After finishing its review of a large-scale safety study of tofacitinib (Xeljanz and Xeljanz XR), the U.S. Food and Drug Administration (FDA) will require new label updates for the medication warning of increased risks of heart attack and stroke, and other serious side-effects.1
The FDA said the trial results showed elevated risks of not only serious heart-related events, but also blood clots, cancer, and death, even with the lower, 5 mg dose of the drug. The new warnings will apply to tofacitinib as well as two other medications in the class of drugs known as Janus kinase (JAK) inhibitors: baricitinib (Olumiant) and upadacitinib (Rinvoq), which were not studied in this trial. All three medications are indicated for rheumatoid arthritis, and tofacitinib is also approved for psoriatic arthritis, ulcerative colitis, and a form of juvenile arthritis.2
The safety trial compared tofacitinib with TNF blockers in patients with rheumatoid arthritis who were also taking methotrexate. Patients in the trial were required to be at least 50 years old and have at least one risk factor for heart disease. Treatment with either dose of the JAK inhibitor (5 mg or 10 mg twice daily) was associated with a greater risk of the major cardiac events noted above and a greater incidence of lymphomas and other cancers, as compared with TNF blockers (previous data had shown the increased risks only with the higher dose).1
“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,” the FDA said in a statement.
Not all JAK inhibitors are the same, but since baricitinib and upadacitinib “share mechanisms of action” with tofacitinib, the statement said, “FDA considers that these medicines may have similar risks as seen in the Xeljanz safety trial.”
The new warnings will not apply to two other JAK inhibitors used to treat certain blood disorders, ruxolitinib (Jakafi) and fedratinib (Inrebic), which are not indicated for arthritis.
If you are taking a JAK inhibitor subject to the new restriction and have an elevated risk of cardiac events or cancers, it’s best that you speak to your doctor.
“In view of the trial, the FDA has come out with a guidance document for providers and patients to discuss alternative medications to treat their conditions. In some situations, JAK inhibitors may be the right choice for you after discussing the pros and cons of all other available therapies, and your individual situation,” said rheumatologist Atul Deodhar, MD, a member of SAA’s Medical and Scientific Advisory Board. “We believe it is important for you to be fully informed, and make a shared decision with your provider.”
Editor’s note: We will present a comprehensive overview of JAK inhibitors – what they are used for, and how they may benefit those with spondyloarthritis – in our winter edition of Spondylitis Plus, coming toward the end of this year.
- 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
- FDA Slaps Restrictions on JAK Inhibitors Over Serious Safety Risks | MedPage Today