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U.S. Department of Health and Human Services
National Pharmacy & Therapeutics Committee

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

September 1, 2021

Janus Kinase (JAK) inhibitors decrease the activity of the immune system and treat conditions such as rheumatoid arthritis and ulcerative colitis. The FDA reviewed the results of large randomized safety clinical trials among patients treated with tofacitinib (Xeljanz®) for arthritis and ulcerative colitis. They observed an increased risk for: (a) heart attack and stroke, (b) cancer, (c) blood clots, and (d) death.

JAK inhibitors that share the same mechanism of action and are used to treat arthritis or ulcerative colitis are included: tofacitinib (Xeljanz®), baricitinib (Olumiant®), and upadacitinib (Rinvoq®).

The FDA is updating the boxed warning section of the package insert and limiting all approved uses to certain patients who have not responded or cannot tolerate one or more TNF blockers.

Note: Ruxolitinib (Jakafi®) and fedratinib (Inrebic®) are not included in this update because they are not used to treat arthritis and other inflammatory conditions; they treat certain blood disorders.

Recommendations for Patients

  • Tell your health care professional if you are a current or past smoker, or have had a heart attack, other heart problems, stroke, or blood clots in the past as these may put you at higher risk for serious problems with the medicines. Before starting these medicines, also tell your health care professional about these risk factors.
  • Seek emergency help right away if you have any symptoms that may signal a heart attack, stroke, or blood clot.
  • Inform your health care professionals if you experience signs and symptoms such as: swelling of lymph nodes in your neck, armpits or groin, constantly feeling tired, fever, night sweats, persistent or worsening cough, difficulty breathing, hoarseness or wheezing, or unexplained weight loss.

Recommendations for Health Care Providers

  • Reserve these medicines for patients who have had an inadequate response or intolerance to one or more TNF blockers.
  • Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with JAK inhibitors, particularly 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.
  • Inform patients about the symptoms of serious cardiovascular events and to seek emergency medical attention if they occur.
  • Provide medication education with each prescription, explaining the safety risks and provide other important information as needed.

To help the FDA track safety issues with JAK inhibitors and other medications, please report adverse events involving this or other medicines to the MedWatch program as recommended in the Indian Health Manual and include “IHS” in the reporter section (section G).

Instructions for reporting can be found online at the NPTC Pharmacovigilance website.