Could Early Treatment Help Delay or Prevent MS in Certain People?

Radiologically isolated syndrome (RIS) is a condition in which a person’s MRI brain scan shows abnormalities and lesions like those seen in multiple sclerosis (MS), but they haven’t experienced any MS symptoms, such as fatigue, numbness, or trouble walking. RIS is usually uncovered accidentally when a person has an MRI to investigate issues like headaches or head trauma.

Research indicates that about 50 percent of people with RIS go on to develop MS within 10 years. But there hasn’t been much evidence for doctors to know if treating at this preclinical stage — before the appearance of symptoms — could make a difference in the disease progression.

Now, a new preliminary phase 3 study, presented on April 19 the American Academy of Neurology’s 75th Annual Meeting in Boston, suggests the MS drug teriflunomide (Aubagio) could provide protective benefits in people with RIS.

“Our findings suggest that early intervention with teriflunomide may be beneficial to those diagnosed with radiologically isolated syndrome, the presymptomatic phase of MS,” said study author Christine Lebrun Frenay, MD, a neurologist and researcher at University Hospital of Nice in France, in a press release. “However, more research is needed in larger groups of people to confirm our findings,” she added.

People Taking Teriflunomide Had a 72 Percent Lower Risk of Experiencing First Symptoms

MS is a disease in which the body’s immune system attacks myelin, the fatty white substance that insulates and protects the nerves. It’s estimated that close to one million people in the United States are living with MS.

The study included 89 people with RIS. One group took 14 milligrams (mg) of teriflunomide daily and the other group took placebo.

During the two-year study, eight people who took the drug developed MS symptoms, compared with 20 who took the placebo.

After adjusting for other factors that could affect the risk of developing symptoms, researchers found that people taking teriflunomide had a 72 percent lower risk of experiencing first symptoms than those taking the placebo.

Sanofi, the maker of Aubagio, helped fund the trial.

This positive result was somewhat expected, because of findings from an earlier trial that looked at RIS and a different approved MS drug, says Scott Otallah, MD, a neurologist and pediatric neurologist who treats MS patients at Atrium Health Wake Forest Baptist in Winston Salem, North Carolina. Dr. Otallah was not involved in this research.

Last year, the ARISE study showed that treatment with MS drug dimethyl fumarate (Tecfidera) resulted in about an 80 percent risk reduction of developing MS in people with RIS, says Otallah.

A third trial investigating ocrelizumab (Ocrevus) for preventing MS in people with RIS is currently in the recruitment phase.

Better Ways to Systematically Screen for MS Are Needed

“It is becoming clear that it is possible to detect MS before the onset of symptoms in a subset of patients,” says Erin Longbrake, MD, PhD, a neurologist who specializes in neuro-immune diseases, including MS, at Yale Medicine in New Haven, Connecticut, who was not involved in the research. Both these trials demonstrate that traditional MS disease modifying medications are also effective in preventing symptoms of MS for these individuals, says Dr. Longbrake.

Now that there’s evidence that these treatments can help people with RIS, the next step is to find better ways to detect people with preclinical MS, says Longbrake. “Right now, we discover these patients by accident, when they have an MRI of the brain for some unrelated reason. Obviously, there are many more people like them who are missed,” she says.

“If we could find a way to more systematically screen for MS, it opens up a lot of opportunity for early treatment, maybe even prevention of disease,” says Longbrake.

A systematic review published in April 2021 in Neurology found that people with MS are “frequently not diagnosed at their first demyelinating event but often years later,” wrote the authors.

The Risks of an MS Misdiagnosis

However, misdiagnosing MS can also be a problem and may result in unnecessary healthcare risks and added expenses. As many as 1 in 5 people may receive a misdiagnosis of MS, according to a study published in 2019 in Multiple Sclerosis and Related Disorders.

“It is important that medical professionals are cautious when using MRI expertise to diagnose this condition, selecting only patients at risk of developing MS and not increasing MRI misdiagnoses,” said Dr. Lebrun Frenay.

Treating MS at this stage is tricky because of the potential for misdiagnosis — especially if you are just going off of what’s observed on the MRI, agrees Otallah.

Many neurologic conditions, including cerebral small vessel disease and systemic lupus erythematosus, can cause lesions to appear on a brain MRI that look like MS, according to Cedars-Sinai.

Diagnosed With RIS? Talk With Your Doctor About Options

As of now, there are no treatments approved by the U.S. Food and Drug Administration for RIS. “These trials are funded by the companies so that if they are found to be effective, they can be submitted to the FDA for approval for treatment in this population,” says Otallah.

There is likely to be a lot of discussion around these medications: how they can be used appropriately for preclinical MS, as well as issues like cost and insurance coverage, he says.

The cost of Aubagio depends on insurance coverage. The list price of branded Aubagio is over $9,000 a month for a 30-day supply.

“I think these medications could be one of the next steps. In the right people, these could be used to get in early and prevent morbidity,” says Otallah.

If a person has RIS but does not yet have symptoms of MS, should they talk with their provider about teriflunomide?

“These people should absolutely see a neuroimmunology or MS specialist to talk about what options they have. This could include teriflunomide, but there may be other options as well,” says Longbrake.

Preclinical disease is a complex situation, and it’s important to get advice from experts who really understand the nuance here, she says. “Some people likely would do well with treatment, while it may be safe to just observe others.”