Early Aggressive Therapy in Juvenile Idiopathic Arthritis

背景：幼年特发性关节炎（JIA）是最常见的儿童风湿性疾病。 40%的JIA儿童患有多发性关节炎（poly-JIA），这与持续活动有关。 以滑膜炎、关节损伤、身体功能能力下降和进行性关节炎为特征的疾病 生活质量下降。最近对成人类风湿性关节炎的研究表明， 在疾病过程的早期，积极的治疗方法会导致 疾病进展的深刻改变。这项临床试验旨在确定积极的治疗是否 在poly-JIA发作后6个月内开始的治疗能够诱导非活动性疾病（ID）状态， 开始治疗6个月，随后药物治疗临床缓解（CRM）。方法论：本提案是一个 持续时间长达1年的随机、多中心、前瞻性临床试验。一项安慰剂对照双盲 长达6个月的阶段是试验的关键部分。86名2-17岁的儿童， 近期发作的JIA将被随机分配至2种积极治疗方案之一：A组=甲氨蝶呤（MTX; 0.5 mg/kg/周;最大40 mg/周SQ）+模拟依那西普SQ每周一次+模拟每日口服泼尼松; B组= MTX（与A组相同）+依那西普（0.8 mg/kg/wk SQ，最大50 mg/wk）+泼尼松（0.5 mg/kg/d;最大剂量50 mg/wk） 60 mg/d，17周时逐渐减少至0）。6个月访视时达到ID的受试者将继续 再治疗6个月，以确定是否达到CRM。那些没有达到 开放标签治疗组B将提供4个月时ACR儿科70缓解或6个月时ID。的 主要分析将比较每个治疗组中6个月时达到ID的受试者比例 以及治疗组的安全性特征。次要分析将确定实现ID的时间， 获得CRM的受试者比例以及CRM对身体功能能力和健康相关 生活质量将在基线和6个月时对30例受试者的1个膝关节进行IV钆MRI (15分别来自A组和B组）以观察活动性和非活动性疾病的生物学相关性。重要性： 如果可以确定一种多聚JRA的治疗策略， 在疾病过程的早期，许多相关的发病率，生活质量下降，卫生保健 与这种疾病相关的费用可能是可以避免的。

BACKGROUND: Juvenile Idiopathic Arthritis (JIA) is the most prevalent pediatric rheumatologic illness. Forty percent of children with JIA have polyarthritis (poly-JIA), which is associated with persistently active disease characterized by synovitis, joint damage, decreased physical functional ability, and a progressive decrease in quality of life. Recent studies in adult rheumatoid arthritis suggest there exists a "window of opportunity" very early in the disease course during which aggressive therapeutic approaches result in profound alteration of disease progression. This clinical trial seeks to determine if aggressive treatment initiated within 6 months of the onset of poly-JIA is capable of inducing a state of inactive disease (ID) within 6 months of initiation and later clinical remission on medication (CRM). METHODOLOGY: This proposal is a randomized, multi-center, prospective clinical trial up to 1 year in duration. A placebo-controlled double-blind phase of up to 6 months represents the pivotal portion of the trial. 86 children aged 2-17 years with poly- JIA of recent onset will be randomized to 1 of 2 aggressive treatment regimens: Arm A = Methotrexate (MTX; 0.5 mg/kg/wk; max 40 mg/wk SQ) + dummy etanercept SQ weekly + dummy daily oral prednisone; Arm B = MTX (as in Arm A) + etanercept (0.8 mg/kg/wk SQ, max 50 mg/wk) + prednisone (0.5 mg/kg/d; max dose of 60 mg/d tapered to zero by 17 weeks). Subjects who achieve ID by or at the 6 month visit will continue treatment for an additional 6 months to determine if CRM is achieved. Those patients who do not achieve an ACR Pediatric 70 response by 4 months, or ID by 6 months will be offered open label Treatment Arm B. The primary analyses will compare the proportions of subjects in each treatment arm that achieve ID by 6 months and the safety profiles of the treatment groups. Secondary analyses will determine time to achieve ID, the proportion of subjects that attain CRM and the effect of CRM on physical functional ability and health related quality of life. MRI with IV gadolinium will be performed at baseline and at 6 months on 1 knee of 30 subjects (15 each from Arm A and B) to observe biologic correlates of active and inactive disease. SIGNIFICANCE: If a therapeutic strategy for poly-JRA can be identified that increases the likelihood of disease quiescence early in the disease course, much of the associated morbidity, decreased quality of life, and health care costs associated with this illness likely can be avoided.