Adalimumab plus Methotrexate for Uveitis in Juvenile Idiopathic Arthritis
Adalimumab plus Methotrexate for Uveitis in Juvenile Idiopathic Arthritis
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DOI：
10.1056/nejmoa1614160
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发表时间：
2017-04-27
影响因子：
158.5
通讯作者：
Beresford, Michael W.
中科院分区：
文献类型：
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作者：
Ramanan, Athimalaipet V.;Dick, Andrew D.;Beresford, Michael W.
研究背景阿达木单抗是一种全人源抗肿瘤坏死因子A单克隆抗体，可有效治疗幼年特发性关节炎（JIA）。我们测试了阿达木单抗在治疗JIA相关葡萄膜炎的疗效。METHODSIn这个多中心，双盲，随机，安慰剂对照试验，我们评估了阿达木单抗在儿童和青少年2岁或以上的活动性JIA相关葡萄膜炎的疗效和安全性。接受稳定剂量甲氨蝶呤的患者以2：1的比例随机分配接受阿达木单抗（剂量为20 mg或40 mg，根据体重）或安慰剂，每2周一次皮下给药。患者继续试验方案，直至治疗失败或直至18个月过去。随机化后随访2年。主要终点是治疗失败的时间，根据基于葡萄膜炎标准化的多组分眼内炎症评分来定义。在114名患者中有90名入选后，达到了预先规定的停止标准。我们观察到阿达木单抗组60例患者（27%）中有16例治疗失败，而安慰剂组30例患者（60%）中有18例治疗失败（风险比，0.25; 95%置信区间[CI]，0.12 - 0.49; P< 0.0001 [预先设定的停止边界]）。阿达木单抗组患者报告不良事件的频率高于安慰剂组（10.07起事件/患者年[95% CI，9.26 - 10.89] vs. 6.51起事件/患者年[95% CI，5.26 - 7.77]），严重不良事件也是如此（0.29起事件/患者年[95% CI，0.15 - 0.43]对比0.19起事件/患者年[95% CI，0.00 - 0.40]）。结论在患有活动性JIA的儿童和青少年中，阿达木单抗治疗控制了炎症，并且与安慰剂相比治疗失败率较低相关。相关的葡萄膜炎患者服用稳定剂量的甲氨蝶呤。接受阿达木单抗治疗的患者的不良事件和严重不良事件发生率远高于接受安慰剂治疗的患者。
BACKGROUNDAdalimumab, a fully human anti-tumor necrosis factor a monoclonal antibody, is effective in the treatment of juvenile idiopathic arthritis (JIA). We tested the efficacy of adalimumab in the treatment of JIA-associated uveitis.METHODSIn this multicenter, double-blind, randomized, placebo-controlled trial, we assessed the efficacy and safety of adalimumab in children and adolescents 2 years of age or older who had active JIA-associated uveitis. Patients who were taking a stable dose of methotrexate were randomly assigned in a 2: 1 ratio to receive either adalimumab (at a dose of 20 mg or 40 mg, according to body weight) or placebo, administered subcutaneously every 2 weeks. Patients continued the trial regimen until treatment failure or until 18 months had elapsed. They were followed for up to 2 years after randomization. The primary end point was the time to treatment failure, defined according to a multicomponent intraocular inflammation score that was based on the Standardization of Uveitis Nomenclature criteria.RESULTSThe prespecified stopping criteria were met after the enrollment of 90 of 114 patients. We observed 16 treatment failures in 60 patients (27%) in the adalimumab group versus 18 treatment failures in 30 patients (60%) in the placebo group (hazard ratio, 0.25; 95% confidence interval [CI], 0.12 to 0.49; P< 0.0001 [the prespecified stopping boundary]). Adverse events were reported more frequently in patients receiving adalimumab than in those receiving placebo (10.07 events per patient-year [95% CI, 9.26 to 10.89] vs. 6.51 events per patient-year [95% CI, 5.26 to 7.77]), as were serious adverse events (0.29 events per patient-year [95% CI, 0.15 to 0.43] vs. 0.19 events per patient-year [95% CI, 0.00 to 0.40]).CONCLUSIONSAdalimumab therapy controlled inflammation and was associated with a lower rate of treatment failure than placebo among children and adolescents with active JIA-associated uveitis who were taking a stable dose of methotrexate. Patients who received adalimumab had a much higher incidence of adverse events and serious adverse events than those who received placebo.