Evaluating the relationship between immune checkpoint inhibitors and osteoarthritis

NIH RePORTER · NIH · R03 · $81,875 · view on reporter.nih.gov ↗

Abstract

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.

Key facts

NIH application ID
10762461
Project number
5R03AR081997-02
Recipient
JOHNS HOPKINS UNIVERSITY
Principal Investigator
Laura Christine Cappelli
Activity code
R03
Funding institute
NIH
Fiscal year
2024
Award amount
$81,875
Award type
5
Project period
2023-01-10 → 2025-12-31