CLINICAL EFFICIENCY AND SAFETY OF FENOFIBRATE, A PPARα AGONIST, IN THE PATIENTS WITH DIABETESASSOCIATED OSTEOARTHRITIS: A CROSS-OVER PILOT STUDY

Abstract

Sixteen female patients with diabetes-associated osteoarthritis (DAOA) participated in an openlabel, randomized, cross-over study. The mean patients’ age was 65.5 (±5.4) years, the patients were obese (mean body mass index, 35.8±5.7 kg/m2 ). They suffered from durable osteoarthritis (14.5±7.6 years) associated with diabetes mellitus (13.08±3.43 years). Clinical and radiographic signs of knee OA were observed in 100% of the cases, all the patients had Kellgren–Lawrence grade III radiographic changes. First group of patients (n = 9) was randomized to Fenofibrate (145 mg/day for 12 weeks), the second group (n = 7) received chondroitine sulfate (1000 mg/day for 12 weeks). Then, following a two-week washout period, the first group was switched to chondroitine sulfate and the second group, to fenofibrate. Clinical examination was performed monthly, and laboratory evaluation was performed at the baseline and by the end of each treatment course. pain level according to VAS scale was used as the primary endpoint, whereas KOOS, WOMAC, ICOAP and other scores served as secondary endpoints. We have also assessed effects of Fenofibrate upon serum biomarkers (IL-6, IL-18, IL-10, lipid profiles, and CRP concentrations). Comparative effect of Fenofibrate was evaluated by means of generalized estimating equation (GEE) models adjusted for the treatment sequence. It was shown that clinical effects of Fenofibrate in patients with DAOA did not significantly differ from those of chondroitine sulfate. However, fenofibrate had broader spectrum of effects including improvement of lipid profiles. E.g., Fenofibrate treatment was associated with increased HDL levels (β coefficient, -0.19; р = 0.02), a decrease in total cholesterol (β coefficient, -0.78; р = 0.01), and triglycerides (β coefficient,0.85; р = 0.002). In addition, Fenofibrate therapy was associated with a decrease in ESR, a laboratory biomarker of systemic inflammation (β coefficient, -7.76; р = 0.01). Cytokine changes following the Fenofibrate treatment did not differ from those registered after chondroitine sulfate therapy. In conclusion, the results of this pilot study provide a rationale for further studies of PPARα agonists and their pleiotropic effects in large-scale controlled clinical trials.

Keywords

• osteoarthritis
• comorbidity
• type 2 diabetes
• peroxisome proliferator-activated receptors α
• lipids
• cytokines
• inflammation