Hamilton K, Clair E W
Division of Rheumatology, Allergy and Clinical Immunology, Department of Medicine, Duke University Medical Centre, Durham, NC 27710, USA.
Expert Opin Pharmacother. 2000 Jul;1(5):1041-52. doi: 10.1517/14656566.1.5.1041.
Tumour necrosis factor (TNF)-alpha inhibitors have emerged as a new treatment option for rheumatoid arthritis (RA). The scientific rationale for targeting TNF-alpha in RA derives from extensive work in the laboratory, showing the importance of this pro-inflammatory cytokine as a mediator of joint inflammation. Proof of principle has now been firmly established in clinical trials where TNF-alpha inhibitors have been shown to decrease the signs and symptoms of joint inflammation and slow radiological progression of joint damage. Presently, the two TNF-alpha inhibitors available for use in RA are etanercept and infliximab. Etanercept is a soluble TNF receptor: Fc fusion protein that competes with the endogenous TNF receptors for TNF-alpha binding. Infliximab is a chimeric anti-TNF-alpha monoclonal antibody, which also binds with high affinity to soluble TNF-alpha. Etanercept and infliximab will be rapidly incorporated into current treatment paradigms, which call for early and intensive treatment of RA using disease-modifying antirheumatic drugs (DMARDs), such as methotrexate, sulfasalazine and hydroxychloroquine. A major drawback to the widespread use of these biologics is their high costs. Some patients with limited financial means may be denied access to these effective anti-inflammatory agents. Moreover, long-term experience with TNF-alpha inhibitor therapy has been limited and concerns linger about the possibility that etanercept and infliximab may cause unforeseen side effects or increase the risk for opportunistic infection. Despite these caveats, TNF-alpha inhibitors represent a major advance for the treatment of RA and will likely spawn new indications for anti-TNF-alpha therapy and the development of novel therapeutic compounds with similar biological activity.
肿瘤坏死因子（TNF）-α抑制剂已成为类风湿性关节炎（RA）的一种新的治疗选择。针对RA中的TNF-α进行治疗的科学依据源于实验室的大量研究工作，这些研究表明这种促炎细胞因子作为关节炎症介质的重要性。目前，在临床试验中已牢固确立了原理验证，其中已证明TNF-α抑制剂可减轻关节炎症的体征和症状，并减缓关节损伤的放射学进展。目前，可用于治疗RA的两种TNF-α抑制剂是依那西普和英夫利昔单抗。依那西普是一种可溶性TNF受体：Fc融合蛋白，它与内源性TNF受体竞争结合TNF-α。英夫利昔单抗是一种嵌合抗TNF-α单克隆抗体，它也以高亲和力结合可溶性TNF-α。依那西普和英夫利昔单抗将迅速纳入当前的治疗模式，该模式要求使用改善病情抗风湿药（DMARDs），如甲氨蝶呤、柳氮磺胺吡啶和羟氯喹，对RA进行早期和强化治疗。这些生物制剂广泛使用的一个主要缺点是成本高昂。一些经济手段有限的患者可能无法获得这些有效的抗炎药物。此外，TNF-α抑制剂治疗的长期经验有限，人们仍然担心依那西普和英夫利昔单抗可能会引起不可预见的副作用或增加机会性感染的风险。尽管有这些警告，TNF-α抑制剂仍是RA治疗的一项重大进展，可能会催生抗TNF-α治疗的新适应症以及具有类似生物活性的新型治疗化合物的开发。
