MS treatment de-escalation: review and commentary

Area of Science:

• Neurology
• Immunology
• Geriatrics

Background:

• Current multiple sclerosis (MS) treatments often require lifelong administration, posing risks like infections and cancers, especially with age-related immune system changes (immunosenescence).
• Inflammatory activity in MS typically declines with age, suggesting potential for modifying treatment intensity in older individuals.
• Existing studies on de-escalating disease-modifying therapies (DMTs) for MS have focused on specific circumstances, with limited data on older populations.

Purpose of the Study:

• To review the evidence supporting DMT de-escalation as a viable strategy for older individuals with MS.
• To explore various de-escalation approaches, including dose adjustments, switching to less potent therapies, or treatment discontinuation.
• To assess the safety and efficacy of DMT de-escalation in the context of age-related immunosenescence and declining MS activity.

Main Methods:

• Review of existing literature on DMT de-escalation strategies in MS, including extended dosing, switching therapies, and discontinuation.
• Analysis of retrospective and observational studies examining the impact of age on DMT efficacy and outcomes.
• Consideration of a recent randomized-controlled discontinuation study in stable MS patients over 55 years old.

Main Results:

• Extended interval dosing of natalizumab maintained efficacy while reducing PML risk; ocrelizumab dosing mitigated Ig decline.
• Age is a significant factor in DMT efficacy; older patients discontinuing treatment showed stable disease, unlike younger counterparts.
• A recent study found stable MS in older patients (>55 years) after DMT discontinuation, with only a minor increase in MRI activity.

Conclusions:

• DMT de-escalation or discontinuation in MS patients over 55 may be non-inferior to continued high-risk immunosuppression, with potentially lower health risks.
• While current evidence is promising, larger, longer-term prospective studies are essential to definitively establish the benefits and risks of de-escalation.
• Future research should include randomized controlled trials comparing de-escalation, continuation, and discontinuation, with subgroup analyses by age and sex, and incorporate immunosenescence markers.