Confirmed disability progression provides limited predictive information regarding future disease progression in...

Area of Science:

• Neurology
• Clinical Trials
• Disease Progression

Background:

• Confirmed disability progression (CDP) is frequently observed in multiple sclerosis (MS) clinical trials.
• The predictive value of CDP for long-term outcomes in MS remains uncertain.

Purpose of the Study:

• To determine if CDP at 24 months predicts subsequent disability accumulation in multiple sclerosis patients.
• To compare the predictive power of CDP against other clinical factors for MS progression.

Main Methods:

• Analysis of data from the Comprehensive Longitudinal Investigation of Multiple Sclerosis (CLIMuS) cohort (N=1214).
• Utilized Cox proportional hazards models to assess CDP as a predictor of time to Expanded Disability Status Scale (EDSS) 6 and secondary progressive MS (SPMS).
• Compared model fit statistics, including Akaike's Information Criterion, for models with and without CDP, incorporating clinical and MRI data.

Main Results:

• Univariate analysis showed a directional association between CDP and faster time to EDSS 6 (HR=1.61).
• After adjusting for month 24 EDSS, CDP showed a directional association with slower time to EDSS 6 (aHR=0.65).
• Models incorporating CDP had poorer fit statistics compared to those using EDSS scores alone; T2 lesion volume improved model fit.

Conclusions:

• CDP at 24 months is less predictive of future disability events in MS than other clinical features.
• Current MS clinical trial metrics may require refinement to better predict long-term patient outcomes.