Stratifying PML Risk in Multiple Sclerosis

The risk of PML in patients with MS receiving Tysabri is a concern.

The risk of progressive multifocal leukoencephalopathy (PML) in patients on treatment with Tysabri for multiple sclerosis (MS) is one of the chief concerns about the use of this otherwise extremely effective therapy. For patients who have MS with active disease, Tysabri is one of the most efficacious treatments for decreasing the incidence of attacks. But the use of this therapy is compromised by concerns about the incidence of PML in patients on therapy.

Generally, patients on Tysabri for long periods and with previous exposure to significant courses of immunosuppressant medications are considered to be at increased risk for PML. Work over the past couple of years has shown that the risk of PML is associated with positive serology demonstrating previous exposure and immune reaction to the JC virus. Now, a new study has refined this understanding further and will be helpful for clinicians faced with the difficult choice about how to manage patients with MS on Tysabri who become positive for JC virus antibodies or are already positive for these antibodies.

In this study,¹ Plavina and colleagues examined the JC virus antibody index using a quantitative test allowing the calculation of a JC virus antibody index. By taking this approach and examining the data from many thousands of patients on Tysabri without PML compared with a much smaller number with PML, the authors were able to extract some additional risk factor information that is potentially helpful for clinicians.

The authors found that under an index value of 1.5 and with no prior immunosuppressant therapy, the risk of PML was very low (about 0.1% or below even when patients were on therapy for up to 6 years). This reflects a low risk considering the benefit in these patients of continued Tysabri treatment. On the other hand, with an index of greater than 1.5 the risk of PML is about 10 times higher and is about 1% in patients on Tysabri for long periods.

This study allows clinicians to help guide the choices of patients who are doing well on Tysabri when it is discovered that they have positive JC virus titers. It is important though to continue monitoring these patients who remain on Tysabri for potential increases in titer as this may indicate an increasing risk of PML.

The study appeared in the December 2014 issue of the Annals of Neurology.

References:

1. Plavina T, Subramanyam M, Bloomgren G, et al. Anti-JC virus antibody levels in serum or plasma further define risk of natalizumab-associated progressive multifocal leukoencephalopathy. Ann Neurol. 2014;76:802-812.