Reynolds Jennifer, Shojania Kam, Marra Carlo A
Division of Rheumatology, Faculty of Medicine, University of British Columbia, Vancouver, Canada
Pharmacotherapy. 2007 Dec;27(12):1693-701. doi: 10.1592/phco.27.12.1693.
Rheumatoid arthritis is a chronic autoimmune disease that often leads to functional disability and reduced quality of life. The pathogenesis of synovial inflammation that is associated with this disease is thought to result from T-cell activation. To become fully activated, T cells require an antigen-specific signal through the T-cell receptor and a second signal through a costimulatory receptor. Abatacept is the first drug in a new class of disease-modifying antirheumatic drugs (DMARDs) known as selective costimulation modulators. Costimulation modulators block the second signal and decrease T-cell activation. Abatacept has been approved by the United States Food and Drug Administration for reducing signs and symptoms, inducing major clinical response, slowing the progression of structural damage, and improving physical function in adults with moderate-to-severe active rheumatoid arthritis who have had an inadequate response to at least one other DMARD, such as methotrexate or tumor necrosis factor (TNF)-alpha inhibitors. Randomized controlled trials have shown that abatacept improves both clinical outcomes and health-related quality of life in patients who have had an inadequate response to other DMARDs. Abatacept has been shown to be well tolerated. In clinical trials, however, abatacept treatment was associated with a higher rate of infections compared with placebo. This finding was compounded when abatacept was used with TNF-alpha inhibitors; thus, this combination should be avoided. Abatacept appears to be a useful treatment option for patients with rheumatoid arthritis who have previously failed other DMARDs. However, additional clinical trials evaluating its long-term effect on patient safety and disease outcomes are needed.
类风湿关节炎是一种慢性自身免疫性疾病，常导致功能残疾和生活质量下降。与该疾病相关的滑膜炎症的发病机制被认为是由T细胞活化引起的。T细胞要完全活化，需要通过T细胞受体获得抗原特异性信号，并通过共刺激受体获得第二个信号。阿巴西普是一类新型改善病情抗风湿药（DMARDs）中首个药物，这类药物被称为选择性共刺激调节剂。共刺激调节剂阻断第二个信号并减少T细胞活化。阿巴西普已获美国食品药品监督管理局批准，用于减轻中度至重度活动性类风湿关节炎成年患者的体征和症状、诱导主要临床反应、减缓结构损伤进展以及改善身体功能，这些患者对至少一种其他DMARD（如甲氨蝶呤或肿瘤坏死因子（TNF）-α抑制剂）反应不佳。随机对照试验表明，阿巴西普可改善对其他DMARD反应不佳患者的临床结局和健康相关生活质量。已证明阿巴西普耐受性良好。然而，在临床试验中，与安慰剂相比，阿巴西普治疗导致的感染发生率更高。当阿巴西普与TNF-α抑制剂联用时，这一发现更为突出；因此，应避免这种联合用药。对于先前使用其他DMARD治疗失败的类风湿关节炎患者，阿巴西普似乎是一种有用的治疗选择。然而，需要更多的临床试验来评估其对患者安全性和疾病结局的长期影响。
