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New Framework for MS Diagnosis, Treatment Proposed


An international panel of experts has proposed a new way to classify multiple sclerosis (MS) that would ultimately change the way patients are diagnosed and treated.

The goal is to eventually move away from the current system, which classifies MS based on disease progression into distinct relapsing-remitting, secondary progressive, and primary progressive subtypes.

Members of the International Advisory Committee on Clinical Trials in Multiple Sclerosis, which developed the framework, note the new framework is based on underlying biology of disease and acknowledges the different trajectories of individual patients.

“The categorization of patients into distinct subtypes or stages is artificial,” framework co-author Jeffrey Cohen, MD, director of Experimental Therapeutics, Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic, Cleveland, Ohio, told Medscape Medical News. “The rationale for the new framework was recent studies demonstrating that the biologic processes that underlie relapses and progression are present to varying degrees throughout the disease course, representing a continuum.”

The proposal was published online November 18 in Lancet Neurology.

A More Responsive System

Since the current MS classification, dubbed the Lublin–Reingold descriptors, was introduced, there have been calls for a different system that is more responsive to biological changes inherent in MS.

The committee, which is jointly sponsored by the European Committee for Treatment and Research in Multiple Sclerosis and the US National Multiple Sclerosis Society, responded by clarifying clinical course descriptions published in 1996 and 2013. The proposed framework grew out of that process.

“One of the main points is the concept that patients don’t evolve into secondary progressive MS,” Cohen said. “The processes that underlie progression and the findings of proxy measures of progression are present from the earliest stages of the disease.”

In its report, the committee reviews current data on the pathophysiology of injury and compensatory mechanisms in MS, presenting findings that suggest disease progression is caused not by a single disease mechanism, but from a combination of several processes that vary from patient to patient.

Current research studies highlighted in the report include those focused on mechanisms of injury, such as acute and chronic inflammation, myelin loss, nerve fiber and neuron loss, and mitochondrial dysfunction. How the body responds to that injury is likely to determine how MS evolves in each patient, the committee writes.

Studies point to a range of factors that influence how MS manifests and progresses, including patients’ age at onset, biological sex, genes, race, ethnicity, comorbid health conditions, health behaviors, therapies, and social and environmental exposures.

Potential for Better Treatments

Any new framework for classifying the disease in the future would enable the development and approval of more biologically based treatment approaches, Cohen said.

“One anticipated advantage of the new framework is that treatments should be evaluated based on their efficacy on biologic processes, not in artificial categories of patients,” Cohen said.

Cohen and other committee members acknowledge that developing the framework is just a first step in what would likely be a long and complicated process.

“This proposal is among many initiatives that the committee has supported over the years as part of its overarching aim to constantly improve, update and enhance clinical trial design and inform clinical care delivery for people living with MS and their healthcare teams,” committee chair Ruth Ann Marrie, MD, PhD, director of the Multiple Sclerosis Clinic at the University of Manitoba Health Sciences Center, Winnipeg, Manitoba, said in a press release.

Commenting on the proposal for Medscape Medical News, Tony Reder, MD, professor of neurology at the University of Chicago Medicine, Chicago, Illinois, said the paper offers a “good framework for all trialists attempting to go beyond the usual markers.”

The authors “have good reasons to propose the need for a new mechanism-driven framework to define multiple sclerosis progression,” writes Takashi Yamamura, MD, PhD, director and chief of the Neuroimmunology Section and director of Multiple Sclerosis Center, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan, in an accompanying commentary.

Adopting biologically based definitions of MS progression will be challenging to implement, the authors admit. The current subtype classification is woven into clinical care and research models and is the basis for regulatory approval of new therapeutics. Replacing it will take time and require external validation in the clinic and the lab.

“Although the goal is distant and many obstacles might arise (such as reaching a consensus between physicians, academia, and stakeholders), the time seems right to launch initiatives to reframe the classification of multiple sclerosis subtypes,” Yamamura adds.

The study was supported by the German Research Foundation and the Intramural Research Program of NINDS. Cohen reports personal compensation for consulting for Biogen, Convelo, EMD Serono, Gossamer Bio, Mylan, and PSI. Yamamura has received support from AMED-CREST, Novartis, and Chiome Bioscience; and speaker honoraria from Novartis, Biogen, Chugai, Alexion, Mitsubishi-Tanabe, and Takeda.

Lancet Neuro. Published online November 18, 2022. Article, Editorial

Kelli Whitlock Burton is a reporter for Medscape Medical News covering neurology and psychiatry.

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