The onset of multiple sclerosis (MS) is most common between ages 25 and 40 years, with the risk of new or changing disease activity existing over the rest of a patient’s life. Disease manifestations, however, typically change over the patient’s lifetime. Acute, new relapses and focal abnormalities on magnetic resonance imaging (MRI) scans are common in younger patients but diminish with age and are often replaced over time by clinical stability or slowly progressive worsening, which is mostly independent of relapses and new MRI lesions. Currently available disease-modifying therapies (DMTs) alter the natural history of MS by diminishing relapses, new MRI lesions, and progression of disability but have a modest impact on older patients and those with slow progression independent of relapses. They are virtually unstudied in patients over 55 years of age, and subgroup analysis of phase 3 clinical trials suggest the greatest DMT impact is in younger patients. In observational studies of patients who discontinue DMT, the return of disease activity is also most likely in younger patients with recent relapses and new MRI changes, but the risks remain poorly defined. Risks of many DMTs, especially infections, increase as people age and use DMTs for longer periods. A major unmet need for patients with MS, therefore, is determining when, if ever, it is reasonable to consider DMT discontinuation, especially in older patients with no recent relapses or scan changes.
