Refining entry criteria and outcome measures for children with axial disease and spondyloarthritis: preparation for clinical trials

细化中轴病和脊柱关节炎儿童的入组标准和结果测量：临床试验的准备

基本信息

批准号：
9816539
负责人：
Pamela Fitch Weiss
金额：
$ 30.32万
依托单位：
CHILDREN'S HOSP OF PHILADELPHIA
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-08-12 至 2022-07-31
项目状态：
已结题

项目摘要

Across the world, spondyloarthritis (SpA) is the most common form of juvenile arthritis, accounting for as much as one-third of all cases. These children are at risk of progression to ankylosing spondylitis, which is characterized by fusion of the joints, functional impairment, and psychologic impact that lasts into adulthood. We lack effective therapy for this condition and fewer than 20% of children with juvenile-onset SpA achieve remission within five years of diagnosis. The major impediment to advancing the care of children with SpA and axial arthritis is an absence of randomized clinical trials (RCTs) despite an increasing number of potential therapies. The over-arching premise of this application is that the presence of valid, comprehensive, and easily employable disease classification criteria as well as well-researched outcome criteria will permit the successful implementation of clinical trials for this population. There are 2 major obstacles to conducting clinical trials in this understudied population, both of which are addressed in this application. The first is the lack of pediatric classification criteria for axial arthritis (arthritis of the spine or sacroiliac joints). Algorithms used for adults are inadequate for children due to the rarity of back pain as a prominent clinical symptom in children. Our inability to classify axial involvement presents a distinct obstacle to the evaluation of therapy effectiveness and efficacy. The second major obstacle is the outcome measures to assess response in juvenile idiopathic arthritis (JIA) trials are not designed to assess the unique disease features of children with SpA and axial arthritis. Without measures to objectively quantify the severity of disease in the pediatric sacroiliac joint or to assess axial symptoms, assessment of interval change and response to medication is not possible. While there are similarities between juvenile and adult SpA, there are also distinct phenotypic differences that merit specific focus on classification and trials in juvenile disease. Our objective is to obtain the data necessary to measure meaningful clinical and subclinical changes in disease activity for use in future clinical trials on children with juvenile SpA and axial arthritis. This application has 2 specific aims: 1) Establish comprehensive classification criteria for axial juvenile SpA, and 2) Define a core-set of outcome measures for pragmatic trials of children with axial SpA. The work proposed in this application will enable the field to conduct not only clinical trials of promising new therapies such as inhibitors of the IL-17/IL-23 and JAK-STAT pathways, but also pragmatic trials embedded within routine clinical care.

在世界范围内，脊椎关节炎（SPA）是少年关节炎的最常见形式所有情况中的三分之一。这些孩子有进展为强直性脊柱炎的风险，以融合关节的融合，功能障碍和持续到成年的心理影响的特征。对于这种情况，我们缺乏有效的疗法，少年发作水疗中心不到20％诊断五年内的缓解。促进水疗中心和儿童护理的主要障碍轴向关节炎是没有随机临床试验（RCT）的，尽管潜力越来越多疗法。该应用程序的整理前提是，存在有效，全面且容易的存在可就业疾病分类标准以及经过深入研究的结果标准将允许成功实施该人群的临床试验。进行临床试验有2个主要障碍这个研究人群进行了研究，这两者都在本申请中解决。首先是缺乏小儿轴向关节炎的分类标准（脊柱或s骨关节关节炎）。成人使用的算法是由于背痛的稀有性是儿童的明显临床症状，因此儿童不足。我们的无能分类轴向参与为评估治疗有效性和有效性的独特障碍。第二个主要障碍是评估青少年特发性关节炎（JIA）反应的结果措施试验并非旨在评估水疗和轴向关节炎儿童的独特疾病特征。没有措施客观地量化小儿sa骨关节中疾病的严重程度或评估轴向症状，间隔变化的评估以及对药物的反应是不可能的。而有少年和成人水疗中的相似之处，也存在明显的表型差异，值得特定专注于少年疾病的分类和试验。我们的目标是获取衡量所需的数据疾病活动的有意义的临床和亚临床变化，用于未来对患有儿童的临床试验青少年水疗和轴向关节炎。该应用程序具有2个特定目的：1）建立全面的分类轴向青少年水疗中心的标准，以及2）定义儿童务实试验的结果核心与轴向水疗中心。本申请中提出的工作将使该领域不仅可以进行临床试验有希望的新疗法，例如IL-17/IL-23的抑制剂和JAK-STAT途径，但也很务实嵌入常规临床护理中的试验。