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Plasma lipid mediator profiles may predict DMARD response in RA

Publish date:: November 23, 2020

Key clinical point: Concentrations of lipid mediators were distinctly different between rheumatoid arthritis patients who responded to disease-modifying antirheumatic drugs (DMARDs) and nonresponders.

Major finding: Cumulative concentrations of docosahexaenoic acid (DHA) and n-3 docosapentaenoic acid (n-3 DPA) metabolomes had accuracy outcomes at predicting DMARD responses of approximately 81% and 69%, respectively; the specific biomarkers that predicted response were RvD4, 10S, 17S-diHDPA, 15R-LXA₄ and MaR1 _{n-3 DPA.}

Study details: The data come from analyses of adult patients with early RA; 30 were DMARD responders and 24 were nonresponders.

Disclosures: The study was supported by the European Research Council and the Barts Charity; additional work associated with the project was supported by the UK Medical Research Council, Arthritis Research UK, and Genentech. One author reported a scientific founder and director of Resolomics Limited.

Commentary

“Biomarkers to predict responses to DMARDs in patients with RA have long been sought in order to improve and target therapy. In this study, levels specialized pro-resolving mediators (SPM) which have been shown to regulate resolution vs. continuing of inflammation in vitro were studied with regard to their ability to predict responsiveness to methotrexate in RA patients. Plasma lipid mediator profiles were evaluated in RA patients prior to DMARD initiation, including derivatives of the essential fatty acids n-3 docosapentaenoic acid (n-3 DPA), docosahexaenoic acid (DHA), eicosapentaenoic acid, and arachidonic acid. Several of these mediators were found to have distinct profiles of elevation in 30 DMARD responders vs. 22 non-responders, with elevated cumulative concentrations of DHA and n-3 DPA lipid metabolomes. Specifically, a model including RvD4, 10S, 17S- diHDPA, 15R-LXA 4 and MaR1 [n-3 DPA] was able to predict DMARD non-response with 81% accuracy. Though this study is a pilot, its findings are promising for the development of biomarker assays that can identify patients with RA who are less likely to respond to methotrexate and may benefit from faster transition to other therapies.”