Strategic De-escalation of Disease-Modifying Therapies in Elderly Patients: Approaches and Considerations

Reich DS, Lucchinetti CF, Calabresi PA. Multiple Sclerosis. N Engl J Med. 2018;378(2):169–80. https://doi.org/10.1056/NEJMra1401483.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Tremlett H, Zhao Y, Rieckmann P, Hutchinson M. New perspectives in the natural history of multiple sclerosis. Neurology. 2010;74(24):2004–15. https://doi.org/10.1212/WNL.0b013e3181e3973f.

Article  PubMed  Google Scholar 

Hua LH, Solomon AJ, Tenembaum S, Scalfari A, Rovira À, Rostasy K, et al. Differential diagnosis of suspected multiple sclerosis in pediatric and late-onset populations: a review. JAMA Neurol. 2024. https://doi.org/10.1001/jamaneurol.2024.3062.

Article  PubMed  Google Scholar 

Faissner S, Plemel JR, Gold R, Yong VW. Progressive multiple sclerosis: from pathophysiology to therapeutic strategies. Nat Rev Drug Discov. 2019;18(12):905–22. https://doi.org/10.1038/s41573-019-0035-2.

Article  CAS  PubMed  Google Scholar 

Gross RH, Corboy J. De-escalation and discontinuation of disease-modifying therapies in multiple sclerosis. Curr Neurol Neurosci Rep. 2024;24(9):341–53. https://doi.org/10.1007/s11910-024-01355-w.

Article  PubMed  Google Scholar 

Coles AJ, Cox A, Le Page E, Jones J, Trip SA, Deans J, et al. The window of therapeutic opportunity in multiple sclerosis: evidence from monoclonal antibody therapy. J Neurol. 2006;253(1):98–108. https://doi.org/10.1007/s00415-005-0934-5.

Article  PubMed  Google Scholar 

Signori A, Schiavetti I, Gallo F, Sormani MP. Subgroups of multiple sclerosis patients with larger treatment benefits: a meta-analysis of randomized trials. Eur J Neurol. 2015;22(6):960–6. https://doi.org/10.1111/ene.12690.

Article  CAS  PubMed  Google Scholar 

Jakimovski D, Eckert SP, Zivadinov R, Weinstock-Guttman B. Considering patient age when treating multiple sclerosis across the adult lifespan. Expert Rev Neurother. 2021;21(3):353–64. https://doi.org/10.1080/14737175.2021.1886082.

Article  CAS  PubMed  Google Scholar 

Macaron G, Larochelle C, Arbour N, Galmard M, Girard JM, Prat A, Duquette P. Impact of aging on treatment considerations for multiple sclerosis patients. Front Neurol. 2023;7(14):1197212. https://doi.org/10.3389/fneur.2023.1197212.

Article  Google Scholar 

Weideman AM, Tapia-Maltos MA, Johnson K, Greenwood M, Bielekova B. Meta-analysis of the Age-Dependent Efficacy of Multiple Sclerosis Treatments. Front Neurol. 2017;10(8):577. https://doi.org/10.3389/fneur.2017.00577.

Article  Google Scholar 

Hartung DM. Health economics of disease-modifying therapy for multiple sclerosis in the United States. Ther Adv Neurol Disord. 2021;17(14):1756286420987031. https://doi.org/10.1177/1756286420987031.

Article  Google Scholar 

Bebo B, Cintina I, LaRocca N, Ritter L, Talente B, Hartung D, Ngorsuraches S, Wallin M, Yang G. The Economic Burden of Multiple Sclerosis in the United States: Estimate of Direct and Indirect Costs. Neurology. 2022;98(18):e1810–7. https://doi.org/10.1212/WNL.0000000000200150.

Article  PubMed  PubMed Central  Google Scholar 

Frischer JM, Weigand SD, Guo Y, Kale N, Parisi JE, Pirko I, et al. Clinical and pathological insights into the dynamic nature of the white matter multiple sclerosis plaque. Ann Neurol. 2015;78(5):710–21. https://doi.org/10.1002/ana.24497.

Article  PubMed  PubMed Central  Google Scholar 

Nicholas R, Magliozzi R, Marastoni D, Howell O, Roncaroli F, Muraro P, et al. High levels of perivascular inflammation and active demyelinating lesions at time of death associated with rapidly progressive multiple sclerosis disease course: a retrospective postmortem cohort study. Ann Neurol. 2024;95(4):706–19. https://doi.org/10.1002/ana.26870.

Article  CAS  PubMed  Google Scholar 

Azevedo CJ, Cen SY, Jaberzadeh A, Zheng L, Hauser SL, Pelletier D. Contribution of normal aging to brain atrophy in MS. Neurol Neuroimmunol Neuroinflamm. 2019;6(6):e616. https://doi.org/10.1212/NXI.0000000000000616.

