Early Aggressive Therapy in Juvenile Idiopathic Arthritis

描述（由申请人提供）：背景：幼年特发性关节炎（JIA）是最常见的儿科风湿性疾病。40%的JIA儿童患有多发性关节炎（poly-JIA），这与持续活动性疾病有关，其特征是滑膜炎，关节损伤，身体功能能力下降，生活质量逐渐下降。最近在成人类风湿性关节炎中的研究表明，在疾病过程的非常早期存在“机会之窗”，在此期间，积极的治疗方法导致疾病进展的深刻改变。这项临床试验旨在确定在poly-JIA发作后6个月内开始的积极治疗是否能够在开始后6个月内诱导非活动性疾病（ID）状态，以及随后的药物临床缓解（CRM）。方法学：本提案是一项持续时间长达1年的随机、多中心、前瞻性临床试验。长达6个月的安慰剂对照双盲期是试验的关键部分。86例2-17岁近期发作的多聚JIA儿童将随机分配至2种积极治疗方案之一：A组=甲氨蝶呤（MTX; 0.5 mg/kg/wk;最大40 mg/wk 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，最大剂量50 mg/wk）+泼尼松（0.5 mg/kg/d;最大剂量60 mg/d，17周时逐渐减少至0）。6个月访视时达到ID的受试者将继续治疗6个月，以确定是否达到CRM。4个月时未达到ACR儿科70缓解或6个月时未达到ID的患者将被分配至开放标签治疗组B。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。次要分析将确定达到ID的时间、达到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的影响。将在基线和6个月时对30例受试者（A组和B组各15例）的1个膝关节进行IV钆MRI，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，增加疾病病程早期疾病静止的可能性，则可能可以避免与这种疾病相关的许多相关发病率，生活质量下降和医疗保健费用。

DESCRIPTION (provided by applicant): 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.