A randomized, placebo-controlled trial of infliximab plus methotrexate for the treatment of polyarticular-course juvenile rheumatoid arthritis
A randomized, placebo-controlled trial of infliximab plus methotrexate for the treatment of polyarticular-course juvenile rheumatoid arthritis
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DOI：
10.1002/art.22838
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发表时间：
2007-09-01
影响因子：
--
通讯作者：
Giannini, Edward H.
中科院分区：
文献类型：
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作者：
Ruperto, Nicolino;Lovell, Daniel J.;Giannini, Edward H.
目标。目的评价英夫利昔单抗治疗幼年类风湿性关节炎(JRA)的安全性和有效性。这是一项国际性、多中心、随机、安慰剂对照、双盲研究。122名接受甲氨蝶呤治疗的持续性多关节JRA儿童随机接受英夫利昔单抗或安慰剂治疗14周，之后所有儿童在44周期间接受英夫利昔单抗治疗。患者在第44周期间服用MTX+英夫利昔单抗3 mg/kg，或MTX+安慰剂治疗14周，然后在第44周期间服用MTX+英夫利昔单抗6 mg/kg。尽管服用3 mg/kg英夫利昔单抗的患者在第14周达到美国风湿病学会(ACR)儿科30(PEDI 30)改善标准的有效率高于安慰剂组(分别为63.8%和49.2%)，但这一主要疗效终点的组间差异没有统计学意义(P=0.12)。到第16周，在所有患者都接受英夫利昔单抗治疗的情况下，从安慰剂交叉到英夫利昔单抗6 mg/kg后，73.2%的患者取得了ACR Pedi 30反应。到52周时，69.6%和51.8%的患者ACR Pedi 50和ACR Pedi 70有效。英夫利昔单抗耐受性良好，但英夫利昔单抗3 mg/kg的安全性不如英夫利昔单抗6 mg/kg，严重不良反应、输液反应、英夫利昔单抗抗体、新诱导的抗核抗体和抗双链DNA抗体的发生率均高于英夫利昔单抗。虽然英夫利昔单抗3毫克/千克和6毫克/千克在一年内显示出持久的疗效，但在英夫利昔单抗治疗和安慰剂治疗的患者中，在3个月达到主要疗效终点的结果没有显著差异。安全数据表明，6毫克/公斤剂量可能提供更有利的风险/益处概况。这些结果值得对JRA儿童进行进一步的研究。
Objective. To evaluate the safety and efficacy of infliximab in the treatment of juvenile rheumatoid arthritis (JRA).Methods. This was an international, multicenter, randomized, placebo-controlled, double-blind study. One hundred twenty-two children with persistent polyarticular JRA despite prior, methotrexate (MTX) therapy were randomized to receive infliximab or placebofor 14 weeks, after which all children received infliximab through week 44. Patients received MTX plus infliximab 3 mg/kg through week 44, or MTX plus placebo for 14 weeks followed by MTX plus infliximab 6 mg/kg through week 44.Results. Although a higher proportion of patients in the 3 mg/kg infliximab group than in the placebo group had achieved responses according to the American College of Rheumatology (ACR) Pediatric 30 (Pedi 30) criteria for improvement at week 14 (63.8% and 49.2%, respectively), the between-group difference in this primary efficacy end point was not statistically significant (P = 0.12). By week 16, after the crossover from placebo to infliximab 6 mg/kg when all patients were receiving infliximab, an ACR Pedi 30 response was achieved in 73.2% of all patients. By week 52, ACR Pedi 50 and ACR Pedi 70 responses had been reached in 69.6% and 51.8%, respectively, of patients. Infliximab was generally well tolerated, but the safety profile of infliximab 3 mg/kg appeared less favorable than that of infliximab 6 mg/kg, with more frequent occurrences of serious adverse events, infusion reactions, antibodies to infliximab, and newly induced antinuclear antibodies and antibodies to double-stranded DNA observed with the 3 mg/kg dose.Conclusion. While infliximab at 3 mg/kg and 6 mg/kg showed durable efficacy at I year, achievement of the primary efficacy end point at 3 months did not differ significantly between infliximab-treated and placebo-treated patients. Safety data indicated that the 6-mg/kg dose may provide a more favorable risk/benefit profile. These results warrant further investigation in children with JRA.