Evaluating the relationship between immune checkpoint inhibitors and osteoarthritis

评估免疫检查点抑制剂与骨关节炎之间的关系

• 批准号: 10577306
• 负责人: Laura Christine Cappelli
• 金额: $ 8.19万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-01-10 至 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10577306
• 关键词: Address; Advanced Malignant Neoplasm; Adverse effects; Affect; Age; Body mass index; Bone Marrow; CTLA4 gene; Cancer Patient; Cancer Survivor; Classification; Clinical; Clinical Investigator; Cohort Studies; Collaborations; Data; Degenerative polyarthritis; Development; Edema; Exposure to; Fostering; Foundations; Goals; Hip Osteoarthritis; Hip region structure; Image; Immune; Immune checkpoint inhibitor; Immunologic Factors; Inflammation; Inflammatory Arthritis; Joints; Long-Term Survivors; Longitudinal cohort; Malignant Neoplasms; Malignant neoplasm of lung; Methods; Modeling; Monitor; Morbidity - disease rate; Musculoskeletal; Oncology; Osteogenesis; Pain; Patients; Pelvis; Prevalence; Prevention strategy; Preventive therapy; Process; Protocols documentation; Provider; Pulmonary Inflammation; Quality of life; Radiation exposure; Radiology Specialty; Regression Analysis; Reporting; Risk; Risk Factors; Severities; Staging; Standardization; Symptoms; Synovitis; System; T-Cell Activation; Testing; Time; Tissues; Translating; Vitiligo; X-Ray Computed Tomography; abdominal CT; body system; cancer therapy; cancer type; checkpoint therapy; clinical care; clinical risk; cohort; comorbidity; cost; experience; hazard; immune activation; immune-related adverse events; improved; improved outcome; joint injury; melanoma; patient stratification; programmed cell death ligand 1; programmed cell death protein 1; prospective; radiological imaging; research clinical testing; rheumatologist; risk stratification; screening; sex; skills; systemic inflammatory response; tumor

Project Summary/Abstract The major goals of this proposal are to: 1) Determine whether hip osteoarthritis (OA) is a risk factor for developing inflammatory arthritis (IA) due to immune checkpoint inhibitors (ICIs). 2) Evaluate whether preexisting hip OA progresses more quickly in patients exposed to ICIs as compared to other patients with cancer. ICIs have improved outcomes for a variety of malignancies, but also cause immune related adverse events (irAEs). ICI-induced IA is the irAE most likely to be encountered by rheumatologists. ICI-induced IA causes significant morbidity, is clinically heterogeneous, and can persist after ICI cessation. Despite its impact on patients, clinical risk factors for ICI-induced IA are not well defined. The proposed project will utilize a cohort of well characterized patients treated with ICIs and CT imaging already obtained as a part of cancer clinical care to address the question of whether hip OA is a risk factor for development of ICI-induced IA. This project tests the hypothesis that an abnormality in the microenvironment of one joint can lead to a systemic inflammatory response that in turn affects other joints in the setting of immune activation by ICIs. Understanding risk factors for development of IA will allow for risk stratification of patients prior to therapy, differential monitoring, and potentially allow for trials of preventive therapies. The proposal will also evaluate progression of hip OA with serial CT scans in patients treated with ICIs and other cancer patients treated with different therapies. Patients on ICI therapy can experience an increase of symptoms of preexisting OA sometimes termed “activated OA”. Whether this increase in symptoms is related to increased progression on imaging is unknown. This study will determine if progressive OA is likely to be a major cause of morbidity and functional limitation in long-term survivors from cancer treated with ICIs. In sum, the proposal will answer important questions about the relationship between ICI therapy and OA using radiographic data from CT scans obtained through routine clinical care, thereby generating no additional cost or radiation exposure for patients.

项目总结/摘要 该提案的主要目标是：1）确定髋关节骨关节炎（OA）是否是 由于免疫检查点抑制剂（ICI）而发展成炎性关节炎（IA）。2)评估是否 与其他暴露于ICI的患者相比，暴露于ICI的患者中既存髋关节OA进展更快， 癌ICI改善了各种恶性肿瘤的结局，但也导致免疫相关不良反应。 事件（irAE）。ICI诱导的IA是风湿病学家最可能遇到的irAE。ICI诱导的IA 导致显著的发病率，临床上是异质性的，并且在ICI停止后可以持续。尽管它的影响 在患者中，ICI诱导IA的临床风险因素尚未明确。拟议的项目将利用一个队列 接受ICI和CT成像治疗的特征良好的患者已经作为癌症临床的一部分获得 注意解决髋关节OA是否是ICI诱导IA发展的风险因素的问题。这个项目 测试了一个关节微环境的异常可能导致全身性关节炎的假设。 炎症反应，这反过来又影响其他关节的免疫激活的设置ICI。 了解IA发生的风险因素将允许在治疗前对患者进行风险分层， 差异监测，并可能允许预防性治疗的试验。该提案还将评估 在接受ICI治疗的患者和接受ICI治疗的其他癌症患者中进行连续CT扫描的髋关节OA进展 不同的疗法。接受ICI治疗的患者可能会出现既存OA症状增加 有时被称为“活化OA”。这种症状的增加是否与 成像未知。这项研究将确定进行性OA是否可能是发病的主要原因， ICIs治疗癌症长期存活者的功能限制。总而言之，该提案将回答 使用CT扫描的影像学数据，探讨ICI治疗与OA之间关系的重要问题 通过常规临床护理获得，从而不会为患者产生额外的成本或辐射暴露。