FDA Slaps Restrictions on JAK Inhibitors Over Serious Safety Risks | MedPage Today
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FDA Slaps Restrictions on JAK Inhibitors Over Serious
Safety Risks
— Use for inflammatory conditions limited to those who fail on TNF blockers
by Ian Ingram, Managing Editor, MedPage Today
September 1, 2021
The FDA has finished its review of a large postmarketing safety study of tofacitinib (Xeljanz, Xeljanz XR), and its
conclusions do not bode well for the popular drug and the larger class of JAK inhibitors.
Data from the trial revealed increased risks for serious heart-related events -- including myocardial infarction (MI) and
stroke -- as well as a higher risk for cancer, blood clots, and death. Even the lower 5-mg dose of tofacitinib turned up an
increased risk of blood clots and death in the final analysis, the agency noted.
FDA is requiring new and updated warnings for tofacitinib, as well as two other arthritis medicines in the JAK inhibitor
class -- baricitinib (Olumiant) and upadacitinib (Rinvoq). All three JAK inhibitors are approved for rheumatoid arthritis
(alone or in combination), while tofacitinib is also approved in psoriatic arthritis, ulcerative colitis, and polyarticular
course juvenile idiopathic arthritis.
"Since they share mechanisms of action with Xeljanz, FDA considers that these medicines may have similar risks," the
agency said.
In the safety trial, tofacitinib was compared to tumor necrosis factor (TNF) blockers in rheumatoid arthritis patients also
on methotrexate. Treatment with the JAK inhibitor was associated with an increased risk for major adverse cardiac
events (MACE), including MI, cardiovascular death, and stroke (HR 1.33, 95% CI 0.91-1.94), which missed criteria for non-
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FDA Slaps Restrictions on JAK Inhibitors Over Serious Safety Risks | MedPage Today
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inferiority, as well as a higher risk for cancer (HR 1.48, 95% CI 1.04-2.09).
"To ensure the benefits of these three medicines outweigh the risks in patients who receive them, we are limiting all
approved uses to certain patients who have not responded or cannot tolerate one or more TNF blockers," FDA said. "This
is particularly the case in patients who are current or past smokers, those with other cardiovascular risk factors, those
who develop a malignancy, and those with a known malignancy other than a successfully treated nonmelanoma skin
cancer."
Notably, the restrictions will not apply to two JAK inhibitors used for certain blood disorders -- ruxolitinib (Jakafi) and
fedratinib (Inrebic) -- as these are not indicated for arthritis and other inflammatory conditions.
Last Updated September 01, 2021
Ian Ingram is Managing Editor at MedPage Today and helps cover oncology for the site.
9/1/21, 12:57 PM