Composite Confirmed Disability Worsening/Progression Is a Useful Clinical Endpoint for Multiple Sclerosis Clinical...

Area of Science:

• Neuroscience
• Clinical Trials
• Biostatistics

Background:

• Meaningful disability worsening measures are crucial for multiple sclerosis (MS) research.
• Composite confirmed disability worsening/progression (cCDW/cCDP) integrates Expanded Disability Status Scale (EDSS) with ambulation and dexterity performance tests.
• The utility of cCDW/cCDP as a clinical trial endpoint requires further assessment.

Purpose of the Study:

• To assess the relationship between changes in performance tests (Timed 25-Foot Walk Test [T25FWT] and Nine-Hole Peg Test [9HPT]) and subsequent Expanded Disability Status Scale (EDSS) changes.
• To evaluate the predictive validity of performance test worsening for disability progression in MS.
• To support the use of cCDW/cCDP as a primary outcome in MS clinical trials.

Main Methods:

• Individual patient-level data from 6 Roche-sponsored Phase III MS trials (n=4,979) were analyzed.
• Associations between T25FWT/9HPT events and subsequent EDSS events were characterized.
• Population-level data from 9 published studies were used to examine the relationship between treatment effects on T25FWT and EDSS events.

Main Results:

• Worsening on T25FWT and 9HPT was associated with an increased risk of subsequent EDSS worsening across various MS subtypes.
• Performance test events predicted subsequent EDSS events, even in patients without early EDSS changes.
• Treatment effects on T25FWT events were predictive of treatment effects on EDSS events (Spearman correlation = 0.82, p=0.005).

Conclusions:

• Worsening on T25FWT or 9HPT serves as an early indicator of EDSS worsening in MS.
• These findings validate the clinical relevance of performance test measures in MS.
• The results support the use of cCDW/cCDP as a primary outcome measure for assessing progression in MS clinical trials.