Comparison of Methotrexate and Biologics in JIA (COMPARE-JIA)

 描述(申请人提供)：与关节较少的儿童相比，患有多关节病程的幼年特发性关节炎(≥5关节；PolyJIA)的儿童通常患有难治性疾病，导致更多的关节损伤，生活质量下降，以及更差的功能结果。现在的治疗选择包括多种不同作用机制的生物制剂(肿瘤坏死因子-α[肿瘤坏死因子α]、抑制T细胞共刺激和白细胞介素6)。然而，与甲氨蝶呤(MTX)相比，不同类别的生物药物的有效性尚未在一项研究中进行评估。拟议的试验-甲氨蝶呤和生物制品在JIA中的比较(COMPARE-JIA)-将是第一次比较不同生物疗法作为多发性JIA的初始治疗的有效性，产生关键的ATA来指导早期多发性JIA儿童的治疗。拟议的试验将通过儿童关节炎和风湿病研究联盟(CARA)进行，这是一个由北美300多名儿科风湿病医生组成的网络，并利用现有的CARA注册基础设施(NIAMS RC2 AR058934)进行数据收集、现场管理、信息学和协调中心(杜克临床研究所)。拟议的试验将解决以下具体目标：1)在随机对照试验的背景下，比较3种不同生物疗法(certolizumab、abatacept和tocilizumab与MTX联合应用)与MTX单一疗法在12个月时在多发性JIA患儿中实现临床非活动期疾病(CID)的有效性；以及2)比较3种生物不同疗法(certolizumab、abatacept和tocilizumab与MTX联合应用)与MTX单一疗法在6个月时实现CID的有效性。试验创新包括使用青少年关节炎疾病活动评分(疾病活动的综合衡量标准)作为中期结果和探索性目标，其中包括比较3个生物分支的CID成就，以及通过分析个别患者的轨迹来分析12个月后反应和无反应的临床和生物预测因素。规划阶段的具体目标是：1)征求利益相关者的意见，并将其纳入研究设计和方案。规划拨款将支持模型招募和研究调查人员、母公司代表和制药公司科学家的会议，以确保研究的可行性、社区支持和相关的结果措施；以及2)最终确定研究设计并实施研究程序。研究设计和试验操作的最终确定，包括研究预算、方案制定、统计分析计划、操作程序手册和知情同意书，将在规划期间完成，最终提交一项创新临床试验的UM1提案，该提案将展示不同类别的生物制剂作为多发性JIA一线治疗的比较有效性，并促进JIA病理生理学的进一步研究。

 DESCRIPTION (provided by applicant): Children with polyarticular-course juvenile idiopathic arthritis (≥ 5 joints; poly-JIA) often have refractory disease resulting in more joint damage, decreased quality of life, and worse functional outcomes compared to children with fewer joints. Treatment options now include multiple biologic agents with different mechanisms of action (tumor necrosis factor-α [TNFα], inhibition of T-cell co-stimulation, and interleukin-6). However the effectiveness of different classes of biologic medications in comparison to methotrexate (MTX) has not been evaluated in a single study. The proposed trial - Comparison of Methotrexate and Biologics in JIA (COMPARE-JIA) - will be the first trial to compare the effectiveness of different biologic therapies as initial therapy for poly-JIA, generating critical ata to guide treatment of children with early poly-JIA. The proposed trial will be conducted through the Childhood Arthritis and Rheumatology Research Alliance (CARRA), a network of over 300 pediatric rheumatologists in North America, and utilize existing CARRA Registry infrastructure (NIAMS RC2 AR058934) for data collection, site management, informatics, and the coordinating center (Duke Clinical Research Institute). The proposed trial will address the following specific aims: 1) Compare the effectiveness of 3 biologically distinct treatments (certolizumab, abatacept, and tocilizumab administered in combination with MTX) to MTX monotherapy, in achieving clinical inactive disease (CID) at 12 months in children with poly-JIA in the context of a randomized controlled trial; and 2) Compare the effectiveness of 3 biologically distinct treatments (certolizumab, abatacept, and tocilizumab administered in combination with MTX) to MTX monotherapy, in achieving CID at 6 months in children with poly-JIA. Trial innovations include use of the Juvenile Arthritis Disease Activity Score (a composite measure of disease activity) as an interim outcome and exploratory aims that include comparison of achievement of CID between the 3 biologic arms and analyses of clinical and biologic predictors of response and non-response at 12 months by analyzing individual patient trajectories. The specific aims for the planning phase are: 1) Solicit and incorporate stakeholder input into study design and protocol. The planning grant will support model recruitment and a meeting of study investigators, parent representative, and pharmaceutical company scientists to ensure study feasibility, community support, and relevant outcome measures; and 2) Finalize study design and operationalize study procedures. Final determination of study design and trial operations including study budget, protocol development, statistical analysis plan, manual of operating procedures, and informed consent forms will be accomplished during the planning period, culminating in the submission of a UM1 proposal for an innovative clinical trial that will demonstrate the comparative effectiveness of different classes of biologic agents as first-line therapy for poly-JIA and foster further study of JIA pathophysiology.