本文由小咖机器人翻译整理

期刊来源：Lancet

原文链接：https://doi.org/10.1016/S0140-6736(23)02650-8

摘要内容如下：

背景

具有抗瓜氨酸蛋白抗体（ACPA）和关节亚临床炎症改变的个体是发展为类风湿性关节炎的高危人群。阻断这种前期临床疾病的治疗策略仍有待开发。我们的目的是评估阿巴西普治疗6个月是否能改善临床前类风湿性关节炎的炎症。

方法

在ACPA阳性关节痛（ARIAA）研究中，通过MRI测量的Abatacept逆转亚临床炎症是一项随机、国际、多中心、双盲、安慰剂对照试验，在欧洲14家医院和社区中心进行（11家在德国，2家在西班牙，1家在捷克共和国）。成人（年龄≥18岁）ACPA阳性、关节疼痛（但无肿胀）、手部MRI出现骨炎、滑膜炎或腱鞘炎体征的患者被随机（1:1）分配至每周皮下注射Abatacept 125 mg或安慰剂，为期6个月，然后进行为期12个月的双盲、无药物观察期。主要结果是6个月时炎性MRI病变减少的参与者比例。主要疗效分析在改良意向治疗人群中进行，包括随机分配并接受研究药物治疗的参与者。在接受研究药物治疗且至少有一次基线后观察的参与者中进行安全性分析。该研究已在EUDRA-CT（2014-000555-93）注册。

调查结果

在2014年11月6日至2021年6月15日期间，139名参与者接受了筛查。在100名参与者中，50名被随机分配至阿巴西普125 mg组，50名被随机分配至安慰剂组。两名参与者（每组一名）因给药失败或拒绝治疗而被排除；因此，98人被纳入改良意向治疗人群。98名参与者中有70名（71%）为女性，28名（29%）为男性。6个月时，阿巴西普组49名受试者中的28名（57%）和安慰剂组49名受试者中的15名（31%）显示MRI亚临床炎症改善（绝对差异26.5%，95%CI 5.9-45.6；P=0.014）。阿巴西普组49名参与者中有4名（8%）和安慰剂组49名参与者中有17名（35%）发展为类风湿性关节炎（风险比[HR]0.14[0.04-0.47]；P=0.0016）。改善MRI炎症（阿巴西普组49名参与者中的25名[51%]，安慰剂组49名参与者中的12名[24%]；P=0.012）和进展为类风湿性关节炎（17[35%]/49，28[57%]/49；心率0·14[0·04-0·47]；P=0.018）在干预结束后18个月、12个月时两组间仍有显著差异。11名参与者中有12例严重不良事件（阿巴西普组48例中有4例[8%]，安慰剂组49例中有7例[14%]）。研究期间未发生死亡。

解释

6个月的阿巴西普治疗降低了高危参与者的MRI炎症、临床症状和类风湿性关节炎发展的风险。干预的效果在1年的无药物观察期内持续存在。

英文原文如下：

Abstracts

BACKGROUND  Individuals with anti-citrullinated protein antibodies (ACPAs) and subclinical inflammatory changes in joints are at high risk of developing rheumatoid arthritis. Treatment strategies to intercept this pre-stage clinical disease remain to be developed. We aimed to assess whether 6-month treatment with abatacept improves inflammation in preclinical rheumatoid arthritis.

METHODS  The abatacept reversing subclinical inflammation as measured by MRI in ACPA positive arthralgia (ARIAA) study is a randomised, international, multicentre, double-blind, placebo-controlled trial done in 14 hospitals and community centres across Europe (11 in Germany, two in Spain, and one in the Czech Republic). Adults (aged ≥18 years) with ACPA positivity, joint pain (but no swelling), and signs of osteitis, synovitis, or tenosynovitis in hand MRI were randomly assigned (1:1) to weekly subcutaneous abatacept 125 mg or placebo for 6 months followed by a double-blind, drug-free, observation phase for 12 months. The primary outcome was the proportion of participants with any reduction in inflammatory MRI lesions at 6 months. The primary efficacy analysis was done in the modified intention-to-treat population, which included participants who were randomly assigned and received study medication. Safety analyses were conducted in participants who received the study medication and had at least one post-baseline observation. The study was registered with the EUDRA-CT (2014-000555-93).

FINDINGS  Between Nov 6, 2014, and June 15, 2021, 139 participants were screened. Of 100 participants, 50 were randomly assigned to abatacept 125 mg and 50 to placebo. Two participants (one from each group) were excluded due to administration failure or refusing treatment; thus, 98 were included in the modified intention-to-treat population. 70 (71%) of 98 participants were female and 28 (29%) of 98 were male. At 6 months, 28 (57%) of 49 participants in the abatacept group and 15 (31%) of 49 participants in the placebo group showed improvement in MRI subclinical inflammation (absolute difference 26·5%, 95% CI 5·9-45·6; p=0·014). Four (8%) of 49 participants in the abatacept group and 17 (35%) of 49 participants in the placebo group developed rheumatoid arthritis (hazard ratio [HR] 0·14 [0·04-0·47]; p=0·0016). Improvement of MRI inflammation (25 [51%] of 49 participants in the abatacept group, 12 [24%] of 49 in the placebo group; p=0·012) and progression to rheumatoid arthritis (17 [35%] of 49, 28 [57%] of 49; HR 0·14 [0·04-0·47]; p=0·018) remained significantly different between the two groups after 18 months, 12 months after the end of the intervention. There were 12 serious adverse events in 11 participants (four [8%] of 48 in the abatacept group and 7 [14%] of 49 in the placebo group). No deaths occurred during the study.

INTERPRETATION  6-month treatment with abatacept decreases MRI inflammation, clinical symptoms, and risk of rheumatoid arthritis development in participants at high risk. The effects of the intervention persist through a 1-year drug-free observation phase.

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