Section of Musculoskeletal Disease, Leeds Institute of Molecular Medicine, University of Leeds.
Ann Rheum Dis. 2010 Mar;69(3):510-6. doi: 10.1136/ard.2009.119016. Epub 2009 Nov 23.
Several agents provide treatment for established rheumatoid arthritis (RA), but a crucial therapeutic goal is to delay/prevent progression of undifferentiated arthritis (UA) or very early RA.
To determine the impact of T-cell costimulation modulation in patients with UA or very early RA.
In this double-blind, phase II, placebocontrolled, 2-year study, anti-cyclic citrullinated peptide (CCP)2-positive patients with UA (not fulfilling the ACR criteria for RA) and clinical synovitis of two or more joints were randomised to abatacept ( approximately 10 mg/kg) or placebo for 6 months; the study drug was then terminated. The primary end point was development of RA (by ACR criteria) at year 1. Patients were monitored by radiography, MRI, CCP2, rheumatoid factor and 28 joint count Disease Activity Score (DAS28) over 2 years.
At year 1, 12/26 (46%) abatacept-treated versus 16/24 (67%) placebo-treated patients developed RA (difference (95% CI) -20.5% (-47.4% to 7.8%)). Adjusted mean changes from baseline to year 1 in Genant-modified Sharp radiographic scores for abatacepttreated versus placebo-treated patients, respectively, were 0 versus 1.1 for total score, and 0 versus 0.9 for erosion score. Mean changes from baseline to year 1 in MRI erosion, osteitis and synovitis scores were 0, 0.2 and 0.2, respectively, versus 5.0, 6.7 and 2.3 in the abatacept versus placebo groups. Safety was comparable between groups; serious adverse events occurred in one patient (3.6%) in each group.
Abatacept delayed progression of UA/very early RA in some patients. An impact on radiographic and MRI inhibition was seen, which was maintained for 6 months after treatment stopped. This suggests that it is possible to alter the progression of RA by modulating T-cell responses at a very early stage of disease. Trial registration number NCT00124449.
有几种药物可用于治疗已确诊的类风湿关节炎（RA），但一个关键的治疗目标是延缓/预防未分化关节炎（UA）或早期 RA 的进展。
确定 T 细胞共刺激调节对 UA 或早期 RA 患者的影响。
在这项双盲、二期、安慰剂对照、为期 2 年的研究中，抗环瓜氨酸肽（CCP）2 阳性的 UA 患者（不符合 RA 的 ACR 标准）和两个或更多关节有临床滑膜炎，随机接受阿巴西普（约 10mg/kg）或安慰剂治疗 6 个月；然后终止研究药物。主要终点是在第 1 年发生 RA（根据 ACR 标准）。在 2 年内，通过影像学、MRI、CCP2、类风湿因子和 28 关节疾病活动评分（DAS28）对患者进行监测。
在第 1 年，26 例接受阿巴西普治疗的患者中有 12 例（46%）和 24 例接受安慰剂治疗的患者中有 16 例（67%）发生 RA（差异（95%CI）-20.5%（-47.4%至 7.8%））。从基线到第 1 年，接受阿巴西普治疗和安慰剂治疗的患者的 Genant 改良 Sharp 放射评分的平均变化分别为 0 与 1.1（总评分）和 0 与 0.9（侵蚀评分）。从基线到第 1 年，MRI 侵蚀、骨炎和滑膜炎评分的平均变化分别为 0、0.2 和 0.2，而阿巴西普组和安慰剂组分别为 5.0、6.7 和 2.3。两组之间的安全性相当；每组均有 1 例（3.6%）发生严重不良事件。
阿巴西普延迟了一些 UA/早期 RA 患者的疾病进展。观察到对影像学和 MRI 的抑制作用，且在停止治疗 6 个月后仍保持。这表明，通过在疾病的早期阶段调节 T 细胞反应，有可能改变 RA 的进展。试验注册号 NCT00124449。
Zotero 插件
