Post-onset ALSFRS-R Slope (POS) as a Predictor of Disease Progression in Patients with Amyotrophic Lateral Sclerosis (ALS)
Larisa Ibric1, John Furey2, Alexander Sherman3, Terry Heiman-Patterson1
1Temple University Lewis Katz School of Medicine, 2Temple University Hospital, 3Massachusetts General Hospital
Objective:
To validate whether POS predicts disease progression.
Background:
The ALSFRS-R is a validated questionnaire-based functional rating scale for determining ALS disease progression. Change in ALSFRS-R slope has also been used as a qualifying parameter for trial entry and as an efficacy endpoint. Recently, change in ALSFRS-R between symptom onset and diagnosis (post-onset slope, POS) has been discussed as a predictor of progression and survival.
Design/Methods:
A retrospective analysis of real-world data from the ALS/MND Natural History Consortium was performed on patients with an initial ALSFRS-R score documented at diagnosis (or within 14 months of disease onset) and the 12-month follow-up interval using a 3-month threshold. POS was defined as [(ALSFRS-R at diagnosis - 48) divided by (duration from onset to diagnosis)]. Interval slope was defined as [(ALSFRS-R at 12 months - ALSFRS-R at diagnosis) divided by (duration from diagnosis to interval visit)].
Results:
Analysis of 210 subjects who had available 12-month follow-up data showed an average POS of -0.972 +/- 0.818 and interval slope of -0.890 +/- 0.649 points/month. A linear regression model was then performed, demonstrating that the POS is a statistically significant predictor of 12-month slope when controlling for sex, site of onset, and baseline ALSFRS-R and FVC scores (t(176) = 2.542, p = 0.0119). For every point/month decrease in POS, the interval slope at 12-month follow-up decreases by 0.206.
Conclusions:
The ALSFRS-R is an accessible and reproducible scale reflecting function in ALS. The positive relationship between POS and 12-month interval slope indicates that individuals who experience a faster decline in ALSFRS-R between onset and diagnosis are likely to show a greater decline in their score at 12-months follow up. Therefore, POS can be used to predict disease progression, guide prognostic discussions and planning, and act as a lead-in period for therapeutic interventions.
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