Risk of PML on natalizumab

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

BACKGROUND: Progressive multifocal leukoencephalopathy (PML) is associated with natalizumab treatment. Biogen-Idec quantified the risk of PML in MSers, according to the presence or absence of three risk factors: positive status with respect to anti-JC virus antibodies, prior use of immunosuppressants, and increasing duration of natalizumab treatment.

METHODS: Data from postmarketing sources, clinical studies, and an independent Swedish registry were used to estimate the incidence of PML among natalizumab-treated MSers, according to positive or negative status with respect to anti-JC virus antibodies, prior or no prior use of immunosuppressants, and duration of treatment (1 to 24 months vs. 25 to 48 months). Blood samples were available for anti-JC virus antibody testing from 5896 MSers and from 54 MSers who were treated with natalizumab and in whom PML later developed.

RESULTS: As of February 29, 2012, there were 212 confirmed cases of PML among 99,571 MSers treated with natalizumab (2.1 cases per 1000 patients). All 54 MSers with PML for whom samples were available before the diagnosis were positive for anti-JC virus antibodies. When the risk of PML was stratified according to three risk factors, the risk of PML was lowest among the MSers who were negative for anti-JC virus antibodies, with the incidence estimated to be 0.09 cases or less per 1000 patients (95% confidence interval [CI], 0 to 0.48). MSers who were positive for anti-JC virus antibodies, had taken immunosuppressants before the initiation of natalizumab therapy, and had received 25 to 48 months of natalizumab treatment had the highest estimated risk (incidence, 11.1 cases per 1000 patients [95% CI, 8.3 to 14.5]).

CONCLUSIONS: Positive status with respect to anti-JC virus antibodies, prior use of immunosuppressants, and increased duration of natalizumab treatment, alone or in combination, were associated with distinct levels of PML risk in natalizumab-treated MSers. 

“This study is the published results of the monthly safety update we provide you via this blog. Therefore it is not really news. I must complement Biogen-Idec and Elan for doing a great job with de-risking Natalizumab therapy. Knowing what your risk is is better than being uncertain. What they now need to do is produce a calculator so that you can individualise risk further. They have the data so it should not be too difficult to programme.”

CoI: Please note that this study was funded by Biogen Idec and Elan Pharmaceuticals.

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