Multiple sclerosis has long been organized into three familiar clinical categories: relapsing–remitting, secondary progressive and primary progressive. These labels have shaped diagnosis, clinical trials and treatment decisions for decades. Yet a new roadmap from the International Advisory Committee on Clinical Trials in Multiple Sclerosis argues that the system is increasingly out of step with what researchers understand about the disease. Rather than representing sharply separated stages, the descriptors often compress a complex and changing biological process into broad clinical labels.
The central problem is that multiple sclerosis is not a single, uniform disorder. It is an immune-mediated disease of the central nervous system in which inflammation, demyelination, axonal injury, neuronal loss and tissue repair can occur at the same time, but in different combinations and at different intensities. Two people assigned the same clinical course may therefore have very different disease mechanisms operating beneath the surface. One may have frequent focal inflammatory attacks visible on magnetic resonance imaging, while another may accumulate disability through slowly evolving neurodegeneration with few obvious relapses.
The relapsing–remitting category illustrates this limitation. It generally describes patients who experience episodes of neurological dysfunction followed by periods of partial or substantial recovery. However, clinical recovery does not necessarily mean that the disease has become biologically inactive. New lesions may develop without symptoms, and damage can accumulate silently between recognized relapses. Conversely, some symptoms may reflect residual injury rather than a new inflammatory event. The label captures the visible pattern of illness, but not always the activity taking place in the brain and spinal cord.
The transition to secondary progressive multiple sclerosis is also more gradual than the terminology suggests. In practice, worsening disability may emerge slowly, fluctuate from year to year or become apparent only after the effects of repeated inflammatory injuries have accumulated. The precise point at which a patient moves from a relapsing pattern to a progressive one can therefore be difficult to define. Primary progressive multiple sclerosis, meanwhile, identifies people whose disability increases from the outset, but it does not necessarily describe a single biological pathway. Progressive disease can involve varying contributions from inflammation, compartmentalized immune activity, mitochondrial dysfunction, synaptic damage and failure of nervous-system repair.
The roadmap proposes that future descriptions should reflect this multidimensional reality. Instead of treating disease course as a fixed sequence of named stages, clinicians could describe multiple sclerosis through continuously updated dimensions, including inflammatory activity, progression independent of relapse activity, and the degree of disability or neurological impairment. Such a framework would recognize that inflammation and progression are not mutually exclusive. A patient may have active new lesions while also experiencing gradual worsening, or may show disability progression with little evidence of conventional inflammatory activity.
This shift would require more than changing terminology. Biologically informed descriptions would depend on increasingly sensitive measurements that can detect disease processes before they become obvious in routine neurological examinations. MRI already provides information about new or enlarging lesions, contrast enhancement, brain-volume loss and damage in the spinal cord, although these measures do not capture every aspect of pathology. Fluid biomarkers, including molecules associated with axonal injury and glial activation, may offer additional insight into ongoing tissue damage. Digital assessments of walking, hand function, vision and cognition could also reveal subtle changes that are missed during intermittent clinic visits.
A dynamic system could improve both patient care and research. Clinicians would be able to distinguish ongoing inflammatory activity from disability that continues independently of relapses, potentially supporting more precise treatment decisions. Researchers could select trial participants according to the mechanism a therapy is designed to target, rather than relying primarily on broad clinical categories. This might make it easier to evaluate treatments aimed at preventing progression, protecting neurons, restoring myelin or modifying chronic inflammation—goals that are difficult to assess when all outcomes are reduced to relapse counts or a single disability scale.
The proposed transition also carries important practical challenges. New descriptors would need to be reliable across hospitals, countries and patient populations, and they would have to remain understandable to patients and healthcare professionals. Biomarkers must be validated, standardized and shown to provide information that changes clinical decisions. Any new framework should avoid creating a more complicated classification that simply replaces one set of rigid labels with another. It must also account for differences in age, disease duration, treatment exposure, comorbidities and access to care, all of which can influence how multiple sclerosis appears clinically.
The roadmap therefore presents evolution rather than an overnight replacement of the current system. Existing relapsing and progressive terms remain useful for communication and for interpreting decades of research, but they may increasingly be supplemented by biological and clinical descriptors that are updated over time. The long-term goal is a living profile of each patient’s disease, combining symptoms, disability, imaging, biomarkers and treatment response. Such a profile could bring medical language closer to the biology of multiple sclerosis—and help move care toward earlier detection, more precise intervention and a clearer understanding of why the disease follows such different paths in different people.
Subject of Research: Multiple sclerosis disease course and the development of biologically informed clinical descriptors
Article Title: Towards a biologically informed description of multiple sclerosis disease course — a roadmap for transition
Article References: Thompson, A.J., Lublin, F.D., Rechtman, L. et al. Towards a biologically informed description of multiple sclerosis disease course — a roadmap for transition. Nature Reviews Neurology (2026). https://doi.org/10.1038/s41582-026-01249-0
Image Credits: AI Generated
DOI: 10.1038/s41582-026-01249-0
Keywords: multiple sclerosis, disease progression, relapsing–remitting multiple sclerosis, secondary progressive multiple sclerosis, primary progressive multiple sclerosis, neuroinflammation, neurodegeneration, biomarkers, MRI, precision medicine
Tags: axonal injuryclinical disease categoriesdemyelinationdisease mechanisms variabilitydisease progressionimmune-mediated central nervous systemMRI imaging in MSMultiple Sclerosisneurodegeneration in MSneuroinflammationneuronal losstissue repair
