THU0142 Fenofibrate reduces inflammation but has no effect on endothelial progenitor cells in patients with rheumatoid arthritis:

Abstract

Background Experimental findings indicate that peroxisome proliferator-activated α (PPARα) receptor agonists (fibrates), apart from their lipid-lowering effects, exhibit anti-inflammatory activity, influence angiogenesis and modulate glucocorticoid effects. Recent data suggest that fibrates may promote the differentiation of endothelial progenitor cells (EPC) which diminished pool in RA is thought to contribute to enhanced atherosclerosis. Thus, this class of drug may be a useful adjunct to the current arsenal of DMARDs. Although there have been no randomized controlled trials, several small reports have shown clinical improvement in RA patients treated with fenofibrate. The influence of fenofibrate on cytokine production and EPC concentrations in vivo in RA patients is unknown Objectives To evaluate changes in disease activity, circulating cytokine concentrations and levels of EPC in RA patients following treatment with fenofibrate. Methods Patients with active (DAS28 >3.2) RA received treatment with 145 mg of micronised fenofibrate per day for 12 weeks. Clinical efficacy outcomes recorded were: DAS28, individual DAS28 components, ACR responses, HAQ, pain levels (VAS), and ESR. TNF-α, IL-6, IL-1, IL-17, IFN-γ, and IL-10 concentrations were measured in sera using specific ELISA. EPC counts in peripheral blood were evaluated by flow cytometry as CD34+/CD144+/CD3- cells within the lymphocyte gate. Analysis was performed using Friedman’s test for clinical variables and ESR and using Wilcoxon matched pairs test for laboratory parameters. Results Twenty four patients (21 women, three men, median age 60.6 years, IQR 52.1- 65.5) were enrolled in the study. Median disease duration was 7.64 (IQR 2.35-17) years. All subjects had been taking methotrexate in stable dose of 13.75 mg/w (IQR 10-15) for at least 3 months prior to the study. At the end of treatment there were significant improvements in DAS28, swollen joint count, general health (VAS), patient and physician global assessment of disease activity (VAS), and morning stiffness (Table). Thirteen (59%), five (22.7%), and one (4.3%) patients developed ACR20, ACR50, and ACR70 responses, respectively. One patient achieved clinical remission (DAS28<2.6). Fenofibrate treatment was associated with significant decrease in serum IL-6 (p=0.04) and IL-10 (p=0.03). Whereas baseline EPC concentrations were lower in RA than in 15 control OA patients (0.17% and 0.3%, p=0.036), no significant changes were observed in circulating EPC levels after fenofibrate treatment (p=0.36). Two patients terminated the study prematurely due to severe acute sciatica and were not included in the analysis. No patient experienced disease flare during the study period. Table 1. Clinical efficacy parameters at baseline and at the end of treatment (median and IQR are presented) Week 0Week 12p DAS286.36 (5.98-6.78)4.73 (3.85-5.64)<0.0001 SJC7 (5–0)3 (1-4)<0.0001 TJC17 (13–20)14 (3–20)0.0563 General health, mm53 (44–70)38.5 (25–54)0.0001 ESR, mm/h35.5 (32–50)14.5 (10–30)<0.0001 Activity by patient, mm57 (...