Q&A: History of MS includes dramatic advances in care, but unmet needs remain
To date, the FDA has approved more than 20 disease-modifying therapies for patients with MS, according to the National MS Society. The first agent in this class, interferon beta-1B, was approved in 1993.
Prior to the approval of interferon, no medications enabled physicians to change the trajectory of this disease, according to Barry Hendin, MD, of Banner Health University Medical Center Phoenix. Hendin noted that the prognosis for patients with MS has drastically changed since that first approval.
Hendin spoke with Healio Neurology about the evolution of treatment for patients with MS, the trajectory of the disease in different patient populations and the greatest unmet needs in the management of this chronic neurological condition.
Q: What are the most common concerns for patients with MS ?
A: The biggest concern that patients feel at every stage of MS, the one concern that is most shared across the patient spectrum, is worry about progressive disability — a gradual or a complete loss of function that keeps them from living their daily life independently, that changes their mobility or their thinking or their function.
If you’re newly diagnosed and in your early 20s, it’s fear about the disability you might hypothetically experience in 10 or 20 years; it’s the worry about whether you will still be able to function fully in society, whether you’ll still be able to meet your needs independently. If you’ve had MS for 20 or 30 years, it’s also about disability, but it’s about the progression of disability, losing the functions you currently have, becoming less independent and less able to take care of yourself.
The prognosis for MS has dramatically changed. Prior to 1993, there were no disease-modifying therapies for this disease. In other words, there wouldn’t have been any treatments for a patient who had MS in 1980 or 1987 or 1990 that would change how they fared with MS: how many attacks they would have, how much disability they would ultimately experience. There was a phrase that neurologists used in those days, “diagnose and adios,” because we had so little that we could do. Adios, in this case, doesn’t mean goodbye. It refers to the literal definition of adios: a dios, to God — you’re in God’s hands. We had done what we could do by making the diagnosis, and we educated patients and treated symptoms, but we couldn’t change the trajectory of the disease.
Between 1993, when the first disease-modifying therapy was approved, and 2020, approximately 20 DMTs have been approved for MS. We’ve been able to use these medications to change the trajectory of the disease so the prognosis is better and better, which means fewer relapses and less disability progression. Multiple studies have shown that what a person could expect with MS 40 years ago and what they can expect today are dramatically different: less disability and improved function. That’s the prognosis now. In addition, our therapies have evolved from being modestly efficacious to highly efficacious. As multiple new therapies have been developed since 1993, we’ve gotten better and better at reducing inflammation and disease progression with increasingly powerful tools.
Q: Is there a generally agreed upon standard of care for MS ?
A: There are things we know and things we don’t know in terms of best care. One of the neglected areas of best care is really the role of the neurologist in attention to comorbidities, the other things that affect outcomes: cigarette smoking, physical activity and exercise, obesity and good health in other systems, such as control of diabetes and hypertension, because those other illnesses affect prognosis and function in MS. Those are the knowns; those are reasonable wellness standards.
In MS, there is still a debate about what the right medication is for any individual patient. At the very least, we say patients with MS should be treated early and maintained on an agent that they can tolerate and that controls their clinical disease, as manifested by the attacks we can see on MRI scans, to avoid relapses and progression. That’s a given. What that exact agent is, though, varies from person to person. There are some patients who start with modest agents and escalate therapy. There are some patients who start with higher efficacy agents in the beginning and maintain higher efficacy agents. Although I tend to be in that latter group, it’s an ongoing debate and there is not yet a standard of care.
Q: Are there agents that are considered the go-to option for these different approaches?
A: That’s where the debate is right now. There are clinicians, particularly in the general neurology community, who begin treating patients with a lower efficacy therapy. In practices or clinics that focus on MS, there is a greater tendency to start with a higher efficacy agent. It depends on who you are as a clinician. The lower, more modestly efficacious agents are often used because they’ve been around the longest and they pose a low immunosuppressant risk. Many in academic centers and MS centers are using higher efficacy agents because of the fear that the greatest risk patients with MS experience is MS itself, so we have to treat MS profoundly or proportionately.
Q: Does treatment vary depending on MS subtype?
A: There are 3 MS subtypes: relapsing MS, secondary progressive MS and primary progressive MS. Most cases of MS — 85% — begin as relapsing MS; approximately 10% to 15% of cases as classified as PPMS. More than half of patients who have relapsing MS ultimately experience secondary progression. Patients who never have attacks or relapses, experiencing only slow progression, are classified as having PPMS.
There is only one approved therapy for PPMS right now in the United States: ocrelizumab. For the relapsing forms of MS, there are approximately 20 approved therapies. There is no one that is used to the exclusion of all the others.
Q: What major breakthroughs have there been in MS ?
A: Before 1993, there were zero disease-modifying therapies. To have even one such agent in 1993 represented a startling improvement in our ability to change the trajectory of MS. That first agent to be approved by the FDA for this disease was interferon beta-1B.
In those early days, the delivery vehicle for treatment evolved, moving from injections to pills to infusions. Associated with that has been an improvement in efficacy for reducing attacks and progression.
There have been two dramatic shifts in MS in the past 10 years. The first was the approval of the first treatment for PPMS. The second was the understanding that we were not only treating T cells with our therapy; we had also developed therapies that were directed against B cells.
In addition, there have been an increasing number of symptomatic therapies that improve quality of life. These therapies are directed toward improving energy, bladder function, mood or spasticity. Improving quality of life has been increasingly important.
The other advances have focused on trying to understand disease markers. The MRI was a great advance in our ability to understand MS; it tells us something about how severe the disease is and whether our treatments are working.
We’re now working on blood tests for soluble markers, which includes neurofilament light; most clinicians think this marker holds promise. Neurofilament light is a breakdown product of the neuron’s axon. If you’re losing nerve cells, neurofilament light is released into the blood. It tells us something about prognosis and also something about response to therapy, which is another marker. Although this isn’t yet an advance we can use in practice, we’re conducting trials to try to repair injury already done to the nervous system. That’s an evolving area of interest.
Q : Despite these advances, w hat areas of unmet need remain in MS?
A: In general, we’ve done an increasingly good job of reducing attacks and acute inflammation, but we still have not done a sufficiently good job in reducing progression of disability over time. One unmet need is understanding MS progression or progressive disability better so that we can treat it better. Another unmet need is repairing damage to the central nervous system. We also need to understand MS sufficiently enough to be able to ultimately predict it, treat it and end it.
Those are the general unmet needs, but I would contend that the unmet needs in MS are also very specific to the individual patient. These unmet needs include cognitive symptoms, bladder symptoms, loss of employment and insurance, and relationship issues, including divorce. There are so many unique needs, too. Those may include gait, spasticity or pain, and those aren’t normally handled easily by general neurologists. Another unmet need, in my opinion, is the increasing need for comprehensive MS care centers, which can manage all the various issues that patients with MS face. Caring for these patients takes a village.
FDA. FDA-approved drugs. https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=103471. Accessed Dec. 1, 2020.
National MS Society. Medications. https://www.nationalmssociety.org/Treating-MS/Medications#section-1. Accessed Dec. 1, 2020.