Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands.
Clin Exp Rheumatol. 2011 Sep-Oct;29(5 Suppl 68):S46-51. Epub 2011 Oct 21.
This article provides a perspective on the immediate and follow-up results of the COBRA trial that compared the combination of step-down prednisolone, methotrexate and sulfasalazine with sulfasalazine monotherapy in early rheumatoid arthritis (RA). The combination provided immediate relief of symptoms and signs of RA, but the clinical benefit compared to monotherapy appeared mostly dependent on low-dose glucocorticoid therapy that was mandatorily discontinued after 28 weeks. Strong benefit was apparent in the slowing of joint damage progression, and this effect persisted for over 10 years despite uncontrolled therapy after the trial period. In the trial toxicity of COBRA was less than monotherapy, and long-term safety of the regimen was comparable to regimens that do not include glucocorticoids. COBRA was the first study to validate the 'reverse-pyramid' concept in RA, and helped to establish the idea of a window of opportunity where the prognosis of RA may be altered with early and intensive therapy. Subsequent studies have shown COBRA is feasible in practice, acceptable to patients, and has efficacy similar to the combination of TNF inhibition and high-dose methotrexate, at a fraction of the cost.
本文提供了对 COBRA 试验的即时和后续结果的看法，该试验比较了在早期类风湿关节炎（RA）中，逐渐减少剂量的泼尼松龙、甲氨蝶呤和柳氮磺胺吡啶与柳氮磺胺吡啶单药治疗的组合。该组合提供了 RA 症状和体征的即时缓解，但与单药治疗相比的临床益处似乎主要依赖于低剂量糖皮质激素治疗，这种治疗在 28 周后必须停止。关节损伤进展的减缓效果明显，尽管在试验后阶段进行了不受控制的治疗，但这种效果持续了 10 多年。在试验中，COBRA 的毒性小于单药治疗，并且该方案的长期安全性与不包括糖皮质激素的方案相当。COBRA 是第一个验证 RA 中“倒金字塔”概念的研究，有助于确立机会之窗的概念，即在早期和强化治疗下，RA 的预后可能会改变。随后的研究表明，COBRA 在实践中是可行的，患者可以接受，并且与 TNF 抑制和高剂量甲氨蝶呤的联合治疗具有相似的疗效，但成本仅为其一小部分。
