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.

在世界各地，脊柱炎(Spa)是幼年性关节炎最常见的形式，占 占所有案件的三分之一。这些儿童有发展为强直性脊柱炎的风险，强直性脊柱炎 关节融合的以关节融合、功能障碍和持续到成年期的心理影响为特征的 我们缺乏对这种情况的有效治疗，只有不到20%的青少年发病的spa儿童实现了 在确诊后五年内缓解。推进Spa和Spa儿童护理的主要障碍 轴性关节炎是缺乏随机临床试验(RCT)，尽管潜在的数量在增加。 治疗。此应用程序的总体前提是存在有效、全面和容易的 可雇用的疾病分类标准以及经过充分研究的结果标准将使成功的 为这一人群实施临床试验。在中国进行临床试验有两大障碍 这一未被研究的群体，这两个群体都在本申请中讨论。首先是儿科医生的缺乏。 中轴性关节炎的分类标准(脊柱或骶骨关节的关节炎)。成人使用的算法有 由于罕见的背部疼痛是儿童的突出临床症状，因此不适合儿童使用。我们的无能 对轴性受累进行分类是评估治疗效果和疗效的一个明显障碍。 第二个主要障碍是评估幼年特发性关节炎(JIA)疗效的结果措施。 试验并不是为了评估患有SpA和中枢性关节炎的儿童的独特疾病特征。如果没有 客观量化儿童骶髂关节疾病严重程度或评估枢椎的措施 症状、间歇变化和药物反应的评估是不可能的。虽然有 青少年和成人温泉的相似之处，也有明显的表型差异，值得具体 注重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 幼年温泉和轴性关节炎。本申请有两个具体目标：1)建立综合分类 轴性青少年SpA的标准，以及2)为儿童实用试验确定一套核心结果衡量标准 带轴向水疗中心。这项申请中提议的工作将使现场不仅能够进行临床试验 有希望的新疗法，如IL-17/IL-23和JAK-STAT通路的抑制剂，但也是务实的 嵌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