Janus kinase inhibitor treatment for inflammatory diseases: excess or no excess risk of venous thromboembolism?

Janus kinase inhibitors (JAKis) have revolutionized the treatment landscape for various inflammatory and autoimmune diseases since their introduction in 2012. The expanded indications of JAKis have raised concerns about the associated risk of thrombosis, venous thromboembolic events (VTEs), and arterial thrombosis. This literature review examines studies reporting the risk of VTEs associated with JAKis in patients with inflammatory diseases. Phase I to III trials showed no increased risk of VTEs. However, these studies were not designed to detect adverse events such as VTEs. The pharmacovigilance data indicated that the frequency of VTE reports was higher than that of other adverse events. An increased risk of VTEs was also observed in the ORAL Surveillance study, a randomized, noninferiority, postmarketing phase IV safety study comparing tofacitinib with anti-tumor necrosis factor in patients with rheumatoid arthritis. However, limitations have to be acknowledged: pharmacovigilance data are declarative and subject to bias, VTE was a secondary outcome in the ORAL study, with noncomparable VTE risk factors between groups and increased thrombosis risks only at high doses of tofacitinib. Nevertheless, these data have led regulatory organizations such as the Food and Drug Administration and the European Medicines Agency to issue precautionary measures regarding the use of JAKis in inflammatory diseases. Most well-conducted real-life studies are in rheumatoid arthritis and do not confirm an excess of VTE risk associated with JAKis. Considering those conflicting results and limitations, future research should focus on specific indications and patient profiles, taking into account the complex interaction between drug treatment and underlying disease activity, to be able to draw definite conclusion about the VTE risk associated with JAKis.