RESUMEN
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. CONCLUSION: Postlicensure surveillance suggests that L monocytogenes infection may be a serious complication of treatment with TNFalpha-neutralizing agents, particularly infliximab.
Asunto(s)
Anticuerpos Monoclonales/efectos adversos , Antirreumáticos/efectos adversos , Artritis Reumatoide/tratamiento farmacológico , Inmunoglobulina G/efectos adversos , Listeriosis/etiología , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Adolescente , Adulto , Sistemas de Registro de Reacción Adversa a Medicamentos , Anciano , Artritis Reumatoide/epidemiología , Artritis Reumatoide/microbiología , Etanercept , Femenino , Humanos , Infliximab , Listeriosis/epidemiología , Masculino , Persona de Mediana Edad , Receptores del Factor de Necrosis Tumoral , Factor de Necrosis Tumoral alfa/inmunologíaRESUMEN
OBJECTIVE: Two tumor necrosis factor alpha (TNFalpha) antagonists were recently licensed in the US. Infliximab was licensed in 1998 for the treatment of Crohn's disease (CD), and since 1999, it has been licensed in combination with methotrexate for treatment of rheumatoid arthritis (RA). Etanercept was licensed in 1998 for treatment of RA and, more recently, for juvenile RA and psoriatic arthritis. Because of potential immunosuppression related to use of anti-TNFalpha agents, we sought to identify postlicensure cases of opportunistic infection, including histoplasmosis, in patients treated with these products. METHODS: The US Food and Drug Administration's (FDA) passive surveillance database for monitoring postlicensure adverse events was reviewed to identify all reports received through July 2001 of histoplasmosis in patients treated with either infliximab or etanercept. RESULTS: Ten cases of Histoplasma capsulatum (HC) infection were reported: 9 associated with infliximab and 1 associated with etanercept. In patients treated with infliximab, manifestations of histoplasmosis occurred within 1 week to 6 months after the first dose and typically included fever, malaise, cough, dyspnea, and interstitial pneumonitis. Of the 10 patients with histoplasmosis, 9 required treatment in an intensive care unit, and 1 died. All patients had received concomitant immunosuppressive medications in addition to infliximab or etanercept, and all resided in HC-endemic regions. CONCLUSION: Postlicensure surveillance suggests that acute life-threatening histoplasmosis may complicate immunotherapy with TNFalpha antagonists, particularly infliximab. Histoplasmosis should be considered early in the evaluation of patients who reside in HC-endemic areas in whom infectious complications develop during treatment with infliximab or etanercept.