After: Paul L Romain, MDMonica Ramirez Curtis, MD, MPH
Cardiovascular and malignancy risk with Janus kinase inhibitors (September 2021)
The level of risk for cardiovascular (CV) events and malignancy with Janus kinase (JAK) inhibitors is uncertain. Unpublished data from a phase 4 open-label trial comparing tofacitinib with a tumor necrosis factor (TNF) inhibitor in over 4300 patients ≥50 years old on methotrexate for rheumatoid arthritis (RA) and with elevated CV risk showed a small, largely dose-dependent increased risk of nonfatal myocardial infarction, thrombosis, lymphoma, and lung cancer with tofacitinib. These findings prompted the US Food and Drug Administration to advise screening for relevant risk factors in patients with serious inflammatory diseases, including RA and ulcerative colitis, and to limit use of tofacitinib, baricitinib, and upadacitinib to patients with an inadequate response or intolerance to TNF inhibitors. European regulators issued a narrower advisory to limit use of tofacitinib in older patients (≥65 years), current or past smokers, and those with other CV and malignancy risk factors.