Immunex, the makers of etanercept (Enbrel®), have revised the prescribing information for etanercept due to recent reports of rare adverse events. These adverse events have included central nervous system demyelinating disorders such as multiple sclerosis, myelitis, optic neuritis, as well as blood disorders including pancytopenia and aplastic anemia. In all cases, any causal relationship to etanercept remains unclear, although other tumor necrosis factor antagonists have been associated with an increase in disease activity when administered to some patients with pre-existing multiple sclerosis. Additionally, although the majority of patients who developed pancytopenia while receiving etanercept had recent or concurrent therapy with other anti-rheumatic medications known to have the potential to decrease blood counts, such as methotrexate and leflunomide, some patients were receiving only etanercept. It has been advised that etanercept be prescribed with caution in patients with preexisting or recent-onset central nervous system demyelinating disorders and in patients with a history of hematologic abnormalities. The following are copies of the revised drug insert sections:
Rare cases of central nervous system demyelinating disorders have been described in spontaneous adverse events reports (see ADVERSE REACTIONS). The causal relationship to ENBREL therapy remains unclear. However, while no clinical trials have been performed evaluating ENBREL therapy in patients with multiple sclerosis, other TNF antagonists administered to patients with multiple sclerosis have been associated with increases in disease activity. Prescribers should exercise caution in considering the use of ENBREL in patients with preexisting or recent-onset central nervous system demyelinating disorders.
Rare reports of pancytopenia, including aplastic anemia, some with a fatal outcome, have been reported in patients with rheumatoid arthritis treated with ENBREL (see ADVERSE REACTIONS). The causal relationship to ENBREL therapy remains unclear. Although no high risk group had been identified, caution should be exercised in patients being treated with ENBREL who have a previous history of significant hematologic abnormalities. All patients should be advised that if they develop signs and symptoms suggestive of blood dyscrasias or infection (e.g., persistent fever, bruising, bleeding, pallor) while on ENBREL, they should seek immediate medical attention. If significant hematologic abnormalities are confirmed, consideration should be given to discontinuation of ENBREL therapy.
Editorial Comment: The numbers of cases of these adverse events is very low in contrast to the 80,000 patients treated with Enbrel since November 1998, and thus the risk of developing these conditions appears to be extremely rare. However, the adverse events described are very serious and physicians need to be aware of these potential side effects when treating patients and to report further cases to the FDA. We note that on review of the available data, the FDA has not changed its current recommendations for monitoring patients on Enbrel therapy.