Listeria monocytogenes infection as a complication of treatment with tumor necrosis factor alpha-neutralizing agents.
OBJECTIVE
Tumor necrosis factor alpha (TNFalpha) has been implicated in the pathogenesis of certain inflammatory diseases. Two TNFalpha-neutralizing agents are licensed in the US. Infliximab is licensed for the treatment of Crohn's disease (CD) and, when used with methotrexate, for the treatment of rheumatoid arthritis (RA). Etanercept is licensed for the treatment of RA, including juvenile RA, and, more recently, was licensed for the treatment of psoriatic arthritis. Because of the potential for decreased host resistance to infectious agents due to treatment with anti-TNFalpha agents, we sought to evaluate postlicensure cases of opportunistic infection, including Listeria monocytogenes, in patients treated with these products.


METHODS
The FDA Adverse Event Reporting System, a passive monitoring system, was reviewed to identify all reports of adverse events (through December 2001) associated with L monocytogenes infection in patients treated with infliximab or etanercept.


RESULTS
Fifteen cases of L monocytogenes infection associated with infliximab or etanercept treatment were identified. In 14 of these cases, patients had received infliximab. The median age of all patients was 69.5 years (range 17-80 years); 53% were female. Six deaths were reported. Among patients for whom an indication for use was reported, there were 9 patients (64%) with RA and 5 patients (36%) with CD (information was not reported for 1 patient). All patients for whom information was reported were receiving concurrent immunosuppressant drugs.


CONCLUSIONS
Postlicensure surveillance suggests that L monocytogenes infection may be a serious complication of treatment with TNFalpha-neutralizing agents, particularly infliximab.
Slifman
Nancy R
NR
Center for Biologics Evaluation and Research, FDA, Rockville, Maryland, USA.
Gershon
Sharon K
SK
Lee
Jong-Hoon
JH
Edwards
Evelyne T
ET
Braun
M Miles
MM
D000293:Adolescent; D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects*; D018501:Antirheumatic Agents / Q000009:adverse effects*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000453:epidemiology / Q000382:microbiology; D000068800:Etanercept; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000009:adverse effects*; D000069285:Infliximab; D008088:Listeriosis / Q000453:epidemiology / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000276:immunology
D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068800:Etanercept