Everolimus in patients with rheumatoid arthritis receiving concomitant methotrexate: a 3-month, double-blind, randomised, placebo-controlled, parallel-group, proof-of-concept study
Everolimus in patients with rheumatoid arthritis receiving concomitant methotrexate: a 3-month, double-blind, randomised, placebo-controlled, parallel-group, proof-of-concept study
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DOI：
10.1136/ard.2007.078808
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发表时间：
2008-08-01
影响因子：
27.4
通讯作者：
van Riel, P. L. C.
中科院分区：
文献类型：
--
作者：
Bruyn, G. A. W.;Tate, G.;van Riel, P. L. C.
目的：依维莫司是一种增殖信号抑制剂，具有改善疾病的特性，可用于治疗类风湿性关节炎(RA)。这项概念验证研究评估了维罗莫司联合甲氨蝶呤(MTX)治疗难治性RA的有效性和安全性。方法：对121名接受MTX治疗的活动期RA患者进行多中心、随机、双盲、安慰剂对照试验。患者被随机分成两组，分别接受伊波利莫(每天6毫克)或安慰剂治疗。主要终点是美国风湿病学会标准，在12周时疾病活动性指标(ACR20)改善20%。结果：作用起效迅速，12周时依维莫司组ACR20有效率(36.1%)显著高于安慰剂组(16.7%；P=0.022)。在使用依维莫司治疗后，在压痛和肿胀关节计数、患者对疼痛的评估以及患者和医生对疾病活动性的全球评估方面较基线的改善明显更大。依维莫司组最常见的不良事件是胃肠道(52.5%比31.7%)、皮肤(29.5%比8.3%)和神经系统紊乱(21.3%比10.0%)，导致停止治疗的患者分别占16.4%和10.0%。与安慰剂相比，与安慰剂相比，维拉莫司对血液学参数、肝功能和血脂水平的影响更频繁，但变化轻微且可逆。结论：该研究表明，维拉莫司加甲氨蝶呤具有可接受的安全性和耐受性，可提供临床益处。它可能为对MTX反应不足的RA患者提供一种新的治疗选择。
Objectives: Everolimus, a proliferation signal inhibitor with disease-modifying properties, may be useful in treating rheumatoid arthritis (RA). This proof-of-concept study assessed efficacy and safety of everolimus in combination with methotrexate (MTX) in patients with refractory RA.Methods: A multi-centre, randomised, double-blind, placebo-controlled trial was performed in 121 patients with active RA receiving MTX. Patients were randomised to receive everolimus (6 mg/day) or placebo. The primary endpoint was the American College of Rheumatology criteria for a 20% improvement in measures of disease activity (ACR20) at 12 weeks.Results: There was a rapid onset of action and at 12 weeks the ACR20 response rate was significantly higher in the everolimus group (36.1%) than in the placebo group (16.7%; p = 0.022). Improvements from baseline in tender and swollen joint counts, patient's assessment of pain, and patient's and physician's global assessment of disease activity were significantly greater after treatment with everolimus. The most common adverse events (AEs) in the everolimus group were gastrointestinal (52.5% vs 31.7% in the placebo group), skin (29.5% vs 8.3%), and nervous system disorders (21.3% vs 10.0%); AEs leading to treatment discontinuation were reported for 16.4% and 10.0% of patients, respectively. Changes in haematological parameters, liver function tests, and lipid levels occurred more frequently with everolimus compared to placebo, but were mild and reversible.Conclusions: The study indicates that everolimus plus MTX provides clinical benefit with an acceptable safety and tolerability profile. It may offer a new treatment option in RA patients with inadequate response to MTX.