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.

项目摘要 全世界，赞助关节炎（SPA）是少年关节炎的最常见形式，占多数 所有情况中的三分之一。自从引入生物疾病修饰剂（例如肿瘤坏死）以来 因子抑制剂（TNFI），非活性疾病是赞助炎儿童（SPA）的现实目标。然而， TNFI的副作用包括增加感染的风险，牛皮癣，脱髓鞘性疾病和恶性肿瘤。 此外，TNFI很昂贵，可能会对患者和看护人的生活质量和动画产生不利影响。 最近，COVID-19大流行促使有关在TNFI上是否增加的众多询问 被感染的风险，如果感染了TNFI是否会增加发病率的风险。在 没有确切的答案，许多家庭的下一个问题是：“我们可以停止药物吗？”我们必须 解决两个关键的知识差距，以告知水疗儿童的TNFI降级策略。首先，是 未知亚临床成像是否代表了耀斑的风险，还是代表良性残留活性。 目前，在骨盆MRI上的亚临床感染是否应影响治疗方面存在临床平衡 关于水疗和轴向疾病儿童的决定，因为我们不知道患病率或临床 这些MRI发现的相关性。其次，细胞生物标志物在治疗后预测耀斑的作用 少年水疗中心升级是未知的。多关节少年关节炎的先前研究已经鉴定出细胞 可以区分与继电器高度相关的疾病状态的人群和生物标志物。相似的 尚未在少年水疗中心进行研究。我们的目标是测试免疫学，血清学的关联 并通过利用基础设施和 父母试验的资源，减少生物学和捕获孩子的成果和耀斑频率 少年水疗中心（助图JSPA）进行机械研究以解决这些关键的知识差距。这 应用具有2个特定目的：1）测试药物时成像生物标志物的能力 升级以预测轴向关节炎儿童的随后耀斑，以及2）测试细胞的能力 在药物降低时，生物标志物可以预测所有水疗中心儿童的随后耀斑。 本应用中提出的工作将直接影响临床护理，并显着增强证据基础 那个临床医生，家庭和患者用来决定是否降低生物学 治疗。