The effects of fenofibrate on inflammation and cardiovascular markers in patients with active rheumatoid arthritis: a pilot study

Abstract

Peroxisome proliferator-activated receptors α (PPARα) agonists, or fibrates, are used in the treatment for dyslipidemia. Experimental data suggest that fibrates have anti-inflammatory properties, and PPARα is essential for the differentiation of endothelial progenitor cells (EPC) which diminished pool in rheumatoid arthritis (RA) contributes to accelerated atherosclerosis. The data on fibrates' effects in patients with RA are limited. The aim of this study was to investigate changes in disease activity, inflammatory markers, lipid profile, and circulating EPC in active RA patients treated with fenofibrate. Twenty-seven patients with active RA taking traditional disease-modifying antirheumatic drugs (DMARDs) were prescribed fenofibrate (145 mg/day) for 3 months. All patients received background traditional DMARDs in stable doses. The outcomes measured were clinical disease activity variables, circulating cytokines, adipokines, lipids, and EPC. Twenty-five patients completed the study. At the end of treatment, there was a significant reduction in DAS28, all individual DAS28 components except tender joint count, the duration of morning stiffness, and in the patient's assessment of disease activity. Fifteen (60 %) patients achieved good/moderate EULAR response, while 10 (40 %) patients satisfied ACR20 response criteria. Treatment with fenofibrate resulted in significant decrease in CRP and IL-6 concentrations and improvement in lipid profile. There was no change in the concentrations of circulating EPC. In conclusion, fenofibrate treatment is associated with reduced inflammation and improved lipid profile in RA patients. Large randomized controlled studies are needed to confirm these results and to define the role of fibrates in the treatment for RA.

PPAR-α activation reduced LPS-induced inflammation in alveolar epithelial cells

“…Fibrates including WY-14643, fenofibrate, or clofibrate are further PPAR-α ligands inducing its activation. Evidence is accumulating that fibrates not only possess lipid-lowering properties but also exert antiinflammatory effects [22][23][24]. This interesting feature is under intense investigation as fibrates might positively modify the progress and prognosis of diseases associated with chronic inflammatory reactions such as rheumatoid arthritis [22,25], colitis [26], diabetes [27], or atherosclerosis [28].…”

Inhibition of JNK signalling mediates PPARα‐dependent protection against intrahepatic cholestasis by fenofibrate

“…Clinically, fenofibrate is prescribed at doses of 150–300 mg·day −1 for dyslipidaemia (Shirinsky et al , ; Harmer et al , ; Masana et al , ). In monotherapy or in combination with UDCA, the fenofibrate dose for cholestatic liver diseases is usually between 100 and 200 mg·day −1 (Nakamuta et al , ; Walker et al , ; Levy et al , ).…”

Current evidence on the role of lipid lowering drugs in the treatment of psoriasis

“…Fibrates are peroxisome proliferator-activated receptor alpha (PPARα) agonists that regulate lipid metabolism and reduce inflammation through transcriptional regulation. A study of 27 patients with RA taking conventional medication and fenofibrate for 3 months showed fibrate treatment reduced the disease activity score (DAS28) and CRP and IL-6 levels ( 54 ). Similarly, ezetimibe, a lipid-lowering drug, also has anti-inflammatory effects.…”