BACKGROUND: People over age 50-55 have historically been excluded from randomized clinical trials for multiple sclerosis (MS). However, more than half of those living with an MS diagnosis are over 55. OBJECTIVE: Explore the unique considerations of treating older people with MS (PwMS) using an iterative and structured Delphi-based assessment to gather expert opinions. METHODS: Eight MS neurologists with an interest in older PwMS developed a 2-round survey. Survey respondents were qualified neurologists with ≥3 years' experience, personally responsible for treatment decisions, and treating ≥20 patients per month, of whom ≥10% were ≥50 years old. Consensus was defined as ≥75% agreement on questions with categorical responses or as a mean score ≥4 on questions with numerical responses. RESULTS: In Survey 1, 224 neurologists responded; 180 of these completed Survey 2. Limited consensus was reached with varying levels of agreement on several topics including identification and assessment of older patients; factors relating to treatment decisions including immunosenescence and comorbidities; considerations for high-efficacy treatments; de-escalation or discontinuation of treatment; effects of COVID-19; and unmet needs for treating this population. CONCLUSION: The results of this Delphi process highlight the need for targeted studies to create guidance for the care of older PwMS.

Biogen Cambridge MA USA

Biogen Cambridge MA USA at the time of this study

Department of Neurology Charles University Prague Czech Republic

Department of Neurology Pontificia Universidad Católica de Chile Santiago Chile

Department of Neurology Renaissance School of Medicine Stony Brook University Stony Brook NY USA

Department of Neurology University of Ulm Ulm Germany

Department of Neurosciences Hospital Universitari Germans Trias i Pujol Badalona Spain

Faculty of Medicine and University Hospital Pilsen Czech Republic

MS Clinic Medicarte Medellín Colombia

Multiple Sclerosis Center ASST Spedali Civili Di Brescia Montichiari Italy

Neuroimmunology Unit Department of Neuroscience Hospital Alemán Buenos Aires Argentina

Zobrazit více v PubMed

Walton C, King R, Rechtman L, et al. Rising prevalence of multiple sclerosis worldwide: insights from the Atlas of MS, third edition. Mult Scler 2020; 26: 1816–1821. PubMed PMC

McGinley MP, Goldschmidt CH, Rae-Grant AD. Diagnosis and treatment of multiple sclerosis: a review. JAMA 2021; 325: 765–779. PubMed

Wallin MT, Culpepper WJ, Campbell JD, et al. The prevalence of MS in the United States: a population-based estimate using health claims data. Neurology 2019; 92: e1029–e1040. PubMed PMC

Prosperini L, Lucchini M, Ruggieri S, et al. Shift of multiple sclerosis onset towards older age. J Neurol Neurosurg Psychiatry 2022: jnnp-2022-329049. PubMed

Marrie RA. Comorbidity in multiple sclerosis: implications for patient care. Nat Rev Neurol 2017; 13: 375–382. PubMed

Magyari M, Sorensen PS. Comorbidity in multiple sclerosis. Front Neurol 2020; 11: 851–851. PubMed PMC

Zhang T, Tremlett H, Zhu F, et al. Effects of physical comorbidities on disability progression in multiple sclerosis. Neurology 2018; 90: e419–e427. PubMed PMC

Monaco S, Nicholas R, Reynolds Ret al. et al. Intrathecal inflammation in progressive multiple sclerosis. Int J Mol Sci 2020; 21: 8217. PubMed PMC

Castle SC. Clinical relevance of age-related immune dysfunction. Clin Infect Dis 2000; 31: 578–585. PubMed

Crooke SN, Ovsyannikova IG, Poland GAet al. et al. Immunosenescence and human vaccine immune responses. Immun Ageing 2019; 16: 25. PubMed PMC

Palacios-Pedrero MÁ, Jansen JM, Blume C, et al. Signs of immunosenescence correlate with poor outcome of mRNA COVID-19 vaccination in older adults. Nature Aging 2022; 2: 896–905. PubMed PMC

Manouchehri N, Salinas VH, Rabi Yeganeh N, et al. Efficacy of disease modifying therapies in progressive MS and how immune senescence may explain their failure. Front Neurol 2022; 13: 854390. PubMed PMC

Grebenciucova E, Berger JR. Immunosenescence: the role of aging in the predisposition to neuro-infectious complications arising from the treatment of multiple sclerosis. Curr Neurol Neurosci Rep 2017; 17: 61. PubMed

Patti F, Penaherrera JN, Zieger Let al. et al. Clinical characteristics of middle-aged and older patients with MS treated with interferon beta-1b: post-hoc analysis of a 2-year, prospective, international, observational study. BMC Neurol 2021; 21: 324. PubMed PMC

Avolio C, Centonze D. Pivotal trials in multiple sclerosis: similarities prove not to be useful. Neurol Ther 2022; 11: 1–8. PubMed PMC

Shirani A, Zhao Y, Petkau J, et al. Multiple sclerosis in older adults: the clinical profile and impact of interferon beta treatment. Biomed Res Int 2015; 2015: 451912. PubMed PMC

Berkovich R, Negroski D, Wynn D, et al. Effectiveness and safety of switching to teriflunomide in older patients with relapsing multiple sclerosis: a real-world retrospective multicenter analysis. Mult Scler Relat Disord 2022; 70: 104472. PubMed

Thompson MT, Virginia D, Nick B, et al. Adherence and discontinuation rates in patients on Tecfidera™ (dimethyl fumarate): long-term Canadian experience from the Biogen ONE™ support program. Mult Scler Relat Disord 2022; 67: 104080. PubMed

