Tuesday, 25 Feb 2020

You are here

Tofacitinib Gets a New Boxed Warning for Blood Clots and Death with Higher Doses

The U.S. Food and Drug Administration has approved new warnings about an increased risk of blood clots and of death with the 10 mg twice daily dose of tofacitinib (Xeljanz, Xeljanz XR), which is used in patients with ulcerative colitis. 

The addition of a Boxed Warning, stems from a review of interim data from an ongoing safety clinical trial of tofacitinib in patients with rheumatoid arthritis (RA) that examined a lower and this higher dose of the medicine.

The 10 mg twice daily dose of tofacitinib is not approved for RA or psoriatic arthritis (PsA). This dose is only approved for ulcerative colitis for initial treatment and for long-term use in limited situations. While the increased risks of blood clots and of death were seen in patients taking this dose for RA, these risks may also apply to those taking tofacitinib for ulcerative colitis.

 

Patients should tell your health care professionals if you have a history of blood clots or heart problems, and talk to them about any questions or concerns. Stop taking tofacitinib and seek emergency medical attention right away if you experience any unusual symptoms, including those that may signal a blood clot such as:

  • Sudden shortness of breath
  • Chest pain that worsens with breathing
  • Swelling of a leg or arm
  • Leg pain or tenderness, or red or discolored skin in the painful or swollen leg or arm

Do not stop taking tofacitinib without first talking to your health care professional, as doing so can worsen your condition.

Health care professionals should discontinue tofacitinib and promptly evaluate patients with symptoms of thrombosis. Counsel patients about the risks and advise them to seek medical attention immediately if they experience any unusual symptoms, including those of thrombosis listed above. Reserve tofacitinib to treat ulcerative colitis for patients who have failed or do not tolerate tumor necrosis factor (TNF) blockers. Avoid tofacitinib in patients who may have a higher risk of thrombosis. When treating ulcerative colitis, use tofacitinib at the lowest effective dose and limit the use of the 10 mg twice daily dosage to the shortest duration needed (See Additional Information for Health Care Professionals for more recommendations).

When FDA first approved tofacitinib in 2012, we required a postmarketing clinical trial in patients with RA on background methotrexate, to evaluate the risk of heart-related events, cancer, and infections. The trial is studying two different doses of tofacitinib (5 mg twice daily, which is the currently approved dose for RA, and a higher, 10 mg twice daily dosage) in comparison to a TNF blocker. An interim analysis of the trial’s results found an increased occurrence of blood clots and of death in patients treated with tofacitinib 10 mg twice daily compared to patients treated with tofacitinib 5 mg twice daily or a TNF blocker. Based on these results, the 10 mg twice daily treatment was stopped and patients were allowed to continue treatment on 5 mg twice daily.

This safety trial is ongoing. Patients in the 5 mg twice daily group and the TNF blocker group continue to be followed. FDA will reassess these safety issues when the trial has completed and final, verified data are available. We will update the public when additional information is available.

The interim results of the trial, as of January 2019, have identified the following:

  • 19 cases of blood clots in the lung out of 3,884 patient-years of follow-up in patients who received tofacitinib 10 mg twice daily, compared to 3 cases out of 3,982 patient-years in patients who received TNF blockers
  • 45 cases of death from all causes out of 3,884 patient-years of follow-up in patients who received tofacitinib 10 mg twice daily, compared to 25 cases out of 3,982 patient-years in patients who received TNF blockers
Disclosures: 
The author has no conflicts of interest to disclose related to this subject

Add new comment

More Like This

Overmedication of America

Recent research from the Lown Institute reports that 750 older Americans are hospitalized daily because of serious side effects from and the core problem is that of polypharmacy, especially in the elderly. 

Best of 2019 - Biologic Safety Guidelines from the British Society for Rheumatology

In the United Kingdom, NICE has looked to the British Society of Rheumatology (BSR) to develop evidence based guidance on the safe use of biologic DMARDs in patients with inflammatory arthritis. This guidance document on biologic safety covers baseline screening, monitoring, effect of co-morbidities, and when or under what circumstances biologic therapy should be interrupted.

Best of 2019 - Methotrexate and the Risk of Lung Disease

Rheumatology has a comprehensive overview of methotrexate (MTX) and the risk of lung injury, MTX-related pneumonitis and interstitial lung disease (RA-ILD) with rheumatoid arthritis (RA). Past reports suggest the frequence of MTX-pneumonitis to be between 0.3 and 11.6%; recent studies suggest it may be much lower.

No Cancer Risk with Systemic Necrotizing Vasculitis

The French Vasculitis Study Group has published that patients with systemic necrotizing vasculitis do not have an increased risk of malignancy; in fact they have a risk that is similar to the general population.

Previous reports have suggested either no risk or a declining risk in the era of better therapies for vasculitis. 

FDA Warns 15 CBD Manufacturers

Today, the U.S. Food and Drug Administration issued warning letters to 15 companies for illegally selling products containing cannabidiol (CBD) in ways that violate the Federal Food, Drug, and Cosmetic Act (FD&C Act).  This warning affirms that the FDA has not determined the many preparations of cannabidiol to be safe or effective.