A randomized trial of parenteral methotrexate comparing an intermediate dose with a higher dose in children with juvenile idiopathic arthritis who failed to respond to standard doses of methotrexate
A randomized trial of parenteral methotrexate comparing an intermediate dose with a higher dose in children with juvenile idiopathic arthritis who failed to respond to standard doses of methotrexate
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DOI：
10.1002/art.20288
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发表时间：
2004-07-01
影响因子：
--
通讯作者：
Martini, A
中科院分区：
文献类型：
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作者：
Ruperto, N;Murray, KJ;Martini, A
目标。目的比较中剂量(15 mg/m(2)/周)和大剂量(30 mg/m(2)/周)甲氨蝶呤(MTX)在标准剂量(8~12.5 mg/m(2)/周)治疗无效的多关节病程幼年特发性关节炎(JIA)患者中的安全性和有效性。在筛查阶段，对595名新开始服用标准剂量MTX的患者进行了6个月的随访。随后，根据美国风湿病学会(ACR)儿科30%改善标准(儿科30%)定义的无应答者被随机分配接受中剂量或更高剂量的MTX肠外注射，持续6个月。筛选和随机化阶段的改善由ACR儿科30个应答以及50%和70%的应答水平(分别为ACR儿科50和ACR儿科70)确定。在筛查阶段，接受标准剂量的MTX后，430名患者(72%)根据ACR儿科标准30有改善，360名(61%)符合ACR儿科50,225名(38%)符合ACR儿科70；在这些患者中，69名(12%)也符合完全疾病控制的定义。在133名无反应者中，80人被随机接受中等剂量或更高剂量的MTX。在随机阶段，中剂量组40名儿童中有25名(62.5%)接受ACR治疗，而高剂量组40名儿童中有23名有效(57.5%)。接受中等剂量的23名患者(57.5%)获得了ACR儿科50的有效率，而接受高剂量组的患者有22名(55%)。接受中等剂量的18名儿童(45%)的ACR儿科有效率为70%，而接受较高剂量的儿童为19名(47.5%)。中剂量组有5名儿童(12.5%)，而接受大剂量MTX治疗的儿童有4名(10%)，也符合疾病完全控制的定义。两组间的应答率差异均不显著。两组患者发生不良事件或实验室异常的频率无显著差异。这项研究表明，MTX在JIA中的疗效在静脉注射15 mg/m(2)/周时达到平台期，进一步增加剂量与任何额外的治疗益处无关。甲氨蝶呤的使用时间应长达9-12个月，以充分发挥其疗效。
Objective. To compare the safety and efficacy of parenteral methotrexate (MTX) at an intermediate dosage (15mg/m(2)/week) versus a higher dosage (30 mg/m(2)/ week) in patients with polyarticular-course juvenile idiopathic arthritis (JIA) who failed to improve while receiving standard dosages of MTX (8-12.5 mg/m(2)/ week).Methods. In the screening phase, 595 patients who were newly started on a standard dose of MTX were followed up for 6 months. Subsequently, the non-responders, defined according to the American College of Rheumatology (ACR) pediatric 30% improvement criteria (pediatric 30), were randomized to receive an intermediate dose or higher dose of parenteral MTX for an additional 6 months. Improvement in the screening and randomization phase was defined by the ACR pediatric 30 response, as well as by the 50% and 70% response levels (ACR pediatric 50 and ACR pediatric 70, respectively).Results. In the screening phase, after receiving standard doses of MTX, 430 patients (72%) improved according to the ACR pediatric 30, while 360 (61%) met the ACR pediatric 50 and 225 (38%) met the ACR pediatric 70; among these patients, 69 (12%) also met the definition of complete disease control. Of the 133 nonresponders, 80 were randomized to receive an intermediate dose, or higher dose of MTX. In the randomization phase, the ACR pediatric 30 response rate was 25 of 40 children (62.5%) in the intermediate-dose group versus 23 of 40 children (57.5%) in the higher-dose group. An ACR pediatric 50 response rate was attained by 23 patients (57.5%) receiving an intermediate dose versus 22 (55%) in the higher-dose group. An ACR pediatric 70 response rate was seen in 18 children (45%) receiving an intermediate dose versus 19 (47.5%) receiving a higher dose. Five children (12.5%) in the intermediate-dose group versus 4 (10%) receiving the higher dose of MTX also met the definition of complete disease control. None of the intergroup differences in response rate were significant. There were no significant differences in the frequency of adverse events or laboratory abnormalities between the 2 randomized groups.Conclusion. This study shows that the plateau of efficacy of MTX in JIA is reached with parenteral administration of 15 mg/m(2) /week and that a further increase in dosage is not associated with any additional therapeutic benefit. MTX should be administered for up to 9-12 months to appreciate its full therapeutic effect.