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首页> 外文期刊>Clinical immunology: The official journal of the Clinical Immunology Society >TNFalpha blockade in human diseases: an overview of efficacy and safety.
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TNFalpha blockade in human diseases: an overview of efficacy and safety.

机译：人类疾病中的TNFalpha阻断：疗效和安全性概述。

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Tumor necrosis factor-alpha (TNFalpha) antagonists including antibodies and soluble receptors have shown remarkable efficacy in various immune-mediated inflammatory diseases (IMID). As experience with these agents has matured, there is an emerging need to integrate and critically assess the utility of these agents across disease states and clinical sub-specialties. Their remarkable efficacy in reducing chronic damage in Crohn's disease and rheumatoid arthritis has led many investigators to propose a new, 'top down' paradigm for treating patients initially with aggressive regimens to quickly control disease. Intriguingly, in diseases such as rheumatoid arthritis and asthma, anti-TNFalpha agents appear to more profoundly benefit patients with more chronic stages of disease but have a relatively weaker or little effect in early disease. While the spectrum of therapeutic efficacy of TNFalpha antagonists widens to include diseases such as recalcitrant uveitis and vasculitis, these agents have failed or evenexacerbated diseases such as heart failure and multiple sclerosis. Increasing use of these agents has also led to recognition of new toxicities as well as to understanding of their excellent long-term tolerability. Disconcertingly, new cases of active tuberculosis still occur in patients treated with all TNFalpha antagonists due to lack of compliance with recommendations to prevent reactivation of latent tuberculosis infection. These safety issues as well as guidelines to prevent treatment-associated complications are reviewed in detail in this article. New data on mechanisms of action and development of newer TNFalpha antagonists are discussed in a subsequent article in the Journal. It is hoped that these two review articles will stimulate a fresh assessment of the priorities for research and clinical innovation to improve and extend therapeutic use and safety of TNFalpha antagonism.
机译：包括抗体和可溶性受体在内的肿瘤坏死因子-α（TNFalpha）拮抗剂已在各种免疫介导的炎症性疾病（IMID）中显示出显着功效。随着这些药物的经验的成熟，出现了一种新的需求，即整合和严格评估这些药物在疾病状态和临床亚专业中的效用。它们在减少克罗恩氏病和类风湿性关节炎的慢性损伤方面具有显着的功效，导致许多研究人员提出了一种新的“自上而下”的范例，用于治疗最初采用积极治疗方案以快速控制疾病的患者。有趣的是，在类风湿性关节炎和哮喘等疾病中，抗TNFα药物似乎对患有更多慢性病的患者更为有益，但对早期疾病的作用相对较弱或影响很小。尽管TNFα拮抗剂的治疗功效范围扩大到包括诸如顽固性葡萄膜炎和血管炎之类的疾病，但这些药物已经失败或加重了诸如心力衰竭和多发性硬化症的疾病。这些药物的越来越多的使用还导致人们认识到新的毒性以及对它们极好的长期耐受性的了解。令人不安的是，由于缺乏对预防潜伏性结核感染再激活的建议的依从性，所有TNFα拮抗剂治疗的患者中仍有新的活动性结核病例。本文对这些安全性问题以及预防与治疗相关的并发症的指南进行了详细审查。 《日刊》的后续文章讨论了有关作用机制和新型TNFα拮抗剂发展的新数据。希望这两篇评论文章将刺激对研究和临床创新的重点进行新的评估，以改善和扩展TNFα拮抗作用的治疗用途和安全性。

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