Aubagio reduces MS risk in people with disease-like signs: Phase 3 trial

Aubagio (teriflunomide) can significantly reduce the risk of developing multiple sclerosis (MS) among adults with signs of MS-like brain damage who don’t yet have any disease symptoms, according to findings from a clinical trial.

The results were presented earlier this year at the American Academy of Neurology 2023 Annual Meeting, and have now been published in JAMA Neurology, in the study “Teriflunomide and Time to Clinical Multiple Sclerosis in Patients With Radiologically Isolated Syndrome The TERIS Randomized Clinical Trial.”

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Radiologically isolated syndrome refers to MS-like lesions on MRI, no symptoms

MS is caused by inflammation that damages the brain and spinal cord, resulting in neurological problems that lead to disease symptoms. MS-related damage is visible on MRI scans as lesions, spots where nerve tissue has been damaged and scarred.

Sometimes, MS-like lesions will incidentally be detected in people without any symptoms undergoing MRI scans for reasons other than suspected MS. This is called radiologically isolated syndrome, or RIS.

Some people with RIS will go on to develop symptoms, at which point a diagnosis of MS can be confirmed. However, there’s limited data on whether current MS treatments can be used to delay or even prevent the disease from developing.

Aubagio is an oral therapy that’s widely approved for relapsing types of MS. It works to reduce MS-driving inflammation by interfering with the expansion and maturation of certain immune cells.

A Phase 3 trial called TERIS (NCT03122652) was launched to test whether treatment with Aubagio could reduce the risk of developing MS for adults with RIS. The study was funded in part by Sanofi, which markets name-brand Aubagio (generic versions are also available).

TERIS enrolled 89 people with RIS, diagnosed after undergoing MRI scans for symptoms such as headache, dizziness, or vision problems, or as a follow-up for other neurological conditions.

Participants were given Aubagio or a placebo daily for up to about two years. The study was originally planned to include more participants, but it was stopped early mostly due to slow enrollment and complications from the COVID-19 pandemic, and also because Sanofi stopped providing noncommercial Aubagio and placebo tablets for the trial after generic versions of Aubagio became available.

… early intervention in [radiologically isolated syndrome] may improve clinical outcomes.

20 people given placebo developed MS compared with 8 given Aubagio

Over the course of the trial, 20 people given a placebo developed MS, compared with eight individuals given Aubagio. That works out to a 63% lower rate of MS for patients given Aubagio.

In statistical models that accounted for factors like sex, age at RIS diagnosis, disability level, and the presence or absence of actively inflamed lesions, the risk of MS was estimated to be 72% lower with Aubagio compared with a placebo.

Patients given Aubagio also tended to have less new disease activity on MRI scans and better quality of life, but the difference from placebo did not reach statistical significance.

The most common side effects associated with Aubagio in the study were digestive issues, painful cramps during menstrual periods (dysmenorrhea), and respiratory infections. One patient given Aubagio experienced a severe infection with COVID-19, which was judged to be possibly related to the immune-suppressing treatment.

Overall, the findings suggest that Aubagio treatment can reduce the risk of developing MS for people with RIS. This makes Aubagio the second MS treatment to show positive results in RIS. Another clinical trial called ARISE (NCT02739542), which tested Tecfidera (dimethyl fumarate) in people with RIS, found similar results.

“The TERIS and ARISE studies demonstrate that different [treatments] with different immune mechanisms of action studied in other populations and derived from diverse health care systems yield comparable results, supporting that early intervention in RIS may improve clinical outcomes,” the scientists wrote.

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2 trials show treatment extends time to symptomatic MS in people with RIS

“The MS community now has 2 multicenter, placebo-controlled, double-blind, randomized clinical trials showing that active treatment extends the time to symptomatic MS in people with RIS,” the researchers concluded.

Although these studies have shown that treatments like Aubagio or Tecfidera may reduce the risk of MS in people with RIS, that doesn’t necessarily mean that everyone with RIS should be getting these treatments, the scientists noted. Like any medication, these therapies come with risks of side effects as well as economic costs, and some people with RIS will never develop MS even without treatment.

Given these considerations, future research is needed to figure out exactly which people with RIS are most likely to benefit from treatment, so that therapies can be given where they are most needed, but not given when they are not necessary, the researchers noted.

“Now that 2 studies (ARISE and TERIS) have demonstrated the efficacy of [MS treatments] in RIS, future study designs can focus on identifying the ideal individuals who would benefit most from treatment,” the scientists wrote.