Bristol-Myers Squibb Company, Research & Development, Rt. 206 & Province Line Road, Princeton, NJ 08543, USA.
Expert Opin Investig Drugs. 2010 Feb;19(2):195-213. doi: 10.1517/13543780903418452.
Autoimmune diseases are pathological conditions in which "self-tolerance" has been broken, and an immune response has been mounted against the body's own tissues. More than seventy autoimmune diseases have been described, some of which are systemic and others of which are organ-specific. Although many of these diseases are rare, the collective prevalence of autoimmune diseases in the United States alone is between 5 and 8%, and is increasing.
Herein, we review the exciting advances made during the past decade (1999 - 2009) in the development of clinically-validated agents for the treatment of autoimmune disease. We focus on five of the most prevalent conditions: rheumatoid arthritis, psoriasis, multiple sclerosis, Crohn's disease, and systemic lupus erythematosus. The discussion is largely restricted to agents - both small molecules and macromolecules - that have advanced through randomized, controlled clinical trials.
An overview of the pathogenesis of each disease is provided, along with a description of the therapies. Results from pivotal clinical trials are tabulated for four of the disease areas. We also provide summaries of experiences with both failed clinical trials and side effects observed during the course of clinical investigations. We conclude the review with thoughts on current challenges in the field and the prospect for future innovations.
During the past decade, some of the largest advances in the treatment of autoimmune disease have arisen from highly potent and selective macromolecule-based therapies (e.g. antibodies, recombinant proteins and fusion proteins). Together, these clinical experiences have provided insight into the critical mechanisms in autoimmune pathogenesis, including inflammatory cytokine release, T-cell migration and co-stimulation, and B-cell function.
自身免疫性疾病是病理条件下的“自身耐受”已经被打破，和免疫反应已对身体的自身组织。七十多种自身免疫性疾病已被描述，其中一些是全身性的，而另一些是器官特异性的。虽然这些疾病中的许多是罕见的，在美国，仅自身免疫性疾病的总体患病率为 5%至 8%，而且还在增加。
这篇综述涵盖了过去十年（1999-2009 年）在开发治疗自身免疫性疾病的临床验证药物方面取得的令人兴奋的进展。我们重点介绍了五种最常见的疾病：类风湿关节炎、银屑病、多发性硬化症、克罗恩病和系统性红斑狼疮。讨论主要限于已经通过随机、对照临床试验的药物-小分子和大分子。
提供了每种疾病的发病机制概述，并描述了治疗方法。列出了四个疾病领域的关键临床试验结果。我们还总结了在临床试验中失败的经验和在临床研究过程中观察到的副作用。我们以对当前领域面临的挑战和未来创新的展望结束了综述。
在过去的十年中，治疗自身免疫性疾病的最大进展之一来自于高活性和选择性的基于大分子的治疗方法（如抗体、重组蛋白和融合蛋白）。这些临床经验共同提供了对自身免疫发病机制的关键机制的深入了解，包括炎症细胞因子的释放、T 细胞迁移和共刺激以及 B 细胞功能。
