Biological Therapies in Rheumatoid Arthritis and the Risk of Opportunistic Infections: A meta-analysis.
Clin Infect Dis. 2014 Mar 18;
Authors: Kourbeti IS, Ziakas PD, Mylonakis E
Objective. Biologic agents are increasingly used to treat patients with rheumatoid arthritis. We aimed to review their association with opportunistic infections (OIs), including fungal, viral (with a focus on herpes virus-related infections), tuberculosis and other mycobacterial infections. Methods. We searched PubMed and EMBASE up to June 2013 and complemented the search with the reference lists of eligible articles. Randomized trials on rheumatoid arthritis that compared any approved biologic agent with controls and reported the risk of opportunistic infections were included in the analysis. Results. Seventy trials that included 32,504 patients (21,916 patients on biologics and 10,588 on placebo) were deemed eligible. Biologic agents increased the risk of opportunistic infections (pooled Peto odds ratio, 1.79; 95% CI, 1.17-2.74; I(2)=3%), resulting in 1.7 excess infections per 1,000 patients treated (number needed to harm, NNH=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 (OR, 1.31; 95% CI, 0.46-3.72), invasive fungal infections (OR, 2.85; 95% CI, 0.68-11.91), Pneumocystis jirovecii pneumonia (OR, 1.77; 95% CI 0.42-7.47), varicella-zoster virus (OR, 1.51; 95% CI 0.71-3.22), as well as overall attributed mortality to OIs (OR, 1.91; 95% CI, 0.29-12.64). Conclusions. Among rheumatoid arthritis patients, biologic agents are associated with a small but significant risk of specific opportunistic infections. This increase is associated with mycobacterial diseases and does not appear to impact overall mortality. Because OIs are a relatively rare complication of biological agents, large registries are needed in order to identify the exact impact in different OIs and to compare the different biological agents.
PMID: 24647016 [PubMed - as supplied by publisher]