Sfikakis Petros P
First Department of Propedeutic and Internal Medicine, Laikon Hospital, Athens University Medical School, Athens, Greece.
Curr Dir Autoimmun. 2010;11:180-210. doi: 10.1159/000289205. Epub 2010 Feb 18.
Results from clinical trials of biologic anti-TNF drugs performed in the late 1990s confirmed the biological relevance of TNF function in the pathogenesis of chronic noninfectious inflammation of joints, skin and gut, which collectively affects 2-3% of the population. Up to April 2009, more than two million patients worldwide have received the first marketed drugs, namely the monoclonal anti-TNF antibodies infliximab and adalimumab and the soluble TNF receptor etanercept. All three are equally effective in rheumatoid arthritis, ankylosing spondylitis, psoriasis and psoriatic arthritis, but, for not clearly defined reasons, only the monoclonal antibodies are effective in inflammatory bowel disease. About 60% of patients who do not benefit from standard nonbiologic treatments for these diseases respond to TNF antagonists. Less than half of responding patients achieve complete remission of disease. Importantly, some of those patients with rheumatoid arthritis in whom long-term anti-TNF therapy induced disease remission remain disease-free after discontinuation of any kind of treatment. There are not yet reliable predictors of which patients will or will not respond on anti-TNF therapy, whereas subsequent loss of an initial clinical response occurs frequently. The spectrum of efficacy anti-TNF therapies widens to include diseases such as systemic vasculitis and sight-threatening uveitis. While paradoxical new adverse effects are recognized, i.e. exacerbation or development of new onset psoriasis, reactivation of latent tuberculosis remains the most important safety issue of anti-TNF therapies. Clinical practice guidelines and consensus statements on the criteria of introduction, duration of treatment and cessation of TNF antagonists, including safety issues, are under constant revision as data from longer periods of patient exposure accumulate. It is hoped that more efficacious drugs that will ideally target the deleterious proinflammatory properties of TNF without compromising its protective role in host defense and (auto)immunity will be available in the near future.
20世纪90年代后期进行的生物抗TNF药物临床试验结果证实，TNF功能在关节、皮肤和肠道慢性非感染性炎症的发病机制中具有生物学相关性，这些炎症共同影响着2%至3%的人口。截至2009年4月，全球已有超过200万患者接受了首批上市药物治疗，即单克隆抗TNF抗体英夫利昔单抗和阿达木单抗以及可溶性TNF受体依那西普。这三种药物在类风湿关节炎、强直性脊柱炎、银屑病和银屑病关节炎中疗效相当，但由于尚不明确的原因，只有单克隆抗体对炎症性肠病有效。约60%未从这些疾病的标准非生物治疗中获益的患者对抗TNF拮抗剂有反应。不到一半的有反应患者实现了疾病的完全缓解。重要的是，一些类风湿关节炎患者在长期抗TNF治疗诱导疾病缓解后，在停止任何治疗后仍保持无病状态。目前尚无可靠的预测指标来判断哪些患者对抗TNF治疗会有反应或无反应，而最初的临床反应随后经常丧失。抗TNF治疗的疗效范围扩大到包括系统性血管炎和威胁视力的葡萄膜炎等疾病。虽然认识到了矛盾的新不良反应，即新发银屑病的加重或发生，但潜伏性结核的再激活仍然是抗TNF治疗最重要的安全问题。随着患者长期暴露数据的积累，关于TNF拮抗剂的引入标准、治疗持续时间和停药标准（包括安全问题）的临床实践指南和共识声明正在不断修订。希望在不久的将来能有更有效的药物，理想地靶向TNF的有害促炎特性，同时不损害其在宿主防御和（自身）免疫中的保护作用。
