Niehues Tim, Lankisch Petra
Department of Pediatric Oncology, Hematology and Immunology, Pediatric Immunology and Rheumatology, Centre for Child Health, Heinrich-Heine-University, Düsseldorf, Germany.
Paediatr Drugs. 2006;8(6):347-56. doi: 10.2165/00148581-200608060-00003.
Juvenile idiopathic arthritis (JIA) is one of the most common rheumatic diseases in childhood. In a significant number of JIA cases the disease is resistant to therapy with NSAIDs, intra-articular corticosteroid injections, and physiotherapy, and methotrexate is used as a second-line agent. The efficacy of methotrexate therapy in children with JIA has been demonstrated in prospective controlled trials and this agent appears to have slightly superior efficacy compared with leflunomide. Data from randomized studies indicate a starting dose of 10-15 mg/m(2)/week orally. The dose of parenteral methotrexate can be increased to 15-20 mg/m(2)/week. Combination therapy with methotrexate and an NSAID is recommended. However, there are still no data on when to initiate methotrexate in JIA and how long children should be treated. The most common adverse effects are aversion to the drug and nausea. In the case of minor adverse effects the use of folic acid at a dosage of 1 mg/day is feasible. In JIA, daily folate supplementation has only been studied in one small heterogeneous cohort with a very short observation period and, at present, a general recommendation on daily folate supplementation cannot be made. In summary, methotrexate is seen by many pediatric rheumatologists as the first-choice, second-line drug; there is good evidence of its efficacy in JIA. However, in light of the recent introduction of biologic agents, the place of methotrexate in the treatment of JIA may have to be redefined in the coming years.
幼年特发性关节炎（JIA）是儿童期最常见的风湿性疾病之一。在大量JIA病例中，该疾病对非甾体抗炎药、关节内注射皮质类固醇和物理治疗均耐药，甲氨蝶呤被用作二线药物。甲氨蝶呤治疗JIA患儿的疗效已在前瞻性对照试验中得到证实，与来氟米特相比，该药似乎疗效略优。随机研究数据表明口服起始剂量为10 - 15mg/m²/周。胃肠外甲氨蝶呤的剂量可增至15 - 20mg/m²/周。推荐甲氨蝶呤与非甾体抗炎药联合治疗。然而，关于JIA何时开始使用甲氨蝶呤以及儿童应治疗多长时间，目前仍无相关数据。最常见的不良反应是药物厌恶和恶心。对于轻微不良反应，每日服用1mg叶酸是可行的。在JIA中，仅在一个观察期很短的小型异质性队列中研究过每日补充叶酸的情况，目前无法给出关于每日补充叶酸的总体建议。总之，许多儿科风湿病学家将甲氨蝶呤视为首选的二线药物；有充分证据表明其在JIA中有效。然而，鉴于近期生物制剂的引入，未来几年甲氨蝶呤在JIA治疗中的地位可能需要重新定义。
