October 20112 – Nalalizumab PML Update

Bloomgren et al. Risk of natalizumab-associated progressive multifocal leukoencephalopathy.N Engl J Med. 2012 May 17;366(20):1870-80.

With regards to antibody testing, with the introduction of the generation 2 assay, preliminary data suggest that ~5-10% of patients will change serostatus from anti-JCV antibody negative to positive on retest. These MSers include true seroconverters, and those with anti-JCV antibody levels that fluctuate around the cut-point of the anti-JCV assay.

As of 3rd October 2012, 98 natalizumab-treated MS PML MSers with known pre-PML anti-JCV antibody status who had samples tested for anti-JCV antibodies, all of which were collected at least 6 months prior to PML diagnosis (range 6-187 months).

Of these 98 MSers:

1. 96 (98%) MSers tested anti-JCV antibody positive at all time points where samples were available. 
2. 1 recent MSer (1%) tested anti-JCV antibody negative 9 months prior to PML diagnosis and anti-JCV antibody positive 6.5 months prior to PML diagnosis. The MSer had > 5 years of natalizumab therapy + prior IS use.
3. 1 MSer (1%) tested anti-JCV antibody negative 9 months prior to PML diagnosis; no additional pre-PML samples were available. The patient had received ~ 3-4 years of therapy + no prior IS use. 

The penultimate slide in deck depicts data on outcomes on PML cases as presented by Dong-Si et al. Functional disability after natalizumab-associated PML in a large cohort of survivors. P108.

“The latest PML figures from Biogen-Idec suggest that natalizumab-associated PMLis still an epidemic with 298 confirmed cases. Hopefully, the increase in the rate of the number of cases with eventually decrease as more, and more, clinicians derisk their practice, by either not starting natalizumab in MSers who are JCV seropositive or by switching JCV seropositive subjects onto less risky therapies Once the rate of increase has plateaued we can start referring to the problem as having become endemic.”