Siponimod: Disentangling disability and relapses in secondary progressive multiple sclerosis

Area of Science:

• Neurology
• Clinical Trials
• Biostatistics

Background:

• Treatment effects on disability progression in multiple sclerosis (MS) can be confounded by relapse reduction.
• Distinguishing direct treatment effects from relapse-modifying effects is crucial for accurate assessment.

Purpose of the Study:

• To differentiate siponimod's direct impact on disability progression from its effect on relapses in the EXPAND trial.
• To evaluate siponimod's efficacy in secondary progressive multiple sclerosis (SPMS) irrespective of relapse status.

Main Methods:

• Utilized three estimands: principal stratum, hypothetical no-relapse scenario, and hypothetical equal-relapse scenario.
• Assessed siponimod's effect on 3- and 6-month confirmed disability progression, controlling for on-study relapses.

Main Results:

• Principal stratum analysis showed siponimod reduced 3-month disability progression risk by 14%-20% and 6-month by 29%-33% in non-relapsing patients.
• Hypothetical scenarios indicated siponimod's relapse-independent risk reduction for 3-month progression was 14%-18% and for 6-month was 23%.

Conclusions:

• Statistical methods were developed to isolate treatment effects on disability progression from confounding relapse data.
• Siponimod demonstrates potential utility in treating SPMS, benefiting both relapsing and non-relapsing patient populations.