Abatacept in children with juvenile idiopathic arthritis:: a randomised, double-blind, placebo-controlled withdrawal trial
Abatacept in children with juvenile idiopathic arthritis:: a randomised, double-blind, placebo-controlled withdrawal trial
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DOI：
10.1016/s0140-6736(08)60998-8
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发表时间：
2008-08-02
期刊：
影响因子：
168.9
通讯作者：
Giannini, Edward H.
中科院分区：
文献类型：
--
作者：
Ruperto, Nicolino;Lovell, Daniel J.;Giannini, Edward H.
一些幼年特发性关节炎患儿对包括抗肿瘤坏死因子（TNF）药物在内的缓解疾病的抗风湿药物治疗无反应或不耐受。我们的目的是评估阿巴西普，一种选择性T细胞共刺激调节剂，在幼年特发性关节炎的儿童谁没有以前的treatment.Methods的安全性和有效性，我们做了一个双盲，随机对照戒断试验之间，2004年2月，2006年6月。我们招募了来自45个中心的190名6-17岁的患者，他们有活动性幼年特发性关节炎病史;至少有5个活动关节;对至少一种疾病缓解抗风湿药物反应不足或不耐受。所有190例患者在4个月的开放标签期内静脉给予10 mg/kg阿巴西普。在170例完成该导入期的患者中，47例根据美国风湿病学会（ACR）儿科标准对治疗无反应，被排除。在对阿巴西普有反应的患者中，有62名关节炎患者被随机分配接受相同剂量和时间的安慰剂。主要终点是关节炎发作的时间。耀斑定义为6个核心变量中至少3个恶化30%或以上，不超过1个变量改善至少30%。我们分析了所有按照方案治疗的患者。该试验已注册，编号为NCT 00095173。结果在双盲治疗期间，62名给予安慰剂的患者中有33名（53%）发生关节炎发作，60名给予阿巴西普的患者中有12名（20%）发生关节炎发作（p=0.0003）。给予安慰剂的患者关节炎发作的中位时间为6个月（不足以计算IQR的事件）;阿巴西普组发生的事件不足以评估中位发作时间（p=0.0002）。在双盲期内，继续使用阿巴西普的患者的发作风险小于对照组的三分之一（风险比0.31，95%CI 0.16-0.95）。在双盲期间，不良事件的频率在两个治疗组中没有差异，在37名阿巴西普接受者（62%）和34名安慰剂接受者（55%）中记录了不良事件（p=0.47）;仅报告了两起严重不良事件，控制器中的按钮（p=0.50）。T-细胞的选择性调节细胞共刺激与阿巴西普是一个合理的替代治疗青少年特发性关节炎的儿童。基金百时美施贵宝。
Background Some children with juvenile idiopathic arthritis either do not respond, or are intolerant to, treatment with disease-modifying antirheumatic drugs, including anti-tumour necrosis factor (TNF) drugs. We aimed to assess the safety and efficacy of abatacept, a selective T-cell costimulation modulator, in children with juvenile idiopathic arthritis who had failed previous treatments.Methods We did a double-blind, randomised controlled withdrawal trial between February, 2004, and June, 2006. We enrolled 190 patients aged 6-17 years, from 45 centres, who had a history of active juvenile idiopathic arthritis; at least five active joints; and an inadequate response to, or intolerance to, at least one disease-modifying antirheumatic drug. All 190 patients were given 10 mg/kg of abatacept intravenously in the open-label period of 4 months. Of the 170 patients who completed this lead-in course, 47 did not respond to the treatment according to predefined American College of Rheumatology (ACR) paediatric criteria and were excluded. Of the patients who did respond to abatacept, arthritis, and 62 were randomly assigned to receive placebo at the same dose and timing. The primary endpoint was time to flare of arthritis. Flare was defined as worsening of 30% or more in at least three of six core variables, with at least 30% improvement in no more than one variable. We analysed all patients who were treated as per protocol. This trial is registered, number NCT00095173.Findings Flares of arthritis occurred in 33 of 62 (53%) patients who were given placebo and 12 of 60 (20%) abatacept patients during the double-blind treatment (p=0.0003). Median time to flare of arthritis was 6 months for patients given placebo (insufficient events to calculate IQR); insufficient events had occurred in the abatacept group for median time to flare to be assessed (p=0.0002). The risk of flare in patients who contined abatacept was less than a third of that for controls during that double-blind period (hazard ratio 0.31, 95% CI 0.16-0.95). During the double-blind period, the frequency of adverse events did not differ in the two treatment groups, Adverse events were recorded in 37 abatacept recipients (62%) and 34 (55%) placebo recipients (p=0.47); only two serious adverse events were reported, bouth in controls (p=0.50).Interpretation Selective modulation of T-cell costimulation with abatacept is a rational alternative treatment for children with juvenile idiopathic arthritis.Funding Bristol-Myers Squibb.