Product Liability

Labels on TNFa blockers get stronger warning

The black box warning for a class of immunosuppressant drugs known as Tumor Necrosis Factor-alpha (TNFa) blockers is being updated to include the risk of potentially deadly infections from two bacterial pathogens, Legionella and Listeria. TNFa blockers are biologic products that include Remicade (infliximab), Enbrel (etanercept), Humira (adalimumab), Cimzia (certolizumab pegol), and Simponi (golmumab).

TNFa blockers are drugs used to treat Crohn’s disease, ulcerative colitis, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, plaque psoriasis, and/or juvenile idiopathic arthritis. Since TNFs blockers are immunosuprresants, patients who take these drugs are at increased risk of serious, including fatal, infections.

These infections can involve various organ systems and sites due to bacterial, mycobacterial (such as tuberculosis), fungal (including histoplasmosis, aspergillosis, candidiasis, coccidioidomycosis, blastomycosis, and pneumocystosis), viral (including hepatitis B), and other opportunistic pathogens. Pathogens are organisms that usually do not cause disease in healthy people but can cause serious illness in people with weakened immune systems.

The addition of Legionella and Listeria to the black box warning on TNFa blockers will provide doctors with more information about these opportunistic pathogens that can cause serious infections in patients treated with TNFa blockers.

There are currently five TNFa blockers available in the United States. Between 1999 and 2010, the FDA has received reports of 80 patients who developed Legionella pneumonia after having received infliximab, adalimumab, etanercept, and golimumab. Of the 80 patients, 14 died.

The FDA also noted reports of 23 patients who developed Legionella pneumonia after being treated with TNFa blockers for rheumatiologic disorders, inflammatory bowel disease, and psoriasis. Three of those patients died. One developed a second episode of Legionella pneumonia following re-initiation of a TNFa blocker.

The FDA also received reports of 26 patients with serious infections due to Listeria monocytogenes in patients treated with TNFa blockers, including meningitis, bacteremia, endophthalmitis, and sepsis. Seven fatalities were reported. In addition, the agency also identified fatal Listeria infections in a review of data regarding laboratory-confirmed infections that occurred in a pre-marketing phase 2 and phase 3 clinical trials and from post-marketing surveillance.

The pathogens Legionella and Listeria have been added to the Boxed Warning for the entire class of TNFa blockers.

Source: FDA