Background:
Clinical Rating Scales have been a hallmark of assessing progression in neuromuscular disease, and in particular in Friedreich’s Ataxia. Such scales are often challenging, especially in terms of clinical relevance and interpretability, both on a population and individual patient level. However, these scales are significantly more sensitive than patient-reported outcomes in assessing progression, complicating the application of traditional anchor- or distribution-based methods for defining clinical significance.
The Upright Stability Score (USS, or FARS E), the axial subscore of the modified Friedreich’s Ataxia rating scale (mFARS) includes a battery of six objective timed balance and stance measures. These functions are lost in a sequential fashion, eventually leading to, and becoming predictive of loss of ambulation.
Objective:
Establish the relationship between FARS E scores and the time to loss of ambulation, by conducting serial of time-to-event analyses. This correlation provides insight into the clinical significance of maintaining individual FARS E functions.
Results: The results indicate that a clear relationship can be demonstrated between time to loss of ambulation and FARS E scores. Each point in the FARS E score corresponds to a median delay of 0.55 years (6.6 months) in the time to loss of ambulation. Specifically, the delay was 0.52 years (6.2 months) in children and 0.68 years (8.2 months) in adults.
Conclusions:
We demonstrate the utility of long-term natural history data to quantify clinical benefit as assessed with the upright Stability subscore. While overall results need to be treated with caution, given the genetic diversity of FA as a disease, the overall concept is transferable to other ataxias and potentially any progressive neuromuscular diseases.