Immunological, serologic, and imaging biomarker predictors of flare in pediatric spondyloarthritis

小儿脊柱关节炎发作的免疫学、血清学和影像学生物标志物预测因子

• 批准号: 10491257
• 负责人: Pamela Fitch Weiss
• 金额: $ 38.2万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-20 至 2026-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10491257
• 关键词: Abate; Accounting; Address; Adolescent; Aftercare; Age; Ancillary Study; Anxiety; Apoptosis; Area; Arthritis; Benign; Biological; Biological Markers; Biological Products; Biological Response Modifier Therapy; CD3 Antigens; COVID-19 pandemic; CTLA4 gene; Caregivers; Cells; Child; Childhood; Chronic Childhood Arthritis; Clinical; Communities; Data Reporting; Databases; Decision Making; Demyelinating Diseases; Disease; Dose; Enrollment; Equipoise; Family; Flare; Frequencies; Funding; Genetic Transcription; Goals; Image; Immune; Immunologic Markers; Immunologics; Inflammation; Inflammatory; Infrastructure; Knowledge; Magnetic Resonance Imaging; Malignant Neoplasms; Memory; Messenger RNA; Mitogen-Activated Protein Kinases; Morbidity - disease rate; NF-kappa B; NIH Program Announcements; Outcome; Parents; Patients; Pelvis; Pharmaceutical Preparations; Phenotype; Population; Predictive Value; Prevalence; Process; Protocols documentation; Psoriasis; Public Health; Quality of life; ROC Curve; Randomized; Receptor Activation; Recording of previous events; Relapse; Research; Residual state; Resources; Risk; Role; Sacroiliac joint structure; Serology; Signal Transduction; Spondylarthritis; T memory cell; T-Cell Activation Pathway; T-Cell Receptor; T-Lymphocyte Subsets; TNF gene; Testing; Time; Withdrawal; Withdrawing Treatments; Work; clinical care; clinical predictors; clinically relevant; cohort; cytokine; disorder risk; evidence base; imaging biomarker; immune checkpoint; improved; infection risk; inhibitor; inhibitor therapy; point of care; pragmatic trial; predictive marker; programmed cell death protein 1; side effect; standard of care; tool

PROJECT SUMMARY Across the world, spondyloarthritis (SpA) is the most common form of juvenile arthritis, accounting for as many as one-third of all cases. Since the introduction of biologic disease modifying agents such as tumor necrosis factor inhibitors (TNFi), inactive disease is a realistic goal for children with spondyloarthritis (SpA). However, side effects of TNFi include increased risk of infection, psoriasis, demyelinating disorders, and malignancy. Additionally, TNFi are expensive and may adversely impact patient’s and caregiver’s quality of life and anxiety. Recently, the COVID-19 pandemic prompted numerous inquiries regarding whether being on a TNFi increased the risk of becoming infected, and, if infected, whether being on a TNFi increased the risk of morbidity. In the absence of definitive answers many families’ next question was, “Can we stop the medication?” We must address two critical knowledge gaps to inform strategies for TNFi de-escalation in children with SpA. First, it is unknown if subclinical imaging represents a risk for flare or whether it represents benign residual activity. Presently, clinical equipoise exists in whether subclinical inflammation on pelvic MRI should impact treatment decisions about children with SpA and axial disease because we do not know the prevalence or the clinical relevance of these MRI findings. Second, the role of cellular biomarkers to predict flare after therapy de- escalation in juvenile SpA is unknown. Prior studies in polyarticular juvenile arthritis have identified cellular populations and biomarkers that can distinguish disease states that are highly associated with relapse. Similar studies have not been done in juvenile SpA. Our objective is to test the association of immunologic, serologic and imaging biomarkers with the risk of disease flare in children with SpA by leveraging the infrastructure and resources of the parent trial, Biologic Abatement and Capturing Kids’ Outcomes and Flare Frequency in Juvenile SpA (BACK-OFF JSpA) to perform mechanistic studies to address these critical knowledge gaps. This application has 2 specific aims: 1) to test the ability of imaging biomarkers at the time of medication de- escalation to predict subsequent flare in children with axial arthritis, and 2) to test the ability of cellular biomarkers at the time of medication de-escalation to predict subsequent flare in all children with SpA. The work proposed in this application will directly impact clinical care and significantly enhance the evidence base that clinicians, families, and patients use to make decisions about whether or not to de-escalate biologic therapy.

项目总结 在世界各地，脊柱炎(Spa)是最常见的青少年关节炎形式，占 占所有案件的三分之一。自从引入了生物疾病修饰剂，如肿瘤坏死 因子抑制物(TNFi)，非活动性疾病是脊柱炎(SpA)儿童的现实目标。然而， TNFi的副作用包括增加感染、牛皮癣、脱髓鞘疾病和恶性肿瘤的风险。 此外，TNFi费用昂贵，可能会对患者和照顾者的生活质量和焦虑产生不利影响。 最近，新冠肺炎疫情引发了大量关于使用TNFI是否会增加的询问 被感染的风险，以及如果被感染，是否使用TNFi会增加发病风险。在 许多家庭的下一个问题是：“我们能停止用药吗？”我们必须 解决两个关键的知识差距，以便为降低温泉儿童的TNFi降级战略提供信息。首先，它是 尚不清楚亚临床影像是否存在红斑的风险，或者是否代表良性残留活动。 目前，盆腔mri亚临床炎症是否影响治疗存在临床均衡性。 关于患有SpA和轴性疾病的儿童的决定，因为我们不知道患病率或临床 这些MRI表现的相关性。第二，细胞生物标记物在预测治疗后红斑的作用。 青少年水疗中心的升级情况尚不清楚。先前对多关节幼年性关节炎的研究已经确认了细胞 可以区分与复发高度相关的疾病状态的人群和生物标记物。类似 还没有在青少年温泉浴场进行过研究。我们的目标是测试免疫学、血清学 以及成像生物标志物，通过利用基础设施和 父母试验、生物治疗和捕获儿童的结果和耀斑频率的来源 青少年温泉(后退JSpA)进行机械性研究，以解决这些关键的知识差距。这 应用程序有两个具体目标：1)测试药物停药时成像生物标记物的能力 升级以预测轴性关节炎儿童随后的闪光，以及2)测试细胞的能力 药物降级时的生物标记物预测所有SpA儿童随后的闪光。这个 本申请中提出的工作将直接影响临床护理，并显著增强证据基础 临床医生、家属和患者用来决定是否降低生物量 心理治疗。