Effect of statins as modulators of CD39+ tregs in patients with rheumatoid arthritis who were unsuccessfully treated with methotrexate

Objective The aim of this study was to determine the effects of combined atorvastatin (AV) with etanercept (ETA) in patients with active rheumatoid arthritis (RA), who were nonresponders to methotrexate (MTX) therapy, and its effect on disease activity and CD39+ regulatory T-cell (Tregs). Patients and methods This study included 50 patients with active RA. Patients with RA were divided into two groups. Group I (n=25) received MTX therapy plus ETA (50 mg/week) (ETA+MTX) and group II (n=25) received MTX and ETA plus AV therapy (20 mg/day) (ETA+MTX+AV). In addition, 25 healthy volunteers were used as controls. DAS-28, erythrocyte sedimentation rate, C-reactive protein, rheumatoid factor, lipid profile, interleukin-6, CD39+ Tregs, ultrasonography 7 score (US7), carotid intima–media thickness, and flow-mediated dilatation (FMD) of the brachial artery were measured before and after 6 months of treatment. Results After 6 months of treatment, statin therapy combined with MTX and ETA significantly decreased disease activity variables, interleukin-6 and US7 synovitis, and tenosynovitis sum score. In addition, FMD% and CD39+ Tregs were significantly elevated. The increase in CD39+ Tregs was correlated with DAS-28 (P<0.001), FMD% (P<0.05), and US7 synovitis and tenosynovitis sum score (P<0.001). Conclusion Combination therapy with AV and ETA provides an added immunomodulatory benefit through enhancement of the immune suppression mediated by CD39+ Treg cells. Therefore, statins can be used safely with antitumor necrosis factor drugs to control disease activity and atherosclerotic changes in patients with RA, who are treated unsuccessfully with MTX