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Understanding Inflammatory Arthritis due to Immune Checkpoint Inhibitors

了解免疫检查点抑制剂引起的炎症性关节炎

基本信息

批准号：
10680524
负责人：
Laura Christine Cappelli
金额：
$ 15.58万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-08-16 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10680524
关键词：
Address Adrenal Cortex Hormones Alleles Antibodies Area Arthritis Autoantibodies Autoimmune Autoimmune Diseases Award Biological Assay Characteristics Clinical Clinical Data Clinical Investigator Collaborations Collection Data Data Science Degenerative polyarthritis Development Diagnosis Disease Dose Epitopes Evaluation Event Family history of Fostering Foundations Future Goals Health IL17 gene Immune Immune checkpoint inhibitor Immunogenetics Immunologic Factors Immunosuppression Immunotherapy Inflammatory Inflammatory Arthritis Interleukin-6 Joints Knowledge Laboratories Literature Machine Learning Malignant Neoplasms Mentors Methods Modeling Monitor Morbidity - disease rate Myositis Oncology Operative Surgical Procedures Pathogenesis Pathogenicity Pathway interactions Patients Phenotype Predictive Factor Prognosis Public Health Schools Research Research Personnel Resolution Resources Rheumatism Rheumatoid Arthritis Rheumatology Risk Risk Factors Science Serum Sjogren&apos s Syndrome Specialist Subgroup Surveys Sushi Domain Syndrome T-Lymphocyte Techniques Time Trauma Treatment Protocols Vasculitis Visit active method anti-PD-1 anti-tumor immune response cancer immunotherapy cancer therapy career development checkpoint therapy clinical heterogeneity clinical phenotype clinical risk clinically relevant cohort cytokine data standards experimental study human leukocyte antigen testing immune-related adverse events improved insight meetings negative affect patient stratification potential biomarker prospective response rheumatologist risk stratification skills symposium targeted treatment therapeutic target translational scientist treatment response tumor tumor immunology

项目摘要

Project Summary/Abstract The major goals of this proposal are to attain skills required to be an independent clinical and translational researcher in rheumatology and to enhance understanding of a new rheumatic disease, inflammatory arthritis (IA) due to immune checkpoint inhibitors (ICIs). ICIs are revolutionizing cancer treatment but also cause immune related adverse events. ICI-induced IA is the immune related adverse event most likely to be encountered by rheumatologists. ICI-induced IA causes significant morbidity, is clinically heterogeneous, and can persist after ICI cessation. The proposed project will utilize a group of well characterized patients with ICI- induced IA and ICI-treated control patients who do not develop IA to address several important questions. First, the clinical heterogeneity within ICI-induced IA will be evaluated and factors that predict persistence of IA beyond cessation of ICI therapy will be established. Next, clinical and immunogenetic risk factors for developing ICI-induced IA will be determined. Finally, serum cytokine profiles and autoantibodies before and after ICI treatment will be compared in patients with ICI-induced IA and control patients who are treated with ICIs and do not develop IA. These experiments will address key knowledge gaps for this emerging clinical entity. Specifically, defining relevant clinical subgroups will allow for differential monitoring and treatment of patients. Understanding risk factors for development of IA will allow for risk stratification of patients prior to therapy. Cytokines that are elevated in ICI-induced IA patient sera could serve as future therapeutic targets. Finally, understanding presence of autoantibodies and when they develop in the course of ICI treatment will give insight into pathogenesis and identify potential biomarkers. Concurrently with conducting research during the proposal, the candidate will participate in a variety of career development activities taking advantage of the rich resources of Johns Hopkins in the Division of Rheumatology, the Bloomberg Kimmel Institute for Cancer Immunotherapy, and the Bloomberg School of Public Health. The candidate will participate in didactic coursework, conferences, and mentoring meetings with a diverse group of mentors from rheumatology, oncology, laboratory science, and data science. At the end of this award, the candidate will be an independent clinical investigator in the area of cancer immunotherapy and autoimmune disease and will establish a multi- center consortium with standardized data and biospecimen collection for rheumatic irAEs and for patients with preexisting autoimmune disease who are treated with ICIs.

项目摘要/摘要这项建议的主要目标是获得成为独立的临床和翻译医生所需的技能研究风湿病并增进对一种新的风湿病-炎性关节炎的认识 (IA)由于免疫检查点抑制剂(ICIS)。ICIS正在给癌症治疗带来革命性的变化，但也导致了免疫相关不良事件。ICI诱导的IA是最有可能发生的免疫相关不良事件风湿病专家所遇到的。ICI诱发的IA导致显著的发病率，在临床上是不同的，并且 ICI停止后仍可持续。拟议的项目将利用一组具有良好特征的ICI患者- 诱导IA和ICI治疗的对照患者谁没有发生IA来解决几个重要问题。首先，我们将评估ICI所致IA的临床异质性以及预测IA持续性的因素。超过停止ICI的治疗将被确立。接下来，临床和免疫遗传风险因素发展ICI诱导的IA将是确定的。最后，检测前、后血清细胞因子谱和自身抗体 ICI后的治疗将对ICI诱发的IA患者和对照组患者进行比较 ICIS，不发展IA。这些实验将填补这一新兴临床领域的关键知识空白实体。具体地说，界定相关的临床亚组将允许区别监测和治疗病人。了解发生IA的风险因素将使患者能够在心理治疗。ICI诱导的IA患者血清中升高的细胞因子可能成为未来的治疗靶点。最后，了解自身抗体的存在以及它们在ICI治疗过程中何时发展将洞察发病机制并确定潜在的生物标志物。在进行研究的同时该提案中，应聘者将参加各种职业发展活动，利用约翰霍普金斯大学在彭博基梅尔癌症研究所风湿病学部的丰富资源免疫疗法和彭博公共卫生学院。候选人将参加说教课程作业、会议和与风湿病不同导师的辅导会议，肿瘤学、实验室科学和数据科学。在这个奖项结束时，候选人将是一名独立的在癌症免疫治疗和自身免疫性疾病领域的临床研究员，并将建立一个多为风湿性虹膜脑脊髓炎和接受ICIS治疗的先前存在的自身免疫性疾病。

项目成果

期刊论文数量（8）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Cutaneous adverse events of immune checkpoint inhibitor therapy: incidence and types of reactive dermatoses.

DOI：
10.1080/09546634.2021.1898529
发表时间：
2022-05
期刊：
The Journal of dermatological treatment
影响因子：
0
作者：
Le TK;Kaul S;Cappelli LC;Naidoo J;Semenov YR;Kwatra SG
通讯作者：
Kwatra SG

Expert Perspective: Immune Checkpoint Inhibitors and Rheumatologic Complications.

DOI：
10.1002/art.41587
发表时间：
2021-04
期刊：
Arthritis & rheumatology (Hoboken, N.J.)
影响因子：
0
作者：
Cappelli LC;Bingham CO 3rd
通讯作者：
Bingham CO 3rd

Checkpoint Inhibitor-Associated Arthritis: A Systematic Review of Case Reports and Case Series.

DOI：
10.1097/rhu.0000000000001370
发表时间：
2021-12-01
期刊：
Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases
影响因子：
0
作者：
Ghosh N;Tiongson MD;Stewart C;Chan KK;Jivanelli B;Cappelli L;Bass AR
通讯作者：
Bass AR

Response to: Correspondence on "Immune checkpoint inhibitor-induced inflammatory arthritis persists after immunotherapy cessation" by Braaten et al.

回应：Braaten 等人关于“免疫检查点抑制剂诱导的炎症性关节炎在免疫治疗停止后持续存在”的通讯。