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FDA Requiring Black Box Warning for Certain JAK Inhibitors

Dermatology TimesDermatology Times, October 2021 (Vol. 42. No. 10)
Volume 42
Issue 10
Pages: 42

The FDA is now requiring black box warning for certain JAK inhibitors used to treat arthritis. This news comes amid delay in FDA approval for multiple JAK inhibitors for the treatment of inflammatory skin conditions.

Following the completion of its safety review of tofacitinib (Xeljanz, Xeljanz XR; Pfizer), a Janus kinase (JAK) inhibitor approved for the treatment of arthritis and ulcerative colitis, the FDA has determined there is an increased risk of serious heart-related events such as heart attack or stroke, blood clots, cancer, and death associated with the medications.

The review consisted of a trial comparing tofacitinib to tumor necrosis factor (TNF) blockers, another medicine used to treat arthritis, in patients with rheumatoid arthritis. Results of the trial demonstrated an increased risk of blood clots and death with the lower dose of tofacitinib. Previously, a FDA Drug Safety Communication from July 26, 2019, reported an increased risk of blood clots and death seen at the higher dose based upon earlier results from this safety trial.2

Now, the regulatory agency is requiring revisions to the boxed warning for tofacitinib, baricitinib (Olumiant; Eli Lilly), and upadacitinib (Rinvoq; AbbVie) to include information about the risks of serious heart-related events, cancer, blood clots, and death. Additionally, the FDA is now limiting all approved uses to certain patients who have not responded or cannot tolerate 1 or more TNF blockers.

The FDA’s decision to require new, updated warnings for 2 other arthritis medicines in the same drug class, baricitinib and upadacitinib, is due to the drugs not being studied in trials like the large safety trial for tofacitinib, thus the risks have not been fully evaluated. Since baricitinib and upadacitinib share the same mechanisms of action (MOA) with tofacitinib, these medicines might have similar risks as seen in the safety trial for tofacitinib, according to a press release from the FDA.

Aside from being approved to treat arthritis, baricitinib and upadacitinib are currently on hold for approval from the FDA for the treatment of atopic dermatitis. 

The FDA suggests physicians consider the risks and benefits for individual patients before beginning or continuing treatment with tofacitinib, baricitinib, or upadacitinib.

“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,” the regulatory agency states. “Reserve these medicines for patients who have had an inadequate response or intolerance to one or more TNF blockers. Counsel patients about the benefits and risks of these medicines and advise them to seek emergency medical attention if they experience signs and symptoms of a heart attack, stroke, or blood clot.”

Ruxolitinib (Jakafi; Incyte) and fedratinib (Inrebic; Bristol Myers Squibb), 2 other JAK inhibitors, are not included in the prescribing information update requirements as they are not indicated for the treatment of arthritis and other inflammatory conditions

“If FDA becomes aware of any additional safety information or data that warrants updates to the prescribing information for these medicines, we may take further action and will alert the public,” stated the FDA.

More information about the new black box warning for these medicines and prescribing advice can be found at www.fda.gov.


1. Research C for DE and. FDA requires warnings about increased risk of serious heart-related events, cancer, blood clots, and death for JAK inhibitors that treat certain chronic inflammatory conditions. FDA. Published online September 1, 2021. Accessed September 2, 2021. https://www.fda.gov/drugs/drug-safety-and-availability/fda-requires-warnings-about-increased-risk-serious-heart-related-events-cancer-blood-clots-and-death

2. Research C for DE and. FDA approves Boxed Warning about increased risk of blood clots and death with higher dose of arthritis and ulcerative colitis medicine tofacitinib (Xeljanz, xeljanz xr). FDA. Published online July 26, 2019. Accessed September 2, 2021. https://www.fda.gov/drugs/drug-safety-and-availability/fda-approves-boxed-warning-about-increased-risk-blood-clots-and-death-higher-dose-arthritis-and

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