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Multiple sclerosis
Original research
Long-term disability trajectories in multiple sclerosis: a group-based trajectory analysis of the AusLong cohort
  1. Amin Zarghami1,
  2. Mohammad Akhtar Hussain2,3,
  3. Ingrid van der Mei1,
  4. Steve Simpson-Yap1,4,
  5. Anne-Louise Ponsonby5,6,
  6. Jeanette Lechner-Scott7,8,
  7. Simon A Broadley9,10,
  8. Robyn M Lucas11,
  9. Yuan Zhou1,
  10. Xin Lin1,
  11. AusLong Investigator Group1,
  12. Bruce V Taylor1
  1. 1Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia
  2. 2Barwon South West Public Health Unit, Barwon Health, Geelong, Australia, Geelong, Victoria, Australia
  3. 3IMPACT-Institute for Mental and Physical Health and Clinical Translation, Deakin University School of Medicine, Geelong, Victoria, Australia
  4. 4Neuroepidemiology unit, The University of Melbourne School of Population and Global Health, Melbourne, Victoria, Australia
  5. 5The Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia
  6. 6Murdoch Children’s Research Institute, Parkville, Victoria, Australia
  7. 7The University of Newcastle Hunter Medical Research Institute, New Lambton, New South Wales, Australia
  8. 8The University of Newcastle School of Medicine and Public Health, Callaghan, New South Wales, Australia
  9. 9School of Medicine, Griffith University, Nathan, Queensland, Australia
  10. 10Department of Neurology, Gold Coast University Hospital, Southport, Queensland, Australia
  11. 11National Centre for Epidemiology and Population Health, The Australian National University, Canberra, Australian Capital Territory, Australia
  1. Correspondence to Professor Bruce V Taylor; bruce.taylor{at}utas.edu.au

Abstract

Background Previous natural history studies highlighted a consistent heterogeneity of disability trajectories among individuals with primary or secondary progressive multiple sclerosis (MS). However, evidence on disability progression in relapsing onset MS is scarce.

The aim of this study was to investigate heterogeneity in disability accumulation over 10 years following a first clinical diagnosis of central nervous system demyelination (FCD) and identify genetic, demographic, environmental and clinical factors associated with these trajectories.

Methods We used group-based trajectory models to measure heterogeneity in disability trajectories based on the Expanded Disability Status Scale (EDSS) in a prospectively assessed cohort of 263 participants. To capture sustained neurological impairments and avoid issues related to significant changes in EDSS associated with relapse, we did not consider EDSS points recorded within 3 months of a relapse.

Results We identified three distinct and clinically meaningful disability trajectories: No/minimal, moderate and severe. Those in the no/minimal disability trajectory showed no appreciable progression of disability (median EDSS∼1 at 10-year review) while those in the moderate and severe disability trajectories experienced disability worsening (median time to reach EDSS 4 was 9 and 7 years, respectively). Compared with the no/minimal disability trajectory, those with older age, a higher number of relapses within the first 5 years post-FCD, and a higher number of comorbidities at baseline were more likely to be in the worse disability trajectory. Surprisingly, baseline MRI and anatomical site of initial symptoms did not influence long-term outcomes.

Conclusions Those at higher risk of faster MS disability progression can be identified based on their early clinical characteristics with potential therapeutic implications for early intervention and treatment escalation.

  • MULTIPLE SCLEROSIS
  • MRI
  • EPIDEMIOLOGY

Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information.

https://doi.org/10.1136/jnnp-2024-333632

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    Data availability statement

    All data relevant to the study are included in the article or uploaded as supplementary information.

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    Footnotes

    • AZ and MAH are joint first authors.

    • X @aydzhouyuan

    • Collaborators AusImmune/AusLong Investigators Group: RML (National Centre for Epidemiology and Population Health, Canberra), Keith Dear (Duke Kunshan University, Kunshan, China), A-LP (The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Australia), A-LP and Terry Dwyer (Murdoch Children’s Research Institute, Melbourne, Australia), IvdM, Leigh Blizzard, SS-Y and BVT (Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia), SAB (School of Medicine and Dentistry, Griffith University, Gold Coast Campus, Australia), Trevor Kilpatrick (Centre for Neurosciences, Department of Anatomy and Neuroscience, University of Melbourne, Melbourne, Australia), David Williams, JLS (School of Medicine and Public Health, University of Newcastle, Newcastle, Australia, Hunter Medical Research Institute, Newcastle, NSW, Australia), Cameron Shaw and Caron Chapman (Barwon Health, Geelong, Australia), Alan Coulthard (University of Queensland, Brisbane, Australia), Michael P Pender (The University of Queensland, Brisbane, Australia) and Patricia Valery (QIMR Berghofer Medical Research Institute, Brisbane, Australia).

    • Contributors BVT, MAH and AZ contributed to the conception and design of the study. MAH and AZ contributed to the acquisition and analysis of data. Ausimmune/AusLong Investigator Group contributed to the design and data collection of AusLong study. BVT and IvdM supervised the study. AZ, MAH, IvdM, SS-Y, A-LP, JLS, SAB, YZ, XL, AusLong Investigator Group and BVT contributed to the interpretations of the findings and the critical revision of the manuscript. BVT is responsible for the overall content as the guarantor.

    • Funding Financial support for this research was provided by grants from the National Multiple Sclerosis Society of the USA (award no. RG3364A1/2) and the National Health and Medical Research Council of Australia (grant nos. APP316901, 224215 and 1127819).

    • Competing interests BVT has received compensation for consulting, talks and advisory/steering board activities for Merck, Novartis, Biogen and Roche. He receives research funding support from MS Research Australia, Medical Research Future Fund Australia and the National Health and Medical Research Council Australia.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.