Stone L A, Frank J A, Albert P S, Bash C, Smith M E, Maloni H, McFarland H F
Neuroimmunology Branch, National Institute for Neurological Disorders and Stroke, Bethesda, MD 20892, USA.
Ann Neurol. 1995 May;37(5):611-9. doi: 10.1002/ana.410370511.
Magnetic resonance imaging (MRI) has been a valuable tool to understand the pathophysiology and natural history of multiple sclerosis (MS), and increasing attention is focusing on the use of MRI findings as outcome measures in treatment trials in MS. The recently completed trial of interferon-beta-1b (IFN-beta 1b) demonstrated a decrease in accumulation of diseased tissue on T2-weighted images and a reduction in new lesions on T2-weighted images. To examine the effect of IFN-beta 1b on blood-brain barrier (BBB) breakdown, and to provide additional insights into the usefulness of MRI in the evolution of effectiveness of experimental treatments in MS, we used the contrast-enhanced lesion frequency of 7-month baseline MRIs compared with the enhanced lesion frequency for 6-month treatment period MRIs in 14 relapsing-remitting (RR) MS patients. Longer baselines were also available for analysis in a subset of 8 patients, as these patients had been followed by monthly MRI in a natural history study for up to 4 years prior to the current study. A significant reduction in the total or new enhancing lesion frequency was detected in the patients analyzed as a whole, and 13 of 14 of the patients demonstrated a reduction in enhancing lesion frequency on treatment over the 6 months studied. These findings suggest that IFN-beta has a mechanism of action that at least temporarily inhibits the opening of the BBB in RRMS patients. This trial also illustrates the usefulness of a baseline versus treatment trial design to evaluate the effect of drug therapy in MS.
磁共振成像（MRI）一直是理解多发性硬化症（MS）病理生理学和自然病程的重要工具，并且越来越多的关注聚焦于将MRI结果用作MS治疗试验中的疗效指标。最近完成的干扰素-β-1b（IFN-β 1b）试验表明，T2加权图像上病变组织的累积减少，且T2加权图像上新发病灶减少。为了研究IFN-β 1b对血脑屏障（BBB）破坏的影响，并进一步深入了解MRI在MS实验性治疗疗效演变中的作用，我们比较了14例复发缓解型（RR）MS患者7个月基线MRI的对比增强病灶频率与6个月治疗期MRI的增强病灶频率。对于8例患者的亚组也有更长的基线可供分析，因为在本研究之前，这些患者在一项自然病程研究中接受了长达4年的每月一次MRI随访。在对整体患者的分析中，检测到总的或新发增强病灶频率显著降低，并且在研究的6个月治疗期间，14例患者中有13例的增强病灶频率降低。这些发现表明，IFN-β具有一种作用机制，至少能暂时抑制RRMS患者血脑屏障的开放。该试验还说明了基线对照与治疗试验设计在评估MS药物治疗效果方面的作用。
