When you have multiple sclerosis (MS), choosing a disease-modifying drug is a big decision. These powerful medications can provide major benefits, but not without some serious risks.

Several of the most common disease-modifying drugs used for MS, for example, can compromise the immune system, and cause people who are infected with the John Cunningham virus (JCV) to develop progressive multifocal leukoencephalopathy (PML).

JCV is a very common virus that affects over half of the world’s population. While in most cases it causes no side effects, for some people affected by MS, it can lead to PML. PML is a debilitating disease that occurs when JCV infects white matter in the brain and attacks the protective myelin coating around the nerve cells. It can lead to severe neurological disabilities, and even death.

Are people who are taking these drugs aware of their risk for developing PML before they begin treatment, or even aware of what PML is?

A Healthline survey of 1,715 people who have MS revealed that fewer than half were aware of both JCV and PML.

Among those who were aware of JCV, almost 60 percent underestimated how common it is.

What are JCV and PML?

JCV is quite common. In fact, about half the population has it. Most will never know, because our immune systems keep the virus under control.

When a weakened immune system allows JCV to become active, it can lead to PML, a life-threatening demyelinating brain disease. PML has a mortality rate of 30 to 50 percent in the first few months after diagnosis. Survivors often have severe disabilities.

Understanding JCV and the Risk for People with MS »

The risk of PML is low in the general population. Although still small, the risk is greater if you use immunosuppressive drugs.

Currently, there are 14 disease-modifying medications used to treat relapsing forms of MS. Three list PML as a potential side effect. You can link to the drug information and warning from the drug manufacturers for more information:

  • Gilenya (fingolimod), an oral medication
  • Tecfidera (dimethyl fumarate), an oral medication
  • Tysabri (natalizumab), which is given by infusion

How can you find out your risk?

A blood test can determine if you have JCV antibodies, which can help estimate your risk of developing PML. However, false-negative results are possible. Plus, you can still acquire the infection any time without realizing it.

About one-third of people who took part in the Healthline survey have been tested for JCV. Of those who take Tecfidera or Tysabri, 68 percent have been tested for JCV, with 45 percent of them testing positive.

Neurologist Bruce Silverman, D.O., F.A.C.N., director of Neurosciences Service Line at Ascension St. John Providence-Park Hospital in Michigan, told Healthline the problem first came to light with the launch of Tysabri.

“Everybody was excited about the robust response the drug offered to MS patients,” he said.

Then, three clinical trial patients developed PML, two fatally. The manufacturer pulled the drug in 2005.

It was found that the risk of PML was greater in people who had been on immunosuppressive drugs prior to or in combination with Tysabri, explained Silverman.

The drug was re-evaluated and returned to the market in 2006. Eventually, Gilenya and Tecfidera were also approved to treat MS.

“Both carry the same potential problem associated with PML,” said Silverman. “It can happen with any immunosuppressant drug. We clinicians have to talk to patients about this issue and closely monitor those at risk of developing PML.”

Silverman said there are no real guidelines for monitoring MS patients using these drugs. He performs imaging tests and JCV antibody tests at least once a year and keeps a close eye on patients who take them.

Knowledge is power

Of those who take Tecfidera or Tysabri, 66 percent are aware of the risk. Why do they choose these medications?

Silverman suggests the main reason is efficacy.

“The original disease-modifying drugs probably improve the relapse rate by around 35 to 40 percent. With these drugs, the benefit might be around 50 to 55 percent or more. Tysabri may be even a littler higher,” he said.

“Most people who have this disease are relatively young and active in life,” he continued. “They want the most robust response, so they pick a drug that will give them that kind of protection. They’re willing to take a risk to do so.”

Why some people take the risk

Desiree Parker, 38, of Williamsburg, Virginia, was diagnosed with relapsing-remitting MS in 2013. She initially chose Copaxone, but switched to Tecfidera earlier this year.

“I know what PML is, and I understand the increased risk while on this medicine, knowledge I got from speaking with my neurologist and from reading about the drug on my own,” she said.

 “I chose it for a number of reasons, the primary one being that it was not an injection or infusion. I had lots of trouble with self-injecting, and was sick of it. I wanted an oral medicine with the lowest risk and most manageable side effects.”

Before taking Tecfidera, Parker tested negative for JCV antibodies.

“I know this doesn't mean I won't be exposed to the virus, and thus the chance of PML, in future. If I had tested positive, I likely still would have selected one of the oral medicines, though I would have been more concerned about this risk,” explained Parker.

“My neuro said that it's only when you get lymphopenia — low white blood cells — that you're at highest risk of developing PML if you're infected. So I really care more about watching that than getting constantly tested for the virus,” she said.

Parker worries about the long-term effects Tecfidera might have on her body, but is more concerned about slowing disease progression.

Vix Edwards of Nuneaton, Warwickshire, U.K., was diagnosed with relapsing-remitting MS in 2010. Just 18 months later, her diagnosis was changed to secondary-progressive MS with relapses. She tried Copaxone and Rebif, but continued to relapse at least once a month.

After much consideration, she switched to Tysabri. She learned about the PML risk from her MS nurse, who explained it in great detail on the phone, again in person, and by mail.

“I’m not overly worried about PML, mainly because the odds that I could contract this are far less than the chances of my relapsing without Tysabri,” Edwards told Healthline.

To date, she’s had 50 infusions without a relapse.

According to Edwards, it may not be standard across the U.K., but she’s tested for JCV every six months.

Room for improvement

Parker and Edwards credit their practitioners with providing them with the necessary information before starting on the drugs. That’s not the case for everyone.

More than one-quarter of those surveyed are taking a drug that increases the risk of PML. One-third of those are unaware of or misinformed about the risks.

“That’s incomprehensible,” said Silverman. “By all estimations, these drugs are big guns with high risk. Staring down PML is an uncomfortable place to be. I would feel very, very compromised if I didn’t have a long conversation with a patient about the potential benefits and risks related to their use.”

Parker believes patients should also conduct their own research on each treatment option and decide on the most important selection criteria.

Silverman agrees, but stresses the need to seek reputable sources when researching online.

He encourages active participation in support groups such as the National MS Society, especially face-to-face local chapter meetings.

“They help disseminate good information that can guide patients toward asking the right questions of their doctors,” said Silverman.