Varying impact on risk of stroke found for DMT use in MS in study
Glatiramer acetate, dimethyl fumarate may have most protective effects
As a whole, disease-modifying therapies (DMTs) for multiple sclerosis (MS) tend to reduce the risk of stroke among patients, though their impact varies depending on the type of medication that’s taken.
Those are the findings of a new analysis of published studies by scientists in Europe, who noted that “epidemiological research indicates a heightened incidence of cerebrovascular disorders among [people] with multiple sclerosis.”
Glatiramer acetate (sold as Copaxone and generics) and dimethyl fumarate (sold as Tecfidera and generics) may have the most protective effects for people with MS, according to the results of the team’s review study. On the other end of the spectrum, fingolimod (sold as Gilenya and generics) may elevate such risk, the data showed. Other DMTs have more complex or unclear effects.
“These findings highlight the importance of personalizing DMT selection and monitoring cardiovascular risk factors to reduce stroke risk in patients with MS,” the researchers wrote. They added that “glatiramer acetate and dimethyl fumarate appear to lower the risk of stroke” while “concerns regarding fingolimod have been raised.”
The article, “Risk of stroke under disease modifying therapies for multiple sclerosis: a systematic review,” was published in the journal Therapeutic Advances in Neurological Disorders.
Scant data available on DMT effects on risk of stroke
A progressive neurodegenerative disease, MS is caused by the immune system targeting the central nervous system, which comprises the brain and spinal cord. In addition to triggering hallmark MS symptoms like fatigue and difficulty walking, these autoimmune attacks may compromise central nervous system blood vessels.
This heightens the risk of stroke, in which disruptions in the blood supply to the brain can cause lasting damage. Additionally, the researchers noted, individuals with MS often have cardiovascular risk factors like high cholesterol, high blood pressure, and diabetes, which increase their risk of stroke.
Some treatments may alter the course of MS, slowing or stopping disease progression. In addition to easing MS symptoms, such medications, known as disease-modifying therapies or DMTs, might lower stroke risk. However, evidence of such effects remains inconclusive.
“While some observational studies have suggested reduced incidence of stroke in MS patient populations under DMTs, other reports have provided contradictory findings, indicating an increased risk for major adverse cardiovascular and cerebrovascular events,” the team wrote.
To address this inconsistency, the researchers, from institutions in Greece and Germany, systematically reviewed published studies about the association between DMTs and stroke. The team identified 21 articles that analyzed these relationships using various methodologies. One study was a randomized trial comparing DMTs, while others retrospectively inspected patient records. Many of the included studies were case reports or case series describing individual patients.
“Overall, DMTs appear to reduce the risk of stroke in MS patients, with DMT exposure linked to a 50% reduction of the risk of stroke compared to no DMT exposure,” the researchers wrote. This estimate came from a registry study involving more than 35,000 participants, which was the largest population of any of the included papers.
However, when broken down by DMT type, the risk of cardiovascular disease varied more. Although some of the included studies had a low overall incidence of strokes, making generalization difficult, some patterns emerged.
Two DMTs — glatiramer acetate and dimethyl fumarate — appeared to reduce stroke risk, per the researchers. Both are widely approved, as brand-name medications and available as generics. Based on the included studies, these medications seemed to have some protective effects against cerebrovascular disease.
Overall, [disease-modifying therapies] appear to reduce the risk of stroke in MS patients, with DMT exposure linked to a 50% reduction of the risk of stroke compared to no DMT exposure.
Conversely, however, fingolimod appeared to increase the risk of cerebrovascular disease. The researchers hypothesized that this was an indirect effect, as fingolimod also increased the risk of high blood pressure. That, in turn, could make stroke more likely.
This medication is also widely approved as a brand-name drug and with generics, though its indication is more narrow in the European Union.
Case reports key in ‘informing DMT monitoring protocols’
Other medications had rare reports of serious cerebrovascular incidents requiring immediate management. These included beta interferons and Lemtrada (alemtuzumab), approved in the U.S. to treat adults with relapsing forms of MS.
For example, rare reports connected interferon beta-1a (sold as Avonex, among others) with a serious condition, called thrombotic thrombocytopenic purpura-hemolytic uremic syndrome. that interrupts blood clotting, potentially leading to stroke. In such cases, “timely initiation of [adequate treatment] … is crucial to prevent fatal outcomes,” the team wrote.
Not enough data were available on stroke risk for the remaining DMTs for the researchers to draw conclusions. Medications in this category included teriflunomide (sold as Aubagio and generics) and natalizumab (sold as Tysabri and the biosimilar Tyruko).
The lack of data for some DMTs was one of several limitations the researchers noted. Another major limitation was that each study used different reporting criteria, making it difficult to directly compare results, according to the team.
Also, many of the included studies were case reports, which typically involve individual patients and might not be generalizable. However, because such reports tend to highlight severe reactions, “they may significantly contribute to clinical practice by informing DMT monitoring protocols that emphasize early detection and prevention of serious adverse events,” the researchers wrote.
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