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Emerging role of anti-tumor necrosis factor therapy in rheumatic diseases. 抗肿瘤坏死因子治疗在风湿性疾病中的新作用。
Pub Date : 2002-01-01 Epub Date: 2002-05-24 DOI: 10.1186/ar552
Joachim R Kalden

Tumor necrosis factor alpha (TNF-alpha) is an inflammatory cytokine that has been implicated in a variety of rheumatic and inflammatory diseases. New understanding of the importance of TNF-alpha in the pathophysiology of rheumatoid arthritis and Crohn's disease led to the development of a new class of targeted anti-TNF therapies. Anti-TNF-alpha agents including etanercept (a fusion protein of the p75 TNF receptor and IgG1) and infliximab (a chimeric monoclonal antibody specific for TNF-alpha) have been approved for the treatment of rheumatoid arthritis. In addition, infliximab has been approved in the treatment of patients with active or fistulating Crohn's disease. A new appreciation of the importance of TNF-alpha in other rheumatic and inflammatory diseases has led to a broadening of the application of anti-TNF agents. Both etanercept and infliximab have been used in open-label and randomized studies in patients with psoriatic arthritis. Although larger randomized trials are needed to confirm early results, both these anti-TNF-alpha agents, etanercept and infliximab, have demonstrated activity in improving the signs and symptoms of psoriatic arthritis and psoriasis. Infliximab has also been shown to be effective in patients with other rheumatic diseases, including ankylosing spondylitis, and may be effective in adult-onset Still's disease, polymyositis, and Behçet's disease. Further investigations will fully elucidate the role of infliximab in these and other rheumatic diseases.

肿瘤坏死因子α(TNFα)是一种炎症细胞因子,与多种风湿性和炎症性疾病有关。对TNF-α在类风湿性关节炎和克罗恩病病理生理学中的重要性的新认识导致了一类新的靶向抗TNF疗法的发展。抗TNF-α药物包括依那西普(p75 TNF受体和IgG1的融合蛋白)和英夫利昔单抗(一种对TNF-α特异性的嵌合单克隆抗体)已被批准用于治疗类风湿性关节炎。此外,英夫利昔单抗已被批准用于治疗活动性或瘘管型克罗恩病患者。对TNF-α在其他风湿性和炎症性疾病中的重要性的新认识导致了抗TNF药物的应用范围的扩大。依那西普和英夫利昔单抗已用于银屑病关节炎患者的开放标签和随机研究。尽管需要更大规模的随机试验来证实早期结果,但这两种抗TNF-α药物,依那西普和英夫利昔单抗,已经证明在改善银屑病关节炎和银屑病的体征和症状方面具有活性。英夫利昔单抗也被证明对其他风湿性疾病(包括强直性脊柱炎)患者有效,并可能对成人斯蒂尔病、多发性肌炎和贝谢病有效。进一步的研究将充分阐明英夫利昔单抗在这些和其他风湿性疾病中的作用。
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引用次数: 53
Perspectives for TNF-alpha-targeting therapies. TNF-α靶向治疗的前景。
Pub Date : 2002-01-01 Epub Date: 2002-05-09 DOI: 10.1186/ar564
Hanns-Martin Lorenz, Joachim R Kalden

Rheumatoid arthritis (RA) is the most common chronic autoimmunopathy, clinically leading to joint destruction as a consequence of the chronic inflammatory processes. The pathogenesis of this disabling disease is not well understood, but molecular events leading to tissue inflammation with cartilage and bone destruction are now better defined. Therapy with slow-acting, disease-modifying antirheumatic drugs (DMARDs), such as low-dose methotrexate, which is generally accepted as a standard, leads to a significant amelioration of symptoms but does not stop joint destruction. Due to these disappointing treatment options and the identification of certain inflammatory mediators as therapeutic targets, novel therapeutic agents such as monoclonal antibodies, cytokine-receptor/human-immunoglobulin constructs or recombinant human proteins have been tested in RA with some success. Clinical trials testing anti-TNF-alpha agents, alone or in combination with methotrexate, have convincingly shown the feasibility and efficacy of these novel approaches to the therapy of RA. A clinical trial testing combination therapy with chimeric (mouse/human) anti-TNF-alpha monoclonal antibody infliximab and methotrexate showed, for the first time in any RA trial, that there was no median radiological progression in the groups given infliximab plus methotrexate over a 12-month observation period. Similar encouraging results might arise from trials employing other TNF-alpha-directed agents, such as the fully human monoclonal antibody D2E7, the p75 TNF-alpha-receptor/Ig construct, etanercept, or others, as discussed in this review. Combination partners other than methotrexate will be established as suitable cotreatment along with anti-TNF-alpha biologicals. Forthcoming new indications for TNF-alpha-targeted therapies are discussed.

类风湿性关节炎(RA)是最常见的慢性自身免疫性疾病,临床上由于慢性炎症过程而导致关节破坏。这种致残性疾病的发病机制尚不清楚,但导致软骨和骨骼破坏的组织炎症的分子事件现在有了更好的定义。使用慢效、改善疾病的抗风湿药物(DMARD)进行治疗,如低剂量甲氨蝶呤,这是一种公认的标准药物,可以显著改善症状,但不能阻止关节破坏。由于这些令人失望的治疗选择和某些炎症介质作为治疗靶点的鉴定,已经在RA中测试了新的治疗剂,如单克隆抗体、细胞因子受体/人免疫球蛋白构建体或重组人蛋白,并取得了一些成功。单独或与甲氨蝶呤联合测试抗TNF-α药物的临床试验令人信服地表明了这些新方法治疗RA的可行性和有效性。一项测试嵌合(小鼠/人)抗TNF-α单克隆抗体英夫利昔单抗和甲氨蝶呤联合治疗的临床试验首次表明,在12个月的观察期内,给予英夫利昔单抗和甲氨蝶呤的组中没有中位放射学进展。类似的令人鼓舞的结果可能来自于使用其他TNF-α导向药物的试验,如本综述中讨论的全人单克隆抗体D2E7、p75 TNF-α受体/Ig构建体、依那西普或其他药物。除甲氨蝶呤外的联合伙伴将与抗TNF-α生物制剂一起被确定为合适的联合治疗。讨论了TNF-α靶向治疗即将出现的新适应症。
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引用次数: 0
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