Risk of Blood Clots, Death with Rheumatoid Arthritis Drug

On February 25, 2019, the FDA alerted the public that a clinical trial found an increased risk of blood clots in the lungs and death when a 10 mg twice daily dose of tofacitinib (Xeljanz, Xeljanz XR) was used in patients with rheumatoid arthritis (RA). The FDA has not approved this 10 mg twice daily dose for RA. A 10 mg twice daily dose was approved only in the dosing regimen for patients with ulcerative colitis.


Tofacitinib works by decreasing the activity of the immune system. It was first approved in 2012 to treat adult patients with RA who did not respond well to methotrexate. In RA, the body attacks its own joints, causing pain, swelling, and loss of function. In 2017, the FDA approved the medicine to treat patients with a second condition, psoriatic arthritis, who did not respond well to methotrexate or other similar medicines called nonbiologic disease-modifying antirheumatic drugs (DMARDs). Psoriatic arthritis is a condition that also causes joint pain and swelling. In 2018, the FDA approved tofacitinib to treat a condition called ulcerative colitis, which is a chronic, inflammatory bowel disease affecting the colon.


When the FDA first approved tofacitinib, the FDA required a clinical trial among patients with RA to evaluate the risk of heart-related events, cancer, and opportunistic infections with the medicine at two doses (10 mg twice daily and 5 mg twice daily) in combination with methotrexate in comparison to another drug called a tumor necrosis factor (TNF) inhibitor. RA patients in the trial were required to be at least 50 years old and have at least one cardiovascular risk factor. During the most recent analysis of the trial, an external data safety monitoring committee found an increased occurrence of blood clots in the lungs and death in patients treated with tofacitinib 10 mg twice daily compared to patients treated with tofacitinib 5 mg twice daily or a TNF inhibitor.


The FDA recommended that healthcare professionals follow the recommendations in the tofacitinib prescribing information for the specific condition they are treating. Healthcare professionals should monitor patients for the signs and symptoms of pulmonary embolism, and advise them to seek medical attention immediately if they experience them.


The FDA advised patients not to stop or change the dose of tofacitinib without first talking to a healthcare professional, as doing so may worsen the condition. Patients taking tofacitinib should seek medical attention immediately if they experience symptoms of a blood clot in the lungs or other unusual symptoms, such as sudden shortness of breath or difficulty breathing, chest pain or pain in the back, coughing up blood, excessive sweating, or clammy or bluish colored skin.


See the FDA Safety Alert


See the FDA Drug Safety Communication


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