Arterial and venous thromboembolic events during anti-TNF therapy: a study of 85 spontaneous reports in the period 2000-2006.
BACKGROUND
Systemic inflammation such as rheumatoid arthritis (RA) and Crohn's disease (CD) may be responsible for vascular comorbidity. TNF-alpha blockade was expected to lower these comorbidities but several cases of arterial and venous thromboembolic events (TE) have been reported.


OBJECTIVE
The aim of this work was to study retrospectively the main characteristics of spontaneously notified TNF-alpha 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-alpha blockers in the database. 42 were arterial events and 43 were venous events. The incidence was not significantly different between the 3 TNF-alpha 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.


CONCLUSIONS
Despite its limitations, this study suggests that venous TE could be favoured by TNF-alpha 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.
Petitpain
Nadine
N
Regional Pharmacovigilance Center of Lorraine, Nancy, France.
Gambier
Nicolas
N
Wahl
Denis
D
Chary-Valckenaere
Isabelle
I
Loeuille
Damien
D
Gillet
Pierre
P
D000293:Adolescent; D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems / Q000706:statistics & numerical data*; D000368:Aged; D000369:Aged, 80 and over; D000893:Anti-Inflammatory Agents; D002648:Child; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology*; D005260:Female; D005602:France / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D018570:Risk Assessment / Q000379:methods; D012307:Risk Factors; D016019:Survival Analysis; D015996:Survival Rate; D013923:Thromboembolism / Q000401:mortality*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D055815:Young Adult
D000893:Anti-Inflammatory Agents; D014409:Tumor Necrosis Factor-alpha