Inflammatory and prothrombotic biomarkers in patients with rheumatoid arthritis: effects of tumor necrosis factor-alpha blockade.
OBJECTIVE
Increased cardiovascular (CV) risk is a rheumatoid arthritis (RA) hallmark and it has been mainly related to chronic systemic inflammation. Since inflammation is linked to coagulation perturbation, both may play a role in increasing CV risk. Treatment with tumor necrosis factor (TNF)-alpha blocking agents is effective in RA and reduces local and systemic inflammation but there is little information on its effect on coagulation. We therefore investigated inflammation and coagulation plasma biomarkers before and after infliximab treatment in RA patients.


METHODS
We studied 20 patients with active RA and 40 healthy controls. Patients were treated with: a stable dose of methotrexate (10mg/week), and infliximab (3mg/kg) at weeks 0, 2, 6 and 14. At baseline and week 14, we determined: disease activity score (DAS-28), visual analogue scale pain, erythrocyte sedimentation rate (ESR), and plasma levels of C-reactive protein (CRP), TNF-alpha, interleukin (IL)-6, prothrombin fragment 1+2 (F1+2) and D-dimer. The same inflammation and coagulation parameters were evaluated 1h after infliximab infusion in 10 patients.


RESULTS
At baseline, ESR, CRP, TNF-alpha, IL-6, F1+2 and D-dimer levels were significantly higher in RA patients than in controls (P=0.0001). After 14weeks of infliximab treatment, there was a significant clinical improvement and ESR and CRP, IL-6, F1+2 and D-dimer level decrease (P=0.001-P=0.008). The levels of TNF-alpha, IL-6, F1+2 and D-dimer significantly decreased 1h after infliximab infusion (P=0.005).


CONCLUSIONS
Infliximab decreases inflammation and coagulation biomarkers in RA patients. Such a combined effect may be pivotal in reducing the whole thrombotic risk in these patients.
Ingegnoli
Francesca
F
Department of Rheumatology, University of Milan, Istituto Gaetano Pini, Milan, Italy.
Fantini
Flavio
F
Favalli
Ennio Giulio
EG
Soldi
Amedeo
A
Griffini
Samantha
S
Galbiati
Valentina
V
Meroni
Pier Luigi
PL
Cugno
Massimo
M
D000328:Adult; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D015415:Biomarkers / Q000097:blood*; D002097:C-Reactive Protein / Q000032:analysis; D005260:Female; D006801:Humans; D000069285:Infliximab; D015850:Interleukin-6 / Q000097:blood; D007558:Italy; D008297:Male; D008875:Middle Aged; D013917:Thrombin / Q000187:drug effects; D013927:Thrombosis / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000097:blood*; D055815:Young Adult
D000911:Antibodies, Monoclonal; D015415:Biomarkers; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein; D000069285:Infliximab; D013917:Thrombin