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

 描述（由申请方提供）：与关节较少的儿童相比，患有多关节病程幼年特发性关节炎（≥ 5个关节;多关节型JIA）的儿童通常患有难治性疾病，导致更多关节损伤、生活质量下降和更差的功能结局。目前的治疗选择包括具有不同作用机制的多种生物制剂（肿瘤坏死因子-α [TNFα]、抑制T细胞共刺激和白细胞介素-6）。然而，不同类型的生物药物与甲氨蝶呤（MTX）相比的有效性尚未在单一研究中进行评估。拟议的试验-甲氨蝶呤和生物制剂在JIA中的比较（COMPARE-JIA）-将是第一个比较不同生物疗法作为poly-JIA初始疗法的有效性的试验，产生指导早期poly-JIA儿童治疗的关键数据。拟定的试验将通过儿童关节炎和风湿病研究联盟（CARRA）（北美300多名儿科风湿病学家组成的网络）进行，并利用现有的CARRA登记基础设施（NIAMS RC 2 AR 058934）进行数据收集、研究中心管理、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）比较3种生物学上不同的治疗方法的有效性在一项随机对照试验的背景下，在患有poly-JIA的儿童中，在12个月时实现临床非活动性疾病（CID）中，将赛妥珠单抗、阿巴西普和托珠单抗与MTX联合给药）与MTX单药相比;和2）比较3种生物学上不同的治疗（与MTX组合施用的赛妥珠单抗、阿巴西普和托珠单抗）与MTX单一疗法在患有poly-JIA的儿童中在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性评分（疾病活动性的综合指标）作为中期结局和探索性目标，包括比较3个生物组之间的CID实现情况，以及通过分析个体患者轨迹分析12个月时缓解和无缓解的临床和生物学预测因素。计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。计划补助金将支持模型招募和研究调查人员，家长代表和制药公司科学家的会议，以确保研究可行性，社区支持和相关结果措施; 2）最终确定研究设计和实施研究程序。研究设计和试验操作（包括研究预算、方案制定、统计分析计划、操作规程手册和知情同意书）的最终确定将在计划期间完成，最终提交了一项创新性临床试验的UM 1提案，该试验将证明不同类别的生物制剂作为多药耐药的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.