This article is part of the Arthritis Archives.
Dateline: May 20, 1999
Physicians Advised About Enbrel
In a recent FDA Talk Paper, physicians were advised about new safety concerns regarding the use of Enbrel (etanercept), the first of a new class of drugs for rheumatoid arthritis known as biologic response modifiers. Enbrel was approved in November 1998.
Since the FDA approval of Enbrel, approximately 25,000 patients have been treated with the drug. Thirty of the 25,000 patients reportedly developed serious infections, including sepsis. Six of the 30 patients died within two to sixteen weeks after beginning treatment with Enbrel. It should be noted that several of these rheumatoid arthritis patients had a prior history of:
Although it is recognized that rheumatoid arthritis patients have a predisposition to infections, the question remains as to whether Enbrel contributed directly to the aforementioned incidents. Suspiciously many of the infections appeared shortly after initiation of treatment with Enbrel. Immunex Corporation, the makers of Enbrel, maintains that the mortality rate due to infection reported during the 5 month postmarket period is in line with the mortality rate observed in clinical trials and also in the population of rheumatoid arthritis patients not taking Enbrel.
Controlled clinical studies have not indicated an increase in serious infections in patients taking Enbrel. The FDA has requested that Immunex initiate additional studies to assess the risk of serious infection related to Enbrel treatment. Currently 1500 clinical trial participants are being monitored for the longterm safety and efficacy of Enbrel use.
Weighing The Risks Versus Benefits
Until the controlled studies are completed and result in conclusions, it is not definitive whether Enbrel is a contributory factor in causing serious infections in patients with rheumatoid arthritis. Even so, the FDA is advising that physicians consider the adverse reports when weighing the risks versus benefits of prescribing Enbrel. The labeling on Enbrel has also been revised to include the new information. The original label for Enbrel warned that the drug not be used for patients who develop a serious infection or who have sepsis. The updated label advises physicians not to prescribe Enbrel for patient who have an active infection, including chronic or localized infections. It is also now recommended that patients who develop an infection while on Enbrel be closely watched. History of recurring infections and underlying conditions which predispose patients to infections must signal a physician to proceed with caution.
Phase III Pivotal Study
Just two days before the FDA Talk Paper was published, newswires carried the story of the positive results from a Phase III pivotal study of Enbrel which evaluated rheumatoid arthritis patients with early, active disease. The results of the study indicated that Enbrel slowed progression of the disease and reduced the signs and symptoms. Based on these study results, Immunex intends to apply for an expanded label for Enbrel indicating its use "to slow structural joint damage in patients with active rheumatoid arthritis and to improve the signs and symptoms of patients with early, active rheumatoid arthritis".
Sources: New Warning For Arthritis Drug Enbrel, FDA Talk Paper, 5/12/99; Positive Results Of Pivotal Phase III Trial With Enbrel In Patients With Early Active RA, PRNewswire 5/10/99; Immunex & Wyeth-Ayerst Announce Label Update For Enbrel, PRNewswire 5/10/99
First published: 5/20/1999