Observational Studies of Infections in Rheumatoid Arthritis: A Metaanalysis of Tumor Necrosis Factor Antagonists

OBJECTIVE: Published metaanalyses of tumor necrosis factor (TNF) antagonists and infection have focused on randomized controlled trials, which tend to have short duration, relatively small size, and stringent inclusion/exclusion criteria that may limit enrollment to patients at low risk of infection. We performed a systematic review and synthesis of observational studies of TNF antagonists and infection risk. METHODS: We conducted a systematic literature search of studies estimating overall risk of serious infection after anti-TNF exposure in rheumatoid arthritis (RA). We estimated a pooled relative risk (RR) for the relevant observational studies, using a random-effects model. RESULTS: Five cohort studies and 2 nested case-control studies were included in the metaanalysis. Anti-TNF therapy appeared to significantly increase risk of serious infection (pooled adjusted RR 1.37, 95% CI 1.18, 1.60). CONCLUSION: Our metaanalysis of observational data demonstrated an increased risk of serious infection in subjects with RA receiving anti-TNF therapy, versus those not receiving these agents.