The U.S. Food and Drug Administration (FDA) has issued a Safety Announcement for the Janus kinase (JAK) inhibitor tofacitinib after a required postmarketing trial of the drug revealed an increased risk of pulmonary embolism and death in patients who were taking tofacitinib 10 mg twice-daily for the treatment of rheumatoid arthritis (RA).
The ongoing trial began in 2012, when the FDA approved tofacitinib for the treatment of adults with RA. Sponsors enrolled patients with RA who were at least 50 years old and had at least one cardiovascular risk factor, then compared the risks of cardiac-related events, cancer, and opportunistic infections in patients treated with tofacitinib (5 mg or 10 mg twice daily) plus methotrexate versus those treated with a tumor necrosis factor inhibitor.
According to the FDA’s announcement, the agency’s Data Safety Monitoring Board identified a safety signal of pulmonary embolism and increased overall mortality in patients who were receiving tofacitinib at the higher 10-mg dose.
Pfizer, which manufactures and markets tofacitinib as Xeljanz and Xeljanz XR, is transitioning patients on the trial to the lower, currently approved dose of 5 mg twice daily. The higher 10-mg dose was approved for patients with ulcerative colitis in 2018, but not for patients with RA.
“The FDA is actively examining the data from the trial and working directly with Pfizer to better understand the safety signal, its impact on patients, and how tofacitinib should be used,” said Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research, in a statement. “The FDA still believes the benefits of taking tofacitinib for its approved uses continue to outweigh the risks.”