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  • Review Article
  • Published:

Assessing disease progression and treatment response in progressive multiple sclerosis

Nature Reviews Neurology volume 20, pages 573–586 (2024)Cite this article

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Abstract

Progressive multiple sclerosis poses a considerable challenge in the evaluation of disease progression and treatment response owing to its multifaceted pathophysiology. Traditional clinical measures such as the Expanded Disability Status Scale are limited in capturing the full scope of disease and treatment effects. Advanced imaging techniques, including MRI and PET scans, have emerged as valuable tools for the assessment of neurodegenerative processes, including the respective role of adaptive and innate immunity, detailed insights into brain and spinal cord atrophy, lesion dynamics and grey matter damage. The potential of cerebrospinal fluid and blood biomarkers is increasingly recognized, with neurofilament light chain levels being a notable indicator of neuro-axonal damage. Moreover, patient-reported outcomes are crucial for reflecting the subjective experience of disease progression and treatment efficacy, covering aspects such as fatigue, cognitive function and overall quality of life. The future incorporation of digital technologies and wearable devices in research and clinical practice promises to enhance our understanding of functional impairments and disease progression. This Review offers a comprehensive examination of these diverse evaluation tools, highlighting their combined use in accurately assessing disease progression and treatment efficacy in progressive multiple sclerosis, thereby guiding more effective therapeutic strategies.

Key points

  • Effective treatment of progressive multiple sclerosis (MS) remains an urgent medical need.

  • The recent approvals of treatments for progressive forms of MS highlight the importance of better disease monitoring measures in clinical trials and practice.

  • Traditional MRI biomarkers do not adequately track progressive MS. Advances in MRI, such as brain atrophy and lesion volume analysis, show promise in assessing disease progression and response to treatment.

  • Remyelination is key in MS neuroprotection. MRI techniques such as magnetization transfer and myelin water fraction imaging, alongside PET scans, provide deeper insights into myelin repair and inflammation.

  • Changes in optical coherence tomography, a non-invasive imaging modality that measures retinal layer thickness, reflect brain atrophy and MS progression, offering a valuable window into neurodegeneration and treatment efficacy.

  • Body fluid biomarkers, such as neurofilament light in blood, and immune activation and neuronal damage markers in cerebrospinal fluid are emerging as important tools for assessing disease activity and treatment response in progressive MS.

  • Patient-reported outcomes capture the unique experience of individuals with MS, which is of particular importance in progressive forms of the disease. These assessments can help evaluate hidden symptoms such as fatigue and cognitive impairment and are becoming vital in clinical trials and routine practice.

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Authors and Affiliations

  1. Department of Neurorehabilitation Sciences, Casa di Cura Igea, Milan, Italy

    Giancarlo Comi

  2. Vita-Salute San Raffaele University, Milan, Italy

    Gloria Dalla Costa & Letizia Leocani

  3. Sorbonne Université, Paris Brain Institute, Institut du Cerveau et de la Moelle Épinière, Centre National de la Recherche Scientifique, Inserm, Paris, France

    Bruno Stankoff

  4. Brain and Mind Center, University of Sydney, Sydney, Australia

    Hans-Peter Hartung

  5. Department of Neurology, Palacky University Olomouc, Olomouc, Czech Republic

    Hans-Peter Hartung

  6. Department of Neurology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany

    Hans-Peter Hartung

  7. Department of Neurology, Danish Multiple Sclerosis Center, University of Copenhagen, Rigshospitalet, Copenhagen, Denmark

    Per Soelberg Sørensen

  8. University of Lille, Inserm U1172, Lille Neuroscience & Cognition, Centre Hospitalier Universitaire de Lille, Fédération Hospitalo-Universitaire Precision Medicine in Psychiatry, Lille, France

    Patrick Vermersch

  9. Multiple Sclerosis Center, Casa di Cura Igea, Milan, Italy

    Letizia Leocani

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Contributions

G.C., G.D.C., B.S., H.-P.H., P.S.S., P.V. and L.L. searched data for the article and made substantial contributions to discussions of the content and each wrote a section. All authors edited and reviewed the document before submission.

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Correspondence to Giancarlo Comi.

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Competing interests

G.C. has received consulting and speaking fees from Bristol Myers, Janssen, Novartis, Rewind, Roche, Sanofi and Squibb. G.D.C. has received funding for research, travel and/or speaker honoraria from Biogen, Celgene, Merck, Novartis, Roche and Teva. B.S. has received research support from Merck, Novartis and Roche and honoraria for lectures from Biogen, Janssen, Novartis, Merck and Sanofi. H.-P.H. received honoraria for serving on steering committees from Roche, Sanofi and TG Therapeutics, for serving on data monitoring committees from Merck KG and Novartis and on the scientific advisory board of Aurinia. P.S.S. has received personal compensation for serving on scientific advisory boards, steering committees or independent data monitoring boards for Biogen, Celgene, Forward Pharma GlaxoSmithKline, Genzyme, MedDay Pharmaceuticals, Merck, Novartis and TEVA and has received speaker honoraria from Biogen, Genzyme Merck, Novartis and Teva. His department has received research support from Biogen, Merck, Novartis, Roche, RoFAR, Sanofi-Aventis/Genzyme and TEVA. P.V. has received honorarium for contribution to meetings from AB Science, Ad Scientiam, Biogen, BMS-Celgene, Imcyse, Janssen, Merck, Novartis, Roche, Sanofi-Genzyme and Teva and research support from Merck, Novartis and Sanofi-Genzyme. L.L. has received research support from Almirall, Biogen, Merck and Novartis and consultancy or speaker fees from Almirall, Biogen, Bristol-Myers Squibb, Janssen-Cilag, Merck, Novartis and Roche.

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Comi, G., Dalla Costa, G., Stankoff, B. et al. Assessing disease progression and treatment response in progressive multiple sclerosis. Nat Rev Neurol 20, 573–586 (2024). https://doi.org/10.1038/s41582-024-01006-1

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