Tuesday, September 04, 2012

natalizumab Omar Khan AAN 2012 notes

These are random notes of interest
 
1  Natalizumab was originally used for MS relapses in the 1990s, published in Neurology; negative study but a secondary outcome , on gad enhancement was positive.
 
2. A later trial by David Miller, sequential trial was also positive and focus changed.  There also was a resurgence of disease activity noted even then when treatment ceased.
 
3.   Khan open label study sequential failure on GA/IFN then change to NAT with no change with first switch, but dramatic decline in RR after second switch to NAT with significant MRI findings as well. Old study, about to be published.
 
4.  Suggests usefulness in non aggressive "run of mill " disease.  Tissue repair study with voxel wise MTR imaging, tracking lesions longitudinally
 
5. Risk management: usually 5 issues: infusion reactions, NAB's, hepatotoxicity, malignancies, opportunistic infections.  Rare cases of toxo, lymphoma but PML is king
 
PML-- mean duration of dosing was 34.1 months, range 8-67 doses.  Overall incidence is 2.08/1000 (CI 95 % 1.8 to 2.39) 3 risk factors. 
 
42 patients have died, 159 alive (79 %) but 80 % plus have severe disability among survivors.
 
3-4 x rise in risk with prior IS use, even one dose, across board therapies.
 
JCV Ab conversion rate is approximately 2-3 percent per year
 
6.  "Not a clear path" how to treat patients when they come off natalizumab

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