Activation of inflammation, coagulation and fibrinolysis in patients with Rheumatoid Arthritis : inhibition by Tumor Necrosis Factor alpha blockade

Abstract

Objective: Rheumatoid arthritis (RA) is associated with increased cardiovascular risk and activation of inflammation and coagulation pathways. Its treatment with infliximab, a chimeric monoclonal antibody to tumour necrosis factor-a (TNF-a), reduces inflammation, but its effects on coagulation and fibrinolysis are unknown. We therefore investigated plasma biomarkers of inflammation, coagulation and fibrinolysis before and after infliximab treatment in RA patients. Methods: We studied 18 patients with active RA and 36 healthy controls. RA patients, receiving a stable dose of methotrexate (10 mg/week), were treated with infliximab (3 mg/kg) at week 0, 2, 6 and 14. At baseline and at week 14, we determined: disease activity score (DAS28), visual analogue scale (VAS) pain, erythrocyte sedimentation rate (ESR), and plasma levels of C-reactive protein (CRP), TNF-a, IL-6, prothrombin fragment 1+2 (F1+2) and D-dimer. In six patients, we also evaluated inflammation and coagulation parameters one hour after infliximab infusion. Results: At baseline, ESR, CRP, TNF-a and IL-6 levels were significantly higher in the RA patients (p=0.001\u2013p=0.0001), as were F1+2 and D-dimer levels (p=0.0001). After 14 weeks of infliximab treatment, there was a significant clinical improvement (decrease in DAS28, VAS pain, number of swollen and tender joints) and a significant decrease in ESR and CRP, IL-6, F1+2 and Ddimer levels (p=0.03\u2013p=0.003). The levels of TNF-a, IL-6, F1+2 and D-dimer significantly decreased one hour after infliximab infusion (p=0.05\u2013p=0.008). Conclusions: In RA patients, infliximab leads to a rapid clinical improvement and a decrease in inflammation and coagulation biomarkers. The reduction in the latter suggests that it may reduce thrombotic risk