SAT0325 Fenofibrate effects on pain, function, cytokine production, and circulating endothelial progenitor cells in patients with erosive osteoarthritis:

Abstract

Background Anti-inflammatory and antiatherogenic properties of peroxisome proliferator-activated α (PPARα) receptor agonists (fibrates) suggest their utility in the treatment of various inflammatory rheumatic disorders associated with accelerated atherosclerosis. They include osteoarthritis (OA), particularly its erosive phenotype (EOA) characterized by pronounced synovial inflammation. Putative EOA biomarkers reflecting extent of chronic inflammation and increased risk of atherosclerosis are serum cytokines and adipokines. Another candidate biomarker for cardiovascular morbidity in OA is number of circulating endothelial progenitor cells (EPC). There have been no published studies evaluating fenofibrate efficacy and its effects on systemic cytokine and adipokine production and EPC concentrations in patients with erosive OA. Objectives To assess the influence of fenofibrate treatment on clinical efficacy parameters, in vivo cytokine and adipokine production and concentrations of EPC in patients with EOA. Methods EOA patients received treatment with 145 mg of fenofibrate per day for 12 weeks. The studied efficacy outcomes were pain levels (100 mm VAS), functional index for hand OA (FIHOA), Cochin index, patient and physician global assessment (100 mm VAS), tender and swollen joint count, duration of morning stiffness, and ESR. Response was assessed in accordance with OMERACT-OARSI criteria. Serum was obtained from each patient and peripheral blood mononuclear cells were isolated on baseline and at week 12 of the treatment. TNF-α, IL-6, IL-1, IL-17, IFN-γ, IL-10, apiponectin and resistin were measured in sera using specific ELISA. Endothelial progenitor cell (EPC) counts in peripheral blood were evaluated by flow cytometry as CD34+/CD144+/CD3- cells within the lymphocyte gate. Results Fifteen patients (all women, median age 61 years, IQR 57-63) were enrolled in the study. Fenofibrate treatment was associated with significant decreases in pain score, TJC, morning stiffness, disease activity score, Cochen index, and ESR (Table). Eight (53%) patients developed OMERACT-OARSI response at the end of treatment. Serum IL-10 concentrations significantly (p=0.03) decreased while no changes in other studied cytokines and adipokines were detected. There were also no differences in circulating EPC numbers before and after the treatment. Fenofibrate was well tolerated, no patient experienced disease flare during the treatment. Table 1. Efficacy parameters at baseline and after the treatment (median and IQR are presented) Week 0Week 12p Pain (100 mm VAS)28 (20-50)20 (10-36)0.0008 TJC8 (5-16)5 (4-8)0.007 SJC7 (3-10)4 (1-7)0.175 Morining stiffness60 (20-130)20 (0-30)0.0035 Disease activity (100 mm VAS)51 (45-60)20 (18-40)<0.0001 Patient’s global assessment (100 mm VAS)50 (38-64)31 (21-43)0.0141 Cochen index8 (4-12)4 (0-14)0.0182 ESR, mm/h21 (7.75-28.5)10.5 (7.25-18.5)0.0195 Conclusions In EOA patients, treatment with fenofibrate is associated with decreased pain, improved hand function and ESR reduction but has no effect on pr...

Clinical Efficacy and Safety of Peroxisome Proliferator-Activated Receptor Alpha Agonists in Rheumatoid Arthritis: An Open-Label Controlled Study

“…Таким образом, при синтропных заболева-ниях возможна альтернатива полипрагмазии [29], агонистов PPARα у больных эро-зивным остеоартритом [28]. Правомочность выбранной стратегии лече-ния синтропных коморбидных заболеваний под-тверждается результатами настоящего исследова-ния.…”