A variety of high-efficacy disease-modifying therapies (DMTs) are available for the treatment of multiple sclerosis (MS). After evaluation and approval by regulatory agencies, DMTs are likely to be administered to patients whose characteristics differ from those enrolled in clinical trials. This may contribute to the emergence of unexpected adverse events observed in the real-world setting. Higher age may be a relevant factor that could change the benefit–risk balance of DMTs, as it may associate with lower efficiency and higher frequency of adverse events.
The absolute and relative number of patients with MS who reach the age of 55 and higher increases. Growing evidence demonstrates lower efficacy of DMTs in older persons with MS. Specific risks during DMTs for MS, such as the risk of developing progressive multifocal leukoencephalopathy (PML) or the outcome following PML, have been associated with age. It is hypothesized that age-related and therapy-induced alterations to the immune system may have (super)additive effects, resulting in an acceleration of physiological immunosenescence and inflamm-aging.
In this article, we review the risks of high-efficacy DMTs in MS with a specific focus on age-related efficacy and risks, including opportunistic infections, malignancies, and autoimmune reactions.
aDepartment of Neurology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne
bCognitive Neuroscience, Institute of Neuroscience and Medicine (INM-3), Research Center Jülich, Jülich, Germany
cBrain and Mind Centre
dNeuroimmunology Clinic, Concord Hospital, University of Sydney, Sydney, NSW, Australia
eDepartment of Neurology, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany
Correspondence to Clemens Warnke, MD, Klinik und Poliklinik für Neurologie Universitätsklinik Köln Kerpener Straße 62, 50937 Köln, Germany. E-mail: firstname.lastname@example.org or Prof. Hans-Peter Hartung, MD, PhD, Department of Neurology, Heinrich-Heine-University, Moorenstr. 5, 40225 Düsseldorf, Germany. E-mail: email@example.com