Namita Kothary1, Ida-Lina Diak2, Allen Brinker2, Shewit Bezabeh2, Mark Avigan2, Gerald Dal Pan2. 1. Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland. Electronic address: namita.kothary@fda.hhs.gov. 2. Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland.
Abstract
BACKGROUND: Progressive multifocal leukoencephalopathy (PML), a rare, potentially fatal demyelinating disease, affects primarily immunocompromised individuals. The Food and Drug Administration (FDA) received reports of PML associated with efalizumab (Raptiva), a biologic agent approved for psoriasis. In July 2009, efalizumab was voluntarily withdrawn from the US market because of the risk of PML. OBJECTIVE: To describe 3 cases of PML in psoriasis patients treated with efalizumab. METHODS: The FDA's Adverse Event Reporting System (AERS) database was searched for post-marketing reports of PML associated with biologic agents that are FDA approved for psoriasis (adalimumab, alefacept, efalizumab, etanercept, infliximab) from market approval to January 30, 2009. RESULTS: Twelve cases suggestive of PML were identified: adalimumab (1), efalizumab (4), etanercept (3), and infliximab (4). Efalizumab was the only drug with cases reporting PML in the setting of psoriasis. All cases of PML in efalizumab-treated patients presented 3 years or more after treatment initiation and resulted in death. Cases of PML in patients treated with adalimumab, etanercept, or infliximab occurred in patients treated for conditions other than psoriasis and were confounded by the use of other immunosuppressive therapies or were not confirmed PML cases. LIMITATIONS: AERS data are limited because of an underreporting of spontaneous post-marketing adverse events and variable quality and quantity of information provided. CONCLUSIONS: These cases suggest that prolonged efalizumab therapy is a risk factor for PML. Although the cases reported treatment for longer than 3 years, a specific treatment duration that does not place patients at risk for PML has not been defined.
BACKGROUND: Progressive multifocal leukoencephalopathy (PML), a rare, potentially fatal demyelinating disease, affects primarily immunocompromised individuals. The Food and Drug Administration (FDA) received reports of PML associated with efalizumab (Raptiva), a biologic agent approved for psoriasis. In July 2009, efalizumab was voluntarily withdrawn from the US market because of the risk of PML. OBJECTIVE: To describe 3 cases of PML in psoriasispatients treated with efalizumab. METHODS: The FDA's Adverse Event Reporting System (AERS) database was searched for post-marketing reports of PML associated with biologic agents that are FDA approved for psoriasis (adalimumab, alefacept, efalizumab, etanercept, infliximab) from market approval to January 30, 2009. RESULTS: Twelve cases suggestive of PML were identified: adalimumab (1), efalizumab (4), etanercept (3), and infliximab (4). Efalizumab was the only drug with cases reporting PML in the setting of psoriasis. All cases of PML in efalizumab-treatedpatients presented 3 years or more after treatment initiation and resulted in death. Cases of PML in patients treated with adalimumab, etanercept, or infliximab occurred in patients treated for conditions other than psoriasis and were confounded by the use of other immunosuppressive therapies or were not confirmed PML cases. LIMITATIONS: AERS data are limited because of an underreporting of spontaneous post-marketing adverse events and variable quality and quantity of information provided. CONCLUSIONS: These cases suggest that prolonged efalizumab therapy is a risk factor for PML. Although the cases reported treatment for longer than 3 years, a specific treatment duration that does not place patients at risk for PML has not been defined.
Authors: A Bellizzi; C Nardis; E Anzivino; D M Rodìo; D Fioriti; M Mischitelli; F Chiarini; V Pietropaolo Journal: J Neurovirol Date: 2012-02 Impact factor: 2.643