Experts propose overhaul of longtime system describing MS types

An international team of experts is calling for an overhaul of the system that has been used for decades to categorize and describe multiple sclerosis (MS).

The researchers presented a roadmap outlining how to begin moving from the current system that divides MS into three major subtypes toward a framework they said better reflects modern understanding of the underlying biology and clinical variability of MS.

“This publication does not change how MS is diagnosed, treated, or classified today,” Tim Coetzee, PhD, president and CEO of the National MS Society and a co-author of the study, said in a statement emailed to Multiple Sclerosis News Today. “But it lays the groundwork for a future where MS can be identified earlier, understood more precisely and treated in a way that reflects each person’s individual disease course.”

The society helped lead the development of the new roadmap, collaborating with other MS-focused groups around the world.

The paper, “Towards a biologically informed description of multiple sclerosis disease course — a roadmap for transition,” was published in Nature Reviews Neurology.

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A ‘more personalized understanding of MS’

“I’m proud of the role we’ve played in convening this effort to help pave the way for better outcomes for everyone affected by the disease,” Coetzee said. “It reflects our long-term commitment to ensuring that every person with MS gets an earlier, more accurate diagnosis and eventually, treatment approaches tailored to their own experience with the disease. This publication is an early but meaningful step toward a deeper, more personalized understanding of MS.”

MS is a chronic disease marked by inflammation that damages the brain and spinal cord. Since the 1990s, the disease has been classified into three major categories: relapsing-remitting MS (RRMS), secondary progressive MS (SPMS), and primary progressive MS (PPMS).

These categories were developed based on how MS manifests clinically. The categories are heavily dependent on whether patients experience relapses — periods during which MS symptoms suddenly worsen, usually followed by periods where symptoms ease.

Patients whose disease is mainly marked by relapses have been categorized as having RRMS. SPMS has been used to describe a later stage of disease following RRMS, where symptoms gradually worsen over time, independent of relapse activity. PPMS, meanwhile, has been used to describe patients whose disease gradually worsens from the onset.

The biggest problem with this system, the new paper argues, is that it assumes that each of these categories is discrete: Someone initially diagnosed with MS will either have RRMS or PPMS, with no room for overlap. Someone with RRMS may eventually transition to SPMS, but moving from SPMS back to RRMS is considered impossible under the old framework.

But in the decades since the system was developed, research has made it abundantly clear that these divisions do not reflect the actual course of MS. While it’s true that MS patients may experience periods of relapse and periods of gradual symptom worsening, these processes exist on a spectrum and can overlap.

Another major flaw with the system, according to the researchers, is that it only accounts for clinical manifestations of the disease, without considering the underlying biology that drives it.

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Dynamic labels, holistic treatment

The paper makes two broad recommendations. First, it suggests phasing out the use of RRMS, SPMS, and PPMS as labels for the type of MS a person has.

Instead, the researchers argued, MS may be described as either relapsing or progressive — but these labels should be dynamic, with reassessments at least once per year. Under this more flexible labeling system, a given patient might experience a relapsing course one year, then a progressive course the next year, then a relapsing course after that.

Another major recommendation is to move away from purely clinical descriptors toward a more holistic understanding of the disease. This would involve incorporating the relapsing/progressive clinical descriptors alongside patient-reported outcomes of how the disease is affecting day-to-day life, biomarker tests of underlying disease biology, and other co-occurring health conditions and lifestyle factors that may influence outcomes.

“Everyone with MS experiences the disease differently, and the end goal of this work is to enable more personalized treatment approaches that address all forms of MS and ultimately lead to better outcomes for every person living with the disease,” Bruce F. Bebo, Jr., PhD, chief research and medical affairs officer at the National MS Society, said in a society press release.

The researchers stressed that moving toward a new framework to describe MS will not be easy, as the old system is deeply entrenched in clinical care and regulatory frameworks for MS therapies. Building a new system “will require sustained, coordinated effort” that brings together stakeholders from across the MS community, including clinicians, patients, policymakers, and insurance providers, they said.

“With such a collaborative approach, we will accelerate progress and continue the transformation of MS treatment and care,” the researchers said.