Newer Biological Agents in the Treatment of Rheumatoid Arthritis Do the Benefits Outweigh the Risks?
Newer Biological Agents in the Treatment of Rheumatoid Arthritis Do the Benefits Outweigh the Risks?
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DOI：
10.2165/11318290-000000000-00000
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发表时间：
2009-01-01
期刊：
影响因子：
11.5
通讯作者：
Nurmohamed, Michael T.
中科院分区：
文献类型：
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作者：
Nurmohamed, Michael T.
最近，三种新的生物制剂，利妥昔单抗，阿巴西普和托珠单抗，已成为可用于治疗类风湿关节炎（RA）的患者活动性疾病，谁没有响应至少一种疾病缓解抗风湿药物（DMARD）。利妥昔单抗是一种抗CD 20单克隆抗体，阿巴西普调节T细胞活化，托珠单抗是一种白细胞介素-6受体拮抗剂。这些药物的临床研究表明，它们对患有中度至活动性疾病的RA患者有效，这些患者对至少一种DMARD和/或肿瘤坏死因子（TNF）抑制剂治疗无反应。到目前为止，还没有令人信服的证据表明这三种新药中的一种具有优于其他药物的上级疗效，或者与TNF抑制剂相比具有其他益处。使用利妥昔单抗，而不是另一种TNF抑制剂，可能是一个选择，在病人谁没有响应TNF封锁。阿巴西普也可以考虑，但这尚未得到正式测试。托珠单抗的一个实际优势是它可以作为一线生物制剂给药。不良事件，包括（通常为轻度）输注反应，是常见的。严重感染的风险略有增加，似乎与TNF抑制剂相似，尽管每种药物可能有其特定的风险特征。到目前为止，还没有令人信服的证据表明新的生物制剂与恶性肿瘤风险增加有关。然而，研究的患者-年数量仍然相当有限，因此有必要进行持续的上市后监测。没有足够的研究直接比较新的生物制剂彼此之间以及与其他生物制剂，如TNF抑制剂。因此，无法得出关于这些药物相对于彼此的获益-风险特征的确切结论。然而，尽管早期进行了药物治疗，但对于患有活动性疾病的个体RA患者而言，给定的新生物制剂的益处目前似乎超过了风险。
Recently, three new biological agents, rituximab, abatacept and tocilizumab, have become available for the treatment of rheumatoid arthritis (RA) in patients with active disease, who have not responded to at least one disease-modifying antirheumatic drug (DMARD). Rituximab is an anti-CD20 monoclonal antibody, abatacept modulates T-cell activation and tocilizumab is an interleukin-6 receptor antagonist. Clinical studies with these agents have demonstrated that they are effective in RA patients with moderate to active disease, who have not responded to treatment with at least one DMARD and/or tumour necrosis factor (TNF) inhibitor. Thus far, there is no convincing evidence to show that one of these three new drugs has a superior efficacy over the others or that they have other benefits compared with the TNF inhibitors. The use of rituximab, instead of another TNF inhibitor, might be an option in patients who have not responded to TNF blockade. Abatacept could also be considered, but this has not yet been formally tested. A practical advantage of tocilizumab is that it may be administered as a first-line biological agent.Adverse events, including (usually mild) infusion reactions, are common. There is a small increased risk of serious infections that appears to be similar to that with TNF inhibitors, although each drug may have its own particular risk profile. Thus far, there is no convincing evidence that the new biological agents are associated with an increased risk of malignancies. However, the number of patient-years studied is still rather limited and, hence, continuous postmarketing surveillance is necessary. Adequate studies directly comparing new biological agents with each other and with other biological agents, such as TNF inhibitors, are not available. Hence, no firm conclusions regarding the benefit-risk profile of these agents versus each other can be reached. However, the benefit for a given new biological agent currently appears to outweigh the risk for an individual RA patient with active disease, despite earlier drug treatment.