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: 10224675
• 负责人: Pamela Fitch Weiss
• 金额: $ 18.78万
• 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 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10224675
• 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 trial 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.

在世界范围内，脊柱关节炎 (SpA) 是幼年关节炎最常见的形式，占 占所有病例的三分之一。这些儿童有发展为强直性脊柱炎的风险，这是 其特征是关节融合、功能障碍和持续到成年的心理影响。 我们缺乏针对这种疾病的有效治疗方法，只有不到 20% 的青少年发病 SpA 儿童能够达到治疗效果 诊断后五年内缓解。推进 SpA 儿童护理的主要障碍是 中轴关节炎缺乏随机临床试验（RCT），尽管潜在的治疗数量不断增加 疗法。该应用程序的首要前提是存在有效、全面且易于使用的 可使用的疾病分类标准以及经过深入研究的结果标准将允许成功 针对这一人群实施临床试验。进行临床试验有两个主要障碍 这个未被充分研究的人群，这两个问题都在本申请中得到解决。首先是儿科的缺乏 中轴关节炎（脊柱或骶髂关节关节炎）的分类标准。用于成人的算法是 由于背痛作为儿童突出的临床症状很少见，因此不适用于儿童。我们的无能 对轴向受累进行分类对评估治疗效果和功效提出了明显的障碍。 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 试验并非旨在评估患有 SpA 和中轴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的措施 症状、间隔变化和药物反应的评估是不可能的。虽然有 青少年和成人 SpA 之间存在相似之处，但也存在明显的表型差异，值得具体研究 重点关注青少年疾病的分类和试验。我们的目标是获得测量所需的数据 疾病活动的有意义的临床和亚临床变化，用于未来针对儿童的临床试验 幼年型 SpA 和中轴关节炎。该应用程序有 2 个具体目标：1) 建立全面的分类 中轴青少年 SpA 的标准，以及 2) 为儿童实用试验定义一套核心结果测量 与轴向 SpA。本申请中提出的工作将使该领域不仅能够进行临床试验 有前途的新疗法，例如 IL-17/IL-23 和 JAK-STAT 通路抑制剂，但也很务实 纳入常规临床护理的试验。

项目成果

Data-Driven Magnetic Resonance Imaging Definitions for Active and Structural Sacroiliac Joint Lesions in Juvenile Spondyloarthritis Typical of Axial Disease: A Cross-Sectional International Study.

轴性疾病典型的青少年脊柱关节炎的活动性和结构性骶髂关节病变的数据驱动磁共振成像定义：一项横断面国际研究。

• DOI: 10.1002/acr.25014
• 发表时间: 2023
• 期刊: Arthritis care & research
• 影响因子: 4.7
• 作者: Weiss,PamelaF;Brandon,TimothyG;Lambert,RobertG;Biko,DavidM;Chauvin,NancyA;Francavilla,MichaelL;Jaremko,JacobL;Herregods,Nele;Kasapcopur,Ozgur;Yildiz,Mehmet;Hendry,AlisonM;Maksymowych,WalterP
• 通讯作者: Maksymowych,WalterP

Consensus-Driven Definition for Unequivocal Sacroiliitis on Radiographs in Juvenile Spondyloarthritis.

青少年脊柱关节炎放射照片上明确的骶髂关节炎的共识驱动定义。

• DOI: 10.3899/jrheum.2022-0890
• 发表时间: 2023
• 期刊: The Journal of rheumatology
• 作者: Weiss,PamelaF;Brandon,TimothyG;Lambert,RobertG;Biko,DavidM;Chauvin,NancyA;Francavilla,MichaelL;Herregods,Nele;Hendry,AlisonM;Maksymowych,WalterP
• 通讯作者: Maksymowych,WalterP

Development and Validation of a Juvenile Spondyloarthritis Disease Flare Measure: Ascertaining Flare in Patients With Inactive Disease.

• DOI: 10.1002/acr.24763
• 发表时间: 2023-03
• 期刊: Arthritis care & research
• 影响因子: 4.7
• 作者: Weiss PF;Brandon TG;Ryan ME;Treemarcki EB;Armendariz S;Wright TB;Godiwala C;Stoll ML;Xiao R;Lovell D
• 通讯作者: Lovell D

Children With Enthesitis-Related Arthritis and Possible Benefits From Treatments for Adults With Spondyloarthritis.

• DOI: 10.1002/acr.24529
• 发表时间: 2022-07
• 期刊: Arthritis care & research
• 影响因子: 4.7
• 作者: Weiss PF;Fuhlbrigge RC;von Scheven E;Lovell DJ;Colbert RA;Brunner HI;PRCSG Advisory Council and the CARRA Executive Committee
• 通讯作者: PRCSG Advisory Council and the CARRA Executive Committee