Increase in Blood Clot and Death Risk Spark FDA Warnings for Tofacitinib

New warnings suggest tofacitinib (Xeljanz), a drug to treat patients with ulcerative colitis (UC), increases the risk of blood clots and death.

On July 26, the US Food and Drug Administration (FDA) issued new warnings about the drug, while limiting the use of 10 mg of twice daily doses of tofacitinib to certain patients who are not treated effectively or who experience severe side effects with certain other medicines.

“We approved these changes, including adding our most prominent Boxed Warning, after reviewing interim data from an ongoing safety clinical trial of tofacitinib in patients with rheumatoid arthritis (RA) that examined a lower and this higher dose of the medicine,” the FDA wrote in a statement. “While the increased risks of blood clots and of death were seen in patients taking this dose for RA, these risks may also apply to those taking tofacitinib for ulcerative colitis.”

Currently, 10 mg of twice daily doses of tofacitinib only approved for the initial treatment of ulcerative colitis or for long-term use in limited situations and is not approved for RA or psoriatic arthritis (PA).

Tofacitinib decreases activity in the immune system as an overactive immune systems contributes to RA, PA, and UC.

The medicine was first approved in 2012 to treat adult patients with RA who did not respond well to methotrexate. It was then approved in 2017 to treat PA for patients who also did not respond well to methotrexate or similar medicines and in 2018 to treat UC.

According to the FDA, some of the unusual symptoms that could signal a blood clot include the sudden shortness of breath, chest pain that worsens with breathing, swelling in the legs or arms, leg pain or tenderness, and red or discolored skin in the painful or swollen leg or arm.

After it was first approved in 2012, the FDA required a postmarketing clinical trial for patients with RA on background methotrexate to evaluate the risk of heart-related events, cancer, and infections. The ongoing safety trial is studying 2 different doses of tofacitinib—5 mg twice daily and 10 mg twice daily—in comparison with a tumor necrosis factor (TNF) blocker.

The interim analysis shows an increased occurrence of blood clots and death in patients treated with the 10 mg twice daily dose of the drug. The 10-mg portion of the study has since been stopped.

As of January, the FDA has identified 19 cases of blood clots in the lung and 45 cases of death out of 3884 patients who received the 10 mg doses in the safety trial. On the other hand, they have found blood clots in only 3 patients and death in 25 cases of the 3982 patients who received TNF blockers.