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. 2024 Sep;30(10):1296-1308.
doi: 10.1177/13524585241272938. Epub 2024 Sep 8.

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

Eline Me Coerver  1 , Sezgi Kaçar  1 , Olga Ciccarelli  2   3 , Maria P Sormani  4 , Frederik Barkhof  2   5   6 , Douglas L Arnold  2   7   8 , Menno M Schoonheim  9 , Zoé LE Van Kempen  1 , Jop Mostert  10 , Marcus W Koch  11 , Joep Killestein  1 , Arman Eshaghi  2   5 , Bernard Mj Uitdehaag  1 , Eva Mm Strijbis  1
Affiliations

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

Eline Me Coerver et al. Mult Scler. 2024 Sep.

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.

Keywords: Aging; inflammation; relapsing MS.

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Conflict of interest statement

Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: E.M.E.C. reports no disclosures. S.K. reports no disclosures. O.C. is a member of independent DSMB for Novartis, gave a teaching talk on McDonald criteria in a Merck local symposium, and contributed to an Advisory Board for Biogen; she is Deputy Editor of Neurology, for which she receives an honorarium. M.P.S. received consulting fees from Biogen, Merck, Novartis, Roche, Sanofi, Immunic, Alexion. F.B. serves on the steering committee and is iDMC member for Biogen, Merck, Roche, and EISAI. He acts as a consultant for Roche, Biogen, Merck, IXICO, Jansen, and Combinostics. He has research agreements with Novartis, Merck, Biogen, GE, and Roche. He is co-founder and share holder of Queen Square Analytics Ltd. D.L.A. reports consulting fees from Biogen, Celgene, Frequency Therapeutics, Genentech, Merck, Novartis, Race to Erase MS, Roche, Sanofi-Aventis, Shionogi, and Xfacto Communications; grants from Immunotec and Novartis; and an equity interest in NeuroRx. M.M.S. serves on the editorial board of Neurology, Multiple Sclerosis Journal and Frontiers in Neurology; receives research support from the Dutch MS Research Foundation, Eurostars-EUREKA, ARSEP, Amsterdam Neuroscience, and ZonMW (Vidi grant, project no. 09150172010056); and has served as a consultant for or received research support from Atara Biotherapeutics, Biogen, Celgene/Bristol Meyers Squibb, EIP, Sanofi, MedDay, and Merck. Z.L.E.V.K. reports no disclosures. J.M. reports no disclosures. M.W.K. received consulting fees and travel support from Biogen Idec, Novartis, Roche, Sanofi Genzyme, and EMD Serono. B.M.J.U. has received research support and/or consultancy fees from Biogen Idec, Genzyme, Merck Serono, Novartis, Roche, TEVA, and Immunic Therapeutics. A.E. has received research grants from the Medical Research Council (MRC), National Institute for Health and Care Research (NIHR), Innovate UK, Biogen, Merck, and Roche. He serves as an advisory board member of Merck Serono and Bristol Myers Squib. He is the founder and equity stakeholder in Queen Square Analytics Ltd. He serves on the editorial board of Neurology (American Academy of Neurology). J.K. has accepted speaker and consulting fees from Merck, Biogen, TEVA, Sanofi, Genzyme, Roche, and Novartis. E.M.M.S. has accepted speaker fees from Merck and Novartis.

Figures

Figure 1.
Figure 1.
Age versus disease activity during follow-up for the different DMT categories. Proportion of trial participants with contrast-enhancing lesions (CELs) or new T2 lesions per age group for the different DMT categories in the different trials. In each of the panels, green means no CELs/new T2 lesions, orange means 1–2 CELs/new T2 lesions, purple means 3–4 CELs/new T2 lesions, and pink means 5 or more CELs/new T2 lesions. In the panels with “first-line DMT,” we included the trial arms with interferon-beta-1a, dimethyl fumarate (twice or three times a day), glatiramer acetate, and laquinimod. In the second-line DMT panel, we included the ocrelizumab arm of the opera trials. CELs: contrast-enhancing lesions; RR: rate ratio; β: regression coefficient.
Figure 2.
Figure 2.
Age versus disease activity during follow-up per disease duration group. Rate ratio or beta coefficient and 95% confidence intervals show the difference between each of the age groups in relation to the reference age group of 25–30 years for the number of CELs, new T2 lesions, and ARR across the different disease duration subgroups. ARR: annualized relapse rate; CELs: contrast-enhancing lesions; β: regression coefficient. *p < 0.050; **p < 0.010; ***p < 0.001.
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