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Obesity-Induced Inflammatory Mediators Predict Lack of Response in Patients with Rheumatoid Arthritis Starting Biological Therapies

Award Number: R01AR083584
ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2024
PERIOD OF PERFORMANCE END DATE: 08/31/2029

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Obesity-Induced Inflammatory Mediators Predict Lack of Response in Patients with Rheumatoid Arthritis Starting Biological Therapies - SUMMARY Obesity-Induced Inflammatory Mediators Predict Lack of Response in Patients with Rheumatoid Arthritis Starting Biological Therapies There is an unmet need to identify predictive biomarkers in rheumatoid arthritis (RA) with respect to outcome and response to therapy. Numerous efforts to identify patients who will respond well to specific biologic agents have begun to yield profiles that might allow more personalized use of these agents, but much more work needs to be done. Given the complexity and heterogeneity of RA, it seems doubtful that a single cytokine or biomarker will be sufficient to inform the optimal choice of therapy. Instead, the inclusion of multiple biomarkers into ‘biomarker signatures’ may represent a more fruitful approach for the future of personalized therapeutic approaches. While clinical factors predicting disease outcomes are few, prior studies have highlighted strong associations between body weight and RA outcomes, although the mechanisms behind these associations are not defined. Obesity-induced inflammatory mediators include both proteins (such as adipokines) and lipids (such as fatty acid–derived bioactive lipids). Both types of obesity-induced mediators have been hypothesized to predict clinical responses in patients with RA, either by directly contributing to lack of response by promoting subclinical inflammation and disease relapse, or by describing metabolic phenotypes that may have prognostic value. Prior studies from our and other groups have described bioactive lipids disturbances in early stages of RA that are linked to therapeutic response. Additional preliminary results on samples from Comparative Effectiveness Registry to Study Therapies for Arthritis and Inflammatory (CERTAIN) cohort, revealed that distinct bioactive lipid profile (including those in the prostaglandin, leukotriene, resolvin, and eicosatrienoate pathways) was associated with response to different biologic therapies (categorized by minimal clinically important difference (MCID) in Clinical Disease Activity Index (CDAI) at 6 months after treatment initiation). Of interest, one of them, the 15-oxoEDE, which derives from eicosadienoic acid, a n-6 polyunsaturated fatty acid (PUFA) that has been associated with obesity and diabetes, was associated with both lack of response to anti-TNF therapy and obesity in the CERTAIN cohort. Taken together, our work suggests that obesity-induced inflammatory mediators profiling has the potential to identify metabolic phenotypes and effectively predict patient response to therapy prior to administration, and has also the potential to identify metabolic pathways that relate to response to biological therapies with distinct mechanisms of action.


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: 2026 ( Subtotal = $461,990 )
2026	2026	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	3	9/1/2026	NON-COMPETING CONTINUATION	$461,990
														Subtotal = $461,990

Issue Date FY: 2025 ( Subtotal = $440,563 )
2025	2025	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	8/7/2025	NON-COMPETING CONTINUATION	$440,563
														Subtotal = $440,563

Issue Date FY: 2024 ( Subtotal = $506,085 )
2024	2024	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	1	9/24/2024	NEW	$0
2024	2024	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	8/16/2024	NEW	$506,085
														Subtotal = $506,085

Grand Total All Awards = $1,408,638

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Obesity-Induced Inflammatory Mediators Predict Lack of Response in Patients with Rheumatoid Arthritis Starting Biological Therapies

Award Number: R01AR083584

ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/01/2024

PERIOD OF PERFORMANCE END DATE: 08/31/2029

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