Nakamura Kunio, Thoomukuntla Bhaskar, Bena James, Cohen Jeffrey A, Fox Robert J, Ontaneda Daniel
Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
Mult Scler. 2024 Mar;30(3):369-380. doi: 10.1177/13524585231224702. Epub 2024 Jan 29.
Ibudilast has shown beneficial effects on several imaging outcomes in progressive multiple sclerosis (MS). Slowly enlarging lesions are a proposed imaging biomarker of compartmentalized inflammation within chronic active lesions.
To assess the treatment effect of ibudilast on slowly enlarging lesion volumes over 96 weeks from a phase II clinical trial of ibudilast (Secondary and Primary Progressive Ibudilast NeuroNEXT Trial in Multiple Sclerosis [SPRINT-MS]).
In total, 255 participants with progressive MS from 28 sites were randomized to oral ibudilast or placebo. Participants with at least four analyzable magnetic resonance imaging (MRI) were included. Slowly enlarging lesions were quantified using Jacobian determinant maps. A linear model was used to assess the effect of ibudilast. Magnetization transfer ratio within slowly enlarging lesions was assessed to determine the effect of ibudilast on tissue integrity.
In total, 195 participants were included in this analysis. Ibudilast significantly decreased slowly enlarging lesion volume (23%, = 0.003). Ibudilast also reduced magnetization transfer ratio change in slowly enlarging lesions: 0.22%/year, = 0.04.
Ibudilast showed a significant effect on baseline volume of lesions that were slowly enlarging and magnetization transfer ratio in slowly enlarging lesions. The results support the use of slowly enlarging lesions for assessment of compartmentalized inflammation represented by chronic active lesions and provide further support for the neuroprotective effects of ibudilast in progressive MS.
异丁司特已在进展性多发性硬化症（MS）的多项影像学指标上显示出有益效果。缓慢扩大的病灶是慢性活动性病灶内局部炎症的一种影像学生物标志物。
通过异丁司特的一项II期临床试验（多发性硬化症异丁司特继发与原发进展性神经NEXT试验[SPRINT-MS]），评估异丁司特在96周内对缓慢扩大病灶体积的治疗效果。
总共255名来自28个地点的进展性MS患者被随机分为口服异丁司特组或安慰剂组。纳入至少有四次可分析磁共振成像（MRI）的患者。使用雅可比行列式图对缓慢扩大的病灶进行量化。采用线性模型评估异丁司特的效果。评估缓慢扩大病灶内的磁化传递率，以确定异丁司特对组织完整性的影响。
本分析共纳入195名患者。异丁司特显著降低了缓慢扩大病灶的体积（23%，P = 0.003）。异丁司特还降低了缓慢扩大病灶内磁化传递率的变化：每年0.22%，P = 0.04。
异丁司特对缓慢扩大病灶的基线体积以及缓慢扩大病灶内的磁化传递率有显著影响。结果支持使用缓慢扩大病灶来评估以慢性活动性病灶为代表的局部炎症，并为异丁司特在进展性MS中的神经保护作用提供了进一步支持。
