To compare the potential adverse e ects of tumor necrosis factor inhibitor (adalimumab, certolizumab, etanercept, golimumab, infliximab), interleukin (IL)-1 antagonist (anakinra), IL-6 antagonist (tocilizumab), anti-CD28 (abatacept), and anti-B cell (rituximab) therapy in patients with any disease condition except human immunodeficiency disease (HIV/AIDS). Methods Randomized controlled trials (RCTs), controlled clinical trials (CCTs) and open-label extension (OLE) studies that studied one of the nine biologics for use in any indication (with the exception of HIV/AIDS) and that reported our pre-specified adverse outcomes (serious adverse events (SAEs), withdrawals due to adverse events (AEs), total AEs, serious infections; specific AEs, namely, tuberculosis (TB) reactivation, lymphoma and congestive heart failure) were considered for inclusion. We searched The Cochrane Library, MEDLINE, and EMBASE (to January 2010). Identifying search results and data extraction were performed independently and in duplicate. For the network metaanalysis, we performed both Bayesian mixed-treatment comparison models and arm-based generalized linear mixed models. Main results We included 160 RCTs with 48,676 participants and 46 extension studies with 11,954 participants. The median duration of RCTs was six months and 13 months for OLEs. Data were limited for TB reactivation, lymphoma, and congestive heart failure. Using standard dose, compared with control, biologics as a group were associated with a statistically significant higher rate of total AEs (odds ratio (OR) 1.28, 95% credible interval (CI) 1.09 to 1.50; number needed to treat to harm (NNTH) = 22, 95% confidence interval (CI) 14 to 60), withdrawals due to AEs (
