Miller D H, Molyneux P D, Barker G J, MacManus D G, Moseley I F, Wagner K
NMR Research Unit, Institute of Neurology, London, UK.
Ann Neurol. 1999 Dec;46(6):850-9. doi: 10.1002/1531-8249(199912)46:6<850::aid-ana7>3.0.co;2-q.
A randomized placebo-controlled trial of interferon-beta1b was performed on 718 patients with secondary progressive multiple sclerosis with follow-up of up to 3 years. In addition to clinical variables, serial magnetic resonance imaging (MRI) studies were performed to determine the effect of treatment on the pathological evolution of the disease. All patients eligible for MRI had annual proton density/T2-weighted brain scans from which total lesion volume was measured and the number of new and enlarging lesions noted. A subgroup of 125 patients also underwent monthly gadolinium-enhanced and proton density/T2-weighted brain MRI from months 0 to 6 and 18 to 24 to determine the effect of treatment on the frequency of new lesion activity, defined as new enhancing lesions and new/enlarging T2 lesions not enhancing with gadolinium. The difference in total lesion volume between treatment groups was highly significant. In the placebo group, there was an increase of 15% from baseline to last scan, whereas in the interferon-beta1b group, a reduction of 2% was seen. Within the placebo group, there was a significant year-on-year increase in total lesion volume, with a mean increase of 16% at year 3 compared with baseline. In the treated group, there was a significant reduction at year 1 (4%) and year 2 (5%) compared with baseline; the 2% decrease at year 3 was not significant. The number of new or enlarging proton density/T2 lesions was also significantly reduced by treatment. In the frequent MRI subgroup, treatment was associated with a significant 65% reduction in new lesion activity between months 1 and 6, and 78% reduction from months 19 to 24. Interferon-beta1b has a substantial and sustained effect on reducing the accumulation of new inflammatory disease foci in secondary progressive MS. This therapeutic mechanism may contribute to the positive clinical benefits of treatment on the progression of sustained neurological disability and relapse activity that were also identified in this trial.
对718例继发进展型多发性硬化症患者进行了一项随机安慰剂对照试验，随访时间长达3年。除临床变量外，还进行了系列磁共振成像（MRI）研究，以确定治疗对疾病病理演变的影响。所有符合MRI检查条件的患者每年进行质子密度/T2加权脑部扫描，测量总病变体积，并记录新出现和扩大的病变数量。125例患者的亚组在第0至6个月以及第18至24个月还每月接受钆增强和质子密度/T2加权脑部MRI检查，以确定治疗对新病变活动频率的影响，新病变活动定义为新的强化病变以及新出现/扩大的不伴有钆强化的T2病变。治疗组之间总病变体积的差异非常显著。在安慰剂组中，从基线到最后一次扫描增加了15%，而在干扰素β-1b组中，减少了2%。在安慰剂组内，总病变体积有显著的逐年增加，与基线相比，第3年平均增加了16%。在治疗组中，与基线相比，第1年（4%）和第2年（5%）有显著减少；第3年2%的减少不显著。治疗也显著减少了新出现或扩大的质子密度/T2病变的数量。在频繁MRI亚组中，治疗使第1至6个月新病变活动显著减少65%，第19至24个月减少78%。干扰素β-1b对减少继发进展型多发性硬化症中新的炎症病灶积累有显著且持续的作用。这种治疗机制可能有助于解释本试验中所确定的治疗对持续神经功能障碍进展和复发活动的积极临床益处。
