Tumor Necrosis Factor-alpha (TNFα) Blockers: Label Change - Boxed Warning Updated for Risk of Infection from Legionella and Listeria

including Remicade (infliximab), Enbrel (etanercept), Humira (adalimumab), Cimzia (certolizumab pegol), and Simponi (golimumab)

AUDIENCE: Rheumatology, Gastroenterology, Oncology

ISSUE: FDA notified healthcare professionals that the Boxed Warning for the entire class of Tumor Necrosis Factor-alpha (TNFa) blockers has been updated to include the risk of infection from two bacterial pathogens, Legionella and Listeria. In addition, the Boxed Warning and Warnings and Precautions sections of the labels for all of the TNFa blockers have been revised so that they contain consistent information about the risk for serious infections and the associated disease-causing pathogens.

Patients treated with TNFa blockers are at increased risk for developing serious infections involving multiple organ systems and sites that may lead to hospitalization or death due to bacterial, mycobacterial, fungal, viral, parasitic, and other opportunistic pathogens.

BACKGROUND: The class of TNFa blockers are used to treat Crohn's disease, ulcerative colitis, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, plaque psoriasis, and/or juvenile idiopathic arthritis.

RECOMMENDATION: The risks and the benefits of TNFa blockers should be considered prior to initiating therapy in patients with chronic or recurrent infection and patients with underlying conditions that may predispose them to infection. See the Drug Safety Communication for a listing of recommendations for healthcare professionals and patients, as well as a data summary.

Healthcare professionals and patients are encouraged to report adverse events or side effects related to the use of these products to the FDA's MedWatch Safety Information and Adverse Event Reporting Program:

Complete and submit the report Online: www.fda.gov/MedWatch/report.htm
Download form or call 1-800-332-1088 to request a reporting form, then complete and return to the address on the pre-addressed form, or submit by fax to 1-800-FDA-0178
Read the MedWatch safety alert, including a link to the FDA Drug Safety Communication, at:

http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm270977.htm

Posted: September 2011

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Legionella - Every Infection Preventionist's Dream—Or Is It?

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Population variation in NAIP functional copy number confers increased cell death upon Legionella pneumophila infection.

Authors: Boniotto M, Tailleux L, Lomma M, Gicquel B, Buchrieser C, Garcia S, Quintana-Murci L Abstract The NAIP gene encodes an intracellular innate immunity receptor that senses flagellin. The genomic region containing NAIP presents a complex genomic organization and includes various NAIP paralogs. Here, we assessed the degree of copy number variation of the complete NAIP gene (NAIPFull) in various human populations and studied the functional impact of such variation on host cell fate using Legionella pneumophila as an infection model. We determined that African populations have a NAIPFull duplication at a higher frequency than Europeans and Asians, with an increased transcription of the gene. In addition, we demonstrated that a higher amount of the NAIPFull protein dramatically i...

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FDA issues label change for TNF-alpha blockers to include risk of infection from Legionella and Listeria

FDA has notified healthcare professionals that the Boxed Warning for the entire class of Tumor Necrosis Factor-alpha (TNFα) blockers has been updated to include the risk of infection from 2 bacterial pathogens, Legionella and Listeria. (Source: Modern Medicine)

View the original article here

Tumor Necrosis Factor-alpha (TNFα) Blockers: Label Change - Boxed Warning Updated for Risk of Infection from Legionella and Listeria

including Remicade (infliximab), Enbrel (etanercept), Humira(adalimumab), Cimzia (certolizumab pegol), and Simponi(golimumab)AUDIENCE: Rheumatology, Gastroenterology, OncologyISSUE: FDA notified healthcare professionals that the... (Source: Drugs.com - Pharma News)

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Biologists discover new way in which bacteria hijack healthy cells during infection

Purdue University biologists identified a new way in which bacteria hijack healthy cells during infection, which could provide a target for new antibiotics.

Zhao-Qing Luo, the associate professor of biological sciences who led the study, said the team discovered a new enzyme used by the bacterium Legionella pneumophila - which causes Legionnaires' disease - to control its host cell in order to take up residence.

"Legionnaires' disease is a severe form of pneumonia, and this finding could lead to the design of a new therapy that saves lives," Luo said. "At the same time it also provides great insight into a general mechanism of both bacterial infection and cell signaling events in higher organisms including humans."

Successful infection by Legionella pneumophila requires the delivery of hundreds of proteins into the host cells that alter various functions to turn the naturally hostile environment into one tailor-made for bacterial replication. These proteins tap into existing communication processes within the cells in which an external signal, such as a hormone, triggers a cascade of slight modifications to proteins that eventually turns on a gene that changes the cell's behavior, he said.

"Pathogens are successful because they know how information in our cells is relayed and they amplify some signals and block others in order to evade the immune system and keep the cell from defending itself," Luo said. "Despite our understanding of this, we do not know much about how the proteins delivered by the bacteria accomplish this - how they work. This time we were able to pinpoint an enzyme and see how it disrupted and manipulated a specific signaling pathway in order to create a better environment for itself."

The signaling pathway involved was only recently identified, and the discovery by Luo and graduate student Yunhao Tan also provides a key insight into its process. A paper detailing their National Institutes of Health-funded work is published online in the current issue of the journal Nature.

The signaling pathway involves a new form of protein modification called AMPylation in order to relay instructions to change cell behavior and has been found to be used by almost all organisms, Luo said.

The bacterial enzyme discovered by the Purdue team, named SidD, reverses or stops the AMPylation process, he said.

"It had not been known before if the AMPylation signaling process was reversible or if it was regulated by specific enzymes," Luo said. "Now we know that it is, and we have a more complete picture that will allow us to use it as a scientific tool to learn more about complex cellular processes. By being able to turn the signaling on and off, we can control different activities and detect mechanisms we wouldn't see under normal physiological conditions."

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