College of Physician and Surgeons, Columbia University, 630 West 168th Street, P&S 10-445, New York, NY 10023, USA.
Ann Rheum Dis. 2011 Nov;70(11):1949-56. doi: 10.1136/ard.2010.145268. Epub 2011 Aug 6.
To assess the efficacy and safety of abatacept plus methotrexate versus methotrexate alone in early erosive rheumatoid arthritis (RA).
The AGREE was a 2-year phase IIIb multinational study in early (≤ 2 years) RA. During the double-blind period (year 1), patients were randomly assigned 1:1 to receive abatacept+methotrexate or methotrexate alone; all patients received open-label abatacept+methotrexate during year 2. Clinical outcomes assessed included 28-joint disease activity score (DAS28) defined remission, low disease activity score (LDAS), American College of Rheumatology (ACR) responses and physical function. Radiographic outcomes were assessed using the Genant-modified Sharp total score (TS). Safety was monitored throughout.
Of the 459 patients completing year 1, 433 patients (94.3%) completed year 2. DAS28-defined remission, LDAS, ACR and physical function were sustained through year 2 in the original abatacept+methotrexate group, with 55.2% in remission at 2 years. Upon introduction of abatacept in the methotrexate-alone group, additional patients achieved DAS28-defined remission (44.5% vs 26.9%), LDAS (60.4% vs 43.2%) and improved ACR 70 (49.8% vs 31.7%) for year 2 versus year 1. Less radiographic progression was observed at 2 years in the original abatacept+methotrexate group than the methotrexate-alone group (change in TS 0.84 vs 1.75, p<0.001). No new safety issues were seen. Similar rates of serious adverse events, serious infections and autoimmune events were observed in years 1 and 2.
The AGREE trial was the first to examine the impact of T-cell co-stimulation modulation with abatacept in patients with early erosive RA. Early treatment with abatacept+methotrexate resulted in greater sustainable clinical, functional and radiographic benefits than methotrexate alone, with acceptable safety and tolerability.
NCT00122382.
评估阿巴西普联合甲氨蝶呤与甲氨蝶呤单药治疗早期侵蚀性类风湿关节炎（RA）的疗效和安全性。
AGREE 是一项为期 2 年的多中心 IIIb 期全球研究，入组早期（≤2 年）RA 患者。在双盲期（第 1 年），患者按照 1:1 随机分组，分别接受阿巴西普联合甲氨蝶呤或甲氨蝶呤单药治疗；所有患者在第 2 年接受开放标签的阿巴西普联合甲氨蝶呤治疗。评估的临床终点包括 28 关节疾病活动度评分（DAS28）缓解、低疾病活动度（LDAS）、美国风湿病学会（ACR）反应和身体功能。采用 Genant 改良 Sharp 总评分（TS）评估放射学结局。整个过程中监测安全性。
459 例完成第 1 年研究的患者中，433 例（94.3%）完成第 2 年研究。在最初的阿巴西普联合甲氨蝶呤组，DAS28 缓解、LDAS、ACR 和身体功能在第 2 年持续存在，第 2 年缓解率为 55.2%。在甲氨蝶呤单药组中引入阿巴西普后，更多患者达到 DAS28 缓解（44.5%比 26.9%）、LDAS（60.4%比 43.2%）和 ACR 70 缓解（49.8%比 31.7%）。在最初的阿巴西普联合甲氨蝶呤组与甲氨蝶呤单药组，2 年时放射学进展更少（TS 变化 0.84 比 1.75，p<0.001）。未发现新的安全性问题。第 1 年和第 2 年严重不良事件、严重感染和自身免疫事件的发生率相似。
AGREE 试验是首个评估 T 细胞共刺激调节对早期侵蚀性 RA 患者影响的研究。早期阿巴西普联合甲氨蝶呤治疗比甲氨蝶呤单药治疗能带来更大的可持续临床、功能和放射学获益，且安全性和耐受性可接受。
NCT00122382。
