Early Aggressive Therapy in Juvenile Idiopathic Arthritis

背景：幼年型特发性关节炎(JIA)是儿童风湿病中最常见的疾病。 40%的JIA儿童患有多发性关节炎(PolyJIA)，这与持续活动有关 一种以滑膜炎、关节损伤、身体机能减退和进行性 生活质量下降。最近对成人类风湿性关节炎的研究表明， 在疾病病程的非常早期，积极的治疗方法导致 疾病进程的深刻改变。这项临床试验试图确定侵入性治疗 在发病后6个月内启动，能够在以下情况下诱导非活动期疾病(ID) 开始服药6个月后临床缓解(CRM)。方法：这项建议是一项 随机、多中心、前瞻性临床试验，持续时间长达1年。安慰剂控制的双盲 长达6个月的阶段是试验的关键部分。86名2-17岁的儿童患有多发性... 近期发病的贾跃亭将随机接受两种积极治疗方案中的一种：ARM A=甲氨蝶呤(MTX； 0.5 mg/kg/wk；最大40 mg/wk sq)+每周假依那西普sq+假每日口服泼尼松；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 60 mg/d在17周时逐渐减少到零)。在6个月内或在6个月内获得身份证的受试者将继续 再治疗6个月，以确定是否实现了客户关系管理。那些没有达到目标的患者 ACR儿科70例缓解4个月或ID缓解6个月将给予开放标签治疗臂B。 初步分析将比较每个治疗组在6个月内获得ID的受试者比例 以及治疗组的安全概况。二次分析将确定实现ID的时间， 获得CRM的受试者比例及CRM对身体机能和健康的影响 生活质量。在基线和6个月时对30名受试者的1个膝关节进行静脉注射Gd的MRI检查 (A组和B组各15例)，观察活动性和非活动性疾病的生物学相关性。重要意义： 如果可以确定一种治疗多发性JRA的策略，可以增加疾病缓解的可能性 在病程早期，许多相关的发病率、生活质量下降和医疗保健 与这种疾病相关的成本很可能是可以避免的。

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.