Disability accrual in primary and secondary progressive multiple sclerosis

Area of Science:

• Neurology
• Clinical Research
• Epidemiology

Background:

• Comparing primary progressive multiple sclerosis (PPMS) and secondary progressive multiple sclerosis (SPMS) has been challenging due to varying diagnostic criteria and cohort effects.
• Previous studies reported conflicting findings regarding the age of onset and disability accrual rates between PPMS and SPMS.

Purpose of the Study:

• To compare the age of onset for the progressive phase and the rate of disability accrual between PPMS and operationally diagnosed SPMS.
• To analyze disability trajectories in different multiple sclerosis phenotypes using a large international cohort.

Main Methods:

• Utilized the international, clinic-based MSBase cohort, including patients with PPMS or SPMS diagnosed since 1995.
• Employed Andersen-Gill hazard ratios to estimate disability accrual rates on the Expanded Disability Status Scale (EDSS), adjusting for multiple covariates.
• Estimated ages at onset of the progressive phase using Kaplan-Meier analysis and ages at EDSS milestones with Turnbull analysis.

Main Results:

• SPMS cases (n=2575) had a later median onset of the progressive phase (46.7 years) compared to PPMS cases (n=1872, 43.9 years).
• SPMS showed slower disability accrual (HR 0.86) despite greater baseline disability.
• Age at wheelchair dependence was similar between PPMS and SPMS.

Conclusions:

• SPMS is characterized by a later onset and slower disability progression compared to PPMS.
• Convergent disability trajectories may result from later onset balancing greater baseline disability in SPMS.
• Distinct disability accrual rates necessitate careful consideration when combining PPMS and SPMS in clinical trials.