# Risk of stroke under disease modifying therapies for multiple sclerosis: a systematic review

## TL;DR

This review finds that disease modifying therapies for multiple sclerosis may reduce stroke risk, but some treatments carry other health risks.

## Contribution

The study systematically evaluates the association between specific DMTs and stroke risk in MS patients.

## Key findings

- DMT exposure is linked to a 50% reduction in stroke risk compared to no DMT exposure.
- Glatiramer acetate and dimethyl fumarate appear to lower stroke risk, while fingolimod raises concerns for heart disease and hypertension.
- Alemtuzumab and β-interferons are associated with rare but serious complications requiring clinical vigilance.

## Abstract

Epidemiological research indicates a heightened incidence of cerebrovascular disorders among patients with multiple sclerosis (MS).

The aim of the present systematic review was to investigate the potential association between disease modifying therapies (DMTs) and the risk of stroke in MS patient populations.

A systematic literature search was performed in MEDLINE and SCOPUS databases up to April 6, 2024, to identify randomized-controlled clinical trials (RCT), registry-based and cohort-studies, case-series, and case-reports reporting on acute ischemic stroke (AIS) or intracerebral hemorrhage (ICH) in MS patients under different DMTs.

Twenty-one studies were included: 1 RCT, 6 registry-based or cohort studies, 2 case-series and 11 case-reports. 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. Although glatiramer acetate and dimethyl fumarate appear to lower the risk of stroke, concerns about fingolimod exists due to an observed elevated risk for ischemic heart disease and hypertension. Despite the absence of detected safety concerns with alemtuzumab at the MS population level, alemtuzumab-related complications, although rare, signal the need for heightened clinical vigilance. Similarly, β-interferons have been linked to life-threatening adverse events, comprising thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS). No associations between the risk of stroke and other DMTs, comprising natalizumab and teriflunomide, were detected; yet, newly approved DMTs were underrepresented.

These findings highlight the importance of personalizing DMT selection and monitoring cardiovascular risk factors to reduce stroke risk in patients with MS.

PROSPERO CRD42024534470.

Risk of stroke under disease modifying therapies for multiple sclerosis: a systematic review

Epidemiological data are sparse regarding the risk of stroke in patients with multiple sclerosis (MS). In addition, there is a paucity of evidence regarding the potential association between disease modifying therapies (DMTs) and the risk of stroke in MS patient populations. We conducted a systematic review with the aim to investigate the incidence of stroke and stroke characteristics in MS patients under different types of currently FDA (Food and Drug Administration)-approved DMTs. Our findings show that DMTs appear to reduce the risk of stroke at the MS population level, with DMT exposure linked to a 50% reduction of the risk of stroke compared to no DMT exposure. Nevertheless, this association likely varies by DMT type. Although glatiramer acetate and dimethyl fumarate appear to lower the risk of stroke, concerns regarding fingolimod have been raised, particularly regarding the observed elevated risk for ischemic heart disease and hypertension. The rare but serious complications linked to alemtuzumab and β-interferons call for rigorous monitoring in clinical practice. Finally, the methodological limitations of existing studies underscore the need for methodologically robust epidemiological research to better delineate the association between specific types of DMTs and stroke subtypes in MS, with the aim to provide a stronger evidence base for clinical decision-making.