What is the risk of infection associated with Enbrel (etanercept)?

From the Guidelines

Enbrel (etanercept) increases the risk of infections, particularly in patients taking concurrent immunosuppressants, with a higher risk of reactivation of latent tuberculosis and other opportunistic infections. The risk of infection is a significant concern when using etanercept, as it suppresses the immune system by blocking tumor necrosis factor (TNF), which is important for fighting infections 1. Common infections associated with Enbrel include upper respiratory tract infections, sinusitis, and bronchitis, while more serious infections can include tuberculosis, invasive fungal infections, bacterial sepsis, and opportunistic infections such as endemic fungi, atypical mycobacteria, candidiasis, aspergillosis, cytomegalovirus, herpes zoster, Pneumocystis, and Listeria monocytogenes 1.

According to a more recent study, the risk of hepatitis B reactivation is lower with etanercept (approximately 1-5%) compared to other TNF-α inhibitors such as infliximab 1. However, patients taking Enbrel should still be vigilant for signs of infection such as fever, cough, shortness of breath, flu-like symptoms, or wounds that don't heal properly. Before starting Enbrel, patients should be screened for tuberculosis and other infections, and during treatment, they should avoid live vaccines and promptly report any signs of infection to their healthcare provider 1.

Key considerations for minimizing the risk of infection in patients taking Enbrel include:

• Screening for tuberculosis and other infections before starting treatment
• Avoiding live vaccines during treatment
• Promptly reporting any signs of infection to their healthcare provider
• Temporarily stopping treatment if a serious infection develops
• Being aware of the higher risk of infection in older adults, those with diabetes, and patients taking other immunosuppressive medications simultaneously 1.

From the FDA Drug Label

Patients treated with Enbrel are at increased risk for developing serious infections involving various organ systems and sites that may lead to hospitalization or death Opportunistic infections due to bacterial, mycobacterial, invasive fungal, viral, parasitic, or other opportunistic pathogens including aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, histoplasmosis, legionellosis, listeriosis, pneumocystosis, and tuberculosis have been reported with TNF-blockers.

The risk of infection associated with Enbrel (etanercept) is increased, with patients being at risk for developing serious infections that may lead to hospitalization or death, including:

• Opportunistic infections due to bacterial, mycobacterial, invasive fungal, viral, parasitic, or other opportunistic pathogens
• Tuberculosis, including reactivation of latent tuberculosis
• Invasive fungal infections, including histoplasmosis, coccidioidomycosis, candidiasis, aspergillosis, blastomycosis, and pneumocystosis
• Bacterial, viral, and other infections due to opportunistic pathogens, including Legionella and Listeria 2, 2, 2.

From the Research

Risk of Infection with Enbrel (Etanercept)

• The risk of infection associated with Enbrel (etanercept) is a significant concern, as it can increase the risk of serious infections, including opportunistic infections and re-activation of latent tuberculosis (LTB) infection 3, 4, 5, 6.
• Etanercept therapy has resulted in serious infections in some patients, and it should be used with caution in any patient with a history of recurring infections or with disease states that may predispose to infections 3.
• The most common adverse effects of etanercept treatment include injection site reactions and upper respiratory tract infections, which can be a sign of an increased risk of infection 3, 7.
• Patients receiving TNF-α inhibitors, including etanercept, are at high risk of infections, and a careful medical history, Mantoux test, and chest-x-ray should always be performed before starting treatment 4, 6.
• Particular attention should be paid to risk factors for Pneumocystis jirovecii infection, and hepatitis B and C virological follow-up should be considered during etanercept treatment 4, 6.

Strategies for Mitigating Infection Risk

• Appropriate vaccinations for influenza, S. pneumoniae, and HBV should be administered to decrease the risk of infection 6.
• Patients who are at high risk of herpes zoster reactivation would benefit from a second vaccination in adulthood when receiving etanercept 4, 6.
• A careful medical history and screening for latent infections should be performed before starting etanercept treatment to minimize the risk of infection 4, 6.