.), Harvard Medical School, Boston; McConnell Brain Imaging Centre (S.N.), Montreal Neurological Institute, McGill University; and NeuroRx Research (S.N.), Montreal, Canada.
Neurology. 2021 Jan 26;96(4):e491-e500. doi: 10.1212/WNL.0000000000011314. Epub 2020 Dec 2.
To determine whether ibudilast has an effect on brain volume and new lesions in progressive forms of multiple sclerosis (MS).
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.
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 ( = 0.82). New T1 hypointense lesions at 96 weeks were observed in 33.3% on ibudilast and 23.5% on placebo ( = 0.11). Gray matter atrophy was reduced by 35% for those on ibudilast vs placebo ( = 0.038). Progression of whole brain atrophy by SIENA was slowed by 20% in the ibudilast group compared with placebo ( = 0.08).
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.
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.
确定伊布地尔对多发性硬化（MS）进展型的脑容量和新病变是否有影响。
一项随机、安慰剂对照、双盲研究评估了伊布地尔在原发性和继发性进展型 MS 中的剂量高达 100mg，为期 96 周。在之前报道的试验的二次分析中，次要和三级终点包括 24 周每测量一次的灰质萎缩、新的或扩大的 T2 病变以及 96 周的新的 T1 低信号。使用结构图像评估的归一化萎缩（SIENA）对全脑萎缩进行了测量，这是一种敏感性分析。
共有 129 名参与者被分配到伊布地尔组，126 名参与者被分配到安慰剂组。伊布地尔组中有 37.2%出现新的或扩大的 T2 病变，安慰剂组中有 29.0%（ = 0.82）。伊布地尔组中有 33.3%在 96 周时出现新的 T1 低信号病变，安慰剂组中有 23.5%（ = 0.11）。与安慰剂组相比，伊布地尔组的灰质萎缩减少了 35%（ = 0.038）。与安慰剂组相比，SIENA 评估的全脑萎缩进展速度在伊布地尔组中减缓了 20%（ = 0.08）。
伊布地尔治疗与灰质萎缩减少有关。伊布地尔治疗与新的或扩大的 T2 病变或新的 T1 病变的减少无关。对脑容量的影响与先前的数据一致，表明伊布地尔似乎影响与神经退行性过程相关的标志物，但不影响炎症过程。
这项研究提供了 II 级证据，表明对于 MS 患者，伊布地尔不会显著减少新的或扩大的 T2 病变或新的 T1 病变。
