THU0044 PRO- AND ANTI-INFLAMMATORY MEDIATORS OF SYSTEMIC INFLAMMATION AND ARTHRITIS IN THE ELDERLY

Background Elderly-onset RA (EORA), which is defined as rheumatoid arthritis (RA) with an onset at >60 years of age, and polymyalgia rheumatica (PMR) are common rheumatic diseases in the elderly. Eicosanoids are biological lipids that serve a specific role as either activators or suppressors of systemic inflammation and have been involved in the development and progression of arthritis. Objectives We hypothesized that eicosanoid-related perturbations are related to arthritic symptoms in the elderly, and that by defining this eicosanoid profile, we might be able to define elements of inflammation pathobiology in this population. Methods Arthritis in the Elderly (ARTIEL) is a recent collection cohort with patients older than 60 years of age who have newly diagnosed arthritis. Blood samples were collected from these patients at baseline (pre-treatment) and 3 months after treatment, along with physician and patient outcome measures through 12 months. These patients were also compared with randomly-selected control individuals of the same age and gender. A thorough clinical examination was conducted and patients completed a health assessment questionnaire (HAQ). Disease activity score (DAS)28CRP was also calculated. Serum eicosanoids were determined by mass spectrometry at baseline and after 3 months of treatment and were classified into groups according to their eicosanoid precursors: eicosapentaenoic acid (EPA), docosohexanoic acid (DHA) or arachidonic acid (AA). Data processing and statistical analysis were performed in R. Results 64 patients (average: 75.15, standard deviation (SD) 6.80) and 18 controls (average: 75.39, SD, 6.04) were analyzed. Of these, 44 were diagnosed with RA and 20 with PMR. At the start of the study, patients had a mean DAS28CRP of 5.72 (SD, 1.05) and a mean HAQ of 1.64 (SD, 0.73). In addition, 84% of the patients reported scapular pain and 56% reported pelvic pain at baseline. After three months of treatment, patients had a mean DAS28CRP of 2.38 (SD, 1.23) and a mean HAQ of 0.36 (SD, 0.41). Several eicosanoids, especially anti-inflammatory species derived from EPA and DHA, were significantly downregulated in both RA and PMR patients at the start of the study as compared to normal controls (Figure 1). Three months after treatment, the levels of anti-inflammatory eicosanoid species derived from EPA and DHA went back to normal only in patients who responded to therapy. Conclusion These results suggest that certain eicosanoids may be key effectors in arthritis in the elderly and that the imbalance between pro and anti-inflammatory eicosanoids before and after treatment might be related to clinical and therapeutic outcomes in this population. References [1] A systematic review on the role of eicosanoid pathways in rheumatoid arthritis. Hoxha M. Adv Med Sci. 2018 Mar;63(1):22-29. [2] Kobak S, Bes C. An autumn tale: geriatric rheumatoid arthritis. Therapeutic advances in musculoskeletal disease. 2018 Jan;10(1):3-11. PMID: 29290762 [3] Quehenberger O, Dennis EA. The human plasma lipidome. New England Journal of Medicine. 2011 Nov 10;365(19):1812-23. PMID: 22070478 Disclosure of Interests Roxana Coras: None declared, Rekha Narasimhan: None declared, Arthur Kavanaugh Grant/research support from: UCB Pharma, Lourdes Mateo Soria: None declared, Oswald Quehenberger: None declared, Monica Guma: None declared, Melania Martinez-Morillo: None declared