TNF-α inhibitors can increase the risk of respiratory infection when used in rheumatism: a meta-analysis and systematic review

Background The risk of tumor necrosis factor-α(TNF-α) inhibitors (infliximab, etanercept, adalimumab) for the treatment of rheumatic diseases leading to infection events has not yet been established. This meta-analysis aims to assess the risk of developing serious infections of three TNF-α inhibitors for rheumatic diseases.Methods A systematic literature search of Pubmed, Embase and Cochrane Library was conducted through December 2018. Selecting the RCTs which subjects were diagnosed as rheumatoid diseases according to ACR criteria or other authoritative diagnostic criteria and over 18-year-old. Finally, RCTs with Jadad score greater than or equal to 4 were included in this meta-analysis. The Odds Ratio (OR), Confidence Interval (CI) and p value were calculated to assess the risk of serious infections. Results 34 RCTs involving 14166 subjects were included, including 11 RCTs for infliximab, 7 RCTs for etanercept, and 16 for adalimumab. Meta-analysis demonstrated that, with the pooled OR of 1.29 (95%CI 1.04 to 1.60), the TNF-α inhibitors group had a higher risk of serious infection than control group. In the subgroup analysis, infliximab and adalimumab had a higher risk of serious infection than control group, and the pooled ORs were 1.48 (p=0.03) and 1.47 (p=0.03), respectively. For other infections including pneumonia, upper respiratory infection, and nasopharyngitis, the risks of these adverse events were higher in experimental group than control group, while the risk of tuberculosis were not, with the pooled OR of 2.31 (p=0.08）.Conclusions TNF-α inhibitors, especially infliximab and adalimumab, can increase the risk of infections. Among the infections, pneumonia, upper respiratory infection and nasopharyngitis have higher risks in TNF-α inhibitors group than control group. As a result, we summarized that TNF-α inhibitors can increase the risks of respiratory infection when used in rheumatic disease. It is suggested that clinicians should pay attention to the prevention of respiratory infections when using TNF-α inhibitors, so as to achieve a better prognosis for patients with rheumatism.