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Early Detection of PML May Lessen Damage Done to MS Patients Using Tysabri

January 16, 2017

Progressive multifocal leukoencephalopathy (PML) in multiple sclerosis patients treated with Tysabri is linked to better outcomes if the condition does not give rise to actual symptoms and is diagnosed early. Limited brain lesions and more protective immune responses were also seen in patients who fared better, but researchers underscored that their findings are still uncertain, considering the study’s small size.

The findings also confirm that brain scans via magnetic resonance imaging (MRI) are valuable for monitoring patients using Tysabri for signs of PML. The study, “Natalizumab-Related Progressive Multifocal Leukoencephalopathy in Multiple Sclerosis: Findings from an Italian Independent Registry,” was published in the journal PLOS ONE.

Tysabri is an effective MS therapy, but one associated with an increased risk of developing PML, which an opportunistic infection of the central nervous system (CNS) is caused by the John Cunningham polyomavirus (JCV).

To better understand the factors associated with PML, a research team from Sapienza University in Italy followed a group of 39 MS patients who were diagnosed with the condition after being treated with Tysabri. The patients were followed for one year.

One-third of the group had previously received one or more immunosuppressive drugs before starting Tysabri treatment. They received an average of 38.6 infusions before developing PML, but the number varied greatly among patients, with a range of 11 to 86.

One patient developed the condition during the first year of treatment, and five (making up 12.8 percent) after the 64th Tysabri infusion. But the majority of patients were relatively evenly spaced between these two extremes.

A closer look at patient characteristics, linked to the length of Tysabri treatment before PML diagnosis, revealed that the 10 patients who fell ill before the 24th infusion were older when they initiated Tysabri treatment. In most cases, 84.6 percent, PML was suspected when the patients started showing sudden deterioration in neurological functions, including the ability to think and move. Other symptoms were epilepsy and hallucinations.

The remaining patients did not develop specific symptoms — a condition known as asymptomatic PML. In these cases, doctors instead suspected PML when they noted unusual changes on MRI scans. All tested positive for antibodies against JCV. Interestingly, researchers noted that patients in whom the infection only caused cognitive problems were diagnosed almost twice as quickly as those with other brain symptoms.

Potential predictive factors of asymptomatic PML identified by the team were more localized brain lesions and gadolinium-enhancement detected by MRI, as well as lower viral load. These were associated with a lesser increase in disability. Gadolinium-enhanced brain lesions show inflammatory changes, and researchers believe that these brain imaging findings may indicate an early attempt by the body to get rid of the virus. Nevertheless, the team cautioned that the studied group was small, and that the findings can only be considered preliminary.