Infections in biological and targeted synthetic drug use in rheumatoid arthritis: where do we stand? A scoping review and meta-analysis

Objectives The advent of biological and targeted synthetic therapies has revolutionised rheumatoid arthritis (RA) treatment. However, this has come at the price of an increased risk of infections. The aim of this study was to present an integrated overview of both serious and non-serious infections, and to identify potential predictors of infection risk in RA patients using biological or targeted synthetic drugs. Design We systematically reviewed available literature from PubMed and Cochrane and performed multivariate meta-analysis with meta-regression on the reported infections. Randomised controlled trials and prospective and retrospective observational studies including patient registry studies were analysed, combined as well as separately. We excluded studies focusing on viral infections only. Results Infections were not reported in a standardised manner. Meta-analysis showed significant heterogeneity that persisted after forming subgroups by study design and follow-up duration. Overall, the pooled proportions of patients experiencing an infection during a study were 0.30 (95%CI, 0.28-0.33) and 0.03 (95%CI, 0.028-0.035) for any kind of infections or serious infections only, respectively. We found no potential predictors that were consistent across all study subgroups. Conclusions The high heterogeneity and the inconsistency of potential predictors between studies show that we do not yet have a complete picture of infection risk in RA patients using biological or targeted synthetic drugs. Besides, we found non-serious infections outnumbered serious infections by a factor 10:1, but only few studies have focused on their occurrence. Future studies should apply a uniform method of infectious adverse event reporting and also focus on non-serious infections and their impact on treatment decisions and quality of life.