Increased Risk of Pulmonary Embolism, Death in RA Patients Reported in Tofacitinib Postmarketing Study

According to data from on an ongoing postmarketing safety trial conducted by Pfizer, tofacitinib dosed at 10mg twice daily was associated with an increased risk of pulmonary embolism and overall mortality in patients with rheumatoid arthritis (RA).

The RA safety study, which the Food and Drug Administration (FDA) required following tofacitinib approval, is currently evaluating the risk of cardiovascular events, cancer, and opportunistic infections associated with 2 dosing regimens, 5mg twice daily and 10mg twice daily, in combination with methotrexate, compared with tumor necrosis factor inhibitor (TNF) use.  As a result of this safety signal, identified by the study’s Data Safety Monitoring Board, patients in the higher dose group will be transitioned to the lower dose regimen; the trial is expected to continue and will be completed by the end of 2019.

Healthcare professionals are being advised to follow the prescribing recommendations in the labeling for tofacitinib; the 10mg twice daily dosing regimen is not approved for the treatment of RA, but is approved for patients with ulcerative colitis. In addition, patients should be monitored for signs and symptoms of pulmonary embolism.

Commenting on the safety trial finding, Janet Woodcock, director of the FDA’s Center for Drug Evaluation and Research Director said “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. The agency will take appropriate action, as warranted, to ensure patients enrolled in this and other trials are protected and that healthcare professionals and clinical trial researchers understand the risks associated with this use.”

In the meantime, the FDA advises that patients continue to take their medications as directed. “The FDA still believes the benefits of taking tofacitinib for its approved uses continue to outweigh the risks,” added Woodcock.

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Tofacitinib, a Janus kinase (JAK) inhibitor, is marketed under the brand names Xeljanz and Xeljanz XR. Xeljanz and Xeljanz XR are both approved for the treatment of certain adults with moderate to severe rheumatoid arthritis and active psoriatic arthritis, while Xeljanz is also indicated for moderate to severe ulcerative colitis.

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