Haemostatic and inflammatory biomarkers in patients with rheumatoid arthritis : effect of tumor necrosis factor alpha blockade

Introduction: Rheumatoid arthritis (RA) is associated with increased cardiovascular risk and activation of coagulation and inflammation pathways. Treatment with Infliximab, a chimeric monoclonal antibody (mAb) to tumor necrosis factor-alpha (TNF) has been shown to reduce inflammation, but the relationship with coagulation is unknown. In the present study, we investigated whether plasmatic biomarkers of haemostasis and inflammation were modified by administration of Infliximab in RA patients. Methods: Eleven patients with active RA and 50 healthy controls were included. RA patients had been taking a stable dose of methotrexate of at least 10 mg/week and Infliximab (3 mg/kg) at week 0, 2, 6 and 14. At baseline and at week 14 the following parameters were determined: disease activity score (DAS28), General Health Questionnaire (GHQ), visual analogue scale (VAS) pain, hemoglobin concentration, erythrocyte sedimentation rate (ESR), plasma levels of C-reactive protein (CRP), TNF, IL-6, prothrombin fragment 1+2 (F1+2) and D-dimer. Results: At baseline, ESR, levels of CRP and IL-6 were significantly higher in RA patients than in controls (p=0.0001), and levels of TNF tended to be increased; also F1+2 and D-dimer levels were significantly higher (p=0.0001). After 14 weeks of Infliximab treatment, there was a significant clinical improvement as judged by a decrease in the DAS28 (p=0.0001), GHQ (p=0.001), VAS pain (p=0.002), number of swollen (p=0.003) and tender joints (p=0.001). Similarly, an increase of hemoglobin concentration (p=0.02), and a decrease of ESR (p=0.03), CRP (p=0.02) and IL-6 (p=0.05) were detected. F1+2 and D-dimer levels significantly decreased during the course of the study (p=0.05). Conclusions: The administration of anti-TNF mAb in RA patients results in a rapid clinical improvement and a decrease of both acute-phase proteins and haemostatic biomarkers. The reduction of prothrombotic biomarkers suggests that Infliximab treatment may reduce the thrombotic risk in RA patients.