Heterogeneity on long-term disability trajectories in patients with secondary progressive MS: a latent class analysis...

Area of Science:

• Neurology
• Clinical Research
• Biostatistics

Background:

• Natural history studies of progressive multiple sclerosis (MS) have reported on patient heterogeneity.
• Previous research demonstrated variability in long-term disability trajectories for primary progressive MS (PPMS).
• The progression patterns in secondary progressive MS (SPMS) require further detailed investigation.

Purpose of the Study:

• To identify distinct subgroups of SPMS patients based on similar longitudinal disability trajectories.
• To analyze disability progression rates in a large cohort of SPMS patients.
• To inform patient stratification for clinical trials and understand disease mechanisms.

Main Methods:

• Latent Class Growth Analysis (LCGA) was employed to model longitudinal Expanded Disability Status Scale (EDSS) scores.
• Data from large international MS registries (cohort 1: N=3613 SPMS; cohort 2: N=7613 SPMS) were utilized.
• Non-linear time functions were used to model disability progression from the first EDSS visit (EDSS 3-4).

Main Results:

• LCGA identified three distinct SPMS disability trajectory subgroups: mild (35.9%), moderate (53.6%), and severe (10.5%).
• Median time to reach EDSS 6 varied significantly: 12.1 years (mild), 5.0 years (moderate), and 1.7 years (severe).
• At 8 years, the probability of reaching EDSS 6 was 14.4% (mild), 78.4% (moderate), and 98.3% (severe).

Conclusions:

• SPMS patients exhibit significantly different rates of disability progression.
• The identified distinct trajectories can optimize patient selection for SPMS clinical trials.
• These subgroups may represent underlying heterogeneous pathological mechanisms driving disease progression.