Food and Drug Administration
U.S. Department of Health and Human Services
Public Health Service 5600 Fishers Lane Rockville, MD 20857
FDA Talk Papers are prepared by the Press Office to guide FDA personnel in responding with consistency and accuracy to questions from the public on subjects of current interest. Talk Papers are subject to change as more information becomes available.
T99-22 Print Media: 301-827-6242
May 12, 1999
Consumer Inquiries: 888-INFO-FDA
FDA is advising physicians about new safety concerns regarding the use of etanercept (Enbrel), a product recently approved to treat moderate to severe rheumatoid arthritis (RA). New postmarketing reports indicate that certain patients receiving Enbrel have developed serious infections, including sepsis, and that several of these patients have died from their infections.
The Immunex Corporation, Seattle, Wash., the co-sponsor of Enbrel, (along with Wyeth-Ayerst Laboratories, Philadelphia, Pa.) is sending a "Dear Doctor" letter alerting physicians to the new safety concerns, reminding them of the current label warning and informing them that the labeling for Enbrel has been revised to incorporate the new information.
Enbrel was approved last November with labeling that says that it should not be given to patients with sepsis and should be discontinued if a patient develops a serious infection.
Because of new information obtained from adverse reaction reports to FDA and Immunex, the warning related to sepsis has been expanded to include patients with any active infection, including chronic or localized infections.
In addition, it is now recommended that patients who develop a new infection while being treated with Enbrel be monitored closely.
It is further recommended that physicians be cautious when considering prescribing Enbrel to patients with a history of recurring infections or with underlying conditions such as advanced or poorly controlled diabetes that may predispose them to infections.
Since the drug's approval, 30 of the estimated 25,000 patients treated with Enbrel are reported to have developed serious infections, including sepsis. Six of these patients died within two to sixteen weeks after starting treatment. A number of these RA patients had a history of chronic or recurrent infections, pre-existing infections, diabetes, or other conditions that predisposed them to infections.
Even though many RA patients are predisposed to infections, significant concerns remain that Enbrel may contribute to the occurrence of serious infections. Many of the infections occurred shortly after initiation of Enbrel therapy. In addition, a controlled study of Enbrel to treat sepsis showed a higher incidence of death in patients treated with Enbrel. Moreover, Enbrel inhibits the action of tumor necrosis factor, a component of the body's natural defenses against serious infection.
To date, controlled clinical studies have not shown an increase in serious infections in patients receiving Enbrel. FDA has requested that Immunex perform additional studies to assess the risk of serious infection related to Enbrel therapy.
At this time, without further controlled clinical studies, it is unclear whether Enbrel truly is the cause of the serious infections in patients with RA. However, as a precautionary measure, physicians should consider these new reports when assessing the risks and benefits of Enbrel.
Enbrel, a genetically engineered protein, was approved to treat patients with symptoms of moderate to severe, active RA who have not responded well to other treatments. It can significantly reduce pain and swollen joints in people disabled with RA, an autoimmune disease that affects more than two million Americans.
FDA requests that all cases of serious infection or sepsis occurring in patients taking Enbrel be reported to the agency through MEDWATCH. Reports to Medwatch should be made by phone to 1-800-FDA-1088, by fax to 1-800-FDA-0178, by mail to MEDWATCH, HF-2, FDA, 5600 Fishers Lane, Rockville, MD 20857. Reports can also be made through the internet at www.fda.gov/medwatch/. Health professionals may also contact Wyeth-Ayerst Product Information at 1-800-934-5556 or Immunex Professional Services at 1-800-IMMUNEX (1-800-466-8639).
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