Abstract
BACKGROUND: The decision to discontinue disease-modifying therapies (DMTs) in patients with multiple sclerosis (PwMS) is a critical clinical challenge. Historically, DMTs were discontinued due to side effects, treatment limitations, or progression to secondary progressive MS. However, advancements in MS therapies, particularly high-efficacy DMTs (HE-DMTs) and the increased knowledge on disease courses and phenotypes have resulted in more personalized treatment approaches and introduced discussion on scheduled DMT discontinuation. This review explores the current evidence on DMT discontinuation, focusing on its implications for aging populations and the interplay between cardiovascular diseases (CVD) and MS. CURRENT EVIDENCE AND INTERPLAY WITH CVD: Randomized trials such as DISCOMS and DOT-MS have provided insights into discontinuing DMTs in stable patients. In summary, both randomized clinical trials highlight the risk of disease reactivation following treatment discontinuation. Due to the limited sample size, neither study was able to conduct subgroup analyses based on age groups. Additionally, DOT-MS was terminated prematurely, direct comparisons with other studies should be avoided. While older studies and observational data (e.g., OFSEP) have shown relapse risks associated with discontinuation, particularly for drugs like natalizumab and fingolimod, there is limited data on HE-DMT discontinuation outcomes. Comorbidities, particularly CVDs, further complicate decisions regarding the continuation of DMTs in older adults. MS patients bear a higher burden of CVD, which is also associated with unfavorable disease courses. While optimizing cardiovascular risk profiles appears advisable, it remains unclear whether DMTs themselves have a positive impact on CVDs. CONCLUSION: Given the complexities associated with discontinuing DMTs in MS patients, it is essential to balance the avoidance of polypharmacy with the potential risks of disease reactivation and the impact of comorbidities, especially CVDs, on disease progression. The interplay between MS and CVD highlights the importance of a holistic risk assessment when considering DMT discontinuation.