Ruperto Nicolino, Lovell Daniel J, Quartier Pierre, Paz Eliana, Rubio-Pérez Nadina, Silva Clovis A, Abud-Mendoza Carlos, Burgos-Vargas Ruben, Gerloni Valeria, Melo-Gomes Jose A, Saad-Magalhães Claudia, Sztajnbok Flavio, Goldenstein-Schainberg Claudia, Scheinberg Morton, Penades Immaculada Calvo, Fischbach Michael, Orozco Javier, Hashkes Philip J, Hom Christine, Jung Lawrence, Lepore Loredana, Oliveira Sheila, Wallace Carol A, Sigal Leonard H, Block Alan J, Covucci Allison, Martini Alberto, Giannini Edward H
IRCCS G Gaslini, PRINTO, Genoa, Italy.
Lancet. 2008 Aug 2;372(9636):383-91. doi: 10.1016/S0140-6736(08)60998-8. Epub 2008 Jul 14.
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.
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, 60 were randomly assigned to receive 10 mg/kg of abatacept at 28-day intervals for 6 months, or until a flare of the 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.
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 continued 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, both in controls (p=0.50).
Selective modulation of T-cell costimulation with abatacept is a rational alternative treatment for children with juvenile idiopathic arthritis.
Bristol-Myers Squibb.
一些幼年特发性关节炎患儿对改善病情抗风湿药物（包括抗肿瘤坏死因子（TNF）药物）治疗无效或不耐受。我们旨在评估选择性T细胞共刺激调节剂阿巴西普对既往治疗失败的幼年特发性关节炎患儿的安全性和疗效。
我们在2004年2月至2006年6月期间进行了一项双盲、随机对照撤药试验。我们从45个中心招募了190例6 - 17岁有活动性幼年特发性关节炎病史、至少有5个活动关节且对至少一种改善病情抗风湿药物反应不佳或不耐受的患者。所有190例患者在4个月的开放标签期内静脉注射10mg/kg阿巴西普。在完成这个导入疗程的170例患者中，47例根据预先定义的美国风湿病学会（ACR）儿科标准对治疗无反应而被排除。在对阿巴西普有反应的患者中，60例被随机分配接受每28天10mg/kg阿巴西普，共6个月，或直至关节炎发作，62例被随机分配在相同剂量和时间接受安慰剂。主要终点是关节炎发作时间。发作定义为六个核心变量中至少三个变量恶化30%或更多，且不超过一个变量改善30%。我们分析了所有按方案治疗的患者。该试验已注册，编号为NCT00095173。
在双盲治疗期间，62例接受安慰剂的患者中有33例（53%）发生关节炎发作，60例接受阿巴西普治疗的患者中有12例（20%）发生关节炎发作（p = 0.0003）。接受安慰剂的患者关节炎发作的中位时间为6个月（事件数不足无法计算IQR）；阿巴西普组发生的事件数不足，无法评估发作的中位时间（p = 0.0002）。在双盲期继续使用阿巴西普的患者发作风险不到对照组的三分之一（风险比0.31，95%CI 0.16 - 0.95）。在双盲期，两个治疗组不良事件的发生率没有差异。37例接受阿巴西普治疗的患者（62%）和34例接受安慰剂治疗的患者（55%）记录到不良事件（p = 0.47）；仅报告了两例严重不良事件，均发生在对照组（p = 0.50）。
用阿巴西普选择性调节T细胞共刺激是幼年特发性关节炎患儿合理的替代治疗方法。
百时美施贵宝公司。
