Spinal Muscular Atrophy Functional Composite Score Revised (SMA-FCR) in Untreated and Nusinersen-Treated Patient...

Area of Science:

• Neurology
• Clinical Trials
• Biostatistics

Background:

• The Spinal Muscular Atrophy Functional Composite (SMA-FC) integrates multiple assessments but has limitations.
• The Hammersmith Functional Motor Scale Expanded (HFMSE) exhibits floor and ceiling effects.
• The Upper Limb Module (ULM) also has limitations in capturing the full spectrum of motor function.

Purpose of the Study:

• To evaluate a revised SMA-FC (SMA-FCR) incorporating the Revised ULM (RULM).
• To assess the SMA-FCR's performance in both untreated and nusinersen-treated Spinal Muscular Atrophy (SMA) patients.
• To determine if the SMA-FCR is more sensitive to treatment-related changes than existing measures.

Main Methods:

• The study included 580 participants with HFMSE, RULM, and Six-Minute Walk Test (6MWT) data.
• SMA-FCR was calculated as the average of normalized scores from HFMSE, RULM, and 6MWT.
• Mean annual rates of change were analyzed in untreated and treated participants.

Main Results:

• The SMA-FCR demonstrated reduced floor effects in nonsitters and ceiling effects in walkers compared to individual scales.
• The mean annual rate of change in SMA-FCR was significantly different between untreated (-0.62) and treated (0.15) participants.
• The SMA-FCR showed a statistically significant difference in change rates between untreated and treated groups (0.77, p=0.009).

Conclusions:

• The SMA-FCR expands the range of abilities assessed in SMA.
• The SMA-FCR appears more sensitive to treatment effects than the HFMSE.
• The SMA-FCR may enable broader eligibility criteria in clinical trials for SMA, including individuals with minimal or maximal function.