Barten Laurie J, Allington Douglas R, Procacci Kendra A, Rivey Michael P
The University of Montana and Community Medical Center, Missoula, MT, USA.
Drug Des Devel Ther. 2010 Nov 24;4:343-66. doi: 10.2147/DDDT.S9331.
Multiple sclerosis (MS) is a central nervous system chronic inflammatory disease that is characterized by an extensive and complex immune response. Scientific advances have occurred in immunology, pathophysiology, and diagnostic and clinical assessment tools, and recent discovery of unique therapeutic targets has spurred numerous Phase II and Phase III clinical trials. Reductions in MS relapse rates and improvements in T₂ or gadolinium-enhancing lesion burdens have been reported from Phase III trials that include fingolimod, alemtuzumab, cladribine, and rituximab. Promising Phase II trial data exist for teriflunomide, daclizumab, laquinimod, and fumarate. The optimism created by these favorable findings must be tempered with evaluation of the adverse effect profile produced by these new agents. Given the discovery of progressive multifocal leukoencephalopathy with the use of natalizumab, ongoing vigilance for rare and life-threatening reactions due to new agents should be paramount. Patients with MS often experience difficulty with ambulation, spasticity, and cognition. Recent clinical trial data from two Phase III dalfampridine-SR trials indicate certain patients receive benefits in ambulation. This article provides an overview of data from clinical trials of newer agents of potential benefit in MS.
多发性硬化症(MS)是一种中枢神经系统慢性炎症性疾病,其特征是广泛而复杂的免疫反应。免疫学、病理生理学以及诊断和临床评估工具方面均取得了科学进展,最近独特治疗靶点的发现推动了众多II期和III期临床试验。在包括芬戈莫德、阿仑单抗、克拉屈滨和利妥昔单抗的III期试验中,已报告MS复发率降低以及T₂加权像或钆增强病灶负担减轻。对于特立氟胺、达利珠单抗、拉喹莫德和富马酸盐,存在有前景的II期试验数据。这些有利发现所带来的乐观情绪必须通过评估这些新药产生的不良反应情况来加以缓和。鉴于使用那他珠单抗后出现进行性多灶性白质脑病,对新药引起的罕见且危及生命的反应保持持续警惕至关重要。MS患者常伴有行走、痉挛和认知方面的困难。两项达氟吡啶缓释剂III期试验的最新临床试验数据表明,部分患者在行走方面有所获益。本文概述了在MS中可能有益的新型药物的临床试验数据。