Rheumatoid arthritis (RA) patients taking tofacitinib (Xeljanz XR) face a higher risk of adverse cardiovascular events and cancer than patients taking a tumor necrosis factor (TNF) inhibitor, according to a recent study published in the New England Journal of Medicine.[1]
Tofacitinib, an RA medication sold by Pfizer under the name Xeljanz XR, was associated with elevated lipid levels and an increased incidence of cancers such as lymphoma, prompting the FDA to investigate. The FDA and Pfizer collaborated on this analysis.
“This noninferiority trial assessed the hypothesis that the risk of major adverse cardiovascular events (MACEs) or cancers, excluding nonmelanoma skin cancer, would not be at least 1.8 times higher with tofacitinib (combined doses of 5 mg and 10 mg twice daily) than with a TNF inhibitor in this patient population,” wrote lead author Steven R. Ytterberg, MD, a rheumatology specialist with Mayo Clinic in Rochester, Minnesota, and colleagues.
Ytterberg’s team examined data from more than 4,300 patients who were treated in one of 30 countries from March 2014 to July 2020. All patients were 50 years old or older and presented with at least one additional cardiovascular risk factor such as hypertension or diabetes. Patients were excluded if they had a history of cancer, unless that cancer was a treated nonmelanoma skin cancer.
While 1,455 patients were given 5 mg of tofacitinib twice daily, 1,456 patients were given 10 mg twice daily. Another 1,451 patients received a TNF inhibitor. The mean duration of treatment ranged from 38 to 41 months.
Overall, after a median follow-up period of 4 years, the MACE rate was 3.4% among tofacitinib patients and 2.5% among TNF inhibitor patients. This did not show noninferiority, the authors emphasized.
In addition, the cancer rate was 4.2% among tofacitinib patients and 2.9% among TNF inhibitor patients. Again, this did not show noninferiority for tofacitinib.
“Taken together, these results show the higher risk of MACE and cancers with tofacitinib than with TNF inhibitors,” the authors wrote.
Tofacitinib update from the FDA
These findings were shared with the FDA before they were published. The agency responded by adding new warnings to tofacitinib in September 2021. These updated warnings were also added to two other medications, baricitinib and upadacitinib, that are part of the same drug class — JAK inhibitors — and prescribed for the same reasons.
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Michael has more than 16 years of experience as a professional writer and editor. He has written at length about cardiology, radiology, artificial intelligence and other key healthcare topics.