HTA160 A Systematic Review and Meta-Analysis of the Janus Kinase Inhibitors Safety Profile in Relation to the Risks of Secondary Bacterial Infections

Abstract

Evaluation of the safety of drugs for preventive pathogenetic therapy of a newcoronavirus infection COVID-19 with the of Janus kinase inhibitors. A systematic review with a meta-analysis was conducted based on search queries in international databases. Search strategy included queries for controlled studies on the use of baricitinib and tofacitinib recommended for use as a preventive therapy for mild and moderate cases of a new coronavirus infection. Data were obtained from three randomized clinical trials. A meta-analysis of the results regarding the total number of serious adverse events (AEs) and adverse events belonging to the class "Infections and infestations" showed statistically significant evidence on the greater safety of baricitinib and tofacitinib in relation to the risks of these events compared with standard therapy: the risk ratio (RR) of serious adverse events in the comparison groups was 0.82 [95%, CI 0.69; 0.96] (p=0.02), the risk ratio of "Infections and invasions" was 0.78 [95% CI 0.63; 0.97] (p=0.03). In both cases RR was in favor of the use of Janus kinase inhibitors. The results of the meta-analysis demonstrated a favorable safety profile of baricitinib and tofacitinib when used in patients with COVID-19 in relation to the risks of developing serious AEs, as well as infections. Conducting studies of various designs in a wider patient population will allow more accurate assessment of the risks of developing secondary bacterial infections against the background of short-term use of Janus kinase inhibitors as part of their use as a preventive pathogenetic therapy during the COVID-19 pandemic.