Article  PubMed  PubMed Central  Google Scholar 

Tokarska N, Tottenham I, Baaklini C, Gawryluk JR. How does the brain age in individuals with multiple sclerosis? A systematic review. Front Neurol. 2023;30(14):1207626. https://doi.org/10.3389/fneur.2023.1207626.

Article  Google Scholar 

Sim FJ, Zhao C, Penderis J, Franklin RJ. The age-related decrease in CNS remyelination efficiency is attributable to an impairment of both oligodendrocyte progenitor recruitment and differentiation. J Neurosci. 2002;22(7):2451–9. https://doi.org/10.1523/JNEUROSCI.22-07-02451.2002.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Neumann B, Segel M, Chalut KJ, Franklin RJ. Remyelination and ageing: Reversing the ravages of time. Mult Scler. 2019;25(14):1835–41. https://doi.org/10.1177/1352458519884006.

Article  PubMed  PubMed Central  Google Scholar 

Dimovasili C, Fair AE, Garza IR, Batterman KV, Mortazavi F, Moore TL, Rosene DL. Aging compromises oligodendrocyte precursor cell maturation and efficient remyelination in the monkey brain. Geroscience. 2023;45(1):249–64. https://doi.org/10.1007/s11357-022-00621-4.

Article  CAS  PubMed  Google Scholar 

Windener F, Grewing L, Thomas C, Dorion MF, Otteken M, Kular L, et al. Physiological aging and inflammation-induced cellular senescence may contribute to oligodendroglial dysfunction in MS. Acta Neuropathol. 2024;147(1):82. https://doi.org/10.1007/s00401-024-02733-x.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Conway BL, Zeydan B, Uygunoğlu U, Novotna M, Siva A, Pittock SJ, Atkinson EJ, Rodriguez M, Kantarci OH. Age is a critical determinant in recovery from multiple sclerosis relapses. Mult Scler. 2019;25(13):1754–63. https://doi.org/10.1177/1352458518800815.

Article  PubMed  Google Scholar 

Benson LA, Healy BC, Gorman MP, Baruch NF, Gholipour T, Musallam A, et al. Elevated relapse rates in pediatric compared to adult MS persist for at least 6 years. Mult Scler Relat Disord. 2014;3(2):186–93. https://doi.org/10.1016/j.msard.2013.06.004.

Article  CAS  PubMed  Google Scholar 

McKay KA, Hillert J, Manouchehrinia A. Long-term disability progression of pediatric-onset multiple sclerosis. Neurology. 2019;92(24):e2764–73. https://doi.org/10.1212/WNL.0000000000007647.

Article  PubMed  PubMed Central  Google Scholar 

Knowles S, Middleton R, Cooze B, Farkas I, Leung YY, Allen K, UK MS Register Research Group, et al. Comparing the pathology, clinical, and demographic characteristics of younger and older-onset multiple sclerosis. Ann Neurol. 2024;95(3):471–86. https://doi.org/10.1002/ana.26843.

Article  CAS  PubMed  Google Scholar 

Mouresan EF, Mentesidou E, Berglund A, McKay KA, Hillert J, Iacobaeus E. Clinical characteristics and long-term outcomes of late-onset multiple sclerosis: a swedish nationwide study. Neurology. 2024;102(6):e208051. https://doi.org/10.1212/WNL.0000000000208051.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Confavreux C, Vukusic S. Natural history of multiple sclerosis: a unifying concept. Brain. 2006;129(Pt 3):606–16. https://doi.org/10.1093/brain/awl007.

Article  PubMed  Google Scholar 

Tremlett H, Zhao Y, Joseph J, Devonshire V, UBCMS Clinic Neurologists. Relapses in multiple sclerosis are age- and time-dependent. J Neurol Neurosurg Psychiatry. 2008;79(12):1368–74. https://doi.org/10.1136/jnnp.2008.145805.

Article  CAS  PubMed  Google Scholar 

Schwehr NA, Kuntz KM, Butler M, Enns EA, Shippee ND, Kingwell E, BeAMS Study Group, et al. Age-related decreases in relapses among adults with relapsing-onset multiple sclerosis. Mult Scler. 2020;26(12):1510–8. https://doi.org/10.1177/1352458519866613.

Article  PubMed  Google Scholar 

Tortorella C, Bellacosa A, Paolicelli D, Fuiani A, Di Monte E, Simone IL, Giaquinto P, Livrea P, Trojano M. Age-related gadolinium-enhancement of MRI brain lesions in multiple sclerosis. J Neurol Sci. 2005;239(1):95–9. https://doi.org/10.1016/j.jns.2005.08.006.

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