The US Food and Drug Administration (FDA) has cautioned about the increased risk of serious cardiovascular events such as myocardial infarction or stroke including a higher risk of cancer, blood clots and death with tofacitinib and other Janus kinase (JAK) inhibitors like baricitinib and upadacitinib.

The approved indications have now been limited to patients who have not responded or cannot tolerate one or more tumor necrosis factor (TNF) blockers.

According to the FDA, safety of baricitinib and upadacitinib has not been evaluated in large-scale trials, but as they share their mechanisms of action with tofacitinib, they may also have similar risks as seen in the tofacitinib safety trial.

All the aforementioned JAK inhibitors are approved to treat patients with rheumatoid arthritis. Tofacitinib is also indicated for use in psoriatic arthritis, ulcerative colitis, and polyarticular course juvenile idiopathic arthritis.

However, the FDA has said that these required updates to the prescribing information do not apply to ruxolitinib and fedratinib, which are used to treat blood disorders like myelofibrosis.

(Source: US FDA Drug Safety Communication & MedPage Today, September 1, 2021)