Pfizer Transitions RA Patients Off 10 mg Dose After Study Shows Risk of Pulmonary Embolism

According to a recent announcement from Xeljanz manufacturer Pfizer, the company has taken steps to transition patients with rheumatoid arthritis (RA) who are taking the 10 mg twice-daily dose to the lower 5 mg twice-daily dose. The company noted that it’s taking this action based on the results of a post-marketing study that indicates significant potential side effects associated with the higher dose.

FDA Alerts the Public to Risk of Blood Clots in the Lungs with Xeljanz

On February 25, 2019, the FDA released a safety communication alerting the public to a concerning finding regarding Xeljanz and Xeljanz XR (tofacitinib and tofacitinib extended-release).

The FDA originally approved Xeljanz in 2012 for the treatment of rheumatoid arthritis at the 5 mg twice-daily dose. They also required the manufacturer conduct a post-marketing safety trial to evaluate the risk of heart-related events, cancer, and infections with the medicine at two doses: 10 mg twice daily and 5 mg twice daily, in comparison to another RA medication.

In the clinical trial, participants were required to be at least 50 years old and to have at least one risk factor for cardiovascular diseases, like high blood pressure. During the most recent analysis of the data from that trial, a data safety monitoring committee found an increased occurrence of blood clots in the lungs and death in patients treated with the higher dose of Xeljanz, compared with the lower dose or with the alternative medication.

As a result of this finding, the FDA advised health care professionals to follow the recommendations in the tofacitinib prescribing information for the specific condition they are treating—in other words, to give RA patients no more than the 5-mg/day dose. They also suggested that doctors monitor patients for signs and symptoms of pulmonary embolism (blood clots in the lungs).

Patients, as well, should be aware of symptoms like sudden shortness of breath or difficulty breathing, chest or back pain, coughing up blood, excessive sweating, and clammy or bluish skin. Anyone experiencing these symptoms should seek medical attention immediately, as pulmonary embolism can be life-threatening.

FDA Alerts the Public to Risk of Blood Clots in the Lungs with Xeljanz

Pfizer echoed these findings in a statement, noting that it used “external, independent, blinded endpoint adjudication committees to review safety events in a standardized manner and an independent, external data safety monitoring board (DSMB) to monitor patient safety for all ongoing tofacitinib rheumatology studies.”

Indeed, the DSMB observed that RA patients treated with the 10 mg twice-daily dose had a significantly increased risk of pulmonary embolism. It also noted an overall increased mortality in the group taking that dose.

The study is ongoing and will continue through to completion. Meanwhile, the DSMB stated it “firmly believes that the risk-benefit profile of tofacitinib 5 mg twice daily” remains “appropriately balanced in this study.”

The FDA has also approved Xeljanz for the treatment of active psoriatic arthritis and moderately to severely active ulcerative colitis.