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

• 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
• 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
• 来源: https://reporter.nih.gov/project-details/9816539
• 关键词: Accounting; Address; Adolescent; Adult; Algorithms; American; Ankylosing spondylitis; Arthritis; Back Pain; Biological Response Modifier Therapy; Child; Child Care; Childhood; Chronic Childhood Arthritis; Classification; Clinical; Clinical Trials; Conduct Clinical Trials; Data; Diagnosis; Disease; Disease remission; Effectiveness; Enrollment; Flare; Future; Goals; Image; Impairment; Inflammation; Interleukin-17; Intervention; Joints; Knowledge; Measurement; Measures; NIH Program Announcements; Outcome; Outcome Measure; Outcomes Research; Pathway interactions; Patient Outcomes Assessments; Peripheral; Pharmaceutical Preparations; Phenotype; Population; Preparation; Property; Psychological Impact; Public Health; Publishing; Randomized Clinical Trials; Research; Rheumatology; Risk; Sacroiliac joint structure; Sample Size; Severity of illness; Spondylarthritis; Symptoms; Systemic Therapy; Therapy Evaluation; Vertebral column; Work; clinical care; clinical implementation; college; disease classification; effective therapy; functional disability; inclusion criteria; inhibitor/antagonist; instrument; interleukin-23; joint injury; novel therapeutics; pragmatic trial; prevent; primary outcome; prospective; response; secondary outcome; targeted treatment; treatment response

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.

在世界各地，脊柱关节炎（SpA）是青少年关节炎最常见的形式， 三分之一的病例。这些儿童有进展为强直性脊柱炎的风险， 以关节融合、功能损伤和持续到成年期的心理影响为特征。 我们缺乏对这种情况的有效治疗，只有不到20%的青少年发作的SpA儿童能够达到 诊断后五年内缓解。推进SpA儿童护理的主要障碍， 尽管有越来越多的潜在的治疗中轴性关节炎的随机临床试验（RCT）， 治疗这个应用程序的过度假设是，有效的，全面的，容易的 可采用的疾病分类标准以及经过充分研究的结果标准将允许成功的 为这一人群开展临床试验。进行临床试验有两个主要障碍， 这两个问题都在本申请中得到了解决。首先是儿科的缺失 中轴关节炎（脊柱或骶髂关节的关节炎）的分类标准。用于成人的算法是 由于背痛在儿童中作为突出临床症状的罕见性，因此不适合儿童。我们无法 对轴向受累进行分类是评价治疗效果和功效的明显障碍。 第二个主要障碍是评估幼年特发性关节炎（JIA）反应的结果指标 临床试验的设计并不是为了评估患有SpA和中轴性关节炎的儿童的独特疾病特征。没有 客观量化小儿骶髂关节疾病严重程度或评估轴向 无法评估间期变化和药物反应。虽然有 尽管幼年和成年SpA之间存在相似性，但也存在明显的表型差异，值得特异性 专注于青少年疾病的分类和试验。我们的目标是获得必要的数据， 疾病活动性的有意义的临床和亚临床变化，用于未来对儿童的临床试验， 青少年SpA和中轴性关节炎。该应用程序有2个具体目标：1）建立全面的分类 轴向青少年SpA的标准，以及2）为儿童的实用试验定义一组核心结果测量 轴向SpA。本申请中提出的工作将使该领域不仅能够进行 有前途的新疗法，如IL-17/IL-23和JAK-STAT通路的抑制剂，但也实用 常规临床护理中的试验。