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

基本信息

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
项目类别：
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

项目摘要

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.

项目概要/摘要该提案的主要目标是： 1) 确定髋骨关节炎 (OA) 是否是以下疾病的危险因素：由于免疫检查点抑制剂 (ICIs) 导致炎症性关节炎 (IA) 2) 评估是否。与其他患有髋关节骨关节炎的患者相比，暴露于 ICI 的患者中先前存在的髋关节 OA 进展得更快 ICI 改善了多种恶性肿瘤的预后，但也会引起免疫相关的不良反应。 ICI 诱发的 IA 事件 (irAE) 是风湿病学家最有可能遇到的 irAE。导致显着的发病率，具有临床异质性，并且在 ICI 停止后仍可能持续存在，尽管有其影响。对于患者来说，ICI 诱发 IA 的临床危险因素尚未明确。拟议的项目将利用一个队列。作为癌症临床的一部分，已获得接受 ICI 和 CT 成像治疗的特征明确的患者本项目旨在解决髋关节 OA 是否是 ICI 诱发 IA 的危险因素这一问题。检验这一假设：一个关节的微环境异常会导致全身性的疾病在 ICI 激活免疫的情况下，炎症反应反过来会影响其他关节。了解 IA 发展的危险因素将有助于在治疗前对患者进行风险分层，该提案还将评估差异化监测，并可能允许进行预防性治疗试验。使用 ICI 治疗的患者和其他接受 ICI 治疗的癌症患者进行系列 CT 扫描后髋部 OA 的进展情况接受 ICI 治疗的患者可能会出现原有 OA 症状的增加。有时被称为“激活的 OA”。这种症状的增加是否与病情进展的加快有关。影像学检查尚不清楚，本研究将确定进行性 OA 是否可能是发病的主要原因。总之，该提案将回答接受 ICI 治疗的癌症长期幸存者的功能限制。使用 CT 扫描的放射线数据了解 ICI 治疗与 OA 之间关系的重要问题通过常规临床护理获得，因此不会给患者产生额外的费用或辐射暴露。