Objective: Rheumatoid arthritis (RA) is a common inflammatory disease associated with many extraarticular features. The aim of the study was to evaluate the effects of pentoxifylline (PTX) as adjuvant therapy to etanercept in moderately to highly active RA. Methods: A single center randomized double-blind placebocontrolled trial of 8 weeks duration was performed. Disease activity was measured via calculating the disease activity score in 28 joints using erythrocyte sedimentation rate

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... and by simplified disease activity score in 28 joints using hsCRP (SDAI-CRP). 40 Patients who were using etanercept (ETN) were randomly allocated to receive each day either pentoxifylline 400mg tablet twice daily or capsules prefilled with glucose as placebo also twice daily and were evaluated at baseline and at week 8 for clinical and hematological parameters. Results: Tumor necrosis factor (TNF), high sensitive C-reactive protein (hsCRP), duration of morning stiffness, and cardiovascular risk were significantly more reduced in pentoxifylline group than placebo group after 8weeks. Non significant changes were observed in clinical parameter like swelling joints counts (SJC),tender joints counts(TJC),visual analogue scale(VAS),evaluator global assessment (EGA),DAS28-ESR, SDAI-CRP and hematological parameter like hemoglobin (Hb) amount, erythrocyte sedimentation rate (ESR) and white blood cells (WBC) count between groups. Conclusion: PTX significantly decreased pro-inflammatory markers (TNF, hsCRP), duration of morning stiffness and cardiovascular risk. This suggests that pentoxifylline may be a promising and useful strategy to reduce the systemic inflammation and cardiovascular morbidity and mortality observed in RA patients.