Serious infections in patients with Ankylosing Spondylitis with and without TNF blockers: A systematic review and meta-analysis of randomized placebo-controlled trials
- Laure Gossec ( )
- Paris Descartes University, Medicine Faculty; UPRES-EA 4058; APHP, Rheumatology B Department, Cochin, France
- Published Online First 28 July 2009
Background: TNF blockers are known to increase the risk of serious infections in rheumatoid arthritis. Despite a wide use of TNF blockers in ankylosing spondylitis (AS), the infection risk has never been evaluated in this disease.
Objectives: To assess serious infections in AS patients not exposed and exposed to TNF blockers.
Methods: A systematic literature review using Pubmed, Embase and Cochrane Library was performed until May 2008. All randomized controlled trials (RCTs), published between 1995 and 2008, monitoring serious infections, with treatment by Non Steroid Anti-Inflammatory Drugs (NSAIDs) or TNF blockers were included. Infection risks were calculated by naive pooling and for 100 patient-years (pyrs) of exposure. To assess the serious infection risk with TNF blockers, a meta-analysis of RCTs was performed using Mantel-Haenszel’s method with several sensitivity analyses.
Results: Fourteen RCTs were included (N patients=3345). With placebo or NSAIDs (N=2202) 2 serious infections were observed (0.09%, 0.01 to 0.3) i.e., 0.4/100pyrs. In TNF blocker trials, 2 serious infections were observed with placebo (2/500, 0.4% (0.0 to 1.4), i.e., 1.0/100pyrs), versus 14 serious infections with TNF blockers (14/996, 0.7% (0.3 to 1.4), i.e., 1.9/100pyrs). By meta-analysis of RCTs, the increase in serious infections with TNF blockers compared to placebo was not significant: risk difference=0.4% (-8% to 1.6%).
Conclusion: Absolute risks of serious infections in AS patients not exposed to TNF blockers are low. Absolute risks of serious infections in patients receiving TNF blockers are higher, but the difference was not significant, possibly through lack of power. Continued monitoring is necessary.