Fantini Flavio
Cattedra di Reumatologia Università, Unità Operativa di Reumatologia, Azienda Ospedaliera Istituto Ortopedico Gaetano Pini, Milano.
Recenti Prog Med. 2003 Sep;94(9):361-79.
The management of rheumatoid arthritis (RA) has changed considerably during the past 15 years. Current strategies emphasize the need for early diagnosis and therapeutic intervention based on the use of disease modifying antirheumatic drugs (DMARDs). More than a dozen drugs or drug classes of DMARDs are currently in common use in RA. After a long hiatus, drug development for RA resumed a few years ago with the introduction of Leflunomide and the biologic agents. Unlike the older DMARDs (apart from the cytotoxics) the newer drugs were designed with strict reference to RA pathophysiology and the intended action of these agents is highly likely the explanation for the observed efficacy. Proinflammatory cytokines, such as interleukin-1 (IL-1) and Tumor Necrosis Factor (TNF), play an important role in maintaining the chronicity of RA and mediating tissue damage. TNF antagonists have rapidly emerged as a valuable class of antirheumatic agents. Etanercept, a dimerized version of the soluble TNF receptor II, and infliximab, a chimeric anti-TNF monoclonal antibody, are currently approved in our country for the treatment of refractory RA in the frame of ANTARES Project. Other two biologic agents, adalimumab, a fully humanized anti-TNF monoclonal antibody, and anakinra, a recombinant human IL-1 receptor antagonist, will be also soon available. It is recommended to initiate pharmacological treatment with an effective DMARD early in the course of the disease. Biological therapies have the potential to revolutionize the treatment of RA; however the use of TNF blocking agents as the first DMARD for the treatment of RA should, at present, be limited, because these compounds are expensive and one needs to include cost considerations along with those of efficacy, effectiveness and long-term safety.
在过去15年中,类风湿关节炎(RA)的管理发生了相当大的变化。当前的策略强调基于使用改善病情抗风湿药(DMARDs)进行早期诊断和治疗干预的必要性。目前有十多种DMARDs药物或药物类别常用于RA的治疗。经过长时间的停滞,几年前随着来氟米特和生物制剂的引入,RA的药物研发重新开始。与较老的DMARDs(除细胞毒性药物外)不同,较新的药物是严格参照RA的病理生理学设计的,这些药物预期的作用很可能是观察到的疗效的解释。促炎细胞因子,如白细胞介素-1(IL-1)和肿瘤坏死因子(TNF),在维持RA的慢性病程和介导组织损伤中起重要作用。TNF拮抗剂已迅速成为一类有价值的抗风湿药物。依那西普是可溶性TNF受体II的二聚体形式,英夫利昔单抗是一种嵌合抗TNF单克隆抗体,目前在我国已被批准用于ANTARES项目框架下难治性RA的治疗。另外两种生物制剂,全人源抗TNF单克隆抗体阿达木单抗和重组人IL-1受体拮抗剂阿那白滞素也将很快上市。建议在疾病病程早期用有效的DMARDs开始药物治疗。生物疗法有可能彻底改变RA的治疗;然而,目前将TNF阻断剂作为治疗RA的首个DMARDs使用应受到限制,因为这些药物价格昂贵,而且在考虑疗效、有效性和长期安全性的同时还需要考虑成本因素。