Preserving Neurological Function in People at High and Low Risk of Aggressive Multiple Sclerosis: An Observational...

Area of Science:

• Neurology
• Immunology
• Pharmacology

Background:

• Aggressive multiple sclerosis (MS) is characterized by early disability accumulation.
• Patients aged ≥35 years with Expanded Disability Status Scale (EDSS) ≥3 at symptom onset are at high risk for aggressive MS.
• Identifying high-risk individuals is crucial for timely, effective treatment.

Purpose of the Study:

• To evaluate if high-efficacy disease-modifying therapy (HE-DMT) reduces relapse and disability progression in high-risk aggressive MS patients.
• To determine if HE-DMT benefits vary based on MS severity.
• To compare HE-DMT effectiveness against lower-efficacy treatments or no treatment.

Main Methods:

• Observational cohort study using MSBase and OFSEP registries.
• Included adults with relapse-onset MS and EDSS within 12 months of onset.
• Classified patients into high-risk and low-risk groups for aggressive MS.
• Used marginal structural models to compare continuous HE-DMT versus non-HE-DMT periods.
• Adjusted for time-varying confounders to estimate cumulative hazards of relapses and disability worsening/improvement.

Main Results:

• Continuous HE-DMT reduced relapse risk in both high-risk and low-risk groups.
• No significant difference in overall disability outcomes between HE-DMT and non-HE-DMT periods.
• No interaction found between MS risk stratum and HE-DMT treatment effect.
• Lowest relapse risk observed in low-risk group treated with HE-DMT.
• HE-DMT reduced disability worsening in high-risk patients during treatment, comparable to low-risk group levels.

Conclusions:

• HE-DMTs effectively reduce relapse risk in all MS patients, irrespective of aggressive MS risk.
• No overall difference in disability progression was observed between HE-DMT and non-HE-DMT periods in the general population.
• However, HE-DMT use was associated with reduced disability worsening among patients treated with it, particularly in the high-risk group.