Keeping MS Functional: Future Trends in MS Therapy

Multiple sclerosis (MS) is a chronic autoimmune disorder that affects the central nervous system, resulting in inflammation and damage to myelin and neurons within the nervous system. While the exact cause of MS is unknown, environmental, viral, and genetic factors are all thought to play important roles.

MD Magazine: Peers and Perspectives recently convened three of the nation’s leading MS experts: Douglas Jeffery, MD, PhD, neurologist for Advance Neurology and Pain, Cornerstone Health Care; R. Philip Kinkel, MD, director of the MS program at Beth Israel Deaconess Medical Center, Harvard Medical School; and Robert Zivadinov, MD, PhD, professor of neurology at the University at Buffalo, State University of New York. The panel was moderated by Peter Salgo, MD, a professor of anesthesiology and internal medicine at Columbia University.

The Best Strategy for Managing Secondary Progressive MS

Managing a progressive form of MS is often more difficult than managing relapse remitting MS. Kinkel explained that patients with progressive MS tend not to benefit from treatment that is clinically relevant. “Some of the interferon trials were positive in secondary progressive cases,” he said, “but those are primarily trials that included a significant number of people that are probably best referred to as just late relapsing.”

Jeffery agreed, noting that patients with inflammation can be treated. “But after many years of disease, the inflammation really tends to subside,” he said. “And, despite a recent paper in Brain, which argued that there was no further axonal loss in patients without inflammation, our clinical experience and numerous studies of progressive disease over the years suggests that even those patients who no longer have an inflammatory process continue to progress on the EDSS. We have nothing that affects that.”

“What we see in these patients is, if anything, an acceleration of this grey matter damage during the stage of the disease,” said Kinkel. “And it doesn’t typically follow the typical pattern of demyelination that we see in white matter, merely because of the nature of the tissue itself.” He added that the actual mechanism responsible for this accelerated involvement in grey matter in this stage of the disease is still unclear.

Kinkel asked whether it is simply a kind of a dying back phenomenon from all the ongoing process within the white matter. “Or is it a primary process taking place within the grey matter? Is it a combination of the two? This is one of the critical problems that we have with effectively treating patients with progressive MS.”

Zivadinov countered that it is more important to understand whether the appearance of new lesions is predictive of brain atrophy. “I would argue with any clinician that, when they say there are no new lesions and then they see one lesion, they change therapy—it depends on what tools you are using to determine the new lesion. If you use 3 Tesla (T) MRI, you are going to see more new lesions than on a 1.5 T MRI. If you are going to use subtraction imaging to determine the activity in the brain, you are going to see the lesions that you are missing by looking at the films of this patient,” he said.

“The problem is that may or may not be completely true,” replied Kinkel. “All of our treatment decisions and all of the information that we have from longitudinal studies is from using the old criterion,” he said. “The main problem that physicians always get themselves into is when they begin to make treatment decisions based on a 3 T scanner but use data from studies that used 1.5 T scanner. Or, even better yet, how about the Queen Square studies with even older-generation scanners? We quote the Queen Square studies all the time. That’s the basis of all our clinically isolated syndrome studies.”

Future Trends in MS Therapy

“What does the future hold for MS therapy?” asked Salgo.

Several of the newer agents may actually have neuroprotective properties, replied Jeffery. “When we look to the future, I think what we’re finding is that we have won the battle with inflammation,” he said. “How do we engage neuroprotective, neurorestorative therapies, and how do we use anti-inflammatory drugs and neuroprotective strategies to improve patient outcomes?”

Salgo then shifted to the topic of chronic cerebrospinal venous insufficiency. “What are your thoughts on vascular surgery for patients with MS?” he asked. “You read about in the popular press. MS patients are clamoring for it. Some swear by it. Some doctors swear at it.”

“I think that’s a bunch of garbage,” Jeffery said, pointing out that some proponents of vascular surgery suggest that cerebrospinal venous insufficiency, which is a blockage that prevents the drainage of blood from the brain, leads to white matter lesions. Patients with a venous sinus thrombosis do not get white matter lesions, he added. “Now, there is iron deposition within the brain, but I would bet that its pathophysiology is not due to venous insufficiency.”

Zivadinov disagreed, noting his recently published pilot study showing that percutaneous transluminal angioplasty in conjunction with disease-modifying therapy reduced T2 lesion volume compared with medical therapy alone. “I would say more research will happen, and we need to understand much more about this than we know now.”

Kinkel empathized with MS patients who hold out hope for vascular surgery. “There are individuals who claim to be doing research studies when, in fact, the only research they’re doing is charging people for the procedure and having an outcome where the patient either has an improved vascular lumen or is not at the end of the procedure.”

To conclude the discussion, Salgo asked the panelists for their opinion on upcoming trends in MS therapy and a take-home message for neurologists who manage patients with MS.

“One of the critical things is to better understand how to attack this disease in a more global manner,” said Zivadinov, adding that it may require a combination of drugs with a balance of anti-inflammatory and neuroregenerative properties to improve patient outcomes.

Jeffery reminded neurologists that the important thing to keep in mind is not which therapy they use, but what they accomplish with a DMT. “Keep an eye on your patients and make sure that your goal is no new relapses, no disability progression, and no new MRI lesions.”

Kinkel underscored the importance of understanding the pathogenesis of MS. “It will be extremely important as the future unfolds for collaborative networks to develop protocols and clinical research strategies that allow us to gain answers that we need, some of which will require non-pharmaceutical-initiated studies.”

We want to know what you think: What are your thoughts on vascular surgery for patients with MS?

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