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. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study did not receive any funding ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present work are contained in the manuscript and the supplementary material