Selection of Clinical Outcome Assessments for Trial Readiness in ARSACS - 2-year Progression and Responsiveness to Change Part 1: Disease Severity, Swallowing, Upper Limb Function, and Participation.

Progress has been made in developing new therapies for certain ataxias. To ensure clinical trial readiness and support the development of robust trial design, it is essential to know the disease progression rate and metrological properties of clinical outcome assessments (COAs), including their responsiveness to change. The objectives of this study were 1) to document over a trial-relevant time frame of two years the progression of disease severity, swallowing, upper limb function, and participation, and 2) to assess the responsiveness to change of related COAs in adults with autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS), one of the most frequent recessive ataxias worldwide. Sixty participants from two neuromuscular clinics (Saguenay and Québec City, Canada) were included. The COAs were the Disease Severity Index for ARSACS (DSI-ARSACS), Scale for the Assessment and Rating of Ataxia (SARA), Swallowing Disturbance Questionnaire, grip and pinch strength, Standardized Finger-to-Nose test, TEMPA, Barthel Index, and Assessment of Life Habits questionnaire. Self-perception of previous-year progression of specific impairments was also documented using a global rating of change scale (GRS). A significant progression in the DSI-ARSACS (-1.5 points), SARA (+ 1.6 points), Barthel Index (-7.4 points), and grip (-2.3 kg) and pinch (-0.25 kg) strength was observed. Only a few COAs were able to specifically detect a difference in participants who reported worsening, with grip strength being the most sensitive COA to assess upper limb function. Since a high proportion of participants reported not having any impairments, the statistical power was limited for responsiveness analyses and further study would be needed.