PMID- 24242357
OWN - NLM
STAT- MEDLINE
DCOM- 20140407
LR  - 20220330
IS  - 1531-8249 (Electronic)
IS  - 0364-5134 (Linking)
VI  - 75
IP  - 1
DP  - 2014 Jan
TI  - Progressive multifocal leukoencephalopathy after natalizumab discontinuation.
PG  - 108-15
LID - 10.1002/ana.24051 [doi]
AB  - OBJECTIVE: To identify cases of laboratory- or biopsy-confirmed progressive 
      multifocal leukoencephalopathy (PML) in patients with multiple sclerosis (MS) who 
      previously discontinued natalizumab (NTZ) for reasons unrelated to suspected or 
      proven PML and assess PML risk factors in these cases. METHODS: We searched the 
      US Food and Drug Administration Adverse Event Reporting System and MEDLINE for 
      reports submitted from 2006 to 2012 of laboratory-confirmed PML with symptom 
      onset >/=30 days following NTZ withdrawal. We only analyzed cases where NTZ 
      discontinuation was unrelated to suspected PML. RESULTS: Seventeen patients 
      discontinued NTZ for reasons unrelated to PML but were subsequently diagnosed 
      with the disease. The median NTZ duration was 47 monthly doses (range = 9-59 
      doses). All patients presented with compatible clinical symptoms within 6 months 
      following withdrawal, and PML was confirmed by brain biopsy or by identifying JC 
      virus in the cerebrospinal fluid by polymerase chain reaction. Immune 
      reconstitution inflammatory syndrome (IRIS) was reported in 11 patients. Eleven 
      patients (65%) received new MS treatments between NTZ discontinuation and PML 
      confirmation. No deaths were reported. At NTZ withdrawal, 16 patients (94%) had 
      >/=1 PML risk factor, including NTZ duration >/=2 years (n = 13), prior 
      immunosuppressive agents (n = 8), and reported anti-JC virus seropositivity 
      (n = 13). INTERPRETATION: NTZ-treated patients presenting clinically with PML 
      within 6 months after NTZ withdrawal frequently have pre-existing PML risk 
      factors. Clinicians need heightened awareness for new onset PML, IRIS, and MS 
      relapse in evaluating neurological decline following NTZ discontinuation. Ann 
      Neurol 2014;75:108-115.
CI  - (c) 2013 American Neurological Association.
FAU - Fine, Andrew J
AU  - Fine AJ
AD  - Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research, 
      US Food and Drug Administration, Silver Spring, MD.
FAU - Sorbello, Alfred
AU  - Sorbello A
FAU - Kortepeter, Cindy
AU  - Kortepeter C
FAU - Scarazzini, Linda
AU  - Scarazzini L
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Ann Neurol
JT  - Annals of neurology
JID - 7707449
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Natalizumab)
SB  - IM
CIN - Ann Neurol. 2014 Mar;75(3):462. PMID: 24442606
CIN - Ann Neurol. 2014 Mar;75(3):462-3. PMID: 24443375
MH  - Adult
MH  - Adverse Drug Reaction Reporting Systems/*trends
MH  - Antibodies, Monoclonal, Humanized/*adverse effects
MH  - Female
MH  - Humans
MH  - Leukoencephalopathy, Progressive Multifocal/*chemically 
      induced/*diagnosis/immunology
MH  - Male
MH  - Middle Aged
MH  - Multiple Sclerosis/*drug therapy/immunology
MH  - Natalizumab
MH  - United States
MH  - Withholding Treatment/*trends
MH  - Young Adult
EDAT- 2013/11/19 06:00
MHDA- 2014/04/08 06:00
CRDT- 2013/11/19 06:00
PHST- 2013/02/07 00:00 [received]
PHST- 2013/10/21 00:00 [revised]
PHST- 2013/11/08 00:00 [accepted]
PHST- 2013/11/19 06:00 [entrez]
PHST- 2013/11/19 06:00 [pubmed]
PHST- 2014/04/08 06:00 [medline]
AID - 10.1002/ana.24051 [doi]
PST - ppublish
SO  - Ann Neurol. 2014 Jan;75(1):108-15. doi: 10.1002/ana.24051.