Ibudilast in relapsing-remitting multiple sclerosis A neuroprotectant?
Ibudilast in relapsing-remitting multiple sclerosis A neuroprotectant?
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DOI：
10.1212/wnl.0b013e3181d7d651
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发表时间：
2010-03-30
期刊：
影响因子：
9.9
通讯作者：
Landin, R.
中科院分区：
文献类型：
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作者：
Barkhof, F.;Hulst, H. E.;Landin, R.
背景：异丁司特是一种磷酸二酯酶抑制剂，影响多发性硬化（MS）的炎症和神经退行性变。本研究评估了2种不同剂量的异丁司特在复发型MS中对MRI参数的安全性、耐受性和影响。方法：在这项多中心、双盲、2期试验中，复发型MS和钆增强病变的患者以1：1：1的比例随机分配至每天接受30或60 mg异丁司特或安慰剂，持续12个月。主要终点是12个月内每两个月一次脑MRI上新活动性病变的累积数量。次要终点包括复发率、扩展残疾状态量表（EDSS）评分的变化、T2高信号和T1低信号病变体积以及脑体积变化百分比（PBVC）。在前12个月内，治疗组之间的平均活动性病变数量和复发率没有差异。与安慰剂组（1.2%）相比，60 mg组（0.8%）的PBVC降低（p = 0.04）。事后分析显示，与安慰剂组（0.24）相比，60 mg（0.14; p = 0.004）和30 mg（0.17; p = 0.036）组中演变为持续黑洞的活动性病变比例降低。2年内，EDSS确认进展的患者较少（p = 0.026）。异丁司特治疗一般是安全的，耐受性良好。结论：异丁司特显示没有新的活动性病变和复发率有益的影响。然而，初步的证据表明，异丁司特似乎采取行动的神经保护的方式作为衡量2个独立的MRI结果，与残疾progress.Classification的证据可能有益的临床效果：这项干预性研究提供了第三类证据异丁司特对疾病活动的影响。神经病学（R）2010; 74：1033-1040
Background: Ibudilast is a phosphodiesterase inhibitor influencing inflammation and neurodegeneration in multiple sclerosis (MS). This study evaluated the safety, tolerability, and effects on MRI parameters of 2 different doses of ibudilast in relapsing forms of MS.Methods: In this multicenter, double-blind, phase 2 trial, patients with relapsing MS and gadolinium-enhancing lesions were randomly assigned 1:1:1 to receive 30 or 60 mg ibudilast or placebo every day for 12 months. The primary endpoint was the cumulative number of newly active lesions on bimonthly brain MRI over 12 months. Secondary endpoints included relapse rate, change in Expanded Disability Status Scale (EDSS) score, T2-hyperintense and T1-hypointense lesion volumes, and percent brain volume change (PBVC).Results: A total of 297 patients were randomized in 19 centers. During the first 12 months, the mean number of active lesions and relapse rate did not differ between treatment arms. A reduction in PBVC (p = 0.04) was found in the 60-mg group (0.8%) compared with placebo (1.2%). Post hoc analysis showed a reduction in the proportion active lesions that evolved into persistent black holes for the 60-mg (0.14; p = 0.004) and 30-mg (0.17; p = 0.036) groups compared with the placebo group (0.24). Over 2 years, there were fewer patients (p = 0.026) with confirmed progression on the EDSS. Treatment with ibudilast was generally safe and well tolerated.Conclusion: Ibudilast showed no beneficial effect on the rate of newly active lesions and relapses. However, preliminary evidence suggests that ibudilast seems to act in a neuroprotective fashion as measured by 2 independent MRI outcomes, with a possible beneficial clinical effect on disability progression.Classification of evidence:This interventional study provides Class III evidence on the effect of ibudilast on disease activity. Neurology (R) 2010; 74:1033-1040