Considering patient age when treating multiple sclerosis across the adult lifespan

ABSTRACT

Introduction: The successful development of anti-inflammatory disease-modifying treatments (DMT) significantly improved disease outcomes and longevity of persons with multiple sclerosis (pwMS). However, the shift toward an elderly MS population has resulted with new concerns regarding DMT efficacy and safety.

Areas covered: This review summarizes the evidence of an age-based decrease in the efficacy of MS DMTs and increase in pharmacovigilance concerns. The age effects on pathophysiological MS processes, immunosenescence and its relevance to DMT selection or discontinuation are also reviewed. Lastly, the authors discuss the influence of age-associated comorbidities on DMT initiation and drug-induced events.

Expert opinion: There is an age discrepancy between pwMS included in regulatory drug trials and an aging real-world MS population. Most trials demonstrate significantly diminished anti-inflammatory efficacy in patients older than 40 years old. Older age is associated with a greater risk for adverse events including serious infections. Age-associated comorbidities influence the risk-benefit analysis and sometimes cause patients to discontinue DMTs. Instead of chronological age cutoffs, therefore, studies should aim at promoting biologically-based age biomarkers.

KEYWORDS:

• Multiple sclerosis
• disease modifying treatment
• age
• adverse events
• immunosenescence
• comorbidities
• infection risk

Article highlights

• There is a significant discrepancy between the age of persons with multiple sclerosis (pwMS) enrolled in clinical trials and the average age of patients seen in real-world settings.

• Majority of anti-inflammatory disease modifying treatments (DMT) have reduced efficacy when administered in aging pwMS.

• Older pwMS treated with DMT have greater risk for common and serious adverse events.

• Age-associated comorbidities may reduce the DMT efficacy and increase the risk for drug intolerance, occurrence of adverse events and drug failure.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Declaration of interest

R Zivadinov received personal compensation from Bristol Myers Squibb, EMD Serono, Sanofi, Novartis and Keystone Heart for speaking and consultant fees. He received financial support for research activities from Bristol Myers Squibb, Sanofi, Novartis, Keystone Heart, V-WAVE Medical, Mapi Pharma and Protembis. Bianca Weinstock-Guttman has participated in speaker’s bureaus and/or served as a consultant for Biogen, Novartis, Genzyme; Sanofi, Genentech, Abbvie, Bayer AG, and Celgene/BMS. B Weinstock-Guttman also has received grant/research support from the agencies listed in the previous sentence as well as Mallinckrodt Pharmaceuticals, Inc. She serves in the editorial board for BMJ Neurology, Journal of International MS and CNS Drugs. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or conflict with the subject matter or materials discussed in this manuscript apart from those disclosed.

Additional information

Funding

On the topic of aging in multiple sclerosis, Dr. Bianca Weinstock-Guttman has recieved funding through Biogen IIS Aging: B.Weinstock-Guttman, US-mSG-15-10855 grant, National Multiple Sclerosis Society (NMSS) - HC1411-02004 grant, and support from Advancing Research in Multiple Scleorsis (ARMS).