Affiliations: Regional Pharmacovigilance Center of Lorraine, Nancy, France | Internal and Vascular Medicine Unit, Nancy University Hospital, Nancy, France | Department of Rheumatology, Nancy University Hospital, Nancy, France
Note: [] Address for correspondence: Prof. Pierre Gillet, Centre Régional de Pharmacovigilance, CHU de Nancy, Hôpital Central, Avenue de Lattre de Tassigny, CO 60034, F 54035 Nancy, France. E-mail: [email protected].
Abstract: Background: Systemic inflammation such as rheumatoid arthritis (RA) and Crohn's disease (CD) may be responsible for vascular comorbidity. TNF-α blockade was expected to lower these comorbidities but several cases of arterial and venous thromboembolic events (TE) have been reported. Objectives: The aim of this work was to study retrospectively the main characteristics of spontaneously notified TNF-α blockers related TE over a 7-year period. Methods: TE related to infliximab, etanercept and adalimumab spontaneously notified to the French adverse drug reporting system database between January 2000 and December 2006 were analyzed. Separate analysis of arterial TE and venous TE was performed. Risk factors for each category of TE were assessed with consensual criteria. Results: 85 TE were analyzed, representing 4.5% of all the spontaneously notified adverse reactions of the 3 TNF-α blockers in the database. 42 were arterial events and 43 were venous events. The incidence was not significantly different between the 3 TNF-α blockers. Mean delay of TE onset after treatment initiation was 10.6 months. It was significantly shorter for etanercept (6.1 months, p=0.001) especially for venous TE (2.4 months). 16 among the 42 patients with arterial TE had 2 or more risk factors whereas 39 among the 43 patients with venous TE had no RF or only one. Most of patients (79/85) received concomitant systemic corticosteroids and/or methotrexate and/or COX-2 selective inhibitors. 23 patients had been investigated for autoimmunity, 13 had antinuclear and/or antiphospholipid antibodies. Main limitations of this study were underreporting and heterogeneous report contents. Conclusion: Despite its limitations, this study suggests that venous TE could be favoured by TNF-α blockers therapy since they occurred in patients with no or few risk factors for venous thrombosis. However, this needs to be more evaluated by controlled studies.
Keywords: Arthritis, rheumatoid, complications, drug therapy, physiopathology, cardiovascular diseases, etiology, mortality, tumor necrosis factor-alpha, antagonists and inhibitors
