patient care perspectives
Elderly Patients With Multiple Sclerosis: Efficacy of Disease-Modifying Therapy
As the probability of active multiple sclerosis (MS) declines with age and the susceptibility to adverse effects increases, the risks vs the benefits of disease-modifying therapy (DMT) in older patients should be carefully considered. Strategies that prevent relapse and protect against neurodegeneration are sought.
Malcolm H. Gottesman, MD
Chief Emeritus, Division of Neurology
“My own thinking is that we should follow a de-escalation paradigm, meaning that we should start with the high-efficacy drugs and back off as the patient ages.”
MS has 2 primary components: the inflammatory component and the degenerative component. The age at which the shift from an inflammatory to a neurodegenerative phenotype begins varies, with reports ranging from the 40s to the mid-50s. We have largely addressed the inflammatory component of MS with our current therapies, but the management of the degenerative component remains a great unmet need. The literature shows that the efficacy of DMT diminishes with advancing age in terms of MS disability; our therapies are effective in preventing relapse, but they are not as effective in preventing the accumulation of disability associated with aging and disease progression.
High-potency DMTs have many complications, some of which are more apparent in older patients, such as progressive multifocal leukoencephalopathy, malignancies, and serious infections. Now, with that said, when is it appropriate to stop these agents? It is sometimes a serious mistake to stop these drugs, particularly in elderly patients who can have severe MS attacks and accrue disability. My own thinking is that we should follow a de-escalation paradigm, meaning that we should start with the high-efficacy drugs and back off as the patient ages. The most important type of monitoring is magnetic resonance imaging (MRI). You need a baseline MRI before stopping treatment, followed by a follow-up in 6 months to 1 year.
I do not think that the more aggressive agents, such as the B-cell–modulating drugs, have any role in the treatment of patients with MS who are in their 80s. The immune system slows down with age, and the inflammatory component of MS begins to dwindle. Senescence also occurs in other areas, and cognitive impairment is frequently observed in those with MS. Individuals who are in their 80s should be using the more benign agents, such as the first-generation drugs, or perhaps agents such as dimethyl fumarate or teriflunomide. I do not think that we can preserve cognition in 70- or 80-year-old patients by giving them these potent drugs.
Benedict RHB, Tomic D, Cree BA, et al. Siponimod and cognition in secondary progressive multiple sclerosis: EXPAND secondary analyses. Neurology. 2021;96(3):e376-e386. doi:10.1212/WNL.0000000000011275
DeLuca J, Schippling S, Montalban X, et al. Effect of ozanimod on symbol digit modalities test performance in relapsing MS. Mult Scler Relat Disord. 2021;48:102673. doi:10.1016/j.msard.2020.102673
Musella A, Gentile A, Rizzo FR, et al. Interplay between age and neuroinflammation in multiple sclerosis: effects on motor and cognitive functions. Front Aging Neurosci. 2018;10:238. doi:10.3389/fnagi.2018.00238
Rae-Grant A, Day GS, Marrie RA, et al. Comprehensive systematic review summary: disease-modifying therapies for adults with multiple sclerosis: report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology [published correction appears in Neurology. 2019;93(17):769]. Neurology. 2018;90(17):789-800. doi:10.1212/WNL.0000000000005345
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. doi:10.1155/2015/451912
Zhang Y, Caldito NG, Shirani A, et al. Aging and efficacy of disease-modifying therapies in multiple sclerosis: a meta-analysis of clinical trials. Ther Adv Neurol Disord. 2020;13:1756286420969016. doi:10.1177/1756286420969016