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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

基本信息

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
项目类别：
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

项目摘要

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.

项目概要在世界范围内，脊柱关节炎 (SpA) 是最常见的幼年型关节炎，占占所有病例的三分之一。自从引入肿瘤坏死等生物疾病调节剂以来因子抑制剂（TNFi），非活动性疾病是脊柱关节炎（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 价格昂贵，可能会对患者和护理人员的生活质量和焦虑产生不利影响。最近，COVID-19 大流行引发了大量询问，询问服用 TNFi 是否会增加被感染的风险，如果被感染，是否服用 TNFi 会增加发病风险。在由于缺乏明确的答案，许多家庭的下一个问题是：“我们可以停止用药吗？”我们必须解决两个关键的知识差距，为 SpA 儿童的 TNFi 降级策略提供信息。首先，它是未知亚临床成像是否代表耀斑风险或是否代表良性残留活动。目前，对于盆腔 MRI 上的亚临床炎症是否会影响治疗，临床上存在着平衡。关于患有 SpA 和中轴病的儿童的决定，因为我们不知道患病率或临床情况这些 MRI 结果的相关性。其次，细胞生物标志物在预测治疗后复发的作用青少年 SpA 的升级情况尚不清楚。先前对多关节幼年关节炎的研究已经确定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志物。相似的尚未对青少年 SpA 进行研究。我们的目标是测试免疫学、血清学之间的关联通过利用基础设施和技术，对 SpA 儿童疾病发作风险的生物标志物进行成像家长试验的资源、生物抑制和捕获儿童的结果以及耀斑频率 Juvenile SpA (BACK-OFF JSpA) 进行机制研究，以解决这些关键的知识差距。这应用程序有 2 个具体目标：1）测试药物治疗时生物标志物成像的能力升级以预测中轴关节炎儿童随后的发作，以及 2) 测试细胞的能力药物降级时的生物标志物可预测所有 SpA 儿童随后的发作。这本申请中提出的工作将直接影响临床护理并显着增强证据基础临床医生、家庭和患者用来决定是否降级生物制剂治疗。