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生物制剂在炎性风湿性疾病治疗中的应用,包括治疗性抗体、细胞因子和细胞因子拮抗剂。

Biologic agents in the therapy of inflammatory rheumatic diseases, including therapeutic antibodies, cytokines, and cytokine antagonists.

作者信息

Kalden J R

机构信息

Medizinische Klinik III MIT Poliklinik, Universitat Erlangen-Nurnberg, Germany.

出版信息

Curr Opin Rheumatol. 1994 May;6(3):281-6. doi: 10.1097/00002281-199405000-00006.

Abstract

As a result of a better understanding of the mechanisms that underlie diseases such as rheumatoid arthritis, biologic agents have been used increasingly in the therapy of inflammatory rheumatic diseases. Monoclonal antibodies directed against either cell surface constituents mainly on CD4+ T cells or cytokines such as tumor necrosis factor-alpha, fusion toxins reactive with cell activation membrane markers, and cytokine inhibitors, have been shown to be safe and possibly efficacious in open trials. At present, most ongoing studies are focused on the treatment of refractory rheumatoid arthritis and lupus nephritis. Open therapeutic trials are followed by double-blind placebo-controlled phase II and III studies, which are necessary to prove the efficacy of the various biologic agents. Open trials, however, already have shown that only a short decrease in the inflammatory activity of arthritis can be induced and that anti-idiotypic and human anti-mouse antibodies are induced even when humanized monoclonal antibodies are used. Nevertheless, a significant improvement in the available therapeutic repertoire for the treatment of inflammatory rheumatic diseases is expected.

摘要

由于对诸如类风湿性关节炎等疾病的潜在机制有了更深入的了解,生物制剂在炎性风湿性疾病的治疗中得到了越来越广泛的应用。针对主要存在于CD4+ T细胞上的细胞表面成分或细胞因子(如肿瘤坏死因子-α)的单克隆抗体、与细胞活化膜标志物反应的融合毒素以及细胞因子抑制剂,在开放试验中已显示出安全性且可能有效。目前,大多数正在进行的研究集中于难治性类风湿性关节炎和狼疮性肾炎的治疗。开放治疗试验之后是双盲安慰剂对照的II期和III期研究,这对于证明各种生物制剂的疗效是必要的。然而,开放试验已经表明,只能诱导关节炎的炎症活动出现短暂下降,并且即使使用人源化单克隆抗体也会诱导抗独特型抗体和人抗鼠抗体的产生。尽管如此,预计在炎性风湿性疾病的现有治疗方法方面会有显著改善。

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