The main safety issue of JAKis, however, concerns cardiovascular (CV) adverse events (AEs) and first emerged during the approval process of baricitinib for RA.52 As a result, the regulatory authorities requested additional studies enrolling RA patients with high CV risk, in order to compare the safety of tofacitinib (ORAL surveillance trial) and baricitinib (NCT03915964) with TNFα blockers. This evidence concerns the gene TNF and rheumatoid arthritis.