Obesity-induced inflammatory mediators predict lack of response in patients with rheumatoid arthritis starting biological therapies

Active Project Grant Awarded Last action

Award ID
R01AR083584
Recipient
Awarding agency
Obligated
$1,408,638

Award facts

Completion date 43% complete
Place of performance
La Jolla, CA 92093, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

Abstract
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.

Transactions

Action Obligated Date
Amendment $461,990
Amendment $440,563
Amendment $0
Original award $506,085

Subawards

Subrecipient Amount Awarded
Philadelphia Research And Education Foundation Mod: 45,544.00 Sub: 48,297.00 6WDWHPHQWRI:RUNDQGBudget JustificatioQ Rui Xiao, PhD, Consultant. $5,000 per year. Professor Xiao is an Associate Professor of… $93,841

Quick answers

Who received award R01AR083584?

R01AR083584 was awarded to University Of California, San Diego by National Insititue of Arthritis and Musculoskeletal and Skin Diseases (National Institutes of Health) on September 1, 2024.

How much is award R01AR083584 worth?

$1,408,638 has been obligated on R01AR083584.

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