CLINICAL TRAILS IN PEDIATRIC RHEUMATOLOGY

描述(摘自申请者的摘要)：本申请重点 关于两项前瞻性多中心试验在儿童中的表现 幼年类风湿关节炎(JRA)。此外，这笔职业发展补助金 旨在增强许多儿科风湿病中心的能力 北美将进行试验以确定其疗效和安全性 用于JRA儿童的当前使用但未经测试的药物和新开发的药物 通过增加首席调查员(PI)专注于 指导和协调儿科风湿科的工作 协作性学习小组(PRCSG)，由PI担任主席。PRCSG是 由超过45个学术儿科风湿病中心组成的财团 在患有JRA的儿童身上进行了30多次试验。 试验1：骨量减少是JRA的一个重要且常见的并发症。这 研究方案包括前瞻性、随机性、多中心、 确定每日口服钙剂疗效的安慰剂对照试验(RCT) 补充碳酸钙(1000毫克/天)两年以增加 与安慰剂相比，全身骨密度(TB BMD)降低10%(1.5SD) 治疗。此外，治疗效果的持久性将是 在随机对照试验后确定为1.5年。这将是第一个纵向的 对JRA和对照组的骨矿化研究将证明 骨矿化的自然历史。 试验2：本研究方案还包括前瞻性、随机化、 主动对照、开放临床试验，以确定其疗效 联合用药诱导儿童长期无药缓解 患有严重系统性JRA(SJRA)。患者将在疾病的早期进行登记 当然，但资格标准将选择风险为115%的人 发展成严重的侵蚀性多发性关节炎。一种治疗方案由以下部分组成 连续3天静脉注射甲基强的松龙，静脉注射 环磷酰胺，第3天，甲氨蝶呤20 mg/m2/wk。这个 第二个脉冲治疗方案与第一个相同，只是没有 给出了环磷酰胺。这些方案最多可以在一年内进行5个周期 9个月。两组患者均可接受背景药物治疗。 包括1种非类固醇消炎药和不超过0.5 mg/kg/d的口服 强的松。这些治疗的短期和中期(0-18个月)安全性 我们将对这些疗法进行比较。 长期目标：1.评估当前和新兴药物的有效性和安全性 药物和生物治疗作为JRA钙的辅助治疗 骨质疏松症患者。2.确定该药的长期疗效和安全性 这些治疗方案在sJRA中使用。

DESCRIPTION (Taken from the applicant's abstract): This application is focused on the performance of two prospective, multicentered trials in children with juvenile rheumatoid arthritis (JRA). In addition, this career development grant is intended to enhance the ability of many pediatric rheumatology centers in North America to perform trials to determine the efficacy and safety of currently used but untested and also newly developed drugs in children with JRA by increasing the ability of the principal investigator (PI) to focus on the direction and coordination of the efforts of the Pediatric Rheumatology Collaborative Study Group (PRCSG) of which the PI is the chairman. The PRCSG is a consortium of over 45 academic pediatric rheumatology centers that have performed over 30 trials in children with JRA. Trial 1: Osteopenia is a significant and frequent complication of JRA. This research proposal includes a prospective, randomized, multicenter, placebo-controlled trial (RCT) to determine the efficacy of daily oral calcium supplementation (1000 mg/day of calcium carbonate) for two years to increase total body bone mineral density (TB BMD) by 10% (1.5 SD) compared to placebo treatment. In addition, the persistence of the treatment effect will be determined for 1.5 years after the RCT. This will be the first longitudinal study of bone mineralization in JRA and the control group will demonstrate the natural history of bone mineralization. Trial 2: This research proposal also includes a prospective, randomized, actively controlled, open clinical trial to determine the efficacy of combination drug therapy to induce prolonged drug-free remission in children with severe systemic JRA (sJRA). Patients will be enrolled early in the disease course but eligibility criteria will select those with a 115% risk of developing severe, erosive polyarthritis. One therapy regimen is composed of intravenous methylprednisolone for 3 consecutive days, intravenous cyclophosphamide on the third day, and up to 20 mg/M2/wk of methotrexate. The second pulse therapy regimen is identical to the first, except no cyclophosphamide is given. Up to 5 cycles of these regimens may be given over a 9-month period. Patients in both groups may also receive background medications including 1 non-steroidal anti-inflammatory drug and up to 0.5 mg/kg/d of oral prednisone. The short and intermediate (0-18 months) safety of these treatment regimens will be compared. Long-term goals: 1. Assess the efficacy and safety of current and emerging pharmacologic and biologic treatments as adjunctive therapy to calcium in JRA patients with osteopenia. 2. Determine the long-term efficacy and safety of these treatment regimens in sJRA.