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Purpose of Review: Janus kinase inhibitors (JAKi) have been available for the treatment of rheumatoid arthritis (RA) since 2012 and are indicated for patients with active disease despite csDMARD therapy. Efficacy and safety, as demonstrated in the clinical trials, was similar to biologics. A recent post marketing trial suggested safety concerns with the JAKi, which will be reviewed., Recent Findings: A post marketing Food and Drug Administration (FDA) mandated open-label randomized clinical trial of tofacitinib 5 and 10 mg twice daily (b.i.d.) compared with adalimumab and etanercept was conducted in RA patients on background methotrexate who were at a high risk for cardiovascular disease. This was a noninferiority study evaluating the incidence of major adverse cardiovascular events (MACE) and malignancy with the therapies. Noninferiority for both doses of tofacitinib was not achieved with a numerical increase in MACEs and malignancy with tofacitinib compared to the TNF inhibitors. A dose-dependent increase in venous thromboembolism (VTE) risk with tofacitinib was observed. The findings from this study resulted in the FDA and European Medicines Agency (EMA) restriction of use for all Jaki to RA patients who had failed TNF inhibitors., Summary: JAK inhibitors are effective treatments for RA. Issues have been raised regarding safety in patients with an increase in cardiovascular risk and VTE risk resulting in the need for risk stratification., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose of Review: To review recently published articles on use of Janus Kinase inhibitors (Jaki) in the clinic for rheumatoid arthritis (RA)., Recent Findings: Several Jaki have been approved for RA patients failing csDMARDS. Over the last 2 years, EULAR and ACR have published updated recommendations for the pharmacologic management of RA providing guidance on the utilization of Jaki after csDMARD failure. Clinical trials have been published addressing the efficacy of Jaki monotherapy as patients often choose monotherapy because of a desire to avoid multiple therapies and aggravating adverse events with csDMARDs. Previous clinical trials have compared the efficacy and safety of Jaki to adalimumab, and a trial comparing abatacept to upadacitinib has recently been published. An increased risk of venous thromboembolism (VTE) has been suggested with Jaki and additional information has recently become available with conflicting results., Summary: Jaki are now standard therapy for RA patients failing csDMARDs and are being utilized frequently as an alternative to biologics in patients without risk factors for VTE. Jaki monotherapy has been demonstrated to be effective, although combination therapy has been demonstrated to be superior in clinical and radiographic outcomes. Preliminary data suggests that cycling through Jaki in patients with incomplete response to initial Jaki treatment may be an appropriate strategy., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)