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

Tofacitinib (Xeljanz®) May Increase Risk of Serious Heart-Related Problems and Cancer

The FDA has issued a Drug Safety Communication (DSC) to alert clinicians about risks of heart-related problems and cancer with the use of tofacitinib. Tofacitinib belongs to a class of medications called Janus Kinase (JAK) Inhibitors. It is approved by the FDA for the treatment of rheumatoid and psoriatic arthritis in patients who do not respond well to methotrexate and for ulcerative colitis.

When first approved, the FDA required a safety trial of tofacitinib in patients with rheumatoid arthritis, age 50 and older, and with at least one cardiovascular risk factor. Interim analysis of this study showed an increased risk of blood clots and death Exit Disclaimer: You Are Leaving www.ihs.gov  among those receiving tofacitinib 10mg twice daily compared to treatment with either tofacitinib 5mg twice daily or a TNF blocker.

The Tofacitinib Boxed Warning was Modified to Reflect the Following Findings

WARNING: SERIOUS INFECTIONS, MORTALITY, MALIGNANCY AND THROMBOSIS

  • Serious infections leading to hospitalization or death, including tuberculosis and bacterial, invasive fungal, viral, and other opportunistic infections, have occurred.
  • If a serious infection develops, interrupt XELJANZ/XELJANZ XR/XELJANZ Oral Solution until the infection is controlled.
  • Prior to starting XELJANZ/XELJANZ XR/XELJANZ Oral Solution, perform a test for latent tuberculosis; if it is positive, start treatment for tuberculosis prior to starting XELJANZ/XELJANZ XR/XELJANZ Oral Solution.
  • Monitor all patients for active tuberculosis during treatment, even if the initial latent tuberculosis test is negative.
  • Thrombosis, including pulmonary embolism, deep venous thrombosis and arterial thrombosis have occurred in patients treated with XELJANZ and other Janus kinase inhibitors. Rheumatoid arthritis patients with at least one cardiovascular (CV) risk factor had a higher rate of all-cause mortality and thrombosis with XELJANZ 10 mg twice daily vs. 5 mg twice daily or TNF blockers.
  • Lymphoma and other malignancies have been observed in patients treated with XELJANZ, including an increased rate of Epstein Barr Virus- associated post-transplant lymphoproliferative disorder.

Although the final results of this study are not yet available, preliminary results show an increased risk of heart-related problems and cancer with both the 5 and 10mg twice daily doses of tofacitinib. FDA is awaiting additional results from the trial and will communicate their final recommendations once the review is completed.