FDA responds to safety signal reported in required postmarketing trial for Xeljanz

SILVER SPRING, Md., Feb. 25, 2019 /PRNewswire/ -- "Today the FDA is warning about a safety signal that emerged in a required postmarketing trial of the drug Xeljanz (tofacitinib) in patients with rheumatoid arthritis. This particular trial was initiated to further evaluate the safety of tofacitinib at two doses (5 mg twice daily or 10 mg dose twice daily) versus a control group of another treatment, and was specifically designed to assess the risk of cardiovascular events, cancer and opportunistic infections. Data review by the study's Data Safety Monitoring Board identified a safety signal of pulmonary embolism and increased overall mortality in patients in the trial who were taking the 10 mg dose of tofacitinib twice daily. The trial's sponsor Pfizer, at the recommendation of the FDA took immediate action to protect patient safety and transitioned patients in the ongoing trial from tofacitinib 10 mg twice daily to tofacitinib 5 mg twice daily, which is the FDA-approved dose for adult patients with moderate to severe rheumatoid arthritis," said Janet Woodcock, director of the FDA's Center for Drug Evaluation and Research Director. "The FDA is actively examining the data from the trial and working directly with Pfizer to better understand the safety signal, its impact on patients, and how tofacitinib should be used. The agency will take appropriate action, as warranted, to ensure patients enrolled in this and other trials are protected and that health care professionals and clinical trial researchers understand the risks associated with this use. We are communicating now, given the serious nature of the safety issue, to ensure that patients taking tofacitinib are aware that the FDA still believes the benefits of taking tofacitinib for its  approved uses continue to outweigh the risks. Patients taking tofacitinib for its approved uses should continue to take their medication as directed by their health care professional. Today's safety alert underscores the importance of monitoring and addressing safety questions that arise in the postmarket setting."

Today, the FDA released a Drug Safety Communication alerting health care professionals and patients about a safety signal seen in a postmarketing trial in patients with rheumatoid arthritis (RA) who were taking tofacitinib 10 mg twice daily. The FDA required the drug manufacturer, Pfizer, to conduct the trial when it approved tofacitinib in 2012. This ongoing trial is evaluating the safety of tofacitinib at two doses (the approved 5 mg twice daily and a higher dose of 10 mg twice daily) versus a tumor necrosis factor inhibitor (TNFi) control group. Data review by the Data Safety Monitoring Board identified a safety signal of pulmonary embolism and increased overall mortality in the 10 mg twice daily treatment group. Pfizer has transitioned patients in the ongoing trial from tofacitinib 10 mg twice daily to tofacitinib 5 mg twice daily, which is the FDA-approved dose for adult patients with moderate to severe rheumatoid arthritis. The 10 mg twice daily dose of tofacitinib is not an FDA-approved dose for rheumatoid arthritis but is approved in the dosing regimen for patients with ulcerative colitis. The postmarketing trial was designed to assess the risk of cardiovascular (CV) events, opportunistic infections and malignancy, and patients were required to be at least 50 years of age and have at least one CV risk factor to be eligible for participation in this study.

Postmarketing studies play a critical role in the FDA's efforts to ensure the safety of FDA-approved drugs and products. They can allow for further evaluation of potential safety issues or enable a better characterization of risk factors for known concerns. These studies provide vital information about the safety of the FDA-approved treatment so the FDA can help ensure that the benefits to the intended patients outweigh the risks. The FDA provides guidance and oversight of companies to ensure the studies are completed safely and in a timely manner. When significant safety issues do arise, the FDA works quickly to prevent further injury or deaths.

Xeljanz is approved for the treatment of certain adults with moderate to severe rheumatoid arthritis, active psoriatic arthritis, and moderate to severe ulcerative colitis. Patients treated with Xeljanz are at increased risk for developing serious infections that may lead to hospitalization or death. The most common serious infections reported with Xeljanz included pneumonia, cellulitis, herpes zoster, urinary tract infection, diverticulitis and appendicitis.

For more information:

• Drug Safety Communication

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation's food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.

Media Inquiries: Amanda Turney, 301-796-2969, [email protected]

SOURCE U.S. Food and Drug Administration

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