Risks and Benefits of Disease-Modifying Therapies in People Aging With Multiple Sclerosis

Worldwide, the average age of people with multiple sclerosis (MS) has increased significantly over the past several decades. Findings from natural history studies reveal that the risk of new relapse and MRI activity diminishes with age. Available since 1993, the use of disease-modifying therapies (DMTs) for MS has expanded dramatically, with many patients using the drugs indefinitely. The participants of most phase 3 clinical trials that have resulted in regulatory approval of MS DMTs have been 55 years or younger at the onset of participation, so there remains a dearth of data as to the benefits and risks of DMT use in older people with MS. Risks associated with DMT use may increase as people age, especially vascular and malignancy comorbidities. Although some people with MS older than 55 years have discontinued DMT, some are reluctant to even consider a trial off DMT. Findings from many observational DMT discontinuation studies and 2 discontinuation randomized controlled trials have confirmed that the greatest risk of recurrent MS disease activity is in younger patients who discontinue DMT. For clinically stable people older than 60 years, the greatest enhanced risk faced by those who discontinue DMT is that of 1 to 2 brain MRI-detected lesions of unclear long-term clinical significance. Thus, although it may be reasonable to consider a personal DMT discontinuation or de-escalation trial, patients, their families, and MS clinicians would benefit from a substantial increase in clinical studies relevant to the risks and benefits of DMT use and nonuse in those older than 55 years.