PML risks linked to MS drug duration

PML risks linked to MS drug duration

1200 797 Peter Stevenson, PhD

Development of progressive multifocal leukoencephalopathy (PML) in multiple sclerosis (MS) patients is linked to treatment medications, not the MS itself, delegates heard at the recent Consortium of Multiple Sclerosis Centers (CMSC) annual meeting in Nashville, USA.

Arguably, PML stepped into the spotlight due to the significant number of HIV patients that developed the disease. While antiretroviral drugs have alleviated the risks in that population considerably, research into the prevalence of PML in MS patients has only more recently gathered momentum.

Natalizumab carries particularly high risk, Joseph R Berger (University of Pennsylvania, PA, USA) noted in an interview, but only when used continuously for more than eight months. Indeed, patients with a history of other immunosuppressant therapies, along with antibodies for the so-called John Cunningham (JC) virus – the driver for PML – can be expected to develop the disease at rate of between 1:50 and 1:100 when exposed to natalizumab for two years or more.

Beyond natalizumab, fingolimod and dimethyl fumarate also carry risk, albeit at lower levels. Only 19 and 5 cases of PML (February 2018) have been linked to these respective drugs, noted Dr Berger, compared to more than 750 cases for natalizumab (December 2017). Another trio of agents – alemtuzumab, ocrelizumab and teriflunomide – have unknown risk, he added.

But a key message from Dr Berger was that PML is potentially a preventable disease. To that end, regular MRI screening for PML should be emphasized, especially in patients receiving natalizumab therapy, taking particular note of red flags, including new neurological symptoms or increased levels of JC antibodies.

If a patient does develop PML, Dr Berger stressed that cessation of therapy in order to restore the immune system is crucial. Some data point towards the utility of plasma exchange in clearing natalizumab (in particular), he added, but the evidence is not clear enough to make solid conclusions at this time. Similarly, PML treatment strategies such as immunisations/inhibitors of DNA replication have also fallen short, largely due to “failed” clinical trials.

“Everything is experimental, with the exception of the one important thing, which is restoring the immune system,” he said in closing.


Dotinga R. PML prevention is possible, even when treating patients with aggressive MS. Clinical Neurology News, June 1, 2018. Available at:

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