News from the FDA/CDC

FDA: Safety signal emerged with higher dose of tofacitinib in RA study


A safety signal of pulmonary embolism and increased mortality has emerged in a postmarketing trial of tofacitinib (Xeljanz) in patients with rheumatoid arthritis, the Food and Drug Administration reported.

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The trial’s Data Safety and Monitoring Board identified the signal in patients taking a 10-mg dose of tofacitinib twice daily, the FDA said in a safety announcement.

Pfizer, the trial’s sponsor, took “immediate action” to transition patients in the ongoing trial from the 10-mg, twice-daily dose to 5 mg twice daily, which is the approved dose for adult patients with moderate to severe rheumatoid arthritis, the agency said. The 10-mg, twice-daily dose is approved only in the dosing regimen for patients with ulcerative colitis. Xeljanz is also approved to treat psoriatic arthritis. The 11-mg, once-daily dose of Xeljanz XR that is approved to treat rheumatoid arthritis and psoriatic arthritis was not tested in the trial.

The ongoing study was designed to assess risks of cardiovascular events, cancer, and opportunistic infections with tofacitinib 10 mg twice daily or 5 mg twice daily versus the risks in a control group treated with a tumor necrosis factor (TNF) inhibitor, according to the statement.

Patients had to be 50 years of age or older and have at least one cardiovascular risk factor to be eligible for the study, which was required by the agency in 2012 when it approved tofacitinib, the statement says.

The FDA is reviewing trial data and working with Pfizer to better understand the safety signal, its effect on patients, and how tofacitinib should be used, Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research, said in a news release. The trial will continue and is expected to be completed by the end of 2019.

“The agency will take appropriate action, as warranted, to ensure patients enrolled in this and other trials are protected and that health care professionals and clinical trial researchers understand the risks associated with this use,” she added.

Health care professionals should follow tofacitinib prescribing information, monitor patients for the signs and symptoms of pulmonary embolism, and advise patients to seek medical attention immediately if they experience those signs and symptoms, according to the statement.

“We are communicating now, given the serious nature of the safety issue, to ensure that patients taking tofacitinib are aware that the FDA still believes the benefits of taking tofacitinib for its approved uses continue to outweigh the risks,” Dr. Woodcock said in the release.

While not approved in rheumatoid arthritis, the 10-mg, twice-daily dose of tofacitinib is approved in the dosing regimen for patients with ulcerative colitis, the release says.

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