title: Treatment of erosive osteoarthritis with peroxisome proliferator-activated receptor alpha agonist fenofibrate: a pilot study.
abstract: Hand osteoarthritis (HOA) is a common condition associated with high disease burden and frequently accompanied by comorbidities including dyslipidemia, atherosclerosis and obesity. The most debilitating HOA phenotype is erosive HOA (EHOA), characterized by synovial inflammation, formation of erosions, and substantial decline in hand function. Currently, there is no proven symptomatic treatment for the EHOA. Due to their broad spectrum effects directed on lipid metabolism, inflammation and pain, the agonists of peroxisome proliferator-activated receptor alpha or fibrates are a candidate class of drugs for the treatment of EHOA. In this study, we assessed the influence of fenofibrate treatment on clinical efficacy parameters, in vivo cytokine and adipokine production and concentrations of endothelial progenitor cells (EPC) in patients with EHOA. Fourteen patients received treatment with 145 mg of fenofibrate/day for 12 weeks. Fenofibrate treatment was associated with significant decreases in pain score, tender joint count, duration of morning stiffness, disease activity score, Cochin index, and ESR. Eight (57.14 %) patients developed Outcome Measures in Rheumatology Clinical Trials-Osteoarthritis Research Society response at the end of treatment. Paracetamol consumption did not change during the treatment course. There was a significant reduction in triglyceride levels. No changes were detected in serum pro-inflammatory cytokine and adipokine concentrations while circulating IL-10 levels significantly decreased. There were no differences in circulating EPC numbers before and after the treatment. Fenofibrate was well tolerated, no patient experienced disease flare during the treatment. In conclusion, in EHOA patients, fenofibrate is associated with pleiotropic effects on pain, inflammation, and lipid profile. Larger, controlled studies are needed to confirm these results.
authors.affiliation: Laboratory of Clinical Immunopharmacology, Institute of Clinical Immunology RAMS, 6 Zalesskogo str., 630099, Novosibirsk, Russia, ishirinsky@mail.ru.
authors.forename: Ivan V
authors.initials: IV
authors.lastname: Shirinsky
authors.forename: Valery S
authors.initials: VS
authors.lastname: Shirinsky
mesh_terms: D018712:Analgesics, Non-Narcotic / Q000627:therapeutic use; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D005260:Female; D011345:Fenofibrate / Q000627:therapeutic use*; D050823:Hand Joints / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D008875:Middle Aged; D010003:Osteoarthritis / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D047493:PPAR alpha / Q000819:agonists* / Q000378:metabolism; D010865:Pilot Projects; D020127:Recovery of Function; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D018712:Analgesics, Non-Narcotic; D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D018836:Inflammation Mediators; D047493:PPAR alpha; D011345:Fenofibrate