Breaking the PROMISE: poor association between brain volume loss and clinical disability worsening over 2 years of follow-up in primary progressive multiple sclerosis

Marcus Koch; Jop Mostert; Eva M Strijbis; Miguel D’haeseleer; Øivind Torkildsen; Jacynthe Comtois; Pavle Repovic; Bernard M. J. Uitdehaag; Joep Killestein; Tarrant McPherson; Gary Cutter

doi:10.1136/jnnp-2025-337940

January 28, 2026Journal of Neurology Neurosurgery & Psychiatry

Breaking the PROMISE: poor association between brain volume loss and clinical disability worsening over 2 years of follow-up in primary progressive multiple sclerosis

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Key Points

The results show a notably weak association between brain volume loss and clinical disability over two years.
MRI measures indicated an inconsistent relationship with clinical outcomes, raising concerns about relevance.
Observational analysis across two-year follow-up reveals that lesion burden accumulation does not predict disability worsening.
Findings highlight the need for better trial endpoints in primary progressive multiple sclerosis, as current measures may not be functionally relevant.

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Implication

Observational analysis explores the link between brain volume loss and clinical disability in primary progressive multiple sclerosis, questioning current trial endpoints.

Abstract

The association of the investigated volumetric MRI measures and clinical disability outcomes was noticeably weak and inconsistent. Our findings question the suitability of brain volume loss and lesion burden accumulation as functionally relevant trial endpoints in PPMS and inform the design and interpretation of clinical trials in PPMS.

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Koch et al. (2026) studied this question.

synapsesocial.com/papers/69a75be0c6e9836116a23fff https://doi.org/10.1136/jnnp-2025-337940

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Breaking the PROMISE: poor association between brain volume loss and clinical disability worsening over 2 years of follow-up in primary progressive multiple sclerosis

Key Points

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Breaking the PROMISE: poor association between brain volume loss and clinical disability worsening over 2 years of follow-up in primary progressive multiple sclerosis

Key Points

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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