Aging is associated with reduced inflammatory disease activity independent of disease duration in relapsing multiple sclerosis trial populations

Author:

Coerver Eline ME1ORCID,Kaçar Sezgi1ORCID,Ciccarelli Olga23,Sormani Maria P4ORCID,Barkhof Frederik256ORCID,Arnold Douglas L278ORCID,Schoonheim Menno M9ORCID,Van Kempen Zoé LE1,Mostert Jop10,Koch Marcus W11ORCID,Killestein Joep1,Eshaghi Arman25,Uitdehaag Bernard MJ1,Strijbis Eva MM1ORCID

Affiliation:

1. MS Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, Location VU Medical Centre, Amsterdam, The Netherlands

2. Queen Square Multiple Sclerosis Centre, Department of Neuroinflammation, UCL Queen Square Institute of Neurology, Faculty of Brain Sciences, University College London, London, UK

3. National Institute for Health and Care Research (NIHR) University College London Hospitals (UCLH) Biomedical Research Centre, London, UK

4. Department of Health Sciences (DISSAL), University of Genova, Genova, Italy; Ospedale Policlinico San Martino IRCCS, Genoa, Italy

5. Queen Square Institute of Neurology and Centre for Medical Image Computing, University College London, London, UK

6. MS Center Amsterdam, Department of Radiology and Nuclear Medicine, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, Location VU medical center, Amsterdam, The Netherlands

7. NeuroRx Research and Montreal Neurological Institute, McGill University, Montreal, QC, Canada

8. Montreal Neurological Institute, McConnell Brain Imaging Centre, McGill University, Montreal, QC, Canada

9. MS Center Amsterdam, Anatomy and Neuroscience, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, Location VU medical center, Amsterdam, The Netherlands

10. Department of Neurology, Rijnstate Hospital, Arnhem, The Netherlands

11. Department of Clinical Neurosciences, University of Calgary, Calgary, AB, Canada

Abstract

Background: Higher age is associated with less inflammatory disease activity in relapsing-remitting multiple sclerosis (RRMS). It is unknown whether age itself or disease duration underlies this association. Objectives: This study investigated the effects of age, disease duration, and inflammatory disease activity in people with RRMS. Methods: Individual patient-level data from five large phase III randomized controlled trials (RCTs) was utilized to investigate the association of both age and disease duration with annualized relapse rate (ARR), contrast-enhancing lesions (CELs), and new T2 lesions on magnetic resonance imaging (MRI) at baseline and follow-up. Results: The data set included 5626 participants. Higher age was associated with lower ARRs, lower CEL number on MRI at baseline and follow-up, and lower new T2 lesion numbers at follow-up. This effect was present in all disease duration groups. For example, we found a lower number of new T2 lesions on MRI during follow-up in higher age groups compared to lower age groups, independent of disease duration. Conclusion: Aging in RRMS is associated with a lower risk of inflammatory disease activity, across different disease durations. Age should be taken into account when designing clinical trials and future research should investigate how age should be integrated into personalized predictions of treatment response and risk profiling.

Funder

International Progressive MS Alliance

Publisher

SAGE Publications

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