AI-driven reclassification of multiple sclerosis progression 2025, Habib Ganjgahi et al

[Mij]

Abstract​

Multiple sclerosis (MS) affects 2.9 million people. Traditional classification of MS into distinct subtypes poorly reflects its pathobiology and has limited value for prognosticating disease evolution and treatment response, thereby hampering drug discovery.

Here we report a data-driven classification of MS disease evolution by analyzing a large clinical trial database (approximately 8,000 patients, 118,000 patient visits and more than 35,000 magnetic resonance imaging scans) using probabilistic machine learning. Four dimensions define MS disease states: physical disability, brain damage, relapse and subclinical disease activity.

Early/mild/evolving (EME) MS and advanced MS represent two poles of a disease severity spectrum. Patients with EME MS show limited clinical impairment and minor brain damage. Transitions to advanced MS occur via brain damage accumulation through inflammatory states, with or without accompanying symptoms. Advanced MS is characterized by moderate to high disability levels, radiological disease burden and risk of disease progression independent of relapses, with little probability of returning to earlier MS states.

We validated these results in an independent clinical trial database and a real-world cohort, totaling more than 4,000 patients with MS.

Our findings support viewing MS as a disease continuum. We propose a streamlined disease classification to offer a unifying understanding of the disease, improve patient management and enhance drug discovery efficiency and precision.
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[Utsikt]

New study shows MS is not fixed subtypes but a dynamic continuum of states across 4 dimensions: disability, brain damage, relapses & silent inflammation.

I thought this was well known already? At least it’s what my family has been told by their doctors.

Judging by their discussion, it seems to me like there has been a view that for the now severe MS patients, the previous diseases states you’ve been in matters in terms of treatment responses, disability and prognosis. But this shows that it doesn’t matter how you got there - and they are pretty much the same.

Regarding the advanced states of MS, our results do not support maintaining a distinction between SPMS and PPMS; patients with SPMS and patients with PPMS were similarly distributed among the advanced states of the disease, both in the NO.MS dataset and in the real-world validation set. Once patients reach the advanced states of the disease, the risk of progression is high, and the chances of a treatment response are low, regardless of whether the previous disease course was characterized by relapses or not. Our results align well with the accumulating evidence that the apparent evolution from EME states to advanced states of the disease reflects a partial shift from predominantly localized acute injury to widespread chronic inflammation and secondary neurodegeneration13,14,41,42,43,44,45,46.