TY - JOUR
T1 - Immune reconstitution inflammatory syndrome in natalizumab-associated PML
AU - Tan, I. L.
AU - McArthur, J. C.
AU - Clifford, D. B.
AU - Major, E. O.
AU - Nath, A.
N1 - Funding Information:
Dr. Tan reports no disclosures. Dr. McArthur serves on a scientific advisory board for CNS Bio Services; receives publishing royalties for Current Therapy in Neurologic Disease, 7th Edition (Mosby, 2006); is an author on patents re: Device for thermal stimulation of small neural fibers and Immunophilin ligand treatment of antiretroviral toxic neuropathy; and receives research support from Biogen Idec, Pfizer Inc., the NIH, the National Multiple Sclerosis Society, and the Foundation for Peripheral Neuropathy. Dr. Clifford serves/has served on scientific advisory boards for Biogen Idec, Elan Corporation, Roche, Forest Laboratories, Inc., Genentech, Inc., GlaxoSmithKline, Millennium Pharmaceuticals, Inc., Schering-Plough Corp., Bristol-Meyers Squibb, and Genzyme Corporation; received speaker honoraria and funding for travel from GlaxoSmithKline, Millennium Pharmaceuticals, Inc., and Genentech Inc.; has received research support from Pfizer Inc, Schering-Plough Corp., Bavarian Nordic, NeurogesX, GlaxoSmithKline, Tibotec Therapeutics, Boehringer Ingelheim, and Gilead Sciences, Inc.; and receives research support from the NIH (NIMH, NINDS, NIAID, and Fogarty Institutes). Dr. Major receives research support from the NIH/NINDS. Dr. Nath serves on scientific advisory boards for Biogen Idec and DioGenix, Inc.; serves as an Associate Editor for the Journal of Neurovirology ; may accrue revenue on patents re: Tat as an immunogen, Diosgenin for treatment of neurodegenerative diseases, Role of Kv channels in neuroregeneration and protection, Role of lominoid compounds as neuroprotective agents, and Tat ELISA; has served as a consultant for Nerveda Inc. and Elan Corporation; receives research support from the NIH; and has served as an expert advice in medico-legal cases.
PY - 2011/9/13
Y1 - 2011/9/13
N2 - Objective: To study the outcome of patients with multiple sclerosis (MS) and with natalizumabassociated progressive multifocal leukoencephalopathy (PML) and immune reconstitution inflammatory syndrome (IRIS). Methods: MedWatch reports from Biogen-Idec (manufacturer of natalizumab, Tysabri®) 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.
AB - Objective: To study the outcome of patients with multiple sclerosis (MS) and with natalizumabassociated progressive multifocal leukoencephalopathy (PML) and immune reconstitution inflammatory syndrome (IRIS). Methods: MedWatch reports from Biogen-Idec (manufacturer of natalizumab, Tysabri®) 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.
UR - http://www.scopus.com/inward/record.url?scp=80155208330&partnerID=8YFLogxK
U2 - 10.1212/WNL.0b013e31822e55e7
DO - 10.1212/WNL.0b013e31822e55e7
M3 - Article
C2 - 21832229
AN - SCOPUS:80155208330
VL - 77
SP - 1061
EP - 1067
JO - Neurology
JF - Neurology
SN - 0028-3878
IS - 11
ER -