European Regulators Impose Xeljanz Restrictions Amid Safety Worries

Published on May 21, 2019 by Sandy Liebhard

Drug regulators in the European Union have decided to limit the use of Xeljanz, months after a post-market safety study flagged pulmonary embolism and a higher death rate as possible safety signals for rheumatoid arthritis patients taking a 10mg-twice daily dose.

European Xeljanz Restrictions Only Temporary, for Now.

The European Medicines Agency’s (EMA) safety committee chose to impose the Xeljanz restrictions even though the trial data remains under review, an indication of the extreme concern surrounding the matter.

The new limits basically ban the 10mg twice-daily Xeljanz regimen for patients at heightened risk for blood clots in the lungs. This includes:

• Heart failure patients
• Cancer patients
• Those with a history of or predisposition to blood clots
• Individuals preparing or recovering from surgery
• Patients taking hormone-based therapies

Doctors should also consider other factors that may increase the risk of blood clots in the lungs including age, obesity, smoking or immobilization.

“The new advice means that, since 10 mg is the only recommended starting dose for ulcerative colitis, patients with this condition who are at high risk of blood clots must not be started on Xeljanz,” the EMA said in a statement dated May 17^th. “Patients at high risk currently taking this dose for any condition must be switched to alternative treatments.”

The new Xeljanz restrictions are temporary, at least for now. The EMA’s safety committee will continue to review all available evidence and provide updated guidance to healthcare providers and the public once that review is complete.

10mg Xeljanz and Pulmonary Embolism

The U.S. Food & Drug Administration (FDA) initially approved Xeljanz (5 mg twice daily) to treat rheumatoid arthritis in 2012. Four years later, the agency cleared Xeljanz XR, an 11 mg, once-daily, extended-release tablet. Both Xeljanz versions were approved to treat adults with psoriatic arthritis in 2017, while the 10 mg twice-daily Xeljanz regimen was approved to treat ulcerative colitis in 2018.

The FDA ordered Pfizer, Inc. to conduct the post-market study referenced by the EMA when Xeljanz first came to market, as a condition of its approval. In February, Pfizer announced that preliminary results suggested 10mg twice-daily Xeljanz patients were 5-times more likely to suffer a pulmonary embolism compared to those treated with a tumor necrosis factor inhibitor and 3-times more likely compared to those on the 5mg twice-daily Xeljanz protocol.

The higher-dose Xeljanz group also had more deaths from all causes compared to the study’s other patient groups.

The findings alarmed even Pfizer, which opted to transition all patients in the study’s high-dose Xeljanz arm to the lower dose protocol.

FDA Xeljanz Pulmonary Embolism Review

Days later, the FDA announced its own review. Although the agency hasn’t imposed Xeljanz restrictions similar to those in Europe, it did remind healthcare providers in the United States that the high-dose regimen is only indicated for ulcerative colitis.

Both the FDA and the EMA cautioned patients against stopping Xeljanz without first talking to their doctor, regardless of the dose. The regulators also urged Xeljanz patients to seek emergency medical attention if they experience signs or symptoms of a pulmonary embolism, including:

• Sudden shortness of breath or difficulty breathing
• Chest pain or pain in your back
• Coughing up blood
• Excessive sweating
• Clammy or bluish-colored skin

Pfizer’s post-market study will conclude in September 2019. The FDA is working with the company to evaluate other currently available Xeljanz safety data and will issue an update once its review is complete.