RIS, or Radiologically Isolated Syndrome, is an intriguing medical condition characterized by anomalies and lesions similar to those seen in Multiple Sclerosis (MS) on an individual’s MRI brain scan.
Remarkably, despite these visual indications, RIS patients have yet to encounter any recognizable MS symptoms, such as fatigue, sensory disturbances, or mobility issues, such as trouble walking. The discovery of RIS usually happens as an incidental finding when a patient undergoes an MRI to look at particular symptoms, like headaches or head trauma.
Research shows that around 50 percent of people with RIS usually develop MS within 10 years. However, there isn’t enough evidence for doctors to know if treating this at a preclinical stage, meaning before the symptoms appeared, could actually make a difference in the progression of the disease.
Currently, there is a new preliminary phase 3 study, which was presented at the American Academy of Neurology’s 75th Annual Meeting on April 19 in Boston, that suggests the MS drug teriflunomide (Abagio) may possibly provide protective benefits for those with RIS.
Neurologist and researcher and study author at the University Hospital of Nice in France, Christine Lebrun Frenay, MD, said in a press release, “Our findings suggest that early intervention with teriflunomide may be beneficial to those diagnosed with radiologically isolated syndrome, the presymptomatic phase of MS.”
“However, more research is needed in larger groups of people to confirm our findings,” she added.
Those On Teriflunomide Had a 72 Percent Lower Risk of Having First Symptoms
Multiple sclerosis is a condition characterized by the immune system’s assault on the protective myelin enveloping the nerves, which afflicts nearly one million people in the United States.
For the study, it included 89 patients with RIS broken into two groups. One group took 14 milligrams (mg) of teriflunomide daily, while the second group took a placebo.
Over the course of two years, eight people who took the drug developed MS symptoms as compared to 20 who took the placebo. After making some adjustments for other factors that could possibly affect the risk of developing symptoms, the researchers found that participants taking teriflunomide had ‘a 72 percent lower risk of experiencing first symptoms than those taking the placebo.’
Notably, the makers of Aubagio, Sanofi, helped fund the trial.
A neurologist and pediatric neurologist who treats MS patients at Atrium Health Wake Forest Baptist in Winston Salem, North Carolina, Scott Otallah, MD, explained that this positive result was kind of expected due to an earlier trial that looked at the effect of another approved MS drug and RIS. Dr. Otallah, however, was not involved in this study.
Just last year, the ARISE study showed how treatment using the MS drug dimethyl fumarate (Tecfidera) had ‘about an 80 percent risk reduction of developing MS in people with RIS,’ explained Dr. Otallah.
Meanwhile, there is a third trial looking into ocrelizumab (Ocrevus) as a preventive for MS in those with RIS that is currently in the recruitment phase.
Better Ways to Screen Systematically for MS are Needed
Erin Longbrake, MD, PhD, a neurologist who specializes in neuro-immune diseases, including MS, at Yale Medicine in New Haven, Connecticut, said, “It is becoming clear that it is possible to detect MS before the onset of symptoms in a subset of patients.” Again, Dr. Longbrake was not involved in the research.
Additionally, Dr. Longbrake says that both these trials show that traditional MS disease-modifying medications are also effective in preventing symptoms of MS for these individuals.
She also says that now, there’s evidence that these treatments can help people with RIS and 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. 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.
Risks of Having an MS Misdiagnosis
Amid these promising developments, the significance of having a precise diagnosis cannot be overemphasized. Misdiagnosing MS can potentially expose individuals to unwarranted healthcare risks and financial burdens. In addition, a study published in 2019 in Multiple Sclerosis and Related Disorders indicates that up to one in five individuals may receive a wrongful MS diagnosis.
Dr. Lebrun Frenay says, “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.”
At this stage, MS treatment can be difficult because of the potential for misdiagnosis, explains Dr. Otallah, especially if you’re just working from what you see on the MRI.
According to Cedars-Sinai, a number of neurological conditions, such as cerebral small vessel disease andsystemic lupus erythematosus, have the ability to cause lesions to appear on a brain MRI that looks like MS.
Have You Been Diagnosed with RIS? Speak To Your Doctor About Options
Currently, there are no treatments approved by the U.S. Food and Drug Administration (FDA) 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 Dr. Otallah.
He also shares that there are probably going to be a lot of talks around these medications, the way they can be appropriately used for preclinical MS, and other issues such as cost and insurance coverage.
When it comes to the cost of Aubagio, it will depend on one’s insurance coverage. Usually, the list price of branded Aubagio is over $9,000 a month or 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 Dr. Otallah.
The question now remains, if someone has RIS but doesn’t have MS symptoms yet, should they speak with their medical 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 Dr. Longbrake.
She adds, preclinical disease is a complex situation, and it’s important to get advice from experts who really understand the nuance here. “Some people likely would do well with treatment, while it may be safe to just observe others.”
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