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Immune reconstitution inflammatory syndrome in natalizumab-associated PML.

Author(s): Tan IL, McArthur JC, Clifford DB, Major EO, Nath A

Affiliation(s): Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, USA.

Publication date & source: 2011-09-13, Neurology., 77(11):1061-7. Epub 2011 Aug 10.

Publication type: Comparative Study; Research Support, N.I.H., Extramural

OBJECTIVE: To study the outcome of patients with multiple sclerosis (MS) and with natalizumab-associated progressive multifocal leukoencephalopathy (PML) and immune reconstitution inflammatory syndrome (IRIS). METHODS: MedWatch reports from Biogen-Idec (manufacturer of natalizumab, Tysabri((R))) were reviewed which comprised all 42 cases of natalizumab-related PML cases since its reintroduction until March 2010. RESULTS: All except 2 patients with natalizumab-related PML were managed by discontinuation of natalizumab and plasmapheresis/immunoadsorption (PLEX/IA). Seventeen patients had contrast enhancement of PML lesions on neuroimaging at the time of diagnosis before withdrawal/removal of natalizumab (early-PML-IRIS) and 23 patients developed contrast enhancement only after withdrawal/removal of natalizumab (late-PML-IRIS). All patients developed IRIS. IRIS was defined as worsening of neurologic deficits during the immune reconstitution following discontinuation of natalizumab, corroborated by inflammatory changes on neuroimaging. Following PLEX/IA, JC viral load in CSF increased by >10 fold in those with early-PML-IRIS but <2 fold in late-PML-IRIS. IRIS developed earlier and was more severe in early-PML-IRIS (p < 0.05). At the last follow-up, all patients had worse EDSS scores but this was higher in patients with early-PML-IRIS compared to those with late-PML-IRIS (p > 0.05). Mortality was comparable between the 2 groups, 29.4 +/- 11% vs 21.7 +/- 8.8%. Corticosteroid therapy during IRIS was associated with better Expanded Disability Status Scale outcome, p < 0.05. CONCLUSION: Early immunologic rebound in natalizumab-associated PML has worse survival and neurologic outcome. PLEX/IA may accelerate IRIS and its impact on the final outcome is unclear. Corticosteroid therapy provides a modest benefit and needs to be systemically studied in a controlled manner in the management of natalizumab-associated PML-IRIS.

Page last updated: 2011-12-09

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