We included 163 RCTs with 50,010 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 tuberculosis (TB) reactivation, lymphoma, and congestive heart failure. Adjusted for dose, biologics as a group were associated with a statistically significant higher rate of total adverse events (odds ratio (OR) 1.19, 95 CI 1.09 to 1.30; number needed to treat to harm (NNTH) = 30, 95 CI 21 to 60) and withdrawals due to adverse events (OR 1.32, 95 CI 1.06 to 1.64; NNTH = 37, 95 CI 19 to 190) and an increased risk of TB reactivation (OR 4.68, 95 CI 1.18 to 18.60; NNTH = 681, 95 CI 143 to 14706) compared to control.
The rate of serious adverse events, serious infections, lymphoma, and congestive heart failure were not statistically significantly different between biologics and control treatment. Certolizumab pegol was associated with significantly higher risk of serious infections compared to control treatment (OR 3.51, 95 CI 1.59 to 7.79; NNTH = 17, 95 CI 7 to 68). Infliximab was associated with significantly higher risk of withdrawals due to adverse events compared to control (OR 2.04, 95 CI 1.43 to 2.91; NNTH = 12, 95 CI 8 to 28).
Indirect comparisons revealed that abatacept and anakinra were associated with a significantly lower risk of serious adverse events compared to most other biologics. Although the overall numbers are relatively small, certolizumab pegol was associated with significantly higher odds of serious infections compared to etanercept, adalimumab, abatacept, anakinra, golimumab, infliximab, and rituximab; abatacept was significantly less likely than infliximab and tocilizumab to be associated with serious infections. Abatacept, adalimumab, etanercept and golimumab were significantly less likely than infliximab to result in withdrawals due to adverse events.