Biologic therapies in rheumatoid arthritis and the risk of opportunistic infections: a meta-analysis

Objective: Biologic agents are increasingly used to treat patients with rheumatoid arthritis (RA). We aimed to review their association with opportunistic infections (OIs), including fungal, viral (with a focus on herpesvirus-related infections), tuberculosis and other mycobacterial infections.

Methods: We searched PubMed and EMBASE through June 24, 2013, and complemented the search with the reference lists of eligible articles. The analysis included randomized trials on RA that compared any approved biologic agent with controls and reported the risk of OIs.

Results: A total of 70 trials that included 32 504 patients (21 916 patients receiving biologic agents and 10 588 receiving placebo) were deemed eligible. Biologic agents increased the risk of OIs (pooled Peto odds ratio [OR], 1.79; 95% confidence interval [CI], 1.17-2.74; I(2) = 3%), resulting in 1.7 excess infections per 1000 patients treated (number needed to harm, 582). A significant risk was noted for mycobacterial (OR, 3.73; 95% CI, 1.72-8.13; I(2) = 0), and viral (OR, 1.91; 95% CI, 1.02-3.58; I(2) = 0) infections. Interestingly, no significant differences were found for invasive and superficial fungal infections (1.31; 95% CI, .46-3.72), invasive fungal infections (2.85; .68-11.91), P. jirovecii pneumonia (1.77; .42-7.47), varicella-zoster virus (1.51; .71-3.22), as well as overall mortality attributed to OIs (1.91; .29-12.64).

Conclusions: Among patients with RA, biologic agents are associated with a small but significant risk of specific OIs. This increase is associated with mycobacterial diseases and does not seem to affect overall mortality. Because OIs are a relatively rare complication of biologic agents, large registries are needed to identify the exact effect in different OIs and to compare the different biologic agents.