Age-dependent response to initial highly effective treatment in relapsing multiple sclerosis.

Area of Science:

• Neurology
• Immunology
• Clinical Research

Background:

• Relapsing forms of multiple sclerosis (MS) require effective disease-modifying treatments (DMTs).
• Highly effective (HE) DMTs offer potential advantages over platform DMTs.
• The impact of patient age on HE-DMT efficacy in real-world settings is not fully understood.

Purpose of the Study:

• To evaluate the age-dependent effectiveness of highly effective (HE) disease-modifying treatments (DMTs) compared to platform DMTs.
• To assess the risk of disability accumulation in relapsing-remitting MS patients based on age and DMT type.

Main Methods:

• Retrospective analysis of 20,984 relapsing-remitting MS patients from the Italian Multiple Sclerosis Register.
• Propensity score matching created comparable groups of patients initiating HE-DMTs or platform DMTs.
• Cox regression models analyzed the risk of 24-week confirmed disability accumulation (CDA) over 2 years and longer follow-up.

Main Results:

• HE-DMTs significantly reduced CDA risk compared to platform DMTs (HR=0.22, p<0.001) after 2 years.
• HE-DMTs demonstrated greater efficacy in patients under 45 years (HR=0.49, p<0.001) but not in those over 45 (HR=0.77, p=0.125).
• Prolonged exposure to any DMT reduced disability accumulation in patients over 45 (HR=0.13, p=0.050).

Conclusions:

• The superior benefit of initial HE-DMTs in relapsing MS patients diminishes with increasing age.
• Regardless of efficacy, sustained DMT exposure is crucial for reducing disability accumulation, even in older MS patients.
• Individualized treatment decisions considering age and DMT exposure duration are essential for optimizing outcomes in multiple sclerosis.