NASHVILLE—What guides decisions to start, stop, switch, or restart disease-modifying therapy (DMT) in patients with multiple sclerosis (MS)—particularly in the absence of extensive robust data? Because multiple treatment options exist, there is a higher bar for a DMT to be considered successful. Clinicians need to base individualized decisions on the best available evidence, according to a presentation at the 2018 CMSC Annual Meeting.
Patricia K. Coyle, MD
“We have practice guidelines, but unfortunately they are almost always out of date,” said Patricia K. Coyle, MD, Professor and Vice Chair of Clinical Affairs and Director of the MS Comprehensive Care Center at Stony Brook University Hospital in New York. “Guidelines have a lot of good things to say and several things that I would not quite agree with, but at least they are a helpful start. In the future, as we use cooperative studies, databases, and meaningful observations on large numbers of patients with MS to maximize our information and data, we will ultimately resolve all of these DMT debates.”
Starting Treatment
Controversies surrounding initiation of DMTs include whether to treat patients with radiologically isolated syndrome, when to start treating relapsing forms of MS that are not active, and, in patients with primary progressive MS, when the monoclonal agent ocrelizumab is appropriate. Current American Academy of Neurology (AAN) practice guidelines recommend both prescribing a DMT to patients with clinically isolated syndrome (CIS), patients with a first attack who have at least two MRI lesions characteristic of MS, and offering DMTs to patients with relapsing forms of MS and recent attacks or MRI activity.
The AAN recommendations stem from the benefits seen with early treatment, Dr. Coyle emphasized. “There may be a critical window of opportunity in treating early,” she said. “If MS involves accumulating permanent damage to the CNS, wouldn’t you want to stop or minimize that as quickly as possible—not wait until there has already been significant injury?” Virtually all studies comparing early versus delayed treatment support early treatment—and “age probably matters.”
In a 2017 meta-analysis of 38 clinical trials that assessed disability worsening and disease progression in a total population of 28,000 subjects with MS, the authors found that DMT efficacy and impact on disability fell with advancing age. The model created from this study predicted that none of the DMTs would be efficacious on disability in patients older than 53. Evidence also suggested that, after patients reached age 40.5, high-efficacy DMTs (eg, ocrelizumab, natalizumab) no longer outperformed lower-efficacy oral agents (fingolimod, teriflunomide, dimethyl fumarate) or injectables (interferon betas and glatiramer acetates).
While skeptical of this latter finding, Dr. Coyle termed it “provocative” because it demonstrates that patients should be treated at a younger age. “When MS declares itself, the disease has probably existed for years, damaging CNS tissue,” she said. Older age at onset probably means that the disease has been present but silent for a long period of time. In addition, CNS and brain reserve become increasingly impaired with age. “The older you are, in theory, the less CNS reserve you have.”