Abstract and Introduction
Abstract
Introduction: The treatment with antitumor necrosis factor agents has often been associated with the induction of autoantibodies (antinuclear antibodies, anti-double stranded DNA antibodies and antiphospholipid antibodies). The clinical significance of these antibodies remains unclear, but they may predispose to antiphospholipid syndrome with thromboembolic complications. The association of etanercept with thromboembolic events has not been reported previously in the literature.
Case presentation: We describe the cases of three patients with rheumatoid arthritis, psoriatic arthritis and seronegative inflammatory arthritis who were treated with etanercept. They developed deep vein thrombosis and/or pulmonary embolism one to three years after the initiation of etanercept therapy. All three patients had a prolonged activated partial thromboplastin time with a positive lupus anticoagulant that persisted even after 12 weeks.
Conclusion: Although the clinical significance of antiphospholipid antibodies during treatment with antitumor necrosis factor agents remains unclear, they may predispose patients to develop antiphospholipid syndrome when associated with prolonged activated partial thromboplastin time, lupus anticoagulant positivity, or the presence of anti-β2 glycoprotein I. Clinicians must keep this in mind during therapy with antitumor necrosis factor agents in order to prevent, detect and treat potential consequences such as deep vein thrombosis and pulmonary embolism.
Introduction
Etanercept (Enbrel; Immunex; Thousand Oaks, California) is a dimeric recombinant DNA protein composed of two naturally occurring soluble human tumor necrosis factor (TNF) receptors linked to the Fc portion of IgG1. TNF plays an important role in inflammatory processes and binds into two different types of receptors, wherein one becomes embedded in white blood cells and is responsible for the immune response and the other becomes a soluble TNF receptor used to deactivate TNF and blunt immune response. Etanercept mimics the inhibitory effects of naturally occurring soluble TNF receptors. The only difference is that etanercept is a fusion protein rather than a simple TNF receptor and has a greatly extended half-life in the bloodstream, and therefore has a more profound and long-lasting biologic effect than a naturally occurring soluble TNF receptor.
Pulmonary embolism (PE) has been previously described in the literature with infliximab (monoclonal antibody against TNF). In this case report, we describe the cases of three patients who developed deep vein thrombosis (DVT) leading to PE during etanercept therapy. All patients were seen at one medical center over a 3-year period.