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Evaluating the relationship between immune checkpoint inhibitors and osteoarthritis

Award Number: R03AR081997
ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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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.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = $81,875 )
2024	2024	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	12/15/2023	NON-COMPETING CONTINUATION	$81,875
														Subtotal = $81,875

Issue Date FY: 2023 ( Subtotal = $81,875 )
2023	2023	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	1/9/2023	NEW	$81,875
														Subtotal = $81,875

Grand Total All Awards = $163,750

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Evaluating the relationship between immune checkpoint inhibitors and osteoarthritis

Award Number: R03AR081997

ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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