Risk of Progressive Multifocal Leukoencephalopathy in Oral Therapies for Multiple Sclerosis


In launching this discussion, Patricia Coyle, MD, examines the oral immunosuppressive medications that have been shown to increase a multiple sclerosis (MS) patient’s risk of developing progressive multifocal leukoencephalopathy (PML).

“None of the 3 oral agents are cytotoxic. As a matter of fact, they’re not, for the most part, even considered immunosuppressive; they’re called immunomoulatory,” Coyle notes.

Although there is not enough research to determine whether the oral options increase the risk of PML, Coyle says they are “not in the category of cytotoxic agents like mitoxantrone and cyclophosphamide, and even azathioprine and methotrexate, which seems to be the drugs that put people at risk.”

Later on in the spirited discussion, Coyle claims natalizumab makes MS patients vulnerable to PML, to which Andrew Goodman, MD, FAAN, adds that “there’s no question that natalizumab is the key factor in people with MS getting PML because, as Pat said, we never saw it before. We never had these agents before, and we never had this sort of sequencing of what somebody took before.”

While it is known that some agents increase the risk for natalizumab-treated patients, it is not yet understood whether the oral agents are also amplifiers, Clyde Markowitz, MD, explains. Stephen Krieger, MD, also points out that, at this time, it is unknown why the other agents increase the likelihood of a patient developing PML.

“I think the mechanism by which immune suppression later engenders a higher risk is really unclear, and it may be something that these new agents do confer, and maybe something that they don’t,” Krieger says. “I don’t think we’re going to know until a few more years pass and we’ll be able to include those into the risk stratification model.”

Asked about the risks and benefits of oral agents compared to therapies administered through injection or infusion, Coyle says the current research has made her a proponent of oral medications.

“I think the interesting thing about the oral agents is that, in their limited head-to-head trials — and each one of them has a head-to-head trial with one of the original parenteral agents — the efficacy was as good or better,” Coyle states.

However, Coyle says it is not as easy to weigh the methods against each other, as the oral agents do not have the long recorded histories of the injected or infused prescriptions.

“It’s very hard to say that you can absolutely exclude that there might not be some nasty surprise as you build up on the number of MS patients who are treated,” Coyle notes.

Even with that being the case, Coyle says drugs like fingolimod, teriflunomide, and dimethyl fumarate have more clinical data that are giving doctors a better sense of their adverse effects. “And, by and large they’re pretty safe,” she adds.

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