Clinical Challenges: Determining When to Stop MS Therapy as Patients Age

Stopping multiple sclerosis (MS) treatment as patients age can be a fraught decision, but there are some signposts to help guide the way.

This neurological disease of inflammatory damage to the brain most commonly starts in the second or third decade of life, and then by the fifth decade patients see declines in the frequency of new lesions on imaging and clinical relapse.

At the same time disease activity is declining, the risks of treatment with immune-modulating therapies increase, such as infection and malignancy.

After the first MS disease-modifying therapy was approved in 1993, “we probably began seeing shot fatigue as early as 1995,” noted John Corboy, MD, of the University of Colorado in Aurora. “That was the earliest sign that there was going to be likely some pushback from patients that they were not going to necessarily want to take these drugs for up to 10, 20, 30 years.”

Along with daily self-injections, some drugs had flu-like side effects and others had injection-site reactions. As individuals started “voting with their feet” to stop medication, observational studies emerged. The evidence was fairly inconclusive until recently, when the DISCOMS trial was published in the Lancet Neurology.

In that trial of 259 patients ages 55 years and older, with no relapse within the past 5 years or new MRI lesion in the past 3 years while continuously taking disease-modifying therapy, discontinuation of those medications didn’t prove non-inferior to continuation for the primary composite outcome of relapse or new or expanding brain MRI lesion within 2 years, with rates of 12.2% versus 4.7%.

This finding was driven by radiological activity, without any definite differences between groups in hard outcomes. Progression of disability as measured by Expanded Disability Status Scale was similar between the discontinue- and continue-medication groups (mean change -0.1 vs +0.1, P=0.39). In a post-hoc analysis, relapse with new disease activity occurred in only three of the 131 discontinue-therapy patients (2%) and one of the 128 continue-therapy patients (
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