Humira, Enbrel and other Tumor Necrosis Factor-alpha blockers are useful in treating serious autoimmune disorders, such as Crohn’s disease and rheumatoid arthritis, which cause constant inflammation in the body. However, the FDA recently notified healthcare professionals that the labels on all TNF blockers were being updated to include warnings about the risk for serious infections — including two bacterial pathogens called Legionella and Listeria — which may lead to hospitalization or death.
TNF Blockers: An Overview
Drugs like Humira and Enbrel belong to a class known as Tumor Necrosis Factor-alpha (TNFα or TNF) blockers, which are used to treat autoimmune conditions such as rheumatologic disorders, inflammatory bowel disease and psoriasis.
These conditions occur because of a problem in the body’s immune system. Normally, the immune system helps to protect the body from illness. But in people who have autoimmune disorders, the body cannot tell the difference between natural body tissue and foreign substances. The result is an overactive immune response, which leads to chronic inflammation and conditions like Crohn’s disease, ulcerative colitis, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, plaque psoriasis and juvenile idiopathic arthritis.
TNF blockers are immunosuppressants — these drugs inhibit or prevent the activity of the immune system. Ideally, immunosuppressants should normalize the immune system, in order to prevent the overactive response and chronic inflammation.
Unfortunately, immunosuppressants carry a serious risk. They often lower the ability of the immune system to fight rare infections — leaving the body susceptible to illnesses that usually do not cause disease in healthy people. The infections may involve multiple organs or tissues and could lead to hospitalization or death, due to various types of pathogens — including bacterial, mycobacterial (example: tuberculosis), fungal (examples: histoplasmosis, aspergillosis, candidiasis), viral (example: hepatitis B) or parasitic.
The risk of infection caused by TNF blockers is not new and is long established.
Recently, however, the FDA added to the list of possible infection types. The FDA now believes patients who use TNF blockers may be at an increased risk of developing serious infections as a result of two bacterial pathogens called, Legionella and Listeria.
FDA Studies and Recommendation
The recent association of TNF blockers and infections forced the FDA to issue a Drug Safety Communication on September 7, 2011 announcing that warning labels on all TNF blockers will be updated to reflect the risk of Listeria and Legionella. Additionally, the labels of all TNF blockers will be revised in order to ensure consistent information pertaining to all risks of serious infections and the disease-causing pathogens.
The label update comes as a response to cases of FDA-reported Legionella pneumonia in patients treated with TNF blockers. According to the FDA, between 1999-2010, there were 80 patients who developed Legionella pneumonia, usually after taking the drug to treat rheumatoid arthritis. 14 of these patients died.
Another evaluation of the English-language medical literature found 23 additional cases of Legionella pneumonia after treatment with TNF blockers. Four of these were severe enough to require mechanical ventilation; five patients received treatment in the hospital intensive care unit. Three of the 23 patients died.
There have also been reports of Listeria-linked illnesses. Through English-language medical literature, the FDA traced 26 cases of infections due to Listeria monocytogenes, which resulted in meningitis, bacteremia, endophthalmitis and sepsis. Seven deaths were reported.
Due to these risks, the FDA is recommending doctors take caution in recommending TNF blockers to patients with a history of infection or to patients who may have underlying conditions that predispose them to infection.
The TNF class includes 5 medications in the United States: Remicade (infliximab), Enbrel (etanercept), Humira (adalimumab), Cimzia (certolizumab pegol), and Simponi (golimumab).
What is Legionella?
Legionella is a bacterium that was discovered in 1976 and can only be transmitted through the inhalation of mist droplets containing the bacteria. Common sources are cooling towers, swimming pools, fountains, hot-water systems, ponds and creeks.
While Legionella is not a threat to most healthy individuals, people with compromised immune systems can be infected. Once a person has been infected, initial symptoms are flu-like, including fever, chills and dry cough. However, Legionella can advance into pneumonia.
What is Listeria?
Listeria is a similarly rare infection, but people with weakened immune systems may be infected after eating food contaminated with bacteria. The two main manifestations of Listeria are sepsis and meningitis. Both meningitis and sepsis are severe illnesses. Sepsis occurs when the body is overcome with bacteria, leading to a whole-body inflammatory state. Meningitis is a bacteria infection of the brain.