Anti-tumor necrosis factor alpha therapy normalizes fibrinolysis impairment in patients with active rheumatoid arthritis.
OBJECTIVE
Rheumatoid arthritis (RA) is associated with increased cardiovascular risk and involvement of inflammation, coagulation and fibrinolysis. Treatment with infliximab, a tumour necrosis factor-alpha (TNF-alpha) blocking chimeric monoclonal antibody, induces a long-term reduction of inflammation and coagulation, but its effect on fibrinolysis is still unknown. We carried out an observational study investigating plasma biomarkers of inflammation and fibrinolysis in RA patients before and after 14 weeks of infliximab treatment given according to the therapeutic guidelines for RA.


METHODS
We studied 20 selected patients with active RA and without any other atherosclerosis risk factor as well as 40 healthy controls. Patients, treated with a stable dose of methotrexate, received infliximab (3 mg/kg) at week 0, 2, 6 and 14. At week 0 and 14, we assessed clinical, inflammatory and fibrinolyitic parameters.


RESULTS
At baseline, plasminogen activator inhibitor (PAI-1) antigen, PAI-1 activity and tissue-type plasminogen activator (t-PA) antigen were significantly higher in RA patients than in controls (p=0.01, p=0.001 and p=0.0001 respectively). After 14 weeks of infliximab treatment, the levels of PAI-1 antigen, PAI-1 activity and t-PA antigen significantly decreased till normalization (p=0.0001). Plasma levels of C reactive protein (CRP) and interleukin-6 (IL-6) were directly correlated with levels of PAI-1 antigen (p=0.011 and p=0.0001), PAI-1 activity (p=0.013 and p=0.027) and t-PA antigen (p=0.017 and p=0.040).


CONCLUSIONS
This study provides evidence that TNF-alpha blockade by infliximab not only decreases inflammation, but also reduces the inhibition of fibrinolysis. Such a combined effect may be pivotal in reducing the whole thrombotic risk in these patients.
Ingegnoli
F
F
Department of Rheumatology, University of Milan, Istituto Gaetano Pini, Milan, Italy.
Fantini
F
F
Griffini
S
S
Soldi
A
A
Meroni
P L
PL
Cugno
M
M
D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000453:epidemiology / Q000276:immunology; D050197:Atherosclerosis / Q000453:epidemiology; D015415:Biomarkers / Q000097:blood; D004359:Drug Therapy, Combination; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D000069285:Infliximab; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D012307:Risk Factors; D013927:Thrombosis / Q000188:drug therapy* / Q000453:epidemiology / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D055815:Young Adult
D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D015415:Biomarkers; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D008727:Methotrexate