Multiple sclerosis (MS) is the leading cause of irreversible neurologic disability in young women in the United States, and the second leading cause of neurologic disability in young men. In a series of debates at the 2016 American Academy of Neurology annual meeting, expert physicians addressed current and controversial issues in neuroscience, including the early aggressive treatment of patients with MS.
Timothy L. Vollmer, MD, Co-Director of the Rocky Mountain MS Center at Anschutz Medical Center, University of Colorado, Aurora, advocated the merits of early aggressive treatment for the majority of patients with MS, and Brian G. Weinshenker, MD, Professor of Neurology, Mayo Clinic, Rochester, MN, argued that aggressive treatment should be limited to patients with aggressive disease.
Early treatment of MS with disease-modifying therapies (DMTs) improves long-term outcomes, according to Dr Vollmer.
“With careful patient selection and monitoring, highly effective DMTs can be used in early MS, and should result in improved late-life neurologic function, improved quality of life, and decreased health-related costs. However, because there are risks from the disease and the therapies, shared decision-making is important,” he said.
Although DMTs slow the progression of disability and decrease the rate of conversion from relapsing-remitting MS (RRMS) to secondary progressive MS, 50% of patients with RRMS will progress to secondary progressive MS after 10 years, if left untreated.
Preserving Brain Reserve
The primary goal of treating MS with DMTs is to maximize lifelong brain health, said Dr Vollmer. Preserving brain volume in early MS is critical to preserving brain reserve to “buffer for the effect of MS and normal aging in late life,” Dr Vollmer emphasized.
The frequency of relapses and new magnetic resonance imaging (MRI) lesion formation are greatest at the onset of MS and decline with age, Dr Vollmer said. In addition, >90% of newly active MRI lesions are clinically silent (ie, not associated with a relapse) but still result in brain atrophy.
“The rate of brain atrophy is a strong predictor of future disability in MS. Brain reserve is compensating for the clinically silent disease in RRMS through cortical remodeling and other mechanisms, and loss of brain reserve may explain progressive MS,” he said.
To preserve brain volume, and thus brain reserve, early diagnosis and effective treatment of MS is essential.
“Help patients adopt a healthy, active lifestyle to avoid comorbidities that would also tax brain reserve, and help them build cognitive reserve through exercise and learning. Use the most effective DMT with an acceptable safety profile for the individual patient with MS as early in the disease course as possible,” said Dr Vollmer.
Aggressive Treatment Only for Aggressive Disease
Although Dr Weinshenker did not oppose aggressive DMT induction in some patients with MS, he encouraged a more individualized approach to treatment, given the disease's variable prognosis. According to population studies, 20% to 40% of patients have a “benign” course and would not merit receiving aggressive treatment, Dr Weinshenker said.
“Predicting disease course is imperfect, but a reasonable guess is possible at first presentation based on a combination of demographic, clinical, and radiologic findings. Observation and monitoring, even over the first few years, significantly refines prediction and facilitates selection of those requiring aggressive treatment, allowing one to tailor treatment,” said Dr Weinshenker.
A more nuanced, individualized approach that considers the combinations of relapse, relapse-related disability, and MRI activity is warranted, he argued.
“We have to consider what treatments have already been tried and the preferences and attitudes of our patients, especially for risk of complications. We must avoid escalation for progressive disability without attacks or MRI disability for which we have no evidence that we can influence,” said Dr Weinshenker, emphasizing that greater efficacy of treatment often comes with greater risks.
Although the relative efficacy of treatments is based on limited head-to-head data, some alternative therapies, such as vitamin D, may have potent benefits, with minimal risk, Dr Weinshenker said. He reminded the audience that for the majority of patients with MS, no evidence of disease activity is not currently an attainable goal.
“There's no absolute ‘window of opportunity.’ I would say aggressive treatment for aggressive disease...but not aggressive treatment for all patients,” Dr Weinshenker concluded.