Biologic Agents in Rheumatoid Arthritis: An Update for Managed Care Professionals
Biologic Agents in Rheumatoid Arthritis: An Update for Managed Care Professionals
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DOI：
10.18553/jmcp.2011.17.s9-b.s14
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发表时间：
2011-11-01
影响因子：
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通讯作者：
Agarwal, Sandeep K.
中科院分区：
文献类型：
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作者：
Agarwal, Sandeep K.
背景：类风湿关节炎(RA)是一种慢性、全身性自身免疫性炎症性关节炎，临床表现为关节疼痛、僵硬和肿胀。如果不治疗，持续性滑膜炎症可能会发展为软骨和骨骼破坏，最终导致严重的长期残疾和死亡。甲氨蝶呤、来氟米特和柳氮磺吡啶等合成抗风湿药物(DMARD)能显著改善RA患者的临床症状，减缓关节损害。然而，尽管合成DMARDS有效，许多使用它们的患者仍然有炎症和进行性关节破坏的临床症状。最近我们对类风湿关节炎发病机制的了解取得了进展，导致了新的细胞和分子治疗靶点的确定。针对这些靶点的生物制剂已经提供了一些有效性的证据，正在改变RA的管理。目的：告知卫生保健提供者在RA发病机制和创新生物疗法方面的一些最新进展，这些进展已经显示出在改善临床结果和抑制放射学进展方面的有效性。总结：尽管RA自身免疫反应的特定触发因素尚不清楚，但发病机制通常被认为与通过抗原提呈细胞与适应性免疫系统(CD4+T细胞和B细胞)相互作用而产生自身抗体有关。类风湿关节炎关节炎症和破坏的主要炎症介质有肿瘤坏死因子-α、白介素1、白介素6、趋化因子和蛋白水解酶。我们对关键细胞和炎性细胞因子的了解的进步导致了靶向生物制剂的发展。截至2011年，FDA批准使用5种肿瘤坏死因子-α抑制剂：英夫利昔单抗、依那西普、阿达利单抗、Golimumab和certolizumab pegol。在随机临床试验中，所有这些药物都被证明在减少合成DMARD失败的RA患者的临床炎症体征方面有效。多项研究表明，早期应用肿瘤坏死因子-α抑制剂联合甲氨蝶呤治疗有显著益处。FDA批准的其他用于治疗中到重度RA的生物制剂包括abatacept、rituximab和tocilizumab。所有的生物制剂都会增加感染的风险。其他潜在的副作用包括静脉给药和皮下给药的输液和注射部位反应。所有考虑使用生物制剂的患者应每年进行结核病筛查，并应接种肺炎球菌疫苗、流感疫苗和乙肝疫苗。
BACKGROUND: Rheumatoid arthritis (RA) is a chronic, systemic autoimmune inflammatory arthritis that clinically manifests as joint pain, stiffness, and swelling. If left untreated, persistent synovial inflammation can progress to cartilage and bone destruction and ultimately to major long-term disability and mortality. Synthetic disease-modifying antirheumatic drugs (DMARDs), such as methotrexate, leflunomide, and sulfasalazine, have markedly improved clinical symptoms and slowed joint damage in RA patients. However, despite the effectiveness of synthetic DMARDs, many patients who use them continue to have clinical symptoms of inflammation and progressive joint destruction. Recent advances in our understanding of the pathogenesis of RA have led to the identification of novel cellular and molecular therapeutic targets. Biologic agents aimed at these targets have provided some evidence of effectiveness that is transforming the management of RA.OBJECTIVE: To inform health care providers about some of the recent advances in RA pathogenesis and innovative biologic therapies that have shown effectiveness in improving clinical outcomes and inhibiting radiographic progression.SUMMARY: Although the specific trigger of the autoimmune response in RA is not known, pathogenesis is generally believed to be associated with the generation of autoantibodies through interactions of antigen-presenting cells with the adaptive immune system (CD4 + T cells and B cells). The main inflammatory mediators of joint inflammation and destruction in RA are tumor necrosis factor (TNF)-alpha, interleukin-1 (IL-1), IL-6, chemokines, and proteases. Advances in our understanding of the key cells and inflammatory cytokines have led to the development of targeted biologic agents. As of 2011, 5 TNF-alpha inhibitors are approved for use by the FDA: infliximab, etanercept, adalimumab, golimumab, and certolizumab pegol. In randomized clinical trials, all of these agents have been shown to be effective in reducing clinical signs of inflammation in RA patients who have failed synthetic DMARDs. Multiple studies have demonstrated significant benefits of early treatment with TNF-alpha inhibitors combined with methotrexate. Other FDA-approved biologic agents for treating moderate-to-severe RA include abatacept, rituximab, and tocilizumab. All biologic agents carry an increased risk of infections. Additional potential side effects include infusion and injection site reactions for intravenous and subcutaneously administered agents, respectively. All patients being considered for biologic agents should be screened annually for tuberculosis and should receive pneumococcal, influenza, and hepatitis B vaccinations.