Jakimovski D, Eckert SP, Zivadinov Ret al. et al. Considering patient age when treating multiple sclerosis across the adult lifespan. Expert Rev Neurother 2021; 21: 353–364. PubMed

Niederberger M, Spranger J. Delphi technique in health sciences: a map. Front Public Health 2020; 8: 457. PubMed PMC

Vollmer BL, Wolf AB, Sillau S, et al. Evolution of disease modifying therapy benefits and risks: an argument for De-escalation as a treatment paradigm for patients with multiple sclerosis. Front Neurol 2021; 12: 799138. PubMed PMC

Weideman AM, Tapia-Maltos MA, Johnson K, et al. Meta-analysis of the age-dependent efficacy of multiple sclerosis treatments. Front Neurol 2017; 8: 577. PubMed PMC

Romero-Pinel L, Bau L, Matas E, et al. The age at onset of relapsing-remitting multiple sclerosis has increased over the last five decades. Mult Scler Relat Disord 2022; 68: 104103. PubMed

Capasso N, Virgilio E, Covelli A, et al. Aging in multiple sclerosis: from childhood to old age, etiopathogenesis, and unmet needs: a narrative review. Front Neurol 2023; 14: 1207617. PubMed PMC

Vaughn CB, Jakimovski D, Kavak KS, et al. Epidemiology and treatment of multiple sclerosis in elderly populations. Nat Rev Neurol 2019; 15: 329–342. PubMed

Ostolaza A, Corroza J, Ayuso T. Multiple sclerosis and aging: comorbidity and treatment challenges. Mult Scler Relat Disord 2021; 50: 102815. PubMed

Brancati S, Gozzo L, Longo L, et al. Rituximab in multiple sclerosis: are we ready for regulatory approval? Front Immunol 2021; 12: 661882. PubMed PMC

Montalban X, Gold R, Thompson AJ, et al. ECTRIMS/EAN guideline on the pharmacological treatment of people with multiple sclerosis. Eur J Neurol 2018; 25: 215–237. PubMed

Prosperini L, Mancinelli CR, Solaro CM, et al. Induction versus escalation in multiple sclerosis: a 10-year real world study. Neurotherapeutics 2020; 17: 994–1004. PubMed PMC

Spelman T, Magyari M, Piehl F, et al. Treatment escalation vs immediate initiation of highly effective treatment for patients with relapsing-remitting multiple sclerosis: data from 2 different national strategies. JAMA Neurol 2021; 78: 1197–1204. PubMed PMC

Thompson AJ, Banwell BL, Barkhof F, et al. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol 2018; 17: 162–173. PubMed

Rae-Grant A, Day GS, Marrie RA, et al. Practice guideline recommendations summary: disease-modifying therapies for adults with multiple sclerosis: report of the guideline development, dissemination, and implementation subcommittee of the American academy of neurology. Neurology 2018; 90: 777–788. PubMed

Filippi M, Danesi R, Derfuss T, et al. Early and unrestricted access to high-efficacy disease-modifying therapies: a consensus to optimize benefits for people living with multiple sclerosis. J Neurol 2022; 269: 1670–1677. PubMed PMC

Inojosa H, Proschmann U, Akgün Ket al. et al. The need for a strategic therapeutic approach: multiple sclerosis in check. Ther Adv Chronic Dis 2022; 13: 20406223211063032. PubMed PMC

Perdaens O, van Pesch V. Molecular mechanisms of immunosenescene and inflammaging: relevance to the immunopathogenesis and treatment of multiple sclerosis. Front Neurol 2021; 12: 811518. PubMed PMC

Corboy JR, Fox RJ, Kister I, et al. Risk of new disease activity in patients with multiple sclerosis who continue or discontinue disease-modifying therapies (DISCOMS): a multicentre, randomised, single-blind, phase 4, non-inferiority trial. Lancet Neurol 2023; 22: 568–577. PubMed

Weinberger B. Vaccines for the elderly: current use and future challenges. Immun Ageing 2018; 15: 3. PubMed PMC

Otero-Romero S, Lebrun-Frénay C, Reyes S, et al. ECTRIMS/EAN consensus on vaccination in people with multiple sclerosis: Improving immunization strategies in the era of highly active immunotherapeutic drugs. Mult Scler 2023; 29: 904–925. PubMed PMC

National Multiple Sclerosis Society. COVID-19 Vaccine Guidance for People Living with MS. https://www.nationalmssociety.org/coronavirus-covid-19-information/covid-19-vaccine-guidance. Published 2023. Updated May 11, 2023. Accessed July 9, 2023.

Hasson F, Keeney S, McKenna H. Research guidelines for the Delphi survey technique. J Adv Nurs 2000; 32: 1008–1015. PubMed

Reilly GD, Mahkawnghta AS, Jelinek PL, et al. International differences in multiple sclerosis health outcomes and associated factors in a cross-sectional survey. Front Neurol 2017; 8: 229. PubMed PMC

Rieckmann P, Centonze D, Elovaara I, et al. Unmet needs, burden of treatment, and patient engagement in multiple sclerosis: a combined perspective from the MS in the 21st Century Steering Group. Mult Scler Relat Disord 2018; 19: 153–160. PubMed

Gómez-López A, Benito-León J, Labiano-Fontcuberta A, et al. Impact of a specific consultation for patients with progressive forms of multiple sclerosis on the response to their unmet care needs: a cross-sectional study. Mult Scler Relat Disord 2023; 72: 104609. PubMed

Lus G, Bassano MA, Brescia Morra V, et al. Unmet needs and gaps in the identification of secondary progression in multiple sclerosis: a Southern Italy healthcare professionals’ perspective. Neurol Sci 2023; 44: 45–58. PubMed PMC