Serious infections in patients with ankylosing spondylitis with and without TNF blockers: a systematic review and meta-analysis of randomised placebo-controlled trials
- Anne Fouque-Aubert1,
- Laetitia Jette-Paulin1,
- Christophe Combescure2,
- André Basch1,
- Jacques Tebib1,
- Laure Gossec3
- 1Service de Rhumatologie, Université Lyon 1, Hôpital Lyon Sud, Pierre Bénite, France
- 2Centre de Recherche Clinique, Hôpital Universitaire de Genève, Suisse
- 3Rheumatology B Department, Paris Descartes University, Cochin Hospital, Paris, France
- Correspondence to Anne Fouque-Aubert, Service de Rhumatologie, Université Lyon 1, Hôpital Lyon Sud, Chemin du Grand Revoyet, 69495 Pierre Bénite, France;
- Accepted 26 June 2009
- Published Online First 28 July 2009
Background Tumour necrosis factor (TNF) blockers are known to increase the risk of serious infections in rheumatoid arthritis. Despite 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 patients with AS not exposed and exposed to TNF blockers.
Methods A systematic literature review up to May 2008 using PubMed, EMBASE and Cochrane Library was performed. All randomised controlled trials (RCTs) published between 1995 and 2008 monitoring serious infections, treated with non-steroidal 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 (3345 patients). With placebo or NSAIDs (N=2202), two serious infections were observed (0.09%, range 0.01% to 0.3%)—that is, 0.4/100 pyrs. In TNF blocker trials, two serious infections were observed with placebo (2/500, 0.4% (0.0% to 1.4%), ie, 1.0/100 pyrs) versus 14 serious infections with TNF blockers (14/996, 0.7% (0.3% to 1.4%), ie, 1.9/100 pyrs). Meta-analysis of the RCTs showed that the increase in serious infections with TNF blockers compared with placebo was not significant: risk difference=0.4% (−8% to 1.6%).
Conclusions The absolute risk of serious infections in patients with AS not exposed to TNF blockers is low. The absolute risk of serious infections in patients receiving TNF blockers is higher, but the difference was found to be not significant, possibly through lack of power. Continued monitoring is necessary.
Competing interests None.
Provenance and peer review Not commissioned; externally peer reviewed.