EDSS variability before randomization may limit treatment discovery in primary progressive MS.

Area of Science:

• Neurology
• Clinical Trials
• Biostatistics

Background:

• The Expanded Disability Status Scale (EDSS) is a key measure for assessing disability in multiple sclerosis (MS).
• Typically, baseline EDSS relies on a single measurement, potentially limiting its sensitivity to detect changes.
• This study investigates optimizing baseline EDSS assessment for clinical trials.

Purpose of the Study:

• To evaluate if a baseline EDSS derived from two pre-treatment measurements improves the detection of progression events.
• To assess the impact of using two baseline EDSS measurements on demonstrating therapeutic effects in delaying MS disability progression.

Main Methods:

• Analysis of real data from the OLYMPUS trial (rituximab in primary progressive multiple sclerosis - PPMS) and simulated data.
• Comparison of different baseline EDSS definitions to capture sustained disability progression (SDP) events.
• Estimation of EDSS variations using linear mixed-effect models.

Main Results:

• Using the higher of two baseline EDSS scores decreased sensitivity but increased specificity for detecting SDP events.
• Using the lower of two baseline EDSS scores increased sensitivity but decreased specificity.
• A ~7% increase in statistical power was observed when using the average of screening and Week 0 EDSS scores as the baseline.

Conclusions:

• Deriving baseline EDSS from two pre-treatment measurements can improve the detection of therapeutic effects in slowing disability progression in PPMS.
• This refined baseline EDSS strategy holds promise for implementation in future MS clinical trials.
• Optimizing baseline EDSS assessment is crucial for enhancing the efficacy of clinical trials in MS.