December 12, 2022

Proposal for a New Framework to Describe Multiple Sclerosis

Summary: An international panel of experts propose the need for a new framework to describe multiple sclerosis (MS) that is based on the underlying biological disease processes, which vary with individuals over time, in place of the current descriptions (i.e., relapsing-remitting MS (RRMS), primary progressive MS (PPMS), and secondary progressive MS (SPMS)). This new framework aims to better describe the disease course across the lifespan and has the potential to improve patient care and drug development.

Background: The clinical presentation of MS is conventionally categorized into subtypes, including relapsing-remitting MS (RRMS), primary progressive MS (PPMS), and secondary progressive MS (SPMS) (learn more about types of MS – here). These classifications are currently used to communicate and inform patient care, research, and regulatory decision-making. However, often times the boundaries between these subtypes of MS are unclear (e.g., the boundary between RRMS and SPMS and the transition of one to the other) and do not take into account the differences between people with MS within the same subtype.

Details: MS researchers and clinicians from the International Advisory Committee on Clinical Trials in Multiple Sclerosis, supported by the National MS Society (USA) and the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), propose a new framework to describe the MS disease course. Based on increasing evidence, MS is proposed as a continuous disease process, driven by the underlying biological mechanisms that vary across individuals and over time. For example, there are mechanisms of injury (e.g., inflammation, demyelination, nerve fiber damage and loss) and compensatory mechanisms (e.g., repair, regeneration, remyelination, and nerve protection), and the interaction and balance between these mechanisms change across the MS disease course. Factors such as age, biological sex, genetic and environmental factors, and disease duration are likely to influence the ability of an individual to compensate for injury caused by MS.

Impact: The proposed framework shifts our view of MS from discrete subtypes (i.e., RRMS, PPMS, SPMS) to a continuous disease process driven by the underlying biological mechanisms (i.e., mechanisms of injury and compensatory mechanisms) across the lifespan. Use of this proposed framework has the potential to enhance patient care through more personalized treatments and accelerate drug discovery through improved clinical trial design. More research is needed to define classifications of MS based on an individual’s biology in addition to building consensus and adoption of a new framework by the global MS community.


Article published in Lancet Neurology on November 18, 2022 – Time for a new mechanism-driven framework to define multiple sclerosis progression. Link to article – here.

We acknowledge the National MS Society (USA) for authoring the original version of this article – here.