Guest editor-in-chief Darin T. Okuda, MD, FAAN, FANA, details the fast moving field of multiple sclerosis and the direction the disease is moving towards in 2021.
Scientific advancement within the field of multiple sclerosis (MS) is moving at a remarkably fast pace. This is demonstrated by the availability of new FDA-approved treatments that expand upon our current therapies, offering enhanced selectivity for key receptors, alternative delivery platforms that enable patients to be treated at home, and lower common adverse effect profiles. The field is also moving toward investigating individuals earlier in the disease course and studying utilization of medical resources prior to the diagnosis of MS, along with identifying the impact of approved treatments in extending the time to a first attack in radiologically isolated syndrome (RIS), new biomarkers that inform on neuronal injury, and enhancements in neuroimaging.
What does the future of MS look like? What are some practical challenges that clinicians are faced with beyond coronavirus disease 2019? Four key themes appear to be important: newly available treatments for MS; incorporating novel and innovative technologies to improve the diagnosis and management of patients; the need to transform how we communicate based on a new generation of patients; and leveraging technology for next-generation care.
At the time this piece was authored, 22 FDA-approved disease-modifying therapies (DMTs) with indications for clinically isolated syndrome, relapsing forms of MS, active secondary progressive MS, and primary progressive MS were available to patients. In the future, an expansion of whom we are able to treat may occur and approved therapies indicated for subjects with RIS may be defined. In addition, as the definitions of how we diagnose MS in patients evolve to include more biological measures as opposed to clinical and radiological-based metrics, it would not be impossible for us to consider that a treatment or regimen be recommended in individuals or families at high risk for the development of a first central nervous system demyelinating lesion.
Beyond these exciting opportunities for treating individuals much earlier or even before the onset of the disease course, a number of time-relevant issues exist. Do we really need more anti-inflammatory treatments? We currently have a wide-based selection of available therapies with differing mechanisms of action but none with scientific evidence for effective myelin or axonal repair. The field will be further challenged with demonstrating how any positive imaging indices suggestive of reassimilation or improvements in myelin integrity translate to a meaningful improvement in physical function. Also, how generalizable will any reparative trial data be to the spectrum of patients with MS that we care for?
A significant inflection point in the treatment landscape has also occurred recently with the introduction of generic dimethyl fumarate, further crowding the fumarate market given the availability of diroximel fumarate and monomethyl fumarate. As if understanding the vast array of differing treatments for MS was not enough for our patients, we are now challenged with providing additional education regarding the innate differences with therapies that are approved through a different FDA regulatory path, as well as corresponding with medical insurance companies to ensure that patients receive the exact treatment prescribed. The introduction of yet another approved generic treatment—whether another fumarate compound or new branded therapy having a similar mechanism of action to our existing therapies—expands the amount of education needed to fully understand the overt or subtle differences as well as the challenges to the infrastructures in place that work in getting our selected therapies approved for care.
Moving beyond medications that reduce clinical relapses, MRI advancement, and clinical disability, the field is also starving for effective and FDA-approved symptomatic treatments. Our patients continue to commonly struggle with symptoms that greatly impact their quality of life and employment. Fatigue, neuropathic pain, and cognitive difficulties are obstacles for many. Some available DMTs have been shown to reduce negative symptoms related to MS. However, it is not uncommon for patients to use over-the-counter or prescribed off-label agents for targeted relief. Having symptomatic treatments specifically indicated for use in MS will allow for a seamless process from prescription to medication possession.
MRI represents one of the cornerstones in the diagnosis and management of MS. More recent novel imaging approaches have revealed physiological alterations within lesions and in surrounding normal-appearing tissue, reductions in the integrity of cortical and central gray matter structures, along with intra- and perilesional characteristics that correlate with physical disability. Improving our ability to accurately recognize lesions related to inflammatory demyelination as compared to nonspecific white matter features is key. Newly developed imaging tools focused on 3-dimensional conformation, evaluating changes in shape, surface texture, and structure provide new insights into disease stability/advancement, enhancing conventional MRI data and allowing for the analysis of historic MRI data from phase 2/3 trials.
How we communicate the value of the newer generation of treatments or insights related to a personalized management plan may require an adjustment in our approach based not only on the age demographic of those we serve but accessibility of digital information, online platforms, and opinions from those connected in MS support groups. Medical care has evolved substantially over the past decade. Whereas patients would simply follow medical advice provided in the past, a movement beyond “trust but verify” seems to exist— with patients seeking additional opinions through family members or friends who also have MS, online searches, support groups, and social media. Patients also seem to self-diagnose more frequently and, to a greater extent, request a specific regimen for medical management. All in all, strategies used to educate and place patients at ease in the past may not be as effective in our current day-to-day practice.
Technology is expected to play a greater role in nearly every facet of MS care in the future. The hope is that through leveraging a variety of platforms, advancements specific to enhancing our diagnostic, surveillance capabilities, and medical care keep pace with the overall growth of technology outside of medicine. An expansion in the development of prescription digital therapeutics, or software prescribed similar to the prescription of medications at a pharmacy, is expected, and it appears easy to forecast in light of recent events that medical care, in general, is trending more toward visits that are not office based. In addition, artificial intelligence platforms designed by a variety of agencies are also currently evaluating outcomes related to MS by incorporating a wealth of traditional and nontraditional data in large MS datasets to reduce the seemingly randomness of MS.
In this special issue of NeurologyLive®, experts expand upon innovations related to the more accurate identification of MS lesions, how age demographics may play a key role in what and how we communicate, current clinical challenges that health care providers face in clinic as it relates to the wealth of treatment choices, the welcomed/unwelcomed introduction of generic therapies, how technology may change how we practice, and much more. The aim is to highlight key efforts that work toward providing better education and care that our patients with MS expect and deserve.