Classifying Patients with Amyotrophic Lateral Sclerosis by Changes in FVC. A Group-based Trajectory Analysis

Area of Science:

• Neurology
• Pulmonology
• Biostatistics

Background:

• Amyotrophic lateral sclerosis (ALS) is characterized by progressive respiratory muscle weakness.
• Stratifying ALS progression is crucial for understanding disease mechanisms and identifying patient phenotypes for clinical trials.
• Forced vital capacity (FVC) is a key indicator of respiratory function in ALS.

Purpose of the Study:

• To identify distinct clinical phenotypes of ALS respiratory progression.
• To categorize ALS progression based on forced vital capacity (FVC) trajectories over time.
• To develop a predictive model for respiratory muscle weakness progression in ALS patients.

Main Methods:

• A group-based trajectory model was derived from a single-center cohort of 837 ALS patients.
• The model was applied to the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) database (7,461 patients).
• Baseline characteristics predicted trajectory group membership, with FVC over time as the primary outcome.

Main Results:

• Three FVC trajectories were identified: "stable low," "rapid progressor," and "slow progressor."
• Rapid progressors showed shorter diagnosis delay, more bulbar-onset disease, and lower ALSFRS-R scores at baseline compared to slow progressors.
• The model predicted respiratory insufficiency in the PRO-ACT cohort with a concordance statistic of 0.78.

Conclusions:

• A validated group-based trajectory model for FVC progression in ALS was developed.
• This model accurately predicts respiratory insufficiency in an external ALS cohort.
• Future research should focus on stratifying patients, particularly those predicted as rapid progressors.