Schiff Michael H
Denver Arthritis Clinic Research Unit, Denver, Colorado 80230, USA.
Drugs. 2004;64(22):2493-501. doi: 10.2165/00003495-200464220-00001.
Rheumatoid arthritis (RA) is a chronic and progressive inflammatory disease that ultimately leads to disability and functional decline. Because patients usually develop RA in mid-life, they may experience its consequences for 20-30 years or longer. Proinflammatory cytokines, notably interleukin (IL)-1 and tumour necrosis factor-alpha, are believed to play significant pathophysiological roles. Clinical trials of biologicals that block these cytokines confirm their importance.Anakinra, a recombinant human IL-1 receptor antagonist, improves clinical signs and symptoms, and slows radiographic progression in patients with active RA. In clinical trials, patients receiving anakinra doses >1 mg/kg, whether administered alone or in combination with methotrexate, were two to three times more likely than patients receiving placebo to achieve a sustained ACR20 (American College of Rheumatology criteria) response. Notably, bone erosion slows to a greater extent and shows accelerated benefit when anakinra treatment is continued for periods beyond 24 weeks. Anakinra has a rapid onset of action, with substantial improvements in biochemical indices (C-reactive protein) seen within 1 week and clinical responses (ACR20 or joint counts) seen within 4 weeks of starting treatment. Anakinra is generally well tolerated, with injection site reactions being the most common adverse event. These reactions are generally mild and typically resolve within 2-3 weeks of treatment. The anakinra product labelling does include a warning regarding an increased risk of infections of 2% in anakinra-treated patients versus <1% in patients receiving placebo.
类风湿关节炎(RA)是一种慢性进行性炎症性疾病,最终会导致残疾和功能衰退。由于患者通常在中年时患上RA,他们可能会在20至30年或更长时间内承受其后果。促炎细胞因子,尤其是白细胞介素(IL)-1和肿瘤坏死因子-α,被认为发挥着重要的病理生理作用。阻断这些细胞因子的生物制剂的临床试验证实了它们的重要性。阿那白滞素是一种重组人IL-1受体拮抗剂,可改善临床体征和症状,并减缓活动性RA患者的影像学进展。在临床试验中,接受阿那白滞素剂量>1mg/kg的患者,无论单独使用还是与甲氨蝶呤联合使用,达到持续ACR20(美国风湿病学会标准)反应的可能性是接受安慰剂患者的两到三倍。值得注意的是,当阿那白滞素治疗持续超过24周时,骨侵蚀减缓的程度更大,且显示出加速的益处。阿那白滞素起效迅速,在开始治疗后1周内生化指标(C反应蛋白)有显著改善,4周内出现临床反应(ACR20或关节计数改善)。阿那白滞素一般耐受性良好,注射部位反应是最常见的不良事件。这些反应通常较轻,通常在治疗2至3周内消退。阿那白滞素的药品标签确实包括一项警告,即接受阿那白滞素治疗的患者感染风险增加2%,而接受安慰剂的患者感染风险<1%。