It is the third set of warnings for certain Janus kinase (JAK) inhibitors due to the risk of heart attack or stroke, cancer, blood clots, and death.
After a review of a large randomized safety clinical trial, the FDA said it “concluded there is an increased risk of serious heart-related events such as heart attack or stroke, cancer, blood clots, and death with the arthritis and ulcerative colitis medicines Xeljanz and Xeljanz XR (tofacitinib).”
This trial compared tofacitinib with tumor necrosis factor (TNF) inhibitors in patients with rheumatoid arthritis, and results showed an increased risk of blood clots and death with the lower dose of tofacitinib.
In July 2019, a previous Drug Safety Communication from the FDA showed an increased risk of blood clots and death at the higher dose of tofacitinib, based on the same trial. That came a few months after the first warning in February 2019, which warned of a higher risk of blood clots.
As a result of the latest finding, the FDA said it would require 2 other JAK inhibitors, baricitinib (Olumiant) and upadacitinib (Rinvoq), to carry the same warning. Although these 2 medicines were not studied in a safety trial similar to tofacitinib, the FDA said it considers the risks to be similar due to shared mechanisms of action.
The FDA said 2 other JAK inhibitors, ruxolitinib (Jakafi) and fedratinib (Inrebic), are not indicated for the treatment of arthritis and other inflammatory conditions and are not a part of these updates, but the agency said it may take further action if it other safety information becomes known.