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[摘要]：Importance of the field. 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. Areas covered in this review. 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. What the reader will gain: 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. Take home message: 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. |
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